Characterization of vaginal lactobacilli in women after kidney transplantation.

Limited number of publications described vaginal microflora after kidney transplantation. Our PubMed search revealed only 18 publications including words "vaginal bacteria & kidney transplant" in the period of 1978-2011. The aim of this study was to characterize lactobacilli isolated from vaginal swabs of women after kidney transplantation, compared with healthy women. Eighteen renal transplant recipients (mean age 36.1) and 20 healthy women (mean age 36.0) were evaluated. Lactobacilli were cultured on MRS and Columbia blood agars. Biochemical identification with API 50 CHL (bioMerieux, Marcy L'Etoile, France) and multiplex PCR according to Song et al. was performed. Lactobacilli were tested for production of H(2)O(2). Minimal inhibitory concentrations (MICs) of selected antimicrobial agents were determined with E-tests (bioMerieux, Marcy L'Etoile, France) and interpreted with CLSI and EUCAST criteria. No bacterial vaginosis was found among studied women. Two strains of group I were identified as Lactobacillus delbrueckii; 18 strains as Lactobacillus gasseri and 15 strains as Lactobacillus crispatus. Only 3 strains from group II were not identified by species-specific mPCR. Group IV was represented with 2 unidentified strains. Vaginal lactobacilli isolated from healthy women represented more homogenous group compared with heterogenous renal transplant recipients. Biochemical identification of lactobacilli by API 50 CHL kits was concordant with mPCR results only in 7 cases (17.5%), all 7 strains were identified as L. crispatus. Majority (93%) of lactobacilli were H(2)O(2) producers. All isolated lactobacilli (100%) demonstrated high resistance to metronidazole (MIC > 256 µg/ml). Only 2 strains resistant to vancomycin (MICs: 32 and 256 µg/ml respectively), in the study and control group, and one to moxifloxacin (MIC = 32 µg/ml), were found. Resistance to metronidazole and vancomycin was concordant in CLSI and EUCAST (2010) criteria. Although significant differences between lactobacilli isolated from vaginas of kidney transplant and healthy women were not demonstrated, we demonstrated strains resistant to metronidazole, vancomycin and moxifloxacin in groups of examined women. Our study was performed on a small group of kidney transplant recipients and further more detailed molecular studies on a larger group of patients are required to confirm our results.

Posttreatment Strategy Against Hypoxia and Ischemia Based on Selective Targeting of Nonnuclear Estrogen Receptors with PaPE-1.

Newly synthesized Pathway Preferential Estrogen-1 (PaPE-1) selectively activates membrane estrogen receptors (mERs), namely, mERα and mERß, and has been shown to evoke neuroprotection; however, its effectiveness in protecting brain tissue against hypoxia and ischemia has not been verified in a posttreatment paradigm. This is the first study showing that a 6-h delayed posttreatment with PaPE-1 inhibited hypoxia/ischemia-induced neuronal death, as indicated by neutral red uptake in mouse primary cell cultures in vitro. The effect was accompanied by substantial decreases in neurotoxicity and neurodegeneration in terms of LDH release and Fluoro-Jade C staining of damaged cells, respectively. The mechanisms of the neuroprotective action of PaPE-1 also involved apoptosis inhibition demonstrated by normalization of both mitochondrial membrane potential and expression levels of apoptosis-related genes and proteins such as Fas, Fasl, Bcl2, FAS, FASL, BCL2, BAX, and GSK3ß. Furthermore, PaPE-1-evoked neuroprotection was mediated through a reduction in ROS formation and restoration of cellular metabolic activity that had become dysregulated due to hypoxia and ischemia. These data provide evidence that targeting membrane non-GPER estrogen receptors with PaPE-1 is an effective therapy that protects brain neurons from hypoxic/ischemic damage, even when applied with a 6-h delay from injury onset.

Prevalence of Cervical Infection With Human Papillomavirus of High Oncogenic Potential in Immunosuppressed Women on Renal Replacement Therapy With and Without Mammalian Target of Rapamycin Inhibitors.

BACKGROUND: Chronic immunosuppression constitutes a risk factor of human papillomavirus (HPV) related cervical cancer development. Maintenance immunosuppression with mammalian target of rapamycin (mTOR) inhibitors is associated with decreased incidence of de novo malignancies in kidney graft recipients. Recently published data suggest that mTOR inhibitors interfere with viral replication. The aim of the study was to assess if there is a difference in prevalence of HPV cervical infection in women on immunosuppressive regimens with or without mTOR inhibitors. MATERIAL AND METHODS: Cervical swabs taken from 64 immunosuppressed women on renal replacement therapy were analyzed for the presence of high-risk (HR) HPV DNA by means of an Amplicor HPV test and assessed taking into account the recorded data on mTOR inhibitor use. RESULTS: The testing revealed the presence of HR HPV DNA in none of the women that were treated with mTOR inhibitors and in 21.4% of patients that were administered immunosuppressive regimens without mTOR inhibitors (P = .08). Interestingly, 32% of women from the mTOR(-) group in contrast to 12.5% in the mTOR(+) group declared having had more than 2 lifetime sexual partners. CONCLUSIONS: Our results suggest that mTOR inhibitors might constitute a promising therapy modification in women at risk of HPV cervical malignancy development, but the effectiveness of such strategy requires further studies.

In Vitro Fertilization and Pregnancy Outcomes Among Patients After Kidney Transplantation: Case Series and Single-Center Experience.

INTRODUCTION: Kidney transplantation (KTx) is the treatment of choice in patients with end-stage renal failure. Among various medical issues in female graft recipients, the need for maternity can become an overriding one. Gonadal dysfunction usually resolves within 6 months after transplantation; however, the prevalence of infertility is similar to this in the general population. MATERIALS AND METHODS: This case series describes the experience in infertility treatment and following perinatal care among KTx women who underwent successful in vitro fertilization (IVF). We followed three patients who previously received KTx and underwent IVF between 2014 and 2015. The 34-year-old (patient A) and 39-year-old (patient B) women received single KTx, and the 31-year-old (patient C) woman had received three previous transplantations. Patients A and C were diagnosed with primary tubal factor infertility, while patient B suffered from secondary idiopathic infertility. The stimulation protocols had no influence on their general condition nor graft function. Viable singleton pregnancies were confirmed in all cases. All newborns were born preterm, via cesarean section, as a consequence of severe preeclampsia. Patients A and C gave birth at 34th week of gestation (WG) (A: 1810 g and C: 2295 g), while patient B gave birth at 36th WG (2655 g). Other pregnancy complications were intrauterine growth restriction (patient A) and gestational diabetes mellitus (patient B). Although mild graft dysfunction was observed prior to delivery, all clinical measures and hypertension resolved during the puerperium. CONCLUSIONS: In these cases, pregnancy after KTx did not implicate persistent graft dysfunction. Regardless of the method of conception, pregnancy following KTx is associated with an increased incidence of complications, therefore it requires a multidisciplinary approach. IVF itself seems to be a safe procedure in KTx recipients if the pregnancy is advisable.

Delivery Method in Patients After Liver or Kidney Transplantation.

Pregnancy following renal or liver transplant is safe for the mother, fetus, and allograft if standard practice guidelines are strictly followed. Cesarean delivery is often required for the safety of the mother and child. The aim of this paper was the evaluation of delivery method in patients after liver (G1) and kidney transplantation (G2) in comparison with the population of healthy pregnant women (G0). MATERIALS: Retrospective analysis included 51 (G1) and 59 (G2) women who delivered between 2000 and 2016. Control group (G0) consisted of 170 nontransplanted patients, who delivered between 2014 and 2016. The results were compared using nonparametric and parametric tests (Fisher exact test, t test). The SAS 9.2 was used for the analysis. RESULTS: The rate of cesarean delivery was high in all pregnancies following kidney (G1 = 80.4%) or liver transplantation (G2 = 67.8%) compared with control group (G0 = 44.1%; P < .05). The most common indication for cesarean delivery in G1 was gestational hypertension/preeclampsia (n = 18; 43.9%), threatening intrauterine asphyxia (n = 12; 29.3%), and failure to progress (n = 2; 4.9%). The most common indications for cesarean delivery in G2 were threatening intrauterine asphyxia (n = 14; 35%), failure to progress (n = 9; 22.5%), and gestational hypertension/preeclampsia (n = 2; 5%). CONCLUSION: Cesarean delivery in patients after kidney or liver transplantation is performed mainly for obstetric reasons. The reported incidence of cesarean delivery in pregnancy following transplant is high, reflecting the high degree of clinical caution exercised in these patients.

Operative treatment of endometrial hyperplasia in kidney graft recipients: report of seven cases.

OBJECTIVES: The high rate of abnormal uterine bleeding associated with endometrial hyperplasia has been observed in women after kidney transplantation. The great majority of these premalignant lesions regress after conservative treatment, mostly with progestagens. There are cases, however, of persistent or recurrent hyperplasia requiring operative treatment. MATERIALS AND METHODS: We report seven cases of endometrial hyperplasia in kidney graft recipients treated with hysterectomy after failure of conservative treatment. The presence of typical risk factors of endometrial hyperplasia and cancer were analyzed as well as their clinical courses and treatment methods. RESULTS: The age of the patients ranged from 35 to 50 years (mean, 42.7). Among typical risk factors, we observed obesity, diabetes, arterial hypertension, and nulliparity in the study group. All patients reported abnormal uterine bleeding and developed anemia. Women underwent two to four dilatation and curettage procedures. Progestagens (medroxyprogesterone or lynesterol) were administered for 3 to 9 months. The initial treatment was ineffective in two cases; in the remaining five cases endometrial hyperplasia recurred within 3 to 12 months. Pathologic findings after hysterectomy in all patients confirmed non-atypical endometrial hyperplasia. CONCLUSION: Hysterectomy is the treatment of last resort for premalignant endometrial lesions. It should be considered in all cases of recurrent or persistent endometrial hyperplasia. It may protect immunocompromised kidney graft recipients from heavy bleeding, severe anemia, and most of all, the of endometrial cancer development.

Oral and transdermal hormonal contraception in women after kidney transplantation.

AIM: The aim of the study was to assess the safety of low-dose oral or transdermal hormonal contraception in kidney recipients. MATERIALS AND METHODS: Twenty-six kidney recipients, aged 18 to 44 years (mean, 31.0) took low-dose contraceptive pills, and 10 kidney recipients, aged 22 to 36 years (mean, 31.4) used transdermal contraceptive systems. Contraception was administered for a period not shorter than 18 months. At the onset of therapy all patients showed stable graft function. The main indication for therapy was effective contraception. Additional indications were mild ovarian cysts and irregular or profuse menstruations. The pills consisted of 20 to 35 microg of etinyl estradiol and generation III progestogen. The contraceptive patch released 20 microg of etinyl estradiol and 150 microg of norelgesromin daily. RESULTS: No case of pregnancy was noted. Oral contraception was discontinued in two cases, in one case due to profound thrombophlebitis of the lower extremity and in the other case deterioration of liver function. No other side effects or symptoms of intolerance were reported. Hormonal contraception did not significantly influence body mass index, mean blood pressure, serum creatinine, or other biochemical parameters. CONCLUSION: Despite the presence of relative contraindications, mainly arterial hypertension and impaired liver function, hormonal contraception should be considered in female kidney recipients to be a highly effective contraceptive method that additionally regulates menstrual bleeding, protects from development of mild ovarian cysts and seems to positively influence women's well-being. The transdermal mode of administration may diminish the chance for drug interactions and therefore be safer for patients.

Mode of delivery in women after liver transplantation.

AIM: A high rate of cesarean sections has been reported among high-risk pregnancies in liver transplant recipients. The aim of this study was to analyze the course of deliveries and the indications for cesarean sections in women after liver transplantation. MATERIALS AND METHODS: From 2001 to 2006, we noted 21 deliveries in 17 liver recipients. The mean age of women was 27.9 +/- 6.6 years and the mean time from transplantation to pregnancy was 4.3 +/- 3.6 years. Most patients were primigravidas on tacrolimus-based immunosuppressive regimens. We retrospectively analyzed obstetric data regarding the delivery and the early puerperium. RESULTS: We noted 6 vaginal deliveries (29%) and 15 cesarean sections (71%). Mean gestational age in the group of vaginal deliveries was 37.6 +/- 2.2 weeks. No labor complications were noted. All neonates were delivered in a good state (Apgar score from 8 to 10 points) with mean birth weight of 2725 g. All cesarean sections were performed for obstetric indications: fetal distress, breech presentation, intrauterine growth retardation, or complications related to premature labor. Mean gestational age was 37.0 +/- 1.9 weeks. The Apgar scores ranged from 4 to 10 points; mean birth weight was 2787 g. The mean period of hospitalization after surgical labor was 4 days longer compared with the vaginal delivery group. CONCLUSION: The high rate of cesarean sections (71%) in liver recipients is associated with a great incidence of obstetric complications of pregnancy. Safe and uneventful vaginal delivery is possible with growing experience in the management of pregnant transplanted women.

High rate of endometrial hyperplasia in renal transplanted women.

UNLABELLED: A high rate of endometrial hyperplasia, an estrogen-dependent premalignant lesion of the endometrium, has been observed among female kidney allograft recipients. The aim of the study was to evaluate the incidence of endometrial abnormalities among renal transplanted women with abnormal uterine bleedings. MATERIAL AND METHODS: A retrospective analysis compared 45 renal transplanted women who underwent dilatation and curettage for abnormal uterine bleeding between January 1999 and September 2004 with 90 consecutive, nontransplanted, control patients who underwent dilatation and curettage for the same reason in 2004. RESULTS: Thirty-one cases (69%) of endometrial hyperplasia and one case (2%) of endometrial cancer were detected among the renal allograft recipients. The majority of transplant patients (28 cases, 62%) developed endometrial hyperplasia without atypia successfully treated with progestagens. There were 29 cases (32%) of hyperplasia without atypia, 2 cases (1%) of atypical hyperplasia, and 4 cases (4%) of endometrial cancer in the control group. CONCLUSIONS: Renal transplanted women seem to have an extremely high risk of endometrial hyperplasia. The majority of cases may be successfully treated with progestagens. Immunocompromised renal graft recipients, however, show other risk factors for carcinogenesis. Thus, frequent clinical surveillance should be recommended in this group of patients, also because there is conflicting evidence with regard to the risk of progression to carcinoma among untreated patients.

Function of the ovaries in female kidney transplant recipients.

OBJECTIVES: One of the effects of an improved general health state after successful kidney transplantation in women of reproductive age is recurrence of regular menstrual function. MATERIALS AND METHODS: Sixty-three ovarian cycles in female kidney transplant recipient, aged from 18 to 44 years, at 1.5 to 15 years after transplantation, were compared with 50 cycles of healthy women. We monitored the menstrual cycle duration as well as follicle stimulation hormone (FSH), leutinizing hormone (LH), estradiol, progesterone, prolactin, creatinine, and testosterone serum concentrations as well as hematocrit and obtained sonographic observations of ovarian follicle growth and ovulation. RESULTS: Of the recipients, 68.1% had regular menstrual cycles. Ovulatory cycles were observed in 45% of patients. Estradiol concentration established in the first phase of the cycle was significantly higher among the transplanted group (mean value 226.86 +/- 97.45 pg/mL vs 140.00 +/- 61.00 in the controls). A significantly lower level of progesterone (15.05 +/- 17.34 ng/mL vs 30.79 +/- 18.48 ng/mL in the controls) and of testosterone were observed in kidney recipients. Other hormonal parameters did not differ significantly between the groups. CONCLUSIONS: Similar serum FSH, LH, and prolactin concentrations as well as increased levels of estrogens were observed in kidney transplant recipients compared with healthy nonrecipients. The rate of ovulatory cycles in regularly menstruated kidney graft recipients was similar to that of healthy women. Stabilization of graft function resulted in restoration of normal ovarian hormone metabolism and ovulatory cycles in female kidney transplanted recipients.

Menstrual cycle and sex hormone profile in perimenopausal women after liver transplantation.

UNLABELLED: Excellent long-term outcomes of transplant patients let many female liver-recipients experience perimenopausal problems. This study assessed menstrual patterns and sex hormone profiles in women of perimenopausal age who experienced end-stage liver failure treated by transplantation (OLT). MATERIALS AND METHODS: Menstrual patterns, sex hormone profiles, and biochemical parameters of liver function were analyzed before and after OLT in 13 liver-transplanted patients of perimenopausal age. Nineteen healthy perimenopausal women served as controls. RESULTS: The most common abnormality of the menstrual cycle observed in the study group was secondary amenorrhea, which affected six liver-transplanted women. Three months after OLT amenorrhea was still observed in six patients, regular menstrual cycles in six and irregular bleeding in one graft recipient. One year after transplantation regular menstruations were noted in four, irregular bleeding in four, and secondary amenorrhea in five liver-transplanted women. Similar levels of follicle stimulating hormone, luteinizing hormone, prolactin, progesterone and testosterone as well as lower levels of estradiol and DHEA-sulfate were observed in patients with liver failure, both before and after grafting, compared with healthy women. After OLT E2 levels increased from 32.05 +/- 18.04 to 49.12 +/- 22.21. CONCLUSIONS: One year after OLT disturbances in menstrual patterns affect most (69%) perimenopausal female liver recipients. Both before and after OLT significantly lower levels of estradiol and DHEA-S were observed in transplanted patients compared with healthy controls. Hormonal therapy of amenorrhea or irregular menstruations may be required in that group of patients.

Safety and efficacy of hormonal therapy in menopausal kidney-allograft recipients.

AIM: A higher risk of premature menopause and osteoporosis has been observed in female kidney-allograft recipients, providing particular indications for hormonal therapy. We have summarized our 10-year-experience with hormonal therapy in menopausal kidney transplant recipients. MATERIALS AND METHODS: From 1995 to 2004, hormonal therapy was administered to 54 kidney transplant recipients. At onset of therapy the ages of the women ranged from 31 to 52 years, and the period from transplantation from 3 months to 13 years. The mean time on therapy was 4.2 years. All patients received transdermal estradiol (E(2)) in combination with oral progestin. RESULTS: Total regression of climacteric symptoms was reported in 75% of patients. After 3 months of the therapy follicle stimulating hormone (FSH) and E(2) levels normalized: FSH from 129 +/- 30.1 IU/L to 38.3 +/- 26.1 IU/L and E(2) from 18.5 +/- 5.8 pg/mL to 98.6 +/- 33.2 pg/mL. No significant change was noted in serum creatinine. Eleven patients developed abnormal uterine bleeding but none had premalignant or malignant lesions of the uterus on endometrial curettage. No incidence of breast cancer was noted during mean treatment period of 5.2 years. Seventeen patients discontinued therapy for medical indications: one for profound thrombophlebitis and 16 for significant deterioration of liver function. Twelve women made their own decision to discontinue therapy. CONCLUSION: Hormonal replacement therapy was effective with no negative impact either on graft function or sex organs among kidney transplant recipients. Liver parameter monitoring seemed to be essential for safe continuation of treatment.

Outcome of four high-risk pregnancies in female liver transplant recipients on tacrolimus immunosuppression.

Pregnancies in women after liver transplantation are considered high risk due to the greater rate of complications observed in immunosuppressed graft recipients. We report successful outcomes of four high-risk pregnancies in female liver transplant recipients on tacrolimus-based immunosuppression. The patients, aged 23 to 32 years, at the time of conception were 12 to 59 months from transplantation (mean 30 months). Preterm labor was the most important pregnancy complication observed in these patients. One episode of acute graft rejection was observed. A variable demand for tacrolimus was noted during pregnancy. Despite complications all four pregnancies were successful. The mean gestational age at delivery was 34.4 weeks. The birth weight of the newborns varied from 1410 to 3490 g (mean 2303 g) and the mean Apgar score was 8. No structural malformations or early complications were observed in the newborns. Excluding the patient with acute rejection, the remaining three cases showed all liver parameters to remain stable.

Should We Be Concerned About Asymptomatic Adnexal Masses in Female Kidney and Liver Graft Recipients?

BACKGROUND: Pathological changes of uterine adnexa are frequently encountered in patients after solid-organ transplantation. The aim of the study was to evaluate the incidence of malignancies among recipients operated with the diagnosis of adnexal tumor with or without clinical symptoms. METHODS: We retrospectively analyzed data from 146 solid-organ recipients who underwent surgery in the First Department of Obstetrics and Gynecology, Medical University of Warsaw, in the years 2000 to 2014. Among them, we identified 80 patients of mean age 40.9 ± 11.1 years with suspected adnexal tumor. Data on symptoms reported by patients were compared with the results of histopathological examination after surgical treatment. RESULTS: Kidney recipients were 76.2% of the group studied (including 5 women after kidney and pancreas transplantation); the remaining 23.75% of patients were liver recipients (including 1 kidney and liver). The majority of patients (71.25%) reported no clinical symptoms. The remaining 28.75% of patients had clinical complaints, with the most common symptom being abdominal pain (in 60% of patients). Analysis of the results of histopathological examination revealed that in both groups, the most often encountered pathological findings were serous cystadenoma (33.3% and 47% of patients, respectively), endometrial cysts (24.6% and 21.7%, respectively), and functional cysts (22.8% and 17.3%, respectively). None of the asymptomatic patients were diagnosed as malignant, whereas 2 cases (both ovarian and fallopian tube cancer) were diagnosed among women who reported clinical symptoms. CONCLUSIONS: Observations of patients after organ transplantation indicate a recurring nature of adnexal changes, resulting in qualification for surgical treatment. The survey results suggest that solid-organ recipients with pathology in the uterine adnexa, with non-suspicious ultrasound image and not reporting clinical symptoms, could safely be subjected to clinical observation providing strict supervision.

Congenital Infections in Neonates of Women With Liver or Kidney Transplants.

BACKGROUND: Immunosuppressive therapy is associated with an increased risk of pregnancy complications and may have adverse effects for the newborn. The aim of this study was to determine the frequency and the type of early congenital infections and to assess typical markers of infections in neonates of liver and kidney recipients. METHODS: A retrospective analysis of 71 neonates born to either liver (39 cases) or kidney transplanted women (32 cases) was conducted. The rate and the type of newborns' infections as well as laboratory and bacteriologic markers of infections were analyzed. RESULTS: There was no significant difference in the frequency of congenital infections between the LT and KT groups (8 vs 7 cases; P = .879).). The rate of infections was not significantly higher in both groups compared with the general population. Infections were detected in 23.9%, 13.6%, and 26.6% of neonates born to mothers using tacrolimus, cyclosporine, and azathioprine respectively. No significant differences in white blood count or levels of neutrocytes and lymphocytes were observed between the groups. No abnormalities in white blood smear, but 1 case of leukopenia in the kidney transplant group, were detected. CONCLUSIONS: The rate of congenital infections in neonates of allograft recipients is not significantly higher than in the general population. Immunosuppressive regimens with azathioprine seem to carry the greatest risk, it is a little lower in the tacrolimus group, and cyclosporine-based regimens have the lowest risk of congenital infections. Differences were not statistically significant. Prenatal exposure to immunosuppressive agents seems not to be associated with any hematologic disturbances in white blood count and white blood smear.

Hypertension in Pregnant Renal and Liver Transplant Recipients.

BACKGROUND: Pregnancies in transplant recipients involve risks for both grafts and the fetus, and need to be carefully managed. Hypertension is the most frequent complications in pregnant transplant recipients, especially in renal transplant recipients. Strict control of blood pressure is essential for a favorable obstetric outcome and long-term graft survival. The aim of the study was to evaluate the influence of hypertension on obstetric outcome and graft function in pregnant renal transplant recipients (RTR) or liver transplant recipients (LTR) in comparison with healthy pregnant women. PATIENTS AND METHODS: This retrospective analysis included 46 RTR and 55 LTR who delivered between the years 2000 and 2014. The control group consisted of 187 nontransplant patients aged 20-45 years who delivered between 2010 and 2013. The analyzed group was divided into 2 subgroups: patients with hypertension and patients without hypertension. Descriptive data analysis, Fisher Exact test, unpaired Student t test, and analysis of the variance were performed. RESULTS: Hypertension prevalence among the RTR, LTR, and control group was 73.5%, 34.5%, and 4.3% respectively. In the RTR group, the mean gestational age at delivery inp patients with hypertension vs without hypertension was 36 vs 34.5 weeks (P < .05); IUGR was diagnosed in 20% vs 8.5% pregnant women (P > .05). In the TRL group, the mean gestational age at delivery in group with hypertension vs without hypertension was 37 vs 3.9 weeks (P < .05); IUGR was diagnosed in 10.5% vs 5% of pregnant women (P > .05). Hypertension in RTR patients had a negative influence on graft function (P > .05). CONCLUSION: Hypertension is common in organ recipients, and is associated with adverse pregnancy outcomes and loss of graft function.

Interaction between ethanol and diazepam in mice: chronobiological aspects.

The mechanism of action of benzodiazepines and ethanol demonstrates that these agents can synergistically affect the central nervous system (CNS). The effects of both ethanol and diazepam are likely to depend on the time of the day when they were administered. Diazepam influence on ethanol-induced sleeping and hypothermic activity in mice as well as the influence of combined administration of these agents on spontaneous locomotor activity and coordination in mice (rota-rod) were investigated. Experiments were carried out in the light phase (10:00-12:00 h) and the dark phase (22:00-24:00 h). It was shown that ethanol-induced sleeping time was longer in the dark phase than the light phase, and that ethanol increased spontaneous locomotor activity both in the light and the dark. Ethanol-induced hypothermia was lower in the dark than in the light. Diazepam decreased locomotor activity more strongly in the dark phase than by day. It impaired the hypothermic action of ethanol in the light phase, but did not have such an effect in the dark phase. Diazepam prolonged ethanol-induced sleep in the light phase, enhanced its action on locomotor coordination and decreased the stimulating effect of ethanol on spontaneous locomotor activity in mice. The chronobiological effect of the interaction between diazepam and ethanol seems to be of practical importance (sleep and motor coordination).

Pregnancy and delivery in women with esophageal varices due to hepatic vein thrombosis.

AIM: Retrospective analysis of the course of pregnancy, labor and mode of anesthesia in women with portal hypertension and esophageal varices induced by portal vein thrombosis. MATERIAL: From 2000 to 2012 seven pregnant were admitted. None had liver transplantation (Ltx), the varicose have been in the 1st stage. Each of them has been consulted by the obstetrician, transplant surgeon and anesthetist. The patient condition during pregnancy, labor and postpartum period was analyzed. RESULTS: Pregnancy in five cases proceeded physiologically. In one threatening miscarriage was diagnosed and treated with gestagens, two patients had tocolytic. One required variceal banding twice. In three thrombocytopenia worsened, with platelet count <70 g/L (up to 59 g/L). They received platelet transfusion before delivery. In one case, significant hipoproteinemia (4.7 g/L) occurred. In a case, GDM G1 and oligohydramnios were found. All women delivered at term (37-40 Hbd). In all general anesthesia with the use of remifentanil was done. There were no fluctuations in MAP and HR. Incision to delivery time was 2.5 min. Time from opioid administration to birth was <4 min. All children were born in good condition, weight 10-90 percentile. Regional anesthesia is contraindicated in patients with thrombocytopenia. In patients with esophageal varices sudden increase in heart rate and blood pressure can cause hemorrhage. CONCLUSION: Patients with portal hypertension can deliver at term. It is a high-risk pregnancy. In this group it is desirable to shorten the second stage of labor or complete it by c-section under general anesthesia with remifentanyl which allows getting desired analgesia without complications in the newborn. Surveillance of pregnant with portal hypertension must include monitoring of liver function and coagulation disorders.

The effect of pregnancy on humoral rejection in patients after vascularized organ transplantation.

The aim of the study was to evaluate the effect of pregnancy on the production of donor- and nondonor-specific anti-human leukocyte antigen antibodies (anti-HLA Abs) in organ allograft recipients. The study group included four pregnant kidney (RT) and four liver (LT) transplant recipients. The genotype of HLA class I (A, B) and class II (DR) antigens was assessed. Anti-HLA antibodies class I and II were evaluated between 36 and 40 weeks' gestation. Two different control groups consisted of the following: group I (n=8) with nonpregnant RT (n=6) and LT recipients (n=2), and group II with healthy pregnant women (n=10) with anti-HLA Abs detected between 38 and 41 weeks' gestation. The HLA genotype was determined in fathers of the fetuses from the study group and group II controls. Half of group II controls had donor-specific anti-HLA (A, B, and/or DR) Abs, while nondonor-specific anti-HLA Abs were detected in all subjects from that group. Anti-HLA Abs were found in all group II controls. In the study group, anti-HLA Abs were found in only two LT recipients and one RT recipient, but they were not confirmed as donor-specific. Anti-HLA antibodies were not detected in the study group, whereas six out of ten group II controls had anti-HLA Abs against the HLA of the child's father. Pregnancy in vascularized organ recipients does not trigger the mechanism of humoral rejection involving anti-HLA class I and II antibodies with a potentially adverse impact on graft function.

Synthesis and evaluation of analogues of 4-androstene-3,17-dione as aromatase inhibitors.

Twenty-three synthetic analogues of 4-androstene-3,17-dione (androstenedione) have been evaluated as inhibitors of human placental microsomal aromatase enzyme. Among the most potent of these compounds were the 4-hydroxy, 6 alpha-fluoro, 6 beta-fluoro, and 4-fluoroandrostenediones and 4-fluoro-19-nor-4-androstene-3,17-dione. 4-Hydroxy-4-androstene-3,17-dione (4HAD) is an irreversible inhibitor of aromatase in vitro, whereas the four fluoro analogues are reversible inhibitors. 4HAD and 4-fluoro-4-androstene-3,17-dione caused significant regression of the nitrosomethylurea-induced mammary tumor in rats, but the other fluoro derivatives were inactive.