A Defective Oxidative Burst and Impaired Antigen Presentation are Hallmarks of Human Visceral Leishmaniasis.

PURPOSE: Survival of the Leishmania parasite within monocytes hinges on its ability to effectively nullify their microbicidal effector mechanisms. Accordingly, this study aimed to delineate this biological niche in patients with visceral leishmaniasis (VL). METHODS: In monocytes, the redox status, antigen presenting capacity, expression of Toll-like receptors (TLRs), co-stimulatory molecules (CD80/86) and generation of intracellular cytokines (IL-8, IL-1ß, IL-10 and LAP-TGF-ß1) was measured by flow cytometry, levels of circulating cytokines (IL-1ß, IL-6, TNF-α, IL-8, IL-4, IL-13, IL-10 and GM-CSF) by ELISA and arginase activity by spectrophotometry. RESULTS: Within monocytes, generation of an oxidative burst was markedly attenuated as evident by decreased generation of nitric oxide and reactive oxygen species, concomitant with raised levels of thiols. This was accompanied by lowered frequency of TLR4(+) monocytes, but the arginase activity remained unaltered. Pathogen persistence was enhanced by the predominance of anti-inflammatory cytokines within monocytes, notably IL-10. Alongside, development of adaptive immunity was severely attenuated as manifested by a pronounced impairment of antigen presentation and co-stimulation evident by down regulation of CD54, HLA-DR and CD86. Treatment corrected the redox imbalance and reversed the impaired antigen presentation. CONCLUSIONS: In VL, monocyte functions were severely impaired facilitating parasite persistence; anti-leishmanial chemotherapy mediated parasite elimination through modulation of the macrophage microenvironment by restoring its redox status and antigen presenting capacity.

Preventing the inappropriate treatment of asymptomatic bacteriuria at a community teaching hospital.

The goal of this study was to assess the overtreatment of asymptomatic bacteriuria (ASB) in hospitalized patients, calculate the total costs of inappropriate treatment, and determine if a multi-faceted educational intervention was effective in reducing the overtreatment of ASB in a resource-limited community hospital. The study encompassed three phases: a retrospective pre-intervention assessment of the baseline cost and treatment of ASB, the implementation of a multi-faceted educational intervention, and a prospective post-intervention assessment of the efficacy of the intervention. A positive urine culture was defined by bacterial counts ≥10(5) cfu/mL. In the pre-intervention group, 64 (83%) of 109 patients were asymptomatic: 30 (47%) were treated. In the post-intervention group, 13 (17%) of 55 patients were asymptomatic: 2 (15%) were treated, (p=0.04). Fewer urine cultures were collected during the post-intervention period than the pre-intervention period (3,127 and 3,419, respectively) (p<0.001). The total cost of inappropriately treating ASB in the pre-intervention group was $1200 compared to $600 in the post-intervention group. The results demonstrated a significant decrease in the inappropriate treatment of ASB and the associated costs.

Encapsulation and extended release of anti-cancer anastrozole by stealth nanoparticles.

To improve delivery efficiency of anastrozole, we applied dendrimer-based stealth nanoparticles to encapsulate anastrozole to formulate stealth anastrozole nanoparticles. This work demonstrated that stealth nanoparticles composed of a PAMAM dendrimers core and a PEG layer could encapsulate anastrozole, hence causing improved water solubility of anastrozole. Anastrozole encapsulation depended on concentration of stealth nanoparticles and generation of dendrimer. The extended release of anastrozole was achieved. We envisioned that this highly structurally adaptable stealth nanoparticle could be further biofunctionalized to construct a targeted therapeutic delivery system for breast cancer treatment.