Inorganic mercury exposure in prairie voles (Microtus ochrogaster) alters the expression of toll-like receptor 4 and activates inflammatory pathways in the liver in a sex-specific manner

Environmental exposure to mercury can cause a number of adverse effects in humans including the disruption of endocrine function that may result in sex-specific effects. The present study was designed to characterize sex-specific effects of chronic inorganic mercury exposure on toll-like receptor (TLR) 2 and TLR4 and inflammatory signaling in the liver of prairie voles (Microtus ochrogaster). Following 10 weeks of exposure to mercury via drinking water, effects on protein expression levels of TLR2 and TLR4 and the downstream p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa (NF-κB) signaling pathways were assessed. Using immunoblot analysis, we found that mercury exposure significantly enhanced the expression of TLR4 and activated p38 MAPK and NF-κB pathways in vole livers. This is the first report indicating that TLR4 may serve as a sensor for chronic mercury exposure in the liver. Further, compared to females, mercury-treated male voles exhibited significant increases in activated p38 MAPK and a greater extent of liver damage. Together, these findings establish sex-specific liver immunomodulation and cellular signaling following chronic inorganic mercury exposure. Furthermore, this study also supports the use of voles as biomarkers of environmental mercury contamination and offers a promising in vivo tool to test various therapeutic strategies for mercury detoxification.     

Determination of urinary iodine excretion to assess iodine deficiency level and iodine intake in primary school children, Bahir Dar, northwest Ethiopia

BACKGROUND: Iodine deficiency is a major public health problem all over the world, particularly among preschool children and pregnant women in low-income countries like Ethiopia and it is known to be the most common cause of preventable brain damage. OBJECTIVES: to determine urinary iodine concentration and to assess the level of iodine deficiency disorders. METHODS: A cross-sectional study was conducted in 386 randomly selected primary school children to determine urinary iodine concentrations as to assess level of iodine deficiency and iodine in take in Bahir Dar town. RESULTS: Median urinary iodine excretion was 58.8 mg/L (12.89 mg/L to 564.5 mg/L) which indicated the presence of mild iodine deficiency. Eighty seven percent of the children had urinary iodine excretion of below 100 mg/L and the intake of iodine was below 150 mg/day. CONCLUSIONS: Mild iodine deficiency disorder was found in Bahir Dar primary school children, Iodine intake was also found insufficient. Therefore, use of salt ionization should be advocated and strengthened.     

The lack of gonadotrophin-releasing hormone (GnRH) receptor desensitisation in alphaT3-1 cells is not due to GnRH receptor reserve or phosphatidylinositol 4,5-bis-phosphate pool size

The phospholipase C (PLC)-activating gonadotrophin-releasing hormone (GnRH) receptor is thought not to rapidly desensitise in alphaT3-1 cells. This extremely unusual characteristic raises the concern that it might be a feature of the cell type, rather than the receptor per se. Here we have used video imaging to establish whether the effects of endogenous PLC-activating G-protein coupled receptors (GPCRs) on Ca2+ ion concentration [Ca2+]i desensitise in these cells. Oxytocin, endothelin-1, methacholine, and UTP all caused [Ca2+]i increases which underwent rapid homologous desensitisation in that they were transient and responses to repeat stimuli were attenuated whereas subsequent responses to GnRH were not. To test whether receptor reserve obscures functional desensitisation of GnRH receptors, a photoaffinity antagonist (Pant-1), was used to effect a partial and irreversible receptor blockade. UV crosslinking in medium with 1000 nM Pant-1 reduced GnRH receptor number to 20 +/- 5% and reduced maximal buserelin-stimulated [3H]IP(X) accumulation to 57 +/- 5%, demonstrating removal of receptor reserve. In control alphaT3-1 cells the initial rate of GnRH-stimulated [3H]IP(X) accumulation was maintained for at least 5 min and GnRH caused a sustained increase in Ins(1,4,5)P3 mass (confirming the resistance of GnRH receptors to desensitisation) and Pant-1 pre-treatment reduced the magnitude of these responses without altering their temporal profiles. In alphaT3-1 cells stably transfected with recombinant human muscarinic receptors (alphaT3-1/M3), responses to methacholine were characteristic of desensitising GPCRs (transient Ins(1,4,5)P3 and curvilinear [3H]IP(X) responses) and were unaltered by Pant-1. To test the relevance of phospholipid pool size, alphaT3-1/M3 cells were pre-treated with GnRH or methacholine in medium with LiCl (to deplete PtdIns(4,5)P2 pools). These pre-treatments reduced subsequent responses to methacholine and GnRH comparably, indicating access to a shared PtdIns(4,5)P2 pool. Partial depletion of this pool (GnRH pre-treatment in medium with LiCl) reduced the magnitude of the [3H]IP(X) and Ins(1,4,5)P3 responses to methacholine and GnRH, without altering their temporal profiles. Thus the GnRH receptor does not undergo rapid homologous desensitisation in alphaT3-1 cells in spite of the fact that they can desensitise other endogenous (and recombinant) PLC-activating GPCRs, and the lack of desensitisation cannot be attributed to the existence of GnRH receptor reserve or access to an atypically large or rapidly re-cycled PtdIns(4,5)P2 pool. This unique functional characteristic (mammalian GnRH receptors are the only PLC-activating GPCRs known not to rapidly desensitise) almost certainly therefore reflects the atypical structure of these receptors (mammalian GnRH receptors are the only PLC-activating GPCRs known to lack C-terminal tails).     

Role of sex steroid receptors in pathobiology of hepatocellular carcinoma

The striking gender disparity observed in the incidence of hepatocellutar carcinoma （HCC） suggests an important role of sex hormones in HCC pathogenesis. Though the studies began as early as in 1980s, the precise role of sex hormones and the significance of their receptors in HCC still remain poorly understood and perhaps contribute to current controversies about the potential use of hormonal therapy in HCC. A comprehensive review of the existing literature revealed several shortcomings associated with the studies on estrogen receptor （ER） and androgen receptor （AR） in normal liver and HCC. These shortcomings include the use of less sensitive receptor ligand binding assays and immunohistochemistry studies for ERα alone until 1996 when ERβ isoform was identified. The animal models of HCC utilized for studies were primarily based on chemical-induced hepatocarcinogenesis with less similarity to virus-induced HCC pathogenesis. However, recent in vitro studies in hepatoma cells provide newer insights for hormonal regulation of key cellular processes including interaction of ER and AR with viral proteins. In light of the above facts, there is an urgent need for a detailed investigation of sex hormones and their receptors in normal liver and HCC. In this review, we systematically present the information currently available on androgens, estrogens and their receptors in normal liver and HCC obtained from in vitro, in vivo experimental models and clinical studies. This information will direct future basic and clinical research to bridge the gap in knowledge to explore the therapeutic potential of hormonal therapy in HCC.     

Parents' perception, students' and teachers' attitude towards school sex education

Background

Sex education is described as education about human sexual anatomy, sexual reproduction, sexual intercourse, reproductive health, emotional relations, reproductive rights and responsibilities, abstinence, contraception, family planning, body image, sexual orientation, sexual pleasure, values, decision making, communication, dating, relationships, sexually transmitted infections (STIs) and how to avoid them, and birth control methods. This study was conducted to explore perception of parents about school sex education and assess the attitude of teachers and students towards school sex education.

Methods

A cross-sectional quantitative and qualitative study was conducted on randomly selected 386 students, total census of 94 teachers and 10 parents in Merawi Town from March 13–27, 2011. Data were collected using self-administered structured questionnaire and in-depth interview guideline. Multiple linear regression analysis was performed using total score to determine the effect of the independent variables on the outcome variable and thematic analysis was used to analyze the qualitative data.

Results

All study participants have favourable attitude towards the importance of school sex education. They also agreed that the content of school sex education should include abstinence-only and abstinence-plus based on mental maturity of the students. That means at early age (Primary school) the content of school sex education should be abstinence-only and at later age (secondary school) the content of school sex education should be added abstinence-plus. The students and the teachers said that the minimum and maximum introduction time for school sex education is 5 year and 25 year with mean of 10.97(SD±4.3) and 12.36(SD±3.7) respectively. Teacher teaching experiences and field of studies have supportive idea about the starting of school sex education. Watching romantic movies, reading romantic materials and listening romantic radio programs appear to have a contribution on the predictor of students'' attitude towards the starting time of school sex education.

Conclusion

All study participants have a need to start sex education at school. All study participants said that at early age (Primary school) the content of school sex education is abstinence-only and at later age (secondary school) is added abstinence-plus. School Sex education should be under considers the need of students, teachers and parents.     

Evaluation du test de diagnostic rapide du paludisme OptiMal-IT® pLDH à la limite de la distribution de <Emphasis Type="Italic">Plasmodium falciparum</Emphasis> en Mauritanie

Performance of the malaria Rapid Diagnostic Test (RDT) OptiMal-IT® was evaluated in Mauritania where malaria is low and dependent on a short transmission season. Slide microscopy was considered as the reference method of diagnosis. Febrile patients with suspected malaria were recruited from six health facilities, 3 urban and 3 rural, during two periods (December 2011 to February 2012, and August 2012 to March 2013). Overall, 780 patients were sampled, with RDT and thick blood film microscopy results being obtained for 759 of them. Out of 774 slides examined, of which 200 were positive, P. falciparum and P. vivax mono-infections were detected in 63.5% (127) and 29.5% (59), while P. falciparum/P. vivax coinfections were detected in 7% (14). Both species were observed in all study sites, although in significantly different proportions. The proportions of thick blood film and OptiMal-IT® RDT positive individuals was 26.3% and 30.3% respectively. Sensitivity and specificity of OptiMal-IT® RDT were 89% [95% CI, 84.7-93.3] and 91.1% [88.6-93.4]. Positives and negative predictive values were 78.1% [72.2-83.7] and 95.9% [94.1-97.5]. These diagnostic values are similar to those generally reported elsewhere, and support the use of RDTs as the main diagnostic tool for malaria in Mauritanian health facilities. In the future, choice of RDTs to be used must take account of thermostability in a hot, dry environment and their ability to detect P. falciparum and P. vivax.