[Physico-chemistry of dinitrosyl iron complexes with thiol-containing ligands underlying their beneficial treatment of endometriosis].

Exogenous dinitrosyl iron complexes (DNIC) with thiol-containing ligands as NO and NO+ donors are capable of exerting both regulatory and cytotoxic effects on diverse biological processes similarly to those characteristic of endogenous nitric oxide. Regulatory activity of DNIC (vasodilation, hypotension, trombosis suppression, red blood cell elasticity increasing, skin wound healing acceleration, penile erection inducing, etc) is determined by their capacity of NO and NO+ transfer to biological targets of the latter (hemo- and thiol-containing proteins, respectively) due to higher affinity of the proteins for NO and NO+ than that of DNIC. Cytotoxic activity of DNIC is endowed with rapid DNIC decomposition under action of iron-chelating compounds resulting in appearance of NO and NO+ in cells and tissues in high amount. The latter mechanism is suggested to cause the blocking effect of DNIC as cytotoxic effectors on the development of benign endometrial tumors in rats with experimental endometriosis. It is also proposed that. a similar mechanism can operate causing at least a delay of malignant tumor proliferation under action of DNIC.

[The morphological substrate and pathogenetic mechanisms of pelvic pain syndrome in endometriosis].

OBJECTION: To study the origin and morphological substrate of pain syndrome in deep infiltrating endometriosis involving the bowel. SUBJECTS AND METHODS: The investigation was conducted using the intraoperative material (resected portions of the large and small bowels, appendix) obtained from 40 women diagnosed as having deep infiltrating endometriosis involving the bowel, which was accompanied by pain syndrome. Paraffin sections were immunohistochemically examined using the standard protocol. Antibodies to Ki-67, PTEN, ER, PR, ("Dako"), CD34 ("Cell Marque", USA), VEGF, EGF, EGFR, COX-2 ("Abcam"), and MMP 1 and 2 ("Abbiotec") were applied. Dako REAL EnVision Detection System kits ("Dako", Denmark) were used as secondary antibodies. RESULTS: The morphological substrate of pelvic pain syndrome in deep infiltrating endometriosis was established to be factors that acted in situ at the location of endometriotic foci and those caused by the infiltrative perivascular, intravascular, and perineural growth of endometrioid heterotopies. CONCLUSION: Inflammation and fibrosis in the endometriotic foci contribute to the accumulation of algogenes, which gives rise to somatogenic pain syndrome, and chronic nerve fiber injury as a source of nociceptive stimulation leads to neuropathic pain syndrome.

[Dinitrosyl iron complexes with glutathione recover rats with experimental endometriosis].

The effect of binuclear dinitrosyl iron complexes (DNIC) with glutathione on endometrioid tumors in rats with experimental endometriosis has been studied. The latter was induced by an autotransplantation model, where two fragments of endometrium with myometrium (2 x 2 mm) from the left uterine horn was grafted to the inner surface of the anterior abdominal wall. The test animals received intraperitoneal injections of 0.5 ml DNIC-glutathione at the dose of 12.5 micromole per kg daily for 12 days 28 days after operation. The injections resulted in more than a 2-fold decrease in the total volume of both large tumors formed from grafts and small additive tumors formed nearby grafts. The disappearance of the additive tumors was also observed in test animals. The EPR signal with g(av) = 2.03 characteristic of protein bound DNIC with thiol-containing ligands was recorded in livers, graft and additive tumors of test and control animals pointing out intensive generation of nitric oxide in rats with experimental endometriosis. Ribonucleotide reductase activation discovered by doublet the EPR signal at g = 2.0 with 2.3 mT hyperfine structure splitting was found in small tumors. The cytotoxic effect of DNIC-glutathione on endometrioid tumors was suggested to be due to DNIC degradation nearby the tumors induced by iron chelating compounds released from the tumors. The degradation resulted in release of a high amount of nitric oxide molecules and nitrosonium ions from DNICs affecting the tumors by way of the cytotoxic effect.

[Anticoagulant therapy in pregnant women with mechanical prosthetic heart valves. Review of international clinical guidelines].

Recently thromboembolic and hemorrhagic complications are main causes of maternal morbidity and mortality. Normal pregnancy is associated with ahypercoagulation. This condition is complicated if the patient has a mechanical prosthetic heart valve. Therefore an anticoagulant therapy in these patients is a challenging task. Effects of anticoagulant drugs on the fetus, pregnancy and delivery must also be taken into consideration. The review deals with international clinical guidelines. Diagrams of anticoagulant therapy in pregnant women with mechanical prosthetic heart valves using direct (unfractionated and low-molecular-weight heparins) and indirect (warfarin) anticoagulants are presented in the review.

[Endometrial pathology in elderly and senile age (a screening study)].

The results of an annual prophylactic medical examination were studied in 288 women aged 60-87 years. Primary and repeated visits revealed that 92.9% of the patients had endometrial pathology presented with glandular-fibrous polyps that both recurred and occurred de novo. Adenocarcinomas developing 4-14 years after polypectomy were diagnosed in 7.1% of the women. Focal impairments in the differentiation of an epithelial component of endometrial polyps in their recurrences and repeated development were noted in 97.3% of cases. In 88% of the patients, complaints were absent and recurrent endometrial pathology, including one of three adenocarcinomas, were diagnosed by prophylactic medical examination. The false-positive diagnoses of endometrial pathology by ultrasound study were 5.2%. Hysteroscopy in combination with morphology study should be recognized to be the gold standard for diagnosing pathologic endometrial lesions.

[Role of multislice spiral computed tomographic angiography in the treatment of uterine myoma].

The study was undertaken to enhance the diagnosis, treatment, and rehabilitation of patients with uterine myoma, by applying multislice spiral computed tomographic angiography (MSCTA) during uterine artery embolization. One hundred and twenty patients were divided into two groups: 1) 75 reproductive-age patients who underwent MSCTA before and after uterine artery embolization; 2) 45 reproductive-age patients who had previously undergone the latter according to the standard protocol. The main criteria for assessing the long-term results of treatment were patient complaints, the state of menstrual cycle and reproductive function, the sizes of the uterus and myomatous nodules, the signs of blood supply and growth of the latter, the presence or absence of new nodules. The most common types of the origin of the uterine arteries were visualized; the angle of uterine artery origin was measured. An algorithm for MSCTA study was elaborated.

[Molecular biological features of ectopic and eutopic endometrium in genital endometriosis].

The molecular biological features of the eutopic and ectopic endometrium were studied in 46 patients with adenomyosis, 44 with endometrioid cysts in the ovaries, and 34 with disseminated mixed forms of genital endometriosis. Reproductive-aged patients with the eutopic endometrium in a proliferation phase with hyperplastic or inflammatory changes were selected. Ten samples of the endometrium in a phase proliferation, which had been obtained at medicolegal autopsy of women without reproductive disorders, were studied as a control group. Both the glandular and stromal components of the ectopic and eutopic endometrium in different forms of endometriosis were shown to differ from the intact endometrium in their molecular biological features (the expression of Ki-67, Bcl-2, Bax, vascular endothelial growth factor, transforming growth factor-beta1, matrix metalloproteinases 2 and 10, matrix metalloproteinase-2 inhibitor, the enzyme cytochrome P450 aromatase.

[Cytochrome P-450 aromatase expression in the ectopic and eutopic endometrium in endometriosis].

An immunoperoxidase test was used to reveal the expression of cytochrome P-450 aromatase in the eutopic and ectopic endometrium of 14 patients with ovarian endometriosis and 26 with adenomyosis, whose age ranged from 21 to 47 years (38+/-2.0 years). Five endometrial samples taken at autopsy from the women who had died from injuries at ages of 32 to 47 years and who had no uterine or ovarian abnormities served as the control. Control observations revealed no aromatase expression by endometrial epithelial and stromal cells. Aromatase expression in the eutopic endometrium was found in patients with ovarian endometriosis and adenomysis in 80 and 58% of cases, respectively; while that in the ectopic endothelium was in all cases in both groups. In external genital endometriosis, the sensitivity and specificity of the test were 75 and 100%, respectively. In the glandular and stromal epithelium of both the ectopic and eutopic endometrium, aromatase expression increased with the higher extent of endometriosis.

[Prospects for using combined three-dimensional injection of gel transplants with autologous and allogenic cell cultures in reproductive medicine].

A combined cellular transplant for injection has been designed, by using lowly differentiated stromal fat tissue cells obtained from Wistar rats and it preserved biological and physical properties after passing through a small-diameter injection needle (an insulin syringe). A morphological study of the results of its transplantation into paraurethral tissues in 28 female rats showed that the transplant cells, autologous ones in particular, activated the proliferation of local connective tissue cell populations and retained their viability and proliferative and synthetic activities up 20 days or more. At the end of the experiment (on days 27-35), marked focal connective tissue enlargement at the site of injection of both allo- and autografts results in the narrowing of the urethral lumen. The injection implantation of combined allo- and autografts opens up new avenues for the treatment of pathological processes of the reproductive and urinary tracts.

[Heterotopic urine derivation in females with urinary bladder extrophy].

Fifteen females aged from 17 to 31 years with bladder extrophy (the condition after ureterosygmostomy) have undergone heterotopic urine derivation with creation of a cutaneous urine-retention catheter mechanism. Surgery was indicated in progressive decline of renal function in the presence of renal reflux, total urine incontinence in the failure of pelvic floor muscles and rectal sphyncter apparatus. Creation of cutaneous urine-retention catheter mechanism was made by the following techniques: heterotopic plastic repair from the ileocecal angle by Mainz pouch I (11 patients, 73.4%); heterotopic W ileocystoplasty by Abol-Enein (4 patients, 26.8%). Implantation of both ureters was conducted by Wallace technique in 4 (26.7%) cases. In 7 (46.6%) patients ureteral implantation was performed with antireflux defense by the method of cross dublicate creation. Four (26.7%) patients with small intestinal derivation have undergone extramural implantation of the ureters according to Abol-Enein. The results show that conversion of ureterosygmostomy in heterotopic urine derivation with one-stage genital reconstructive interventions decreases the number of potential complications, improves surgical outcomes and provides much better medico-social rehabilitation. Heterotopic intestinal continent derivation of urine is an operation of choice in women with urinary malformations. In such patients orthotopic urine derivation is impossible.

[Magnetic resonance imaging in the diagnosis of different forms of endometriosis]. / Magnitno-resonansnaia tomografiia v diagnostike razlichnykh form éndometriozov.

The present paper examines the capacities of non-invasive MRI in the diagnosis of endometriosis. A standardized study algorithm is proposed, indications and methodology for MRI in different forms of endometriosis (EM) are specified. It is shown that in the diagnosis of different types of EM there are specific changes in the MR pattern of small pelvic organs, which allow one to make a differential diagnosis of this disease with a higher sensitivity (96%) and specificity (87%) as compared with ultrasound study. MRI makes it possible to assess the degree of invasion of endometrioid heterotopies into the wall of the intestine and cervix uteri with a high degree of accuracy and to judge the degree and extent of intestinal luminal narrowing. Diagnostic errors in solving these problems (as well as those associated with the detection of extragenital foci of EM in the small pelvis) are due first of all to movement artefacts a (respiration and intestinal motility) particularly in the presence of a significant adhesive process and/or after surgical intervention. MRI does not virtually yield false-negative conclusions in the diagnosis of different forms of genital endometriosis (less than 3%), which, in the authors' opinion, rather justifies some hyperdiagnosis (about 11%) made by this method in the diagnosis of endometriosis of the rectovaginal septum. MRI is a closing, specifying stage of instrumental diagnosis of not only EM, but also other small pelvic diseases.

[One-stage formation of urinary bladder, restoration of symphysis with correction of congenital defects of external and internal genital organs]. / Odnomomentnoe formirovanie iskustvennogo mochevogo puzyria, vosstanovlenie lonnogo sochleneniia s ustraneniem vrozhdennykh defektov naruzhnykh i vnutrennikh polovykh organov.

One-stage combined surgery in a female patient with total extrophy of the urinary bladder after uretherosigmostomy was performed for the first time with participation of surgeons, gynecologists and urologists. Corrective surgeries in these patients must be performed for the purpose of creation of isolated urinary reservoir for prophylaxis of pyelonephritis and chronic renal insufficiency. Correction of symphysis defect was carried out with polypropylene endograft. This surgery was performed to provide quality of life and reproductive function of the patient.

[Genetic aspects of endometriosis: features of the distribution of polymorphic gene frequencies]. / Geneticheskie aspekty éndometrioza: osobennosti raspredeleniia chastot polimorfnykh genov.

In a group of patients with endometriosis and in a control group of healthy women, the polymorphism of the following systems were studied: ABO and RH blood-group systems; serum proteins haptoglobin (HP), transferrin (TF), vitamin D-transporting protein (GC), protease inhibitor (PI), and the third component of the complement (C3); serum enzymes-amylase of the loci 1 and 2 (AMY1 and AMY2), pseudocholinesterase (E2), and alkaline phosphatase (PP); erythrocytic enzymes-acid phosphatase (ACP1), phosphoglucomutase (PGM1), superoxide dismutase (SOD-A), esterase D (ESD), and glyoxalase (GLO1). Statistically significant differences between the groups compared were established for five genetic systems: ABO, E2, C3, TF, and PGM1. Among patient with endometriosis, the rare alleles of the locus ESD-ESD5 and ESD7-were found, along with ESD 5-5 homozygotes. Several genetic loci can be involved in the pathogenesis of endometriosis; their products can be specifically realized due to peculiarities of biochemical reactions in the organisms of people predisposed to this pathology.

Medicogenetic features and surgical treatment of patients with congenital malformations of the uterus and vagina.

OBJECTIVE: To analyze clinical examination, surgical treatment, main features of the surgical plan, and course of the early postoperative period and immediate results of surgery in 624 patients with various malformations of the uterus and vagina. METHODS: General clinical examination: endoscopic methods, including hysteroscopy and laparoscopy, cytogenetic and genealogic investigation, estimation of biochemical markers (serum levels) of patients with Müllerian anomalies (polymorphous and monomorphous loci). RESULTS: Karyotype examination revealed that 90.7% of 86 patients examined had normal 46XX karyotype, while sex chromosome mosaicism was present in 9.3% of cases. Genealogic analyses have shown that 39.8% of probands' relatives had reproductive system disorders. Genetic analysis of genealogical trees of patients with malformations of uterus and vagina revealed the recessive type of inheritance. Utilization of up-to-date procedures (hysteroscopy, resectoscopy, laparoscopy) facilitates performing the operations for genital malformations, provides reduction of operation time and postoperative hospital stay, and considerably increases the efficacy of surgical treatment. CONCLUSIONS: Factors of heredity play an important role in etiology of congenital malformation of the uterus and vagina. Modern endoscopic procedures can be successfully used in differential diagnosis of genital malformations, as well as during surgical treatment.

Laparoscopy in surgical treatment of vaginal aplasia: laparoscopy-assisted colpopoiesis and perineal hysterectomy with colpopoiesis.

OBJECTIVE: To optimize methods of surgery in patients with malformations of the genitalia. METHODS: Comparative evaluation of effectiveness of reconstructive plastic operations for malformations of uterus and vagina, performed by conventional methods or via laparoscopy. RESULTS: Laparoscopy permits identification of the pelvic peritoneum plus opening it and using the most mobile portion to create the vaginal fornix. In patients with vaginal and cervical aplasia and non-communicating functional rudimentary uterus, laparoscopy assists hysterectomy performed by the vaginal approach, as well as the last step of colpopoiesis. CONCLUSIONS: Laparoscopy significantly facilitates the procedure, reduces operating time and risks, and makes the operation available to the wide range of surgeons skilled in laparoscopy.