Relation between aerobic fitness and brain structures in amnestic mild cognitive impairment elderly

Mild cognitive impairment (aMCI) is a clinical condition, with high risk to develop Alzheimer’s disease. Physical exercise may have positive effect on cognition and brain structure in older adults. However, it is still under research whether these influences are true on aMCI subjects with low Ab_42 and high total tau in cerebrospinal fluid (CSF), which is considered a biomarker for AD. Therefore, we aimed to investigate a possible relation between aerobic fitness (AF) and gray matter (GM) volume and AF and white matter (WM) integrity in aMCI with a CSF biomarker. Twenty-two participants with aMCI acquired the images on a 3.0-T MRI. AF was assessed by a graded exercise test on a treadmill. Voxel-based morphometry and tract-based spatial statistic methods were used to analyze the GM volume and WM microstructural integrity, respectively. We correlated AF and GM volume and WM integrity in aMCI (p < 0.05, FWE corrected, cluster with at least five voxels). There was a positive relation between AF and GM volume mostly in frontal superior cortex. In WM integrity, AF was positively correlated with fractional anisotropy and negatively correlated with mean diffusivity and radial diffusivity, all in the same tracts that interconnect frontal, temporal, parietal, and occipital areas (longitudinal fasciculus, fronto-occipital fasciculus, and corpus callosum). These results suggest that aerobic fitness may have a positive influence on protection of brain even in aMCI CSF biomarker, a high-risk population to convert to AD.     

Demographic and clinical predictors of depressive symptoms among incarcerated women

Background  

Imprisonment may lead to the development of mental illness, especially depression. This study examines the clinical and sociodemographic profiles of imprisoned women, identifies indicative signs of depression, and relates these indicators to other variables.     

Cystatin C and carotid intima-media thickness in asymptomatic adults: the Multi-Ethnic Study of Atherosclerosis (MESA)

BACKGROUND: Persons with early kidney disease have an increased risk of cardiovascular events and mortality, but the importance of accelerated atherosclerosis in promoting these outcomes is unclear. We therefore explored whether serum cystatin C level is associated with carotid intima-media thickness (IMT) in ambulatory adults without clinical heart disease. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: We evaluated 6,557 ethnically diverse persons free of clinical cardiovascular disease aged 45 to 84 years at the baseline visit of the Multi-Ethnic Study of Atherosclerosis. PREDICTORS: Kidney function was estimated by using 2 methods: serum cystatin C level and estimated glomerular filtration rate, based on creatinine and cystatin C levels. OUTCOMES & MEASUREMENTS: Study outcomes were internal and common carotid IMT, measured by using high-resolution B-mode ultrasound. Multivariate linear and logistic regressions were used to evaluate the independent association of kidney function with carotid IMT. RESULTS: In unadjusted linear analysis, each SD (0.23 mg/L) greater cystatin C level was associated with 0.091-mm greater internal carotid IMT (P < 0.001), but this association was diminished by 70% after adjustment for age, sex, and race/ethnicity (0.027 mm; P < 0.001) and was no longer significant after adjustment for cardiovascular risk factors (0.005 mm; P = 0.5). Similarly, the strong unadjusted associations of cystatin C level with common carotid IMT disappeared after adjustment. Chronic kidney disease, defined by using either creatinine level or cystatin C-based estimated glomerular filtration rate less than 60 mL/min/1.73 m(2), had no independent association with internal and common carotid IMT. LIMITATIONS: There were few participants with severe kidney disease. CONCLUSIONS: Cystatin C level had no independent association with carotid IMT in a population free of clinical heart disease. This observation suggests that accelerated atherosclerosis is unlikely to be the primary mechanism explaining the independent association of cystatin C level with cardiovascular risk.     

Inhibition of 2-amino-3-methylimidazo[4,5-f]quinoline-DNA adducts by indole-3-carbinol: dose-response studies in the rat colon

Indole-3-carbinol (I3C) inhibits the formation of colonic aberrant crypt foci and DNA adducts in rats given heterocyclic amine colon carcinogens, such as 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Mechanism studies indicate that I3C induces cytochromes P4501A1 and 1A2 (CYP1A1 and CYP1A2), isozymes that respectively metabolize IQ via ring hydroxylation or activate the carcinogen by N-hydroxylation. The present study examined the dose-response for induction of CYP1A1 versus CYP1A2 by I3C, and compared the profiles of induction with the dose- response for inhibition of IQ-DNA adducts in the colon of the F344 rat. Dietary equivalent doses of I3C in the range 100-1000 p.p.m. increased in a dose-related manner both ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) activities in the liver and colonic mucosa, and Western blots showed a corresponding induction of CYP1A1 and CYP1A2 proteins. However, dietary equivalent doses of I3C in the range 10-25 p.p.m. (i) reduced hepatic EROD and MROD activities and CYP1A protein levels compared with controls, (ii) increased the ratio of CYP1A2 versus CYP1A1, and (iii) activated IQ to a more potent mutagen when liver microsomes from rats given I3C were used for metabolic activation in the Salmonella assay. Rats given a single oral dose of I3C shortly before administering IQ (5 mg/kg body wt, p.o.) exhibited dose-related inhibition of colonic IQ-DNA adducts in the range 25-100 p.p.m. I3C, reaching 95% inhibition at doses > or = 100 p.p.m. I3C, but IQ-DNA adducts were elevated slightly at the lowest I3C dose as compared with the controls. The possible significance of the low versus high dose effects of I3C are discussed in the context of human dietary exposures to I3C and the reported chemopreventive mechanisms of I3C in vivo.      

Deletion/insertion mutation that causes biotinidase deficiency may result from the formation of a quasipalindromic structure

Biotinidase is responsible for recycling the vitamin biotin from biocytin that is formed after the proteolytic degradation of the biotin- dependent carboxylases. We have identified a deletion/insertion mutation within exon D of the human biotinidase gene in a child with biotinidase deficiency. The mutation causes a frame shift and premature termination which are predicted to result in a truncated protein. We propose that the mutation occurred during DNA replication by either of two mechanisms. Both mechanisms involve formation of a quasipalindromic hairpin loop in the template and dissociation of DNA polymerase alpha. This mutation supports the formation of palindromic structures as a possible cause of deletions in eukaryotes, and supports the proposal, derived from in vitro studies, that polymerase alpha may preferentially arrest or dissociate at specific template sequences.      

去氢表雄酮硫酸酯钠盐对妊娠大鼠子宫颈张力的影响及作用机理

去氢表雄酮硫酸酯为正常人体肾上腺所分泌,是合成雄激素和雌激素的前体。1970年日本钟仿制药厂正式生产该产品作为宫颈成熟剂,用于治疗宫颈成熟不全和产程延长等。Mochizuki给妊娠末期的妇女ⅳ去氢表雄酮硫酸酯钠盐(OHA-S)100 mg,共2次,发现DHA-S能促进子     

二苯乙烯类化合物对蛋白激酶C的抑制作用

报道15种二苯乙烯类化合物对蛋白激酶C(PKC)活性的影响。其中从中药金雀根中分得的3种二苯乙烯类低聚体α-viniferin,kobophenol A 和 miyabenolC,它们抑制PKC的IC₅₀分别为62.5,52.0和27.5μmol·L^-1。另外6种含酚羟基的二苯乙烯化合物对PKC也显示不同程度的抑制作用,但当酚羟基全甲基化或全乙酰化后其抑制作用大大降低甚至消失。酶动力学研究证明miyabenolC对PKC的抑制作用属于非竞争性抑制。     

Mental vulnerability as a predictor of early mortality

BACKGROUND: Studies have demonstrated that mental vulnerability (ie, a tendency to experience psychosomatic symptoms or inadequate interpersonal interactions) is associated with various diseases. The objective of our study is to evaluate whether mental vulnerability is a risk factor for early mortality. METHODS: We conducted a prospective cohort study of 3 random samples of the population in Copenhagen County, Denmark selected in 1976, 1982-1984, and 1991 (n = 6435). Baseline data collection included measures of mental vulnerability, social factors, comorbidity, biologic risk markers (eg, blood pressure, lipid levels), and lifestyle factors. We determined vital status of the study sample through linkage to the Civil Registration System until 2001 and to the Cause of Death Registry until 1998. The mean follow-up time was 15.9 years for analysis of total mortality and 13.6 years for analysis of mortality as the result of natural causes. The association between mental vulnerability and survival was examined using Kaplan-Meir plots and Cox proportional-hazard models adjusting for possible confounding factors. RESULTS: With respect to mental vulnerability, 79% of the sample was classified as not vulnerable, 13% as moderately vulnerable, and 8% as highly vulnerable. Compared with the nonvulnerable group, highly vulnerable persons showed increased total mortality (hazard ratio = 1.6; 95% confidence interval = 1.3-1.9) and increased mortality from natural causes (1.6; 1.2-2.0). The inclusion of the mental vulnerability score as a continuous variable gave similar results. CONCLUSIONS: Mental vulnerability may be an independent risk factor for premature mortality. The biologic mechanisms that may underlie this association need further exploration.