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Background: The average lifespan of persons living with HIV (PLWH) on antiretroviral therapy approximates the general population. However, PLWH are susceptible to early aging and frailty. Behaviors such as alcohol consumption may contribute to frailty among PLWH., Objective: To determine the relationships between recent and lifetime alcohol use and frailty among PLWH., Design: Cross-sectional, prospective cohort study of in-care PLWH (n = 365) participating in the New Orleans Alcohol Use in HIV Study., Methods: Recent alcohol exposure was measured by the 30-day alcohol timeline follow-back (TLFB) assessment and by whole-blood-spot phosphatidylethanol (PEth) quantitation. Lifetime alcohol exposure (LAE) was estimated by a modified lifetime drinking history instrument. Frailty was assessed by a 58-item deficit index (DI58) and the phenotypic frailty index (PFI). The Veterans Aging Cohort Study Risk Index 2.0 was calculated., Results: Using generalized linear regression, LAE was positively associated with the DI58 (95% CI 0.001--0.006) and PFI severity (95% CI 0.004--0.023) after adjustment for age and other factors. Conversely, recent alcohol exposure was negatively associated with the DI58 [TLFB 95% CI: (-0.126 to -0.034), PEth: (-0.163 to -0.058)] and PFI severity [TLFB 95% CI (-0.404 to -0.015), PEth (-0.406 to 0.034)]. The VACS was not associated with alcohol use. Median per-decade alcohol exposure peaked in the second decade and tapered with aging thereafter. Increasing LAE and decreasing TLFB were co-associated with a specific subset of health deficits., Conclusion: Lifetime alcohol use is positively associated with frailty among PLWH. Specific health deficits may discourage alcohol consumption in some PLWH.

Objective: Granulocytopenia frequently occurs in alcohol abusers with severe bacterial infection, which strongly correlates with poor clinical outcome. Knowledge of the molecular mechanisms underlying the granulopoietic response to bacterial infection remains limited. This study investigated the involvement of stem cell antigen-1 expression by granulocyte lineage-committed progenitors in the granulopoietic response to septicemia and how alcohol affected this response., Design: : Laboratory investigation., Setting: University laboratory., Subjects: Male Balb/c mice., Interventions: Thirty mins after intraperitoneal injection of alcohol (20% ethanol in saline at 5 g of ethanol/kg) or saline, mice received an intravenous Escherichia coli challenge., Measurements and Main Results: E. coli septicemia activated stem cell antigen-1 expression by marrow immature granulocyte differentiation antigen-1 precursors which correlated with an increase in proliferation, granulocyte macrophage colony-forming unit production, and expansion of this granulopoietic precursor cell pool. Acute alcohol treatment suppressed stem cell antigen-1 activation and inhibited the infection-induced increases in proliferation, granulocyte macrophage colony-forming unit production, and expansion the of immature granulocyte differentiation antigen-1 precursor cell population. Consequently, recovery of the marrow mature granulocyte differentiation antigen-1 cell population after E. coli challenge was impaired. Stem cell antigen-1 was induced in sorted granulocyte differentiation antigen-1, stem cell antigen-1' cells by lipopolysaccharide-stimulated C-Jun kinase activation that was also inhibited by alcohol. Furthermore, stem cell antigen-1 knockout mice failed to expand the marrow immature granulocyte differentiation antigen-1 cell pool and demonstrated fewer newly produced granulocytes in the circulation after the E. coli challenge., Conclusions: Alcohol suppresses the stem cell antigen-1 response in granulocyte lineage-committed precursors and restricts granulocyte production during septicemia, which may serve as a novel mechanism underlying impaired host defense in alcohol abusers.

Purpose: To examine the influence of a unilateral exercise training protocol on brachial artery reactivity (BAR) in 12 men (aged 81 +/- 5 yr)., Methods: Brachial artery diameters and blood flow parameters were assessed, in both arms, using high-resolution ultrasonography, before and after 5 min of forearm occlusion, before and at the end of each week of a 4-wk training program. Training consisted of a unilateral handgrip training protocol (nondominant arm) at 60% of maximal voluntary handgrip strength, performed for 4 wk, 4 d x wk(-1), 20 min per session, and a cadence of one contraction per 4 s., Results: After training, handgrip strength increased 6.2% (baseline = 32.4 +/- 7.0 kg vs week 4 = 34.4 +/- 6.7 kg) in the trained arm only but failed to reach statistical significance (P = 0.10). No statistical changes were observed for blood pressure or resting HR. In contrast, BAR increased 45% (Pre = 2.9% vs Post = 4.1%, P = 0.05) in the trained arm only. Improvements in BAR were observed after the second week of training, without significant changes in the main vasodilatory trigger, defined as the relevant shear stimulus after forearm occlusion (P > 0.05)., Conclusions: These data indicate that a localized short-term exercise program results in significant improvements in vascular function in the trained arm of elderly men compared with the control arm. Furthermore, the findings indicate a statistically significant increase in BAR at the end of the second week of training, despite a similar trigger for dilation versus before training.

Mechanical ventilation is associated with several harmful effects mainly related to high tidal volumes (Vt). Ventilator-induced lung injury can be responsible for an increased production of inflammatory mediators. We evaluated remote consequences on the gut of lung triggered inflammatory response, neutralizing anti-tumor necrosis factor (TNF) antibody was administered to assess the role of TNF in lung and gut permeability changes. Rats were anesthetized and ventilated for 2 h. A control group (Con: Vt = 10 mL/kg) was compared with a high Vt group (HV: Vt = 30 ml/kg). One microCi of I125-labeled human serum albumin was injected to measure extravascular albumin space. Gut permeability was evaluated by plasma-to-lumen ratio leakage of I125 human serum albumin. Extravascular albumin space increased in the HV group from 446 +/- 50 microL to 2783 +/- 887 microL. Gut index of permeability increased from 5.1 +/- 1.2 to 14.2 +/- 4.9. Anti-TNF antibody prevented both lung and gut increase in permeability. High tidal volume ventilation resulted in an increase in lung edema and gut permeability, antagonism of TNF with neutralizing antibodies abrogated the increase in gut permeability as well as lung edema.