A prospective observational study was conducted in a tertiary care hospital to study clinicoepidemiological profile of potentially rabid animal bite cases from rural India. Total of 308 children (median age 6 years) admitted to hospital, were recruited over 1 year and followed up till completion of antirabies vaccine course. Dog was the commonest (77.27%) offending animal. Of the exposures, 66.88% were scratches, 88.96% were unprovoked and 27.27% were categorized as Class III. The median times to wound toileting and reporting to health facility were 1 and 6 h, respectively. Majority received prompt PEP in hospital, and RIG was administered in 34.55% of Class II and 90.48% of Class III exposures. Compared with their older counterparts, children aged <5 years suffered more bites on face and trunk and more Class III exposures. The rabies prophylaxis scenario is encouraging, when compared with earlier studies, but there are gaps to be addressed.
BackgroundInhalation of crystalline silica is associated with pulmonary inflammation and silicosis. Although silicosis remains a prevalent health problem throughout the world, effective treatment choices are limited. Imipramine (IMP) is a FDA approved tricyclic antidepressant drug with lysosomotropic characteristics. The aim of this study was to evaluate the potential for IMP to reduce silicosis and block phagolysosome membrane permeabilization.MethodsC57BL/6 alveolar macrophages (AM) exposed to crystalline silica ± IMP in vitro were assessed for IL-1β release, cytotoxicity, particle uptake, lysosomal stability, and acid sphingomyelinase activity. Short term (24 h) in vivo studies in mice instilled with silica (± IMP) evaluated inflammation and cytokine release, in addition to cytokine release from ex vivo cultured AM. Long term (six to ten weeks) in vivo studies in mice instilled with silica (± IMP) evaluated histopathology, lung damage, and hydroxyproline content as an indicator of collagen accumulation.ResultsIMP significantly attenuated silica-induced cytotoxicity and release of mature IL-1β from AM in vitro. IMP treatment in vivo reduced silica-induced inflammation in a short-term model. Furthermore, IMP was effective in blocking silica-induced lung damage and collagen deposition in a long-term model. The mechanism by which IMP reduces inflammation was explored by assessing cellular processes such as particle uptake and acid sphingomyelinase activity.ConclusionsTaken together, IMP was anti-inflammatory against silica exposure in vitro and in vivo. The results were consistent with IMP blocking silica-induced phagolysosomal lysis, thereby preventing cell death and IL-1β release. Thus, IMP could be therapeutic for silica-induced inflammation and subsequent disease progression as well as other diseases involving phagolysosomal lysis.Electronic supplementary materialThe online version of this article (10.1186/s12989-017-0217-1) contains supplementary material, which is available to authorized users.
A B S T R A C TBackground and Objectives: Neonatal hypoglycemia, a common metabolic problem, often goes unnoticed owing to lack of specifi c symptoms. We designed this study to assess the incidence of hypoglycemia in healthy normal birth weight and low birth weight babies, including both preterm and small for gestational age (SGA) newborns, to evaluate the impact of early breastfeeding on hypoglycemia and to assess the impact of exclusive breast feeding on glucose values up to 48 h of age. Design and Settings: A hospital-based prospective longitudinal study. Materials and Methods: The study was conducted over six months involving one hundred fi fty healthy (both term and preterm) appropriate for gestational age (AGA) or SGA babies with birth weight between 1.5 kg and 3.99 kg. Blood glucose values were measured at the age of 1 h, 6 h, 12 h, 24 h and 48 h after delivery which was independent of feeding time. Blood glucose value less than 40 mg/dl (2.2 mmol/l) was defi ned as hypoglycemia. Sick newborns, those less than 34 weeks of gestation or less than 1500 g, infant of diabetic mother, those with birth asphyxia, congenital malformations and endocrine defi ciencies were excluded. Results: Overall incidence of hypoglycemia was 32%. Hypoglycemia was signifi cantly greater in SGA and preterm as compared to AGA and term newborns respectively (P<0.001). Incidence of hypoglycemia was signifi cantly more in newborns with delayed breast feeding than early breast feeding (64% vs 17%; P<0.001). Conclusion: Low birth weight babies (both preterm and small-for-date) are prone to develop hypoglycemia especially in fi rst 24 h of life with delayed introduction of breast feeding being an additional risk.
MARCO is the predominant scavenger receptor for recognition and binding of silica particles by alveolar macrophages (AM). Previously, it was shown that mice null for MARCO have a greater inflammatory response to silica, but the mechanism was not described. The aim of this study was to determine the relationship between MARCO and NLRP3 inflammasome activity. Silica increased NLRP3 inflammasome activation and release of the proinflammatory cytokine, IL-1β, to a greater extent in MARCO−/− AM compared to wild type (WT) AM. Furthermore, in MARCO−/− AM there was greater cathepsin B release from phagolysosomes, Caspase-1 activation, and acid sphingomyelinase activity compared to WT AM, supporting the critical role played by lysosomal membrane permeabilization (LMP) in triggering silica-induced inflammation. The difference in sensitivity to LMP appears to be in cholesterol recycling since increasing cholesterol in AM by treatment with U18666A decreased silica-induced NLRP3 inflammasome activation, and cells lacking MARCO were less able to sequester cholesterol following silica treatment. Taken together, these results demonstrate that MARCO contributes to normal cholesterol uptake in macrophages; therefore, in the absence of MARCO, macrophages are more susceptible to a greater inflammatory response by particulates known to cause NLRP3 inflammasome activation and the effect is due to increased LMP.
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