Soluble VEGFR-1 in pathophysiology of pregnancies complicated by hypertensive disorders: the Indian scenario.

An imbalance between angiogenic and anti-angiogenic factors has been hypothesized to have a major role in hypertensive disorders during pregnancy, which account for significant morbidity and mortality for the mother and neonate in India. There is a paucity of information on soluble vascular endothelial growth factor receptor-1 (sVEGFR-1, anti-angiogenic factor) concentrations in different subgroups of pregnancy-induced hypertensive (PIH) disorders particularly in gestational hypertension (GH) and eclampsia during pregnancy. This cross-sectional study was conducted in order to test the above hypothesis and to get more insight into the role of sVEGFR-1 in these disorders. The concentrations of sVEGFR-1 in serum were measured from women with 22-39 weeks of gestation in the control (n=180) and gestationally matched hypertensive (n=360) pregnant mothers by ELISA. These sVEGFR-1 concentrations were found to be significantly elevated in the study groups as the severity of disease increases from GH to eclampsia (24 076 pg ml(-1); 42000 pg ml(-1), P=0.0001) as compared with controls (3360 pg ml(-1)). According to Receiver operating characteristic curve analysis, at ≤ 34 weeks, the concentration cutoff, sensitivity, specificity for sVEGFR-1 in differentiating GH, pre-eclampsia and eclampsia were ≥ 7619.2 pg ml(-1), 75%, 75%; ≥ 16726.6 pg ml(-1), 89.1%, 89.1%; ≥ 26222.8 pg ml(-1), 91.6%, 91.6%, respectively. The gradual upregulation of sVEGFR-1 concentrations in these groups may be due to its intimate involvement in the etiopathogenesis of severity of various hypertensive disorders by antagonizing effects of VEGF during the placental development. These observations indicate the clinical utility of sVEGFR-1 in differentiating PIH disorders and also will be helpful for the evaluation of increased monitoring system for successful pregnancy.

Morphology and morphometric analysis of stromal capillaries in full term human placental villi of smoking mothers: an electron microscopic study.

OBJECTIVES: The capillaries of placental villi play a very important role in the feto-maternal exchange of gases and nutrients. A morphological change in their structure may lead to the impairment of placental function. In this study an attempt has been made to find out the morphological and morphometric features of the capillaries in full term placental villi of non smoking mothers as well as active and passive smoking mothers under an electron microscope. MATERIALS AND METHODS: A total number of 163 placentae from active, passive and nonsmoking mother (n = 61+42+60) were processed for electron microscopic study. The ultrathin sections were examined under electron microscope and images were recorded. Morphometry and statistical analysis were carried out with the help of software. RESULTS: The study revealed that the endothelial cells of stromal capillaries of the placental villi were oedematous and the cytoplasm was rich in dilated endoplasmic reticulum, mitochondria, fibrils and fine filaments in both groups of the smokers' placenta in comparison to control. Morphometric analysis showed a significant reduction in the perimeter of the stromal capillary of the tertiary villi of placenta in both active and passive smokers from mean value of 71.65 ± 47.82 µ to mean value of 59.77 ± 29.72 µ (p = 0.07) and 49.49 ± 20.94 µ (p = 0.0005) respectively. In case of passive smoker, area of the capillary (µm²) reduced significantly (p = 0.00004) from mean value of 266.29 ± 331.86 µm² to 116.64 ± 83.62 µm² whereas the number of capillary per villus increased significantly (p = 0.046) from mean value 2.42 ± 1.84 to 4.2 ± 3.16. The thickness of basement membrane of the endothelial cells of stromal capillaries of the placenta increased significantly in active as well as passive smokers (p = 0.00001). CONCLUSIONS: The ultrastructural changes noticed in the endothelial cells of placental villi may be due to hypoxia resulting from tobacco consumption either in active or passive form by the pregnant mothers. Thus, targeted therapy may be implicated for hypoxia, which is one of the major cause of the life threatening disorders of pregnancy.

Bcl-2 and p53 expressions in Indian women with complete hydatidiform mole.

INTRODUCTION: Hydatidiform moles have a high incidence rate in Asian countries like India. The molecular pathway leading to the pathogenesis and progression of hydatidiform moles is not yet understood. This study aimed to investigate the biological significance of Bcl-2 and p53 in complete hydatidiform moles (CHMs) as well as their influence on disease progression in the Indian population. METHODS: Archival tissues from 35 patients with CHMs and 35 age-matched controls were examined for Bcl-2 and p53 expressions by immunohistochemistry. RESULTS: Bcl-2 was found to be immunolocalised in the cytoplasm of the syncytiotrophoblast, whereas p53 was observed in both the nucleus and cytoplasm of the syncytiotrophoblast and cytotrophoblasts. In CHMs, Bcl-2 was detected in 23 percent of patients and p53 nuclear expression, in 66 percent. A significant decrease in Bcl-2 expression was observed in CHMs (p-value is 0.015), and the down-regulation of Bcl-2 significantly correlated with higher nuclear expression of p53 (p-value is 0.002), indicating an inverse association between the two proteins (p-value is 0.0001). However, no correlation was found between the clinical progress of patients with CHMs and p53 and those with Bcl-2 protein expression. CONCLUSION: The current study demonstrated the significance of Bcl-2 and p53 in the pathogenesis of CHMs but did not reveal any association with disease progression.

Apoptosis and Bcl-2 protein expression in human placenta over the course of normal pregnancy.

Apoptosis plays a central role in organ development, homeostasis and immune defence in multicellular organisms and is strictly controlled in part by members of Bcl-2 family. The Bcl-2 is a pro-survival molecule identified through its involvement in B-cell lymphomas. The aim of the study was to evaluate the incidence of apoptosis in the human placenta at different stages of pregnancy and to correlate it further with Bcl-2 expression. A total of 96 placental samples from first trimester, mid-trimester and uncomplicated term pregnancies were collected (n = 32 + 32 + 32). M30 cyto death monoclonal antibody was used to identify apoptotic cells. The apoptosis index of first trimester placentae was 2.33 ± 1.70, mid- trimester was 1.77 ± 1.36 and term placenta was 1.15 ± 0.21. Bcl-2 protein was found immunolocalized in the cytoplasm of syncytiotrophoblast. Apoptosis index was significantly reduced in term cases as compared with first trimester (P < 0.002) and mid-trimester placentae (P = 0.01). On the contrary, Bcl-2 expression was significantly higher at term cases than in first trimester (P < 0.0001) and mid-trimester cases (P < 0.001). The present study divulges the importance of apoptosis in permitting normal physiological turnover of villous trophoblast and also exhibits the contribution of bcl-2 in maintaining syncytial integrity throughout normal pregnancy.

Mucosal and peripheral immune responses to chlamydial heat shock proteins in women infected with Chlamydia trachomatis.

Most of the studies on 60-kDa and 10-kDa chlamydial heat shock proteins (HSPs) to date have been carried out with blood lymphocytes or serum antibody responses, which do not provide a clear picture of the actual pathogenesis as they do not differentiate primary infection from recurrent infection. Thus, in the present study induction of the immune response was evaluated by studying lymphoproliferation of both cervical and peripheral lymphocytes to synthetic peptides of cHSP60, cHSP10 and major outer membrane protein (MOMP) antigen. In addition, cervical antibody prevalence to MOMP antigen, cHSP60 and cHSP10 and cytokine levels in cervical washes was also determined. Positive proliferative responses of cervical lymphocytes to cHSP10 peptide were significantly higher (P < 0.05) in women with recurrent infections and that to MOMP antigen were significantly higher in primary infection. On proliferation of PBMCs with the above antigens, no significant difference was observed between primary and recurrent infection. Prevalence of cervical IgG and IgA antibodies to Chlamydia trachomatis was significantly higher (P < 0.05) during primary infection than recurrent infections. In contrast, prevalence of IgG and IgA antibodies to cHSP10 and IgG antibodies to cHSP60 was higher during recurrent infections than primary infections. Interferon (IFN)-gamma levels were significantly higher in cervical washes of women with recurrent infection and correlated strongly with cHSP60 antibody titres. Our data thus suggest that mucosal responses are more appropriate in understanding the pathogenesis of chlamydial infection and IFN-gamma could be involved in the modulation of immune responses towards chlamydial infection directly, by causing acute inflammation, or indirectly through modulation of HSP expression.

Evaluation of expression of apoptosis-related proteins and their correlation with HPV, telomerase activity, and apoptotic index in cervical cancer.

OBJECTIVE: The aim of this study was to examine the expression of apoptosis-related proteins in cervical cancer, and investigate their correlation with the apoptotic index (AI), telomerase activity, human papilloma virus (HPV) infection and clinicopathological characteristics. METHODS: Fifty cervical cancer samples and 20 normal cervical tissues were assessed for the protein expression of survivin, Bcl-2, Cox-2, p53 and p73 by immunohistochemistry. HPV DNA was detected by PCR, telomerase activity by PCR-ELISA, and AI by TUNEL assay. RESULTS: 46/50 cervical tumors (92%) showed an increased telomerase activity as compared to 3/20 (15%) controls. 45/50 (90%) cervical tumors were positive for HPV, of which 30 were HPV-16 positive and 5 were HPV-18 positive. 24/50 (48%) tumors were positive for survivin, 14 (28%) for Bcl-2, 13 (26%) for Cox-2, 19/45 (42%) for p73, 10/45 (24%) for p53. Telomerase activity was highest in tumors with the poorest grade. A positive correlation was seen between survivin and Bcl-2, survivin and tumor stage, Bcl-2 and Cox-2, p73 and p53 and p73 and the AI. Despite the overexpression of various antiapoptotic proteins, no significant difference was observed in the AI between tumors and controls. CONCLUSIONS: Since deregulation of the apoptotic pathway appears to occur in cervical cancer, some apoptosis-related proteins could be assessed as potential markers for progression/prognosis in cervical cancer. Additionally, newer proteins such as p73 may play a compensatory role for the nonfunctional proteins such as p53.

Detection of Chlamydia trachomatis antigen in spontaneous abortions. Is this organism a primary or secondary indicator of risk?

In order to investigate whether or not Chlamydia trachomatis infection is a risk factor for pregnancy loss, 77 spontaneous abortion patients (6-24 weeks gestation), admitted to gynaecology emergency of Safdarjang Hospital, New Delhi, India. Twenty-five pregnant women (6-16 weeks gestation) attending the same hospital for induced abortion, were included in the study. C. trachomatis antigen was detected in endometrial curretage tissue by enzyme immunoassay (EIA). The detection rate was 15.6% (12/77) among spontaneous abortion patients and 4% (1/25) among women undergoing induced abortion. There was no statistically significant association between the mean age/mean gestational age of those experiencing spontaneous abortion, with and without C. trachomatis infection (26.9 years versus 25.06 years and 11.1 weeks versus 9.6 weeks, respectively). High prevalence of C. trachomatis was found in multigravidae and parous spontaneous abortion patients, compared with that in primigravidae and nulliparous Chlamydia-negative spontaneous aborters (75.0% versus 25.0%; 66.7% versus 33.3%, respectively). The prevalence of chlamydial antigen in patients with no prior history of spontaneous abortion was 16.1% (10/62) compared with 18.1% (2/11) in women with one prior abortion. Further study is required to determine whether C. trachomatis infection is a primary or secondary indicator of risk.

Clinico-pathological profile of carcinoma of the vulva.

There is a need for patient and physician education with regard to the early diagnosis of carcinoma of the vulva. Physicians must be made more aware of the importance of taking a biopsy diagnosis before treating a vulvar lesion. Biopsy of the vulva is a simple procedure that can be performed in any physician's office. Now we must all shift to the 3-incision operative procedure as it has proven to have less morbidity & mortality.