Monocytes mediate homing of circulating microvesicles to the pulmonary vasculature during low-grade systemic inflammation

Microvesicles (MVs), a plasma membrane-derived subclass of extracellular vesicles, are produced and released into the circulation during systemic inflammation, yet little is known of cell/tissue-specific uptake of MVs under these conditions. We hypothesized that monocytes contribute to uptake of circulating MVs and that their increased margination to the pulmonary circulation and functional priming during systemic inflammation produces substantive changes to the systemic MV homing profile. Cellular uptake of i.v.-injected, fluorescently labelled MVs (J774.1 macrophage-derived) in vivo was quantified by flow cytometry in vascular cell populations of the lungs, liver and spleen of C57BL6 mice. Under normal conditions, both Ly6Chigh and Ly6Clow monocytes contributed to MV uptake but liver Kupffer cells were the dominant target cell population. Following induction of sub-clinical endotoxemia with low-dose i.v. LPS, MV uptake by lung-marginated Ly6Chigh monocytes increased markedly, both at the individual cell level (~2.5-fold) and through substantive expansion of their numbers (~8-fold), whereas uptake by splenic macrophages was unchanged and uptake by Kupffer cells actually decreased (~50%). Further analysis of MV uptake within the pulmonary vasculature using a combined model approach of in vivo macrophage depletion, ex vivo isolated perfused lungs and in vitro lung perfusate cell-based assays, indicated that Ly6Chigh monocytes possess a high MV uptake capacity (equivalent to Kupffer cells), that is enhanced directly by endotoxemia and ablated in the presence of phosphatidylserine (PS)-enriched liposomes and β3 integrin receptor blocking peptide. Accordingly, i.v.-injected PS-enriched liposomes underwent a redistribution of cellular uptake during endotoxemia similar to MVs, with enhanced uptake by Ly6Chigh monocytes and reduced uptake by Kupffer cells. These findings indicate that monocytes, particularly lung-marginated Ly6Chigh subset monocytes, become a dominant target cell population for MVs during systemic inflammation, with significant implications for the function and targeting of endogenous and therapeutically administered MVs, lending novel insights into the pathophysiology of pulmonary vascular inflammation

Price Reversal Pattern of ARV Drugs: A Transaction-Cost Approach Digression

A price reversal pattern of ARV drugs was noted across lower and middle income countries in that the lower-income countries have higher prices relative to higher-income countries based on a 2008-2009 Summary Report by World Health Organization. The transaction costs affecting AVR drug pricing can be broadly classified into two kinds: One between the final users and the opinion/knowledge experts, and the other between the opinion/knowledge experts and the manufacturers. Economist’s version of price discrimination needs to be modified by including transaction costs. Transaction costs also point to institution creditability factors that will affect NGO procurement

Association Between Nutritional Status and Hypertension in a Rural Community in Dang District, Gujarat, India

Background: Hypertension is a leading risk factor for mortality in South Asian countries. The overweight-obesity status in India is increasing faster than the global average, especially in vulnerable and low-income communities. The purpose of this study is to explore the association between BMI and hypertension in a sample population from Ahwa, Dang District, Gujarat, Inda. Methods: A cross-sectional chart review study was conducted using secondary data of patients from medical outreach camps in Ahwa, Dang District, Gujarat, India (2018 and 2019). Hypertension was defined by American Heart Association cut-offs for blood pressure. BMI was calculated using height and weight measurements using WHO and South Asian cut-offs used for nutritional status indicators. Odds ratios estimated strength of association of hypertension and nutritional status. Results: A total of 953 adults were included in the study. Age-specific prevalence of hypertension was high in the sample population from Gujarat, India. Male hypertension declined at age 55-64 years and increased at 64+ years. Individuals with overweight-obese status had higher odds of being hypertensive when compared to normal and underweight individuals. Conclusions: The association between overweight-obese status and hypertension was positive. Using South Asian cutoffs (BMI\u3e23) includes a wider range of people at risk for hypertension, diabetes, CVD, and other chronic disease. A focus on reducing BMI will help in lowering the high burden of hypertension, improving the health and quality of life in the Ahwa region. This can be accomplished with a collective sense of awareness and public health interventions targeting a reduction in BMI

Rehabilitation of a Patient with Amelogenesis Imperfecta: A Case Report

Amelogenesis imperfecta (AI) is a diverse collection of inherited diseases that exhibit quantitative or qualitative tooth enamel defects in the absence of systemic manifestations. It can be characterized by enamel hypoplasia, hypomaturation, or hypocalcification of the teeth. AI may be associated with some other dental and skeletal developmental defects. Restoration for patients with this condition should be oriented toward the functional and esthetic rehabilitation. This article presents a case reported to post graduate department of Prosthodontics, Government Dental College and Hospital, Srinagar, India diagnosed with the hypoplastic type of AI