The aim of the study was to evaluate the usefulness of Bresol in the management of bronchial asthma and its adverse effects if any, and to determine patient compliance with the study drug. Patients were administered Bresol tablets at a dosage of two tablets twice daily for a period of 30 days in adults and one tablet twice daily for the same period in children in the age group of 12-18 years. They were evaluated on Days 0, 15 and 30 for subjective improvements in dyspnea, cough, wheezing, rhonchus, tightness of the chest, difficulty in expectoration, rhinitis, sneezing, fever and paroxysmal nocturnal dyspnea. Changes in various parameters from the values at baseline level to the values at the end of the study were pooled and analyzed cumulatively using Fisher's exact test. Statistical analysis was done using GraphPad Prism Version 4.03 for Windows. Results of the study showed a significant improvement in all the clinical parameters of asthma such as dyspnea, cough, wheezing, rhonchus, tightness of the chest, difficulty in expectoration, rhinitis, sneezing, fever and paroxysmal nocturnal dyspnea. None of the patients presented with any adverse effects. All the patients completed the treatment and compliance to the study drug was good without any dropouts. This indicates safety and efficacy of Bresol tablets in patients of bronchial asthma.
The workfare scheme, the National Rural Employment Guarantee Scheme (NREGS), and the direct food subsidy programme, the Targeted Public Distribution Scheme (TPDS), represent two social safety nets instituted in India as anti-poverty measures. This paper examines whether from the point of view of individual households the two programmes are substitutes or complements, as this will shed light on the appropriateness of the design of the two programmes. Based on primary household data collected for the Indian states of Rajasthan and Madhya Pradesh (MP), we show that, in Rajasthan, a large percentage of households consider TPDS and NREGS programmes to be substitutes for each other, while in MP the households often perceive the two programmes as complements. Thus it appears that the two programmes are better designed in MP since an incentive for participation in one programme has desirable side effects on participation in the other. Correlates of participation in the two states are identified and the paper advances several policy conclusions.
This paper examines the effect of domestic violence on the health of ever-married women of reproductive age group in India. Micro-level National Family Health Survey (NFHS-III) data for the year 2005-06 has been used in the study. We employ disease, body mass index, under nutrition level and anemia as the measures of health and physical, emotional and sexual forms of domestic violence are used as indicators of domestic violence at both national and state levels. We find that domestic violence has negative impact on the overall women’s health and nutritional status. However, national level results are not consistent with that of the states level. Based on the findings, we argue that the issue of domestic violence should be addressed in national and state level health policies and programmes.
Abstract GBA1 mutations lead to defective lysosomal glucocerebrosidase resulting in accumulation of glucosylceramide (GC) in Gaucher disease (GD). Patients with GD have an increased risk to develop B cell lymphomas. The exact mechanistic bases for this propensity remain elusive. Recently, we uncovered formation of GC-specific IgG autoantibodies in Gba1 D409V/knockout (Gba19V/−) mice, which recapitulate features of human GD, and in humans with untreated GD. In vivo formation of IgG-GC immune complexes induced massive complement activation and C5a generation. Importantly, C5a-mediated activation of its cognate C5a receptor 1 (C5aR1) on immune cells enhanced GC synthesis, thereby fueling GC accumulation and excess tissue recruitment and activation of inflammatory myeloid and lymphoid immune cells, leading to visceral tissue damage in GD. Here, the expression of Runt-related transcription factor 1 (RUNX-1) was determined in Gba19V/− mice, to evaluate if C5a/C5aR1 axis activation may control the development of lymphomas in GD. RUNX-1 is a member of the Runt oncogene family linked to hematologic malignancies. We determined RUNX-1 expression in tissue from C5aR1 sufficient (+/+) and deficient (−/−) Gba19V/− mice as well as strain-matched control WT and C5aR1−/− mice. Compared to WT, Gba19V/− mice had increased RUNX-1 expression. Strikingly, RUNX-1 expression was markedly downregulated in C5aR−/−Gba19V/− vs. C5aR1+/+Gba19V/− mice. Our findings suggest that the C5a-C5aR1 axis activation in GD drives RUNX1 expression as a novel mechanism to control the development of hematologic malignancies in GD that may be diminished by targeting the C5aR1 axis in GD.
Abstract This study is a crucial step in understanding the dynamics of the maternal immune response directed at paternal human leukocyte antigen (HLA) molecules. HLA molecules are proteins on cell surfaces that play a critical role in immune system regulation. Our findings focus on the pivotal role of maternal antibodies targeting fetal HLA molecules in inhibiting antigen-induced activation of uterine immune cells, which is essential for successful pregnancies. Antibodies are proteins produced by the immune system that recognize and neutralize foreign substances. The primary focus is to unravel maternal anti-fetal rejection by drawing parallels to transplant rejection and emphasizing the role of allorecognition—the process by which an individual’s immune system recognizes and responds to antigens from another individual of the same species—in both cellular (involving immune cells) and humoral (involving antibodies) refusal. Although exploring anti-HLA antibodies in preventing fetal loss in patients with recurrent spontaneous abortion is captivating, there are still significant knowledge gaps that need to be addressed. Further studies are imperative to reveal the precise mechanism by which these antibodies generate and prevent maternal immune responses, critical determinants of pregnancy outcomes. It is vital to investigate the specificity of these antibodies and whether they exclusively target specific HLA molecules on trophoblasts (cells forming the outer layer of a blastocyst, providing nutrients to the embryo). This review paper not only offers insights into the development of these protective antibodies in pregnancy but also lays the foundation for future research on therapeutic implications, particularly in cases of recurrent spontaneous abortion.
A field experiment was conducted during 1995–96 to examine the effect of RSC irrigation water on the yield, chemical composition and uptake of nutrients by periwinkle leaves. It was observed that N, P, K, Na, Ca and Mg content in cultivated soil ranged from 2.0–3.5, 0.2–3.5, 0.52–1.60, 1.08–1.80 and 0.16–0.74% respectively. Increased level of RSC irrigation water, decreases P, K, Ca and Mg content in soil and N and Na content in leaf increases. The uptake values of N, P, K, Na, Ca, and Mg were reduced significantly with higher level of RSC irrigation waters. Yield (Fresh weight and dry weight of leaves) decreased with increasing RSC irrigation water. Increased the levels of RSC, decreased the EC and increased pH values of soil.
The objective of this analysis is mainly to construct an intuitive measure of the performance of the National Rural Employment Guarantee Scheme (NREGS) in India. The focus is on divergence between demand and supply at the district level. Some related issues addressed are: (i) whether the gap between demand and supply responds to poverty; and (ii) whether recent hikes in NREGS wages are inflationary. Our analysis confirms responsiveness of the positive gap between demand and supply to poverty. Also, apprehensions expressed about the inflationary potential of recent hikes in NREGS wages have been confirmed. More importantly, higher NREGS wages are likely to undermine self-selection of the poor in it.
Abstract Introduction: Cancer immunotherapy is the emerging paradigm in the search for a cure for cancer. AT1965 is a novel therapeutic that demonstrates remarkable anti-tumor activity across different preclinical tumor models, mediated through the activation of B-cells. In this study, we have evaluated the metabolism, pharmacokinetics (PK) and toxicity of AT1965 in rodent and non-rodent species. Methods: AT1965 metabolism was studied in rodent, canine and primate liver microsomes. The PK of AT1965 was determined in 4T1 tumor bearing female Balb/c mice; female Sprague Dawley rats and female Beagle dogs at a variety of doses and schedules following single intravenous (i.v) injections. The extent and duration of the exposure was monitored over 120 hours in mice and rats, and till 192 hours in dogs, post dosing. Concentrations of AT1965 in plasma samples were determined either by LC-MS/MS or Atomic Absorption Spectroscopy. The toxicity of AT1965 in male and female Sprague Dawley Rats following single dose i.v. administration of 43.7, 87.4 and 174.8 mg/kg dosage of AT1965 were examined. During toxicity studies, clinical health status was observed daily for 14 days after treatment, followed by necropsy. Results: AT1965 metabolism evaluated in mouse, rat, dog, monkey and human liver microsomes indicated high stability across all species. PK studies reveal that AT1965 exhibited a high exposure, slow systemic clearance and a proportional increase in dose normalized exposure across species. The elimination half-life (T1/2) varied from 34-40 hours in tumor-bearing mice to 29-44 hours in rats and ~ 66 hours in dogs. The excretion of AT1965 was predominantly through hepatobiliary route, with minimal renal clearance. Single i.v. administered acute dose toxicity studies for AT1965 reveal 87.4 mg/kg and 174.8 mg/kg as MTD and toxic doses respectively in rats. Conclusion: The excellent pharmacokinetic profile of AT1965 showing high exposure and enhanced elimination half-life tested across species, in addition to striking antitumor activity coupled with low toxicity in multiple rodent tumor models, provide a compelling rationale for the development of AT1965 as a novel immunotherapeutic agent in the clinic. Citation Format: Aniruddha Sengupta, Mallik Samarla, Manoj Pandey, Arindam Sarkar, Monideepa Roy, Shiladitya Sengupta. Pharmacokinetics and toxicity studies of AT1965, a B-cell activating immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4918.
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