Melatonin ameliorates myocardial infarction in obese diabetic individuals: The possible involvement of macrophage apoptotic factors.

In recent days, the hike in obesity-mediated epidemics across the globe and the prevalence of obesity-induced cardiovascular disease has become one of the chief grounds for morbidity and mortality. This epidemic-driven detrimental events in the cardiac tissues start with the altered distribution and metabolism pattern of high-density lipoprotein and low-density lipoprotein (LDL) leading to cholesterol (oxidized LDL) deposition on the arterial wall and atherosclerotic plaque generation, followed by vascular spasms and infarction. Subsequently, obesity-triggered metabolic malfunctions induce free radical generation which may further trigger pro-inflammatory signaling and nuclear factor kappa-light-chain-enhancer of activated B cells transcriptional factor, thus inducing interferon-gamma, tumor necrosis factor-alpha, and inducible nitric oxide synthase. This terrifying cardiomyopathy can be further aggravated in type 2 diabetes mellitus, thereby making obese diabetic patients prone toward the development of myocardial infarction (MI) or stroke in comparison to their nondiabetic counterparts. The accelerated oxidative stress and pro-inflammatory response induced cardiomyocyte hypertrophy, followed by apoptosis in obese diabetic individuals, causing progression of athero-thrombotic vascular disease. Being an efficient antioxidative and anti-inflammatory indolamine, melatonin effectively inhibits lipid peroxidation, pro-inflammatory reactions, thereby resolving free radical-induced myocardial damages along with maintaining antioxidant reservoir to preserve cardiovascular integrity. Prolonged melatonin treatment maintains balanced body weight and serum total cholesterol concentration by inhibiting cholesterol synthesis and promoting cholesterol catabolism. Additionally, melatonin promotes macrophage polarization toward the anti-inflammatory state, providing a proper shield during the recovery period. Therefore, the protective role of melatonin in maintaining the lipid metabolism homeostasis and blocking the atherosclerotic plaque rupture could be targeted as the possible therapeutic strategy for the management of obesity-induced acute MI. This review aimed at orchestrating the efficacy of melatonin in ameliorating irrevocable oxidative cardiovascular damage induced by the obesity-diabetes correlation.

Prevalence and predictors of water-borne diseases among elderly people in India: evidence from Longitudinal Ageing Study in India, 2017-18.

BACKGROUND: India suffers from a high burden of diarrhoea and other water-borne diseases due to unsafe water, inadequate sanitation and poor hygiene practices among human population. With age the immune system becomes complex and antibody alone does not determine susceptibility to diseases which increases the chances of waterborne disease among elderly population. Therefore the study examines the prevalence and predictors of water-borne diseases among elderly in India. METHOD: Data for this study was collected from the Longitudinal Ageing Study in India (LASI), 2017-18. Descriptive statistics along with bivariate analysis was used in the present study to reveal the initial results. Proportion test was applied to check the significance level of prevalence of water borne diseases between urban and rural place of residence. Additionally, binary logistic regression analysis was used to estimate the association between the outcome variable (water borne diseases) and the explanatory variables. RESULTS: The study finds the prevalence of water borne disease among the elderly is more in the rural (22.5%) areas compared to the urban counterparts (12.2%) due to the use of unimproved water sources. The percentage of population aged 60 years and above with waterborne disease is more in the central Indian states like Chhattisgarh and Madhya Pradesh followed by the North Indian states. Sex of the participate, educational status, work status, BMI, place of residence, type of toilet facility and water source are important determinants of water borne disease among elderly in India. CONCLUSION: Elderly people living in the rural areas are more prone to waterborne diseases. The study also finds state wise variation in prevalence of waterborne diseases. The elderly people might not be aware of the hygiene practices which further adhere to the disease risk. Therefore, there is a need to create awareness on basic hygiene among this population for preventing such bacterial diseases.

Household expenditure for immunization among children in India: a two-part model approach.

BACKGROUND: Despite the Indian government's Universal Immunization Program (UIP), the progress of full immunization coverage is plodding. The cost of delivering routine immunization varies widely across facilities within country and across country. However, the cost an individual bears on child immunization has not been focussed. In this context, this study tries to estimate the expenditure on immunization which an individual bears and the factors affecting immunization coverage at the regional level. METHODS: Using the 75th round of National Sample Survey Organization data, the present paper attempts to check the individual expenditure on immunization and the factors affecting immunization coverage at the regional level. Descriptive statistics and multivariate regression analysis were used to fulfil the study objectives. The two-part model has been employed to inspect the determinants of expenditure on immunization. RESULTS: The overall prevalence of full immunization was 59.3 % in India. Full immunization was highest in Manipur (75.2 %) and lowest in Nagaland (12.8 %). The mean expenditure incurred on immunization varies from as low as Rs. 32.7 in Tripura to as high as Rs. 1008 in Delhi. Children belonging to the urban area [OR: 1.04; CI: 1.035, 1.037] and richer wealth quintile [OR: 1.14; CI: 1.134-1.137] had higher odds of getting immunization. Moreover, expenditure on immunization was high among children from the urban area [Rs. 273], rich wealth quintile [Rs. 297] and who got immunized in a private facility [Rs. 1656]. CONCLUSIONS: There exists regional inequality in immunization coverage as well as in expenditure incurred on immunization. Based on the findings, we suggest looking for the supply through follow-up and demand through spreading awareness through mass media for immunization.

Groundwater inhabited Bacillus and Paenibacillus strains alleviate arsenic-induced phytotoxicity of rice plant.

Arsenic contamination in agricultural soil now imposing a major threat to crop productivity and causing several hazardous health effects through percolation in food chain. Bioremediation, an efficient way of soil health restoration toward sustainability offered by some soil-borne microorganisms, has been reported. The present work deals with application of two potent arsenic-tolerant bacterial strains (Bacillus thuringiensis A01 and Paenibacillus glucanolyticus B05), obtained from natural sources in modulating overall growth and antioxidant defense against arsenic-treated rice plants. Between the two, former could reduce arsenic uptake up to 56% (roots) and 85% (shoots), and the preceding one up to 31% (roots) and 65% (shoots) in a hydroponic environment. Germination percentage was noted to be enhanced significantly (p ≤ 0.05). Expression of oxidative stress defensive enzymes such as superoxide dismutase, peroxidase and catalase have been augmented at seedling stages (21 days) toward detoxification of arsenic imposed excess ROS generation. Increment of leaf Thiobarbituric acid reactive substances due to arsenic exposure have been ameliorated by both the bacterial application. Phenolic and flavonoid mediated free radical scavenging ability of the test plants elevated significantly (p ≤ 0.05). The present work revealed that, selected bacterial strains can perform efficient bioremediation against arsenic pollutant rice cultivation.

Melatonin protects against diclofenac induced oxidative stress mediated myocardial toxicity in rats: A mechanistic insight.

Diclofenac, a traditional non-steroidal anti-inflammatory drug, is commonly used for treating chronic pain and inflammation. Recently, a number of articles have highlighted the toxicities associated with diclofenac. The current study explores the molecular mechanism of diclofenac induced cardiac toxicity following oxidative stress. Diclofenac inhibits catalase, disrupts the redox balance in cardiac tissue, accelerates the monoamine oxidase induced hydroperoxide generation and eventually inhibits crucial mitochondrial enzyme, viz., aldehyde dehydrogenase, thereby causing myocardial injury. Melatonin, the pineal indoleamine with high antioxidative efficacy, is well known for its cardio-protective properties and its dietary consumption has profound impact on cardiac health. The present study demonstrates perhaps for the first time, that apart from ameliorating oxidative load in the cardiac tissue, melatonin also attenuates the inhibition of catalase and aldehyde dehydrogenase, and prevents stress mediated stimulation of monoamine oxidase. Moreover, favourable binding of diclofenac with melatonin may protect the myocardium from the deleterious effects of this drug. The results indicate toward a novel mechanism of protection by melatonin, having future therapeutic relevance.

Investigating the association between floods and low birth weight in India: Using the geospatial approach.

BACKGROUND: Frequent natural disasters like floods pose a major threat to India, with significant implications for public health. Low birth weight (LBW) is a critical global health concern, contributing to neonatal mortality. However, the association between floods and LBW remains underexplored. This study aims to address this gap by investigating the association between flood hazards and LBW in India using a geospatial approach. By analyzing data from the National Family Health Survey (NFHS-5) and flood zonation maps, the study aims to uncover the spatial dynamics of this association, offering insights into the implications of floods on birth weight across diverse geographical regions. METHODS: The study used the fifth round of NFHS data, 2019-21, which involved 202,194 children selected through a multi-stage stratified sampling technique. The Vulnerability Atlas of India 2019 maps were also utilized to classify areas as flood or non-flood zones. Birth weight data from the NFHS-5 were categorized into three groups: very low, low, and normal birth weight (VLBW, LBW and NBW). Control variables including flood exposure, socio-demographic attributes, and geographic region were considered. Bivariate analysis and multinomial logistic regression were employed for statistical analysis. The spatial analysis involved Moran's I statistics and Geographically Weighted Regression to explore spatial dynamics of the association between floods and birth weight in India. RESULTS: Floods predominantly affect India's lower Himalayan belts and western coastal regions. Flood-affected areas show higher proportions of VLBW and LBW infants. Groundwater usage and unimproved sanitation are associated with higher risk of VLBW and LBW. Sex, wealth, maternal education, residence type, and geographic region significantly influence birth weights. Multinomial logistic regression reveals 8 % and 27 % higher risks for LBW and VLBW in flood-affected regions. LISA cluster maps identify high-risk areas for both LBW and floods. Geographically Weighted Regression highlights 52 % of the variability in LBW occurrences can be attributed to the influence of flood hazards. Families hailing from the poorest wealth background and exposed to flood hazards bear a 5 % heightened likelihood of delivering LBW infants, in stark contrast to their counterparts from the same economic background yet unaffected by floods. CONCLUSIONS: The significant association between floods and LBW underscores the importance of robust disaster preparedness and public health strategies. By unraveling the spatial intricacies of flood-induced LBW disparities, this research provides valuable insights for promoting healthier birth outcomes and reducing child mortality rates, particularly in flood-prone regions. These findings emphasize the importance of holistic policies that address both environmental challenges and socioeconomic inequalities to safeguard maternal and infant health across the nation.

Melatonin protects against ketorolac induced gastric mucosal toxic injuries through molecular mechanism associated with the modulation of Arylakylamine N-Acetyltransferase (AANAT) activity.

Ketorolac tromethamine (KT), is a widely used non-steroidal anti-inflammatory drug (NSAID) for treating moderate to severe pain. However, the use of KT has been restricted due to its highly toxic attributes that lead to severe gastric ulceration and bleeding. The protective effects of exogenous melatonin (MT) has been reported in conditions associated with gastro-intestinal disorders. This study aims at exploring the role of gastric endogenous MT level and it's metabolizing enzyme AANAT, at the onset of ketorolac mediated toxicities in the gastric mucosa. Gastric mucosal damage was induced in experimental rats by oral administration of graded doses of KT, where 50 mg/kg b.w. of KT was observed to incur maximum gastric lesions. However, gastric damages were found to be protected in rats, pre-treated with 60 mg/kg b.w. of MT. Post-sacrifice, mean ulcer index, oxidative status, total melatonin levels and enzyme activities associated with MT biosynthesis and catabolism were estimated. The results reveal that KT decreases AANAT activity with a concomitant decline in endogenous MT level which cumulatively aggravates gastric toxicity. Moreover, exogenous MT administration has been found to be protective in ameliorating this ulcerogenic process in rats, challenged with KT. Biochemical and histo-pathological observations revealed the reduction in oxidative stress level and replenishment of depleted gastric MT levels in MT pre-treated animals, which might be the causative factors in conferring protection to the gastric tissues and residing mitochondria. The results revealed a correlation between depleted gastric MT level and ulcer formation, which unveiled a novel ulcerogenic mechanism. This may bring forth future therapeutic relevance for treating patients suffering from KT mediated acute gastric toxicities.

Oleic acid prevents erythrocyte death by preserving haemoglobin and erythrocyte membrane proteins.

Haemolysis of erythrocytes upon exposure to haemato-toxic phenylhydrazine (PHZ), makes it an experimental model of anaemia and a partial model of ß-thalassaemia, where oxidative stress (OS) was identified as principal causative factor. Oleic acid (OA) was evidenced to ameliorate such stress with antioxidative potential. Erythrocytes were incubated in vitro using 1 mM PHZ, 0.06 nM OA. Erythrocyte membrane protein densities and haemoglobin (Hb) status were examined. Any interaction of Hb with PHZ/OA was checked by calorimetric and spectroscopic analysis using pure molecules. Occurrence of erythrocyte apoptosis and involvement of free iron in all groups were evaluated. PHZ exposure to erythrocytes results in OS with subsequent apoptosis as evidenced from increased lipid peroxidation and translocation of phosphatidylserine in outer membrane. Preservations of erythrocyte cytoskeletal architecture and membrane bound enzyme activity were found in presence of OA. Moreover, both heme and globin of Hb was examined to be conserved by OA. Presence of OA, impeded apoptosis also, possibly by thwarting Hb breakdown followed by free iron release and consequent free radical generation. Additionally, direct sequential binding of OA with PHZ endorsed another protective mechanism of OA toward erythrocytes. OA affords protection to erythrocytes by conserving its major components and prevents haemolysis which project OA as a haemato-protective agent. Apart from combating PHZ toxicity, anti-apoptotic action of OA strongly suggests its usage in anaemia and ß-thalassaemia patients to curb irreversible erythrocyte breakdown. This research strongly recommends OA in pure form or from dietary sources as a therapeutic against haemolytic disorders.

Fused Furan Moieties from Enol-like Compounds and ß-Keto Sulfoxonium Ylides Involving sp2 C-H Activation and Concomitant Tandem C-O Annulation.

An efficient and fascinating protocol has been devised for the preparation of fused furan moieties involving a Rh(II) catalyzed one-pot C-H activation/concomitant tandem annulation process, employing an enolic compound and ß-keto sulfoxonium ylide as the reacting conjugates. The developed technique demands only Rh2(TFA)4 as the catalyst to proceed forward and is devoid of additional metallic or nonmetallic additives. The skeletal transformation of naphthoquinone fused furan to highly decorated naphthoquinone fused indolizines is a promising synthetic application.

Exploration of spatial clustering in maternal health continuum of care across districts of India: A geospatial analysis of demographic and health survey data.

INTRODUCTION: The continuum of care (CoC) throughout pregnancy, delivery and post-delivery has recently been highlighted as an integrated intervention programme for maternal, new-born, and child health. Existing literature suggests the importance of continuum of care (CoC) for improved maternal and child health outcomes. However due to unavailability of data at the lowest administrative levels, literature on spatial pattern of uptake of full CoC is lacking. The present study attempts to focus on the spatial analysis of CoC in maternal health care in India. DATA AND METHODS: The study is based on the fourth round of National Family Health Survey data conducted in 2015-16 in India. The outcome variable used is maternal health continuum of care which includes- at least 4 ANC visits, delivery through skilled birth attendant and postnatal check-up within 48 hours of delivery. Univariate and bivariate Local Indicator of Spatial Association (LISA) maps have been generated to show the spatial pattern of CoC across 640 districts in India. We also employed spatial regression techniques to explore the determinants of CoC. FINDINGS: Percentage of women who followed full CoC was observed to be least for East Kameng (0.0%) district of Arunachal Pradesh and highest in North Goa district (90.4%). Majority of districts where uptake of full CoC was more than 80 percent were found concentrated in southern region on India. Equivalently, findings indicated a strong spatial clustering of full CoC with high-high clusters mostly concentrated in southern districts. Low-low district clusters are concentrated in the states of Uttar Pradesh, Bihar and Madhya Pradesh. For complete CoC the global Moran's I is 0.73 indicating the spatial dependence. The spatial regression analysis suggested that modern contraceptive use, meeting with health worker, urbanization and secondary or above education for women have positive impact on the utilisation of CoC. CONCLUSION: The spatial pattern indicates district level clustering in uptake of CoC among women. The study suggests policymakers and stakeholders to implement comprehensive interventions at sub-regional levels for ensuring the completion of CoC for women which acts as a preventive measure for adverse outcomes such as-maternal and child mortality.

Association of anthropometric measures of obesity and physical activity with cardio-vascular diseases among older adults: Evidence from a cross-sectional survey, 2017-18.

BACKGROUND: With the increase in elderly population, the risk of cardiovascular diseases (CVD) among Indian older adults is also increasing. The present paper tries to assess how different anthropometric measures of obesity and physical activity affects cardiovascular disease risk among older adults in India. METHODS: The data from Longitudinal Ageing Study in India (LASI) has been used. The total sample size for the present study is 31,464 older adults aged 60 years and above. Chi-square test and binary logistic regression has been used to measure the association of obesity measures and CVD prevalence. RESULTS: About 35.2% (n = 11,058) of the older adults suffered from CVD. Moreover, 22.2% (n = 6,217) of the older adults were obese/overweight, 23.7% (n = 6,651) had high risk waist circumference and 77.0% (n = 21,593) had high risk waist-Hip ratio. The likelihood of CVD was 60%, 50%, and 34% significantly higher among older adults who were obese/overweight [Adjusted odds ratio (AOR): 1.60; CI: 1.48-1.72], had high risk waist circumference [AOR: 1.50; CI: 1.39-1.62] and high risk waist-Hip ratio [AOR: 1.34; CI: 1.25-1.44], respectively compared to older adults with normal BMI and those who do not have a high risk waist circumference and high risk waist hip ratio. Moreover, older adults who never did physical activity had 22 per cent higher risk of CVD than those who did frequent [AOR: 1.22; CI: 1.13-1.32] physical activity. CONCLUSION: The burden of overweight and obesity along with physical inactivity increases the risk of CVD in older adults. These findings highlight the urgent need for framing direct and indirect strategies to control obesity in order to reduce the burden of CVD among older adults in India.

Oleic acid as a restorative agent in alleviating adrenaline induced altered morphofunctional milieu of gastric tissue and mitochondria.

The role of oleic acid as a protective antioxidant has recently been recognized. The present study is aimed to explore whether oleic acid can afford protection to rat gastric tissue when challenged with adrenaline. Sixty adult healthy male albino rats were divided into 10 groups comprising of 6 animals each. First group constituted the control. Rats of the second group were injected sub-cutaneously with adrenaline bitartrate at the dose of 0.3mg/kg body weight, every day for a period of 17 days. Rats of the third, to the sixth groups were orally fed with different doses of oleic acid (2.5, 5, 10, 20 mg/kg body weight/day) respectively. The rats of seventh to tenth groups were orally fed with doses of oleic acid as mentioned above and subsequently injected with adrenaline bitartrate at 0.3mg/kg body weight sub-cutaneously. After the treatment period, the animals were euthanized through cervical dislocation following light ether anaesthesia and gastric tissues were collected for morphological and biochemical studies. Subcutaneously administered pharmacological dose of adrenaline bitartrate caused oxidative stress inducing gastric lesion in male albino rats as evident from the altered levels of biomarkers of oxidative stress, activities of antioxidant and mitochondrial enzymes related to energy metabolism with changes in tissue morphology. Pre-treatment of rats with oleic acid dose-dependently protected against these gastric injuries induced by adrenaline indicating the potentiality of oleic acid in protecting against adrenaline induced gastric injury in male albino rats where antioxidant mechanisms appear to play a pivotal role in mediating such protection.

Insights into the ameliorative effect of oleic acid in rejuvenating phenylhydrazine induced oxidative stress mediated morpho-functionally dismantled erythrocytes.

Phenylhydrazine (PHZ), an intermediate in the synthesis of fine chemicals is toxic for human health and environment. Despite of having severe detrimental effects on different physiological systems, exposure of erythrocytes to PHZ cause destruction of haemoglobin and membrane proteins leading to iron release and complete haemolysis of red blood cells (RBC). Involvement of oxidative stress behind such action triggers the urge for searching a potent antioxidant. The benefits of consuming olive oil is attributed to its 75% oleic acid (OA) content in average. Olive oil is the basic component of Mediterranean diet. Hence, OA has been chosen in our present in vitro study to explore its efficacy against PHZ (1 mM) induced alterations in erythrocytes. Four different concentrations of OA (0.01 nM, 0.02 nM, 0.04 nM and 0.06 nM) were primarily experimented with, among which 0.06 nM OA has shown to give maximal protection. This study demonstrates the capability of OA in preserving the morphology, intracellular antioxidant status and the activities of metabolic enzymes of RBCs that have been diminished by PHZ, through its antioxidant mechanisms. The results of the present study firmly establish OA as a promising antioxidant for conserving the health of erythrocyte from PHZ toxicity which indicate toward future possible use of OA either singly or in combination with other dietary components for protection of erythrocytes against PHZ induced toxic cellular changes.

Beta-estradiol protects against copper-ascorbate induced oxidative damage in goat liver mitochondria in vitro by binding with ascorbic acid.

AIMS: ß-Estradiol (ß-E), one of the chemical forms of female gonad hormone exhibited antioxidant efficacy in biochemical system, in vitro. The aim of the study was to investigate whether any other mechanism of protection by ß-E to hepatic mitochondria in presence of stressor agent i.e.,a combination of Cu2+ and ascorbic acid is involved. MAIN METHODS: Freshly prepared goat liver mitochondria was incubated with stressors and 1 µM ß-E and post incubated with the same concentration at 37 °C at pH 7.4. Mitochondrial viability, biomarkers of oxidative stress, activities of Krebs cycle enzymes, mitochondrial membrane potential, Ca2+ permeability were measured. Mitochondrial morphology and binding pattern of ß-E with stressors were also studied. KEY FINDINGS: Upon incubation of mitochondria with Cu, ascorbic acid and their combination there is a significant decline in activities of four of Krebs cycle enzymes in an uncompetitive manner with a concomitant increase in Ca2+ permeability and membrane potential of inner mitochondrial membrane, which is withdrawn during co-incubation with ß-E, but was not reversed during post incubation with the ß-E. The final studies on mitochondrial membrane morphology using scanning electron microscope also exhibited damage. Isothermal titration calorimetry data also showed the negative heat change in the mixture of ß-E with ascorbic acid and also its combination with Cu2+. SIGNIFICANCE: Our results for the first time demonstrated that ß-E protects againstCu2+-ascorbate induced oxidative stress by binding with ascorbic acid. The new mechanism of binding of ß-E with stress agents may have a future therapeutic relevance.