“” One of the most investigated examples is the developmentally r

“” One of the most investigated examples is the developmentally regulated shift of actions of the transmitter GABA that inhibit adult neurons but excite

immature ones because JPH203 research buy of an initially higher intracellular chloride concentration [Cl-](i), leading to depolarizing and often excitatory actions of GABA instead of hyperpolarizing and inhibitory actions. The levels of [Cl-](i) are also highly labile, being readily altered transiently or persistently by enhanced episodes of activity in relation to synaptic plasticity or a variety of pathological conditions, including seizures and brain insults. Among the plethora of channels, transporters, and other devices involved in controlling [Cl-](i), two have emerged as playing a particularly important role: the chloride importer NKCC1 and the chloride exporter KCC2. Here, the authors stress the importance of determining how [Cl-](i) is dynamically regulated and how this affects brain operation in health and disease. In a clinical DNA Damage inhibitor perspective, agents

that control [Cl-](i) and reinstate inhibitory actions of GABA open novel therapeutic perspectives in many neurological disorders, including infantile epilepsies, autism spectrum disorders, and other developmental disorders.”
“Hyperactivity of the hypothalamic-pituitary-adrenal axis (HPAA) resulting from fetal programming may play a rote in the development of high blood pressure (BP) in black people. We assessed the diurnal salivary cortisol profile in children with and without increased BP and evaluated their

mother’s HPAA. In a cross-sectional study, 20 Afro-Caribbean children (mean age 9.6 years) with higher blood pressures and Phospholipase D1 20 children with lower blood pressures were chosen from a prospective study of 569 mothers and children in Jamaica. Daytime salivary cortisol profiles were collected in the children and their mothers. The mothers were also assessed for features of the metabolic syndrome.

Children with higher BP had higher mean morning salivary cortisol concentrations than those with lower BP (7.9 S.D. 1.9 vs. 4.5 S.D. 2.4 nmol/l; p = 0.03). Their mothers also had increased morning salivary cortisol concentrations (9.9 S.D. 1.8 vs. 5.5 S.D. 2.5 nmol/l; p = 0.02), but no changes in fasting glucose, insulin, lipids, BP or adiposity. Maternal and offspring cortisol concentrations correlated significantly (r = 0.465, p = 0.004). Maternal cortisol concentrations were significantly associated with the child’s BP. We conclude that Afro-Caribbean children with higher BP have higher morning salivary cortisol concentrations. The children’s cortisol concentrations correlate significantly with the mother’s cortisol concentrations. These findings suggest that the HPAA may play a role in the development of raised BP in Afro-Caribbean people. (C) 2008 Elsevier Ltd. All rights reserved.

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