Interaction landscape of a ‘CαNN’ motif with arsenate and arsenite: a potential peptide-based scavenger of arsenic

Arsenic (As) is a toxic metalloid that has drawn immense attention from the scientific community recently due to its fatal effects through its unwanted occurrence in ground water around the globe. The presence of an excess amount of water soluble arsenate and/or arsenite salt (permissible limit 10 μg L⁻¹ as recommended by the WHO) in water has been correlated with several human diseases. Although arsenate (HAsO₄²⁻) is a molecular analogue of phosphate (HPO₄²⁻), phosphate is indispensable for life, while arsenic and its salts are toxic. Therefore, it is worthwhile to focus on the removal of arsenic from water. Towards this end, the design of peptide-based scaffolds for the recognition of arsenate and arsenite would add a new dimension. Utilizing the stereochemical similarity between arsenate (HAsO₄²⁻) and phosphate (HPO₄²⁻), we successfully investigated the recognition of arsenate and arsenite with a naturally occurring novel phosphate binding ‘C^αNN’ motif and its related designed analogues. Using computational as well as biophysical approaches, for the first time, we report here that a designed peptide-based scaffold based on the ‘C^αNN’ motif can recognize anions of arsenic in a thermodynamically favorable manner in a context-free system. This peptide-based arsenic binding agent has the potential for future development as a scavenger of arsenic anions to obtain arsenic free water.

Potential peptide-based scavenger of toxic metalloid arsenic causing fatal effects through its unwanted occurrence in ground water around the globe.     

Rifabutin but not clarithromycin prevents cryptosporidiosis in persons with advanced HIV infection

BACKGROUND: Macrolides have been reported to be effective for the prevention of cryptosporidiosis in persons with HIV infection. OBJECTIVE: To evaluate the efficacy of clarithromycin and rifabutin for the prevention of cryptosporidiosis in persons with advanced HIV infection. DESIGN: Cross-protocol analysis involving 2288 individuals with a history of a CD4 cell counts of < or = 100 x 10(6) cell/l who were enrolled in two prospective clinical trials to prevent Mycobacterium avium complex (MAC) infection and cytomegalovirus (CMV) end-organ disease. INTERVENTIONS: Clarithromycin 500 mg twice daily, rifabutin 300-450 mg daily, the combination of the two or no MAC prophylaxis. MAIN OUTCOME MEASUREMENT: Laboratory-confirmed cryptosporidiosis. Subjects were analyzed in an intent-to-treat and as-treated manner using time-to-event analyses (Cox proportional hazards models). RESULTS: The median length of follow up was 463 days. The median CD4 count at entry was 29 x 10(6) cell/l (range 0-182). There were 60 cases of cryptosporidiosis during the prospective observational period, with an event rate of 2.2 per 100 person-years. In the intent-to-treat [relative risk (RR) 0.50; 95% confidence interval (CI) 0.26-0.96; P = 0.041 and as-treated (RR 0.42; 95% CI 0.20-0.91; P = 0.03) analyses, rifabutin alone was significantly associated with a lower rate of cryptosporidiosis. Clarithromycin alone was not protective in similar analyses (P = 0.98 and 0.90, respectively). CONCLUSIONS: In doses used to prevent MAC infection, rifabutin but not clarithromycin decreases the risk of developing cryptosporidiosis in persons with advanced HIV infection who are not receiving potent combination antiretroviral therapy.     

Educational attainment and response to HAART during initial therapy for HIV-1 infection

OBJECTIVE: Previous research has demonstrated an association between educational attainment (EA) and negative physical and psychological outcomes. This study investigated whether EA is associated with regimen failure during initial therapy with highly active antiretroviral treatment (HAART) and whether adherence self-efficacy (ASE), a coping resource, moderates the relationship between EA and regimen failure. METHODS: A secondary analysis of AIDS Clinical Trial Group Protocol 384, an international, multicenter, randomized, partially double-blinded trial, included 799 male and 181 female antiretroviral-na?ve subjects (age, 37.0+/-9.5 years). Participants were recruited from 1998 to 1999 and followed for a median of 2.3 years across 81 centers. The dependent variable was "time to first regimen failure." Covariates include baseline HIV-1 log(10)RNA and CD4(+) counts, self-reported adherence, study site, ASE, age, sex, race, treatment assignment, and baseline use of nonantiretroviral medications. RESULTS: ASE significantly moderated the relationship between EA and regimen failure. Results showed that for every 10-unit increase in ASE, individuals with "less than high school" education had a 17% reduction in regimen failure (hazard ratio=0.83; 95% confidence interval=0.70-0.98) when compared to the reference group "college/graduate," even after adjusting for baseline factors known to contribute to regimen failure. The time to first regimen failure was shorter with decreasing EA, trending toward significance (P=.08). CONCLUSIONS: There is a social gradient in HAART effectiveness, and ASE reduces the deleterious effects of lower EA on regimen failure. We recommend designing controlled interventions to evaluate the effectiveness of programs that increase ASE prior to initiation with HAART, particularly for those with lower EA.