No 2 (2013)

The paper presents data as an analytical literature review on recent trials in order to search for biomarkers to diagnose preeclampsia, including at the early stages of pathology development in the absence of clinical manifestations. It gives the panels of markers, which have been obtained by both biochemical and mass spectrometric methods and included proteins, peptides, glycoproteins, and metabolites in serum/plasma and urine. Among a lot of these biomarkers, there are separately substances (groups of substances) that have undergone trials on a large number (more than 200) of patients, which have shown their high sensitivity and specificity, good reproducibility, as well as the possibility of their use to assess the risk of preeclampsia at the early stages of a pathological condition. It is also concluded that the additional use of Doppler ultrasound studies enhances the diagnostic accuracy of the pathology, by increasing not only the sensitivity of the marker panel, but also the specificity of the test.

The review gives an update on the role of regulatory T cells in the development and maintenance of immune tolerance that is necessary to the physiological development of pregnancy. It considers immune dysregulation in pregnancy complications and describes the possibility of using regulatory T cells to correct gestation.

Objective. To comparatively estimate the levels of the neurospecific proteins NSE and GFAP in the sera of healthy pregnant women, pregnant women with preeclampsia or chronic arterial hypertension without preeclampsia and to perform an immunomorphological study of placental tissue in women with preeclampsia or chronic arterial hypertension without preeclampsia. Subjects and methods. A prospective study was conducted in 21 pregnant women with chronic arterial hypertension, 84 pregnant women with varying degrees of preeclampsia, as well as 24 healthy pregnant women with physiological pregnancy who formed a control group. The levels of the neurospecific proteins NSE and GFAP were studied in the sera of patients in the above groups; placental tissues were immunomorphologically examined in the women with preeclampsia and chronic arterial hypertension. Results. In chronic arterial hypertension versus preeclampsia, the pregnant women’s sera and placental tissues showed no neurospecific proteins that had high immunogenic activity and were able to lead to the development of a severe immunopathological process. Pregnancy can be prolonged during adequate antihypertensive therapy and good blood pressure control. Conclusion. The development of preeclampsia is characterized by a dramatic increase in the levels of the neurospecific proteins, severe immune injury of the endothelium of macro- and microcirculatory vessels. Progression of this process can be stopped only by delivery that is indicated for eclampsia, severe preeclampsia, and ineffective therapy for its moderate form.

Objective. To assess differences in the hemodynamic parameters of ophthalmic arteries and superior ophthalmic veins in non-pregnant women of reproductive age and in women with physiological pregnancy. Subjects and methods. A study group included 48 pregnant women aged 26 to 34 years at 30-40 weeks gestation. A comparison group consisted of 55 healthy, non-pregnant women aged 24-34 years. The number of previous pregnancies and births, the period of gestation (in the group of pregnant women), and blood pressures (BP) were recorded in both groups. The hemodynamic values of ophthalmic vessels were examined in both eyes. Results. In the pregnant women with normal BP levels, the blood flow velocity values were not found to practically differ from those in the ophthalmic arteries and veins in non-pregnant women. Conclusion. Analysis of the findings revealed no significant correlation between the period of gestation and the blood flow velocity values in the ophthalmic arteries and veins in the group of pregnant women.

Subjects and methods. Endometrial morphological and immunohistochemical features were studied in 52 patients with intramural uterine myoma (or concurrent with subserous myoma) up to 4 cm in diameter with no deformity of the uterine cavity, 53 patients after laparoscopic myomectomy (for intramural uterine myoma) without opening the uterine cavity, and 53 women with tuboperitoneal factor infertility with no myometrial pathology. Results. Conception rates were 23.1% in Group 1, 30.2% in Group 2, and 41.5% in the control group, the decrease in the conception rate being statistically significant in the uterine myoma group as compared with the control. Implantation rates were 11.9, 16.2, and 23.9%, respectively, those being significantly higher in the control group than in the uterine myoma and postmyomectomy groups. Patients with a successful IVF attempt showed a higher level of mature pinopodia-containing cells, higher expression of progesterone receptors in the endometrial stroma, and less pronounced expression of estrogen receptors in the surface epithelium and glands. Conclusion. In the patients who had undergone laparoscopic myomectomy prior to the IVF program, the conception rate was comparable with that in the patients without uterine myoma, which supports the need for myomectomy if intramural nodules are 4 cm or more in diameter. It is necessary to conduct an in-depth investigation involving the determination of a wider range of markers to study the mechanisms of action of uterine myoma on endometrial receptivity.

Sperm autoimmune reactions accompanied by elaboration of anti-sperm antibodies (AsAb) are one of the causes of male infertility. Objective. To specify the role of different factors (apart from obstruction) in the etiology of immune male fertility. Subjects and methods. Clinical and laboratory examination was made in 536 men from infertile couples aged 18—45 years; a control group consisted of 82 fertile men, the wives of whom were 8-16 weeks pregnant. Their sperm was examined in accordance with the WHO requirements. AsAbs were determined in the sperm by MAR test. Oxidative stress (OS) was assessed by luminol-dependent chemiluminescence assay. Chromosome damage was evaluated from DNA fragmentation by the chromatin dispersion test in inert agarose gel with visual microscopic estimation of halo formation after acid denaturation of DNA and lysis of nuclear proteins. The blood levels of interferons (IFN) and natural and in vitro induced IFN production were determined by the Campbell method. Reproductive tract infections were diagnosed using a polymerase chain reaction assay. Results. There is a highly significant correlation between AsAb counts, on the one hand, and experienced orchitis and subclinical testicular damage, on the other hand. There is no correlation between varicocele and AsAb, but in the former, the risk of immune infertility and orchitis increases after injury; varicocelectomy contributes to a reduction in AsAb with the higher degree of varicocele and a less marked autoimmune process. AsAbs are observed in the presence of Chlamydia infection and higher IFN-γ production. Cryptorchidism and orchiopexy, parotitis, epididymitis, herniotomy, chronic bacterial prostatitis, and other potential risk factors for reduced male fertility had no significant impact on OR for the development of immune infertility. In most cases (41%) immune infertility seems idiopathic, but it is accompanied by hyperproduction of reactive oxygen species and DNA damage (fragmentation). Conclusion. Male immune infertility is polyetiologic: blood-testis barrier impairment, cross reactions with microorganisms, immunopathological reactions. Autoimmune reactions against sperm can be considered as both a cause and a consequence of its poor quality caused by genetic and different endo- and exogenous factors.

The paper gives the results of examining patients with acne vulgaris, by using a set of clinical and laboratory studies involving hormonal blood test, estimation of the microflora, and determination of the degree of sebaceous excretion in the standard areas of the facial skin, as well as dermatology life quality indices. Acne vulgaris is shown to be associated with hyperandrogenism and ovarian insufficiency in 74.5% of the women. Combination therapy comprising a combined antiandrogenic contraceptive and topical antibacterial and anti-inflammatory agents could achieve remission of acne vulgaris in the majority of women (95.7%).

In clinical practice one has to encounter the situations when different congenital hemostatic defects threatened by hemorrhages are concurrent with one or another of the congenital or acquired predictors of thrombophilia. The paper describes a clinical case of the course of pregnancy, labor, or postpartum in women with combined congenital hemostatic disease and a history of late postpartum hemorrhage. The non-pregnant women showed a decrease in the level of factor XII to 20% (normal range, 75—125%) and factor IX to 50% (normal range, 75—125%) and an increase of factor VII to 145% (normal range, 75—125%). During pregnancy, there were adaptive changes in the hemostatic system: the level of factor XII increased up to 50% (normal range, 100—200%), factor IX up to 95% (normal range, 100—150%), and factor VII up to 190% (normal range, 150—250%). The total recordings of hemostasiograms corresponded to the normal gestational values during pregnancy. Fresh frozen plasma was intravenously injected in a volume of 500 ml in the first stage of labor to prevent postpartum hemorrhage. Blood loss during childbirth was 350 ml. The postpartum period was uncomplicated as long as 16 days. The hemostasiogram recordings over time were consistent with insignificant hypocoagulation with no signs of thrombinemia and hyperfibrinolysis.

Objective. To determine whether it is expedient to use inosine pranobex in human papillomavirus (HPV)-associated diseases with minimal cervical epithelium involvement and HPV infection. Subjects and methods. 302 women aged 18 to 60 years (mean age 35±3 years), including 113 (37.4%) HPV DNA-negative women and 189 (62.6%) HPV DNA-positive ones, were examined. To estimate a viral load, the HPV DNA-positive women were divided into 5 groups: 1) 40(26%) women with latent HPV infection (HPV carriers); 2) 16 (10.3%) with subclinical HPV infection; 3) 34 (22%) with low-grade squamous intraepithelial lesion (LSIL); 4) high-grade squamous intraepithelial lesion (HSIL), and 5) 11 (7.1%) with cancer of the cervix uteri (CCU). Results. The viral load was 3.9 (2.7—5.7) log in Group 1, 4.4 (3.5—6.5) log in Group 2, 5.0 (4.3—6.5) log in Group 3, 5.9 (4.6—6.6) log in Group 4, and 6.7 (6.2—7.8) log in Group 5. It was significantly higher in the CCU group than in the other groups (p<0.01). In the HPV carriers, the viral load was significantly lower than that in LSIL (p=0.021), HSIL (p=0001), and CCU (р=0.00007). A group of patients with cytoplasmic HPV lesion and a positive HPV test (n=34) were given 3 courses of inosine pranobex therapy by the scheme: 2 tablets t.i.d. for 10 days at an 8-day interval with the subsequent determination of HPV and a viral load after 6 months when HPV elimination was noted in 76.4% of cases. Conclusion. The early diagnosis, timely detection, and treatment of HPV-associated diseases promote the prevention of CCU. The use of antiviral agents having an immunomodulatory effect may be warranted in the long-term persistence or reinfection of HPV. Antiviral treatment decreases the likelihood of HPV persistence and recurrent infection.

To evaluate the efficiency of using fenticonazole (Lomexin) in doses of 1200 mg (600 mg twice at a 3-day interval) and 600 mg once in reproductive-aged women with Candida vulvovaginitis. Subject and methods. The randomized multicenter open-labeled trial enrolled 66 patients with Candida vulvovaginitis. The patients were divided in 2 groups of 33 women in each, by applying the envelop method. Group 1 patients were given lomexin 1200 mg (600 mg intravaginally twice at a 3-day interval) and group 2 patients received the drug in a single dose of 600 mg. Results. In groups 1 and 2, the microbiological efficacy of lomexin was 91.9 and 60.6%, respectively; the clinical subjective (rated by the patients) and objective (assessed by the physician) efficacies were 97.0% и 84.8% and 93.9 and 87.9%, respectively. Conclusion. The trial results showed the high efficiency of both fenticonazole (Lomexin) dosage regimens for the treatment of Candida vulvovaginitis; however, the microbiological treatment eficiency, patients’ subjective efficiency, and full cure with the physichian’s objective assessment were significantly more frequently recorded in the use of Lomexin 1200 mg (600 mg twice at a 3-day interval) versus 600 mg intravaginally.

Objective. To evaluate the clinical, immunological, and microbiological efficiency, validity, and safety of livarol in the combination therapy for inflammatory diseases of the female urogenital tract. Design. An open-label, short-term, prospective, randomized study. Material and methods. Real-time polymerase chain reaction, cervical canal discharge microscopy, and examination of local immunity parameters (cell-mediated immunity parameters, sIgA, IgA, IgM, IgG concentrations) and microbiocenosis were made. The antimycotic Livarol was given in accordance with its instruction. Results. The patients with inflammatory diseases of the urogenital tract were found to have significant impairments of cellular and humoral immunity of the genital tract and disorders of vaginal biocenosis. According to the treatment option, the patients were divided into two groups: 1) etiotropic therapy (a basis group); 2) basic therapy in combination with the antimycotic Livarol (a basis + livarol group). A comparison group consisted of 50 apparently healthy women. The most marked normalization of cellular immunity parameters, sIgA levels, and vaginal biotope microbiocenosis was observed in the patients treated with Livarol. Conclusion. The incorporation of the antimycotic livarol for the treatment of inflammatory diseases of the urogenital tract contributes to the normalization of local anti- infective defense factors, the recovery of colonization resistance, and the prevention of vaginal colonization with yeast-like fungi and produces a substantial pharmacoeconomic effect.

The paper gives an update on the diagnosis and management of women with human papillomavirus (HPV)-associated genital diseases and low- and high-grade squamous intraepithelial lesions (LSIL, HSIL). The management of the latter continues to be ambiguous, is constantly being improved by evidence-based studies, and involves ablation and excision and the observational tactic without destructive interventions is justified. LSIL is a particular problem since the majority of its histologically verified cases regress spontaneously and less than 1% gives rise to invasive carcinoma. No specific drugs that completely eliminate HPV have been designed today, but investigations of alternative antiviral and immunomodulatory agents are being continued. Isoprinosine (inosine pranobex) is one of the most tested immune system activators. The data of trials dealing with the use of various drugs are presented.