15-deoxy-delta 12, 14-Prostaglandin J(2 )prevents reactive oxygen species generation and mitochondrial membrane depolarization induced by oxidative stress

BACKGROUND: With the use of cultured human retinal pigment epithelial cells, we have previously described a number of cellular responses to oxidative stress caused by H(2)O(2). We also demonstrated that the cytotoxicity caused by H(2)O(2 )could be prevented by the prostaglandin derivative, 15-deoxy-delta 12, 14-Prostaglandin J(2 )(15d-PGJ(2)). RESULTS: Further characterization of the experimental system indicated that the half-life of H(2)O(2 )in cultures was ~1 hour. At a fixed H(2)O(2 )concentration, the cytotoxicity was dependent on the volume of H(2)O(2 )solution used in the culture, such that higher volume caused more cytotoxicity. Most cells were committed to die if the culture was treated for 2 hours with a cytotoxic concentration of H(2)O(2). The prostaglandin derivative, 15d-PGJ(2), could prevent oxidative damage caused by t-butyl hydroperoxide, in addition to H(2)O(2). Further studies indicated that both H(2)O(2 )and tBH caused an increase in reactive oxygen species and depolarization of mitochondrial membrane potential. Pretreatment of cells with 1 μM 15d-PGJ(2 )led to a modest decrease in reactive oxygen species generation, and a significant restoration of mitochondrial membrane potential. CONCLUSION: This agent may be used in the future as a pharmacological tool for preventing cellular damage caused by oxidative stress

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Microbicides for the Treatment of Sexually Transmitted HIV Infections

Approximately 34 million people were living with human immunodeficiency virus (HIV-1) at the end of 2011. From the last two decades, researchers are actively involved in the development of an effective HIV-1 treatment, but the results intended are still doubtful about the eradication of HIV. The HIV-1 virus has gone from being an “inherently untreatable” infectious agent to the one liable to be affected by a range of approved therapies. Candidate microbicides have been developed to target specific steps in the process of viral transmission. Microbicides are self-administered agents that can be applied to vaginal or rectal mucosal surfaces with the aim of preventing, or reducing, the transmission of sexually transmitted infections (STIs) including HIV-1. The development of efficient, widely available, and low-cost microbicides to prevent sexually transmitted HIV infections should be given high priority. In this review, we studied the various forms of microbicides, their mechanism of action, and their abundant approaches to control the transmission of sexually transmitted infections (STIs)

Basking behavior, sweating and thermal ecology of the Indian tree frog, Polypedates maculatus

We reported previously that Indian free frogs, Polypedates maculatus, periodically wipe themselves with mucus-borne lipids secreted from cutaneous mucous glands. When dried, these skin secretions decrease water loss but provide only modest resistance to cutaneous evaporation when compared with lipid barriers of so-called "waterproof" species of tree frogs. Aqueous mucous secretions also allow frogs to increase evaporative water loss when they are expelled repetitively during sweating. In P. maculatus, spontaneous sweating of mucous secretions was shown to begin at threshold body temperatures of approximately 30 C, compared with 39-40 C in the waterproof species. Here we report that Indian tree frogs voluntarily tolerate body temperatures in the range 28-38 C when they are normally hydrated and exposed to direct sunlight. In contrast, dehydrated tree frogs (approximately 16% of body mass) avoid direct sunlight when body temperatures increase above the 30 C threshold for sweating. Basking tree frogs respond to thermal stress by sweating, panting, and adopting lighter skin coloration, with the result that body temperatures are maintained 10-15 C lower than equilibrial temperatures of a dry model frog in sunlight. Both field and laboratory observations suggest that during periods of combined heat and drought, P. maculatus secludes itself in sheltered microenvironments where body temperature equilibrates below 30 C to avoid rapid losses of water to thermally induced sweating. This behavior contrasts with that of the "waterproof" anuran species which remain more exposed and tolerate considerably higher body temperatures without sweating

A Prospective Observational Study of Clinicopathological and Biochemical Profile of Patients with Cholecystitis Visiting a Teaching Tertiary Care Centre of Haryana

Introduction Gallstone diseases constitute a major part of patients visiting hospitals, and more than 50% of operation theaters are occupied by it or diseases related to it. It also imposes significant financial burden on health resources. The 21st century has opened with an improved foundation to our understanding of the basis of bile formation by defining the key transporters of the lipids in bile and the responsible genes. The specter of obesity as an epidemic in developed countries, and the recent recognition of the metabolic syndromes and their links to gallstone formation, emphasize the expectation of a rise in the frequency of cholesterol cholelithiasis. Materials and Methods Data pertaining to patients who were admitted/received surgery for a diagnosis of gallstone diseases at the Department of General Surgery of BPS GMC Khanpur Kalan was collected. The collected data was entered in a Microsoft Excel spreadsheet. Mean ± standard deviation (SD) was calculated for quantitative data, using Student’s “t” test/Kruskal test. Chi-square test was used to find out the association for categorical data. Results and Discussion Most of the patients were experiencing right hypochondriac pain (79.23%) as presenting complaints, with the most common age range being 31 to 40 years, followed by 41 to 50 years, that is, 31.85% and 20.74%, respectively. Females were most commonly affected, approximately 90%, and only 10% of patients with gallstones visiting our hospital were males. Maximum patients had chronic cholecystitis (80%) on histopathological examination, followed by cholesterosis (6.15%). As much as 82.6% of patients presented with mixed gallstones, followed by cholesterol stones, that is, 10.43%. All types of stones are more common in patients with abdominal adiposities, that is, having waist-to-hip ratio more than 0.85, and these findings are statistically significant. Conclusion Our study concluded that gallstones were more common in females of younger population (31–40 years) with right hypochondriac pain as presenting complaints. The most common histopathology was chronic cholecystitis with mixed types of stones, which is associated with increased waist-to-hip ratio. All biochemical markers were within normal range