The Association of Brain-Derived Neurotrophic Factor Gene Polymorphism with Obstructive Sleep Apnea Syndrome and Obesity.

BACKGROUND: Obesity represents a major risk factor for Obstructive Sleep Apnea Syndrome (OSAS). Brain-derived neurotrophic factor (BDNF) affects the mechanisms that regulate weight, eating behavior, and metabolism. This project aims to investigate the possible association of BDNF gene polymorphism with obesity and OSAS, and to contribute knowledge to the understanding of the pathophysiology of OSAS. METHODS: The subjects included in this study were selected among the individuals who were hospitalized in the Erciyes University Medical School Chest Diseases Sleep Medicine Laboratory. Subjects were divided into four groups based on the presence of OSAS and/or obesity. Group 1 included OSAS+ obesity+ patients, Group 2 included OSAS+ obesity- patients, Group 3 included OSAS- obesity+ patients, and Group 4 included OSAS- obesity- patients. The targeted patient number per each study group was 45, but only 32 patients could be enrolled into Group 3. RESULTS: Out of a total number of 167 subjects, 117 (70.1 %) had BDNF 196G/G, 48 (28.7 %) had BDNF 196G/A, and 2 (1.2 %) had BDNF 196A/A genotype. Of 48 subjects having BDNF 196G/A genotype, 32 (66.6 %) were obese, and 16 (33.3 %) were non-obese. Out of 90 subjects with OSAS, 64 (71.1 %) had BDNF 196G/G, and 25 (27.8 %) had BDNF 196G/A genotype. Out of 77 subjects without OSAS, BDNF 196G/G, and BDNF 196G/A genotypes were detected in 53 (68.8 %) and 23 (29.9 %) subjects, respectively. A statistically significant difference was demonstrated between the four study groups in terms of BDNF rs6265 polymorphism (p = 0.013). This difference was attributed to OSAS+ obesity- Group, in which BDNF 196G/G genotype was more common and BDNF 196G/A polymorphism was less common than the patients in other groups. CONCLUSION: In conclusion, BDNF 196G/A genotype was found to be more frequent among obese patients compared to the non-obese individuals, but it was not significantly related to OSAS in the present study. BDNF196G/G genotype was more common and BDNF 196G/A polymorphism was less common among OSAS+ obesity- subjects compared to the other study groups.

The role of Wnt signaling members in the uterus and embryo during pre-implantation and implantation.

Wnt family members are best known for their roles in cell fate determination, differentiation, proliferation and apoptosis during embryonic development. Wnt signaling becomes effective during these cellular processes through the proper interaction between its ligands, receptors, effectors and inhibitors. Here we review Wnt signaling in terms of embryonic development to the blastocyst stage implantation with emphasis on endometrial changes that are critical for receptivity in the uterus. The relationship between Wnt signaling and implantation clearly reveals that, Wnt family members are critical for both early embryonic development and changing of the endometrium before implantation. Specific Wnt signaling pathway members are demonstrated to be critical for endometrial events such as decidualization and endometrial gland formation in addition to cyclic changes in the endometrium controlled by reproductive hormones. In conclusion, specific roles of Wnt members and associated factors for both uterine function and embryonic development should be further investigated with respect to the efficiency of human ARTs.

Triamcinolone up-regulates GLUT 1 and GLUT 3 expression in cultured human placental endothelial cells.

The placenta is a glucocorticoid target organ, and glucocorticoids (GCs) are essential for the development and maturation of fetal organs. They are widely used for treatment of a variety of diseases during pregnancy. In various tissues, GCs have regulated by glucose transport systems; however, their effects on glucose transporters in the human placental endothelial cells (HPECs) are unknown. In the present study, HPECs were cultured 24 h in the presence or absence of 0.5, 5 and 50 µmol · l(-1) of synthetic GC triamcinolone (TA). The glucose carrier proteins GLUT 1, GLUT 3 and GC receptor (GR) were detected in the HPECs. We showed increased expression of GLUT 1 and GLUT 3 proteins and messenger RNA (mRNA) levels (p < 0.05) after 24-h cell culture in the presence of 0.5, 5 and 50 µmol · l(-1) of TA. In contrast, GR protein and mRNA expressions were down-regulated (p < 0.05) with 0.5, 5 and 50 µmol · l(-1) of TA 24-h cell culture. The results demonstrate that GCs are potent regulators of placental GLUT 1 and GLUT 3 expression through GR. Excessive exposure to GCs causes maternal and fetal hypoglycemia and diminished fetal growth. We speculate that to compensate for fetal hypoglycemia and diminished fetal growth, the expression of placental endothelial glucose transporters might be increased.

Effects of abamectin exposure on male fertility in rats: potential role of oxidative stress-mediated poly(ADP-ribose) polymerase (PARP) activation.

Despite the known adverse effects of abamectin pesticide, little is known about its action on male fertility. To explore the effects of exposure to abamectin on male fertility and its mechanism, low (1mg/kg/day) and high dose (4 mg/kg/day) abamectin were applied to male rats by oral gavage for 1week and for 6weeks. Weight of testes, serum reproductive hormone levels, sperm dynamics and histopathology of testes were used to evaluate the reproductive efficiency of abamectin-exposed rats. Abamectin level was determined at high concentrations in plasma and testicular tissues of male rats exposed to this pesticide. The testes weights of animals and serum testosterone concentrations did not show any significant changes after abamectin exposure. Abamectin administration was associated with decreased sperm count and motility and increased seminiferous tubule damage. In addition, significant elevations in the 4-hydroxy-2-nonenal (4-HNE)-modified proteins and poly(ADP-ribose) (PAR) expression, as markers for oxidative stress and poly(ADP-ribose) polymerase (PARP) activation, were observed in testes of rats exposed to abamectin. These results showed that abamectin exposure induces testicular damage and affects sperm dynamics. Oxidative stress-mediated PARP activation might be one of the possible mechanism(s) underlying testicular damage induced by abamectin.

The prevalence of occupational asthma among denim bleachery workers in Kayseri.

The bleachery procedure is the most frequent method used to decolorize denims since sandblasting has been shown to cause silicosis. The aim of this study was to determined the prevalence of occupational asthma among denim bleachery workers in Kayseri. The study was conducted in 4 factories, in which jean bleachery was performed, in Kayseri between December 2008 and February 2009. Overall, forty-four subjects, 22 from the bleachery section and 22 from the other sections, were included. A questionnaire about respiratory symptoms was administered. Pulmonary function tests (PFTs) and serial peak expiratory flow (PEF) measurements were performed. All subjects were evaluated by posteroanterior chest x-rays. The prevalence of occupational asthma (OA) in the bleachery and other section workers was 23.8% and 9.1%, respectively (p> 0.05). Within workers, exercise dyspnea (23.3%) and wheezing (20.9%) were the most frequent symptoms. The relationship between the duration of employment and PFTs in bleachery workers (n= 21) was negatively correlated and statistically significant with FEV1, FEF25-75 (moderate; r= -0.477, -0.449, respectively; p< 0.05) and FEV1/FVC, FEV1% (well; r= -0.588, -0.509, respectively; p< 0.05). The results of the present study suggest that exposure to denim-bleaching agents plays an important role in the occurrence of respiratory symptoms, reduction in pulmonary functions, and induction of occupational asthma.

Evaluation of diagnostic accuracy of computed tomography to assess the angioarchitecture of pulmonary sequestration.

Bronchopulmonary sequestration is an unusual congenital malformation consisting of abnormal lung tissue that lacks normal communication with the tracheobronchial tree. The diagnosis of pulmonary sequestration is based on identifying this systemic arterial supply. We aimed to evaluate the sensitivity of multidetector computed tomography in demonstrating the feeding artery and draining veins. Between 2003 and 2008, 8 patients (6 males, 2 females) ranging in age from 5 to 49 years with a diagnosis of pulmonary sequestration were identified. All patients underwent evaluation with chest tomography (spiral or multi detector tomography) and digital subtraction angiography. Aberrant systemic arterial supply was demonstrated in all cases: from the descending thoracic aorta (n= 6); arcus aorta (n= 1), internal mammarial artery (n= 1), intercostal arteries (n= 2) and celiac axis (n= 1). Four patients underwent surgery which confirmed the angioarchitecture depicted on angiography. One patient underwent angiography with embolization using. Computed tomography especially multidetector computed tomography is a powerful noninvasive technique for the detection of pulmonary sequestration.

Lung surfactant proteins in the early human placenta.

Pulmonary surfactant is a complex mixture of phospholipids and four surfactant-associated proteins (SP-A, SP-B, SP-C and SP-D). The biological functions of SP-A and SP-D are primarily twofold, namely surfactant homeostasis and host defense. The hydrophobic surfactant proteins, SP-B and SP-C, are required for achieving the optimal surface tension reducing properties of surfactant by promoting the rapid adsorption of surfactant phospholipids along the alveolar surface. Despite the promising findings, only little is known about the extrapulmonary distribution of these proteins. Therefore, in this study, the presence of SP-A, SP-B, SP-C and SP-D in early human placenta has been investigated. First-trimester placental tissues (22-56 days) were obtained from women undergoing curettage during normal pregnancies. In parallel tissue sections, vimentin, cytokeratin-7 and CD-68 immunostainings were used for the identification of mesenchymal cells, trophoblast cells and Hofbauer cells, respectively. According to immunohistochemistry (IHC) results, SP-A, SP-B, SP-C and SP-D immunoreactivities with different staining intensities were observed in trophoblastic layers of chorionic villous tree, trophoblastic cell columns, stromal cells, Hofbauer cells, angiogenic cell cords and vascular endothelium. Fetal hematopoietic cells showed a variable staining pattern for all four surfactant proteins ranging from none to strong intensity. Western blotting of tissue extracts confirmed our IHC results. The presence of surfactant glycoproteins in early human placenta may yield a very important feature of surfactants during first trimester and enables further studies of the role of surfactants in various pregnancy complications.

Arrangement of collagen fibers in human placental stem villi.

The aim of the study was to investigate the arrangements and related localization patterns of different collagen types in the stroma of placental stem villi by immunohistochemistry and electron microscopy. A total of 14 normal human term placental tissue samples were studied. Immunohistochemistry was performed in order to localize collagen types I, III, IV, V and cytokeratin 7 on tissue sections. Parallel tissue samples were examined by transmission electron microscopy. Semi-quantitative analysis of immunolabeling intensities was also performed to determine the distribution of fibers in stem villi stroma. All collagen types, especially collagen type V, were strongly immunopositive in the triangular areas of the stem villi stroma. However, there was no collagen type I or type III immunolabeling in the sub-trophoblastic regions. Membrane collagen type IV immunolabeling was also observed in the stroma of stem villi. Ultrastructurally, collagen fibers showed different configurations in cross, longitudinal, circular, oblique and parallel directions compared to the villous axis. We conclude that the organization of collagen fiber bundles in stem villi shows a very specific arrangement: a compact coat formed by fibrillar bundles between the vascular wall and extravascular stroma of stem villi correlated with the functional activity.

Is there a relationship between PCNA expression and diabetic placental development during pregnancy?

We aimed to investigate the distribution pattern of proliferating cell nuclear antigen (PCNA) by immunohistochemistry and Western blot in placentas of control and diabetic rats at different stages of pregnancy. It is still not clear how proliferation is coordinated and how this coordination is affected by diabetes in the placenta. Diabetes was induced by streptozocin on the first day of pregnancy. Animals were sacrificed on days 11, 13, 17 and 21 of pregnancy. In control placentas immunolabeling intensity of PCNA was the highest on days 11 and 13 of pregnancy and decreased with progression of pregnancy. In the diabetic groups immunolabeling was less intense on days 11 and 13 of pregnancy compared to controls. However, in parallel with placental weights, PCNA immunopositivity was more intense in diabetic groups than control groups on days 17 and 21 of pregnancy, and the difference was statistically significant on day 17. According to Western blot data, on days 11 and 13 of pregnancy the amount of PCNA was greater in control groups than in the diabetics, whereas it was greater in diabetic groups than the controls on days 17 and 21 of pregnancy. We conclude that PCNA may play a role in abnormal placenta formation resulting from diabetes.

The immunohistochemical localization of notch receptors and ligands in human articular cartilage, chondroprogenitor culture and ultrastructural characteristics of these progenitor cells.

The presence of progenitor/stem cells in human articular cartilage remains controversial. Therefore, we attempted to isolate and culture progenitor/stem cells and to investigate their phenotypic characteristics. Biopsies were obtained (with consent) from patients undergoing arthroscopic surgery. Full depth explants were fixed and cryosectioned or enzymatically digested and the resulting cells cultured and plated on fibronectin-coated dishes. Chondrocytes were cultured until colonies of >32 cells were present. Colonies were trypsinized and expanded in monolayer for pellet culture. Immunolocalization of Notch and its ligands were detected in vivo and in vitro using immunocytochemistry. In vitro studies investigated differences in immunolocalization of Notch and its associated ligands in colony-forming cells and small clusters of non-colony-forming cells. The ultrastructure of the chondroprogenitors was examined by scanning and transmission electron microscopy. Results revealed that the immunolocalization of Notch-1 and its ligand Delta were concentrated in regions closest to the articular surface. Notch-1 was also densely localized in the deeper zone of articular cartilage. Notch-2 immunolabeling was densely localized in all zones of articular cartilage. Jagged-1 was concentrated in the deeper regions of articular cartilage. Notch-1, Delta and Jagged-1 were more abundant in colony-forming cells than non-colony-forming chondrocytes in vitro. Notch-3, Notch-4 and Jagged-2 were absent from all regions of the articular cartilage tissues and cultured cartilage cells in vitro. Ultrastructurally, chondrocytes cultured in monolayer dedifferentiated to fibroblast-like cells with cell surface processes of varying lengths, pellet cultured cells varied in morphology, as flattened and rounded. In conclusion, we propose that adult human articular cartilage may contain cells having progenitor cell features.

Leptin levels in various manifestations of pulmonary tuberculosis.

BACKGROUND: Proinflammatory cytokines are prime candidates as causative agents of the metabolic changes that eventually result in tuberculosis-associated weight loss. Microbial products and cytokines such as TNF and IL-1 increase leptin expression dose dependently in adipose tissue. Leptin plays an important role in cellular immunity. OBJECTIVES: In this study, we investigated serum leptin and TNF-alpha levels before and after antituberculosis therapy in patients with active pulmonary tuberculosis (TB). METHODS: Twenty five in patients with active pulmonary TB and 18 healthy controls participated in the study. Leptin and TNF-alpha levels were measured before treatment and six months after the treatment and they were compared with the control group. Body mass index (BMI) and chest X-rays before and after the treatment were also evaluated. RESULTS: The leptin levels before and after the treatment were 1.66+/-1.68 ng/mL and 3.26+/-3.81 ng/mL, respectively. The leptin levels of tuberculous patients were significant than in healthy patients (P < .05). The BMI was 19.36+/-2.55 kg/m2 before the treatment and 22.87+/-3.13 kg/m2 after the treatment. The TNF-alpha level was 23.19+/-12.78 pg/mL before the treatment and 15.95+/-6.58 pg/mL after the treatment. There was no correlation between leptin and TNF-alpha levels. Leptin levels were low in patients who had sequela lesion on chest radiographs. CONCLUSION: Leptin levels are suppressed in tuberculous patients and low leptin levels may contribute to increased susceptibility to infection and recovery with sequela lesions.

Vasculogenesis and angiogenesis in the early human placenta.

Vasculogenesis and angiogenesis are two consecutive processes during blood vessel development in the human placenta. While vasculogenesis, which is the formation of first blood vessels, is achieved by differentiation of pluripotent mesenchymal cells into haemangiogenic stem cells. The subsequent step, angiogenesis, is characterized by development of new vessels from already existing vessels. In this review, we aim to give an overview of vasculogenesis and angiogenesis during the first trimester of human placental development. Recent studies have shown that at the very early stages of placental development, cytotrophoblasts trigger vasculogenesis and angiogenesis, whereas as pregnancy progresses Hofbauer and stromal cells take over the task of triggering blood vessel development. Important growth factors in this scenario are the vascular endothelial growth factor (VEGF) family and their receptors, as well as Tie-1 and Tie-2. This review depicts the molecular and morphological steps of vasculogenesis and angiogenesis, which can give further insights into human placental development and maturation disorders.

Matrix metalloproteinases-2, -3 and -9 in human term placenta.

Matrix metalloproteinases (MMPs) are zinc-dependent enzymes that degrade the components of the extracellular matrix (ECM) and are known to be the main mediators of human placentation and parturition. Although there are many studies on the roles and distribution of MMPs in human term placenta, so far none of the studies has investigated the distribution of MMP-2, -3 and -9 in different cells of various placental sites. In this study, we aimed to determine the distribution and enzymatic activities of MMP-2, -3 and -9 with regard to different regions of term human placenta, such as amnion, basal plate, chorionic plate, decidua, chorion laeve, Nitabuch's stria, umbilical cord and placental villi. Eighteen normal human term placentas were obtained after vaginal deliveries. Immunohistochemistry and zymography were performed for MMP-2, -3 and -9 on placental tissue sections and protein extracts, respectively. Nearly all tissues showed immunoreactivity for MMPs. The strongest enzymatic activity for MMP-2 was seen in areas where invasive trophoblast cells invaded maternal tissues. MMP-9 had the highest enzymatic activity at the contact region of fetal and maternal parts, suggesting the importance of MMP-9 in separation of the placenta from the uterine wall during labor. MMP-3 had a similar localization to MMP-9, suggesting that besides gelatinases like MMP-2 and -9, MMP-3 (stromelysin-1) may also have important roles during labor. This study describes the site-specific distribution and activities of MMPs and therefore might help in elucidating the molecular mechanisms in pathologies such as premature rupture of membranes.

Cellular diversity of human placental stem villi: an ultrastructural and immunohistochemical study.

The aim of the study was to investigate the distribution and differentiation of cell types in the stroma of human placental stem villi (SV). A total of 14 human term placental tissues were studied. Double immunolabeling was performed for desmin-vimentin, desmin-alpha-smooth actin and vimentin-alpha-smooth actin. Cytokeratin 7, proliferating cell nuclear antigen immunolabeling was also performed. Parallel tissue samples were examined by transmission electron microscopy. HSCORE was performed for the semi-quantitative analysis of distribution of cells in the stroma of SV. Vimentin-labeled cells were mostly distributed in the subtrophoblastic area. Desmin-vimentin double immunolabeling was mainly localized in the triangular area and to a lesser degree in the perivascular area and vessel walls (p=or<0.001). However, desmin-alpha smooth actin labeling was observed predominantly in the vessel wall and perivascular area. Vimentin-alpha smooth actin immunoreactivity was significantly stronger in the triangular and perivascular areas compared to the vessel walls (p=0.003). Ultrastructurally, cells in the stroma of SV were mesenchyme cells, reticulum cells, fibroblasts, myofibroblasts, smooth muscle cells, and Hofbauer cells, filamented and vacuolated cells. The differentiation of myofibroblasts in the triangular and perivascular areas may play a role in maturation of SV and villous contractility, modulation of the intervillous space and this may have effects on maternofetal placental circulation.

Immunolocalization of glial cell-derived neurotrophic factor (GDNF) and its receptor GFR-alpha1 in varicocele-induced rat testis.

The aim of the study was to determine the immunolocalisation of glial cell-derived neurotrophic factor (GDNF) and its receptor (GFRalpha1) in testicular dysfunction induced by experimental left varicocele. Male Wistar rats were divided randomly into two groups: a varicocele-induced group and a sham-operated group for 9, 11 and 13 weeks (each group n=6). After orchiectomy, part of the left testis from each animal was fixed, processed and embedded in paraffin wax for immunohistochemistry and the other part was fixed for ultrastructural investigations. GDNF immunoreactivity was localized in the interstitial space in Leydig cell cytoplasm and there was no significant difference (P=0.5) between the varicocele-induced groups at the various time points. GFRalpha1 localization was perinuclear in spermatids and cytoplasmic in Leydig cells. The decrease of GFRalpha1 immunoreactivity was significant (P=0.001) in varicocele-induced testis at 13 weeks when compared with the age-matched sham group. This is the first study to describe the immunolocalization patterns of GDNF and GFRalpha1 in a rat model of varicocele. Although there was no change in GDNF labelling at the different time points after varicocele, GFRalpha1 was significantly decreased in the 13-week group. Distribution of GDNF and its receptor GFRalpha1 in normal and varicocele-induced rat testes suggests both autocrine and paracrine regulation of spermatogenesis.

The effect of CPAP therapy on insulin-like growth factor and cognitive functions in obstructive sleep apnea patients.

OBJECTIVES: Cognitive impairment is common among patients with obstructive sleep apnea syndrome (OSAS). In this study, we aimed to investigate the effect of continuous positive airway pressure (CPAP) therapy on serum insulin-like growth factor-1 (IGF-1) levels and cognitive functions in patients with OSAS. PATIENT/METHODS: Thirty-three patients with newly diagnosed OSAS and 17 healthy-control subjects enrolled in the study. All individuals completed the mini-mental state examination (MMSE) to evaluate cognitive function. Blood samples were taken at the end of the polysomnography in the morning and the same procedures were repeated 3 months after starting CPAP treatment. RESULTS: In the OSAS group, the baseline MMSE score was 23.5 ± 3.6, and serum IGF-1 level was 79.1 ± 36.1 ng/mL. Both values were significantly lower compared with the control group (mean MMSE score = 28.1 ± 1.4, P = 0.0001; mean serum IGF-1 level = 147.1 ± 49.1 ng/mL, P < 0.0001). Three months after CPAP treatment, OSAS patients showed a significant improvement in MMSE scores (26.5 ± 2.8, P = 0.0001) and serum IGF-1 level (129.1 ± 58.2, P = 0.0001). In contrast, baseline and third-month measurements for IGF-1 levels and MMSE scores were not significantly different in the control group. CONCLUSIONS: The results indicate that effective CPAP therapy in OSAS patients leads to significant improvement in cognitive functions and IGF-1 even in a short-term follow-up. Cognitive function assessment might be a part of evaluation in OSAS patients.

Expression of nidogens in rat uterus and embryo during decidualization and implantation.

The purpose of this study was to demonstrate the expression of nidogen-1 and nidogen-2 and their possible role in decidualization and implantation events during early pregnancy in rats. The tissue samples were examined from pregnant animals between gestational days 1-8 using immunocytochemistry. The uterine luminal epithelium, the glandular epithelium, and the myometrial smooth muscle cells stained strongly from gestational days 1-8 with both nidogen antibodies. At day 4 the decidual reaction areas began to appear in the stromal matrix and immunostaining of both nidogens revealed that the basement membrane of the surface epithelium was discontinuous. The differentiation of stromal cells into decidual cells was seen at gestational day 5 and both nidogens were weakly expressed in the decidualizing cells. At day 6, nidogen-2 immunoreactivity was higher in the primary decidual cells close to the embryo than nidogen-1, and during development of the decidual tissue both nidogens appeared in the endometrial stromal cells. At day 7, while expression of both nidogens declined in the primary decidual cells, their expression was markedly observed in the secondary decidual cells close to the myometrium. At day 8, expression of both nidogens was also observed to increase in the primary decidual cells. While nidogen-2 expression was seen in the parietal endoderm and primary ectoderm of the rat embryos at this developmental stage, nidogen-1 expression was only detected in the parietal endoderm. These results indicate that nidogen-1 and nidogen-2 could play important roles during embryogenesis, decidualization, and implantation in the endometrium of rat uterus.

Ultrastructural and immunohistochemical analysis of rat uroepithelial cell junctions after partial bladder outlet obstruction and selective COX-2 inhibitor treatment.

The present study was undertaken to evaluate alterations in uroepithelial cell junctional complexes in partial bladder outlet obstruction (PBOO) of rat bladders using ultrastructural morphometry and immunohistochemistry, and to determine whether selective COX-2 inhibitors have any effects on these structures. A total of 18 male rats were separated into three groups of six rats each: (1) sham-operated animals served as controls; (2) a PBOO group, without further treatment (3) and a group that immediately after PBOO, received treatment for 4 weeks with oral Celecoxib, a selective COX-2 inhibitor. Uroepithelial cell junctions were evaluated using transmission electron microscopy combined with morphometry. Results were also assessed by E-cadherin and alpha-catenin immunohistochemistry. Morphometrical analysis of ultrastructural evaluations revealed that 4 weeks of PBOO caused a significant reduction in the electron density of zonula adherens and zonula occludens junctional complexes. Moreover, some desmosomes located between the deeper cells of the uroepithelium showed signs of disintegration. Selective COX-2 inhibitor treatment during 4 weeks of PBOO showed protective effects on adherens and occludens junctions, as well as on desmosomes. Immunohistochemical analysis of E-cadherin confirmed that the decreased E-cadherin immunolabelling in 4 weeks of PBOO was prevented by selective COX-2 inhibitor treatment. Based on ultrastructural morphometrical analysis, we conclude that PBOO alone and in combination with selective COX-2 inhibitors can have considerable effects on uroepithelial cellular junctions. Our findings provide a novel area of investigation regarding the selective use of COX-2 inhibitors following PBOO.

Localization of NGF and nNOS in varicocele-induced rat testis.

Nerve growth factor (NGF) is synthesized in male germ cells. The presence of neuronal nitric oxide synthase (nNOS) in Leydig cells is related to its role in the regulation of testosterone release. Varicocele is often characterized by abnormal sperm quality and influences the fertilizing capacity of the haploid gamete. We investigated the localization of NGF and nNOS in testes of adult Wistar rats with experimentally induced varicocele after 9, 11, and 13 weeks, as well as in sham-operated controls by immunohistochemistry and Western blot. In control testis, we detected NGF in nuclei of Sertoli cells and also as small vesicular-like structures in the cytoplasm of primary spermatocytes, and in round and elongating spermatids. Varicocele-induction revealed a slight decrease of NGF at 13 weeks, especially in Sertoli cells. In control tissue, nNOS protein was present mainly in Leydig cells and in Sertoli cell cytoplasm. Additionally, nNOS immunoreactivity was present in the heads of elongated spermatids. Western blot results revealed that the decrease of NGF was not significant in the 13-week varicocele group, moreover, the amount of nNOS was not altered in any of the varicocele groups. In conclusion, NGF and nNOS have important roles for normal gametogenesis and our data for the first time indicates that varicocele induction does not necessarily affect the expression of NGF and nNOS. Thus, these two molecules do not appear to be related to varicocele induction.

Altered expression of human endogenous retroviruses syncytin-1, syncytin-2 and their receptors in human normal and gestational diabetic placenta.

INTRODUCTION: Syncytins belong to the Human Endogenous Retrovirus family. The syncytin-1 receptor, SLC1A5, and syncytin-2 receptor, MFSD2, interact with their respective syncytin proteins to induce syncytiotrophoblast formation. However, there is no information about syncytins in gestational diabetic placenta. Therefore, we studied the expression and localization of syncytins and their receptors during normal placental development and in gestational diabetic placenta. METHODS: Immunohistochemistry and Western-blot methods were performed with antibodies against syncytin-1, syncytin-2, SLC1A5 and MFSD2 in human first trimester placental tissues, normal term and gestational diabetic placentas. Syncytin-1, syncytin-2 and MFSD2 mRNA transcripts were determined by qRT-PCR in normal and diabetic term placentas. RESULTS: Cytoplasmic syncytin-1, syncytin-2, SLC1A5 and MFSD2 immunoreactions were observed in the trophoblastic layers in all placental samples. Some of the stromal cells showed strong cytoplasmic punctate staining. There were significantly weak syncytin-2 and MFSD2 immunoreaction intensities in diabetic placentas by ImageJ analysis, in parallel with decreased syncytin-2 and MFSD2 proteins in diabetic placentas by Western-blot. Protein expression of SLC1A5 increased dramatically in early pregnancy compared to term placenta. Syncytin-1, syncytin-2 and MFSD2 mRNA transcripts showed similar relative expression pattern by qRT-PCR. DISCUSSION: Syncytins were localized not only in cytotrophoblast cells and the basement membrane of the syncytiotrophoblast but also in the apical microvillous membrane and cytoplasm of syncytiotrophoblast, and some of the stromal cells and endothelium. Decreased syncytin-2 and MFSD2 proteins in gestational diabetic placentas might cause abnormal syncytiotrophoblast formation and possibly be involved in the pathology. Therefore, our study highlights an important potential relationship between syncytins and gestational diabetic placenta.