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111.
Natalie J. Frost Michael Weinborn Gilles E. Gignac Stephanie R. Rainey-Smith Shaun Markovic Nicole Gordon Hamid R. Sohrabi Simon M. Laws Ralph N. Martins Jeremiah J. Peiffer Belinda M. Brown 《The American journal of geriatric psychiatry》2021,29(2):129-140
BackgroundThere is a paucity of interventional research that systematically assesses the role of exercise intensity and cardiorespiratory fitness, and their relationship with executive function in older adults. To address this limitation, we have examined the effect of a systematically manipulated exercise intervention on executive function.MethodsNinety-nine cognitively normal participants (age = 69.10 ± 5.2 years; n = 54 female) were randomized into either a high-intensity cycle-based exercise, moderate-intensity cycle-based exercise, or no-intervention control group. All participants underwent neuropsychological testing and fitness assessment at baseline (preintervention), 6-month follow-up (postintervention), and 12-month postintervention. Executive function was measured comprehensively, including measures of each subdomain: Shifting, Updating/ Working Memory, Inhibition, Verbal Generativity, and Nonverbal Reasoning. Cardiorespiratory fitness was measured by analysis of peak aerobic capacity; VO2peak.ResultsFirst, the exercise intervention was found to increase cardiorespiratory fitness (VO2peak) in the intervention groups, in comparison to the control group (F =10.40, p≤0.01). However, the authors failed to find mean differences in executive function scores between the high-intensity, moderate intensity, or inactive control group. On the basis of change scores, cardiorespiratory fitness was found to associate positively with the executive function (EF) subdomains of Updating/Working Memory (β = 0.37, p = 0.01, r = 0.34) and Verbal Generativity (β = 0.30, p = 0.03, r = 0.28) for intervention, but not control participants.ConclusionAt the aggregate level, the authors failed to find evidence that 6-months of high-intensity aerobic exercise improves EF in older adults. However, it remains possible that individual differences in experimentally induced changes in cardiorespiratory fitness may be associated with changes in Updating/ Working Memory and Verbal Generativity. 相似文献
112.
Shuhong Guo Rana Al-Sadi Hamid M. Said Thomas Y. Ma 《The American journal of pathology》2013,182(2):375-387
Bacterial-derived lipopolysaccharides (LPS) play an essential role in the inflammatory process of inflammatory bowel disease. A defective intestinal tight junction (TJ) barrier is an important pathogenic factor of inflammatory bowel disease and other inflammatory conditions of the gut. Despite its importance in mediating intestinal inflammation, the physiological effects of LPS on the intestinal epithelial barrier remain unclear. The major aims of this study were to determine the effects of physiologically relevant concentrations of LPS (0 to 1 ng/mL) on intestinal barrier function using an in vitro (filter-grown Caco-2 monolayers) and an in vivo (mouse intestinal perfusion) intestinal epithelial model system. LPS, at physiologically relevant concentrations (0 to 1 ng/mL), in the basolateral compartment produced a time-dependent increase in Caco-2 TJ permeability without inducing cell death. Intraperitoneal injection of LPS (0.1 mg/kg), leading to clinically relevant plasma concentrations, also caused a time-dependent increase in intestinal permeability in vivo. The LPS-induced increase in intestinal TJ permeability was mediated by an increase in enterocyte membrane TLR-4 expression and a TLR-4–dependent increase in membrane colocalization of membrane-associated protein CD14. In conclusion, these studies show for the first time that LPS causes an increase in intestinal permeability via an intracellular mechanism involving TLR-4–dependent up-regulation of CD14 membrane expression.An integral function of intestinal epithelial cells is to act as a physical barrier, separating the noxious luminal environment from the underlying lamina propria and the deeper intestinal layers.1,2 The apically located tight junctions (TJs) form a paracellular seal between the lateral membranes of adjacent intestinal epithelial cells, and act as a structural and functional barrier against paracellular flux of luminal substances. Defective intestinal epithelial TJ barrier has been shown to be an important pathogenic factor of inflammatory bowel disease (IBD) and necrotizing enterocolitis (NEC) by allowing paracellular permeation of luminal antigens that elicit and promote inflammatory response.1,2 Both clinical and animal studies have shown the importance of a defective intestinal TJ barrier in the development and prolongation of intestinal inflammation in IBD and NEC.1–5 These studies have shown that normalization of intestinal barrier in patients with active Crohn’s disease predicts prolonged clinical remission, whereas a persistent increase in intestinal permeability portends poor clinical outcome with rapid recurrence of the disease.6,7 Additionally, animal studies have also shown that a primary defect in intestinal junctional complexes was sufficient to induce or aggravate intestinal inflammation in murine models of IBD,8,9 whereas therapeutic tightening or enhancement of the intestinal TJ barrier prevented the development of intestinal inflammation.3,10The terms endotoxin and lipopolysaccharide (LPS) are used interchangeably and refer to the major cell wall component of Gram-negative bacteria.11,12 LPS are complex amphiphilic molecules having a hydrophobic (consisting of lipid A) and a hydrophilic (consisting of carbohydrate core and polysaccharide O-antigen) component and are released from bacterial cell wall by shedding or through bacterial lysis.11–13 LPS concentrations are highest in the gut lumen, where many trillions of commensal bacteria reside. Normally, LPS in the gut lumen do not penetrate across the healthy intestinal epithelium14,15; however, in intestinal permeability disorders, the defective TJ barrier allows paracellular flux of LPS and other luminal antigens.11–13,16–19 The intestinal tissue and circulating LPS levels are markedly elevated in IBD and NEC, and play an important role in mediating inflammatory response.11–13,16–18 The involvement of LPS in the initiation and propagation of intestinal inflammation in IBD and NEC has been well demonstrated.20–23 These studies have shown LPS to be an important contributing factor of intestinal inflammation, and removal of circulating LPS accelerated the clinical improvement of IBD and NEC.20,22,23 Despite the importance of a defective intestinal barrier in the accentuation and prolongation of intestinal inflammation in IBD and NEC,3,6,9,20,22 the effects of circulating levels of LPS on the intestinal epithelial barrier remain unknown. Because LPS levels are markedly elevated in these diseases and play an important role in the inflammatory process, understanding the effects of LPS on intestinal barrier function has important potential clinical significance.In normal healthy individuals, plasma concentrations of LPS range from undetectable levels up to 0.2 ng/mL.11,12,20,22 A variety of physiological factors such as prolonged physical exertion, high-fat diet, physiological stresses, or heat can lead to elevated plasma LPS levels as high as 1 to 2 ng/mL.24–27 Patients with intestinal permeability disorders such as Crohn’s disease, NEC, acute pancreatitis, alcoholic liver disease, and critical illnesses also have elevated plasma LPS levels ranging up to 2 to 10 ng/mL.11–13,20,22,28 Based on these reports, we consider LPS levels of 0 to 1.0 ng/mL to be physiologically relevant and 0 to 10 ng/mL to be clinically relevant. (For reference, the concentration of LPS in the gut lumen has been reported to be 1.8 μg/mL in the rat distal ileum.29,30) Inexplicably, in most of the published studies, extreme pharmacological concentrations of LPS ranging between 50 and 1000 μg/mL, which exceed the physiologically achievable concentrations by 104- to 107-fold, have been used to assess various biological responses.30–34 At these extreme concentrations, LPS causes rapid cell death in various cell types studied, including in intestinal and immune cells,30,33–35 and does not provide accurate depiction of biological activity of LPS. Herein, we show that LPS, at physiologically and clinically relevant concentrations (0 to 10 ng/mL), does not cause intestinal epithelial cell death, but causes a selective increase in intestinal TJ permeability in vitro and in vivo. These studies also show for the first time that pattern recognition receptors Toll-like receptor 4 (TLR-4) and CD14 play a central role in the modulation of the intestinal epithelial TJ barrier. 相似文献
113.
Lewis H Mervin Ekaterina Mitricheva Nikos K Logothetis Angelo Bifone Andreas Bender Hamid R Noori 《Journal of cerebral blood flow and metabolism》2021,41(4):874
Functional magnetic resonance imaging (fMRI) is an extensively used method for the investigation of normal and pathological brain function. In particular, fMRI has been used to characterize spatiotemporal hemodynamic response to pharmacological challenges as a non-invasive readout of neuronal activity. However, the mechanisms underlying regional signal changes are yet unclear. In this study, we use a meta-analytic approach to converge data from microdialysis experiments with relative cerebral blood volume (rCBV) changes following acute administration of neuropsychiatric drugs in adult male rats. At whole-brain level, the functional response patterns show very weak correlation with neurochemical alterations, while for numerous brain areas a strong positive correlation with noradrenaline release exists. At a local scale of individual brain regions, the rCBV response to neurotransmitters is anatomically heterogeneous and, importantly, based on a complex interplay of different neurotransmitters that often exert opposing effects, thus providing a mechanism for regulating and fine tuning hemodynamic responses in specific regions. 相似文献
114.
A Recessively Inherited Risk Locus on Chromosome 13q22-31 Conferring Susceptibility to Schizophrenia
Tariq Mahmood Mohammed E El-Asrag James A Poulter Alastair G Cardno Anneka Tomlinson Sophia Ahmed Ahmed Al-Amri Jamshid Nazari Joanna Neill Rifka S Chamali Nancy Kiwan Suhaila Ghuloum Hamid A Alhaj Juliette Randerson Moor Shabana Khan Hassen Al-Amin Colin A Johnson Peter Woodruff Iain D Wilkinson Manir Ali Steven J Clapcote Chris F Inglehearn 《Schizophrenia bulletin》2021,47(3):796
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118.
The present study deals with designing and synthesizing novel dyes using the drug combination of edaravone and azo compounds which can be used as an indicator for anions and cations. The desired product synthesis was accomplished via a two-step process involving diazotizing the aromatic amines followed by the resultant salts coupling with edaravone. The resulting dyes were obtained with high yields under mild conditions. The structures of the dyes were identified with UV-vis, FT-IR, 1H NMR and 13C NMR spectra and CHN analysis. To investigate the solvatochromism effect, the interaction of different solvents with the selected dyes was evaluated using several parameters including the dielectric constant, refractive index, hydrogen bond donating ability, hydrogen bond accepting ability and dipolarity/polarizability scale. To achieve deep understanding about the stability and geometrical characteristics of the azo–hydrazo tautomers of the synthesized dyes and their UV-visible spectra prediction, some DFT calculations were also carried out on the synthesized dyes. The antibacterial activities of some synthesized compounds were also evaluated using the disk diffusion method. The results revealed different activity of the selected synthesized dyes for antibacterial tests against selected Gram positive and Gram negative bacteria.The present study deals with designing and synthesizing novel dyes using the drug combination of edaravone and azo compounds which can be used as an indicator for anions and cations. 相似文献
119.
Shannon J Ernst P Yamauchi Y Olivenstein R Lemiere C Foley S Cicora L Ludwig M Hamid Q Martin JG 《Chest》2008,133(2):420-426
BACKGROUND: Some studies of severe asthma suggest that persistence or alteration in the pattern of inflammation may be associated with the severity of the disease. Whether there are differences in the expression of the principal cytokines and chemokines relevant to eosinophilic and neutrophilic inflammation in the airway tissues of severe compared to moderate asthmatics has not been determined. The aim of this study was to compare the patterns of expression of representative T-helper (Th) type 1 (interferon [IFN]-gamma) and Th-2 cytokines (interleukin [IL]-4, IL-5) and the neutrophil- and eosinophil-associated chemokines (IL-8 and eotaxin) in the airway tissues of patients with severe and moderate asthma. METHODS: Subjects with severe asthma (n = 24) and a comparison moderate asthma group (n = 26) were assessed using spirometry, induced sputum, exhaled nitric oxide, and bronchial biopsy. The expression of proteins of interest in the epithelium and subepithelium of the airway wall was examined by immunocytochemistry. RESULTS: Subjects with severe asthma were more symptomatic, had a lower FEV(1), and had more sputum neutrophilia (p = 0.007) and eosinophilia (p = 0.001). Exhaled nitric oxide was similar between groups. IL-8 and IFN-gamma expression were increased and IL-4 expression was decreased in severe asthma compared to moderate disease (p < 0.001 for each comparison). Eotaxin and IL-5 expression did not differ between the groups. CONCLUSION: Patients with severe asthma have increases in neutrophils and eosinophils in the sputum, and differ in airway cytokine/chemokine expression from moderate asthmatics. Excess neutrophilia may be explained by increased expression of IL-8, but differences in eosinophilia do not appear to be associated with IL-5 and eotaxin expression. 相似文献
120.
Seyyed Hamid Hashemi Fariba Keramat Mitra Ranjbar Mojgan Mamani Ali Farzam Shirin Jamal-Omidi 《International journal of infectious diseases》2007,11(6):496-500
OBJECTIVE: To determine the frequency and clinical characteristics of osteoarticular complications of brucellosis in an endemic region in Iran. METHODS: In a prospective study we evaluated 245 patients with brucellosis diagnosed between January 2004 and December 2005. Patients included were those older than 8 years of age and who had clinical features suggestive of brucellosis and specific antibodies at significant titers, and/or positive blood or body fluid culture for Brucella species. A bone scan was performed in those with a clinical suspicion of osteoarticular involvement. RESULTS: Seventy patients (28.6%) had osteoarticular complications. Sacroiliitis was the most common complication (75.7%), followed by spondylitis (21.4%) and peripheral arthritis (8.6%). Spondylitis was the most common osteoarticular complication in the elderly. Relapses occurred in five (2%) patients, three of them with spondylitis. CONCLUSIONS: Osteoarticular disease is the most common complication of brucellosis in Western Iran. Sacroiliitis is the most common form of osteoarticular complication. With the use of a proper treatment regimen, the prospect for recovery is good. 相似文献