Method for modeling autoimmune oophoritis. Morphofunctional state of the uterine appendages in chronic inflammation and complex treatment using mud extract (experimental clinical study) Nevostruev Sergey Aleksandrovich

That year the army lost an excellent officer, but medicine was an undeniable winner. Yesterday's schoolboy Vladimir Tkachev wanted to become a military man, but he was unable to enroll in the specialty he liked. But a friend offered to take exams with him at the Tomsk Medical Institute at the Faculty of Medicine. And he, without especially thinking about why he needed it, agreed.

The competition for “doctor” was considerable, but this was not an obstacle, and both were enrolled. Only the first one dreamed of “healing people”, the second one came here for company. But how often His Majesty chance reshapes a person’s fate, pushing him in the right direction! There is no doubt that in a different scenario, and in a different field, Vladimir Nikolaevich Tkachev would also have achieved professional heights, because he belongs to that blessed galaxy of people who, no matter what they undertake, do it well. That's the character. But, thank God, he came to medicine, and one day the spontaneous decision he made turned out to be very accurate.
Suddenly, he became fascinated by his studies, and what was so far from his desires yesterday became decisive. The future profession was already declaring itself as a vocation, growing into a business without which it was impossible to imagine further life. I wanted to know more - I started studying in a scientific circle. Around the third or fourth year, he firmly decided that his specialization was obstetrics and gynecology. A serious and inquisitive student then attracted the attention of teacher Irina Evtushenko, now professor, head of the department of obstetrics and gynecology of Siberian State Medical University.
“The classes were held in the first maternity hospital, the group was new to me,” recalls Irina Dmitrievna. - When discussing the topic, one of the students asked several questions; it was felt how deeply he knew the material and how he wanted to find an answer to something that was still unknown to him. This was Vladimir Tkachev. He always took his studies very seriously, and that earned him respect.
By the way, the habit of studying has remained to this day, although today Vladimir Nikolaevich is capable of the most complex operations, professionally he has achieved a lot. But I will refer once again to the opinion of Irina Dmitrievna, “he always wants more.” When he worked in an obstetrics clinic, they also said about him that “he can do everything,” and he was highly valued as a specialist. But he set other, more ambitious goals for himself - to operate more. Irina Yevtushenko, by that time already the head of the department, decided to transfer Tkachev to the gynecology clinic, where endoscopic operations were mastered, and where he could devote himself entirely to surgery. Why did you choose her? He answers simply and briefly: “ I always wanted and knew that I would be a surgeon" Colleagues note that even the first operations performed by Tkachev confirmed how much these hands can do.
Once upon a time, the Roman philosopher and physician Cornelius noted that “the effect of surgery among the branches of medicine is the most obvious.” Yes, the successes of surgeons are much more noticeable, more visible, perhaps, than the achievements of other specialists, but defeats, if they happen in a battle with the disease, are instantaneous. And no one is safe from them. How much you need to know and how much you need to be able to do in order to still win at the operating table at a crucial, difficult and dangerous moment. Thinking like a doctor, acting like a doctor, learning new things all your life, sacrificing a lot in the name of it - that’s what, in my opinion, this profession is. Besides everything it's still hard physical work, and also poorly paid, which is extremely unfair. In the Hippocratic Oath, which health officials and our journalistic brethren, who expose “bad doctors,” are so fond of remembering, it is not appropriate and inappropriate to remember, there is not a word about the fact that a doctor is obliged to live in poverty. Today the situation surrounding surgery is almost tragic. In any case, this is how Vladimir Naidenkin, deputy, characterizes her. the chief physician of the Siberian State Medical University clinics and a highly qualified surgeon himself. It may be said emotionally, but in many respects it is probably true, which is confirmed by statistics. Today everyone knows that there is a shortage of doctors in various specialties in Russia, the biggest shortage of personnel is in surgery.
“To become a real professional in our business, you need to work for 15 years, and study, study, study... Spare no effort or time,” says Vladimir Ivanovich. “And that would be normal, because people entrust their lives to us.” If only there were adequate material rewards to some extent. And so... A young doctor has a salary of six thousand, usually there is no housing, no benefits, but he has a family that he is obliged to take care of. Nowadays, among senior students and university graduates, rarely do anyone choose surgery. Although, of course, there are talented young people, those who, in spite of everything, devote themselves to surgery. Then you are glad that there is someone to pass on your experience to, there will be a change. And they want to say: it’s happiness, real luck, when you can learn from surgeons like Tkachev!
He defines the secret of his colleague’s professional credo in one short but succinct phrase: Tkachev is a real, correct doctor. Still, I ask you to express this verbally in more detail. “And now I’ll show you the summary,” Vladimir Ivanovich responds to the request. - You see, in a year Tkachev performed more than 700 operations, many of them related to the so-called high technologies. But it’s one thing to operate, another thing to get out; complications can only be prevented during a period of diagnostic observation. And so, after standing at the operating table for 5-6 hours, he then monitors the patient’s condition without fail and maintains constant contact with the attending physician. He comes to the clinic in the evening, on Saturday and Sunday... And such control is exercised not only over his patients, he is also the head of the clinic, which means he is in charge of everything that happens there. Responsible and reliable, you can always rely on him, he will never let you down. I would also note one more feature of his. What can I say, he is a wonderful surgeon, but absolutely devoid of any snobbery! He himself is happy to advise his colleagues, but he can also ask them for advice. By the way, he has a wonderful team at his clinic, and he is also a team man.”
I have heard more than once about the well-coordinated and professional team in the gynecology clinic, which includes not only surgeons and doctors, but also nursing and junior medical staff. And the highest praise seemed to be the words spoken by the chief physician of the Siberian State Medical University clinics, Vitaly Shevelev. In my opinion, it is worth a lot when a leader medical institution, who has to be very careful about spending money (there is never enough of it), states: “ I don’t mind the money for this clinic; I know it will be spent wisely. There's a payoff there" And he lists what he puts into it: they set themselves the highest goals, actively implement advanced ideas and technologies, keep abreast of all modern advances, and give preference to organ-preserving minimally invasive surgery. “Of course, this is a considerable merit of Vladimir Nikolaevich Tkachev, both as the head of the clinic and as a surgeon of the highest qualifications,” adds Vitaly Mikhailovich. “He strives for excellence himself, and the entire team aims for this. In fact, the level that exists in Russia, and in many ways in the world, has been achieved in the clinic. Although there is something to strive for, and we will help with this. In addition, he is a wonderful person, non-conflict, reasonable, always responds to requests for help. You can calmly solve the most complex issues with him.”
Yes, the clinic today provides the full range of diagnostic, therapeutic and high-tech surgical care to its patients. Promising directions are being developed here. What was a miracle yesterday is almost commonplace today. Medical and scientific work is aimed at preserving a woman’s reproductive health, the ability to have children, and improving the quality of life at any age. And a lot of things succeed. Although other ambitious tasks immediately appear, for example, mastering robotics during operations. It is believed that this goal will be achieved. Moreover, the clinic’s specialists, working in close collaboration with the department’s staff, are quite capable of doing this. It's a matter of equipment. The current state of the team, personnel and scientific potential allow us to look into the future with optimism. And the inexhaustible desire of the head of the Tkachev clinic to learn plays a beneficial role in this process. It is also on his initiative that interesting conferences are held in real time, leading specialists from the country are invited, with whom they operate together, which, of course, opens up new horizons, contributes to the development of a greater number of techniques and techniques, and ultimately to better preservation of the health of patients.
Over all these years, Vladimir Nikolaevich has never regretted his decision to enter medical school, although, like every person who works hard and fruitfully, there are times when fatigue accumulates. But this does not affect the clinic staff, especially the patients. What is called professional deformation is unusual for him. He is always calm, confident, friendly, and if necessary, politely strict, which seems to be an absolutely correct tactic in communicating with patients. In moments of despair, women are especially susceptible to emotions that cannot always be contained. Someone cries, someone panics and says goodbye to life, someone hates this whole healthy world... But I myself witnessed when, after communicating with Vladimir Nikolaevich, women returned to the ward calm, smiled, called their relatives, discussed with their neighbors various important trifles. And the next day there was an operation, the outcome of which was now beyond any doubt. Only those who have experienced this themselves know how important it is to believe and hope at such a moment.
There are no trifles in the recovery process, at least that’s how things are set up in the gynecology clinic. There is a well-oiled mechanism at work here both in treatment and in ordinary everyday life. The atmosphere is benevolent, there is cleanliness and order all around, even where, in the words of a famous literary character, “ruin in our heads” begins. To the uninitiated, it seems that everything happens by itself.
“And that’s how it should be,” I’m sure. head nurse Tatyana Bugaeva. - We solve our problems in such a way that it does not affect patients in any way. Vladimir Nikolaevich and I came to our new positions in 2004. It seems to me that everything worked out for him right away, he knows how to organize things and assign everyone responsibilities. For all his goodwill, he has strict demands and does not tolerate sloppiness, because, first of all, he himself is very responsible. But you know, if official disputes happen, they pass without offense or tears. Our team is selected in such a way that people who love their work and value it remain here. I believe that this is also the merit of Vladimir Nikolaevich as a leader. After all, we are one team.
Here again about the team... The ability to form it was also noted by the clinic’s doctor, candidate of medical sciences, associate professor of the department of obstetrics and gynecology Sergei Nevostruev, who considers Vladimir Nikolaevich not only his teacher, but also the undisputed leader operative surgery. And besides, in his opinion, Tkachev is also a talented teacher, because not only students and interns learn their skills from him, but already established doctors improve their skills. “Vladimir Nikolaevich has a special gift of openness,” says Sergei Alexandrovich. “He generously shares his accumulated experience with others, and this ability is not given to everyone.”
In any professional environment, the opinions of colleagues are important. Who else, if not them, can appreciate the results of what has been achieved.
“We trust Vladimir Nikolaevich unconditionally,” emphasizes Marina Petrova, Candidate of Medical Sciences, Associate Professor of the Department of Obstetrics and Gynecology. - I say this not only as a colleague. I am grateful to him on a personal level, he helped my daughter not lose her child. When patients come to him, they are such reliable hands, you can be sure that he will do everything possible. He appears at the clinic early, at 7.30 he is already at his workplace, always aware of what is happening. Operates uniquely! It seems that there is no case that Tkachev cannot cope with. Not only is he not afraid to try new things, he strives for it. The most complex operations that are carried out in the leading central clinics of Russia, and those that are told to us at foreign congresses and symposiums - Vladimir Nikolaevich is fully proficient in all of this. The only thing left is the highest level - robotics. When we have such an opportunity, we will be the first to master it.
Vladimir Nikolaevich himself does not see anything special in his profession: work is like work, he says, but everywhere has its difficulties. He calls the operation that does not need to be performed the best, the most difficult situation is the one when it is already extremely clear that the disease has taken hold. Yes, over time, experience is gained that helps you always make quick, clear, specific decisions. But still, before each operation, he is collected and focused. The situation can turn out to be much more difficult than expected, and it is good to have a reliable team nearby.
“I can’t say that I came to an empty place and created a team,” emphasizes Vladimir Nikolaevich. - And before me, real professionals worked here, who had something to learn from. A surgeon cannot be alone, except to some extent... It is a big misconception to think that you know everything and can do everything. Each of us has our own teachers, and I do too, and I am very grateful to them for science. You can’t read a textbook and start doing something well - sharpening parts, building a house... But here we are talking about the most important thing in everyone’s life - health. And your own development and movement forward is possible if you have people working nearby who pick up your ideas and bring something of their own to them. This is exactly the case in our clinic. I am very interested in the experience of surgeons from other clinics, for example, how Viktor Ravilyevich Latypov works, because operations on adjacent organs add confidence and expand your field of activity. The surgeon needs to know more than what he himself is doing. This means that you must always study, choose the time for this, which is so lacking.
- The clinic is very closely connected with the department of obstetrics and gynecology, which is understandable: you are, in fact, one university...
- This is an excellent scientific school, a certain style of work, nurtured over the years, strong traditions that we are proud of, support and develop. And this is a great merit of the head of the department, Irina Dmitrievna Evtushenko. She is very kind to our veterans, who have achieved a lot in medicine and whose work we continue. In addition, we cannot afford to focus on one direction, because we teach students, and they must know not only the theory, but also see how this happens in practice. Training qualified personnel capable of effectively mastering innovative technologies is also our task.
- Today the clinic is not only one of the largest hospitals in the city and region, but in many areas you are pioneers, introducing the most advanced technologies for the treatment of non-operative and operative gynecology. But during the entire time of our conversation, I never once heard from you the usual complaints about poor funding, poor equipment...
- I can’t say that there are no problems at all; you always want more. But if we already lived through the 90s, when there was nothing at all... We make full use of the opportunities we have, and they are not bad. I must note with gratitude that we always find support from the chief physician of the clinics, Vitaly Mikhailovich Shevelev, he understands our requests and helps as much as he can. We also work in close cooperation with Vladimir Ivanovich Naidenkin, he is a surgeon himself and knows what we need. We dream about robotics and hope that we will soon use it too.
I also asked Vladimir Nikolaevich about his doctoral dissertation; his colleagues asked me to remind him that it was time... Several years ago he brilliantly defended his candidate’s thesis, and for a long time now he has had enough material for his doctoral dissertation. I promised to improve, because “he himself understands what is necessary,” which is what I report through the press.
I also want to tell you about a pleasant event for everyone who knows Vladimir Nikolaevich in the life of the surgeon Tkachev. Most recently in Sochi at the All-Russian Scientific and Practical Seminar “ Reproductive potential of Russia: versions and counter-versions“He was awarded a victory in the nomination “Mastery”. In a solemn ceremony, Vladimir Nikolaevich was presented with a commemorative figurine. His services at the Russian level were recognized by the professional community, and he was applauded by his colleagues gathered in the hall, who know the value of such an award. In his response, Vladimir Nikolaevich said that this award was not only for him, but for the entire clinic. These were not stock words, he sincerely thinks so. But he runs the clinic.
Nina MASKINA.

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CHAPTER 1. LITERATURE REVIEW

1.1. Modern look on the problem of chronic inflammatory diseases of the uterine appendages

1.2. Morphological changes in the uterine appendages in inflammatory diseases

1.3. Principles of complex therapy of chronic inflammatory diseases of the uterine appendages

1.4. The importance of peloid therapy in the treatment of chronic inflammatory diseases of the uterine appendages

1.5. Characteristics of silt sulfide mud extract

1.6. Summary

CHAPTER 2. MATERIAL AND METHODS OF RESEARCH 2.1 Experimental part

2.2. Clinical part

2.3. Statistical processing of results

CHAPTER 3. RESEARCH RESULTS 3.1. Morphological changes in the uterine appendages during chronic inflammation and their correction using silt sulfide mud extract

3.1.1. The course of experimental inflammation of the oviducts and ovaries in white rats

3.1.2. Morphology of the oviducts and ovaries of white rats during chronic inflammation caused by the introduction of a culture of Staphylococcus aureus

3.1.3. Morphology of the oviducts and ovaries of white rats during chronic inflammation caused by the introduction of a culture of Staphylococcus aureus after a course of abdominal-sacral galvanization

3.1.4. Morphology of the oviducts and ovaries of white rats during chronic inflammation caused by the introduction of a culture of Staphylococcus aureus, after a course of abdominal-sacral electrophoresis of a 1% solution of silt sulfide mud extract

3.1.5. Morphology of oviducts and ovaries of white rats with chronic aseptic inflammation

3.1.6. Morphology of the oviducts and ovaries of white rats during chronic aseptic inflammation and a course of galvanization

3.1.7. Morphology of the oviducts and ovaries of white rats with chronic aseptic inflammation and after a course of abdominal-sacral electrophoresis of a 1% solution of silt sulfide mud extract

3.1.8. Indicators of morphoquantitative examination of the ovaries. white rats with experimental chronic inflammation and peloid physiotherapy

3.9. Summary

3.2. The influence of complex treatment using electrophoresis of a 1% solution of silt sulfide mud extract on the clinical course and outcome of chronic inflammation of the uterine appendages

3.2.1. Clinical and laboratory characteristics of patients with chronic inflammatory diseases of the uterine appendages

3.2.2. Principles of complex treatment of patients with chronic inflammatory diseases of the uterine appendages

3.2.3. Dynamics of clinical and laboratory parameters depending on the complex therapy used.

3.2.4. Medical and social effectiveness of treatment of patients with CIDP using in combination therapeutic activities electrophoresis of a 1% solution of silt sulfide mud extract

3.2.5. Summary

CHAPTER 4. DISCUSSION OF RESULTS

Introduction of the dissertation (part of the abstract) on the topic "Morphofunctional state of the uterine appendages during chronic inflammation and complex treatment using mud extract (experimental clinical study)"

Relevance of the problem. Chronic inflammatory diseases of the uterine appendages (CIUD), despite advances in the development of new treatment methods and the widespread introduction of laparoscopy into practical medicine, continue to remain one of the pressing problems of clinical practice [Kulakov V.I., 2001; Smetnik V.P., 2003; Henry-Suchet J., 2000]. Patients with inflammatory diseases of the uterine appendages make up 60-65% of all gynecological patients [Serov V.N., 2003; Risser W.L., 2002]. CIDP are common cause pelvic pain syndrome, infertility, miscarriage, ectopic pregnancies and, as a consequence, a large number of surgical interventions [Veren J., 2002; Taylor R.C., 2001; Vilos G.A., 2002]. In this regard, improving the quality of treatment of patients with CIPV using complex, pathogenetically based approaches is of particular importance [Savelyeva G.M., 1997; Ross J.D., 2001].

In domestic and foreign literature there is numerous data on the pathomorphogenesis of chronic inflammation in the uterine appendages [Kovalsky G.B., 1996; Krasnopolsky V.I., 1998; Herschlag A., 2000; Furuya M., 2002]. However, the degree of involvement of the ovaries in the inflammatory process, the reversibility of morphological disorders in the uterine appendages against the background of CIPR, and the possibility of influencing reparative processes in the ovaries and fallopian tubes remain the subject of debate to this day. There are isolated experimental studies devoted to this problem, but their results are often contradictory [Tikhonovskaya O.A., Logvinov S.V., 1999; Ordonez JL, 1999; Leese H.J., 2001].

In modern conditions, with CIPV, clear trends are visible, on the one hand, towards the use of minimally invasive methods of surgical diagnosis and treatment, on the other hand, towards the optimization of measures aimed at rehabilitating the functions of the organs of the female reproductive system [Strugatsky V.M., 2003; Cibula D., 2001; Ness R.B., 2002]. Achievements of recent years give reason to consider methods of physiotherapy as one of the most promising, taking into account their possibility of differentiated and targeted action on various parts of the pathogenesis of the disease, increasing adaptive capabilities with a minimal risk of developing adverse reactions [Bogolyubov V.M., 1998; Strugatsky V.M., 2002].

An undoubted reserve for optimizing the treatment of CIPM is the use of natural therapeutic muds and preparations obtained on their basis, which have the ability to regulate neurohumoral and immune processes, prevent and reduce dystrophic changes, stimulate the regeneration of cellular elements [Arkhipova L.V., 1995; Strugatsky V.M., 2003].

At the Institute of Petroleum Chemistry of the TSC SB RAS (Tomsk), a dry extract of silt sulfide mud was created, containing a complex of mineral salts, trace elements, organic matter, which has a wide range of medicinal properties: anti-inflammatory, analgesic, hepatoprotective, etc. [Saratikov A.S., 2001; Vengerovsky A.I., 2002]. The use of the extract in acute inflammation of the uterine appendages has an anti-alterative, anti-exudative effect mainly due to the membrane-stabilizing antioxidant effect, expressed in a decrease in the concentration of lipid peroxidation products and catabolism of cell membrane receptors [Tikhonovskaya O.A., 1998, 1999, 2000].

At the same time, the mechanisms and patterns of the therapeutic effect of the silt sulfide mud extract in CIPM remain poorly understood.

Purpose of the study. To study the effect of silt sulfide mud extract on the morphofunctional state of the uterine appendages during chronic inflammation in an experiment and evaluate its clinical effectiveness.

Based on the above, the purpose and objectives of the study were formulated.

1. To develop models of chronic inflammation of the uterine appendages with a pronounced proliferative component.

2. To study, using the created models of chronic inflammation of the uterine appendages in experimental animals, the nature, dynamics and sequence of changes in various tissue elements: epithelium, connective tissue stroma, blood vessels, generative and endocrine elements.

3. To evaluate, using models of chronic inflammation, the effect of electrophoresis of silt sulfide mud extract on the dynamics of the morphofunctional state of the oviducts and ovaries, the intensity of reparative processes, and to experimentally substantiate the possibility of using it in the complex treatment of chronic inflammation of the uterine appendages.

4. To develop a method of treating women with chronic inflammatory diseases of the uterine appendages, including peloid physiotherapy from the early stages after laparoscopy.

5. To analyze the effectiveness of the method of treating women with chronic inflammatory diseases of the uterine appendages based on immediate and long-term results.

Scientific novelty. Experimental models of chronic monocultural and aseptic inflammation of the ovaries and oviducts in white outbred sexually mature female rats have been developed. The experiment studied in detail the pathomorphogenesis in the uterine appendages during chronic inflammation, analyzed the role of various structural elements in the tissue mechanisms of inflammation of the oviducts and ovaries, and determined the sequence and nature of pathological disorders.

For the first time, it was established that the extract of silt sulfide mud reduces atresia of the ovarian follicular apparatus initiated by inflammation, prevents the formation of fibrosclerotic adhesive changes and promotes regression of fibrous tissue due to the activation of macrophages and fibroclasts and the normalization of the processes of collagenogenesis and collagenolysis.

The high efficiency of electrophoresis of a 1% solution of silt sulfide mud has been clinically proven as a pathogenetically substantiated component of the treatment of CIPM. For the first time in this pathology, the dynamics of the hormonal function of the ovaries and the functional activity of the fallopian tubes under the influence of peloid physiotherapy were studied. The data obtained prove that electrophoresis of the extract, carried out in the early stages after laparoscopic organ-preserving interventions on the uterine appendages, has a stimulating effect on ovarian function, increasing the secretion of estrogen and progesterone; restores the functional activity of the fallopian tubes.

Practical significance. The developed models make it possible to perform preclinical testing of new methods of treating CIPV.

As a result of the research, a pathogenetically substantiated method for the complex treatment of CIPM using an extract of silt sulfide mud was developed. The proposed method of treatment increases therapeutic effectiveness in terms of immediate and long-term results: it reduces the frequency of relapses, prevents the formation of pelvic pain syndrome, tubo-peritoneal infertility, and ectopic pregnancy.

Application in gynecological practice Peloid physiotherapy in non-resort conditions makes it economically accessible to wide sections of the population and has important socio-economic significance.

Provisions submitted for defense.

1. In the pathomorphogenesis of experimental chronic inflammation of the uterine appendages, regardless of phlogogen, there are similar changes, manifested by microcirculatory disorders, massive atresia of growing follicles, fibrous-sclerotic and adhesive processes. In the mechanism of tissue disorders, an important role is played by disruption in the collagen synthesis-collagenolysis system.

2. The use of silt sulfide mud extract for chronic inflammation of the uterine appendages in an experiment limits the increase in atresia of the ovarian follicles, accelerates the regeneration of the oviduct mucosa, normalizes hemodynamics in the microvasculature, and promotes the reverse development of fibrosclerotic and adhesive processes.

3. In the mechanism of the therapeutic effect of peloid therapy on the uterine appendages during chronic inflammation in the experiment, one of the leading places belongs to the activation of macrophages and fibroclasts and the normalization of the processes of collagenogenesis and collagenolysis, restoration of the ultrastructural organization of the hematofollicular barrier

4. Electrophoresis of a 1% solution of silt sulfide mud extract increases the effectiveness of complex treatment of chronic inflammation of the uterine appendages in women based on immediate and long-term results.

Introduction into practice. The results of the study are used in the educational process at the Department of Obstetrics and Gynecology, Faculty of Medicine, Siberian State Medical University on the topic “Inflammatory diseases of the pelvic organs”; at the Department of Histology, Embryology and Cytology of Siberian State Medical University on the topic “Female reproductive system”; medical activities of the gynecological clinic of Siberian State Medical University and the Women's Health Center LLC MADEZ.

Approbation of work. The main results of the work were reported and discussed at the scientific and practical conference of students and graduate students "Youth Health - Health of the Nation" (Tomsk, 1998), the Final Conference "Tatiana's Day" based on the results of the Russian competition for the best scientific work of students in 1998 in the section " Medical Sciences" (Moscow, 1999), conference "Modern problems of fundamental and clinical medicine" (Tomsk, 1999), at the School of Young Researchers "Achievements in Molecular Biology and the Development of New Effective Methods for the Treatment of Human Diseases" (Moscow, 1999), VI and IX Russian National Congresses “Man and Medicine” (Moscow, 1999, 2002), I, II, III International Congresses of Young Scientists and Specialists “Scientific Youth on the Threshold of the 21st Century” (Tomsk, 2000, 2001, 2002), Russian scientific and practical conference “Current issues of endoscopic surgery in gynecology and obstetrics” (Tomsk, 2001), VI international scientific and practical conference “Quality - strategy of the 21st century” (Tomsk, 2001), Tomsk, 2001), Russian scientific conference with the participation of CIS countries “Current problems of experimental and clinical morphology” (Tomsk, 2002), city scientific and practical conference dedicated to the 40th anniversary of the Central Research Laboratory of the city

Siberian State Medical University “Modern aspects of biology and medicine” (Tomsk, 2003), Russian conference “Current issues of urogynecology” (Tomsk, 2003), meetings of regional scientific and practical societies of obstetricians-gynecologists and morphologists (Tomsk, 2003-2004).

Scope and structure of the dissertation. The dissertation is presented on 204 pages and consists of an introduction, literature review, personal observations, discussion, conclusions and practical recommendations. The bibliographic index contains 422 sources, of which 250 are in Russian and 172 in foreign languages. The dissertation contains 16 tables, 4 photographs, 32 microphotographs, 10 electron diffraction patterns, 5 graphs.

Conclusion of the dissertation on the topic "Obstetrics and Gynecology", Nevostruev, Sergey Alexandrovich

1. The developed experimental models make it possible to obtain chronic inflammation of the uterine appendages with a pronounced adhesive process in the area of ​​the ovaries and oviducts, and are characterized by relative ease of reproduction and stability of the inflammatory process.

2. Chronic monocultural and aseptic inflammation of the uterine appendages in the experiment causes pronounced proliferation and fibrosclerotic changes in the connective tissue in the ovaries and oviducts, a decrease in the content of primordial, growing and mature follicles, corpus luteum, and increases their atresia.

3. Electrophoresis of a 1% solution of silt sulfide mud extract promotes regression of fibrous changes caused by inflammation, reducing the specific volume of connective tissue and the severity of the adhesive process. The extract limits atretic processes in the ovaries and stimulates the growth, maturation of follicles and the formation of corpus luteum.

4. In the tissue mechanisms of the anti-sclerotic effect of the silt sulfide mud extract, an important role is played by the activation of fibroclasts and macrophages, which regulate the processes of collagen synthesis and resorption. The extract reduces inflammation-induced hemodynamic vascular disorders and ultrastructural changes in the blood-follicular barrier.

5. Conducting laparoscopy and early initiation of peloid physiotherapy in the postoperative period can improve the results of complex treatment of women with chronic inflammatory diseases of the uterine appendages.

6. The use of electrophoresis of a 1% solution of silt sulfide mud extract from 1-2 days after laparoscopy increases the effectiveness of treatment of chronic inflammatory diseases of the uterine appendages according to immediate and long-term results: clinical recovery during treatment with the developed method was noted in 91% of cases; the frequency of episodes of exacerbation and recurrence of pelvic pain syndrome decreases by 3 times, restoration of reproductive function is achieved in 55% of patients.

1. For patients with CIPV after laparoscopy, it is recommended to prescribe a course of electrophoresis of a 1% solution of silt sulfide mud extract from 1-2 days after surgery. The procedures are carried out according to the standard abdominal-sacral technique. Electrodes with an area of ​​200-300 cm are placed transversely on the sacrum (cathode) and above the pubis (anode). Hydrophilic pads are moistened with a 1% solution of the extract. l

The current density is 0.03-0.06 mA/cm, the duration of exposure is 10-20 minutes. The course consists of 10-12 procedures carried out in the morning, daily, with compulsory rest within 1-2 hours after physiotherapy.

2. The criteria for the effectiveness of treatment for CIDP is the achievement, in the short term after therapy, of the first and second levels of rehabilitation - clinical recovery (absence of subjective and objective signs of inflammation in combination with normalization of the echoscopic picture) in combination with recovery endocrine function reproductive system (according to the results of TPD and the level of sex steroid hormones in the blood plasma). In the longer term, the effectiveness of the treatment is assessed by the absence of relapses of the disease, normalization of computer cympertubation data and rehabilitation of the woman’s reproductive function - the onset of pregnancy (III level of rehabilitation). >

3. If pregnancy does not occur within 6-12 months after complex treatment, or repeated laparoscopy for CIDP is performed, pregnancy planning using assisted reproductive technologies is recommended.

List of references for dissertation research Candidate of Medical Sciences Nevostruev, Sergey Alexandrovich, 2004

1. Avtandilov G.G. Medical morphometry. M.: Medicine, 1990. - 384 p.

2. Agapov A.I., Avvakumova N.P., Korshikova T.V. and others. Method of treatment of chronic adnexitis. BIPM No. 16 (II part), 06/10/2000. - P.252-253.

3. Adamyan L.V., Mynbaev O.A. Vardanyan V.G. Evaluation of the effectiveness of an ultrasonic scalpel on experimental models of laparoscopic gynecological operations // Endoscopy in gynecology (Ed. V.I. Kulakov, L.V. Adamyan), M., 1999. P.46-48.

4. Adamyan L.V., Beloglazova S.E. Differential diagnosis of adhesions with the formation of cystic cavities (serosocele) during laparoscopy // Endoscopy in gynecology (Ed. V.I. Kulakov, L.V. Adamyan), M., 1999. P.236-241.

5. Ailamazyan E.K., Ustinkina T.I. Genital inflammatory diseases in infertility in the family // Issue. protection of motherhood and childhood. - 1991. No. 6. - P.35-37.

6. Akker L.V., Deryavkina R.S. The role of microbial factor in the pathogenesis of chronic recurrent diseases of the uterine appendages // Journal. obstetrics and women's diseases. St. Petersburg, 1998. - pp. 12-13.

7. Aksenenko K.B. Non-gonococcal urogenital infections in marital infertility // Ways of development of modern gynecology: Proc. report M., 1995. -P.51.

8. Aksenenko V.A., Zhikhareva I.V., Lavrinenko E.B. Features of laparoscopic treatment of inflammatory diseases of the appendages of uterine chlamydial etiology // Endoscopy in gynecology (Ed. V.I. Kulakov, L.V. Adamyan), M., 1999. P.448-449.

9. Yu.Aksenenko V.A., Lavrinenko E.B., Nekhaeva O.I. and others. Some features of the immune response during laparoscopic treatment of inflammatory diseases of the uterine appendages // Endoscopy in gynecology (Ed. V.I. Kulakov, L.V. Adamyan), M., 1999. P.450-452.

10. Obstetric and gynecological care/Ed. IN AND. Kulakova. - M.: Medicine, 1995. 304 p.

11. Obstetrics and gynecology/Ed. G.M. Savelyeva, L.G. Sichinava. M.: GEOTAR, 1997.-719 p.

12. Antibacterial therapy. Practical Guide/Ed. L.S. Strachunsky, Yu.B. Belousova, S.N. Kozlova. M., 2000. - 190 p.

13. Arslanyan K.N. Early restorative treatment after microsurgical operations on the fallopian tubes (differential use of preformed physical factors): Abstract of thesis. dis. . Ph.D. honey. Sci. -Moscow, 1991.-25 p.

14. Arslanyan K.N., Strugatsky V.M., Yarotskaya E.L. New opportunities for restorative physiotherapy after combined endosurgical operations in gynecology // Endoscopy in gynecology (Ed. V.I. Kulakov, L.V. Adamyan), M., 1999. P.207-210.

15. Arkhipov V.V., Maganev V.A. The state of pelvic hemodynamics in patients with chronic salpingoophoritis against the background of peloid therapy // Resortology and balneophysiotherapy. 1993. - P.149-150.

16. Arkhipova J.I.B., Kulavsky V.A. The use of mud therapy and vacuum therapy in women with chronic diseases of the uterine appendages // Ways of development of modern gynecology: Abstract. report -M., 1995. P.53.

17. Bakuridze E.M., Fedorova T.A., Dubnitskaya L.V. and others. Plasmapheresis and medical ozone in the rehabilitation of women after endoscopic operations on the pelvic organs // Mat. IV Ross, Mother and Child Forum. -T.P.-M., 2002.- P.54-56

18. Baranov V.N. Method for treating chronic salpingoophoritis. BIPM No. 17 (II part), 06.20.2000. - P. 320.

19. Bezhenar V.F., Maksimov A.S. Tubal-peritoneal infertility. Problems and prospects // Journal. obstetrics and women's diseases. 1999. - Issue 3. - T.XLVIII. - P.48-54.23. Infertility in marriage/Ed. I.F. Yundy. Kyiv, “Health”, 1990. -464 p.

20. Bilich G.L., Kolla V.E. Modern problems of pharmacological regulation of regeneration // Modern problems of regeneration. - Yoshkar-Ola, 1980.-N.Z-27.

21. Blagoveshchenskaya L.K. Treatment of tubal infertility by hydrotubation in combination with vibration massage through the anterior abdominal wall: Abstract of thesis. dis. . Ph.D. honey. Sci. - Chelyabinsk, 1977. - 26 p.

22. Bobro L.P. Fibroblasts and their significance in tissue reactions // Arch. pathology. 1990. - Issue 12. - P.37-42.

23. Bogdanova I.V., Lyutova O.V. Comparative characteristics of the chemical composition of liquid and dry preparations of medicinal mud and brine of Lake Karachi // Preparations from medicinal mud and brine: Sat. scientific tr. Tomsk, 1983. - P.7-11.

24. Bogolyubov V.M., Zubkova S.M. Ways. optimization of physiotherapeutic effects // Issue. balneology, physiotherapy and medical treatment. physical culture. - 1998. - No. 2. P.3-6.

25. Bodyazhina V.I. Chronic nonspecific inflammatory diseases of the female genital organs. M.: Medicine, 1978. - 460 p.

26. Bodyazhina V.I. ABOUT pain syndrome with salpingo-oophoritis // Obstetrics. and gynecology. - 1978. No. 1. - P.10-17.

27. Bodyazhina V.I., Zheleznov B.I. Morphofunctional changes in foci of inflammation of the female reproductive system // Obstetrics. and gynecol. 1979. - No. 3. -P.3-9.

28. Bodyazhina V.I., Smetnik V.P., Tumilovich L.G. Non-operative gynecology: a guide for doctors. - M.: Medicine, 1990. 542 p.

29. Bolotova V.P. Pulse endovaginal vibration hydromassage in the treatment of chronic and residual inflammatory processes of the internal genital organs: Abstract of thesis. dis. . Ph.D. honey. Sci. - Tomsk, 1973.-17 p.

30. Brezitsky O.V., Chernetsova L.F. Immunological aspects of the pathogenesis of chronic nonspecific salpingo-oophoritis // Tyum. honey. zhur. - 2002. No. 3-4. - P.82-83.

31. Brezitsky O.V. Optimization of treatment of chronic recurrent salpingoophoritis in women living in the Far North: Abstract of thesis. dis. . Ph.D. honey. Sci. Tomsk, 2004. - 22 p.

32. Brusilovsky I.A. Brusilovsky A.I. Histochemical changes in the genitals during inflammation during mud therapy // Issue. spa treatment of patients with diseases of the female reproductive system. Kyiv, 1965. -P.13-15.

33. Weisfeld D.N. Vegetative ganglioneuritis in chronic inflammatory diseases of the female genital area. - Kyiv, 1967. - 62 p.

34. Vasiltsov M.K., Izatulin V.G., Lebedinsky V.V. Modeling, assessment and regulation of inflammatory processes // IV Russia-Jap. international, honey symp.: Abstract. report Irkutsk, 1996. - P. 142.

35. Vengerovsky A.I., Sibileva L.A., Taran D.D. Natural drugs in pharmacotherapy of adjuvant disease // Act. problems of pharmacology and the search for new medicine drugs. - Tomsk, 1984. - T. 1. - P. 173-176.

36. Vengerovsky A.I. Efficiency and mechanism of action of hepatoprotectors during experimental toxic damage liver: Author's abstract. dis. . Dr. Ramed. nauk.-M., 1991.-40 p.

37. Vengerovsky A.I. Pharmacological approaches to the regulation of liver function // Bulletin. Siberian medicine. - T.1, No. 1, 2002. P.25-29.43. Volkova O.V. Functional morphology of the female reproductive system. -M.: Medicine, 1983. -224 p.

38. Volkova O.V., Borovaya T.G. Morphogenetic basis of ovarian development and function. M.: 1999. - 248 p.

39. Vorobyov A.A., Beburishvili A.G. Surgical anatomy of the operated abdomen and laparoscopic surgery of adhesions. Volgograd: Publisher, 2001. -240 p.

40. Vorobyova T.G. Analysis of histochemical changes in the ovaries of white rats under the influence of preparations from medicinal mud and brine // Preparations from medicinal mud and brine: Sat. scientific tr. Tomsk, 1983. - P.33-35.

41. Vorona I.G., Bergman A.S. Hormonal homeostasis in patients with nonspecific salpingoophoritis. Riga: Zinante, 1990. - 98 p.

42. Gerasimovich G.N., Peresada O.A. Immunological reactivity of patients with chronic salpingoophoritis when ultrasound and levamisole are included in the treatment complex // Akush. and gynecol. - 1982. No. 4. - P.31-33.

43. Gynecology according to Emil Novak. Ed. J. Berena, I. Adami, and P. Hillard. Translation from English M.: Praktika, 2002. - 896 p.

44. Glanz S. Medical and biological statistics. Per. from English - M.: Praktika, 1998.-458 p.

45. Glukhovets B.I., Lebedev S.S., Ryazantsev E.L. The significance of vascular disorders in the pathogenesis of chronic salpingitis // Akush. and gynecol. 1983. - No. 9. -P.67-68.

46. ​​Gorchakova G.A. Research on the endocrine mechanisms of action of resort and physical factors in the Ukrainian SSR // Resort and physiotherapy. - Kyiv, 1986.-P.5-6.

47. Grigoryan M.M. Chronic pelvic pain: a comprehensive clinical and endoscopic examination // Endoscopy in gynecology (Ed. V.I. Kulakov, L.V. Adamyan), M., 1999. P. 163-167.

48. Gurtovoy B.L., Kulakov V.I., Voropaeva S.D. The use of antibiotics in obstetrics and gynecology. M., 1996. - 141 p.

49. Guryev A.V., Rogachev M.V., Goda I.V. Inflammatory changes in the fallopian tubes in patients with tubal pregnancy // Journal. obstetrics and female diseases. -1998. No. 5. - P.21-22.

50. Dergacheva T.I. Reactivity of patients with nonspecific inflammatory diseases of the uterine appendages: abstract. dis. . Dr. med. Sci. - Tomsk, 1996. 46 p.

51. Dergacheva T.I., Anastasyeva N.V., Trufakin V.A. and others. A method of complex therapy for patients with chronic adnexitis, an infectious-toxic variant of nonspecific etiology. -BIPM No. 6, 02.27.2000. pp. 188-189.

52. Deryabkina R.S. Potentiating physiotherapy in the complex treatment of patients with chronic inflammatory diseases of the uterine appendages in the acute stage: Abstract of thesis. dis. . Ph.D. honey. Sci. Barnaul, 1997. - 19 p.

53. Dzhabarova N.K., Karelina O.A. Klopotova N.T. Vitamin complexes as one of the indicators of the biological activity of peloids // Issue. balneology, physiotherapy and medical treatment. physical culture. 1997. - No. 2. - P.25-27.

54. Diamant I.I., Dikke G.B., Loktev B.I., Ruzaeva Yu.F. Way rehabilitation treatment women who have undergone surgery on the fallopian tubes. - BIPM No. 1, 01/10/2001. -P.34.

55. Diamond I.I. Mechanical and electromagnetic oscillations in the rehabilitation treatment of women after operations on the fallopian tubes: Abstract of thesis. dis. . Dr. med. Sci. Tomsk, 1996. - 33 p.

56. Dolgov G.V. Purulent-inflammatory complications in surgical gynecology. Forecasting. Prevention. St. Petersburg: “ELBI-SPb”, 2001. - 173 p.

57. Dyachuk A.V. Correction of immune disorders in patients with inflammatory diseases of the uterus and appendages: Abstract of thesis. diss. . Ph.D. honey. Sci. - M, 1992.-38 p.

58. Evseeva M.M. Intensive treatment of chronic salpingo-oophoritis with low-frequency pulsed electrostatic field: clinical and physiological rationale: Abstract of thesis. diss. . Ph.D. honey. Sci. - M., 1997-22 p.

59. Ermoshenko L.V. Etiological structure of chronic salpingo-oophoritis and optimization of complex therapy with immunocorrection with leukinferon:

61. Zhabina E.S. Rehabilitation of the reproductive function of women after reconstructive plastic surgery on the fallopian tubes: Abstract of thesis. diss. . Ph.D. honey. Sci. Tomsk, 2002. - 19 p.

62. Zheleznov B.I. Morphological aspect of acute inflammation of the uterine appendages in women of reproductive age // Obstetrics. and gynecol. 1990. - No. 6.- P.65-70.

63. Zhenchevsky R.A. Adhesive disease. M.: Medicine, 1989. - 168 p.

64. Zuev V.M. Some issues of pathogenesis, diagnosis and complex therapy of women with inflammatory processes and benign neoplasms of the reproductive system: Abstract. diss. . Dr. med. Sci. M, 1998. - 58 p.

65. Ivanyuta L.P., Vovk I.B., Melnik L.p. Intrauterine electrophoresis in complex rehabilitation of women with tubal infertility inflammatory etiology // Issue. security mat. and childhood. - 1986. T.31. - No. 10. - P.58-61.

66. Ird E.A. Follicular ovarian cysts and dyshormonal tumors. L.: Medicine, 1966. - 119 p.

67. Kaznacheev V.P., Dzizinsky A.A. "Patophysiological foundations of balneotherapy// Issues of balneology, physiotherapy and physical therapy. - 1969. - No. 4. - P. 319-325.

68. Karpovich O. A. Clinical and experimental substantiation of the therapeutic effect of Western Siberian mud in inflammatory processes of the genitals: Abstract. report XV All-Union. Congress of Obstetrics and Gynecology Donetsk, 1989. - P.288-289.

69. Kaufman O.Ya., Podzolkova N.M., Ermakova N.G. Patho- and morphogenesis of purulent inflammatory diseases of the uterine appendages // Arch. pathology. - 1993. -№1.- P. 43-48.

70. Kachalina T.S., Shakhova N.M., Kachalina O.V. Application medical ozone for inflammatory diseases of the female genital organs // Journal. obstetrics and women's diseases (special issue). 1998. - P. 163.

71. Kira E.F., Ponomarenko T.N., Skvortsov V.G. Practical reference book for obstetrician-gynecologist. St. Petersburg, 1997. - 312 p.

72. Kira E.F. Infections and reproductive health (Part II). Biochemical and biological properties of vaginal fluid // Journal. obstetrics and women's diseases. 1999. - Issue 3. - Volume XLVIII. - P.60-66.

73. Kitaev E.M. Davydov M.S., Usova A.A. Histoenzymological and hormonal parallels in the study of the ovaries and uterus in conditions of experimental salpingoophoritis // Akush. and gynecol. - 1985. No. 2. - pp. 52-54.

74. Kovalsky G.B. Age-related features of structural support for ovarian function // Bulletin. let's experiment biol. and medicine. 1984. - T.TCVIII. - No. 12.-S. 32-34.

75. Kovalsky G.B., Kitaev E.M., Ryzhakovsky B.Ya., Melnikova JI.M. Structural basis of the generative and endocrine function of the ovaries in normal and pathological conditions. St. Petersburg, 1996. - 204 p.

76. Kozachenko V.P. Elements of innervation of the fallopian tubes in their various pathologies: Abstract of thesis. diss. . Ph.D. honey. Sci. Voronezh, 1960. - 16 p.

77. Komarova JI.A. Problems and ways of development of clinical physiotherapy // Issues. balneology, physiotherapy and medical treatment. physical culture. 1997. - No. 1. -P.35-37.

78. Kondrikov I.P. Structural and some histochemical features of the fallopian tubes during inflammation // Actual. question obstetrics and gynecol. M., 1967. -Issue Z.-S.13-15.

79. Korolev N.V. Interstitial cells of mammalian ovaries // Cytology and genetics. 1984. - No. 2. - pp. 147-154.

80. Korotkikh I.N., Khodasevich E.V. The use of low-frequency pulsed magnetic therapy in the complex treatment of inflammatory diseases of the uterine appendages // Vest. Ross. assoc. obstetricians-gynecologists. 1999. - No. 32. - P.62-65.

81. Korotovskikh L.I. Examination and surgical treatment of women with infertility using endoscopic methods // Endoscopy in gynecology (Ed. V.I. Kulakov, L.V. Adamyan), M., 1999. P. 184-187.

82. Krstyuchek D.F., Bairov K.T. Hormonal changes in patients with purulent-inflammatory diseases of the uterine appendages // Journal. obstetrics and women's diseases. 1998. - No. 4. - P.28.

83. Koshurnikova N.A. Histopathology of the ovaries in chronic inflammation of the fallopian tubes and its residual effects: Abstract of thesis. diss. . Ph.D. honey. Sci. - M, 1958.-7 p.

84. Krasavsky E.B., Dmitrieva L.I., Korotkov Yu.P. Pathological examination of the uterus, ovaries and fallopian tubes in inflammatory diseases in women. M., 1974. - P.92-102.

85. Krasnopolsky V.I. Buyanova S.N., Shchukina N.A. Purulent inflammatory diseases of the uterine appendages. - M., 1999. 233 p.

86. Kulakov V.I. Adamyan L.V., Mynbaev O.A. Postoperative adhesions (etiology, pathogenesis and prevention). - M.: Medicine, 1998. - 528 p.

87. Kulakov V.I., Gasparov A.S., Volkov N.I. and others. Endoscopic treatment of tubo-peritoneal infertility // Endoscopy in gynecology (Ed. V.I. Kulakov, L.V. Adamyan), M., 1999. P.452-454.

88. Kulakov V.I., Adamyan L.V., Mynbaev O.A. Operative gynecology - surgical energies: Guide. M.: Medicine, Antidor, 2000. - 860 p.

89. Kulakov V.I., Prilepskaya V.N., Rogovskaya S.I. Methodology for conducting randomized studies // Obstetrics. and gynecol. 2003. - No. 1. - P. 2429.

90. Balneology and physiotherapy/Ed. V.M. Bogolyubova. M. Medicine, 1985. -T.1.-559 p.

91. Lazarev N.I., Ird E.A., Smirnova I.O. Experimental models of endocrine gynecological diseases. - M., 1967. - 112 p.

92. Levitsky E.F., Gridneva T.D., Kharlova V.A. and others. Method of treatment of chronic adnexitis. BIPM No. 9. - 03/27/2001. - P.42-43.

93. Lesnoy S.K. Treatment of hypoovarian disorders with mud and endocrine drugs. - M.: Medgiz, 1950. - 168 p.

94. Letuchikh A.A., Pedder V.V., Rudakova E.B. Low-frequency ultrasound in obstetrics and gynecology. Omsk, 1996. - 139 p.

95. Leshchinsky A.F., Zuza Z.I. Peloid therapy for inflammatory diseases. Kyiv: Health, 1985. - 184 p.

96. Lurina N.Yu. Morphofunctional characteristics of the fallopian tubes in normal conditions and with purulent inflammation: Abstract of thesis. diss. . Ph.D. honey. Sci. -Ryazan, 1990.-21 p.

97. Mavrov G.I. Clinical and morphological characteristics of chlamydial salpingitis//Vestn. dermatol. and venerol. 1994. - No. 4. - P. 18-22.

98. Mazorchuk B.F. Some histochemical and structural changes in the tissues of the tubes and ovaries during inflammatory processes of the uterine appendages // Actual. question obstetrics and gynecology. Lvov, 1969. - P. 418-420.

99. Maleva E.A., Avramov I.A., Kaprelyan G.A. Functional and morphological changes in the ovaries of white rats under the influence of infectious factors // Akush. and gynecol. 1975. - No. 3. - P. 63-64.

100. Malevich K.I., Rusakevich P.S. Treatment and rehabilitation for gynecological diseases. Minsk, 1994. - 367 p.

101. Malysheva S.M. Complex treatment of patients with gynecological inflammatory diseases with silt mud and UHF // Issue. resort treatment of patients with diseases of the female genital organs. Kyiv, 1965. - P.35-37.

102. Malyavin A.G. About some problems of physical therapy // Question. balneology, physiotherapy and medical treatment. physical culture. - 1995. No. 6. - P.38-41.

103. Matasova S.A., Ryzhova G.L. Study of humic substances of brine and aqueous extract of medicinal mud of Lake Karachi // Therapeutic use of peloids and preparations based on them. - Tomsk, 1988. - P.35-40.

104. Matveeva V.F., Rubtsova E.M., Krikunova R.K. The use of physical methods in the complex treatment of acute and subacute stages inflammation of the internal genital organs of women // Obstetrics and gynecology. 1972. - No. 2. - P.3-6.

105. Matveeva N.K., Lapik T.N., Sotnikova E.I., et al. The use of immunocorrectors in the complex treatment of chronic inflammatory diseases of the internal genital organs // Immunology. - 1995. No. 5. - P.48-49.

106. Matis E.Ya. Current problems of pharmacology and the search for new drugs. Tomsk, 1984. - 4.1. - P.168.

107. Matis E.Ya., Reshetova G.G., Novikova S.V. Experimental justification for the introduction of therapeutic mud lipids into the body using vibration // Issue. balneology, physiotherapy and medical treatment. physical culture. - 1996. No. 4. - P.22-24.

109. Mayansky D.N. On the pathogenesis of chronic inflammation // Therapist, arch. -1992. No. 12. - P.3-7.

110. Medvedev B.I., Astakhova T.V., Kazachkova E.A. Tuboovarian inflammatory formations: nosological and therapeutic aspects of the problem // Obstetrics. and gynecol. - 1991. No. 2. - P.64-66.

111. Medvedev B.I., Teplova S.N., Uzlova T.V. and others. Indicators of humoral immunity in women with tubo-peritoneal infertility // Journal. obstetrics and female diseases (Special issue). St. Petersburg, 1998. - P.31-32.

112. Melnikova S.E., Kustarov V.I. The use of laser therapy for the prevention and treatment of purulent-septic complications in the postpartum period // Infections of the fetus, amniotic fluid and newborn. -Krasnoyarsk, 1997. P.56-57.

113. Melnikova T.V., Borovskaya V.D. Method for treating female infertility of inflammatory origin. BIPM No. 9, 03/27/2000. - P.207-208.

114. Melnikova T.V., Tsybulko A.A. Method for treating chronic salpingoophoritis. BIPM No. 18 (I part), 06/27/2000. - P.55-56.

115. Melnikova T.V., Babaytseva A.Yu. Method for treating chronic salpingoophoritis. BIPM No. 13 (I part), 05/10/2001. - P.10.

116. Metreveli D.M. Pathogenetic rationale for complex treatment of salpingo-oophoritis: Abstract of thesis. diss. . Dr. med. nauk.- Kharkov, 1991. - 48 p.

117. Mikheeva JI.C. Therapeutic mineral sulfide mud: Tr. Central Research Institute of Balneology and Physiotherapy. M., 1984. - P.84-93.

118. Myshuk A.V., Gorelkzh I.P. The use of chloride-sulfate potassium-magnesium-sodium mineral water and direct current (experimental research) // Issue. balneology, physiotherapy and medical treatment. physical culture. 1989. - No. 3. - P.65-66.

119. Morozova N.n. Therapeutic use of the combined effects of mud and direct current // Therapeutic mud Kirg. SSR: Proceedings of the Research Institute of Balneology and Physiotherapy. Frunze, 1973. - Issue. 10. - P.156-162.

120. Myzenskaya M.E., Yarustovskaya O.V., Kuznetsov O.F., Esipova T.V. Vaginal cryotherapy of patients with chronic salpingo-oophoritis // Issue. balneology, physiotherapy and medical treatment. physical culture. 1996. - No. 6. - P.25-26.

121. Myzenskaya M.E., Yarustovskaya O.V., Kuznetsov O.F. and others. Comparative effectiveness of various methods of cryotherapy for patients with chronic salpingo-oophoritis // Issue. balneology, physiotherapy and medical treatment. physical culture. 1997. - No. 6. - P.35-37.

122. Myzenskaya M.E. The use of cryotherapy in the treatment of patients with chronic nonspecific salpingo-oophoritis: Abstract of thesis. diss. . Ph.D. honey. Sci. M, 2000. - 26 p.

123. Mynbaev O.A. Postoperative adhesions in gynecological patients: etiology, pathogenesis and principles of surgical treatment and prevention // Endoscopy in gynecology (Ed. V.I. Kulakov, L.V. Adamyan), M., 1999. P.163-167.

124. Navashin S.M., Fomina I.P. Rational antibiotic therapy. M., Medicine. - 1992. - 495 p.

125. Nazarova G.I. Indicators of cellular and humoral immunity in patients with inflammatory diseases of the uterine appendages in the dynamics of treatment: Abstract of thesis. diss. . Ph.D. honey. Sci. - Andijan, 1984. 21 p.

126. Nechai G.M. The influence of sapropel lipids on the parameters of the kallekrein-kinin blood system in an experiment // Therapeutic use of peloids and drugs based on them. Tomsk, 1988. - P.65-71.

127. Nizkodubova S.B., Kishakovskaya V.P., Gorshkova V.K. and others. On the question of the biological activity of mud lipids // Mud preparations. - Tomsk, 1981. P.68-72.

128. Nikolova JI., Takeeva Ts. Cytoenzyme and ultrastructural characteristics of the state of the ovaries when exposed to centimeter waves // Issue. balneology, physiotherapy and medical treatment. physical culture. - 1980. - No. 1. P.31-35.

129. Nnauri D.A. Ovarian insufficiency in chronic nonspecific salpingoophoritis // Human Physiology. - 1995. - T.21. -No. 3. P.166-169.

130. Oransky I.E. Regarding the article by S.V. Andreeva, B.N. Semenova "The importance of the skin in the mechanism of action of therapeutic media on the patient's body" // Issue. balneology, physiotherapy and medical treatment. physical culture. 1998. - No. 2. - P.3-6.

131. Oransky I.E. Tsarfis P.G. Biorhythmology and chronotherapy (chronobiology and chronobalneotherapy). M., 1989. - 158 p.

132. Oransky I.E., Tereshina L.G., Likhacheva E.I. Prospects for the biorhythmological organization of physiotherapy // Problems of optimization of sanatorium and resort care. - Tomsk, 1998. - P. 126-127.

133. Orlova L.S., Ordynsky V.F., Prilepo V.K., Poruchikov P.V. The use of EHF therapy in the treatment of chronic diseases of the pelvic organs in women // Mat. IV Ross, Mother and Child Forum. - T.N. M., 2002. - P.283-284.

134. Osipov V.I. Pathogenetic treatment and prevention of adhesive disease of the abdominal organs: Abstract of thesis. dis. . Doctor of Medical Sciences - Saratov, 1994. -19 p.

135. Industry standards for the scope of examination and treatment in obstetrics, gynecology and neonatology. M.: Triada-X, 1999. - 246 p.

136. Panfilova E.L. Chronic inflammation of the uterine appendages: rationale for intensive FNC therapy: Abstract of thesis. diss. . Ph.D. honey. Sci. M., 1997. -18 p.

137. Pastukhov M.I. Comparative study of some phlogotropic agents in the treatment of inflammatory diseases of the female genital area: Abstract of thesis. diss. . Ph.D. honey. Sci. Sverdlovsk, 1970. - 22 p.

138. Petrova M.S. Morphofunctional state of the uterine appendages under the influence of the mud preparation “Eplir” in normal conditions and during inflammation: Abstract of thesis. diss. . Ph.D. honey. Sci. Tomsk, 1999. - 18 p.

139. Petrova M.S., Tikhonovskaya O.A., Logvinov S.V. Ultrastructural changes in the ovaries during experimental inflammation / Actual. Question Experimental and clinical morphology. Ed. S.V. Logvinova. -Tomsk, SSMU, 2002. Issue 2. - pp. 158-160.

140. Podzolkova N.M., Strizhakov A.N., Strugatsky V.M. Pathogenesis of pain in chronic salpingo-oophoritis // Obstetrics. and gynecol. 1984. - No. 8. - P.5-8.

141. Podzolkova N.M., Zheleznov B.I., Strizhakov A.N. Clinical and morphological aspect of purulent inflammatory diseases of the uterine appendages // Obstetrics. and gynecol. 1991. - No. 9. - P.45-50.

142. Pozdnyakova L.I. On the question of the mechanism of the immunoregulatory effect of peloids // Immunological concepts in balneology. Pyatigorsk, 1987. - P.30-35.

143. Posiseeva L.V., Boyko E.L., Shekhlova N.V. A method for restoring ovarian function. BIPM No. 25 (I part), 09/10/2000. - P. 236.

144. Radionchenko A.A., Kreimer A.Ya. Vibration therapy in obstetrics and gynecology. Tomsk, 1986. - 248 p.

145. Reproductive health: in 2 volumes. T. 1. Common infections: Transl. from English/Ed. L.G. Keita, G.S. Berger, D.A. Edelman. -M.: Medicine, 1988. 400 p.

146. Romanova A.P. Microwave therapy in postoperative rehabilitation of patients with inflammatory tubo-ovarian formations: Abstract of thesis. diss. . Ph.D. honey. Sci. - Tomsk, 2002. - 19 p.

147. Guide to contraception. R.F. Hatcher, D. Koval, F. Guest et al. / Russian international H3flaHHe: Bridging the Gap Communications, 1994. 504 p.

148. Guide to reproductive health / Ed. IN AND. Kulakova, V.N. Serova, L.V. Adamyan et al. -M., Triada-X, 2001. 568 pp.

149. Ryzhova G.L., Bratchikov A.V., Solomatina I.P. and others. On the organic composition of an aqueous extract from medicinal mud and brine of Lake Karachi // Mud preparations. - Tomsk, 1981. P.13-18.

150. Ryzhova G.L., Kravtsova S.S., Prokopova E.I. Gas chromatographic study of aromatic carbohydrates in the brine of Lake Karachi // Preparations from medicinal mud and brine. - Tomsk, 1983. - P.3-6.

151. Ryzhova G.L. Khasanov V.V. Nature complex of the Tomsk region. - Tomsk, 1995.-68 p.

152. Rymashevsky N.V., Rymashevsky A.N., Okorokov A.A. and others. Prevention of purulent-inflammatory complications in obstetric and gynecological practice // Gedeon Richter in the CIS. No. 3 (7), 2001. - P.64-66.

153. Savelyeva G.M., Antonova L.V. and others. New approaches in the diagnosis and treatment of inflammatory diseases of the uterine appendages // Vestn. Ross. acad. honey. Sci. 1997. - No. 2. - pp. 12-16.

154. Savitsky G.A. Ivanova R.D. Some results of the study of the hematofollicular barrier in the ovary // Obstetrics. and gynecol. 1981. - No. 12. -P.8-11.

155. Savitsky G.A., Ivanova R.D., Shcheglov I.Yu., Popov P.A. Surgical treatment of pelvic pain syndrome in gynecology. St. Petersburg, 2000. - 138 p.

156. Samorodinova L.A. Methodology for creating experimental infectious salpingitis // Bulletin. let's experiment biol. and medicine. 1966. - No. 2.-S. 123-124.

157. Samorodinova L.A., Malkova L.N., Sychev E.P. and others. Risk factors for the development of purulent inflammatory diseases of the internal genital organs in women // Journal. obstetrics and women's diseases (Special issue). - St. Petersburg, 1998. P.35-36.

158. Samutin N.M., Krivobokov N.G. Current problems of peloid therapy // Issue. balneology, physiotherapy and medical treatment. physical culture. - 1997. - No. 3. -P.33-35.

159. Saratikov A.S., Vengerovsky A.I., Prishchep T.P. Adjuvant disease (morphology, pathogenesis, experimental therapy). - Tomsk: Tomsk University Publishing House, 1983. 104 p.

160. Saratikov A.S., Vengerovsky A.I., Burkova V.N. and ■ others. Anti-inflammatory and analgesic properties of esobel // Chem.-farm. magazine T. 35, No. 5. - 2001. - P.20-21.

161. Sarkisov D.S. Essays on the history of general pathology. M.: Medicine, 1993 -512 p.

162. Seitenov E.S., Akhanova E.K. Musabaeva M.A. Magnetic therapy and mud therapy for exacerbation of inflammatory processes in the uterine appendages // Health. Kazakhstan. 1988. - No. 9. - P.54-55.

163. Semenov B.N. Nesterov N.I., Anosov I.A. and others. On the organization of medical rehabilitation services // Issue. balneology, physiotherapy and medical treatment. physical culture. 1998. - No. 2. - P.44-47.

164. Serov V.V., Shekhter A.B. Connective tissue (Functional morphology and general pathology). - M.: Medicine, 1981. 312 p.

165. Serov V.N., Ilyenko J.I.H., Popova O.N. The influence of bifidumbacterin forte on anti-endotoxin immunity in chronic inflammatory diseases of the female genital organs // Vestn. Ross, Assoc. obstetrics-gynec. -1996. - No. 3. P.75-77.

166. Serov V.N., Kozhin A.A., Tikhomirov A.JI. and others. Pathogenesis of secondary reproductive disorders in women // II Congress of Ross. Ass. obstetrics-gynec. M., 1997. - P.96-98.

167. Serov V.N., Kudryavtseva L.I. Benign tumors and tumor-like formations of the ovaries. M.: Triada-X, 1999. - 152 p.

168. Serov V.N., Tikhomirov A.L., Lubnin D.M. Modern principles of therapy for inflammatory diseases of the female genital organs // Methodological manual for obstetricians and gynecologists, ed. 2, add. M., 2003.-24p.

169. Sidorova I.S., Guriev T.D. Laparoscopy in the treatment of tubo-peritoneal infertility // Endoscopy in gynecology (Ed. V.I. Kulakov, L.V. Adamyan), M., 1999. P.454-456.

170. Slaveykova O.V. The effect of sinusoidal modified currents of various parameters in chronic infectious salpingitis // Issue. balneology, physiotherapy and medical treatment. physical culture. 1992. - No. 1. - P.28-33.

171. Smetnik V.P., Tumilovich L.G. Non-operative gynecology: A guide for doctors. St. Petersburg, SOTIS, 1995. - 224 p.

172. Solsky Y.P., Ivanyuta L.I. Inflammatory diseases of the female genital organs. M., 1975. - 215 p.1

173. Strizhakov A.N., Kagramanova Zh.A. The role of laparoscopy in the diagnosis and treatment of ascending chlamydia in women with tubo-peritoneal infertility // Endoscopy in gynecology (Ed. V.I. Kulakov, L.V. Adamyan), M., 1999. P.445-448.

174. Strugatsky V.M. Physical factors in obstetrics and gynecology. M.: Medicine, 1981. - 205 p.

175. Strugatsky V.M., Arslanyan K.N., Grechikhina N.F. Early restorative physiotherapy after surgical laparoscopy in gynecology // Obstetrics. and gynecol. 1995. - No. 5. - P.46-49.

176. Strugatsky V.M., Evseeva M.M. Restorative treatment of patients with chronic pelvic inflammation: experience of out-of-resort hydro-, peloid- and electrotherapy // Mat. IV Ross, Mother and Child Forum. T.P. - M., 2002.-P.383-384.

177. Strugatsky V.M., Evseeva M.M., Silantyeva E.S. Improving electrotherapy of chronic inflammation of the uterine appendages: new technologies // Mat. IV Ross, Mother and Child Forum. T.P. - M., 2002. - P.384-385.

178. Strugatsky V.M., Silantyeva E.S., Korneeva I.E. and others. Rationale and effectiveness of restorative treatment after surgical correction of tubo-peritoneal infertility: hemodynamic aspect // Obstetrics. and gynecol. 2003. - No. 1. - P.33-34.

179. Strukov A.I., Kaufman O.Ya. Granulomatous inflammation and granulomatous diseases. -M.: Medicine, 1989. 181 p.

180. Suvorov A.P., Kobzev Yu.A., Golbraykh E.B. and others. Experience of the center of therapeutic urology: Mater, symp. “New in urology, andrology, dermatovenereology” (Moscow). Publishing house SMU, Saratov, 1996. - 19 p.

181. Tardaskina A.V., Kokh L.I., Efimenko Yu.V. Clinical and experimental parallels in the pathology of parovarium // Issue. plastic, reconstruction surgeon, and wedge, anatomy. - Tomsk, 2002. - T.1. - P.153-158.

182. Tardaskina A.V. The role of parovarium in disruption of the reproductive potential of the ovaries during inflammation of the uterine appendages: Abstract of thesis. diss. . Ph.D. honey. Sci. Tomsk, 2002. - 19 p.

183. Tikhonovskaya O.A. Modeling of acute and chronic inflammation of the uterine appendages // Youth and scientific and technical progress: Proc. report - Tomsk, 1986.-P.76.

184. Tikhonovskaya O.A. The influence of brine and mud extract from Lake Karachi on the morphofunctional state of the uterine appendages during experimental inflammation // Issue. balneology, physiotherapy and medical treatment. physical culture. - 1998. -№5. P.33-35.

185. Tikhonovskaya O.A. Structural changes in the uterine appendages during inflammation after complex treatment using peloid preparations // Current issues in experimental morphology: Coll. scientific tr. Tomsk, 1999. - P.89-90.

186. Tikhonovskaya O.A., Logvinov S.V., Evtushenko I.D., Nevostruev S.A. The influence of eplier phonophoresis on ultrastructural changes in the ovaries and oviducts during experimental inflammation // Morphology. 2000. - T. 117. - Issue 2. - P.68-72.

187. Tikhonovskaya O.A. General patterns and mechanisms of tissue disorders of the uterine appendages during inflammation and complex treatment with the use of mud preparations: Abstract of thesis. dis. . Dr. med. Sci. - Tomsk, 2000.-38 p.

188. Torchinov A.M. Possibilities for increasing the effectiveness of prevention and treatment of acute inflammatory diseases of the internal female genitalia: Abstract of thesis. dis. . Dr. med. Sci. - M., 1985. 42 p.

189. Trapeznikova N.K., Orlova L.P. On the issue of introducing into practice new achievements in the field of therapeutic use of mud preparations // Therapeutic use of peloids and preparations based on them. Tomsk, 1988. -P.28-35.

190. Trdatyan A.A. Application of ultrasound in gynecology // Selected issues of obstetrics and gynecology. - Novokuznetsk, 1970. - T. 4. - P.212-217.

191. Ulashchik V.S., Danusevich I.K. Pharmacological basis of electro- and phonophoresis. Minsk, 1975. - 216 p.

192. Ulashik B.C. Essays on general physiotherapy. Minsk, 1994. - 200 p.

193. Ulashik B.C. Features of the distribution of drugs in the body under the influence of various types electric current// Question balneology, physiotherapy and medical treatment. physical culture. 1997. - No. 4. - P.6-7.

194. Ulashik B.C. On the influence of physical factors on the action of other therapeutic agents (to the problem of therapeutic interference) // Issue. balneology, physiotherapy and medical treatment. physical culture. 1998. - No. 3. - P.46-49.

195. Fedorova T.A., Abubakirova A.M., Gasparov A.S. The use of discrete plasmaphoresis in the treatment of chronic recurrent salpingoophoritis in women of reproductive age // Ways of development of modern gynecology: Proc. report M. 1995. - P.83.

196. Fedorova T.A. Principles of treatment and rehabilitation of patients with chronic nonspecific salpingo-oophoritis using plasmapheresis: Abstract of thesis. dis. . Dr. med. Sci. M., 1996. - 42 p.

197. Fedorova T.A., Abubakirova A.M., Dubnitskaya L.V. and others. Laparoscopy in patients with chronic salpingoophoritis // Endoscopy in gynecology (Ed. V.I. Kulakov, L.V. Adamyan), M., 1999. P.458-460.

198. Fillipov O.S., Radionchenko A.A., Zhabina E.S. Method for rehabilitation of patients after tubal surgery. BIPM No. 10. - 04/10/2000. -P.15.

199. Fletcher R., Fletcher S., Wagner E. Clinical epidemiology. Fundamentals of evidence-based medicine. Per. from English M.: Media Sphere, 1998. - 352 p.

200. Franchuk A.E. Immunological characteristics of patients operated on for chronic purulent salpingo-oophoritis // Obstetrics. and gynecol. 1983. - No. 9. - P.68-69.

201. Khmelnitsky O.K. Pathology of the fallopian tubes. - D.: Medicine, 1982. 22 p.

202. Khmelnitsky O.K. Pathomorphological diagnosis of gynecological diseases. St. Petersburg, 1996. - 197 p.

203. Khomasuridze A.G., Sakandelidze V.M. Immunobiological changes in married couples for chronic inflammation of the genital organs // J. on immunorehabilit. 1997. - No. 6. - P.132-134.

204. Tsaregorodtseva M.V., Orlov V.I., Zaitseva A.V., Shamraeva E.N. Autoimmune aspects of chronic salpingitis // Mat. IV Ross, Mother and Child Forum. T.N. - M., 2002. - P.450-451.

205. Tsarfis P.G. By the forces of nature, by the mind of a doctor. - Mn.: Higher. school, 1989. -S. 18-49.

206. Tsarfis P.G., Kiselev V.B. Therapeutic mud and other natural coolants. M., 1990. - 127 p.

207. Tsarfis P.G., Frenkel I.D. Biochemical foundations of physical therapy. -M., 1991.- 158 p.

208. Tsvelev Yu.V., Kira E.F., Plekhanov A.N. and others. Clinical and bacteriological diagnostics and complex treatment of chronic salpingo-oophoritis // Vestn. Ross. Ass. obstetrics-gin. - 1996. - No. 33. P.59-61.

209. Tsvelev Yu.V., Kira E.F., Baskakov V.P., Kocherovets V.I. Bacterial infection in obstetrics and gynecology // Journal of Obstetrics and Women's Diseases (special issue). 1998. - pp. 188-189.

210. Choi Son O.K. Clinical and pathophysiological features and complex therapy of exacerbation of chronic salpingoophoritis using physical factors: Abstract of thesis. dis. . Ph.D. honey. Sci. - M., 1983. 20 p.

211. Cherepanova M.N., Kotova T.I. Chemical composition of organic matter of therapeutic mud // Mud preparations. Tomsk, 1981. - P.27-29.

212. Shakhova S.S. The influence of the drug of natural origin Eplir on the morphofunctional state of cells of the mononuclear phagocyte system in acute toxic hepatitis in an experiment: Abstract of thesis. diss. . Ph.D. honey. Sci. - Tomsk, 1996. - 18 p.

213. Shekhter A.B. Sclerotic processes // General human pathology. M.: Medicine, 1990. - T.2. - P.124-150.

214. Shtyrov S.V. Morphofunctional state of the ovaries in tubal and peritoneal infertility: Abstract of thesis. dis. . Ph.D. honey. Sci. M., 1990. -22 p.

215. Shustov L.P. Extracts of silt sulfide mud and their medicinal uses. Tomsk, 1996. - 182 p.

216. Shukhman M.G., Minakov A.A., Cherkasov I.V., Nikolaeva E.V. The effect of laparoscopy in the diagnosis and treatment of female infertility // Endoscopy in gynecology (Ed. V.I. Kulakov, L.V. Adamyan), M., 1999. P.191-192.

217. Helen R. J. Nonspecific resistance to infection // Immunological aspects of infectious diseases (ed. J. Dick). -M.: Medicine, 1982. P.14-35.

218. Endoscopy in gynecology/Ed. G.M. Savelyeva. - M.: Medicine. 1983.-200 p. ,

219. Yakovlev S.V., Yakovlev V.P. Antibacterial therapy in tables // Consilium medicum. -1999.-T. 1. -No. 1. P.25-33.

220. Yakovlev S.V. Form of antibacterial therapy and prevention of infections in obstetrics and gynecology // Gynecology. - 2001. T.I. - No. 3. - P.3-9.

221. Yalovega Yu.A. A complex method of treating patients with purulent-inflammatory diseases of the uterine appendages using a magnetic laser after organ-preserving operations: Abstract of thesis. dis. . Ph.D. honey. Sci. - Tomsk, 2003. - 15 p.

222. Yasnogorodsky V.G. Scientific basis for the therapeutic and prophylactic use of natural and modern preformed factors // Abstracts. report IV All-Russian Congress of Physiotherapists and balneologists. M. 1994 - P.3-9.

223. Ajonuma L.C., Ng E.N., Chan N.S. New insights into the mechanisms underlying hydrosalpinx fluid formation and its adverse effect on IVF outcome// Hum. Reprod. Update. 2002. - V.8 - No. 3. - P.255-264.

224. Alatas C., Aksoy E., Akarsu C. et al. Hemodynamic assessment in pelvic inflammatory disease by transvaginal color Doppler ultrasonography // Eur. J. Obstet. Gynecol. 1996. - V.70 - P.75-8-22.

225. Aral S.O. Sexually transmitted diseases: magnitude, determinants and consequences // Int. J. STD&AIDS. 2001. - V. 12. - No. 4. - P.211-215.

226. Arora M., Malhotra S., Sharma M. Role of Chlamydia trachomatis in pelvic inflammatory disease // Indian. J. Med. Res 1992. - V.95- P.41-42.

227. Ault K.A., Faro S. Pelvic inflammatory disease. Current diagnostic criteria and treatment guidelines//Postgrad. Med. J.- 1993. V.93-P.85-86, 89-91.

228. Baier H. Das vegetative nerve system in neirner badeutung fur die Balneotherapie der trauenkran kneiten// Z. Angew. Bader. Und Klimatheilkv. -1976. V.23. - No. 2. - S. 164-181.

229. Balak K. Ambulathi pelloidoa balneotherapia v gynekologii // Cs. Genek. -1969. -No. 34. S.135-137.

230. Balkwill F.R. Possible role of ovarian epithelial inflammation in ovarian cancer// J. Natl. Cancer Inst. 2000. - V.21. - No. 7. - P.1456-1467.

231. Bassil S, Le-Bouedes G, Mage G et al. The role of anti-inflammatory agents in the treatment of acute salpingitis. A randomized study of 40 patients with celioscopy control // J. Gynecol. Obstet. Biol. Reprod. Paris. 1991. - V.20. -No. 8. - P.1063-1067.

232. Battaglia D.F., Krasa H.B., Padmanabhan V. et al. Endocrine alterations that underlie endotoxine-induced disruption of the follicular phase in ewes // Biol. Reprod. 2000. - No. 1. - P.45-63.

233. Baveja G., Saini S., Sangwan K., Arora D.R. A study of bacterial pathogens in acute pelvic inflammatory disease // J. Commun. Dis. - 2001. V.33. - No. 2. -121-125.

234. Bevan CD, Johal BJ, Mumtaz G, et al. Clinical, laparoscopic and microbiological findings in acute salpingitis: report on a United Kingdom cohort // Br. J. Obstet. Gynaecol. 1995. - V. 102 - P 407-414

235. Blaner K.L., Collins R.L. The effect of intraperitoneal progesterone on postoperative adhesion for pregnancy in rabbits // Fertil. Steril. 1988. - V.49. -P.144-149.

236. Broadnax J. Pelvic inflammatory disease/ Ambulatory Pediatric Care, 2nd, (Ed. by R.A. Dersewitz), Philadelphia// J.B. Lippincott. 1993. - P.471-475.

237. Brookoff D. Compliance with doxycycline therapy for outpatient treatment of pelvic inflammatory disease // South. Med. J. 1994. - V.87. - No. 11. - P.1088-1091.

238. Bjersing L. Maturation morphology and endocrine function of the ovarian follicle//Adv. Exp. Med. Biol. 1982. - V.147. -No. 2. -P.l-14.

239. Bogavant H, Adams S, Terranova P et al. Autoimmune ovarian inflammation triggered by proinflammatory (Th 1) T cells is compatible with normal ovarian function in mice // Biol. Reprod. 1999. - V.61. - No. 3. - P.635-642.

240. Bolte A., Tibach H.W. Genital infection. Infektiologische probleme in gynekologie und geburtshilfe. Steinkopff Verlag. Darmstad, 1990. - 270 h.

241. Bowman M.C., Cooke I.D. Comparison of fallopian tube intraluminal pathology as assessed by salpingoscopy with pelvic adhesions // Fertile. Steril. -1994. V.61. -P.464-469.

242. Buculmez O., Arid A. Leukocytes in ovarian function // Hum. Reprod. Update. 2000. -№1. -P.l-15.

243. But I., Reljic M. The value of serum CA 125 for the management of tubo-ovarian abscesses // Wien. Klin. Wochenschr. 2000. - V.24. - P. 1044-1048

244. Byrne G.I., Krueger D.A. Lymphokine-mediated inhibition ofChlamydia replication in mouse fibroblasts is neutralized by anti-gamma interferon immunoglobulin // Infect. Immun. 1983. - V.42. - P. 1152-1158.

245. Cariton A., Eddy Ph. D., Carl J. Anatomy and physiology of the fallopian tube // Clin. Obstet. Gynecol. 1980. - V.23. - No. 4. -P.l 177.

246. Cates W. Jr., Joesoef M.R., Goldman M.B. Atypical pelvic inflammatory disease: can we identify clinical predictors? // Am. J. Obstet. Gynecol. 1996. - V.169. -P.341-346.

247. Champion J.D., Piper J., Shain R.N. et al. Minority women with sexually transmitted diseases: sexual abuse and risk for pelvic inflammatory disease // Res. Nurs. Health. 2001. - V.24. - No. 1. - P.38-43.

248. Charming C.P., Anderson L.D., Hoober D.J. The role of nonsteroidal regulations in control of oocyte and follicular maturation // Recent. Prog. Horm. Res. 1982. - V.38. - No. 6. - P.331-408.

249. Cibula D., Kuzel D., Fucikova Z. et al. Acute exacerbation of recurrent pelvic inflammatory disease. Laparoscopic findings in 141 women with a clinical diagnosis // J. Reprod. Med. 2001. - V.46. - No. 1. - P.49-53.

250. Corson S. L., Batzer F. R., Gocial B. et al. Intraobserver and interobserver variability in scoring laparoscopic diagnosis of pelvic adhesions // Hum. Reprod.1995. V.10.-P.161-164.

251. Crowley T., Low N., Turner A. et al. Antibiotic prophylaxis to prevent postabortal upper genital tract infection in women with bacterial vaginosis: randomized controlled trial // B.J.O.G. 2001. - V.108. - No. 4. - P.396-402.

252. Dan M., Samra Z., Katz A. Etyology of acute pelvic inflammatory disease. Proven by laparoscopy // Sex. Transm. Dis. 1993. - V.20. - P.158-163.

253. De Punzio C., Neri E., Guazzelli G. Incidence of Chlamydia trachomatis in women with PID: effectiveness of therapy // Acta. Eur. Fertil. - 1995. V.26. -P.149-151.

254. De Vries J.E. Immunosuppressive and anti-inflammatory properties of interleukin 10 // Ann. Med. 1995. - V.27. - P.537-541.

255. Dieterle S., Mesrogli M., Triebler B. et al. Is there a correlation between tubal occlusions in chronic salpinginis and urogenital Chlamydia infections // Geburtshilfe. frauenheilkd. 1994. - V.54. - No. 8. - P.455-459.

256. Doody K.J., Dunn R.C., Buttram V.C.J. Recombinant tissue plasminogen activator reduces adhesion formation in a rabbit uterine horn model// Fertil. Steril.- 1989. -V.51. -P.509-512.

257. Downing S.J., Tay J.I., Maguiness S.D. et al. Effect of inflammatory mediators on the physiology of the human Fallopian tube // Hum. Fertil. - 2002. - V.5. No. 2.- P.54-60.

258. Duron J. J., Keilani K., Barrat C. et al. Peroperative contamination of the peritoneal cavity with micro-foreignbodies // Chirurgie. - 1996. V. 121. - No. 3. - 175-180.

259. Eschenbach D.A., Wolner-Hanssen P., Hawes S.E. et al. Acute pelvic inflammatory: associations of clinical and laboratory findings with laparoscopic findings// Obstet. Gynecol. 1997. - V.89. - No. 2. - P. 184-192.

260. Evrard V.A.C., De Bellis A., Boekx W. Peritoneal healing after fibrin glue application: a comparative study in a rat model // Hum. Reprod. - 1996. - No. 11.- P.1877-1880.

261. Faro S., Martens M., Maccato M. Vaginal flora and pelvic inflammatory disease // Am. J. Obstet. Gynec. 1993. - V. 169. - P.470-474.

262. Furuya M., Murakami T., Sato O. et al. Pseudoxanthomatous and xanthogranulomatous salpingitis of the fallopian tube: a report of four cases and a literature review // Int. J. Gynecol. Pathol. 2002. - V.21. - No. 1. - P.56-59.

263. Gardo S. Inflammation of the pelvis minor // Orv. Hetil. 1998. - V.139. -No. 36.-P.2115-2120.

264. Gareen I.F., Greenland S., Morgenstern H. Intrauterine devices and pelvic inflammatory disease: meta-analyses of published studies, 1974-1990 // Epidemiology. 2000. - V.l 1. - P.589-597.

265. Gerber V., Wilken H., Zachrias K. Treatment of acute salpingitis with tetracycline/metronidazole: a second-look laparoscopy study// Geburshilfe. Frauenheilkd. 1992. -V.52. -No. 3. -P.l65-170.

266. Goecke C. Balneogynecologie in der vorsoge // Arbeitsmed. Socialmed. 1986. -V.21. - No. 9. - S.256-258.

267. Goldstein F.W., Acar I.F. Microbiology des salpingites. La strategie du traitment antibiotigue // Contracept. Fertil. Sex. 1994. - V.l2. - No. 1. - P.220c222.

268. Gordts S., Campo R., Rombauts L. et al. Transvaginal salpingoscopy: An office procedure for infertility investigation // Fertil. Steril. 1998. - V70. - No. 2. -P.523-526.

269. Grimes D.A. Intrauterine device and upper-genital-tract infection/ Lancet. - 2000. V.356(9234). - P.1013-1019.

270. Gurgan T, Urman V, Yarali H et al. Salpingoscopic findings in women with occlusive and nonocclusive salpingitis isthmica nodosa // Fertil. Steril. 1994. -V.61. -No. 3. -P.461-463.

271. Gurgan T., Yaraly H., Bukulmez O. Salpingoscopy // Endoscopy in gynecology (Ed. by V.I. Kulakov, L.V. Adamian), Moscow, 1999. P. 436-443.

272. Haddix A.C., Hillis S.D., Kassler W.J. The cost effectiveness of azithromycin for Chlamydia trachomatis infections in women // Sex. Transm. Dis. - 1995. - V.22. No. 5. - P.274-280.

273. Haggerty C.L., Ness R.B., Amortegui A. Endometritis does not predict reproductive morbidity after pelvic inflammatory disease // Am. J. Obstet. Gynecol. 2003. - V188. - No. 1. - P.141-148.

274. Hefler L., Temfer C., Heinzl H. et al. M3/m21 serum levels in women with adnexal masses and inflammatory disease // Int. J. Cancer. 1998. - V.79. - No. 4. -P.434-438.

275. Henry-Suchet J., Catalan F., Loffredo V. et al. Chlamydia trachomatis associated with chronic iflammation in abdominal specimens from women selected for tuboscopy // Fertil. Steril. 1981. - V.36. - P.559-605.

276. Hemy-Suchet J. PID: clinical and laparoscopic aspects // Am. N.Y. Acad. Sci. -2000. V.900. - P.301-308.

277. Herschlag A., Seiofer D.B., Carcangiu M.L. et al. Salpingoscopy: light microscopic and electron microscopic correlations // Obstet. Gynecol. 2000. -V.77. -P.399-405.

278. Hillier S.G., Tetsuka M. An anti-inflammatory role for glucocorticoids in the ovary? // J. Reprod. Immunol. 1998. - V.39. - No. 1-2. - P.21-27.

279. Holdmahl L. The role of fibrinolysis in adhesion formation// Eur. J. Surg. Suppl. 1997. - V.577. -P.24-31.

280. Hubacher D., Lara-Ricalde R., Taylor DJ. et al. Use of copper intrauterine devices and the risk of tubal infertility among nulligravid women // N. Engl. J. Med. 2001. - V.345. - P.561-567.

281. Jamieson D.J., Duerr A., ​​Macasaet M.A. et al. Risk factors for a complicated clinical course among women hospitalized with pelvic inflammatory disease // Infect. Dis. Obstet .Gynecol. 2000. - V 8. - P.88-93.

282. Jossens M.O.R., Sweet R.L. Pelvic inflammatory disease: Risk factors and microbial etiologies // J. Obstet. Gynecol. Neonatal. Nurs. 1993. - V.22. - No. 2. -P.169-172.

283. Karagyezov I., Burgudzhieva T. Krutimen treatment with ultrasound for subacute inflammatory gynecological diseases // Obstetrics. gynek. - 1984. No. 4. - P.338-340.

284. Kontoravdis A., Hassan E., Hassiakos D. et al. Laparoscopic evaluation and management of chonic pelvic pain during adolescence // Clin. Exp. Obstet. Gynecol. 1999. - V.26. - No. 2. - P.76-77.

285. Kottmann L.M. Pelvic inflammatory disease: clinical overview // J. Obstet. Gynec. Neonatal. Nurs. 1995. - V.24. - P.759-767.

286. Kovacs E.J. Fibrogenic cytokines: the role of immune mediators in the development of scar tissue// Immunol. Today. - 1991. V. 12. - P. 17-23.

287. Landers D.V., Sung M.L., Bottles K. et al. Does addition of anti-inflammatory agents to antimicrobial therapy reduce infertility after murine chlamidial salpingitis?// Sex. Transm. Dis. 1993. - V.20-№3. -P.121-125.

288. Le-Bouedes G., Pouly J.L., Canis M. et al. Acute salpingitis celioscopy before and after treatment: 110 cases // J. Gynecol. Obstet. Biol. Reprod. Paris. - 1991. -V.20. No. 5. - P.680-684.

289. Leese H.J., Tay J.I., Reischl J., Downing S.J. Formation of Fallopian tubal fluid: role of a neglected epithelium // Reproduction. 2001. - V.121. - No. 3. -P.339-346.

290. Lepine L.A., Hillis S.D., Marchbanks P.A. et al. Severity of pelvic inflammatory disease as a predictor of the probability of live birth // Am. J. Obstet. Gynecol. 1998. - V. 178. - No. 5. - P.977-981.

291. Levgur M., Duvivier R. Pelvic inflammatory disease after tubal sterilization: a review // Obstet. Gynecol. Surv. 2000. - V.55. - No. 1. - P.41-50.

292. Liles W.C., Van Voorhis W.C. Review: nomenclature and biological significance of cytokines involved in inflammation and the host immune response//J. Infect. Dis. 1995. - V.172.-P.1573-1580.

293. Lou Y.H., Park K.K., Agesborg S. et al. Retargeting T-cell mediated inflammation: a new perspective on autoantibody action// J. Immunol. - 2000. -V.16. -No. 10 P.5251-5257.

294. Macmillan S. Chlamydia trachomatis in subfertile women undergoing uterine instrumentation. The clinician's role // Hum. Reprod. 2002. - V.17. - No. 6. - P.1433-1436.

295. Mandegar M., Schaff E.A. Is the clinical, spectrum of gonorrhea changing? // J. Ad. Health. 1995. - V.17. -P.123-127.

296. Marana R., Luciano A. A., Muzii L. et al. Laparoscopy versus laparotomy for ovarian conservative surgery: a randomized trial in the rabbit model // Am. J. Obstet. Gynecol. 1994. - V.171. -P.861-864.

297. Marks C., Tideman R.L., Estcourt C.S. et al. Assessment of risk for pelvic inflammatory disease in an urban sexual health population // Sex. Transm. Infect. -2000. V.76. - No. 6. - P.470-473.

298. Martens M.G. et al. Comparison of cefotaxine, cefoxitin and the treatment of uncomplicated pelvic inflammatory disease // J. Antimicr. Chemoter. 1990. -V.26 (Suppl).-P.34-43.

299. Maruotti T., Reverberg L. Pelvic inflammatory disease // Medicina Firenze. -1990. V.10. - No. 2. - P.108-128.

300. McGee Z.A., Jensen R.L., Clemens C.M. et al. Gonococcal infection of human fallopian tube mucosa in organ culture: relation of mucosal tissue TNF-alphaconcentration to sloughing of ciliated cell// Sex. Transm. Dis. 1999. - V.26. - No. 3. - P.160-165.

301. McNeeley S.G., Hendrix S.L., Mazzoni M.M. et al. Medically found, cost-effective treatment for pelvic inflammatory disease and tuboovarian abscess // Am. J. Obstet. Gynecol. 1998. - V.178. - No. 6. -P.1272-1278.

302. Mercer LJ. Pelvic inflammatory disease decision making in the pharmacy and therapeutics committee // J. Reprod. Med. 1988. - V.33. - No. 1. - P.135-141.

303. Miyake Y., Hirokama M., Kanahara T. et al. Diagnostic value of hair shafts and squamous cell in peritoneal washing cytology // Acta. Cytol. 2000. - V.44. -No. 3. -P.356-360.

304. Molander P., Cacciatore V., Sioberg J., Paavonen J. Laparoscopic management of suspected acute pelvic inflammatory disease// J. Am. Assoc. Gynecol. Laparosc. - 2000. V.7. - No. 1. - P. 107-110.

305. Molander P., Sjoberg J., Paavonen J. et al. Transvaginal power Doppler findings in laparoscopically proven acute pelvic inflammatory disease // Ultrasound Obstet Gynecol. 2001 - V 17 - P.233-238

306. Morgan RJ. Clinical aspects of pelvic inflammatory disease // Am. Fam. Physician. 1996. - V.43. - P.l 127-1135.

307. Murdoch W.J., Wilken C., Young D.A. Sequence of apoptosis and inflammatory necrosis within the formative ovulatoty site of sheep follicles // J. Reprod. Fertil. 1999. - V.l 17. - No. 2. - P.325-329.

308. Murdoch W. J. Proteolytic and cellular death mechanisms in ovulatory ovarian rupture // Biol. Signals. Recipe. 2000. - V.9. - No. 2. - P. 102-114.

309. Ness R.B., Grisso J.A., Cottreau C. et al. Factors related to inflammation of the ovarian epithelium and risk of ovarian cancer // Epidemiology. 2000. - V.12. -No. 2. - P.97-98.

310. Ness R.B., Soper D.E., Holley R.L. et al. Hormonal and barrier contraception and risk of upper genital tract disease in the PID Evaluation and Clinical Health (PEACH) study // Am. J. Obstet. Gynecol. 2001. - V. 185. - P. 121-127.

311. Newkirk G.R. Pelvic inflammatory disease: a contemporary approach // Am. Fam. Physician. 1996. - V.53. - No. 4.- P. 1127-1135.

312. Olson K.K., Townson D.N. Prolactin-induced expression of intercellular adhesion molecule-1 and the accumulation of monocytes/ macrophages during regression of the rat corpus luteum// Biol. Reprod. 2000. - No. 6. - P.1571-1578.

313. Ordonez J.L., Dominguez J., Evrard V., Koninckx P.R. The effect of training and duration of surgery of adhesion formation in the rabbit model // Endoscopy in gynecology (Ed. by V.I. Kulakov, L.A. Adamian), Moscow, 1999. P.56-68.

314. Orfila J., Haider F. Can various antibiotics be combined for treating salpingitis // Rev. Fr. Gynecol. Obstet. 1992. - V.87. - No. 3. - P. 117-119.

315. Ostensen, Almberg, Koksvic. Sex, reproduction and gynecological disease in yang adults with a history of juvenile chronic arthritis // J. Rheumatol. 2000. -№7. - P.1783-1787.

316. Paavonen J., Feisala K., Heinonen P.K. Microbiological and histopathological finding in acute pelvic inflammatory disease // Brit. J. Obstet. Gynecol 1987. -V.94. - No. 34 - P.454-460.

317. Paavonen J., Lentinen M. Chlamydial pelvic inflammatory disease // Hum. Reprod. Update. 1996. - V.2. - No. 1. - P.519-529.

318. Paavonen J. Pelvic inflammatory disease. From diagnosis to prevention // Dermatol. Clin. 1998. - V.16. - No. 4 - P.747-756.

319. Padian N.S., Washington A.E. Pelvic inflammatory disease. A brief overview // Ann. Epidemiol. 1994. - V.4. - No. 4. - P. 128-132.

320. Pavletic A. J., Eschenbach D. A., Wolner-Hanssen P., et al. Infertility following pelvic inflammatory -disease // Infect. Dis. Obstet. Gynecol. 1999. - V.7. -P.145-152.

321. Paternoster D.M., Costantini W., Uglieeti A. et al. Congenital or torsion-induced abscesse of Fallopian tubes. Two case reports // Minerva Ginecol. - 1998. V.50. -No. 5. -P.191-194.

322. Patton D.L., Kuo C.C., Wang S.P. Halbert S.A. Distal, tubal obstruction induced by repeated C. trachomatis salpingeal infections in pigtailed macaques // J. Infect. Dis. 1987. - V.155. - P.1292-1299.

323. Patton D.L., Kuo C.C., Wang S.P. Brenner M.D. et al. Chlamydial infection of subcutaneous fimbrial transplants in cynomolgus and rhesus monkeys // J. Infect. Dis. 1987. - V.155. - P.229-235.

324. Patton D.L., Kuo C.C. Histopathology of Chlamydia trachomatis salpingitis after primary and repeated reinfections in the monkey subcutaneous pocket model // J. Reprod. Fertil. 1999. - V.85. - P.647-656.

325. Peipert JF, Ness RB, Blume J, et al. Clinical predictors of endometritis in women with symptoms and signs of pelvic inflammatory disease // Am. J. Obstet. Gynecol. 2001. - V.184. - P.856-866.

326. Perkins J.D., Carter C., Kines D.C. Bilateral ruptured tubo-ovarian abscesses following bilateral tubal ligation several years earlier // J. Natl. Med. Assoc. -1998. V.90. -№11.- P.689-691.

327. Peterson H.B., Galaid E.L., Cates W. Jr. Pelvic inflammatory disease // Med. Clin. North. Am. - 1990. - V.74. -No. 1. -P.1603-1615.

328. Piyadigamage A., Wilson J.D. An audit of outpatient management of pelvic inflammatory disease // Int. J. STD. & AIDS. 2002. - V.13. - No. 8. - P.577-579.

329. Puttemans P., Brosens I., Dellatin Ph. et al. Salpingoscopy versus hysterosalpingography in hydrosalpinges // Fertil. Steril. 1987. - No. 2. - P.535-540.

330. Quan M. Pelvic inflammatory disease: diagnosis and management // J. Am. Board. Fam. Pract. 1994. - V.7. -No. 7. - P. 110-123.

331. Rachinsky I., Boguslavsky L., Goldstein D. et al. Diagnosis of pyogenic pelvic inflammatory diseases by 99mTc-HMPAO leucocyte scintigraphy // Eur. J. Nucl. Med. 2000. -№12. - P. 1774-1777.

332. Rasmussen K.L. Pelvic inflammation - pelvic pain // Ugeskr. Laeger. 1994. -V.156. - No. 34. - P.4839-4840.

333. Redecha M., Niznanska Z., Korbel M., et al. Laparoscopic findings in women with chronic pelvic pain // Bratisl. Lek. Listy. 2000. - V. 101. - No. 8. - P.460-464.

334. Ren K., Weil F., Dubner R. et al. Progesterone attenuates persistent inflammatory hyperalgesia in female rats: involvement of spinal NMBA receptor mechanisms// Brain. Res. 2000. - V.86. - No. 2. - P.272-277.

335. Rice P.A., Schacheter J. Pathogenesis of pelvic inflammatory disease. What are the questions?//JAMA. 1991. - V.266. -No. 18. - P.2587-2593.

336. Ripa K.T., Svennsson L., Treharne J.D. et al. Chlamydia trachomatis infection in patients with laparoscopically verified acute salpingitis // Am. J. Obstet. Gynecol. 1990. - V. 138. - No. 7 (Part 2). -P.960-964.

337. Risser W.L., Risser J.M., Cromwell P.F. Pelvic inflammatory disease in adolescents: a review // Tex. Med. 2002. - V.98. - No. 2. - P.36-40.

338. Roberts L.M., Sanfilippo J.S., Raab S. Effects of laparoscopic lavage on adhesion formation and peritoneum in an animal model of pelvic inflammatory disease // J. Am. Assoc. Gynecol. Laparosc. 2002. - No. 4. - P.503-507.

339. Romagnani S. Biology of human Thl and Th2 cells // J. Clin. Immunol. 1995. - V.15. -P.121-129.

340. Ross J.D. European guideline for management of pelvic inflammatory disease and perihepatitis // Int. J. STD&AIDS. 2001. - No. 12 (Suppl. 3). - P.84-87.

341. Ross J.D.1 Pelvic inflammatory disease // Clin. Evid. 2002. - No. 7. - 14521457.

342. Ross J.D. An update on pelvic inflammatory disease// Sex. Transm. Infect. - 2002. V.78. -No. 1. -P.18-19.

343. Schuiling G.A., Valknof N., Faas M.M. Suppression by developing follicles of the low-dose endotoxin-induced glomerular inflammatory reaction in the pregnant rat// Am. J. Obstet. Gynecol. 2000. - V.45. - No. 3. - P.241-247.

344. Schillinger J.A., Kissinger P., Calvet H. et al. Patient-delivered partner treatment with azithromycin to prevent repeated Chlamydia trachomatis infection among women: a randomized, controlled trial // Sex. Transm. Dis. - 2003. - No. 1. - 49-56.

345. Silva J. S., Morrissey P. J., Grabstein K. H. et al. Interleukin 10 and interferon gamma regulation of experimental Trypanosoma cruzi infection // J. Exp. Med. -1992. V.175.-P.169-174

346. Simon C., Stille W., Wilkinson PJ. Antibiotic therapy in clinical practice. 2nd edition. New York, 1993. - 623 p.

347. Skibsted L., Sperling L., Hansen U., Hertz J. Salpigitis isthmica nodosa in female infertility and tubal diseases // Hum. Reprod. 1991. - V.6. - No. 6. - P.828-831.

348. Soper D.E. Pelvic inflammatory disease // Infect. Dis. Clin. North. Am. 1994. - V.8-No.4.-P.821-840.

349. Soper D.E., Brockwell N.J., Dalton H.P., Jonson D. Observations concerning the microbial etiology of acute salpinginis// Am. J. Obstet. Gynecol. 1994. -V.170. -No. 4. -P.1008-1017.

350. Soper D.E. The semantics of pelvic inflammatory disease // Sex. Transm. Dis. -1995. V.22. - No. 6. - P.342-343.

351. Stacey C.M., Munday P.E., Taylor-Robinson D.A. Longitudinal study of pelvic inflammatory disease // Brit. J. Obstet. Gynaec. 1992. - V.99. - P.994-999.

352. Stary A. European Guideline for management of chlamydial infection // Int. J. STD&AIDS. 2001. - No. 12 (Suppl. 3). - P.31 -33.

353. Stovall T.G., Thorpe E.M., Zing F.W. Treatment of postcesarean section endometritis with ampicillin and sulbactam or clindamycin and gentamycin // J. Reprod. Med. 1993. - V.35. -№11.- P.843-848.

354. Strobelt N., Mariani E., Ferrari L. et al. Fertility after ectopic pregnancy. Effects of surgery and expectant management // J. Reprod. Med. 2000. - V.45. -No. 10. - P.803-807.

355. Sweet R.L., Bartlett J.G., Hemsell D.L. et al. Evolution of new anti-infective drugs for the treatment of acute pelvic inflammatory disease // Clin. Infect. Dis. -1992.-V.15. (Suppl.l). P.553-561.

356. Sweet R. L., Roy S., Faro S. et al. Piperacillin and tazobactam versus clindamycin and gentamycin in the treatment of hospitalized women with pelvic infection. The piperacillin/ tazobactam study group // Obstet. Gynecol. - 1994. -V.83. -No. 2. -P.280-286.

357. Szumala-Kakol A., Szymanowski K., Owedyk M. et al. Microbiological flora cultured from peritoneal fluid of women in reproductive age // Ginekol. Pol. - 2000. V.71. - 9. -P.1026-1230.

358. Taipale P., Tarjanne H., Ylostalo P. Transvaginal sonography in suspected pelvic inflammatory disease // Ultrasound. Obstet. Gynecol. 1995. - V.6. -P.430-434.

359. Taylor R.C., Berkowitz J., McComb P.F. Role of laparoscopic salpingostomy in the treatment of hydrosalpinx // Fertil. Steril. 2001. - V.75. - No. 3. - P.594-600

360. Tempfer C., Hefler L., Heinzl H. et al. CYFRA 21-1 serum levels in women with adnexal masses and inflammatory disease // Br. J. Cancer. - 1998. V.78. -No. 8. -P.1108-1112.

361. Tepper R., Aviram R., Cohen N. et al. Doppler flow characteristics in patients with pelvic inflammatory disease: responders versus nonresponders to therapy // J. Clin. Ultrasound. 1998. - V.26. - P.247-249.

362. Tessler F.N., Perrella R.R., Fleischer A.L., Grant E.G. Endovaginal sonographic diagnosis of dilated fallopian tubes // Am. J. Roentgenol. 1989. -V.153. -P.523-525.

363. Thomas D., Orfilia J., Bissac E. Evolution of the activity of different gainliness in the experimental chlamidial salpingitis maus model // Drugs. 1995. - V.49 (Suppl. 2). - P.261-263.

364. Timor-Tritsch I.E., Lerner J.P., Monteagudo A. et al. Transvaginal sonsgraphic of tubal inflammatory disease // Ultrasound. Obstet. Gynecol. - 1998. V.12. - No. 1. -P.56-66.

365. Thurmond A.S., Burry K.A., Novy M.J. Salpingitis isthmica nodosa: result of transcervical fluoroscopic catheter recanalization // Fertil. Steril. 1995. - V.63. - No. 4.-P.715-722.

366. Tsanadis G., Kalantaridou S.N., Kaponis A. et al. Bacteriological cultures of removed intrauterine devices and pelvic inflammatory disease // Contraception. -2002. V.65. - No. 5. - P.339-342.

367. Tukeva T.A., Aronen H.S., Karjalainen P.T. et al. MR imaging in pelvic inflammatory disease: comparison with laparoscopy and US// Radiology. 1999. - V.210. - No. 1. - P.209-216.

368. Vasquez G., Winston R.M., Boeckx W. The epithelium of human hydrosalpinges a light optical and electron microscope study // Brit. J. Obstet. Gynecol. 1983. - V.90. - P.764.

369. Vasquez G., Boeckx W., Brosens I. No correlation between peritubal and mucosal adhesions in hydrosalpinges // Fertil. Steril. - 1995. V.64. - P. 10321033.

370. Varela R., Gonçalves V., Telhado C. et al. Tubo-ovarian abscess. An analysis of 20 cases // Act. Med. Port. 1995. - V.8. - No. 10. - P.537-542.

371. Vilos G.A., Vilos A.W., Haebe JJ. Laparoscopic findings, management, histopathology, and outcome of 25 women with cyclic leg pain // J. Am. Assoc. Gynecol. Laparosc. 2002. - V.9. - No. 2. - P. 145-151.

372. Walker C.K., Lander D.V., Ohm-Smith M.J. et al. Comparison of cefotetan plus doxycycline with cefoxitin plus doxycycline in the inpatient treatment of acute salpingitis // Sex. Transm. Dis. 1991. - V.18. - No. 2. - P.l 19-123.

373. Walker C.K., Kahn J.L., Washington A.E. et al. Pelvic inflammatory disease: Metaanalysis of antimicrobial regimen effectively // J. Infect. Dis. 1993. - V.168. -P.969-978.

374. Walsh T., Grimes D., Frezieres R. et al. Randomized controlled trial of prophylactic antibiotics before insertion of intrauterine devices. IUD Study Group // Lancet 1998. - V.351. - P. 1005-1008

375. Washington A.E., Berg A.O. Preventing and managing pelvic inflammatory disease: key questions, practices and evidence // J. Fain. Pract. - 1996. - V.43. - P.283-293.

376. Watrelot A., Dreyfus J.M., Andine J.P. Evaluation of the performance of fertilioscopy in 160 consecutive infertile patients with no observable pathology// Hum. Reprod. 1999. - V. 14. - No. 3. - P.707-711.

377. Welte R., Kretzschmar M., Leidl R. et al. Cost-effectiveness of screening programs for Chlamydia trachomatis: a population-based dynamic approach // Sex. Transm. Dis. 2000. - V.27. - No. 9. - P.518-529.

378. Westrom L. Diagnosis and treatment of salpingitis // J. Reprod. Med. 1983. -V.28. -P.703-708.

379. Westrom L. Epidemiologie das salpingites et leurs conseguences // Contracept. Fertil. Sex. 1984.-V.2.-No.1.-P.235-241.

380. Westrom L. Pelvic inflammatory disease // JAMA. 1991. - V.266. - No. 18. -P.26.

381. Westrom L., Joesoef G., Reynolds A. Pelvic inflammatory disease and fertility. A cohort study of 1,844 women with laparoscopically verified disease and 657 control women with normal laparoscopic results // Sex. Transm. Dis. - 1992 - V 19. -P.185-192.

382. Whiteside J.L., Katz T., Anthes T. et al. Risks and adverse outcomes of sexually transmitted diseases. Patients" attitudes and beliefs// J. Reprod. Med. -2001. V.46. -№1.- P.34-38.

383. Wiesenfeld H.C., Hillier S.L., Krohn M.A. et al. Lower genital tract infection and endometritis: insight into subclinical pelvic inflammatory disease // Obstet. Gynecol. 2002. - V. 100. - No. 3. - 45 6-463.

384. Williams J.K. Noncontraceptive benefits of oral contraceptive use: an avidence-based approach // Int. J. Fertil. Women Med. 2000. - V.45. - No. 3. -P.241-247.

385. Wollen A.L., Sandvei R., Mork S. In situ characterization of leucocytes in the fallopian tube in women with or without an intrauterine contraceptive device // Acta Obstet. Gynecol. Scand. 1994. - V.73. - No. 2. - P.103-112.

386. Wylie S.N., Roche P.J., Gibson W.R. Evulation after sympathetic denervation of the rat ovary produced by freezing it is nerve supply // J. Reprod. Fertil. - 1985. V.75.-No.2.-P.3 69-373.

387. Yanky E., Skjeldestad F.E. The salpingitis diagnoses under scrutiny // Tidssker. Nor. Laegeformen. 1999. - V.l 19. - No. 7. - P.928-930.

388. Zrubek H. Wstepua ocean skutesznsti ambulatoryjaej balneotherapii nektorych schosen kobiecych //Balneol. Pol. 1974. - No. 3. - S.34-38.

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The invention relates to medicine, in particular to experimental gynecology, and can be used to model autoimmune oophoritis. To do this, immunize outbred female rats with an antigen, which is an extract of the ovaries of intact animals. In this case, the antigen is additionally purified by freezing three times. The antigen is administered intraperitoneally to females in the resting phase of the estrous cycle at a dose of 20 μg/ml five times every other day. The method ensures that the pathomorphological changes and pathogenetic features of autoimmune oophoritis in the experiment are closer to those that are important in the clinic, and also reduces the modeling time, increases the stability of reproduction, which expands the scope of use of the autoimmune oophoritis model. 11 ill.

Drawings for RF patent 2439712

The invention relates to medicine, specifically to experimental gynecology, and concerns methods for modeling autoimmune oophoritis.

There are known methods for modeling autoimmune oophoritis by removing the thymus in the neonatal period in mice, by introducing T lymphocytes from healthy mice into isogenic thymectomized mice, using crude antigen using xenogeneic and allogeneic antibodies, purified antigen such as ZP3.

The essence of modeling by removing the thymus in the neonatal period in mice is as follows. On the third day after birth, mice undergo thymectomy. This model allows us to study autoimmune inflammation in the ovaries, as well as the manifestation of autoimmune processes in other organs, such as the thyroid gland and stomach. However, the model has disadvantages: the thymectomy procedure is traumatic for the experimental animal, the microsurgical technique of the operation has a high risk of vital outcomes, the autoimmune process is systemic in nature, since the general process of regulation of cellular immunity is disrupted, which will complicate further isolated study of autoimmune oophoritis, the duration of the experiment with objective criteria for the formation of autoimmune oophoritis reaches 14 weeks.

In the T-lymphocyte injection model, thymectomized mice are transplanted with CD4+CD8+ thymocytes in the neonatal period from healthy isogenic adult mice. However, this method is limited by the reproduction capabilities of thymectomy and transplantation of CD4+CD8+ thymocytes; it is not specific for autoimmune oophoritis; the development of autoimmune oophoritis and gastritis is possible only in 50-75% of recipients.

A method for modeling autoimmune oophoritis using purified ZP3 antigen consists of immunizing experimental animals (rabbits, mice, rats) with a specially prepared zona pellucida protein extract (ZP3) by intravenous or subcutaneous administration. This model of autoimmune oophoritis is specific in nature and highly stable in reproduction. However, preparing the extract is expensive.

The closest to the proposed method is the method of modeling autoimmune oophoritis using an unrefined antigen, proposed by Alekseeva I.N., Bryzgina T.M., Sukhina V.S., Makogon N.V., Voznesenskaya T.Yu., Grushka N.G. , based on the method of Spasokukotsy Yu.A. when he studied cytotoxic sera. The authors selected CBA mice weighing 18-20 g as experimental animals. When reproducing immune damage to the ovaries using xenogeneic antiovarian antibodies, they used antibodies obtained by immunizing rabbits with a water-salt extract of mouse ovary. The gamma globulin fraction was isolated from the serum of immunized rabbits by salting out with ammonium sulfate. Gamma globulin at a dose of 0.2 mg protein was administered intravenously to mice for 3 consecutive days. After 24 h, mice were sacrificed under Nembutal anesthesia and the ovaries were isolated. When reproducing immune damage to the ovaries using immunization with allogeneic ovarian tissue, mice were immunized at the first stage by subcutaneous administration of a water-salt extract of the ovaries of outbred mice at a dose of 2 mg of protein in Freund's complete adjuvant. Subsequently, immunization was carried out with increasing doses of antigenic material intravenously (0.5, 0.75, 1.0 and 1.4 mg of protein per mouse) every two to three days. 6 days after the last administration, ovarian studies were performed.

The disadvantages of the prototype include the rather long formation time when performing the model using xenogeneic antibodies, the complexity of intravenous administration of allogeneic antigens and xenogeneic antibodies. In addition, with the introduction of xenogeneic antiovarian antibodies, the pathogenesis of the development of autoimmune oophoritis, which is clinically important, is disrupted.

The new technical problem solved by this invention is to bring the pathomorphological changes, pathogenetic features (conditions for the formation) of autoimmune oophoritis in the experiment closer to those that are important in the clinic, as well as reducing the modeling time, increasing the stability of reproduction, reducing economic costs, expanding the scope of use of this models.

To solve the problem in the method of modeling autoimmune oophoritis, which consists in immunizing outbred female rats with an antigen, which is an extract of the ovaries of intact animals, the antigen is additionally purified by three times freezing, administered intraperitoneally to female rats in the resting phase of the estrous cycle at a dose of 20 μg/ml five times in one day.

These distinctive features facilitate the preparation of alloantigen and reduce modeling time. Intraperitoneal administration makes it easier to technically implement the model, and also allows you to achieve new positive effects, namely, to bring pathomorphological changes and pathogenetic features closer to those that are clinically important, increase the stability of reproduction, and expand the scope of use of this model.

The proposed method was tested on 36 outbred mature white female rats in the Department of Experimental Physiology and Surgery of the Central Research Laboratory of the Siberian State Medical University. The experiment was approved by the ethics committee of the State Educational Institution of Higher Professional Education of the Siberian State Medical University of Roszdrav (protocol No. 1231 of December 21, 2009). Thus, the technical solution meets the invention criteria of “novelty”, “inventive step”, “industrially applicable”.

The method is carried out as follows

As experimental material, sexually mature white outbred female rats (weighing 180-220 g) are used, which are in the resting phases (metaestrus, diestrus) of the estrous cycle.

Under inhalation anesthesia with ether vapor, decapitation is performed on an intact animal. Using lower median laparotomy, the ovaries are removed under sterile conditions. The ovaries are thoroughly cleaned of fatty tissue and placed in a saline solution in a sterile tube. Pre-test tube with saline solution weighed in order to then determine the mass of the ovaries in it. Under sterile conditions, the ovaries are crushed with scissors, the ovarian tissue is ground using a sterile homogenizer to a homogeneous mass suspended in saline, and the resulting suspension is placed in a sterile tube. At the temperature of a household freezer (-18-20°C), the resulting suspension is frozen three times and thawed to a liquid consistency. Then centrifuge for 15 minutes at 2500 rpm. The supernatant is filtered under sterile conditions. The resulting suspension is diluted with physiological solution at the rate of 20 μg of ovarian tissue per 1 ml, poured into sterile tubes and used for immunization. Store the finished extract in an industrial freezer at a temperature of -70°C. Shelf life up to 3 months.

The finished extract is administered to experimental animals in a volume of 1 ml intraperitoneally using an insulin syringe in compliance with the rules of asepsis and antisepsis five times with intervals between injections of one day.

Experimental animals are kept in standard vivarium conditions on a normal diet with the addition of vegetables under dosed lighting (12:12, light from 8 o'clock). All animals are examined daily, their general condition, appearance, behavior, food excitability and motor activity are noted. Body weight is measured. A colpocytological study is performed to diagnose the phase of the estrous cycle. Animals are removed from the experiment under inhalation anesthesia with ether vapor in the diestrus phase, which is determined colpocytologically, on the 5th, 10th, 15th and 30th day.

The evidence-based criteria for the experimental model of autoimmune oophoritis were the following:

During the autopsy of experimental animals, the initial manifestations of autoimmune oophoritis were detected on the 5th day in the form of single leukocytes surrounding the secondary follicles (Figure 2), microcirculation disorders in the form of sweating of red blood cells and their release into the luteal tissue, the formation of typical cysts of the corpus luteum, ovaries in diameter was 0.7-1.0 cm (with the norm being 0.5-0.6 cm). On the 30th day of the experiment, the ovaries in diameter were 0.3-0.4 cm (with the norm being 0.5-0.6 cm), the characteristic pattern of the surface of the ovaries was absent, the ovaries had a smooth surface or had cysts, which, according to some authors is a macroscopic sign of autoimmune oophoritis;

Antiovarian antibodies on the 5th day in the serum of animals in the experimental group amounted to 1.52±1.05 U|ml, however, by the 30th day there was a significant increase in antiovarian antibodies to 10.7±2.16 U|ml (at 1. 65±0.97 U|ml control), which is the most conclusive criterion of a mature autoimmune process in the ovaries.

Specific example

As experimental material, we used a mature white outbred female rat weighing 180 g, in the meta- and diestrus phases of the estrous cycle, obtained at the Central Vivarium of the Siberian State Medical University. The experiment was carried out at the Department of Experimental Physiology and Surgery of the Central Research Laboratory of the Siberian State Medical University. The animal was removed from the experiment on day 30 (at the diestrus stage, which was determined by colpocytology) by decapitation under inhalation anesthesia with ether vapor.

Under inhalation anesthesia, decapitation was performed on an intact animal using ether vapor. The ovaries were removed using lower median laparotomy under sterile conditions. The ovaries were thoroughly cleaned of fatty tissue and placed in a saline solution in a sterile tube. The test tube with saline solution was first weighed in order to then determine the mass of the ovaries in it. Under sterile conditions, the ovaries were crushed with scissors, the ovarian tissue was ground using a sterile homogenizer to a homogeneous mass suspended in saline, and the resulting suspension was placed in a sterile tube. At the temperature of a household freezer (-18-20°C), the resulting suspension was frozen three times and thawed to a liquid consistency. Then centrifuged for 15 minutes at 2500 rpm. The supernatant was filtered under sterile conditions. The resulting suspension was diluted with physiological solution at the rate of 20 μg of ovarian tissue per 1 ml, poured into sterile tubes and used for immunization. The finished extract was stored in an industrial freezer at a temperature of -70°C. Shelf life up to 3 months.

The finished extract was administered to an experimental animal in a volume of 1 ml intraperitoneally using an insulin syringe in compliance with the rules of asepsis and antisepsis five times with intervals between injections of one day.

The animal was removed from the experiment by decapitation under inhalation anesthesia with ether vapor in the diestrus phase, which was determined by colpocytology, on the 30th day.

Immediately after collection, the ovaries were fixed in a 10% formaldehyde solution, embedded in paraffin, and after preparing sections 4-5 µm thick, they were stained with hematoxylin and eosin, according to Van Gieson. Histological examination was carried out at the Department of Histology, Cytology and Embryology of the Siberian State Medical University.

When opening the abdominal cavity of an animal removed from the experiment on the 30th day, a small amount of exudate was noted, the uterine horns and ovaries on both sides were hyperemic, and the adhesive process was not expressed. Histological examination revealed an inflammatory process in the ovaries. In the area of ​​venous type vessels, cellular infiltrates containing mononuclear cells are visible. Vessels of the venous type in the medulla of the ovaries are moderately full-blooded, and phenomena of stasis of blood cells are observed. In the area of ​​formation of inflammatory infiltrates, cells with karyopyknosis phenomena are found. Secondary and tertiary follicles are subject to degenerative changes, which are manifested by destruction and cytolysis of oocytes; oocyte nuclei are not detected. In some oocytes, thickening of the zona pellucida is detected.

Using the proposed method, we created a model of autoimmune oophoritis in 36 experimental animals (outbred white mature female rats weighing 180-220 g). It is necessary to note the relative simplicity of reproducing the model of autoimmune oophoritis, the absence of deaths in experimental animals, and the stable reproduction of the results obtained.

Research results

The experiment was carried out on 36 mature outbred female rats in which autoimmune oophoritis was created. The controls were intact animals (10 animals) of the same age as the experimental animals and kept with them under standard vivarium conditions. The control material was taken on the 15th and 30th days simultaneously with the experimental ones to take into account age-related changes. Rats were chosen as experimental material, since in rats the mechanisms of regulation of the ovarian-menstrual cycle are close to those in women and, unlike other laboratory animals, spontaneous ovulation occurs.

When opening the abdominal cavity, the condition of the abdominal organs was visually studied: the presence and nature of the effusion, the condition of the peritoneum, the ovaries were measured and weighed, their color, the nature of the structure of the cortical layer, the presence of follicles, cysts, and hemorrhages were noted. All animals underwent colpocytological examination to determine the stage of the estrous cycle. Immediately after collection, the ovaries were fixed in Carnoy's fluid and neutral formalin, embedded in paraffin, and after preparing sections 5 μm thick, they were stained with hematoxylin and eosin, according to Van Gieson, and the PIC reaction was performed. Histological studies were performed at the Department of Histology, Embryology and Cytology of the Siberian State Medical University.

When opening the abdominal cavity of animals in the experimental group, the presence of serous-hemorrhagic exudate in moderate quantities was noted at all points of the study. There was practically no adhesive process, the ovaries lay free in the abdominal cavity. The uterine horns, oviducts and ovaries were moderately hyperemic, and a pronounced vascular pattern was noted. Unlike the animals in the control group, the ovaries in the experimental group had a less pronounced follicular apparatus. The size of the ovaries in the experimental group on the 5th, 10th, 15th day of the experiment increased by 0.2-0.3 mm, but by the 30th day they became smaller by 0.1-0.2 mm compared to the ovaries of the control group groups (Figure 1).

Colpocytologically, in animals of the experimental group at all points of the study, the stage of diestrus was noted, which reflects the stage of functional rest. In animals of the control group, smears corresponded to the phases of the estrous cycle.

A detailed study of histological preparations of the ovaries on the 5th day of experimental inflammation revealed single leukocytes surrounding the secondary follicles (Figure 2). Corpus luteum with microcirculation disorders in the form of sweating of red blood cells and their release into the luteal tissue were encountered in large numbers. The presence of developing typical corpus luteum cysts was also noted.

By the 10th day, a more pronounced hemodynamic disturbance was observed, manifested by prestasis and stasis of the formed elements (Figure 3), numerous hemorrhages in the corpus luteum (Figure 4). The marginal location of leukocytes and their migration through the vascular wall were also detected (Figure 3). The generative apparatus of the ovaries on the 10th day of the experiment was characterized by mild desquamation of the follicular epithelium, edema of the stroma, edema of the cytoplasm of oocytes, and increased condensation of chromatin in their nuclei (Figure 5).

On the 15th day, in addition to the changes described above, pronounced microcirculation disorders with thrombosis phenomena were observed (Figure 6). There was massive infiltration of leukocytes into the walls of the corpus luteum and follicles (Fig. 7, 8). In the follicular apparatus, swelling of the intercellular substance, destruction of oocytes, discomplexation and desquamation of the follicular epithelium were detected (Figure 7).

On the 30th day of experimental inflammation, most of the growing follicles were destructively changed, leukocytes were found in their cavities (Figure 9). Tissue basophils are found near the destroyed follicles (Figure 10).

In the control group, upon histological examination, the ovaries had a normal structure.

The changes described above correspond to the descriptions of altered ovaries presented in the literature in autoimmune oophoritis.

Thus, in order to bring the pathomorphological changes and pathogenetic features of autoimmune oophoritis in the experiment closer to those that are clinically important, as well as to shorten the modeling time, increase the stability of reproduction and expand the use of this model, intraperitoneal administration of alloantigen purified by triple freezing at a dose of 20 μg/ml is proposed .

When modeling autoimmune oophoritis, changes occurred in 100% of cases. A study of the morphology of the ovaries over time showed the presence of leukocyte infiltration in the follicular environment from moderately pronounced on the 5th day to massive infiltrates with the presence of tissue basophils on the 30th day. Increasing destructive changes were detected in the follicular apparatus until the complete destruction of the majority of oocytes and their surroundings on the 30th day. Hemodynamic disturbances were identified, including massive hemorrhages with thrombosis in the follicular apparatus and its surroundings on the 30th day, and luteal cysts formed by the 30th day of the experiment.

The dilution and dose of alloantigen was selected experimentally by us in a preliminary series of experiments and was based on the results of a study by Alekseeva I.N., Bryzgina T.M., Sukhina V.S., Makogon N.V., Voznesenskaya T.Yu., Grushka N.G. (2006) taking into account the species characteristics of experimental animals. During the experiment, the dose of alloantigen was unchanged, since the model is close to the clinical course of autoimmune oophoritis, the trigger of which is not an increasing antigen load over time. The intraperitoneal route of administration was chosen, since the ovaries do not have peritoneal cover, and the peritoneum itself has high ability absorb waste products thanks to numerous vessels supplying intraperitoneal organs. The experiment was carried out in the resting phase of the estrous cycle (metaestrus, diestrus) to reduce the animals’ tolerance to infection [Pastukhov M.I. 1970; Petrova M.S. 1999; Tikhonovskaya O.A. 2000].

The proposed method makes it possible to create a model of autoimmune oophoritis in experimental animals (outbred mature female rats weighing 180-220 g).

It is necessary to note the relative simplicity of reproducing this model, the absence of deaths in experimental animals, the stable reproduction of the results obtained, and the relatively short duration of the simulation.

The proposed model of autoimmune oophoritis allows us to study the pathogenesis in more detail and test new treatment regimens for this pathology.

Information sources

1. Ailamazyan E.K., Gabelova K.A., Gzgzyan A.M., Potin V.V. Autoimmune oophoritis (pathogenesis, diagnosis, treatment prospects). // Obstetrics and gynecology. - 2002. - No. 2. - P.7-9.

2. Alekseeva I.N., Bryzgina T.M., Sukhina V.S., Makogon N.V., Voznesenskaya T.Yu., Grushka N.G. Changes in the thymus and lymph nodes during immune damage to the ovaries in mice. // Problems of reproduction. - 2006. - No. 4. www.mediasphera.ru

3. Spasokukotsky Yu.A. The effect of cytotoxic specific serums on the gonads. - Kyiv: “Naumkova Dumka”, 1977. - 169 p.

4. Tsaregorodtseva M.V. Pathogenetic aspects of the formation of autoimmune oophoritis in chronic inflammatory diseases of the pelvic organs and its rehabilitation therapy. // Ag-info. - 2007. - No. 2. - P.32-36.

5. Damjanovic M. Experimental autoimmune oophoritis. II. Both Iymphoid cells and antibodies are successful in adoptive transfer / Autoimmunity. - 1991. - Vol.9. - P.217-223.

6. Damjanovic M., Janovic B.D. Experimental autoimmune oophoritis. 1. Inhibition of fertility in rats isoimmunized with homogenates of the ovary / Am J Reprod Immuno. - 1989. - Vol.l20. - P.1-8.

7. Hoek A., Schoemaker J., Drexhage H.A. Premature ovarian failure and ovarian autoimmunity // edrv.endocjournals.org the endocrine society. - 1997. - Vol.18, No. 1. - P. 107-134.

8. Ivanova M., Bourneva V., Gitsov L., Angelova Z. / Experimental immune oophorit is as a model for studying the thymus ovary interaction. I. Morphological studies / Am J Reprod Immunol. - 1984. - Vol.6. - P.99-106.

9. Jankovic B.D., Markovic B.M., Petrovic S., Isakovic K. Experimental autoimmune oophoritis in the rat / Eur J Immuno. - 1973. - Vol.13. - P.375-377.

10. Peterson M., Koothan P. Thillai, Morris Keith D., O'Byrne Kevin T., Braude P., Williams A., Aitken R. John. Analysis of the contraceptive potential of antibodies against native and deglycosylated porcine ZP3 in vivo and in vitro / Biology of reproduction. - 1992. - Vol. 46. - P. 523-534.

11. Rhim Sung Ne, Millar Sarah E., Robey F., Luo An-Ming, Lou Ya-Huan, Yule T., Allen P., Dean J., Tung S.K. Kenneth. Autoimmune disease of the ovary induced by a ZP3 peptide from the mouse zona pellucida // Journal clin invest. - January 1992. - Vol.89. - P.28-35.

12. Skinner S.M., Mills T., Kirchick H.J., Dunbar B.S. Immunization with zona pellucid proteins results in abnormal ovarian follicular differentiation and inhibition of gonadotropin-induced steroid secretion / Endocrinology. - 1984. - Vol.115. - P.2418-2432.

13. Smith H., Chen I.M., Kubo R., Tung K.S. Neonatal thymectomy results in a repertoire enriched in T cells deleted in adult thymus / Science. - 1989. - Vol.245. - P.749-752.

14. Taguchi O., Nishizuka Y. Autoimmune oophoritis in the thymectomized mice: T cell requirement in the adoptive cell transfer / Clin Exp Immunol. 1980. - Vol.42. -P. 324-331.

15. Taguchi O., Nishizuka Y., Sakakura T., Kojima A. Autoimmune oophoritis in thymectomized mice: detection of circulating antibodies against oocytes / Clin Exp Immunol. - 1980. - Vol.40. - P. 540-553.

16. Wood D.M., Liu C., Dunbar B.S. The effect of all immunization and heteroimmunization with zonae pellucidae on fertility in rabbits / Biol Reprod. - 1981. - Vol.25. - P.439-450.

Application

Captions for illustrations

Fig.1. Rat ovaries (after fixation in neutral formalin) on the 30th day of the experiment: a - ovary of an intact rat; b - rat ovary after 5-fold administration of alloantigen.

Fig.2. Single leukocytes in the area of ​​the secondary follicle on the 5th day of modeling. Hematoxylin and eosin staining. Uv. 700.

Fig.3. Hemodynamic disturbances in the ovarian medulla on the 10th day of modeling. Prestasis and stasis of formed elements. Marginal location of leukocytes. Migration of leukocytes and erythrocytes through the vascular wall. Hematoxylin and eosin staining. UV.400.

Fig.4. Fragment of the yellow body. Numerous hemorrhages into the corpus luteum. 10th day of simulation. Hematoxylin and eosin staining. UV.400.

Fig.5. Secondary follicle, oocyte degeneration, desquamation of follicular epithelium. 10th day of simulation. Staining a - hematoxylin and eosin; b - according to Van Gieson. UV.150.

Fig.6. Hemodynamic disturbances in the ovarian medulla on the 15th day of modeling. Thrombosis phenomena. Swelling of the intercellular substance. Prestasis and stasis of formed elements. Marginal location of leukocytes. Migration of leukocytes and erythrocytes through the vascular wall. Hematoxylin and eosin staining. UV.200.

Fig.7. a - Secondary follicle, destruction of the oocyte, discomplexation and desquamation of the follicular epithelium; b - secondary follicles, destruction of the oocyte. 15th day of simulation. Coloring a. - according to Van Gieson; b - hematoxylin and eosin. UV.200.

Fig.8. Hemorrhage into the corpus luteum on the 15th day of the simulation. Massive infiltration into the wall of the corpus luteum. Hematoxylin and eosin staining. UV.200.

Fig.9. - Complete destruction of the tertiary follicle with the phenomena of migration of leukocytes into its cavity. Hematoxylin and eosin staining. UV.200.

Fig. 10. Destruction of the follicular apparatus. Infiltration. Tissue basophils in the area of ​​destruction (arrows). 30th day of simulation. CHIC reaction. UV.200.

Fig. 11. Massive infiltration in the area of ​​the secondary follicle. Tertiary follicle with oocyte destruction. Hemorrhage into the wall of the tertiary follicle. Hematoxylin and eosin staining. UV.200.

CLAIM

A method for modeling autoimmune oophoritis, which consists in immunizing outbred female rats with an antigen, which is an extract of the ovaries of intact animals, characterized in that the antigen is additionally purified by three times freezing, administered intraperitoneally to female rats in the resting phase of the estrous cycle, at a dose of 20 μg/ ml five times every other day.

480 rub. | 150 UAH | $7.5 ", MOUSEOFF, FGCOLOR, "#FFFFCC",BGCOLOR, "#393939");" onMouseOut="return nd();"> Dissertation - 480 RUR, delivery 10 minutes, around the clock, seven days a week and holidays

Nevostruev Sergey Alexandrovich. Morphofunctional state of the uterine appendages during chronic inflammation and complex treatment using mud extract (experimental clinical study): dissertation... Candidate of Medical Sciences: 14.00.01 / Nevostruev Sergey Aleksandrovich; [Place of defense: State educational institution of higher professional education "Siberian State Medical University"]. - Tomsk, 2004. - 176 p.: ill.

Introduction

CHAPTER 1. Literature review 12

1.1. Modern view on the problem of chronic inflammatory diseases of the uterine appendages 12

1.2. Morphological changes in the uterine appendages in inflammatory diseases 18

1.3. Principles of complex therapy of chronic inflammatory diseases of the uterine appendages 26

1.4. The importance of peloid therapy in the treatment of chronic inflammatory diseases of the uterine appendages 34

1.5. Characteristics of silt sulfide mud extract 38

1.6. Summary 43

CHAPTER 2. Material and research methods 45

2.1 Experimental part 48

2.2. Clinical part 52

2.3. Statistical processing of results 57

CHAPTER 3. Results of our own research

3.1. Morphological changes in the uterine appendages during chronic inflammation and their correction using silt sulfide mud extract 59

3.1.1. The course of experimental inflammation of the oviducts and ovaries in white rats 59

3.1.2. Morphology of the oviducts and ovaries of white rats during chronic inflammation caused by the introduction of a culture of Staphylococcus aureus 60

3.1.3. Morphology of the oviducts and ovaries of white rats during chronic inflammation caused by the introduction of a culture of Staphylococcus aureus after a course of abdominal sacral galvanization 76

3.1.4. Morphology of the oviducts and ovaries of white rats during chronic inflammation caused by the introduction of a culture of Staphylococcus aureus, after a course of abdominal-sacral electrophoresis of a 1% solution of silt sulfide mud extract 79

3.1.5. Morphology of oviducts and ovaries of white rats with chronic aseptic inflammation 86

3.1.6. Morphology of the oviducts and ovaries of white rats during chronic aseptic inflammation and a course of galvanization 96

3.1.7. Morphology of the oviducts and ovaries of white rats during chronic aseptic inflammation and after a course of abdominal-sacral electrophoresis of a 1% solution of silt sulfide mud extract 98

3.1.8. Indicators of a morphoquantitative study of the ovaries of white rats with experimental chronic inflammation and peloid physiotherapy 105

3.9. Summary

3.2. The influence of complex treatment using electrophoresis of a 1% solution of silt sulfide mud extract on the clinical course and outcome of chronic inflammation of the uterine appendages 117

3.2.1. Clinical and laboratory characteristics of patients with chronic inflammatory diseases of the uterine appendages 117

3.2.2. Principles of complex treatment of patients with chronic inflammatory diseases of the uterine appendages 128

3.2.3. Dynamics of clinical and laboratory parameters depending on the complex therapy used. 130

3.2.4. Medical and social effectiveness of treatment of patients with CIDP using electrophoresis of a 1% solution of silt sulfide mud extract in a complex of therapeutic measures 135

3.2.5. Summary 143

CHAPTER 4. Discussion of results 146

References 163

Introduction to the work

Relevance of the problem. Chronic inflammatory diseases of the uterine appendages (CIUD), despite advances in the development of new treatment methods and the widespread introduction of laparoscopy into practical medicine, continue to remain one of the pressing problems of clinical practice [Kulakov V.I., 2001; Smetnik V.P., 2003; Henry-Suchet J., 2000]. Patients with inflammatory diseases of the uterine appendages make up 60-65% of all gynecological patients [Serov V.N., 2003; Risser W.L., 2002]. CIPP are a common cause of pelvic pain syndrome, infertility, miscarriage, ectopic pregnancies and, as a consequence, a large number of surgical interventions [Veren J., 2002; Taylor R.C., 2001; Vilos G.A., 2002]. In this regard, improving the quality of treatment of patients with CIPV using complex, pathogenetically based approaches is of particular importance [Savelyeva G.M., 1997; Ross J.D., 2001].

In domestic and foreign literature there is numerous data on the pathomorphogenesis of chronic inflammation in the uterine appendages [Kovalsky G.B., 1996; Krasnopolsky V.I., 1998; Herschlag A., 2000; Furuya M., 2002]. However, the degree of involvement of the ovaries in the inflammatory process, the reversibility of morphological disorders in the uterine appendages against the background of CIDP, and the possibility of influencing reparative processes in the ovaries and fallopian tubes remain the subject of debate. There are isolated experimental studies devoted to this problem, but their results are often contradictory [Tikhonovskaya O.A., Logvinov S.V., 1999; Ordonez JL, 1999; Leese H.J., 2001].

In modern conditions, with CIPV, clear trends are visible, on the one hand, towards the use of minimally invasive methods of surgical diagnosis and treatment, on the other hand, towards the optimization of measures aimed at rehabilitating the functions of the organs of the female reproductive system [Strugatsky V.M., 2003; Cibula D., 2001; Ness R.B., 2002]. Achievements of recent years give reason to consider methods of physiotherapy as one of the most promising, taking into account their possibility of differentiated and targeted action on various parts of the pathogenesis of the disease, increasing adaptive capabilities with a minimal risk of developing adverse reactions [Bogolyubov V.M., 1998; Strugatsky V.M., 2002].

An undoubted reserve for optimizing the treatment of CIPM is the use of natural therapeutic muds and preparations obtained on their basis, which have the ability to regulate neurohumoral and immune processes, prevent and reduce dystrophic changes, stimulate the regeneration of cellular elements [Arkhipova L.V., 1995; Strugatsky V.M., 2003].

At the Institute of Petroleum Chemistry of the TSC SB RAS (Tomsk), a dry extract of silt sulfide mud was created, containing a complex of mineral salts, trace elements, organic substances, which has a wide range of medicinal properties: anti-inflammatory, analgesic, hepatoprotective, etc. [Saratikov A.S., 2001; Vengerovsky A.I., 2002]. The use of the extract in acute inflammation of the uterine appendages has an anti-alterative, anti-exudative effect mainly due to the membrane-stabilizing antioxidant effect, expressed in a decrease in the concentration of lipid peroxidation products and catabolism of cell membrane receptors [Tikhonovskaya O.A., 1998, 1999, 2000].

At the same time, the mechanisms and patterns of the therapeutic effect of the silt sulfide mud extract in CIPM remain poorly understood.

Purpose of the study. To study the effect of silt sulfide mud extract on the morphofunctional state of the uterine appendages during chronic inflammation in an experiment and evaluate its clinical effectiveness.

Based on the above, the purpose and objectives of the study were formulated.

1. To develop models of chronic inflammation of the uterine appendages with a pronounced proliferative component.

2. To study, using the created models of chronic inflammation of the uterine appendages in experimental animals, the nature, dynamics and sequence of changes in various tissue elements: epithelium, connective tissue stroma, blood vessels, generative and endocrine elements. To evaluate, using models of chronic inflammation, the effect of electrophoresis of silt sulfide mud extract on the dynamics of the morphofunctional state of the oviducts and ovaries, the intensity of reparative processes, and to experimentally substantiate the possibility of using it in the complex treatment of chronic inflammation of the uterine appendages.

3. To develop a method of treating women with chronic inflammatory diseases of the uterine appendages, including peloid physiotherapy from the early stages after laparoscopy.

4. To analyze the effectiveness of the method of treating women with chronic inflammatory diseases of the uterine appendages based on immediate and long-term results.

Scientific novelty. Experimental models of chronic monocultural and aseptic inflammation of the ovaries and oviducts in white outbred sexually mature female rats have been developed. The experiment studied in detail the pathomorphogenesis in the uterine appendages during chronic inflammation, analyzed the role of various structural elements in the tissue mechanisms of inflammation of the oviducts and ovaries, and determined the sequence and nature of pathological disorders.

For the first time, it was established that the extract of silt sulfide mud reduces atresia of the ovarian follicular apparatus initiated by inflammation, prevents the formation of fibrosclerotic adhesive changes and promotes regression of fibrous tissue due to the activation of macrophages and fibroclasts and the normalization of the processes of collagenogenesis and collagenolysis.

The high efficiency of electrophoresis of a 1% solution of silt sulfide mud has been clinically proven as a pathogenetically substantiated component of the treatment of CIPM. For the first time in this pathology, the dynamics of the hormonal function of the ovaries and the functional activity of the fallopian tubes under the influence of peloid physiotherapy were studied. The data obtained prove that electrophoresis of the extract, carried out in the early stages after laparoscopic organ-preserving interventions on the uterine appendages, has a stimulating effect on ovarian function, increasing the secretion of estrogen and progesterone; restores the functional activity of the fallopian tubes.

Practical significance. The developed models make it possible to perform preclinical testing of new methods of treating CIPV.

As a result of the research, a pathogenetically substantiated method for the complex treatment of CIPM using an extract of silt sulfide mud was developed. The proposed method of treatment increases therapeutic effectiveness in terms of immediate and long-term results: it reduces the frequency of relapses, prevents the formation of pelvic pain syndrome, tubo-peritoneal infertility, and ectopic pregnancy.

The use of peloid physiotherapy in gynecological practice in non-resort conditions makes it economically accessible to a wide segment of the population and has important socio-economic significance.

Provisions submitted for defense.

1. In the pathomorphogenesis of experimental chronic inflammation of the uterine appendages, regardless of phlogogen, there are similar changes, manifested by microcirculatory disorders, massive atresia of growing follicles, fibrous-sclerotic and adhesive processes. In the mechanism of tissue disorders, an important role is played by disruption in the collagen synthesis-collagenolysis system.

2. The use of silt sulfide mud extract for chronic inflammation of the uterine appendages in an experiment limits the increase in atresia of the ovarian follicles, accelerates the regeneration of the oviduct mucosa, normalizes hemodynamics in the microvasculature, and promotes the reverse development of fibrosclerotic and adhesive processes.

3. In the mechanism of the therapeutic effect of peloid therapy on the uterine appendages during chronic inflammation in the experiment, one of the leading places belongs to the activation of macrophages and fibroclasts and the normalization of the processes of collagenogenesis and collagenolysis, restoration of the ultrastructural organization of the hematofollicular barrier 4. Electrophoresis of a 1% solution of silt sulfide mud extract increases the effectiveness of complex treatment chronic inflammation of the uterine appendages in women according to immediate and long-term results.

Introduction into practice. The results of the study are used in the educational process at the Department of Obstetrics and Gynecology, Faculty of Medicine, Siberian State Medical University on the topic “Inflammatory diseases of the pelvic organs”; at the Department of Histology, Embryology and Cytology of Siberian State Medical University on the topic “Female reproductive system”; medical activities of the gynecological clinic of Siberian State Medical University and the Women's Health Center LLC MADEZ.

Approbation of work. The main results of the work were reported and discussed at the scientific and practical conference of students and graduate students "Youth Health - Health of the Nation" (Tomsk, 1998), the Final Conference "Tatiana's Day" based on the results of the Russian competition for the best scientific work of students in 1998 in the section " Medical Sciences" (Moscow, 1999), conference "Modern problems of fundamental and clinical medicine" (Tomsk, 1999), at the School of Young Researchers "Achievements in Molecular Biology and the Development of New Effective Methods for the Treatment of Human Diseases" (Moscow, 1999), VI and IX Russian National Congresses “Man and Medicine” (Moscow, 1999, 2002), I, II, III International Congresses of Young Scientists and Specialists “Scientific Youth on the Threshold of the 21st Century” (Tomsk, 2000, 2001, 2002), Russian scientific and practical conference “Current issues of endoscopic surgery in gynecology and obstetrics” (Tomsk, 2001), VI international scientific and practical conference “Quality - strategy of the 21st century” (Tomsk, 2001), Tomsk, 2001), Russian scientific conference with the participation of CIS countries “Current problems of experimental and clinical morphology” (Tomsk, 2002), city scientific and practical conference dedicated to the 40th anniversary of the Central Scientific Research Laboratory of Siberian State Medical University “Modern aspects of biology and medicine” (Tomsk , 2003), Russian conference “Current issues of urogynecology” (Tomsk, 2003), meetings of regional scientific and practical societies of obstetricians-gynecologists and morphologists (Tomsk, 2003-2004).

Scope and structure of the dissertation. The dissertation is presented on 204 pages and consists of an introduction, literature review, personal observations, discussion, conclusions and practical recommendations. The bibliographic index contains 422 sources, of which 250 are in Russian and 172 in foreign languages. The dissertation contains 16 tables, 4 photographs, 32 microphotographs, 10 electron diffraction patterns, 5 graphs.

Modern view on the problem of chronic inflammatory diseases of the uterine appendages

In most countries of the world, an increase in the incidence of inflammatory gynecological diseases has been noted over the past decade. Thus, in the USA, about 1 million women with acute inflammation of the uterine appendages are registered annually, every fifth of them (15-20%) are diagnosed with purulent-septic complications that require surgical correction, the transition to a chronic course of the inflammatory process is noted in 45-70% [Hatcher R.F. et al., 1994; Savelyeva G.M. et al., 1997; Ms Neeley S.G. et al, 1998; Paternoster D.M. et al., 1998; Marks C. et al., 2002]. The age range of inflammatory diseases of the uterine appendages is very wide: young women - 14-17 years old - 4-15%; 18-35 years old 44-75%; over 36 years old - 10-22% [Smetnik V.P., Tumilovich L.G., 1998, 2003; Kolgushkina T.N. et al., 1998, Paavonen J., 1998; Westrom L., 1992; Ostensen et al., 2000]. The dynamics of the general morbidity of various population groups during the reforms that took place in Russia in the last decade of the 20th century were characterized by unfavorable trends. Despite the fact that the overall incidence for 1991-1999 as a whole increased by only 10.5%, the proportion of diseases with a chronic and recurrent course has increased significantly. Frequency of inflammatory diseases of the pelvic organs for 1994-2001. increased in girls by 5.4 times, in women - by 1.3 times [Kulakov V.I. et al., 2001]. Inflammatory diseases of the female genital organs are characterized by a frequent transition to a chronic relapsing course with the formation of pelvic pain syndrome; disorders of reproductive, menstrual and sexual functions; lead to long-term disability [Bodyazhina V.I., 1978, 1981; Savelyeva G.M. et al., 1997; Ailamazyan E.K., Ustinkina T.I., 1991; Dergacheva T.I., 1996; Strizhakov A.N., Podzolkova N.M.. 1996; Tsvelev Yu.V., Kira E.F., 1996, 1998; Krasnopolsky V.I. et al., 1998; Savitsky G.A. et al., 2000; Kulakov V.I. et al. 2001; Westrom L., 1991; Brookoff D., 1994; Kottmann L.M., 1995; Gardo S., 1998; Watrelot A. et al., 1999].

Risk factors for the formation of CIDP are social disadaptation, changes in sexual motivation, high infection index, use of intrauterine contraception, intrauterine interventions (primarily abortion), untimely and inadequate treatment of acute inflammatory diseases of the pelvic organs [Savelyeva G.M., Sichinava L.G. , 1997; Samorodinova L.A. et al., 1998; Varela R. et al., 1995; Gareen I.F. et al., 2000; Grimes DA., 2000; Williams J.K., 2000; Champion J.D. et al, 2001; Crowley T. et al., 2001].

With inflammation of the pelvic organs of women, the pathological process in the uterine appendages in 60-78% of cases, according to the International Classification of Diseases (tenth revision) and Industry standards for the scope of examination and treatment in obstetrics, gynecology and neonatology (1999), corresponds to the diagnosis of “salpingitis” or “ salpingo-oophoritis." In the English-language literature, the term “pelvic inflammatory disease” is used, which means “a clinical syndrome associated with a microbial infection.” This definition emphasizes the ascending nature of the process associated with infection, inflammatory in nature developing changes [Kate L.G. et al., 1988; Kulakov V.I. et al., 1998; Soper D.E., 1995].

The literature of recent years provides numerous data on changes clinical course and the etiological structure of inflammatory diseases of the uterine appendages. Currently, there is a tendency towards the predominance of sluggish diseases with a protracted, asymptomatic course [Bodyazhina V.I. et al., 1990; Dyachuk A.V.1992; Savelyeva G.M., Antonova L.V., 1992; Akker L.V., Deryavkina R.S., 1998; Evseev A.A., 1998; Kira E.F., Tsvelev Yu.V., 1998; Krasnopolsky V.I. et al, 1999; Cates WJr. et al., 1996; Kottmann L.M., 1995; Broadnax J. 1993; 1997; Yanky E. et al., 1999].

Thanks to the development of new endoscopic and puncture methods for sampling directly from the site of inflammation, improvement of basic cultivation technologies, by the 90s of the last century, most researchers came to the consensus that the main causative agents of inflammatory diseases of the uterine appendages are associations of non-clostridial anaerobic microorganisms, gram-negative and gram-positive microbial flora [Ermoshenko L.V., 1992; Aksenenko K.B., 1995; Tsvelev Yu.V. et al., 1998; Faro S. et al, 1993; Jossens M.O.R. et al., 1993; Super D.E. et al., 1994; Szumala-Kakol A. et al., 2000; Baveja G. et al., 2001; Tsanadis G. et al., 2002]. Frequent components in the structure of CVID pathogens are also sexually transmitted infections (STI), and, above all, gonococci, trichomonas, chlamydia, mycoplasma, ureaplasma and viruses [Aksenenko V.A. et al., 1996; Goldstein F.W. et al., 1994; Mandegor M. et al., 1995; Paavonen J. et al., 1996; Mc Gee Z.A., et al., 1999; Aral S.O., 2001]. The association of opportunistic pathogens deprives the disease of nosological specificity. Due to these features etiological diagnosis represents a dynamic process, including assessment of clinical signs of the disease, classical microbiological studies and other methods (immunodiagnostics, PCR, gas-liquid chromatography, etc.) [Tsvelev Yu.V. et al., 1996; Dan M. et al., 1993; Eschenbach D.A. et al, 1997; Hefler L. et al, 1998; Rachinsky I. et al, 2000].

The importance of peloid therapy in the treatment of chronic inflammatory diseases of the uterine appendages

Many works have been devoted to the study of the chemical composition, sanitary-biological state, and biological effects of medicinal mud [Cherepanova M.N., Kotova T.I., 1981; Bogolyubov D.N., Ulashchik B.C., 1985; Leshchinsky A.F., Zuza Z.I., 1985; Tsarfis P.G., Kiselev V.B., 1990; Shustov L.P., 1996, etc.].

The medicinal effects of mud are caused by a combination of mechanical, thermal, biological and chemical effects, but the specificity of medicinal mud is determined mainly by their physicochemical characteristics. They are determined by the gas and mineral composition, pH of the environment, the presence of various microelements, as well as organic substances that enter into certain relationships with the cellular elements of the skin, exteroreceptors, sweat and sebaceous glands [Nizkodubova SV. et al., 1981; Mikheeva L.S., 1984; Gorchakova G.A., 1986]. Under the influence of these processes, both local and general reactions of various functional systems of the body arise. Mineralization and chemical composition of natural factors determine the specificity of the body's responses that occur against the background of their nonspecific influence [Zolotoreva T.A., 1988; Karpovich O.A., 1989; Balak K., 1969; Zrubek N., 1974]. According to I.E. Oransky, P.G. Tsarfis (1989) specificity for the effect of the physical therapy factor is most likely manifested at the tissue, cellular, subcellular and molecular levels by primary physicochemical changes. For more high level this specificity of action is obscured by the involvement of general response systems in the body's response - the endocrine glands, pituitary-adrenal and nervous systems. The implementation of the therapeutic effect of peloids is carried out by increasing the synthesis of their own hormones, neurotransmitters, biologically active substances, influencing immunomorphological and enzyme-chemical processes, with the help of which impaired body functions are regulated and restored [Gorchakova G.A., 1986; Tsarfis P.G., 1989].

The results of clinical, biochemical and morphological studies indicate that the use medical complexes, including sulfide mud with a temperature of 44 C, has a negative effect on the central myogenic and metabolic regulation of blood circulation, which affects an increase in vascular tone, a decrease in blood supply and leads to a deterioration in tissue trophism [Oransky I.E., Tsarfis P.G., 1989] . Clinically, this was expressed in excessive activity of the inflammatory process and an increase in its exudative component. Many researchers explain the negative role of the temperature factor in peloid therapy for inflammatory diseases by the increased release of histamine and a decrease in its inactivation [Yasnogorodsky V.G., 1984; Leshchinsky A.F.. Zuza Z.I., 1985]. Mitigated, gentle methods of peloidotherapy, excluding temperature and mechanical components of stimuli, help improve peripheral circulation, reduce the level of hexoses and seromucoid in the blood serum, hydroxyproline in daily urine, which together indicates a decrease in dystrophy and an increase in the regeneration of cellular structures in altered tissues [Tsarfis P .G., 1989]. In gynecological practice, therapeutic mud is mainly used for inflammatory diseases and, as a rule, in chronic stage The process uses native mud. In addition, traditional mud therapy is carried out with conditioned material and, mainly, in the conditions of functioning resorts. An important scientific problem in the use of natural factors is the creation of mud preparations that would be as effective as native mud due to the preserved chemical composition, and in order to optimize treatment could be prescribed in combination with various preformed physical factors [Ryzhova G.L., Khasanov V. .V., 1995; Samutin N.M., Krivobokov N.G., 1997; BaierH., 1976; Goecke S, 1986].

The first attempts to create such mud preparations and use them in non-resort conditions were made in Germany in the second half of the 19th century, and somewhat later in Russia. But the most intensive development of methods for obtaining new mud preparations, the study of their chemical composition, experimental and clinical assessment of the effectiveness of their therapeutic use began only a hundred years later, in the second half of the 20th century [Lesnoy S.K., 1950]

The created filtrates, water-mud extracts, steam distillates, mud solutions began to be successfully used in ophthalmology, neurology, arthrology, pulmonology, gastroenterology and gynecology [Bogolyubov V.M., 1985; Trapeznikova N.K., Orlova L.P., 1988; Shustov L.P., 1996; Dzhabarova N.K. et al., 1997].

Subsequently, there was a scientific search and development of methods for the production of mud preparations, allowing to preserve the chemical composition of native muds and the creation of dry preparations that are cost-effective, have a long shelf life and allow their use in different dosages depending on the severity of the pathological process [Altunina L.K. . et al., 1987; Agapov A.I. et al., 1999]. Since 1980, development has been carried out in Tomsk complex problem“Mud preparations” and new methods for obtaining silt mud extracts and dry preparations based on extracts and brine have been created. Chemical analysis of solutions of dry preparations showed their qualitative similarity with liquid extracts [Ryzhova G.L. et al., 1983. 1985; Bogdanova I.V., Lyutova O.V., 1983; Matasova S.A., Ryzhova G.L., 1988], and experimental studies revealed their high biological activity [Matis E.Ya. et al., 1984; Vengerovsky A.I. et al., 1984; Saratikov A.S. et al., 1986, 2001; Vorobyova T.G., 1988; Nechai G.M., 1988; Shustov L.P., 1988; Tikhonovskaya O.A., Logvinov S.V. et al., 1987, 1998, 1999, 2000; Vengerovsky A.I., 2002; Petrova M.S., 2002].

The creation of mud preparations containing the entire complex of biologically active substances contained in native mud makes it possible to expand the indications of peloid therapy for CIPM and use it in a complex of rehabilitation measures in the early stages after laparoscopic treatment for chronic inflammation of the uterine appendages. Treatment procedures using mud preparations exclude thermal and mechanical factors effects significantly reduce the load on the cardiovascular system. The clinical effectiveness of peloid therapy is increased by combination with preformed physical factors: low voltage direct current (peloelectrophoresis), ultrasound (pelophonophoresis), magnetic field (peloinductothermy) and others [Malysheva SM., 1965; Morozova N.N., 1973; Seitenov E.S. et al., 1988; Mishchuk A.V., Gorelyuk I.P., 1989; Shafikova G.V., 1989; Matis E.Ya. et al., 1996; Petrova M.S., 1999; Tikhonovskaya O.A., 2000].

Morphology of the oviducts and ovaries of white rats during chronic inflammation caused by the introduction of a culture of Staphylococcus aureus

When opening the abdominal cavity of animals removed on the 30th day from the experiment with monocultural inflammation in combination with deserosis of the visceral peritoneum of the oviducts and scarification of the integumentary epithelium of the ovaries, the adhesive process is moderately pronounced, but widespread. Multiple thin, avascular, transparent and translucent adhesions are identified, which are removed with slight tension on the mesosalpinx or mesoovary (Fig. 1). The uterine horns are somewhat swollen, hyperemic, and sometimes present in the distal parts, with the involvement of the oviducts, hydrosalpinx-type changes. When opening the latter, a clear liquid in a volume of up to 0.5-1.0 ml is discovered. There is a small amount of free fluid in the abdominal cavity. exudative fluid. The parietal and visceral peritoneum is moderately hyperemic.

Histological examination of the ovaries and oviducts reveals a picture of a chronic inflammatory process with a significant proliferative component. Numerous adhesions of the ovaries, oviducts with the omentum and the formation of fibrous tissue are revealed. In the described areas, infiltrates containing cells of the macrophage series are found (Fig. 2), as well as oxyphilic masses in the area of ​​adhesions and a violation of the integrity of the integumentary epithelium of the ovaries.

By the 30th day of the experiment, hemodynamic disturbances were detected in the cortex and medulla of the ovaries and the wall of the oviducts. Vessels of the venous type in the medulla of the ovary are moderately plethoric. In some of them, phenomena of prestasis and stasis of blood cells, marginal location of leukocytes, migration of the latter through the vascular wall are noted, and in some - phenomena of thrombosis, edema of the intercellular substance (Fig. 3). Sometimes hemorrhages are detected in the medulla and cortex of the ovary. Along the course of individual blood vessels of the ovarian medulla and in the wall of the oviducts, the phenomena of perivascular sclerosis are determined. These disorders are accompanied by karyopyknosis and necrobiosis of interstitial cells (Fig. 4).

Focal proliferation of fibrous loose connective tissue is noted between the generative elements of the ovarian cortex. In the medulla of the ovaries, phenomena of fibrosis, proliferation of connective tissue cells, and the formation of cellular infiltrates are detected. When stained by Brachet, lymphoplasmacytic infiltrates are detected in the medulla of the ovaries and the wall of the oviducts (Fig. 5), as well as accumulations of tissue basophils with symptoms of partial degranulation.

Some of the primordial, secondary and tertiary follicles are subject to degenerative changes, which are manifested by the destruction and cytolysis of oocytes, homogenization of the cytoplasm of the latter. In some primordial and growing follicles, oocyte nuclei are not detected, and their cytoplasm is either sharply vacuolated or subject to destruction. In some follicles, along with these changes, the follicular epithelium is discomplexed, subject to necrobiotic and necrotic changes, and the eviction of macrophages into the cavity of such follicles is noted (Fig. 6). Sometimes in secondary and tertiary follicles the initiation of meiosis and pseudofragmentation of oocytes is determined, blastomeres with micronuclei are detected (Fig. 7).

With electron microscopy, some follicular epithelial cells are susceptible to rough destructive changes. The nuclei in them are pyknotic, with an unevenly high electron density of karyoplasm and homogenized chromatin, and contain cavities of unequal size. The nuclear envelope is mostly destroyed, and the contents of the nucleus disintegrate.

Morphology of oviducts and ovaries of white rats with chronic aseptic inflammation

When opening the abdominal cavity of animals removed on the 30th day from the experiment with deserosis of the visceral peritoneum in combination with spraying microdoses of talc, the adhesive process is pronounced and widespread. Multiple thin, translucent and opaque adhesions are identified, which are removed with significant tension on the mesosalpinx or mesoovary. The uterine horns, as in the experiment with the introduction of a culture of Staphylococcus aureus, are somewhat swollen, hyperemic, and in some cases intimately fused with the ovaries, mesosalpinx, omentum and fatty pendants of the intestines. A small amount of free exudative fluid is noted in the abdominal cavity. The parietal and visceral peritoneum are moderately hyperemic.

Histological examination of the ovaries and oviducts reveals a picture of a chronic inflammatory process with a pronounced proliferative component. Numerous adhesions of the ovaries, oviducts with the omentum and the formation of fibrous tissue are revealed (Fig. 29). In these areas, infiltrates containing macrophage cells, numerous inclusions of talc crystals, as well as giant cells are found foreign bodies(Fig. 30).

By the 30th day of the experiment, as in the model with monocultural inflammation, hemodynamic disturbances are detected in the cortex and medulla of the ovaries, the wall of the oviducts, manifested by prestasis and stasis of blood cells, marginal arrangement of leukocytes, migration of the latter through the vascular wall, and sometimes by the phenomenon thrombosis and edema of the intercellular substance.

In the cortex of the ovaries and the wall of the oviducts, giant cells of foreign bodies are often found near talc crystals. The described cells have an elongated shape, as well as several nuclei. In the medulla of the ovaries, fibrosis and proliferation of connective tissue cells are detected. Moderately pronounced phenomena of fibrosis are observed in the lamina propria of the oviduct mucosa.

A significant part of primordial, secondary and tertiary follicles are susceptible to atresia. Atretic follicles and bodies with a homogenized, thickened PAS-positive zona pellucida are detected (Fig. 31). The oocytes of such follicles have low glycogen content and cytoplasmic edema, and the follicular epithelium is discomplexed and subject to necrobiotic and necrotic changes (Fig. 32).

On the 40th day of the experiment in the abdominal cavity, the adhesive process becomes even more pronounced. Adhesions of various shapes, with small visualized vessels, are removed with damage, fate

A giant cell of a foreign body and talc microcrystals in the area of ​​adhesions between the omentum and the ovary on the 30th day of experimental aseptic inflammation. Hematoxylin and eosin staining. Uv. 600. animals, mesosalpinx and mesoovary. In some cases, hydrosalpinxes with serous-hemorrhagic contents occur.

Histological examination shows proliferation and pronounced sclerotic changes in the connective tissue in the cortex and medulla of the ovaries and in the wall of the oviducts. In the adventitia of blood vessels, there is a proliferation and homogenization of collagen fibers, which have intense fuchsinophilia when stained according to Van Gieson and exhibit a high affinity for leukofuchsin when performing the CHIC reaction.

On the part of the generative apparatus of the ovaries, the phenomena of atresia and reduced content of the corpus luteum still persist. Destruction, karyolysis of oocytes, homogenization of the cytoplasm of the latter, metaplasia and discomplexation of the follicular epithelium are detected. Between the generative elements in the cortical layer of the ovaries, directly under the covering epithelium, foreign body cells, as well as talc crystals, are often detected.

Similar to the previous period of the experiment, hemodynamic disorders are detected in the form of microcirculation disorders, single hemorrhages in the cortex and medulla of the ovary, and the wall of the oviducts.

Dystrophic processes are also detected in the mucous membrane of the oviducts. Thus, in a number of cases, uneven height of epithelial cells and a low content of PAS-positive substance on the apical surface of the latter are detected.

On the 60th day of the autopsy experiment, the adhesive process is even more pronounced. Dense adhesions with visualized vessels intimately surround the ovaries and oviducts, involving intestinal loops and the omentum in the process (Fig. 33). Changes in the distal parts of the uterine horns and oviducts in the form of hydrosalpinxes are noted in two-thirds of the observations.