Morphometric Changes following 4 Months of Treatment.

<p>Morphometric Changes following 4 Months of Treatment.</p

Resveratrol Co-Treatment Attenuates the Effects of HIV Protease Inhibitors on Rat Body Weight and Enhances Cardiac Mitochondrial Respiration

<div><p>Since the early 1990s human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) emerged as a global health pandemic, with sub-Saharan Africa the hardest hit. While the successful roll-out of antiretroviral (ARV) therapy provided significant relief to HIV-positive individuals, such treatment can also elicit damaging side-effects. Here especially HIV protease inhibitors (PIs) are implicated in the onset of cardio-metabolic complications such as type-2 diabetes and coronary heart disease. As there is a paucity of data regarding suitable co-treatments within this context, this preclinical study investigated whether resveratrol (RSV), aspirin (ASP) or vitamin C (VitC) co-treatment is able to blunt side-effects in a rat model of chronic PI exposure (Lopinavir/Ritonavir treatment for 4 months). Body weights and weight gain, blood metabolite levels (total cholesterol, HDL, LDL, triglycerides), echocardiography and cardiac mitochondrial respiration were assessed in PI-treated rats ± various co-treatments. Our data reveal that PI treatment significantly lowered body weight and cardiac respiratory function while no significant changes were found for heart function and blood metabolite levels. Moreover, all co-treatments ameliorated the PI-induced decrease in body weight after 4 months of PI treatment, while RSV co-treatment enhanced cardiac mitochondrial respiratory capacity in PI-treated rats. This pilot study therefore provides novel hypotheses regarding RSV co-treatment that should be further assessed in greater detail.</p></div

Left Ventricular Parameters as Measured with Echocardiography after 4 Months of Treatment.

<p>Left Ventricular Parameters as Measured with Echocardiography after 4 Months of Treatment.</p

Blood Metabolite Levels following 4 Months of Treatment.

<p>Blood Metabolite Levels following 4 Months of Treatment.</p

Associations of baseline characteristics with retinol binding protein 4 concentrations.

<p>Data were analyzed in mixed regression models in which sex and race, age at study time and race, age at study time and sex, and all 3 demographic characteristics were adjusted for in the 1^st and 2^nd, 3^rd, 4^th and the remaining models, respectively. Significant associations are shown in bold type. RA  =  rheumatoid arthritis, CDAI  =  Clinical Disease Activity Score.</p><p>*Logarithmically transformed variables.</p

Independent relationships of retinol binding protein 4 concentrations with endothelial activation and atherosclerosis.

<p>Retinol binding protein 4-endothelial activation and retinol binding protein 4-atherosclerosis relations were assessed in mixed regression models with adjustment for the log Framingham score (calculated from age, sex and major conventional risk factors), race, alcohol use, waist-hip ratio, glomerular filtration rate, and systemic inflammation (C-reactive protein and interleukin-6 concentrations). Significant association is shown in bold type.</p><p>VCAM  =  vascular cell adhesion molecule, ICAM  =  intercellular adhesion molecule, OR  =  odds ratio, CI  =  confidence interval.</p><p>*Characteristics that were non-normally distributed and were logarithmically transformed prior to entering them in linear regression models.</p

Independent relationships of retinol binding protein 4 concentrations with metabolic risk factors.

<p>Data were analyzed in mixed regression models in which demographic characteristics, alcohol use, the waist-hip ratio, the glomerular filtration rate and cardiovascular drugs were adjusted for. Significant associations are shown in bold type. HDL  =  high-density lipoprotein, LDL  =  low-density lipoprotein, VCAM  =  vascular adhesion molecule, ICAM  =  intercellular adhesion molecule, MCP  =  monocyte chemoattractant protein. *Logarithmically transformed variables.</p

Independent relationships of retinol binding protein 4 concentrations with systolic and mean blood pressure, and glucose levels amongst subgroups.

<p>Data were analyzed in adjusted mixed regression models as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092739#pone-0092739-t003" target="_blank">Table 3</a>. Significant differences amongst relations are shown in bold type. *Logarithmically transformed variable.</p

Independent relationships of retinol binding protein 4 concentrations with those of E-selectin and atherosclerosis amongst subgroups.

<p>Data were analyzed in adjusted mixed regression models as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092739#pone-0092739-t005" target="_blank">Table 5</a>. Significant association is shown in bold type. cIMT  =  carotid intima-media thickness, OR  =  odds ratio, CI  =  confidence intervals, CV  =  cardiovascular, MetS  =  metabolic syndrome, RA  =  rheumatoid arthritis, CDAI  =  Clinical Disease Activity Score.</p

Large Vessel Adventitial Vasculitis Characterizes Patients with Critical Lower Limb Ischemia with as Compared to without Human Immunodeficiency Virus Infection

<div><p>Objectives</p><p>Whether a human immunodeficiency virus (HIV)-associated vasculitis in-part accounts for occlusive large artery disease remains uncertain. We aimed to identify the histopathological features that characterize large vessel changes in HIV sero-positive as compared to sero-negative patients with critical lower limb ischemia (CLI).</p><p>Materials and Methods</p><p>Femoral arteries obtained from 10 HIV positive and 10 HIV negative black African male patients admitted to a single vascular unit with CLI requiring above knee amputation were subjected to histopathological assessment. None of the HIV positive patients were receiving antiretroviral therapy.</p><p>Results</p><p>As compared to HIV negative patients with CLI, HIV positive patients were younger (p<0.01) and had a lower prevalence of hypertension (10 vs 90%, p<0.005) and diabetes mellitus (0 vs 50%, p<0.05), but a similar proportion of patients previously or currently smoked (80 vs 60%). 90% of HIV positive patients, but no HIV negative patient had evidence of adventitial leukocytoclastic vasculitis of the vasa vasorum (p<0.0001). In addition, 70% of HIV positive, but no HIV negative patient had evidence of adventitial slit-like vessels. Whilst T-lymphocytes were noted in the adventitia in 80% of HIV positive patients, T-lymphocytes were noted only in the intima in HIV negative patients. The presence of femoral artery calcified multilayered fibro-atheroma was noted in 40% of HIV positive and 90% of HIV negative patients with CLI.</p><p>Conclusions</p><p>An adventitial vasculitis which characterizes large artery changes in CLI in HIV-infected as compared to non-infected patients, may contribute toward HIV-associated occlusive large artery disease.</p></div