Rising level of arsenic in water and fodder: a growing threat to livestock and human populations in Pakistan

Arsenic (As) is considered to be one of the top environmental contaminants of concern worldwide. In many regions in Pakistan, there are reports of increased levels of As in the environment, and this metalloid remains a major source of contamination of soil, water and fodder. This pathway of exposure has emerged as a new threat for both wildlife and the surrounding human communities because of the mobilization and accumulation of As via the food chain. The objective of this critical review is to synthesize historical information about As levels in the environmental resources of Pakistan to better characterize the risk to livestock and humans in the region. The South Punjab and Sindh are the dominant areas which are reported to contain the highest As contamination compared to other regions. This is a concern as millions of animals as well as the human population are facing significant health issues due to As. For example, some of the population of Sindh province are potentially faced with As levels ～10–50?μg/L in drinking water, which is well above safe drinking limits of 10?μg/L outlined by the World Health Organization. These collective data on As are anticipated to be a useful source of information for decisions by the environmental protection agency in Pakistan regarding the adoption of preventive measures against its adverse impacts and toxicity.     

Multi-constituent synergism is responsible for anti-inflammatory effect of Azadirachta indica leaf extract

Context: Azadirachta indica A. Juss. (Meliaceaes) leaves have been used traditionally to treat swelling and rheumatism in Indian cultures.

Objective: To fractionate A. indica leaf extracts using bioactivity guided manner for identification of the active anti-inflammatory principles.

Materials and methods: Polarity-gradient sequential extracts (petroleum ether, chloroform, methanol, and water) of A. indica leaves were screened for their anti-inflammatory potential using the carrageenan-induced rat paw edema model (1?g/kg). The chloroform extract was sequentially fractionated to obtain n-hexane (F-1), n-hexane-chloroform (F-2), and chloroform (F-3) fractions and their inhibitory effect on rat paw edema was evaluated (500?mg/kg). Inhibitory effect of F-2 on granuloma formation, plasma interleukin (IL-1), and tumor necrosis factor (TNF-α) was assessed at the doses of 100, 200, and 400?mg/kg using the cotton pellet assay in rats. Three sub-fractions (SF-1, SF-2, and SF-3) were obtained upon chromatography of F-2, and their inhibitory effect on cyclooxygenase was assessed at 200?µg/mL concentration. The sub-fractions were subjected to gas chromatography–mass spectrometry (GC-MS).

Results: All the extracts showed significant anti-inflammatory effect; however, chloroform extract was the most effective against paw edema (53.25% inhibition). The three fractions of chloroform extract showed significant effect, while F-2 being the most potent (51.02%). F-2 demonstrated dose-dependent inhibition of granuloma and cytokines. Interestingly, all the sub-fractions of F-2 inhibited COX-1 and COX-2 with almost equal potential. GC-MS revealed that chemically the sub-fractions were totally different from each other.

Discussion and conclusion: Anti-inflammatory effect of A. indica is a result of cumulative and synergistic effects of diversified constituents with varying polarities that collectively exert the effect via suppression of cyclo-oxygenases and cytokines (IL-1 and TNF-α).     

Blocking “don't eat me” signal of CD47-SIRPα in hematological malignancies,an in-depth review

Hematological malignancies express high levels of CD47 as a mechanism of immune evasion. CD47-SIRPα triggers a cascade of events that inhibit phagocytosis. Preclinical research supports several models of antibody-mediated blockade of CD47-SIRPα resulting in cell death signaling, phagocytosis of cells bearing stress signals, and priming of tumor-specific T cell responses. Four different antibody molecules designed to target the CD47-SIRPα interaction in malignancy are currently being studied in clinical trials: Hu5F9-G4, CC-90002, TTI-621, and ALX-148. Hu5F9-G4, a humanized anti-CD47 blocking antibody is currently being studied in four different Phase I trials. These studies may lay the groundwork for therapeutic bispecific antibodies. Bispecific antibody (CD20-CD47SL) fusion of anti-CD20 (Rituximab) and anti-CD47 also demonstrated a synergistic effect against lymphoma in preclinical models. This review summarizes the large body of preclinical evidence and emerging clinical data supporting the use of antibodies designed to target the CD47-SIRPα interaction in leukemia, lymphoma and multiple myeloma.     

Low-cost tools for diagnosing and monitoring HIV infection in low-resource settings

Low-cost technologies to diagnose and monitor human immunodeficiency virus (HIV) infection in developing countries are a major subject of current research and health care in the developing world. With the great need to increase access to affordable HIV monitoring services in rural areas of developing countries, much work has been focus on the development of point-of-care technologies that are affordable, robust, easy to use, portable and of sufficient quantitative accuracy to enable clinical decision-making. For diagnosis of HIV infection, some low-cost tests, such as lateral flow tests and enzyme-linked immunosorbent assays, are already in place and well established. However, portable quantitative tests for rapid HIV monitoring at the point of care have only recently been introduced to the market. In this review, we discuss low-cost tests for HIV diagnosis and monitoring in low-resource settings, including promising technologies for use at the point of care, that are available or close to market.