Sex-Specific Differences in Chromosome-Dependent Regulation of Vascular Reactivity in Female Consomic Rat Strains from a SS x BN Cross.

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Sex-Specific Differences in Chromosome-Dependent Regulation of Vascular Reactivity in Female Consomic Rat Strains from a SS x BN Cross.

Am J Physiol Regul Integr Comp Physiol. 2008 May 28;

Authors: Kunert MP, Dwinell MR, Drenjancevic-Peric I, Lombard JH

High-throughput studies in the Medical College of Wisconsin Program for Genomic Applications (Physgen) were designed to link chromosomes with physiological function in consomic strains derived from a cross between Dahl salt sensitive SS/JrHsdMcwi (SS) and Brown Norway normotensive BN/NHsdMcwi (BN) rats. The specific goal of the vascular protocol was to characterize the responses of aortic rings from these strains to vasoconstrictor and vasodilator stimuli (phenylephrine, acetylcholine, sodium nitroprusside and bath hypoxia) in order to identify chromosomes that either increase or decrease vascular reactivity to these vasoactive stimuli. Because previous studies demonstrated sex-specific quantitative trait loci (QTLs) related to regulation of cardiovascular phenotypes in an F2 cross between the parental strains, males and females of each consomic strain were included in all experiments. As there were significant sex-specific differences in aortic sensitivity to vasoconstrictor and vasodilator stimuli compared to the parental SS strain, we report the results of the females separately from the males. There were also sex-specific differences in aortic ring sensitivity to these vasoactive stimuli in consomic strains that were fed a high salt diet (4% NaCl) for three weeks to evaluate salt-induced changes in vascular reactivity. Differences in genetic architecture could contribute to sex-specific differences in the development and expression of cardiovascular diseases via differential regulation and expression of genes. Our findings are the first to link physiological traits with specific chromosomes in female SS rats, and support the idea that sex is an important environmental variable that plays a role in the expression and regulation of genes. Key words: phenylephrine, acetylcholine, sodium nitroprusside, hypoxia, vascular reactivity.

PMID: 18509103 [PubMed - as supplied by publisher]

June 3, 2008 | Filed Under Nursing | Leave a Comment 

Biochemical markers in persons with preclinical familial Alzheimer disease.

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Biochemical markers in persons with preclinical familial Alzheimer disease.

Neurology. 2008 May 28;

Authors: Ringman JM, Younkin SG, Pratico D, Seltzer W, Cole GM, Geschwind DH, Rodriguez-Agudelo Y, Schaffer B, Fein J, Sokolow S, Rosario ER, Gylys KH, Varpetian A, Medina LD, Cummings JL

BACKGROUND: Persons at risk for familial Alzheimer disease (FAD) provide a model in which biomarkers can be studied in presymptomatic disease. METHODS: Twenty-one subjects at risk for presenilin-1 (n = 17) or amyloid precursor protein (n = 4) mutations underwent evaluation with the Clinical Dementia Rating (CDR) scale. We obtained plasma from all subjects and CSF from 11. Plasma (Abeta40, Abeta42, F2-isoprostanes) and CSF (F2-isoprostanes, t-tau, p-tau181, Abeta40, Abeta42, and Abeta42/Abeta40 ratio) levels were compared between FAD mutation carriers (MCs) and noncarriers (NCs). RESULTS: Plasma Abeta42 levels (25.1 pM vs 15.5 pM, p = 0.031) and the ratio of Abeta42/Abeta40 (0.16 vs 0.11, p = 0.045) were higher in presymptomatic MCs. Among MCs, those with CDR scores of 0.5 had lower plasma Abeta42 levels than those with CDR scores of 0 (14.1 pM vs 25.1, p = 0.02). The ratio of Abeta42 to Abeta40 was also reduced in the CSF (0.08 vs 0.15, p = 0.046) of nondemented MCs compared to NCs. Total CSF tau and p-tau181 levels were elevated in presymptomatic FAD MCs. CSF levels of F2-isoprostanes were also elevated in MCs (n = 7, 48.6 pg/mL) compared to NCs (n = 4, 21.6 pg/mL, p = 0.031). CONCLUSIONS: Our data indicate that Abeta42 is elevated in plasma in familial Alzheimer disease (FAD) mutation carriers (MCs) and suggests that this level may decrease with disease progression prior to the development of overt dementia. We also demonstrated that the ratio of Abeta42 to Abeta40 was reduced in the CSF of nondemented MCs and that elevations of t-tau and p-tau181 are sensitive indicators of presymptomatic disease. Our finding of elevated F2-isoprostane levels in the CSF of preclinical FAD MCs suggests that oxidative stress occurs downstream to mismetabolism of amyloid precursor protein.

PMID: 18509095 [PubMed - as supplied by publisher]

June 3, 2008 | Filed Under Nursing | Leave a Comment 

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