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Guided by the Double ABCX Model of Family Adjustment and Adaptation, this study explored the coping strategies and adaptation processes employed by grandparent caregivers as they moved from the initial crisis phase of taking in their grandchildren to settling down and carrying out the daily tasks of childrearing. Using qualitative methods, we analyzed data from in-depth family life history interviews conducted with 26 grandfamilies. Our analyses revealed five themes: capturing grandparents' adaptation processes or shifts in roles, identities, relationships, resources, and perceptions of the situation in order to cope with their family transitions and stressors. We conclude with considerations for future research that are needed to identify and support positive adaptations within these complex family constellations. [ABSTRACT FROM AUTHOR]

The mechanism(s) by which glucose regulates glucagon secretion both acutely and in the longer term remain unclear. Added to isolated mouse islets in the presence of 0.5 mmol/l glucose, gamma-aminobutyric acid (GABA) inhibited glucagon release to a similar extent (46%) as 10 mmol/l glucose (55%), and the selective GABA(A) receptor (GABA(A)R) antagonist SR95531 substantially reversed the inhibition of glucagon release by high glucose. GABA(A)R alpha4, beta3, and gamma2 subunit mRNAs were detected in mouse islets and clonal alphaTC1-9 cells, and immunocytochemistry confirmed the presence of GABA(A)Rs at the plasma membrane of primary alpha-cells. Glucose dose-dependently increased GABA(A)R expression in both islets and alphaTC1-9 cells such that mRNA levels at 16 mmol/l glucose were approximately 3.0-fold (alpha4), 2.0-fold (beta3), or 1.5-fold (gamma2) higher than at basal glucose concentrations (2.5 or 1.0 mmol/l, respectively). These effects were mimicked by depolarizing concentrations of K(+) and reversed by the L-type Ca(2+) channel blocker nimodipine. We conclude that 1) release of GABA from neighboring beta-cells contributes substantially to the acute inhibition of glucagon secretion from mouse islets by glucose and 2) that changes in GABA(A)R expression, mediated by changes in intracellular free Ca(2+) concentration, may modulate this response in the long term. [ABSTRACT FROM AUTHOR]

Accumulating evidence supports a role for κ-opioid receptor antagonists in the treatment of mood disorders. Standard κ-antagonists have an unusual pharmacodynamic action, with a single injection blocking receptor signaling for several weeks. Here, we have characterized the κ-selective properties of two ligands, 5'-(2-aminomethyl) naltrindole (5'-AMN) and N-((Naltrindol-5-yl) methyl) pentanimidamide (5'-MABN), to identify whether modifications of the naltrindole side chain produces short-acting κ-antagonists. Opioid receptor binding affinity and activity were assessed using [(3)H]-diprenorphine binding, guanosine-5'-O-(3-[35S]-thio) triphosphate ([(35)S]-GTPγS) binding and isolated guinea-pig ileum. Pharmacodynamic profiles of 5'-AMN and 5'-MABN (1-10 mg/kg) were investigated using the tail-withdrawal assay and diuresis. Efficacy was also determined in depression- and anxiety-related behavioral paradigms in CD-1 mice. Both 5'-AMN and 5'-MABN had high affinity for κ-receptors (K (i) 1.36 ± 0.98 and 0.27 ± 0.08, respectively) and were revealed as potent κ-antagonists (pA(2) 7.43 and 8.18, respectively) and μ-receptor antagonists (pA(2) 7.62 and 7.85, respectively) in the ileum. Contrary to our hypothesis, in vivo, 5'-AMN and 5'-MABN displayed long-lasting antagonist effects in mice, reducing the antinociceptive actions of U50,488 (10 mg/kg) at 28 and 21 days post-injection, respectively. Interestingly, while 5'-AMN and 5'-MABN were not κ-selective, both compounds did show significant antidepressant- and anxiolytic-like effects at 7-14 days post-injection in mice. [ABSTRACT FROM AUTHOR]