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排序方式: 共有685条查询结果,搜索用时 15 毫秒
121.
122.
Ahmet I Tae HJ de Cabo R Lakatta EG Talan MI 《Journal of molecular and cellular cardiology》2011,51(2):263-271
Multiple health benefits of calorie restriction (CR) and alternate day fasting (ADF) regimens are widely recognized. Experimental data concerning the effects of calorie restriction on cardiac health are more controversial, ranging from evidence that ADF protects heart from ischemic damage but results in developing of diastolic dysfunction, to reports that CR ameliorates the age-associated diastolic dysfunction. Here we investigated the effects of chronic CR on morphology and function of the cardiovascular system of aged rats and cardioprotective effect of CR against ischemic damage in the experimental rat model of MI. Cardiovascular fitness of 24-month old Fisher 344 rats maintained through life on ad libitum (AL) or CR diets was extensively evaluated via echocardiography, dobutamine stress test, pressure-volume loop analyses, pulse wave velocity measurements, and histology. Groups of 2-month old AL and 29-month old CR rats were studied for comparison. Myocardial infarction (MI) was induced by a permanent ligation of the anterior descending coronary artery in 5-month old rats maintained for 3 months on CR or AL. MI size was evaluated histologically 24 hrs following coronary ligation. Cardiac remodeling was followed-up via echocardiography. Age-associated changes in 24-month old rats consisted of 33% increase of fibrosis in the myocardium and more than 2 fold increase of the collagen in the tunica media of the aorta. There was a significant decrease in the density and total number of cardiomyocytes, while their size was increased. These morphological changes were manifested in a decline of systolic and diastolic cardiac function, increase of left ventricular and aortic stiffness, and arterio-ventricular uncoupling. Tachycardic response to dobutamine challenge was absent in the old rats. Compared to AL rats, 24-month old CR rats had reduced levels of cardiac and aortic fibrosis, increased density of cardiomyocytes that were smaller in size, attenuated diastolic dysfunction, normal systolic function and arterio-ventricular coupling. Tachycardic response to dobutamine was also intact in CR 24-month old rats and aortic stiffness was reduced. Adjustment for body weight differences through ratiometric or allometric scaling did not affect the overall pattern of differences between AL and CR rats. Attenuation of morphological and functional age-associated changes in 24-month old CR rats either was not observed at all or was smaller in 29-month old CR rats. Size of MI induced by a permanent coronary ligation as well as post-MI cardiac remodeling and function were similar in CR and AL rats. CR does not increase tolerance of myocardium to ischemic damage, but attenuates the age-associated changes in the heart and major vessels. The attenuation of age-associated changes by CR cannot be explained by the effect of lower body weight but are attributable to more intimate cellular mechanisms of CR itself. Attenuation of age-associated changes by CR waned with advancing age, and is consistent with the idea that CR postponed senescence. 相似文献
123.
Mitchell SJ Huizer-Pajkos A Cogger VC McLachlan AJ Le Couteur DG Jones B de Cabo R Hilmer SN 《The journals of gerontology. Series A, Biological sciences and medical sciences》2011,66(4):400-408
We investigated the effect of age-related pseudocapillarization of the liver sinusoidal endothelium on the hepatic disposition of acetaminophen. The multiple indicator dilution technique assessed the hepatic disposition of tracer (14)C-acetaminophen and reference markers in isolated perfused livers of young (n = 11) and old (n = 12) rats. Electron microscopy confirmed defenestration of the sinusoidal endothelium in old rats compared with young rats. Acetaminophen recovery following a single pass through the liver was significantly increased in old rats (0.64 ± 0.04, old; 0.59 ± 0.05, young; p < .05). In old age, there was significant reduction of the intercompartmental rate constant k(1) (0.34 ± 0.10 s(-1), old; 0.61 ± 0.38 s(-1), young; p < .05) and the permeability-surface area product for the transfer of acetaminophen across the sinusoidal endothelium (0.034 ± 0.006 mL/s/g, old; 0.048 ± 0.014 mL/s/g, young; p < .005). There was no difference in k(3), the measure of sequestration of acetaminophen that reflects enzyme activity. Age-related pseudocapillarization of the liver sinusoid resulted in increased acetaminophen recovery and decreased transfer of acetaminophen into the liver. 相似文献
124.
Dong-Hoon Hyun Mohamed R. Mughal Hyunwon Yang Ji Hyun Lee Eun Joo Ko Nicole D. Hunt Rafael de Cabo Mark P. Mattson 《Experimental neurology》2010,225(2):423-429
Membrane-associated oxidative stress has been implicated in the synaptic dysfunction and neuronal degeneration that occurs in Alzheimer's disease (AD), but the underlying mechanisms are unknown. Enzymes of the plasma membrane redox system (PMRS) provide electrons for energy metabolism and recycling of antioxidants. Here, we show that activities of several PMRS enzymes are selectively decreased in plasma membranes from the hippocampus and cerebral cortex of 3xTgAD mice, an animal model of AD. Our results that indicate the decreased PMRS enzyme activities are associated with decreased levels of coenzyme Q10 and increased levels of oxidative stress markers. Neurons overexpressing the PMRS enzymes (NQO1 or cytochrome b5 reductase) exhibit increased resistance to amyloid β-peptide (Aβ). If and to what extent Aβ is the cause of the impaired PMRS enzymes in the 3xTgAD mice is unknown. Because these mice also express mutant tau and presenilin-1, it is possible that one or more of the PMRS could be adversely affected by these mutations. Nevertheless, the results of our cell culture studies clearly show that exposure of neurons to Aβ1–42 is sufficient to impair PMRS enzymes. The impairment of the PMRS in an animal model of AD, and the ability of PMRS enzyme activities to protect neurons against Aβ-toxicity, suggest enhancement PMRS function as a novel approach for protecting neurons against oxidative damage in AD and related disorders. 相似文献
125.
126.
Rita Vidal Hernández Silvia Campos Arca Marta Vázquez Rodríguez Ovidio Vidal Vázquez Emilio Salvador Cabo Silva 《Progresos de Obstetricia y Ginecología》2012
Steroid cell tumors account for 0.1% of ovarian tumors and are classified within the group of stromal tumors, also known as sex cord tumors. These neoplasms can appear at any age but are more common in menopausal women and are associated with endocrine syndromes. The most significant clinical findings are hirsutism and virilization. Management should be individualized according to histological findings, surgical stage and the woman's reproductive wishes. 相似文献
127.
Michel Bernier Devin Wahl Ahmed Ali Joanne Allard Shakeela Faulkner Artur Wnorowski Mitesh Sanghvi Ruin Moaddel Irene Alfaras Julie A. Mattison Stefano Tarantini Zsuzsanna Tucsek Zoltan Ungvari Anna Csiszar Kevin J. Pearson Rafael de Cabo 《Aging》2016,8(5):899-914
Previous studies have shown positive effects of long-term resveratrol (RSV) supplementation in preventing pancreatic beta cell dysfunction, arterial stiffening and metabolic decline induced by high-fat/high-sugar (HFS) diet in nonhuman primates. Here, the analysis was extended to examine whether RSV may reduce dietary stress toxicity in the cerebral cortex of the same cohort of treated animals. Middle-aged male rhesus monkeys were fed for 2 years with HFS alone or combined with RSV, after which whole-genome microarray analysis of cerebral cortex tissue was carried out along with ELISA, immunofluorescence, and biochemical analyses to examine markers of vascular health and inflammation in the cerebral cortices. A number of genes and pathways that were differentially modulated in these dietary interventions indicated an exacerbation of neuroinflammation (e.g., oxidative stress markers, apoptosis, NF-κB activation) in HFS-fed animals and protection by RSV treatment. The decreased expression of mitochondrial aldehyde dehydrogenase 2, dysregulation in endothelial nitric oxide synthase, and reduced capillary density induced by HFS stress were rescued by RSV supplementation. Our results suggest that long-term RSV treatment confers neuroprotection against cerebral vascular dysfunction during nutrient stress. 相似文献
128.
Liu D Chan SL de Souza-Pinto NC Slevin JR Wersto RP Zhan M Mustafa K de Cabo R Mattson MP 《Neuromolecular medicine》2006,8(3):389-413
The high-metabolic demand of neurons and their reliance on glucose as an energy source places them atrisk for dysfunction
and death under conditions of metabolic and oxidative stress. Uncoupling proteins (UCPs) are mitochodrial inner membrane proteins
implicated in the regulation of mitochondrial membrane potential (ΔΨm) and cellular energy metabolism. The authors cloned UCP4 cDNA from mouse and rat brain, and demonstrate that UCP4 mRNA is
expressed abundantly in brain and at particularly high levels in populations of neurons believed to have high-energy requirements.
Neural cells with increased levels of UCP4 exhibit decreased ΔΨm, reduced reactive oxygen species (ROS) production and decreased mitochondrial calcium accumulation. UCP4 expressing cells
also exhibited changes of oxygen-consumption rate, GDP sensitivity, and response of ΔΨm to oligomycin that were consistent with mitochondrial uncoupling. UCP4 modulates neuronal energy metabolism by increasing
glucose uptake and shifting the mode of ATP production from mitochodnrial respiration to glycolysis, thereby maintaining cellular
ATP levels. The UCP4-mediated shift in energy metabolism reduces ROS production and increases the resistance of neurons to
oxidative and mitochondrial stress. Knockdown of UCP4 expression by RNA interference in primary hippocampal neurons results
in mitochondrial calcium overload and cell death. UCP4-mRNA expression is increased in neurons exposed to cold temperatures
and in brain cells of rats maintained on caloric restriction, suggesting a role for UCP4 in the previously reported antiageing
and neuroprotective effects of caloric restriction. By shifting energy metabolism to reduce ROS production and cellular reliance
on mitochondrial respiration, UCP4 can protect neurons against oxidative stress and calcium overload.
These authors made equal contributions to this research. 相似文献
129.
Adeladza Kofi Amegah Jouni JK Jaakkola 《Bulletin of the World Health Organization》2016,94(3):215-221
Globally, 41% of households, over 2.8 billion people, rely on solid fuels (coal and biomass) for cooking and heating. In developing countries in Asia and sub-Saharan Africa where these fuels are predominantly used, women who are customarily responsible for cooking, and their young children, are most exposed to the resulting air pollution. Solid fuels are still in widespread use and it appears that intervention efforts are not keeping pace with population growth in developing countries. Here we pinpoint the challenges and identify opportunities for addressing household air pollution while mitigating global climate change and promoting the sustainable development goals. We recommend the following actions: implementation of the WHO indoor air quality guidelines
on household fuel combustion; effective promotion and dissemination of improved cookstoves through formation of country alliances for clean cookstoves; expansion of liquefied petroleum gas production facilities and distribution networks; harnessing renewable energy potential; promotion of biogas production at both household and community level; ensuring improved ventilation of homes through education and enforcement of building standards; and exploiting opportunities in the health and other sectors for changing health-damaging cooking behaviour. 相似文献
130.
Cleft lip and palate (CLP) is one of the commonest congenital malformations and although the aetiology is still very unclear, a familial genetic component is considered to be an important factor in certain individuals. Molecular biology techniques are being used to identify the genes involved and this paper reviews current knowledge and the advances that have already been made. Recent evidence suggests a potential major gene on 6p, and a modifying role for transforming growth factor alpha (TGFA). Moreover retinoic acid receptor alpha (RARA) (17q), MSXl (4p), 4q and BCL3 (19q) could all be implicated in certain CLP families. In addition, the potential modifying role of various genes with the environment are considered to be important areas of research in the future. The identification of a genetic locus associated with this disease would be an important advance in CLP genetic counselling and lead to a better understanding of the genetic basis of CLP. 相似文献