European journal of clinical investigation
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Eur. J. Clin. Invest. · May 2004
Sex hormone regulation of systemic endothelial and renal microvascular reactivity in type-2 diabetes: studies in gonadectomized and sham-operated Zucker diabetic rats.
Male Zucker diabetic rats exhibit a more severe endotheliopathy in comparison with their female diabetic litter mates. The plasma concentrations of both thromboxanes and endothelins are elevated in diabetes, and the receptor cross-talk between TXA(2) and ET-1 receptors may be enhanced in type-2 diabetic Zucker rats. ⋯ Testosterone and estradiol regulate systemic and microvascular reactivity to TXA(2) receptor stimulation in type-2 diabetic Zucker rats. The impact of testosterone on blood glucose concentration, blood pressure, and the systemic and renal microcirculatory response to ET-1 and NO, as well as the endothelin-thromboxane receptor cross talk, is greater, and opposite to that of estradiol. The effects of testosterone withdrawal may at least in part be mediated by the ET-B receptor subtype and NO generation. Androgen blockade should be investigated further for the reversal or delay of hypertensive-diabetic endotheliopathy.
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Eur. J. Clin. Invest. · Apr 2004
Rat duodenal IRP1 activity and iron absorption in iron deficiency and after HO perfusion.
Iron regulatory protein 1 (IRP1), a post-transcriptional regulator of iron metabolism, is activated in the duodenum of iron-deficient animals, which is associated with increased iron absorption. In cell cultures IRP1 was also activated by iron-independent signals, such as H(2)O(2). Here we investigate whether luminal perfusion of rat duodenum with H(2)O(2) activates duodenal IRP1 and modulates duodenal iron absorption. ⋯ Duodenal (59)Fe uptake is not affected by the H(2)O(2)-mediated activation of IRP1.
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Eur. J. Clin. Invest. · Dec 2003
Gender, age and menopause effects on the prevalence and the characteristics of obstructive sleep apnea in obesity.
In the 1970s and 80s it was believed that obstructive sleep apnea (OSA) was primarily a disease of men. The present study was addressed to evaluate the effect of gender and menopause on the prevalence and the characteristics of OSA and on anthropometric, clinical, respiratory and polysomnographic data in a population of obese individuals. ⋯ Our study demonstrates that (i) the male dominance regarding the prevalence and the severity of OSA disappears in men older than 55 years, and (ii) menopause seems to play a pivotal role in modulating both the presence and the degree of sleep disorder.
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Eur. J. Clin. Invest. · Nov 2003
ReviewPharmacogenetics of cytochrome p4502D6: genetic background and clinical implication.
Interindividual differences in the pharmacokinetics of a number of drugs are often due to hereditary polymorphisms of drug-metabolizing enzymes. Most important is cytochrome p4502D6 (CYP2D6), also known as debrisoquine/sparteine hydroxylase. It catalyzes hydroxylation or demethylation of more than 20% of drugs metabolized in the human liver, such as neuroleptics, antidepressants, some beta-blockers and many others like codeine. ⋯ About 1%-3% of Middle-Europeans, but up to 29% of Ethiopians display gene duplications, leading to elevated so-called ultrarapid metabolization rates. Meanwhile there is now a much better understanding of the genetic background of poor, intermediate, extensive and ultrarapid metabolizers, enabling a more precise DNA genotyping-based prediction of plasma levels. Since there is evidence that deteriorated drug elimination partly accounts for drug side-effects, CYP2D6 genotyping could contribute to an individualized and therefore optimized drug therapy.