Determination of PCNA, cyclin D3, p27, p57 and apoptosis rate in normal and dexamethasone-induced intrauterine growth restricted rat placentas.

Intrauterine growth restriction (IUGR) is a major clinical problem, which causes perinatal morbidity and mortality. One of the reasons for IUGR is abnormal placentation. In rats, fetal-placental exposure to maternally administered glucocorticoids decreases birth weight and placental weight. Proper placental development depends on the proliferation and differentiation of trophoblasts. Our knowledge about the mitotic regulators that play key roles in synchronizing these events is limited. Also the mechanisms underlying the placental growth inhibitory effects of glucocorticoids have not been elucidated. The aim of this study was to investigate the immunolocalization, mRNA and protein levels of proliferating cell nuclear antigen (PCNA), cyclin D3, p27 and p57 in normal and dexamethasone-induced IUGR Wistar rat placentas by reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry and Western blot. We also compared apoptotic cell numbers at the light microscopic level via terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) and transmission electron microscopy. Glucocorticoid levels were higher in IUGR rats than in control rats after 60 and 120min of injection. We showed reduced gene and protein expressions of PCNA and cyclin D3 and increased expressions of p27 and p57 in IUGR placentas compared to control placentas. Apoptotic cell number was higher in the placentas of the IUGR group. In brief we found that maternal dexamethasone treatment led to a shift from cell proliferation to apoptosis in IUGR placentas. Dexamethasone induced placental and embryonal abnormalities which could be associated with reduced expressions of PCNA and cyclin D3, increased expressions of p27 and p57 and increased rate of apoptosis in IUGR placentas.

[E-learning and problem based learning integration in cardiology education]. / Kardiyoloji egitiminde e-ögrenme ve probleme dayali ögrenme entegrasyonu.

OBJECTIVE: The aim of this study was to determine students' satisfaction with an e-learning environment which is developed to support classical problem-based learning (PBL) in medical education and its effect on academic achievement. METHODS: In this cross-sectional study, students were provided with a web-based learning environment including learning materials related to objectives of the subject of PBL module, which could be used during independent study period. The study group comprised of all of the second year students (164 students) of Akdeniz University, Medical Faculty, during 2007-2008 education period. In order to gather data about students' satisfaction with learning environment, a questionnaire was administered to the students. Comparison of students' academic achievement was based on their performance score in PBL exam. Statistical analyses were performed using unpaired t test and Mann Whitney U test. RESULTS: Findings indicated that 72.6% of the students used e-learning practice. There is no statistically significant difference between mean PBL performance scores of users and non-users of e-learning practice (103.58 vs. 100.88) (t=-0.998, p=0.320). It is found that frequent users of e-learning application had statistically significant higher scores than non-frequent users (106.28 vs. 100.59) (t=-2.373, p=0.01). In addition, 72.6% of the students declared they were satisfied with the application. CONCLUSION: Our study demonstrated that the most of the students use e-learning application and are satisfied with it. In addition, it is observed that e-learning application positively affects the academic achievement of the students. This study gains special importance by providing contribution to limited literature in the area of instructional technology in PBL and Cardiology teaching.

Effects of L-carnitine on neutrophil-mediated ischemia-reperfusion injury in rat stomach.

Reactive oxygen metabolites play an important role in ischemia-reperfusion related gastric injury. Primary sources of reactive oxygen metabolites seem to be the xanthine/xanthine oxidase system and neutrophils accumulating within the reperfused tissue. Tissue myeloperoxidase activity is an important index of neutrophil accumulation. The purpose of the present study was to clarify the effect of L-carnitine on the accumulation of neutrophils and neutrophil-induced gastric mucosal damage in rats exposed to ischemia-reperfusion. Rats were randomly divided into three groups: sham-operated, ischemia-reperfusion and ischemia-reperfusion plus L-carnitine groups. Ischemia was induced by clamping the celiac artery for 30 min and then reperfusion was established for 60 min. Gastric injury was assessed by measuring myeloperoxidase activity in gastric tissue. The neutrophil accumulation and hemorrhagic lesions due to ischemia-reperfusion in gastric mucosa were ascertained in a histological study. L-Carnitine (100 mg kg(-1)) administrated intravenously 5 min before ischemia significantly reduced both the gastric injury and myeloperoxidase activity compared with the ischemia-reperfusion group. The results suggest that L-carnitine provides marked protection against ischemia-reperfusion-related gastric injury which could be due to its ability to reduce neutrophil accumulation in ischemic tissue.

Distribution patterns of matrix metalloproteinase (MMP)-2 and -9 and their inhibitors (TIMP-1 and TIMP-2) in the human decidua during early pregnancy.

Early human trophoblast shows dramatic invasive properties during early pregnancy. A tightly-regulated activation of matrix metalloproteinases (MMPs) is considered to be of critical importance for the control of trophoblast invasion. The aim of the present study was to determine MMP-2, MMP-9, TIMP-1 and TIMP-2 protein expression in decidual endometrium during the first trimester of pregnancy (22-42 days post coitus) with special attention to their expression patterns in endometrial compartments. Cytokeratin staining applied to adjacent sections was used to identify epithelial and trophoblast cells. We observed that MMP-2, particularly in the fourth week, appeared to be expressed more strongly in extravillous trophoblasts (EVTs) and vascular endothelial cells in the first trimester of pregnancy. Therefore, MMP-2 is likely to be the primary mediator in invasion of the trophoblast into the decidual endometrium, as well as in vascular remodeling and angiogenesis in the first trimester of pregnancy. The high expression of TIMP-1 and TIMP-2 in EVTs and glandular epithelium suggests that a restricted and balanced expression of these molecules is important for matrix remodeling and controlled trophoblast invasion during placentation. We conclude that (1) MMP-2 and MMP-9 and their inhibitors TIMP-1, and TIMP-2 determine the invasive behavior of trophoblast into the endometrium, and in particular, (2) MMP-2 may be the key regulator of trophoblast invasion in early human pregnancy.

Immunohistochemical and ultrastructural changes in the renal cortex of cadmium-treated rats.

The aim of this study was to determine the cadmium-induced immunohistochemical and morphological changes in the renal cortex of adult male rats exposed to high doses of cadmium for 30 d. Animals used as controls received a standard diet and water ad libitum. The animals used for this study received 15 ppm CdCl2 in their drinking water for 1 mo. The mean arterial pressure (MAP), the mean blood Cd level, and the mean tissue Cd content were significantly higher when compared to controls (p < 0.01). Immunohistochemical studies demonstrated a weak labeling to type IV collagen and laminin, but a strong labeling to fibronectin in the renal cortex of the Cd-treated animals when compared to controls. The ultrastructural alterations found in Cd-treated rats were a diminution in the amount of filtration slits, increased fusion of foot processes in epithelial cells of the glomeruli, increase of lysosomal structures and pinocytic vesicles as well as large mitochondria in proximal tubule cells, and degenerated cells in distal tubules. Additionally, the glomerular basement membrane was slightly thickened. In conclusion, cadmium toxicity results in alterations in the renal extracellular matrix and tubular or glomerular cells, which could play an important role in renal dysfunction.

Immunocytochemical detection of neuronal nitric oxide synthase (nNOS)-IR in embryonic rat stomach between days 13 and 21 of gestation.

In this study, the localization and appearance of neuronal nitric oxide synthase-immunoreactive (nNOS-IR) nerve cells and their relationships with the developing gastric layers were studied by immunocytochemistry techniques and light microscopy in embryonic rat stomach. The stomachs of Wistar rat embryos aged 13-21 days were used. The first nerve cells containing nNOS-IR were seen on embryonic Day 14. The occurrence of mesenchymal cell condensation near nNOS-IR neuroblasts on embryonic Day 15 may reflect an active nerve element-specific mesenchymal cell induction causing the morphogenesis of muscle cells. Similarly, the appearance of glandular structures after nNOS-IR neuroblasts, on embryonic Day 18, suggests that the epithelial differentiation may depend on inputs coming from nNOS-IR neuroblasts, as well as other factors. Observation of nNOS-IR nerve fibers on embryonic Day 21 demonstrates that at this stage they contribute to nonadrenergic noncholinergic relaxation. In conclusion, depending on this study's results, it can be said that cells and tissues might be affected by NO secreted by nNOS-IR nerve cells during the development and differentiation of embryonic rat stomach.