Association between endometrial senescent cells and immune cells in women with repeated implantation failure.

PURPOSE: The aim of this study was to compare women with recurrent implantation failure (RIF) and control group in terms of the associations between p16-positive senescent cells and certain types of immune cells in human endometrium during the mid-luteal phase METHODS: Immunohistochemical staining was performed in 116 endometrial biopsies taken from 57 women presenting RIF, and control group of 59 women who became pregnant after the first intracytoplasmic sperm injection. Endometrial tissue sections were stained immunohistochemically for p16 (Senescent cells), CD4 (T-helpers), CD8 (T-killers), CD14 (Monocytes), CD68 (Macrophages), CD56 (Natural killers), and CD79α (B-cells). The percentage of positively stained cells for each marker was calculated by HALO image analysis software. The quantity and the relationship between senescent cells and immune cells were assessed and compared between the two groups. RESULTS: The correlation coefficient was highest between senescent cells and CD4+ cells and was lowest between senescent cells and CD14+ cells in RIF women, similarly to the control group. However, most of the observed correlations among senescent and immune cells weaken notably or disappear in the RIF group. When comparing senescent cell-to-immune cell quantitative ratios, only p16+/CD4+ cell ratio was significantly higher in RIF women as compared with patients from the control group. CONCLUSION: Our study indicates that the quantity of senescent cells in human endometrium during the mid-luteal phase has the strongest association with the amount of T helpers. Moreover, the specificity of this association might have an important impact on the occurrence of RIF.

Genome-wide methylation profiling of schizophrenia.

Schizophrenia is one of the major psychiatric disorders. It is a disorder of complex inheritance, involving both heritable and environmental factors. DNA methylation is an inheritable epigenetic modification that stably alters gene expression. We reasoned that genetic modifications that are a result of environmental stimuli could also make a contribution. We have performed 26 high-resolution genome-wide methylation array analyses to determine the methylation status of 27,627 CpG islands and compared the data between patients and healthy controls. Methylation profiles of DNAs were analyzed in six pools: 220 schizophrenia patients; 220 age-matched healthy controls; 110 female schizophrenia patients; 110 age-matched healthy females; 110 male schizophrenia patients; 110 age-matched healthy males. We also investigated the methylation status of 20 individual patient DNA samples (eight females and 12 males. We found significant differences in the methylation profile between schizophrenia and control DNA pools. We found new candidate genes that principally participate in apoptosis, synaptic transmission and nervous system development (GABRA2, LIN7B, CASP3). Methylation profiles differed between the genders. In females, the most important genes participate in apoptosis and synaptic transmission (XIAP, GABRD, OXT, KRT7), whereas in the males, the implicated genes in the molecular pathology of the disease were DHX37, MAP2K2, FNDC4 and GIPC1. Data from the individual methylation analyses confirmed, the gender-specific pools results. Our data revealed major differences in methylation profiles between schizophrenia patients and controls and between male and female patients. The dysregulated activity of the candidate genes could play a role in schizophrenia pathogenesis.

Survival role of superoxide dismutase 1 on human granulosa luteinized cells in vitro.

OBJECTIVE: Deleterious effects of free radicals do not only result from the amount of free radicals produced but also are related to the efficiency and to the activities of enzymatic antioxidant systems. We investigated the effect of exogenous superoxide dismutase (SOD1) or Cu-chelating agent diethyldithiocarbamate (DDC) on the apoptosis (caspase-3 activity) of human granulosa luteinized cells (hGLC) in vitro. METHODS: The effects of SOD1 and DDC were studied using in vitro culture system, caspase-3 and the total SOD activity in hGLCs were measured using AcDEVD-PNA substrate and Beaushap and Fridovich methods, respectively, after 48 h of the culture period. RESULTS: The activity of SOD1 was the lowest in GLCs treated with 100 µM DDC as compared to control cells and to the cells supplemented with Cu, Zn-SOD or DDC (10 µM). The effect of DDC was associated with elevated caspase-3 activity as compared to control cells. CONCLUSIONS: It was demonstrated for the first time that the supplementation of cultured hGLCs with Cu2+, Zn2+-SOD (200 U/ml) maintains the viability of hGLCs via caspase-3 suppression.

[Expression of activating and inhibitory receptors on peripheral blood natural killer cell subsets of women with reproductive failures].

It is now apparent that immunologic implantation failure and recurrent abortions are more than likely mediated through activation of natural killer (NK) cells. The NK cell activity is mediated by a balance between activating and inhibitory receptors upon recognition of MHC class I molecules. In this study, we investigated by flow cytometry the expression of activating and inhibitory receptors on NK cells of women with reproductive failures- recurrent spontaneous abortion (RSA) and implantation failures (IF). In women with implantation failures CD56+CD16+ NK cell subset was significantly increased (p = 0.017) and CD158a expressing NK cells was significantly decreased (p = 0.027). CD161-activating receptor expressing CD56+ NK cells were significantly decreased in women with RSA (p = 0.033). These data further support an imbalance in NK cell subsets in women with reproductive failures.

[Laparoscopy with low abdominal pressure]. / Laparoskopiia s nisko intraabdominalno naliagane.

The authors present their experience from operative laparoscopies performed with lower than usually accepted intaabdominal pressure.

[Factors influencing successful rate of intrauterine insemination]. / Faktori, vliiaeshti vurkhu rezultativnostta na programite za intrauterinna inseminatsiia.

Intrauterine insemination (IUI) is a method for the treatment of marital infertility involving the intrauterine or fallopian deposition of washed spermatozoa, depending on the amount of inseminated semen. Numerous factors may be affect of pregnancy rates after IUI.

[Preimplantation genetic diagnosis: current status and perspective]. / Preimplantatsionna genetichna diagnostika: s'vremenno s'stoianie i perspektivi.

Scientific and clinical aspects of preimplantation genetic are represented.

[Effect of different co-culture systems on human sperm motility and longevity]. / Vliianie na razlichni sistemi za ko-kultivirane vurkhu motiliteta i prezhiviaemostta na choveshki spermatozoidi.

The experiments were conducted to evaluate the ability of different somatic-cell monolayers (human oviductal cells, granulose cells, MDBK-cells) for supporting motility and survival rates of human spermatozoa in-vitro. Results indicate that co-culture with epithelial cells enhanced human sperm longevity.

[The possibility for treating the premenstrual syndrome with Periodin]. / Vuzmozhnost za lechenie na premenstrualniia sindrom s Periodin.

We examined the possibility of treatment of premenstrual syndrome (PMS) with Periodin (Walmark). Periodin is a combination of polyvitamins, oligoelements and phytoextracts which have a relation with prostaglandin's synthesis and regulation of prolactin secretion. A group of 24 women with PMS and regular cycles in premenopausal period (mean age of 44.7) was examined and took Periodin 1-2 caps daily for a period of 3 months as a food supplement. The assessment was made by modified J. Mortola score system. After treatment the PMS symptoms decreased with 52.3% compared with the beginning. The authors conclude that Periodin has a considerable influence on PMS symptoms, no contraindications and could be useful widely in gynecological practice.

[Influence of the phytoestrogen drug, SoyaVital, on climacteric symptoms]. / Povliiavane na klimakterichnata simptomatika chrez fitoestrogenen preparat, SoyaVital.

The results of phytoestrogen drug SoyaVital on the climacteric symptoms are presented. The preparation consists of 35 mg isoflavones with high content of genistein in one capsule. A group of 26 patients having climacteric symptoms have been treated by one capsule per day for a period of 12 weeks. The evaluation of the symptoms by Kuppermann score decreased statistically significant by 30.06%. The authors recommend SoyaVital as an alternative to the hormonal replacement therapy.

[Use of the balloon catheter before induction of labor with oxytocin in cases with unfavorable pelvic score and premature delivery]. / Prilozhenie na balon katetur predi induktsiia na razhdaneto s oxytocin pri sluchai s neblagopriiaten pelvic score i nedonosena bremennost.

The purpose of this prospective work is to communicate the experience with preinduction treatment with Folly's catheter on the Pelvic score (Ps), labor and neonatal outcome in 52 cases in 27 to 34 wg, preterm premature labor and unfavourable cervix. The first control group consist of 24 pregnancies with the same characteristics but with favourable cervix at the begging of labor induction and the second control group include 31 cases with spontaneous premature labor. The Folly's catheter is introduced through the cervical canal and the bulb inflated with 75 ml of sterile normal saline. After the Foley's catheter dropped out the Ps is reassessed and proceed with oxytocin infusion. In the first control group with favourable cervix the induction of labor is only with oxytocin via infusion pump. More than half of all patients are treated with with tocolysis. The results show that for the period of tocolysis and/or PPROM there is significant improvement of the Ps (from 0.90 +/- 0.9 to 2.35 +/- 1.5). The change in the Ps doesn't depend on the g.w., the length of tocolysis or on the initial Ps. The balloon catheter improve the Ps from 2.35 +/- 1.5 to 6.24 +/- 1.3 for y period of 3 h 20 min (2 h 40 min to 4 h, 95% confidence). After the Foley catheter dropped out the duration of labor with oxytocin infusion is 6 h (5 to 7 h, 95% confidence) and is not different from this in the control groups. The time for the catheter to drop out, the achieved Ps and especially the effacement of the cervix are essential features in the prognosis of the difficulties in the labor process and the neonate state.

[Myomectomy during cesarean section]. / Miomektomiia po vreme na tsezarovo sechenie.

The purpose of this prospective study is to assess the possibility of myomectomy during CS as a routine method. The material includes 21 cases of myomectomy during CS. 162 consecutive CS without myomectomy are control group for hemorrhage during the operation. The myomectomy is accomplish according classical technique. Our data show that the myomas and pregnancy is found mainly in women after 30 years of age and is prevalent in nulliparas (70%). Single myomas were found in 85% of cases, 63% located in the corpus uteri and 46% of all myomas are confined to the myometrium. Related to the isthmus uteri are 23% of myomas. Myomectomy as a separate operation during CS increases the hemorrhage by 10%. The analysis of the cases with severe hemorrhage point to the placental disorders (abruptio placentae and placenta praevia) as a main cause of overall increased blood lost. Our limited experience with myomectomy as a protocol during CS irrespective of number and magnitude of myomas shows that this is possible. The postoperative period is without complications.

[The overall and step-by-step duration of cesarean section]. / Obshta i poetapna produlzhitelnost na tsezarovoto sechenie.

The purpose of this study is to define the time for different steps of Caesarean section from the moment the women lays on the operating table to the last stitch on the skin. The study is prospective and include 82 elective and emergent CS. The traditional surgical technique is used without omitting any step. The mean stay of the women in the operating theater is 90 min. The preparation for the anesthesia/analgesia is 23 min (range 8-41). The proper time of the operation is 44.3 min. The laparotomy by Pannenstiel incision takes 3 min. The opening time of the uterus is 37 sec (10-190) and the closer on two layers is 17 min (10-35). The extraction of the foetus takes 53 sec (15-180). The exteriorization of the uterus doesn't affect the repair time. Leaving the visceral and parietal peritoneum unsutured can spare 5.5 min. The elective CS takes more time than the emergent one. The time from the beginning of the operation to the extraction of the foetus is longer in resection (7 min) than in first CS (5 min).

[The Multiload--a modern intrauterine device]. / Multiload--modernata vutrematochna spirala.

In the first part of publication the authors make a profound review of history of development and qualities of Intra Uterine Devices/IUD's/. There are reflected the first steps dated from the ancient times to come to modern IUD's (Multiload, Copper T. Slimline). In Table 1 and 2 (on W.A.A. van Os) are represented single cases (pregnancy, expulsion and extracted IUD's) related to the modern intrauterine devices: MLCu 250 and MLCu 375 for the periods of 1, 3 and 5 years. In the second part the authors represent their scientific and practical results which has been obtained at the Bulgarian Family Planning and Sexual Health Association and the Ob./Gyn. Department of Medical University-Sofia. A retrospective research has been conducted on 406 women who delivered between 18 and 42 years of age and to which MLCu 375 have been inserted. The so analyzed and presented results show very good qualities of MLCu 375 IUD. The cases' frequency corresponds to the one announced by the world leading practice of contraception.

[An analysis of the indications for episiotomy in current obstetrical practice]. / Analiz na indikatsiite za epiziotomiia v suvremennata akusherska praktika.

The aim is to analyze the accepted indications for episiotomy in nowadays practice. The investigations is retrospective for the period from April to May 1996. The material includes 459 term singleton pregnancy in vertex presentation and 46 cases of premature neonates with weight from 1300 to 1499 g. The results show high risk (77.1%) of episiotomy in nulliparous women. The multiparity, the length of second period and the high risk pregnancies have not effect on the use of episiotomy. The wight of the fetus is essential factor. The highest rate of episiotomy is at premature births (65.2%) followed by the group of neonates with weight over 4000 g (61.5%). The lowest rist of episiotomy is then the weight of newborn is between 2500 and 3800 g (21.8%). Almost hundred percent rate of episiotomy in operative vaginal and breech deliveries show that we accept the episiotomy as obligatory of these vaginal deliveries.

[The results of the limited use of episiotomy in managing the second stage of labor]. / Rezultati ot ogranicheno prilozhenie na epiziotomiia pri vodene na vtori period na razhdaneto.

The purpose is to asses the effect of restrictive use of mediolateral episiotomy on the spontaneous laceration of the low birth canal. The material includes 613 labors some of which gave birth with indication for episiotomy and control group of 441 retrospective cases with routine management of the second period of labor. The restrictive use of episiotomy decreases the rate from 45.6% in the routine practice to 32.8%. The reduced rate of episiotomy has as a consequent increase rate of second degree perineal laceration adn insignificant increase of vaginal lacerations. The management of restrictive and liberal use of mediolateral episiotomy has not effect on third and four degree perineal laceration, on the accessory tears of the vagina and on the rate of perineotomy. If from all labors are subtracted operative deliveries, surgical intervention for repairing the laceration of the birth canal and pathology of the placental period the rate of labors without any intervention is only 13.3%. Our results suggest that labor nowadays is operative activity.