Inhibition of poly(ADP-ribose) polymerase may have preventive potential for varicocoele-associated testicular damage in rats.

Varicocele is ordinarily accompanied by testicular damage and male infertility. Several theories have been proposed to explain the detrimental effect of varicocele on testis tissue, including the possible effects of oxidative stress. The poly(ADP-ribose) polymerase (PARP) pathway has been established as a major downstream intracellular pathway of oxidative stress. Recently we have reported that PARP pathway has been activated in varicocele-induced rat testicular damage model. The aim of the present study was to investigate the possible protective effect of PARP inhibition in varicocele-associated testicular damage. Fifty male Wistar rats were divided into five groups: control, sham, varicocele-induced, varicocele-induced 1,5-isoquinolinediol (ISO, a PARP inhibitor)-treated, and ISO treated groups. The ISO-treated rats received intraperitoneal injections of 3 mg/kg ISO daily for 13 weeks. After 13 weeks of varicocele induction, body and testes weights were investigated in all groups. Histopathology of testes were evaluated by light microscopy. Expressions of PAR, p53 and cytochrome c were detected by immunohistochemistry and cleaved PARP-1, PAR, p53 and cytochrome c by western blot. The degree of apoptosis was determined by TUNEL. Light microscopy revealed testicular damage comprising various degrees of seminiferous tubule degeneration in varicocele-induced rats and their testes weights decreased significantly, whereas ISO administration prevented it. Expressions of cleaved PARP-1, PAR, cytochrome c, and p53 increased significantly in varicocele-induced rats, whereas the level of these molecules were similar to controls in varicocele-induced rats treated with ISO. In conclusion, increased PARP activation in testes seems to be related with testicular damage and apoptosis associated with varicocele and pharmacological inhibition of this pathway might be an effective intervention to prevent varicocele-induced testicular injury.

Sudden death of a pregnant woman in third trimester with no risk factor.

Acute myocardial infarction in pregnancy is rare and life-threatening for both the mother and the fetus. We present the case of a 31-year-old previously healthy woman with no risk factors at 32 weeks of gestation who applied with vomiting, dyspnea and orthopnea. A respiratory arrest developed followed by loss of the fetal viability, cardiac arrest, and failure of resuscitation. We aim to raise awareness about the clinical approach to pregnant patients who are to be considered with a broad spectrum of differential diagnosis.

Hyperemesis gravidarum: current aspect.

An advanced state of nausea and vomiting, which are common symptoms of early pregnancy, is known as hyperemesis gravidarum and may result in dehydration, ketonuria, catabolism and require hospitalisation. Aetiological factors include increased hCG and steroids, multiple pregnancy and vitamin deficiency. Differential diagnosis of nausea and vomiting should be made and supportive treatment as well as antiemetic therapy is recommended. This review discusses aetiology and management modalities of hyperemesis gravidarum including fluid therapy, antiemetics, vitamins, psychological support and non-pharmacological measures.

The effect of oestradiol and neta on immunohistochemical staining of iNOS and eNOS in coronary arteries of ovariectomized rats.

AIM: The postmenopausal period is associated with increased risk for coronary atherosclerosis, and the effect of hormone replacement therapy in reducing this risk is controversial. Previous studies reported that nitric oxide synthetase (NOS) level might be important for the development of atherosclerosis, but no study has shown the interaction between hormone replacement therapy and endothelial NOS and inducible NOS intensity on coronary arteries yet. Our goal was to find out the immunostaining intensity of endothelial NOS and inducible NOS in ovariectomized rats which received oestradiol and norethisterone treatment. METHODS: We performed bilateral ovariectomy in 15, female, 90-day-old Wistar rats with an average weight of 250 grams. After waiting for 4 weeks for the menopausal state, they were divided into 3 groups to receive either placebo, 0.1 mg/day 17-beta-oestradiol (group E2), or 0.1 mg/day 17-beta-oestradiol + 0.1 mg/day norethisterone acetate (group E2-NETA) for 5 weeks. Another group included 5, normal, adult, female intact rats and served as controls. At the end of the treatment, all rats were sacrificed and coronary arteries were stained with inducible NOS and endothelial NOS polyclonal antibodies using streptavidin-biotin technique. RESULTS: The immunostaining of inducible NOS was prominent in perivascular connective tissue of the ovariectomized group but not in the control group. The inducible NOS immunostaining immunoreactivity was not detected in either treated groups. Immunostaining intensity of endothelial NOS did not differ in any 4 groups with similar staining. CONCLUSION: The present findings indicate that hormone replacement therapy down-regulates iNOS expression in coronary arteries of ovariectomized rats, and reduced iNOS may likely be involved in estrogen's beneficial effects.

Sexual life following total abdominal hysterectomy.

AIM: The goal of this study was to evaluate the effect of total abdominal hysterectomy (TAH) on sexual lives of patients in the postoperative period. MATERIALS AND METHODS: Eighty-six patients who accepted to participate a phone-questionnaire were recruited in the study after TAH or TAH + BSO. They were asked about sexual desire, pain during sexual intercourse, frequency and satisfaction of sexual intercourse at pre- and postoperative periods, and loss of "feeling a woman" in the postoperative period. Sexual desire, pain during sexual intercourse, loss of "feeling a woman" questions were answered as "yes" or " no", number of weekly sexual intercourse was recorded, and satisfaction was graded as no = 0, mild = 1 and complete = 2 points. RESULTS: While sexual desire and frequency were found to be significantly lower (p=0.026 and p=0.01 respectively), no difference was noted in dyspareunia and satisfaction. When the patients were divided into two groups according to the presence of endogenous or exogenous estrogen, no difference was seen between the two groups in the postoperative period. CONCLUSION: We concluded that the effect of TAH or TAH+BSO operations were mainly on sexual desire and the number of weekly intercourse, and estrogen in the postoperative period did not make any difference between the two groups.

Immunolocalization of integrins and fibronectin in tubal pregnancy.

Integrins are a large family of cell adhesion molecules that serve as receptors involved in cell-to-cell and cell-to-matrix interactions during implantation. We studied immunohistochemical staining of integrins (alpha 3, alpha V, beta 1, and alpha 2 beta 1) and fibronectin in ectopic tubal pregnancy. Thirty fallopian tube samples with ectopic pregnancies and five normal tubal segments were obtained during ligation operations; the latter specimens served as controls in the study. Formalin-fixed paraffin-embedded tissue sections were stained with hematoxylin-eosin or primary antibodies against alpha 3, beta 1, alpha V, and alpha 2 beta 1 integrins and fibronectin, using the avidin-biotin-peroxidase method. A semi-quantitative grading system was used to compare staining intensities. In the control samples, immunostaining of all integrins was found in a single layer of tall columnar epithelial cells, the lamina propria (Lp) and the muscular layer. Fibronectin staining was detected in the Lp and the muscular layer. Staining intensities of alpha 3 and beta 1 integrins and fibronectin were increased in the normal part of fallopian tubes with ectopic pregnancies. Staining of beta 1 integrin was more intense than staining of alpha 3 and fibronectin, whereas there was no difference in alpha V and alpha 2 beta 1 integrin expression between normal tubal tissue in the ectopic pregnancy group and control tubal tissue. In the tubal pregnancy group at the site of implantation, staining intensity of alpha 3 and beta 1 integrins and fibronectin was strong in decidual cells, supporting tissue and placental villi, whereas alpha V and alpha 2 beta 1 staining was mild. We concluded that integrins, especially beta 1 and alpha 3, and fibronectin may play a role in progression of tubal implantation. Although the role of integrins has not yet been clearly defined, these molecules may function as markers of normal and abnormal states of receptivity. We like to suggest that integrins and fibronectin, which are needed in utero implantation, are expressed in tubal tissues during ectopic pregnancy and are involved in ectopic implantation.

Endothelial dysfunction in preeclampsia. Increased homocysteine and decreased nitric oxide levels.

Endothelial dysfunction underlies the pathogenesis of preeclampsia, but its mechanism has not yet been completely understood. Elevated oxygen free radicals may partially explain the endothelial cell damage. In this study, we have aimed to measure homocysteine (Hcy) and nitric oxide (NO) levels as endothelial dysfunction markers in preeclamptic women. Nineteen preeclamptic (33.9 +/- 1.4 weeks) and 15 gestational-age-matched normal pregnant women (35.5 +/- 0.7 weeks) were included in the study. Mean NO level was significantly lower (p < 0.001) and mean Hcy level was significantly higher (p < 0.001) in the preeclamptic group. Elevated Hcy and oxygen free radical levels could decrease NO levels due to the reaction with each other and reduced NO may increase blood pressure and ischemia in preeclamptic patients. We have concluded that increased Hcy and oxygen free radical levels, and decreased NO levels are closely associated with preeclampsia-related endothelial dysfunction.

Increased vascular surface density in ovarian endometriosis.

Our goal in this study was to investigate the presence of angiogenesis-related factors in endometriomas by evaluating their vascular surface densities. Thirty ovarian samples were included in the study. Of these, ten were histologically confirmed endometriomas, ten were ovarian specimens in the follicular phase and ten were ovarian specimens in the luteal phase, serving as controls. Histological specimens were immunostained for von Willebrand factor (vWF: factor VIII-related antigen) and CD34. The area with the highest microvessel density in endometriosis and in the normal ovary was evaluated by using an intercept grid. All microvessels in a specific field (x 100 magnification) were counted and vascular surface density was measured, as 164.01 +/- 21.26 vs. 125.15 +/- 11.28 and 117.44 +/- 9.27 by using vWF, and as 172.97 +/- 25.64 vs. 138.65 +/- 32.21 and 120.34 +/- 18.40 by using CD34 in endometriotic, follicular and luteal ovarian samples, respectively (p < 0.001). The mean vascular surface density was significantly higher in endometriosis than in the ovarian samples of the follicular phase or the luteal phase. No significant difference was seen between normal ovarian samples. Endometriosis was associated with angiogenic properties. Having demonstrated elevated angiogenic factors in endometriotic samples, we concluded that activation of angiogenesis might be a key factor in the pathogenesis of endometriosis.

Atherogenic profile in preeclampsia.

Atherosis is accepted to underlie the pathogenesis of preeclampsia, therefore we aimed to determine malonyldialdehyde (MDA) levels as a marker of lipid peroxidation, and lipoprotein(a) (Lp(a)), apolipoprotein A-1 (Apo A-1) and apolipoprotein B (Apo B) levels as a marker of atherogenic profile in preeclamptic and normal pregnant women. Twenty preeclamptic and 20 gestational-age matched normal pregnant patients were enrolled in the study, mean gestational ages for the preeclamptic and the control group were 33.9+/-1.4 and 35.5+/-0.7 weeks, respectively. Blood was withdrawn from the patients soon after diagnosis, and from the controls at their routine prenatal visits. MDA levels was significantly higher in preeclamptic patients (P=0.0003), but no difference was observed in Apo A-1 and Apo B and Lp(a) levels between the 2 groups. We consider that higher MDA was due to oxidative stress seen in preeclampsia, and similar Apo A-1 and Apo B and Lp(a) levels were due to lack of systemic atherosis.

The effect of tibolone on endometrial IGF-1 and IGFBP-1 levels in ovariectomized rats.

OBJECTIVE: The goal of this study was to search the effects of two different doses of tibolone on endometrial IGF-1 and IGFBP-1 levels in ovariectomized rats. METHODS: Eighteen adult, female, 80-90-days-old, Wistar rats with an average weight of 250 g underwent bilateral ovariectomy under general anesthesia. After waiting for 4 weeks, they were randomized into three groups to receive either oral tibolone in two different doses or placebo. The treatment was continued for 5 weeks, and then the rats were sacrificed and the endometria were analyzed. RESULTS: Low columnar epithelium of the endometrial surface, longer epithelium and stratified squamous epithelium were seen in the control, low-dose and high-dose groups, respectively. The staining intensity of IGF-1 was mild in control, and moderate in both treatment groups, the difference between control the treatment groups was significant (P=0.015 for group L, and P=0.03 for group H). The staining intensity of IGFBP-1 was moderate in control, and strong in groups L and H. Again the difference was significant between control and both treatment groups (P=0.039 for grup L, and P=0.03 for group H). No significant difference was noted between each treatment group for both IGF-1 and IGFBP-1. CONCLUSION: Tibolone caused histological changes in endometrium and stimulated IGF-1 and IGFBP-1 staining. Both low and high dose treatments led to moderate and strong staining intensities for IGF-1 and IGFBP-1, respectively. The strong staining intensity of IGFBP-1 is likely due to the progestagenic effect of tibolone.

Immunohistochemical staining of IGF-I, IGF-binding proteins-1 and -3, and transforming growth factor beta-3 in the umbilical cords of preeclamptic patients.

BACKGROUND: To detect the immunoreactivity of insulin-like growth factor-I, insulin-like growth factor-binding proteins-1 and -3 and transforming growth factor beta-3 in the umbilical cords of normal and preeclamptic patients. METHODS: Umbilical cords were obtained from 15 normal and 15 preeclamptic patients. Immunoreactivities were determined using either indirect immunofluorescence or immunoperoxidase techniques on formalin-fixed, paraffin-embedded sections. Staining intensity was graded by a semiquantitative scoring method. The results were compared by Mann-Whitney U-test. RESULTS: The umbilical cords were thinner and the vessels were hypoplastic in the preeclamptic group. Moderate staining intensity for insulin-like growth factor-I, insulin-like growth factor binding protein-1 and -3 and transforming growth factor-beta 3 was observed in normal patients. The preeclamptic group had mild and strong intensities for insulin-like growth factor-I and insulin-like growth factor binding protein-1, respectively, and intensity for insulin-like growth factor binding protein-3 did not change, but diffuse and increased intensity was observed for transforming growth factor-beta 3. CONCLUSION: Changes in the intensity of insulin-like growth factor-I and its major binding protein and the transformation of growth factor-beta 3 may play a role in the pathogenesis of preeclampsia by altering the structure and responsiveness of the umbilical cord.

Clomiphene citrate does not adversely affect endometrial leukemia inhibitory factor levels.

The aim of this study was to compare endometrial leukemia inhibitory factor (LIF) levels in spontaneous and clomiphene citrate (CC)-induced cycles of patients with unexplained infertility. The patients were followed in two consecutive cycles. Endometrial samples were obtained 7 days after ultrasonographic evidence that ovulation has occurred during the spontaneous cycle, then the patients were induced with CC from day 5 to day 9 during the subsequent cycle with 50 mg/day, and ovulation monitoring and endometrial biopsy were performed in the same manner. The samples were obtained using a Pipelle biopsy device without using local anesthesia, and kept in formaldehyde solution until the day of measurement. Then they were homogenized in phosphate buffered distilled water, and LIF levels were detected in the homogenized fluid by ELISA method. Endometrial LIF levels were 470 +/- 52 and 501 +/- 45 pg/1 gram wet tissue in spontaneous and CC-induced cycles respectively, revealing no significant difference. Ovulation induction with CC did not adversely affect endometrial LIF levels.

Hyperemesis gravidarum: current concepts and management.

Hyperemesis gravidarum is a common problem for an obstetrician. Though nausea and vomiting are quite common in pregnancy, hyperemesis is found in only 1-20 patients per 1000. In this practical review, a general outline of the syndrome, its relation to the gastrointestinal system and thyroid, mild and rare severe complications, and conventional treatment versus newer options are discussed.

Insulin: does it induce follicular arrest in the rat ovary?

The goal of this study was to investigate histological changes of the rat ovary treated with either insulin or insulin plus human chorionic gonadotropin (hCG). The study was conducted in Celal Bayar University, School of Medicine, Animal Research Laboratory. Eighteen adult female Wistar rats were divided into three groups to receive saline, or insulin, or insulin plus hCG for 4 weeks. At the end of treatment the rats were sacrificed and the ovaries were evaluated with hematoxylin and eosin. There was no abnormal change in rats treated with saline. A thickened capsule, stromal hypertrophy and stromal cell hyperplasia, and no developing follicles, were observed in the insulin-only group. A thin capsule, developing follicles and corpora lutea, and normal theca cells and stroma were observed in the insulin-plus-hCG group. We conclude that insulin may lead to histological changes similar to stromal hyperthecosis and polycystic ovary syndrome, and may be one of the factors causing follicular arrest.

Clomiphene citrate does not affect the secretion of alpha3, alphaV and beta1 integrin molecules during the implantation window in patients with unexplained infertility.

BACKGROUND: The expression of integrin molecules on the endometrium suggests that certain integrins may participate in the cascade of molecular events leading to successful implantation. A prospective, controlled study was carried out to investigate the effect of clomiphene citrate (CC) on secretions of beta1, alpha3 and alphaV integrin molecules in the endometrium of patients with unexplained infertility during the implantation window. METHODS: A total of 40 endometrial samples was evaluated in both spontaneous (n = 13) and ensuing clomiphene-treated cycles (100 mg on days 5-9) and also from fertile women serving as controls (n = 14) during postovulatory 7th or 8th day of menstrual cycle. A semiquantitative grading system (H-score) was used to compare the immunohistochemical staining intensities. Endometrial thickness and serum oestradiol and progesterone concentrations were also measured on the day of sampling. RESULTS: Staining of alpha(v) but not beta1 and alpha3 integrins was significantly less intense in infertile cases than fertile control cases (1.42 +/- 0.12 versus 2.21 +/- 0.13 respectively, P = 0.012) and this was not restored to normal concentrations with treatment. CONCLUSIONS: Our study indicated that cc treatment significantly decreased the endometrial thickness and increased oestradiol and progesterone concentrations. However, secretion of alpha(v), beta1 and alpha3 integrin molecules, which might play a role in implantation, was not affected.

Laser therapy in chronic cervicitis.

Chronic cervicitis is one of the common disorders encountered in daily practice. To overcome this problem first step should be antibiotic therapy in acute phase. If this fails, the infection becomes chronic and may spread to internal genital organs leading to pelvic inflammatory disease and eventually to infertility. Chronic form of infection may necessitate tissue destruction to prevent the development of dysplasia and neoplasm. Various methods such as electrocautery, loop diathermy, cryotherapy or laser are used to destroy the inflamed area. In this study we present 26 cases of chronic cervicitis managed with Nd-YAG laser with a success rate of 93%. We advice this method to block the development of cervical intraepithelial neoplasm.

Immunolocalization of transforming growth factor-beta 3 in pregnant human myometrium.

BACKGROUND: Transforming growth factor-beta 3 is a cytokine which is involved in cell growth regulation and differentiation, stimulation of extracellular matrix and modulation of immune responses. The goal of this study was to detect the presence of this cytokine in the myometrium of preterm and term, nonlaboring and laboring patients, and to measure serum levels of interleukin-1 beta (IL-1 beta), IL-6 and IL-8 before cesarean section. METHODS: In this prospective study, we obtained samples of myometrium from the lower uterine segment during elective and emergency cesarean sections (term non-laboring, n=8; term laboring, n=7; preterm non-laboring, n=3; and preterm laboring, n=19) and stained for transforming growth factor-beta 3. Blood was also sampled from the same patients to determine IL-1 beta, IL-6 and IL-8 levels. RESULTS: Different intensities of staining were detected in preterm laboring, term nonlaboring and term laboring groups, but there was no staining in preterm nonlaboring group. We also found a statistically significant difference in IL-6 levels between laboring and nonlaboring groups (p=0.028). CONCLUSION: Different intensities of TGF-beta 3 which appeared in different stages of myometrium made us consider that TGF-beta 3 might prepare myometrium to labor, and IL-6 was more important than the other interleukins in initiation of labor.