Stress Biomarkers as Outcomes for HIV+ Prevention: Participation, Feasibility and Findings Among HIV+ Latina and African American Mothers

Mothers living with HIV (MLH) are at high risk for acute and chronic stress, given challenges related to their HIV status, ethnicity, economic and urban living conditions. Biomarkers combined into a composite index show promise in quantifying psychosocial stress in healthy people, but have not yet been examined among MLH. According, we examined potential biomarker correlates of stress [cortisol and catecholamines from home-collected urine and basic health indicators (blood pressure, height and weight, waist-to-hip ratio) measured during an interview] among 100 poor African American and Latina mothers MLH and demographic-matched control mothers without HIV (n = 50). Participants had been enrolled in a randomized controlled trial about 18 months earlier and had either received (MLH-I) or were awaiting (MLH-W) the psychosocial intervention. Participation was high, biomarkers were correctly collected for 93% of cases, and a complete composite biomarker index (CBI) calculated for 133 mothers (mean age = 42). As predicted, MLH had a significantly higher CBI than controls, but there was no CBI difference across ethnicity or intervention group. CBI predicted CD4 counts independently after controlling for age, years since diagnosis, prior CD4 counts, medication adherence, and depression symptoms. The study demonstrates acceptability, feasibility and potential utility of community-based biomarker collections in evaluating individual differences in psychosocial stress

CXCL10 induces the recruitment of monocyte‐derived macrophages into kidney, which aggravate puromycin aminonucleoside nephrosis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111251/1/cei12579.pd

Tryptophan Metabolism and Its Relationship with Depression and Cognitive Impairment Among HIV-infected Individuals

Objective: Cognitive impairment (CI) and major depressive disorder (MDD) remain prevalent in treated HIV-1 disease; however, the pathogenesis remains elusive. A possible contributing mechanism is immune-mediated degradation of tryptophan (TRP) via the kynurenine (KYN) pathway, resulting in decreased production of serotonin and accumulation of TRP degradation products. We explored the association of these biochemical pathways and their relationship with CI and MDD in HIV-positive (HIV+) individuals. Methods: In a cross-sectional analysis, concentrations of neopterin (NEO), tumor necrosis factor-alpha, TRP, KYN, KYN/TRP ratio, phenylalanine (PHE), tyrosine (TYR), PHE/TYR ratio, and nitrite were assessed in the cerebrospinal fluid (CSF) and plasma of HIV+ (n = 91) and HIV-negative (HIV-) individuals (n = 66). CI and MDD were assessed via a comprehensive neuropsychological test battery. A Global Deficit Score $0.5 was defined as CI. Nonparametric statistical analyses included Kruskal–Wallis and Mann–Whitney U tests, and multivariate logistic regression. Results: Following Bonferroni correction, NEO concentrations were found to be greater in CSF and TRP concentration was found to be lower in the plasma of HIV+ versus HIV- individuals, including a subgroup of aviremic (defined as HIV-1 RNA ,50 cps/mL) HIV+ participants receiving antiretroviral therapy (n = 44). There was a nonsignificant trend toward higher KYN/TRP ratios in plasma in the HIV+ group (P = 0.027; Bonferroni corrected α = 0.0027). In a logistic regression model, lower KYN/TRP ratios in plasma were associated with CI and MDD in the overall HIV+ group (P = 0.038 and P = 0.063, respectively) and the aviremic subgroup (P = 0.066 and P = 0.027, respectively), though this observation was not statistically significant following Bonferroni correction (Bonferroni corrected α = 0.0031). Conclusions: We observed a trend toward lower KYN/TRP ratios in aviremic HIV+ patients with CI and MDD

Podocyte culture: Tricks of the trade

Podocytes (glomerular epithelial cells) lie on the urinary aspect of the glomerular capillary and play a key role in the selective filter that underlies kidney function. They are injured in various forms of renal disease: the extents of this injury and its reversibility have major implications for treatment and prognosis. Until recently, podocytes were difficult to study in vitro because of a previous lack of techniques for obtaining differentiated cells in quantities adequate for research. In recent years, this problem has been solved for rodent and human podocytes and there has been an explosion of research using cultured cells. These authors have led the development and characterization of human podocyte cell lines and in this article describe the methods that have allowed them to do this. Podocyte cell lines are becoming widely used in renal research. This article gives a detailed description of the production and culture of immortalized podocyte cell lines. Furthermore, these methods can be applied to essentially any cell type, providing a practical approach to study the interactions of renal cell types in vitro. © 2012 The Authors. Nephrology © 2012 Asian Pacific Society of Nephrology.link_to_subscribed_fulltex

Progressive dysregulation of autonomic and HPA axis functions in HIV-1 clade C infection in South India

Human immunodeficiency virus type 1 (HIV-1) infection causes a wide spectrum of abnormalities in neurological, neuropsychological, and neuroendocrinological functions. Several studies report disturbance in autonomic nervous system (ANS) and hypothalamic pituitary–adrenal (HPA) axis function in HIV-1B infected individuals. However, no such investigations on the effect of HIV-1 clade C infection, particularly during the initial phase of the disease progression, have been reported. The present investigations were carried out longitudinally over a 2-year period at 12 monthly intervals in clinically asymptomatic HIV-1 clade C seropositive patients ( n=120) and seronegative control subjects ( n=29). We determined both the basal levels and the dynamic changes in plasma levels of norepinephrine (NE), epinephrine (E), adrenocorticotrophic hormone (ACTH) and cortisol (CORT). Studies were also extended longitudinally (at three separate yearly visits of each participant), to evaluate the response of autonomic and HPA axis to mirror star tracing challenge test (MSTCT) and the values were determined as area under the curve (AUC, corrected for baseline levels of NE, E, ACTH, and CORT). The findings show that the values of basal plasma NE levels, as well as NE response to MSTCT (AUC) at the first visit of HIV-1 seropositive individuals did not differ from those found in the control subjects (NE, pg/ml, HIV-1C=313.5±12.7 vs. controls=353.0±21.3; p=NS; AUC, HIV-1C=225±14.75 vs. controls=232.7±19.34; p=NS, respectively). At the subsequent two visits of HIV-1 positive patients however, NE response to MSTCT challenge was progressively attenuated (AUC=235±19.5 and 162.7±13.6; p<0.01 and 0.05, respectively) compared to that found at the first visit. On the other hand, plasma levels of E as well as E response to MSTCT at the first visit were significantly lower in HIV-1C seropositive individuals compared to those in the control subjects (pg/ml, HIV-1C=77.30±5.7 vs. controls=119.1+10.5; p<0.05; AUC, HIV-1C =83.29±7.5 vs. controls=172.3±18.9; p<0.001), but no further change was observed in AUC of E in response to MSTCT at the two subsequent yearly visits. The basal plasma levels of ACTH in HIV-1C seropositives were not different than in the control subjects (pg/ml: HIV-1C=20.0±0.9 vs. controls=23.1±1.6; p=NS), but ACTH response to MSTCT in HIV-1C seropositive patients at the first visit was lower than in the controls (AUC, HIV-1C=23.57±1.5 vs. controls=30.94±3.5; p<0.05), and fluctuated between high and low at the second and third visits (AUC, 28.89±2.3 and 21.69±2.36, respectively). However, the baseline plasma levels of cortisol as well as the response of cortisol to MSTCT (AUC) in HIV-1C seropositive individuals were higher than in the control subjects at the first visit (μg/dl, HIV-1C=9.83±0.39 vs. controls=6.3±0.56; p<0.05; AUC, HIV-1C=12.31±0.7 vs. control=9.18±0.9; p<0.05), and remained high at the two subsequent yearly follow up visits of HIV-1C (AUC, 11.8±0.86 and 11.98±0.77, respectively). These findings demonstrate attenuated autonomic functions, a disconnection between response of ACTH and cortisol to the MSTCT challenge, and an inverse relationship between plasma levels of catecholamine(s) and cortisol. Since plasma catecholamines and cortisol are the peripheral mediators of the autonomic and HPA axis function, the findings of this study reflect the overall adverse effect of HIV-1C infection on autonomic as well as HPA axis functions. The findings, apart from being the first to demonstrate the progressive dysregulation of autonomic nervous system and HPA axis function among HIV-1C infected seropositive individuals much ahead of the onset of acquired immunodeficiency syndrome (AIDS), also suggest that MSTCT, involving visuoconstructive cognitive abilities, is an effective stressor for unraveling the underlying dysfunctions in the neuroendocrine functions in health and disease