Serdar Filiz

Expression of insulin-like growth factor in the placenta of intrauterine growth-retarded human fetuses

Many cases of intrauterine growth retardation (IUGR) are the result of placental and fetal tissue insufficiency. Insulin-like growth factor-I (IGF-I) is known to play a role in placental and fetal growth. An immunocytochemical study was performed to localize IGF-I peptides in human placenta and umbilical cords of normal (n = 3) and IUGR (n = 3) fetuses. The peripartum fetal conditions were evaluated as well. Immunoreactive IGF-I was detected in the cytotrophoblast, syncytiotrophoblast, amnion, endothelial cells of fetal capillaries and in the decidua in both normal and IUGR placental tissue. A more robust immunostaining and increased numbers of positively stained cells were found in the decidua of IUGR placenta (p < 0.001). Intense immunostaining was also found in endothelial cells, smooth muscle cells and fibroblasts of the umbilical vein. IGF-I immunoreactivity was also present in stroma (Hofbauer cells and/or fibroblasts) of IUGR villi. Our results indicate that expression of IGF-I is high in specific sites in placenta and umbilical cords, which indicates a paracrine and/or endocrine function. The increased expression of IGF-I in placenta of IUGR fetuses indicates its involvement in restoring normal growth by means of a positive feed-back mechanism.

Localization of neural cell adhesion molecule (N-CAM) immunoreactivity in adult rat tissues

Neural cell adhesion molecule (N-CAM) mediates homophilic adhesion between cells and heterophilic adhesion between cells and extracellular matrix in a Ca2+-independent manner. N-CAM is widely expressed during development and plays a crucial role in cell division, migration, and differentiation, but its expression is restricted in adults. The distribution of N-CAM immunoreactivity in adult rat tissues was investigated in the present study. N-CAM immunoreactivity was present in the nervous system in the molecular layer of the cerebellum, ependymal cells surrounding the central canal, axons of the white matter, and in Lamina X of the gray matter of the spinal cord. N-CAM immunoreactivity also was found in autonomic nerves. In the digestive system, N-CAM immunoreactivity was found in the stratified squamous epithelium and nerve plexus of the esophagus, glandular cells of the stomach and pylorus, lamina propria, and epithelium of the villi of the duodenum, jejunum, and ileum. N-CAM immunoreactivity was demonstrated in the secretory cells of the adenohypophysis, islets of Langerhans, and acinar cells of the exocrine pancreas. Alveolar cells of the lung were also N-CAM immunoreactive. In the urinary system, N-CAM immunoreactivity was seen in the proximal convoluted tubules of the kidney. In the male reproductive system, N-CAM immunoreactivity was demonstrated in the nerve plexus around the urethral epithelium and in the nerve fibers around the smooth muscle cells of the corpus cavernosum penis. In the visual system, N-CAM immunoreactivity was seen in the epithelial cells of the corpus ciliaris. Cornea and lens epithelium also showed positive immunoreactivity. Our results suggest that cells in many tissues and organs of the adult rat synthesize N-CAM.

Protective effects of vitamin E and selenium on the renal morphology in rats fed high- cholesterol diets.

The histopathological effects of cholesterol and the protective effects of vitamin E and selenium (Se) on renal histology were examined in Sprague-Dawley rats. Light-microscopic evaluation of the renal cortex revealed: glomerular fibrosis, cellular and mesangial proliferation, capillary obliteration and cholesterol crystals in the tubular lumina of the cholesterol-fed group. These results suggest that oxidated LDL (O-LDL) is a cytotoxic factor which stimulates mesangial cell and matrix proliferation. Ultrastructurally, small and large lipid vacuolization in intracapillary lumina, adhesion of epithelial foot processes, mesangial foam cells and polymorphonuclear leukocytes were seen in the cholesterol-fed group. In the groups fed cholesterol + vitamin E, cholesterol + Se and cholesterol + vitamin E + Se, morphological improvements were observed. It appeared that an excess in O-LDL, reactive oxygen species and growth factors might play an important role in the pathogenesis of glomerulosclerosis. In addition, it was concluded that antioxidant therapy may prevent LDL oxidation and generation of free radicals.

Effects of chronic ethanol treatment on glial fibrillary acidic protein expression in adult rat optic nerve: an immunocytochemical study

Glial fibrillary acidic protein (GFAP) is used as a marker of astrocyte response to various central nervous system injuries. In the present study, the effects of chronic ethanol administration on GFAP immunoreactivity were evaluated in astrocytes of the adult optic nerve head. The results demonstrated that ethanol exposure significantly and dramatically increases GFAP immunoreactivity and the number of immunoreactive astrocytes (p<0.001). In addition, GFAP immunoreactive cells in the optic nerve showed extensive hypertrophy (p<0.001).

Immunohistochemical analysis of neural cell adhesion molecule (N-CAM) and pan-cadherin in the small intestine of intrauterine growth-retarded newborn rats caused by maternal protein malnutrition.

Cell-cell and cell-matrix adhesion molecules play an important role in morphogenesis, cell signaling and are involved in cell proliferation, cell death, cell polarization and differentiation. In the present study, we investigated N-CAM and pan-cadherin expression in small intestine of intrauterine growth-retarded (IUGR) newborn rats after maternal protein malnutrition during pregnancy. N-CAM and pan-cadherin immunostaining was increased in small intestine of IUGR newborn rats. This increase was evident in epithelial cells on villi, lamina propria, submucosa, muscularis mucosa and muscularis externa. The increase in numbers of villous N-CAM-positive and pan-cadherin-positive epithelial cells was statistically significant (p < 0.001). In most areas, crypts did not show any immunopositive epithelial cells or showed decreased expression of the adhesion molecules. Although the villous height was decreased in IUGR rats, the decrease was statistically not significant. Expression and recruitment of N-CAM and pan-cadherin in small intestine of newborn IUGR rats may indicate a direct or indirect involvement of adhesion mechanisms or signaling in the growth retardation process.

Hormonal and functional biomarkers in ovarian response

PurposeSuccess rates of any artificial reproduction techniques depend on a correct protocol for ovarian stimulation. This can be decided only by proper assessment of ovarian reserve before commencing ovarian stimulation. This study has been conducted to investigate the role of hormonal and functional biomarkers in the prediction of ovarian response.MethodsA total of 689 women between July 2012 and July 2013 undergoing IVF at Kocaeli University have been enrolled in the study. Patients have been categorized into three groups according to the number of oocytes retrieved: 0–3 oocytes (poor responders), 4–15 oocytes (normoresponders), and >16 oocytes (hyperresponders). Groups have been compared according to follicle-stimulating hormone (FSH), E2, luteinizing hormone (LH) levels, antral follicle counts, and E2 levels on hCG days. Furthermore, regression analysis has been performed with parameters such as age, FSH, LH, E2, anti-mullerian hormone (AMH) and antral follicle counts (AFC) that can affect the total number of oocytes retrieved and pregnancy rates and their interactions with each other have been investigated.ResultsFSH, age, hCG day LH level, cycle cancellation rate, total gonadotropin dose were significantly higher in the poor responder group, but in this group, AFC, AMH, hCG day E2 level, and the number of MII oocytes were significantly lower. Cut-off values of normal responders for FSH, AMH, and AFC were 8.43 area under curve [AUC: 0.541 (0.491–0.590)], 0.62 [AUC: 0.704 (0.638–0.764)], and 6 [AUC: 0.715 (0.667–0.760)], respectively. Cut-off values for the absolute poor response group (cycle cancellation) were 12.75 for FSH [AUC: 0.533 (0.49–0.57)], 0.23 for AMH [AUC: 0.678 (0.618–0.733)], and 6 for AFC [AUC: 0.576 (0.531–0.613)]. AMH and AFC were the best markers for the prediction of total oocyte count, independent of age, FSH, and LH levels.ConclusionsAMH and AFC were found to be the best ovarian reserve tests that can determine the total oocyte count retrieved, without any significant effects on pregnancy rates.

Is sildenafil citrate affect endometrial receptivity? An immunohistochemical study.

The authors aimed to investigate the effect of sildenafil citrate (Sc) on expressions of β3 integrin and vascular endothelial growth factor (VEGF), which is taking part in endometrium receptivity in implantation window period in controlled ovarian hyperstimulation (COH) performed rats. In this study, Wistar albino female rats were used and were divided into four groups as control, COH, Sc, and COH + Sc groups. They were sacrificed on the third, fourth, and fifth day of pregnancy, uteruses were resected, and uteri sections were stained with immunohistochemical method and evaluated. β3 integrin immunoreactivity was most intensely observed in the endometrial glandular epithelium (GE) and stromal cells in the Sc group on the third day, whereas immunoreactivity was most intensely detected in the luminal epithelium (LE), GE, and stromal cells in the Sc group on the fourth day. VEGF immunoreactivity was most intensely observed in the endometrial LE in the Sc group on the third day, in the Sc and COH + Sc groups on the fourth day, and in the COH + Sc group on the fifth day. Our results indicated that Sc plays a role in both implantation and decidualization by affecting β3 integrin and VEGF expressions in implantation window period in rats.

LOCALIZATION OF PAN‐CADHERIN IMMUNOREACTIVITY IN ADULT RAT TISSUES

Cadherins, being responsible for selective cell recognition and normal tissue integrity in adults, regulate morphogenesis in a variety of organs during development. In this study, anti‐rat pan‐cadherin antibody, specific to all subgroups of the cadherin family, was used to map the distribution of the pan‐cadherin immunoreactivity in adult rat organs. Pan‐cadherin immunoreactivity positive tissues were: secretory cells of the adenohypophysis, autonomic nerve, corneal epithelium, oesophageal nerve plexus, stomach and pyloric glandular cells, epithelium of the ileum and its nerve plexus, alveolar cells of the lung, proximal convoluted tubules of the kidney, islet cells of Langerhans, and the acinar cells of the exocrine pancreas. For the first time, positive pan‐cadherin immunoreactivity was demonstrated in the epithelial cells of the corpus ciliaris and in the nerve plexus of corpus cavernosum of the penis. In conclusion, our results suggest that cells in many tissues and organs of the adult rat synthesize cadherins.

Efficacies of caspofungin and a combination of caspofungin and meropenem in the treatment of murine disseminated candidiasis

Disseminated candidiasis is relatively common in immunocompromised patients. The treatment protocol of these patients usually includes broad‐spectrum antibiotics and also emprical antifungals initiated due to unresponsiveness to antibiotics. In this study the efficacies of caspofungin and meropenem – separately and together – in mice with disseminated candidiasis were studied. Immunocompetent mice were infected intravenously with 2×106 CFU of Candida albicans. At 24 h postinfection, intraperitoneal therapy was initiated and was continued for 7 days. Therapy groups included those given caspofungin (0.5, 1.25, 5 mg/kg/day), meropenem (20 mg/kg/day), and a combination of the two drugs. The outcome of therapy was evaluated by kidney tissue burden studies and histologic examination. In vitro, drug susceptibilities were tested by checkerboard analysis. Kidney CFU counts showed that mice that had received both drugs had lower residual burdens. Caspofungin was effective at doses of 0.5, 1.25, 5 mg/kg compared to infected untreated controls. In vitro, MICs of caspofungin and meropenem were <0.075 μg/ml and >64 μg/ml, respectively. Synergism was observed with the combination. Histopathology showed that the degree of inflammation was 25% less and tubular necrosis was more restricted in combined therapy than monotherapy. The results indicate that concurrent caspofungin and meropenem therapy may be beneficial

Expression of cell adhesion molecules in the adriamycin-induced esophageal atresia rat model

Cell adhesion molecules are well‐known membrane glycoproteins widely expressed during embryonic development that play a crucial role in cell division, migration and differentiation. We investigated the cell—matrix relationship using N‐CAM and pan‐cadherin adhesion molecules in the adriamycin‐induced esophageal atresia (EA) rat model in the hope of finding a clue to the mechanisms of this unique anomaly.