Journals
2012 EN
Jennifer A. Juno · Jeffrey Tuff · Robert Y. Choi
+10 more
Background The GNB3 C825T polymorphism is associated with increased G protein-mediated signal transduction, SDF-1α-mediated lymphocyte chemotaxis, accelerated HIV-1 progression, and altered responses to antiretroviral therapy among Caucasian subjects. The GNB3 825T allele is highly prevalent in African populations, and as such any impact on HIV-1 acquisition or progression rates could have a dramatic impact. This study examines the association of the 825T polymorphism with HIV-1 acquisition, disease progression and immune activation in two African cohorts. GNB3 825 genotyping was performed for enrolees in both a commercial sex worker cohort and a perinatal HIV transmission (PHT) cohort in Nairobi, Kenya. Ex vivo immune activation was quantified by flow cytometry, and plasma chemokine levels were assessed by cytokine bead array. Results GNB3 genotype was not associated with sexual or vertical HIV-1 acquisition within these cohorts. Within the Pumwani cohort, GNB3 genotype did not affect HIV-1 disease progression among seroconverters or among HIV-1-positive individuals after adjustment for baseline CD4 count. Maternal CD4 decline and viral load increase in the PHT cohort did not differ between genotypes. Multi-parametric flow cytometry assessment of T cell activation (CD69, HLA-DR, CD38) and Treg frequency (CD25 + FOXP3 + ) found no differences between genotype groups. Plasma SDF-1α, MIP-1β and TRAIL levels quantified by cytokine bead array were also similar between groups. Conclusions In contrast to previous reports, we were unable to provide evidence to suggest that the GNB3 C825T polymorphism affects HIV-1 acquisition or disease progression within African populations. Ex vivo immune activation and plasma chemokine levels were similarly unaffected by GNB3 genotype in both HIV-1-negative and HIV-1-positive individuals. The paucity of studies investigating the impact of GNB3 polymorphism among African populations and the lack of mechanistic studies make it difficult to assess the true biological significance of this polymorphism in HIV-1 infection.
Journals
2012 EN
Shingo Iwami · Benjamin P. Holder · Catherine A. A. Beauchemin
+5 more
Background Developing a quantitative understanding of viral kinetics is useful for determining the pathogenesis and transmissibility of the virus, predicting the course of disease, and evaluating the effects of antiviral therapy. The availability of data in clinical, animal, and cell culture studies, however, has been quite limited. Many studies of virus infection kinetics have been based solely on measures of total or infectious virus count. Here, we introduce a new mathematical model which tracks both infectious and total viral load, as well as the fraction of infected and uninfected cells within a cell culture, and apply it to analyze time-course data of an SHIV infection in vitro . Results We infected HSC-F cells with SHIV-KS661 and measured the concentration of Nef - negative (target) and Nef - positive (infected) HSC-F cells, the total viral load, and the infectious viral load daily for nine days. The experiments were repeated at four different MOIs, and the model was fitted to the full dataset simultaneously. Our analysis allowed us to extract an infected cell half-life of 14.1 h, a half-life of SHIV-KS661 infectiousness of 17.9 h, a virus burst size of 22.1 thousand RNA copies or 0.19 TCID 50 , and a basic reproductive number of 62.8. Furthermore, we calculated that SHIV-KS661 virus-infected cells produce at least 1 infectious virion for every 350 virions produced. Conclusions Our method, combining in vitro experiments and a mathematical model, provides detailed quantitative insights into the kinetics of the SHIV infection which could be used to significantly improve the understanding of SHIV and HIV-1 pathogenesis. The method could also be applied to other viral infections and used to improve the in vitro determination of the effect and efficacy of antiviral compounds.
Journals
2012 EN
Soula Fillipas · Flavia Cicuttini · Anne E. Holland
+1 more
Physical activity (PA) and cardiovascular fitness (CVF) are beneficial for HIV-infected individuals, however long-term effects are unknown. This study aimed to document long-term habitual PA and CVF in stable, HAART-treated individuals with HIV, explore relationships to body composition, body image and cardiovascular disease (CVD) risk and evaluate PA determinants.
Journals
2012 EN
Julie Daigre · Meriem Mendjel · Sylvie Brégigeon
+1 more
With the improvement of HAART, life expectancy of HIV-infected patients sharply increased. The incidence of cancerous diseases is therefore increasing in this population. This raises the problem of drug-drug interactions between HIV treatment and cancer chemotherapy poorly understood because few data are available. However, the potential risk of interactions is important because of the involvement of similar metabolic enzymes and transporters between these drugs and due to the inhibitory and/or inducer effects on different CYP450 isoforms of the PI and NNRTI. These interactions may both lead to inefficiency and/or an increased risk of toxicity of the chemotherapy which can be life-threatening for the patient.
Journals
2012 EN
Catherine Riou · Melissa-Rose Abrahams · Koleka Mlisana
+7 more
HIV-specific early-differentiated cells of a central memorylike phenotype (CD45RO+CD27+) exhibited a higher proportion of cells positive for three or four functions (p<0.001) and a lower proportion of mono-functional cells (median 27% [IQR: 16-38], p<0.001) compared to terminally-differentiated cells. In contrast, CMV-specific CD8+ T cell polyfunctional capacities were similar across all memory subpopulations, with terminally and early-differentiated cells endowed with comparable polyfunctionality. Conclusion Overall, these data show that for HIV-specific responses, the memory differentiation stage can influence the polyfunctional properties of CD8+ T cells, suggesting that terminal differentiation of HIV-specific CD8+ T cells might be detrimental for viral control. These results may help in understanding phenotypic attributes related to effective T cell responses against HIV-1.
Journals
2012 EN
Cyril Duclos · Carole Miéville · Dany H. Gag
+1 more
Background In rehabilitation, training intensity is usually adapted to optimize the trained system to attain better performance (overload principle). However, in balance rehabilitation, the level of intensity required during training exercises to optimize improvement in balance has rarely been studied, probably due to the difficulty in quantifying the stability level during these exercises. The goal of the present study was to test whether the stabilizing/destabilizing forces model could be used to analyze how stability is challenged during several exergames, that are more and more used in balance rehabilitation, and a dynamic functional task, such as gait.Methods Seven healthy older adults were evaluated with three-dimensional motion analysis during gait at natural and fast speed, and during three balance exergames (50/50 Challenge, Ski Slalom and Soccer). Mean and extreme values for stabilizing force, destabilizing force and the ratio of the two forces (stability index) were computed from kinematic and kinetic data to determine the mean and least level of dynamic, postural and overall balance stability, respectively.Results Mean postural stability was lower (lower mean destabilizing force) during the 50/50 Challenge game than during all the other tasks, but peak postural instability moments were less challenging during this game than during any of the other tasks, as shown by the minimum destabilizing force values. Dynamic stability was progressively more challenged (higher mean and maximum stabilizing force) from the 50/50 Challenge to the Soccer and Slalom games, to the natural gait speed task and to the fast gait speed task, increasing the overall stability difficulty (mean and minimum stability index) in the same manner.Conclusions The stabilizing/destabilizing forces model can be used to rate the level of balance requirements during different tasks such as gait or exergames. The results of our study showed that postural stability did not differ much between the evaluated tasks (except for the 50/50 Challenge), compared to dynamic stability, which was significantly less challenged during the games than during the functional tasks. Games with greater centre of mass displacements and changes in the base of support are likely to stimulate balance control enough to see improvements in balance during dynamic functional tasks, and could be tested in pathological populations with the approach used here.
Journals
2012 EN
MarieEve Landry · Irving E. Salit · Catherine Rodrigues-Coutlée
+8 more
Background Human papillomavirus type 97 (HPV97) DNA was detected in nearly 5% of anal samples collected from HIV-seropositive men living in Montreal, Canada. The rate of detection of HPV97 in the genital tract of Canadian women is unknown. Whether HPV97 is a local epidemic in HIV-seropositive men living in Montreal is also unknown. The prevalence of human papillomavirus type 97 (HPV97) was assessed in cervicovaginal cells from women living in Canada and in anal samples from HIV-seropositive men living in Toronto. Findings Cervicovaginal lavages collected from 904 women (678 HIV-seropositive, 226 HIV-seronegative) women living in Canada and anal cells collected from 123 HIV-seropositive men living in Toronto were tested for the presence of HPV97 with PCR. HPV97-positive samples were further tested by PCR-sequencing for molecular variant analysis to assess if all HPV97-positive men were infected with the same strain. All cervicovaginal samples were negative for HPV97. HPV97 was detected in anal samples from 6 HIV-seropositive men (4.9%, 95% confidence interval 2.0-10.5%), of whom five had high-grade and one had low-grade anal intraepithelial neoplasia, in addition to 2 to 8 HPV genital genotypes per sample. Four HPV97 variants were defined by four variation sites in the viral control region. Conclusion These findings indicate that HPV97 infects in the anal canal of HIV-seropositive men but is not detected in the genital tract of women.
Journals
2012 EN
Juan Patricio Nogueira · Marie Maraninchi · Sophie Béliard
+11 more
Background Low plasma high-density lipoprotein-cholesterol (HDL-c) level is commonly present in obesity and represents an independent cardiovascular risk factor. However, obese patients are a very heterogeneous population and the factors and mechanisms that contribute to low HDL-c remain unclear. The aim of this study was to investigate the association between plasma HDL-c levels and plasma hormonal profiles (insulin, adiponectin, resistin, leptin and ghrelin) in subsets of class II and III obese patients. Methods Fasting plasma levels of glucose, total cholesterol, LDL-c, HDL-c, triglycerides, free fatty acids, apoproteins A-I, B-100, B-48, C-II, C-III, insulin, hs-CRP, adipocytokines (adiponectin, resistin, leptin), unacylated ghrelin, body composition (DXA) and resting energy expenditure were measured in three subsets of obese patients: 17 metabolically abnormal obese (MAO) with metabolic syndrome and the typical metabolic dyslipidaemia, 21 metabolically healthy obese (MHO) without metabolic syndrome and with a normal lipid profile, and 21 isolated low HDL-c obese patients (LHO) without metabolic syndrome, compared to 21 healthy lean control subjects. Results Insulin resistance (HOMA-IR) increased gradually from MHO to LHO and from LHO to MAO patients ( p < 0.05 between MHO and MAO and between LHO and MAO). In multiple regression analysis, serum unacylated ghrelin levels were only positively and independently associated with HDL-c levels in the LHO group ( p = 0.032). Conclusions These results suggest that, in class II and III obese patients with an isolated low HDL-c phenotype, unacylated ghrelin is positively associated with HDL-c level independently of insulin resistance and CRP levels, and may contribute to the highly prevalent low HDL-c level seen in obesity.
Journals
2012 EN
Penelope AE Main · Manya Angley · Catherine O‘Doherty
+2 more
Background Glutathione has a wide range of functions; it is an endogenous anti-oxidant and plays a key role in the maintenance of intracellular redox balance and detoxification of xenobiotics. Several studies have indicated that children with autism spectrum disorders may have altered glutathione metabolism which could play a key role in the condition. Methods A systematic literature review and meta-analysis was conducted of studies examining metabolites, interventions and/or genes of the glutathione metabolism pathways i.e. the γ-glutamyl cycle and trans-sulphuration pathway in autism spectrum disorders. Results Thirty nine studies were included in the review comprising an in vitro study, thirty two metabolite and/or co-factor studies, six intervention studies and six studies with genetic data as well as eight studies examining enzyme activity. Conclusions The review found evidence for the involvement of the γ-glutamyl cycle and trans-sulphuration pathway in autistic disorder is sufficiently consistent, particularly with respect to the glutathione redox ratio, to warrant further investigation to determine the significance in relation to clinical outcomes. Large, well designed intervention studies that link metabolites, cofactors and genes of the γ-glutamyl cycle and trans-sulphuration pathway with objective behavioural outcomes in children with autism spectrum disorders are required. Future risk factor analysis should include consideration of multiple nutritional status and metabolite biomarkers of pathways linked with the γ-glutamyl cycle and the interaction of genotype in relation to these factors.
Journals
2012 EN
Sarah Robertson · Gillian A. Gray · Rodger Duffin
+5 more
Background Inhalation of diesel exhaust impairs vascular function in man, by a mechanism that has yet to be fully established. We hypothesised that pulmonary exposure to diesel exhaust particles (DEP) would cause endothelial dysfunction in rats as a consequence of pulmonary and systemic inflammation. Methods Wistar rats were exposed to DEP (0.5 mg) or saline vehicle by intratracheal instillation and hind-limb blood flow, blood pressure and heart rate were monitored in situ 6 or 24 h after exposure. Vascular function was tested by administration of the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent vasodilator sodium nitroprusside (SNP) in vivo and ex vivo in isolated rings of thoracic aorta, femoral and mesenteric artery from DEP exposed rats. Bronchoalveolar lavage fluid (BALF) and blood plasma were collected to assess pulmonary (cell differentials, protein levels & interleukin-6 (IL-6)) and systemic (IL-6), tumour necrosis factor alpha (TNFα) and C-reactive protein (CRP)) inflammation, respectively. Results DEP instillation increased cell counts, total protein and IL-6 in BALF 6 h after exposure, while levels of IL-6 and TNFα were only raised in blood 24 h after DEP exposure. DEP had no effect on the increased hind-limb blood flow induced by ACh in vivo at 6 or 24 h. However, responses to SNP were impaired at both time points. In contrast, ex vivo responses to ACh and SNP were unaltered in arteries isolated from rats exposed to DEP. Conclusions Exposure of rats to DEP induces both pulmonary and systemic inflammation, but does not modify endothelium-dependent vasodilatation. Other mechanisms in vivo limit dilator responses to SNP and these require further investigation.