Case Control Study to Compare Serum Vascular Endothelial Growth Factor (VEGF) Level in Women with Recurrent Pregnancy Loss (RPL) Compared to Women with Term Pregnancy.

INTRODUCTION: Recurrent pregnancy loss (RPL) is defined as three or more spontaneous pregnancy losses before the 20th week of gestation or fetal weight of < 500 gm from the last menstrual period. Vascular endothelial growth factor (VEGF) is essential for implantation, development of embryo and placental angiogenesis. Women with low VEGF level are believed to be at higher risk of RPL. OBJECTIVE: To measure the level of VEGF in women with RPL and compare it with women with 1 or more successful pregnancies. METHODS: This is a Case control study carried out in King George Medical University, Lucknow from August 2015 to 2016. Participants sample size was 60 women. Thirty women with 3 or more spontaneous abortions were included as cases, and 30 women with at least 1 successful term pregnancy were controls. Serum VEGF level was analyzed using ELISA kit. Main outcome measured: 1. Serum VEGF level in the two groups. 2. Serum VEGF level in different underlying etiologies in women with RPL. RESULTS: Mean VEGF level was 105.3 pg/mL in RPL cases, while it was 156.8 pg/mL in fertile controls. (p = 0.01). VEGF level was 86.2 pg/mL in patients with anatomical defects, 109 pg/mL in APLA syndrome, 85.1 pg/mL in hypothyroidism and 122.2 pg/mL in unexplained RPL. CONCLUSION: The mean serum VEGF level was significantly lower in women with recurrent pregnancy loss compared with women with successful term pregnancy, implicating its role in maintaining pregnancy.

Prediction of Poor Ovarian response by Biochemical and Biophysical Markers: A Logistic Regression Model.

OBJECTIVES: To study correlation between ovarian reserve with biophysical markers (antral follicle count and ovarian volume) and biochemical markers (S. FSH, S. Inhibin B, and S. AMH) and use these markers to predict poor ovarian response to ovarian induction. METHODS: This is a prospective observational study. One hundred infertile women attending the Obst & Gynae Dept, KGMU were recruited. Blood samples were collected on day 2/day 3 for assessment of S. FSH, S. Inhibin B, and S. AMH and TVS were done for antral follicle count and ovarian volume. Clomephene citrate 100 mg 1OD was given from day 2 to 6, and patients were followed up with serial USG measurements. The numbers of dominant follicles (> or = 14 mm) at the time of hCG administration were counted. Patients with <3 follicles in the 1st cycle were subjected to the 2nd cycle of clomephene 100 mg 1OD from day 2 to day 6 with Inj HMG 150 IU given i.m. starting from day 8 and every alternate day until at least one leading follicle attained ≥18 mm. Development of <3 follicles at end of the 2nd cycle was considered as poor response. RESULTS: Univariate analyses showed that s. inhibin B presented the highest (ROCAUC = 0.862) discriminating potential for predicting poor ovarian response, In multivariate logistic regression model, the variables age, FSH, AMH, INHIBIN B, and AFC remained significant, and the resulting model showed a predicted accuracy of 84.4 %. CONCLUSION: A derived multimarker computation by a logistic regression model for predicting poor ovarian response was obtained through this study. Thus, potential poor responders could be identified easily, and appropriate ovarian stimulation protocol could be devised for such pts.

Neuroimaging features and predictors of outcome in eclamptic encephalopathy: a prospective observational study.

BACKGROUND AND PURPOSE: Posterior reversible encephalopathy syndrome is associated with eclampsia. We assessed the distribution and nature of typical and atypical cranial MR imaging findings in these patients and their correlation with clinical and laboratory data and predictors of outcome. MATERIALS AND METHODS: Forty-five clinically confirmed cases of eclampsia were included in this prospective observational study. Subjects with hemolysis, elevated liver enzymes, and low platelets syndrome (n = 9) and pre-existing neurologic conditions (1 with cerebral solitary cysticercus granuloma) were excluded. Patients underwent blood investigations and cranial MR imaging. RESULTS: Twenty-seven patients had abnormal while 8 had normal MR imaging findings. Involvement of brain regions was as follows: frontal, 88.89%; temporal, 44.44%; parietal, 100%; occipital, 100%; deep gray matter, 29.63%; cerebellum, 22.22%; brain stem, 14.81%. Cytotoxic edema was present in 33.33% of cases; 66.67% of patients had mild posterior reversible encephalopathy syndrome; 25.92% had moderate posterior reversible encephalopathy syndrome; and 7.41% had severe posterior reversible encephalopathy syndrome. Abnormal neuroimaging findings were significantly associated with altered sensorium; visual disturbances; status epilepticus; and elevated serum creatinine, uric acid, and lactate dehydrogenase (P=.006, P=.018, P=.015, P=.019, P=.003, and P=.001, respectively). Serum creatinine, uric acid, and lactate dehydrogenase values and the presence of moderate or severe posterior reversible encephalopathy syndrome were significantly associated with mortality (P<.001, P<.001, P=.009, and P=.027, respectively). CONCLUSIONS: Neuroimaging in eclampsia demonstrates a higher incidence of atypical distributions and cytotoxic edema than previously thought. Altered sensorium; visual disturbances; status epilepticus; and elevated serum uric acid, lactate dehydrogenase, and creatinine are associated with abnormal neuroimaging findings. Higher serum creatinine, uric acid, and lactate dehydrogenase levels and moderate and severe forms of posterior reversible encephalopathy syndrome are possible predictors of poor outcome.

The anti-proliferative effect of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b) pyran is potentiated via induction of estrogen receptor beta and p21 in human endometrial adenocarcinoma cells.

In an effort to develop novel therapeutic agents for endometrial cancer, benzopyran derivatives synthesized at our institute display significant inhibitory activity on cellular growth in uterine cancer cells. The current study was undertaken to demonstrate and explore the estrogen receptor (ER) subtype mediated mechanism of action of benzopyran derivative 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b) pyran (K-1) in human endometrial cancer cells. K-1 competitively inhibited the estradiol binding to human ERα and ERß and showed growth inhibitory activity in human endometrial Ishikawa, HEC1B and primary endometrial adenocarcinoma cells. Transient transactivation assays carried out in COS-1 cells have demonstrated the diminished ERα-ERE mediated- and induced the ERß-ERE mediated-transactivation triggered by compound. It also induced ER-mediated transactivation of the cyclin-dependent kinase inhibitor (CDKI) p21(WAF-1) in both COS-1 cells and in Ishikawa cells. ERß inducing effects of compound were blocked by ICI182,780. In endometrial adenocarcinoma cells, it induced ERß and p21 expression significantly whereas the expression of fos, jun and ERα were significantly reduced. In addition, compound promoted ERα-ß heterodimerization as observed in Ishikawa cells. These results demonstrate that the benzopyran compound suppressed the cellular growth via ERß agonism, induction of p21 and via promoting the ERα-ß heterodimerization, in addition to its antagonistic effects exerted on ERα, in human endometrial cancer cells. The study suggests that the dual action of benzopyran molecule may be of significant therapeutic value in ERα/ß-positive cases of endometrial cancer.

2,3-Diaryl-2H-1-benzopyran derivatives interfere with classical and non-classical estrogen receptor signaling pathways, inhibit Akt activation and induce apoptosis in human endometrial cancer cells.

OBJECTIVES: The present study was undertaken to explore the mechanism of anti-proliferative action of benzopyran compound D1 (2-[piperidinoethoxyphenyl]-3-phenyl-2H-benzopyran) and its hydroxy-(D2) and methoxy-(D3) derivatives in Ishikawa and human primary endometrial adenocarcinoma cells. METHODS: Transcriptional activation assays were performed using luciferase reporter system and cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The stage of cell cycle was determined by flow-cytometry and real time analysis of cyclinE1 and cdc2 genes. The apoptotic effects were measured by AnnexinV/PI staining and TUNEL. The expression of PCNA, cyclinD1, pAkt, XIAP, cleaved caspase-9, -3, PARP, Bax and Bcl2 were determined by immunoblotting. The caspase-3 activity and mitochondrial membrane potential were measured by colorimetric assay. RESULTS: All three compounds inhibited E(2)-induced ERE- and AP-1-mediated transactivation and proliferation in endometrial adenocarcinoma cells dose-dependently. Compound D1 caused the arrest of cells in the G(2) phase while D2 and D3 caused arrest in G(1) phase of the cell cycle. All compounds interfered with Akt activation, decreased XIAP expression leading to an increased cleavage of caspase-9, -3, PARP, increased Bax/Bcl2 ratio and caspase-3 activity. CONCLUSION: Findings suggest that benzopyran derivatives inhibit cellular proliferation via modulating ER-dependent classical and non-classical signaling mechanisms, interfere with Akt activation and induce apoptosis via intrinsic pathway in endometrial adenocarcinoma cells.