Cytokine gene polymorphisms in preeclampsia and eclampsia

The clinical spectrum of preeclampsia ( PE) ranges from mild hypertension to severe vasospasm associated with convulsions and multiple organ damage. the biological factors that determine the progression of PE to eclampsia ( E) are unknown. Endothelial cell activation seems related to an impaired maternal immune response. the production of cytokines, IL-10 and TGF-beta 1, is apparently suppressed, and altered IL-2/IL-10 and TNF-alpha/IL-10 ratios have been reported in preeclamptic cases. the relationship between PE and cytokine gene polymorphism has been studied, but there are few studies that include eclamptic patients. This study aimed at investigating whether polymorphisms in genes, TNF-alpha promoter (-308 G>A), IL6 promoter (-174 G>C), IFN-gamma intron 1 (+874 A>T), IL10 promoters (-1082 A>G), (-819 C>T) and (-592 C>A) and TGF-beta 1 codon 10 (+869 T>C) and codon 25 (+915 G>C) are associated with E and/or PE. Genotyping was carried out in 266 Mulatto women from the northeastern region of Brazil who were referred to a single maternity hospital: 92 with PE, 73 with E and 101 normotensive controls. the chi(2) or Fisher's exact tests were used to compare genotype frequencies. Among the six single-nucleotide polymorphisms ( SNPs) studied, we found no difference in genotype frequencies between the groups. There was a higher frequency of IFN-gamma (+874 A) in eclamptic patients in comparison with that in controls. (70.3 vs. 57.8%, respectively; P=0.02). There were no other significant differences in allelic frequencies between eclamptic, preeclamptic and control groups We found no independent association between any single SNP and PE or E risk in this population of Mulatto women from the northeastern region of Brazil. Hypertension Research ( 2009) 32, 565-569; doi: 10.1038/hr.2009.58; published online 1 May 2009Fundacao de Amparo a Pesquisa do Estado de Alagoas (FAPEAL)Universidade Federal de São Paulo, Dept Obstet, BR-04145002 São Paulo, BrazilAlagoas State Univ, Dept Obstet & Gynecol, Alagoas, BrazilUniversidade Federal de São Paulo, Dept Obstet, BR-04145002 São Paulo, BrazilWeb of Scienc

Neurokinin B and pre-eclampsia: a decade of discovery

ABSTRACT: At the start of the last decade, we provided evidence that levels of the peptide neurokinin B were highly elevated in pre-eclampsia. We hypothesized that elevated levels of neurokinin B may be an indicator of pre-eclampsia and that treatment with certain neurokinin receptor antagonists may be useful in alleviating the symptoms. At the time of the original hypothesis many questions remained outstanding. These included - Does neurokinin B have any diagnostic value in the detection and diagnosis of pre-eclampsia? - What is the cause of the elevated levels of neurokinin B during pre-eclampsia? - What is the physiological significance of neurokinin B in the placenta? This review discusses the answers to these questions taking into account the subsequent developments of the past ten years and analyzing the plethora of discoveries that have arisen from those initial observations

A dominant connexin43 mutant does not have dominant effects on gap junction coupling in astrocytes

Dominant mutations in GJA1, the gene encoding the gap junction protein connexin43 (Cx43), cause oculodentodigital dysplasia (ODDD), a syndrome affecting multiple tissues, including the central nervous system (CNS). We investigated the effects of the G60S mutant, which causes a similar, dominant phenotype in mice (Gja1Jrt/+). Astrocytes in acute brain slices from Gja1Jrt/+ mice transfer sulforhodamine-B comparably to that in their wild-type (WT) littermates. Further, astrocytes and cardiomyocytes cultured from Gja1Jrt/+ mice showed a comparable transfer of lucifer yellow to those from WT mice. In transfected cells, the G60S mutant formed gap junction (GJ) plaques but not functional channels. In co-transfected cells, the G60S mutant co-immunoprecipitated with WT Cx43, but did not diminish GJ coupling as measured by dual patch clamp. Thus, whereas G60S has dominant effects, it did not appreciably reduce GJ coupling.</jats:p