Immune Cell Activation: Stimulation, Costimulation, and Regulation of Cellular Activation

Opiate receptor (uOR) is expressed in central nervous system, gastrointestinal tract, male and female reproductive tissues, and immune cells. Morphine, a ligand for opioid receptor family, is known to activate the hypothalamic-pituitary-adrenal axis and release immunosuppressive glucocorticoids. Herein we present that minor changes, in the form of nonsynonymous single nucleotide polymorphisms, in μOR have cumulative impact on receptor-mediated signaling and functions of specific cell type(s). Significant reduction was seen in cells in M and S phases with coactivation of immune receptors with μOR. Flow cytometry-based experiments established a reduction in B and T lymphocytes, NK cells, and macrophages. Differences in types of immune cells were found to be significant to reduce immune response(s) mounted by GG(mutant allele)-bearing individuals. This is the first report on cross-talk between LPS-binding and μOR, explaining the reduction in the number of T and B cells after chronic opiate use and also the association of this impact on immunocytes with functional SNP, rs1799972/118G allele of OPRM1 gene as an explanation for the immune suppression in opiate users. Initially present lower cell titers can be further lowered by exogenous opiates and account for immunosuppression seen in chronic opiate users or after long-term treatment with opiate drugs for chronic pain

MANGIFERIN: A POTENTIAL NATURAL MOLECULE FOR MANAGEMENT OF METABOLIC SYNDROME

The incidence of metabolic syndrome is rising at an unprecedented pace. The technological advancements, lifestyle changes and mechanization are all considered responsible for this rising global health issue. Nature-derived phytochemicals possess several unique properties that may be usefulformanagement of metabolic syndrome. Mangiferin, present in various plant species, has been shown to have anti-obesity, anti-diabetic, anti-oxidant and anti-inflammatory properties. Mangiferin also modulates glucose and lipid metabolisms and restores glucose and lipid homeostasis.In this review, we attempt to provide the latest information available on mangiferin and its effects on various biological processes associated/implicated in metabolic syndrome.Â

Unraveling the Novel Bacterial Assisted Biodegradation Pathway of Morpholine

Most xenobiotics are biodegradable, persistent or recalcitrant in nature. Morpholine, a typical xenobiotic, was initially regarded as recalcitrant, however, later proved to be biodegradable by bacterial species like Mycobacterium and Pseudomonas in particular. However, establishing the metabolic pathways involved for the successful biodegradation of morpholine is challenging because of its extreme level of water solubility that affects various analytical procedures. In addition, to date, no suitable analytical methods have been reported to directly estimate the activity of morpholine and its degradable products or intermediates. Nevertheless, methods, especially optical density, gas chromatography and mass spectrophotometric analysis, could indirectly estimate the degradation product(s) of morpholine formed as a result of its biotransformation. In this present study, the degradation pathway of morpholine was scertained by selected bacterial isolates by measuring their capacity to degrade morpholine. Based on this analysis of culture filtrates, it was determined that the novel isolate is the genus Halobacillus blutaparonensis which utilizes the diglycolic acid route from the metabolic degradation pathway of morpholine to induce one of two branches of the morpholine biodegradation pathway in the presence of morpholine while the other branch is inhibited. Whatever the branches with regard to the degradation pathway of morpholine exhibited by bacteria are, ammonia is the final end product of degradation which might be biochemically utilized by the isolate

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Phosphorus balance and prostate cancer

623-626Prostatic diseases affect men over the age of 45 and increase in frequency with age so that by the eighth decade more than 90% of men have Benign Prostatic Hyperplasia, (BPH), of which some progress to Carcinoma of Prostate (CaP). CaP, the most common malignancy in men, is also the second most common cause of death in men. Over the last three decades the mortality rate for CaP has steadily increased. There, however, are scant clues to the aetiology/pathogenesis of CaP. As treatment failures of advanced carcinoma continue to frustrate clinicians, emphasis has recently been focused on possible preventive strategies. Several studies support the view that higher levels of 1,25-(OH)2 D, the active metabolite of vitamin D, reduce the risk of BPH and CaP. Men with high serum levels of 1,25-(OH)2D have a reduced risk of poorly differentiated and clinically advanced CaP. Hypercalcemic activity of 1, 25-(OH)2D or its analogues, however, thwart their use for therapy in humans. Incidentally, a low dietary intake of phosphorus has been reported to increase serum levels of 1, 25-(OH)2 D. In addition, dietary fructose reduces plasma phosphate levels by 30 to 50% for more than 3 hr. Fruit intake has, indeed, been shown to be associated with reduced risk of CaP, particularly the advanced type. These observations, taken together, Support that dietary determinants of hypophosphatemia, leading to increased plasma levels of 1, 25 -(OH)2D, could reduce the risk of ageing men to develop prostatic diseases, both BPH and/or carcinoma of Prostate

Learning together from the experiences : writeshop to capture CBRM studies from Asia, 30th October - 2nd November 2007, Goa International Centre, India; a report

The ‘‘writeshop’’ in Goa provided time and opportunity to participating members of partner organisations to further develop case studies on resource mobilization. Participants could rework their drafts with a focus on resource mobilization and planning, institutionalization of resource mobilization in policy, innovative resource mobilization activities, and issues of accountability and credibility. Secondly, the workshop aimed to arrive at a group analysis of the case studies to deepen understanding of specific cases and develop cross case analysis. This report outlines activities and feedback

Rapid Diagnostic Test for Antimicrobial Susceptibility

Safe Harbour Data for Diagnostic Accuracy Study of a Rapid Diagnostic Test to Ensure Antimicrobial Susceptibilit

Association of <it>ADHIB </it>and <it>ALDH2 </it>gene polymorphisms with alcohol dependence: A pilot study from India

Abstract Functional polymorphism in the genes encoding alcohol dehydrogenase (ADH) 1B and aldehyde dehydrogenase (ALDH) 2 are considered most important among several genetic determinants of alcohol dependence, a complex disorder. There is no report on the widely studied Arg47His and Glu487Lys polymorphisms from Indian alcoholdependent populations. In this paper, we report, for the first time, allelic and genotypic frequencies of Arg47His and Glu487Lys single nucleotide polymorphisms (SNPs) in North Indian alcohol-dependent subjects. A total of 174 alcohol-dependent males, recruited using DSM IV criteria (American Psychiatric Association, 1994), were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. The results obtained from genetic analysis were correlated with clinical parameters using Student's t-test or Mann Whitney's U test. The highlight of the study findings was the uniquely high frequency of the ALDH2*2/*2 genotype (among alcohol-dependent subjects) being a risk-conferring factor for alcohol dependence.</p

TROPICAL AGRICULTURAL SCIENCE Garlic: An Effective Functional Food to Combat the Growing Antimicrobial Resistance

ABSTRACT Emerging multidrug resistant bacterial infections are burning public health concerns worldwide. There is an urgent need to explore alternative antimicrobial agents for effective management of bacterial infections. Garlic (Allium sativum) has been traditionally used for the treatment of different diseases since ancient times. The present study aims to evaluate the antimicrobial activity of aqueous extract of Allium sativum against multidrug resistant clinical isolates of pathogenic bacteria found in human urine in cases of urinary tract infection (UTI). A total of 166 uropathogens were evaluated for antibiotic susceptibility, 56% clinical isolates were found to have high degree of resistance with multiple antibiotic resistance (MAR) index &gt;0.5. About 82% bacterial isolates with MAR index &gt;0.5 were found to be susceptible to crude aqueous garlic extract. Thus, aqueous garlic extract (AGE) was found to possess effective anti-bacterial activity against multidrug resistant clinical pathogens and may be tested further as a natural dietary component to manage drug resistance bacteraemia. Therefore, alternate medicine practices with natural plant extract including garlic may be of great importance in combating public health challenges like UTI