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Medical Sciences	100%

Selected Abstracts

Mothering in Public: A Meta-Synthesis of Homeless Women With Children Living in Shelters

JOURNAL FOR SPECIALISTS IN PEDIATRIC NURSING, Issue 4 2003
MPHArticle first published online: 24 AUG 200, Mikki Meadows-Oliver MSN
ISSUES AND PURPOSE The purpose of this paper is to synthesize the current qualitative literature on homeless women with children living in shelters. METHODS Eighteen qualitative studies on homeless women with children living in shelters were included in the synthesis. The meta-synthesis was conducted using the meta-ethnographic approach of Noblit and Hare (1988). RESULTS Six reciprocal translations (themes) of homeless mothers caring for their children in shelters emerged: On becoming homeless, protective mothering, loss, stressed and depressed, survival strategies, and strategies for resolution. PRACTICE IMPLICATIONS The results may be used by healthcare workers as a framework for developing intervention strategies directed toward helping mothers find new solutions to dealing with shelter living and innovative ways to resolve their homelessness. [source]

Reduced signal transduction by 5-HT4 receptors after long-term venlafaxine treatment in rats

BRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2010
R Vidal
BACKGROUND AND PURPOSE The 5-HT4 receptor may be a target for antidepressant drugs. Here we have examined the effects of the dual antidepressant, venlafaxine, on 5-HT4 receptor-mediated signalling events. EXPERIMENTAL APPROACH The effects of 21 days treatment (p.o.) with high (40 mg·kg,1) and low (10 mg·kg,1) doses of venlafaxine, were evaluated at different levels of 5-HT4 receptor-mediated neurotransmission by using in situ hybridization, receptor autoradiography, adenylate cyclase assays and electrophysiological recordings in rat brain. The selective noradrenaline reuptake inhibitor, reboxetine (10 mg·kg,1, 21 days) was also evaluated on 5-HT4 receptor density. KEY RESULTS Treatment with a high dose (40 mg·kg,1) of venlafaxine did not alter 5-HT4 mRNA expression, but decreased the density of 5-HT4 receptors in caudate-putamen (% reduction = 26 ± 6), hippocampus (% reduction = 39 ± 7 and 39 ± 8 for CA1 and CA3 respectively) and substantia nigra (% reduction = 49 ± 5). Zacopride-stimulated adenylate cyclase activation was unaltered following low-dose treatment (10 mg·kg,1) while it was attenuated in rats treated with 40 mg·kg,1 of venlafaxine (% reduction = 51 ± 2). Furthermore, the amplitude of population spike in pyramidal cells of CA1 of hippocampus induced by zacopride was significantly attenuated in rats receiving either dose of venlafaxine. Chronic reboxetine did not modify 5-HT4 receptor density. CONCLUSIONS AND IMPLICATIONS Our data indicate a functional desensitization of 5-HT4 receptors after chronic venlafaxine, similar to that observed after treatment with the classical selective inhibitors of 5-HT reuptake. [source]

RESEARCH PAPER: Effects of drug interactions on biotransformation and antiplatelet effect of clopidogrel in vitro

BRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2010
Anja Zahno
BACKGROUND AND PURPOSE The conversion of clopidogrel to its active metabolite, R-130964, is a two-step cytochrome P450 (CYP)-dependent process. The current investigations were performed to characterize in vitro the effects of different CYP inhibitors on the biotransformation and on the antiplatelet effect of clopidogrel. EXPERIMENTAL APPROACH Clopidogrel biotransformation was studied using human liver microsomes (HLM) or specific CYPs and platelet aggregation using human platelets activated with ADP. KEY RESULTS Experiments using HLM or specific CYPs (3A4, 2C19) revealed that at clopidogrel concentrations >10 µM, CYP3A4 was primarily responsible for clopidogrel biotransformation. At a clopidogrel concentration of 40 µM, ketoconazole showed the strongest inhibitory effect on clopidogrel biotransformation and clopidogrel-associated inhibition of platelet aggregation with IC50 values of 0.03 ± 0.07 µM and 0.55 ± 0.06 µM respectively. Clarithromycin, another CYP3A4 inhibitor, impaired clopidogrel biotransformation and antiplatelet activity almost as effectively as ketoconazole. The CYP3A4 substrates atorvastatin and simvastatin both inhibited clopidogrel biotransformation and antiplatelet activity, less potently than ketoconazole. In contrast, pravastatin showed no inhibitory effect. As clopidogrel itself inhibited CYP2C19 at concentrations >10 µM, the CYP2C19 inhibitor lansozprazole affected clopidogrel biotransformation only at clopidogrel concentrations ,10 µM. The carboxylate metabolite of clopidogrel was not a CYP substrate and did not affect platelet aggregation. CONCLUSIONS AND IMPLICATIONS At clopidogrel concentrations >10 µM, CYP3A4 is mainly responsible for clopidogrel biotransformation, whereas CYP2C19 contributes only at clopidogrel concentrations ,10 µM. CYP2C19 inhibition by clopidogrel at concentrations >10 µM may explain the conflicting results between in vitro and in vivo investigations regarding drug interactions with clopidogrel. [source]

Emodin, a natural product, selectively inhibits 11,-hydroxysteroid dehydrogenase type 1 and ameliorates metabolic disorder in diet-induced obese mice

BRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2010
Ying Feng
BACKGROUND AND PURPOSE 11,-Hydroxysteroid dehydrogenase type 1 (11,-HSD1) is an attractive therapeutic target of type 2 diabetes and metabolic syndrome. Emodin, a natural product and active ingredient of various Chinese herbs, has been demonstrated to possess multiple biological activities. Here, we investigated the effects of emodin on 11,-HSD1 and its ability to ameliorate metabolic disorders in diet-induced obese (DIO) mice. EXPERIMENTAL APPROACH Scintillation proximity assay was performed to evaluate inhibition of emodin against recombinant human and mouse 11,-HSDs. The ability of emodin to inhibit prednisone- or dexamethasone-induced insulin resistance was investigated in C57BL/6J mice and its effect on metabolic abnormalities was observed in DIO mice. KEY RESULTS Emodin is a potent and selective 11,-HSD1 inhibitor with the IC50 of 186 and 86 nM for human and mouse 11,-HSD1, respectively. Single oral administration of emodin inhibited 11,-HSD1 activity of liver and fat significantly in mice. Emodin reversed prednisone-induced insulin resistance in mice, whereas it did not affect dexamethasone-induced insulin resistance, which confirmed its inhibitory effect on 11,-HSD1 in vivo. In DIO mice, oral administration of emodin improved insulin sensitivity and lipid metabolism, and lowered blood glucose and hepatic PEPCK, and glucose-6-phosphatase mRNA. CONCLUSIONS AND IMPLICATIONS This study demonstrated a new role for emodin as a potent and selective inhibitor of 11,-HSD1 and its beneficial effects on metabolic disorders in DIO mice. This highlights the potential value of analogues of emodin as a new class of compounds for the treatment of metabolic syndrome or type 2 diabetes. [source]