IN VIVO ANTIOXIDANT AND HEPATOPROTECTIVE EFFECTS OF HUGONIA MYSTAX IN PARACETAMOL INDUCED HEPATOTOXICITY IN RATS.

Objectives: The objective of the present work is to study the in vivo anti-oxidant and hepatoprotective effects of Hugonia mystax in paracetamol (PCM)induced hepatotoxicity in rats.Methods: The in vivo anti-oxidant activity of 70% ethanol extract of leaves of H. mystax (HMEE) was assessed by determining the tissue glutathioneand lipid peroxidation (LPO) levels. HMEE 200 and 400 mg/kg p.o. doses and silymarin p.o.100 mg/kg were administered to the PCM challengedrats. The effect of HMEE and silymarin on physical (liver weight and liver volume) and biochemical parameters (serum enzymes [serum glutamicoxaloacetic transaminase (SGOT) and serum glutamate-pyruvate transaminase (SGPT)], alkaline phosphate [ALP], and bilirubin) were measured.Furthermore, histopathological changes in the liver were studied.Results: The HMEE showed in the vivo anti-oxidant activity. Pre-treatment with HMEE for 7 days significantly reduced the elevated biochemicalparameters (SGOT, SGPT, ALP, and bilirubin levels). The hepatic damage in animal pretreated with HMEE was minimal with distinct preservation ofstructures and architectural frame of the hepatic cells.Conclusion: These findings demonstrate the protective nature of HMEE against PCMKeywords: Hugonia mystax, Hepatoprotective, In vivo anti-oxidant, Paracetamol

Assay of phospholipases A2 and their inhibitors by kinetic analysis in the scooting mode

Several cellular processes are regulated by interfacial catalysis on biomembrane surfaces. Phospholipases A2 (PLA2) are interesting not only as prototypes for interfacial catalysis, but also because they mobilize precursors for the biosynthesis of eicosanoids and platelet activating factor, and these agents ultimately control a wide range of secretory and inflammatory processes. Since PLA2 carry out their catalytic function at membrane surfaces, the kinetics of these enzymes depends on what the enzyme ‘sees’ at the interface, and thus the observed rate is profoundly influenced by the organization and dynamics of the lipidwater interface (‘quality of the interface’). In this review we elaborate the advantages of monitoring interfacial catalysis in the scooting mode, that is, under the conditions where the enzyme remains bound to vesicles for several thousand catalytic turnover cycles. Such a highly processive catalytic turnover in the scooting mode is useful for a rigorous and quantitative characterization of the kinetics of interfacial catalysis. This analysis is now extended to provide insights into designing strategy for PLA2 assays and screens for their inhibitors

Monocrotophos Induced Apoptosis in PC12 Cells: Role of Xenobiotic Metabolizing Cytochrome P450s

Monocrotophos (MCP) is a widely used organophosphate (OP) pesticide. We studied apoptotic changes and their correlation with expression of selected cytochrome P450s (CYPs) in PC12 cells exposed to MCP. A significant induction in reactive oxygen species (ROS) and decrease in glutathione (GSH) levels were observed in cells exposed to MCP. Following the exposure of PC12 cells to MCP (10−5 M), the levels of protein and mRNA expressions of caspase-3/9, Bax, Bcl2, P53, P21, GSTP1-1 were significantly upregulated, whereas the levels of Bclw, Mcl1 were downregulated. A significant induction in the expression of CYP1A1/1A2, 2B1/2B2, 2E1 was also observed in PC12 cells exposed to MCP (10−5 M), whereas induction of CYPs was insignificant in cells exposed to 10−6 M concentration of MCP. We believe that this is the first report showing altered expressions of selected CYPs in MCP-induced apoptosis in PC12 cells. These apoptotic changes were mitochondria mediated and regulated by caspase cascade. Our data confirm the involvement of specific CYPs in MCP-induced apoptosis in PC12 cells and also identifies possible cellular and molecular mechanisms of organophosphate pesticide-induced apoptosis in neuronal cells

Functional outcome of hybrid external fixator in proximal tibial fractures Schatzker type V and VI with Gustillo grade-II

Background: Management of high energy tibial plateau fractures along with extensive soft tissue damage is still challenging to many orthopaedic surgeons. This study evaluates the purpose of hybrid external fixator intreating high energy tibial plateau fractures with minimal invasion and accurate reduction.Methods: Twenty patients with high energy Schatzker type V and VI tibial plateau fractures with severe soft tissue injury were enrolled into the study in RNT medical college, Udaipur.Results: The results- bony union, range of movements and associated complications were assessed. All fractures united in an average time period of 20 weeks. Ten patients developed knee stiffness, five patients developed delayed union andthreenon-union.15 patients required split skin graft. Final outcome showed excellent score in 53 patients.Conclusions: Hybrid external fixation is a safe option for managing complex high energy tibial plateau fractures by simultaneously providing adequate fracture stabilization and necessary protection to soft tissue healing to achieve bony union

Immunomodulatory potential of a bioactive fraction from the leaves of Phyllostachys bambusoides (Bamboo) in Balb/c mice

In order to evaluate the role of ethyl acetate fraction (PB-EtAC) obtained from the Phyllostachys bambusoides leaves in the modulation of immune responses, detailed studies were carried out using a panel of in vivo assays. Oral administration of PB-EtAC (50–200 mg/Kg) stimulated the IgM and IgG titre expressed in the form of haemagglutination antibody (HA) titre. Further, it elicited a dose related increase in the delayed type hypersensitivity reaction (DTH) after 24 and 48 h in BALB/c mice. Besides augmenting the humoral and cell mediated immune response, the concentration of cytokines (IFN-γ, IL-2, and IL-4) in serum with respect to T cell interactions also increased significantly. It also induced macrophage phagocytosis, and nitric oxide (NO) production which resulted in a high degree of protection against Candida albicans and carbon clearance. Moreover, the enhancement in CD4 and CD8 cell populations as revealed by flow cytometry. Taken together this in vivo and ex vivo preclinical data, our results suggested that PB-EtAC acts as an effective immunostimulator eliciting both Th1 and Th2 immune responses. We are reporting first time the immunostimulatory potential of P. bambusoides and it might be regarded as a biological response modifier

Neoadjuvant chemotherapy or chemoradiotherapy in head and neck cancer

The multidisciplinary approach to treating squamous cell carcinoma of the head and neck is complex and evolving. Chemotherapy is increasingly being incorporated into the treatment of squamous cell carcinoma of the head and neck. Previously, radiotherapy following surgery was the standard approach to the treatment of loco regionally advanced resectable disease. Data from randomized trials have confirmed the benefits of concurrent chemo radiotherapy in the adjuvant setting. Chemo radiotherapy is also the recommended approach for unresectable disease. Advanced loco regional disease is the most frequent clinical situation in Head and Neck cancer. The standard of care for most clinicians is a multidisciplinary treatment with concomitant chemotherapy plus radiotherapy (CRT). However, retrospective studies have shown that in patients treated with CRT there was a relative increase in systemic relapse due to a lack of systemic control. For this reason a renewed interest has appeared for the incorporation of induction chemotherapy in the treatment of locally advanced Head and Neck Cancer. Furthermore new combination regimens with taxanes have shown to be more active than the classical cisplatin and 5-fluorouracil induction regimen. Novel targeted agents, such as epidermal growth factor receptor antagonists, are showing promise in the treatment of patients with both loco regionally advanced and recurrent/metastatic squamous cell carcinoma of the head and neck

Patterns of migration/mobility and HIV risk among female sex workers: Andhra Pradesh 2007-08

This report presents the findings from the female sex workers study in Andhra Pradesh, India implemented by TNS India Private Limited and the Population Council in New Delhi. Specifically the study was undertaken to assess the volume and patterns of mobility of female sex workers; to describe the characteristics of mobile female sex workers; and too examine the determinants of HIV risk among female sex workers, with particular emphasis on mobility-related characteristics. The report concludes that targeting such highly mobile female sex workers in intervention programs requires a comprehensive understanding of their places of solicitation and sex. Female sex workers who move frequently to different places and who visit other areas for a short time are at greater risk of HIV, and special efforts are needed in HIV-prevention programs to address the needs of such workers

Clinical and functional outcome of isolated posterior cruciate ligament avulsion fractures treated by open reduction and internal fixation

Background: PCL ligament avulsion fracture injuries constitute about 3-20% of all the knee injuries. Isolated posterior cruciate ligament injuries are uncommon and often go undiagnosed in acutely injured knees. fracture. In the long run they cause severe functional disability of the knee joint. There is no consensus concerning the optimal surgical treatment approach for these injuries. Our study was to assess the functional and clinical outcome of isolated PCL avulsion fractures with open reduction and internal fixation.Methods: This is a prospective study of 27 patients with isolated PCL avulsion fractures, done in the department of orthopaedics in RNT medical college over a 2-year period. All were treated with open reduction and internal fixation with 4 mm cannulated cancellous screw and washer. Postoperatively, patient leg was immobilized in posterior POP slab for 2 weeks, allowing toe touch weight bearing. All patients were regularly followed-up. 3 cases of post operative wound infection were detected.Results: Of the 27 patients, there were 19 males and 8 females. All the cases showed good fracture union in an average of 12 weeks post operatively. In the first 6 weeks, all of them acquired an average knee flexion of 90 degrees and by 3 months, all of them had 125 degrees of free flexion possible.2 cases showed negative posterior draw sign. The knee scoring system assessment showed 21 cases of excellent result, 4 cases of good result and 2 cases of fair result.Conclusions: Though rare, PCL avulsion fractured are to be managed properly and treated surgically. PCL tibial avulsion fractures treated through Burk and Schaffer approach with open reduction and internal fixation produces good results

Patterns of migration/mobility and HIV risk among female sex workers: Maharashtra 2007-08

According to recent estimates, Maharashtra, India recorded high HIV prevalence among female sex workers, however there is a dearth of research documenting the migration patterns of sex workers and the linkages between their mobility and vulnerability to HIV. This Population Council study attempts to answer some of the questions on mobility and migration of female sex workers in Maharashtra as they relate to the HIV epidemic. Findings show an association between degree of mobility and the indicators of HIV risk such as consistent condom use with different types of partners, STI symptoms reported, sexual violence, and self-perception of risk for HIV. Targeting such a highly mobile population of female sex workers who appear to be vulnerable to HIV requires a comprehensive understanding of their places of solicitation and sex. Programs that want to ensure better coverage of their interventions should focus on five major places: brothels, railway/bus stations, dhabas, bars, and hotels/lodges

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic