Effect of chronic treatment with a cyclooxygenase inhibitor on reproductive parameters in male rat

BACKGROUND: Indomethacin is a member of non-steroidal anti-inflammatory drugs (NSAIDs) commonly used for treatment of gout, arthritis, and other inflammatory conditions. It has been shown to inhibit ovarian prostaglandins synthesis in mammals, birds, fish and reptiles. However, the effects of its chronic administration on male reproductive functions remain largely unknown. Using rat as a model, we studied the effect of chronic treatment with indomethacin on the male reproductive system. METHODS: Testosterone was measured in the serum, testicular tissue, and testicular interstitial fluid by radioimmunoassay. Moreover, we also studied the direct effect of indomethacin in vitro on luteinizing hormone stimulated testosterone secretion from the Leydig cells isolated from various treatment groups. RESULTS: Indomethacin treatment for 50 days caused a significant but reversible decrease in prostate weight, epididymal sperm reserves and sperm motility score compared with control rats (p \u3c 0.05). In vitro stimulation of Leydig cells isolated from treated rat\u27s testes with luteinizing hormone (250 microIU) produced significantly reduced testosterone compared with cells from control groups (p \u3c 0.05). Furthermore, stimulatory effect of luteinizing hormone on the control Leydig cells was significantly reduced when these cells were challenged with luteinizing hormone in the presence of indomethacin, (p \u3c 0.05). Testosterone concentration in the testicular tissue and testicular interstitial fluid reduced after indomethacin treatment (p \u3c 0.05). CONCLUSION: Due to its significant inhibition of key reproductive hormones, indomethacin effectively inhibits reproductive functions if used on a long-term basis. In his study, we have identified potential risks in the long-term use ofcyclooxygenase inhibitors

Thermal Characterization of Purified Glucose Oxidase from A Newly Isolated Aspergillus Niger UAF-1

An intracellular glucose oxidase was isolated from the mycelium extract of a locally isolated strain of Aspergillus niger UAF-1. The enzyme was purified to a yield of 28.43% and specific activity of 135 U mg−1 through ammonium sulfate precipitation, anion exchange and gel filtration chromatography. The enzyme showed high affinity for D-glucose with a Km value of 2.56 mM. The enzyme exhibited optimum catalytic activity at pH 5.5. Temperature optimum for glucose oxidase, catalyzed D-glucose oxidation was 40°C. The enzyme showed a high thermostability having a half-life 30 min, enthalpy of denaturation 99.66 kJ mol−1 and free energy of denaturation 103.63 kJ mol−1. These characteristics suggest the use of glucose oxidase from Aspergillus niger UAF-1 as an analytical reagent and in the design of biosensors for clinical, biochemical and diagnostic assays

Diabetes Prevalence Survey of Pakistan (DPS-PAK): prevalence of type 2 diabetes mellitus and prediabetes using HbA1c: a population-based survey from Pakistan

Objectives: We conducted a Pakistan-wide community-based survey on the prevalence of type 2 diabetes using glycated haemoglobin (HbA1c) as the screening test. The aim was to estimate diabetes prevalence across different demographic groups as well as all regions of Pakistan. Design, settings and participants: Multistaged stratified cluster sampling was used for the representative selection of people aged ≥20 years, residing in 378 sampled clusters of 16 randomly selected districts, in this cross-sectional study. Eligible participants had blood drawn for HbA1c analyses at field clinics near to their homes. The oral glucose tolerance test (OGTT) was conducted on a subsample of the participants. Overall and stratified prevalence of type 2 diabetes and its association with risk factors were estimated using logistic regression models. Main outcome measures: Prevalence of prediabetes and type 2 diabetes. Results: Of 18 856 eligible participants the prevalence of prediabetes was 10.91% (95% CI 10.46 to 11.36, n=2057) and type 2 diabetes was 16.98% (95% CI 16.44 to 17.51, n=3201). Overall, the mean HbA1c level was 5.62% (SD 1.96), and among newly diagnosed was 8.56% (SD 2.08). The prevalence was highest in age 51–60 years (26.03%, p\u3c0.001), no formal education (17.66%, p\u3c0.001), class III obese (35.09%, p\u3c0.001), family history (31.29%, p\u3c0.001) and female (17.80%, p=0.009). On multivariate analysis, there was a significant association between type 2 diabetes and older age, increase in body mass index and central obesity, positive family history, and having hypertension and an inverse relation with education as a categorical variable. On a subsample (n=1027), summary statistics for diagnosis of diabetes on HbA1c showed a sensitivity of 84.7%, specificity of 87.2% and area under the receiver operating characteristic curve 0.86, compared with OGTT. Conclusions: The prevalence of type 2 diabetes and prediabetes is much higher than previously thought in Pakistan. Comprehensive strategies need to be developed to incorporate screening, prevention and treatment of type 2 diabetes at a community level

Diabetes Prevalence Survey of Pakistan (DPS-PAK): prevalence of type 2 diabetes mellitus and prediabetes using HbA1c: a population-based survey from Pakistan

Objectives: We conducted a Pakistan-wide community-based survey on the prevalence of type 2 diabetes using glycated haemoglobin (HbA1c) as the screening test. The aim was to estimate diabetes prevalence across different demographic groups as well as all regions of Pakistan. Design, settings and participants: Multistaged stratified cluster sampling was used for the representative selection of people aged ≥20 years, residing in 378 sampled clusters of 16 randomly selected districts, in this cross-sectional study. Eligible participants had blood drawn for HbA1c analyses at field clinics near to their homes. The oral glucose tolerance test (OGTT) was conducted on a subsample of the participants. Overall and stratified prevalence of type 2 diabetes and its association with risk factors were estimated using logistic regression models. Main outcome measures: Prevalence of prediabetes and type 2 diabetes. Results: Of 18 856 eligible participants the prevalence of prediabetes was 10.91% (95% CI 10.46 to 11.36, n=2057) and type 2 diabetes was 16.98% (95% CI 16.44 to 17.51, n=3201). Overall, the mean HbA1c level was 5.62% (SD 1.96), and among newly diagnosed was 8.56% (SD 2.08). The prevalence was highest in age 51–60 years (26.03%, p<0.001), no formal education (17.66%, p<0.001), class III obese (35.09%, p<0.001), family history (31.29%, p<0.001) and female (17.80%, p=0.009). On multivariate analysis, there was a significant association between type 2 diabetes and older age, increase in body mass index and central obesity, positive family history, and having hypertension and an inverse relation with education as a categorical variable. On a subsample (n=1027), summary statistics for diagnosis of diabetes on HbA1c showed a sensitivity of 84.7%, specificity of 87.2% and area under the receiver operating characteristic curve 0.86, compared with OGTT. Conclusions: The prevalence of type 2 diabetes and prediabetes is much higher than previously thought in Pakistan. Comprehensive strategies need to be developed to incorporate screening, prevention and treatment of type 2 diabetes at a community level

Origanum majorana L. polyphenols: in vivo antiepileptic effect, in silico evaluation of their bioavailability, and interaction with the NMDA receptor

Introduction: Epilepsy is a chronic brain disease characterized by repeated seizures and caused by excessive glutamate receptor activation. Many plants are traditionally used in the treatment of this disease. This study aimed to evaluate the bioavailability of a polyphenolic extract obtained from Origanum majorana L. (OMP) leaves, as well as its antiepileptic activity and its potential mechanism of action.Methods: We have developed and validated a simple, rapid, and accurate stability-indicating reversed-phase liquid chromatographic method for the simultaneous determination of caffeine and quercetin in rat plasma. The OMP antiepileptic effect was evaluated with pilocarpine-induced seizures, and a docking method was used to determine the possible interaction between caffeic acid and quercetin with the N-methyl-D-aspartate (NMDA) receptor.Results and Discussion: Both compounds tested showed low bioavailability in unchanged form. However, the tested extract showed an anticonvulsant effect due to the considerably delayed onset of seizures in the pilocarpine model at a dose of 100 mg/kg. The molecular docking proved a high-affinity interaction between the caffeic acid and quercetin with the NMDA receptor. Taken together, OLP polyphenols demonstrated good antiepileptic activity, probably due to the interaction of quercetin, caffeic acid, or their metabolites with the NMDA receptor

Vitamin D Levels in Asymptomatic Adults-A Population Survey in Karachi, Pakistan

Background: It is well established that low levels of 25(OH) Vitamin D (/dL) are a common finding world over, affecting over a billion of the global population. Our primary objective was to determine the prevalence of vitamin D deficiency and insufficiency in the asymptomatic adult population of Karachi, Pakistan and the demographic, nutritional and co-morbidity characteristics associated with serum vitamin D levels. Methods: A cross-sectional population survey was conducted at two spaced out densely populated areas of the city. Serum levels of 25OH vitamin D were measured and GFR as renal function was assessed by using 4 variable MDRD formula. Results: Our sample of 300 had a median age of 48(interquartile range 38-55) years. The median level of serum vitamin D was 18.8 (IQ range 12.65-24.62) ng/dL. A total of 253 (84.3%) respondents had low levels (/dL) of 25OH vitamin D. Serum PTH and vitamin D were negatively correlated (r = -0.176, p = 0.001). The median PTH in the vitamin D sufficiency group was 38.4 (IQ range28.0-48.8)pg/mL compared with 44.4 (IQ range 34.3-56.8) pg/mL in the deficiency group (p = 0.011).The median serum calcium level in the sample was 9.46(IQ range 9.18-9.68) ng/dL. Low serum levels of vitamin D were not associated with hypertension (p = 0.771) or with an elevated spot blood pressure (p = 0.164).In our sample 75(26%) respondents had an eGFR corresponding to stage 2 and stage 3 CKD. There was no significant correlation between levels of vitamin D and eGFR (r = -0.127, p-value = 0.277). Respondents using daily vitamin D supplements had higher 25 OH vitamin D levels (p-value = 0.021). Conclusion: We observed a high proportion of the asymptomatic adult population having low levels of vitamin D and subclinical deterioration of eGFR. The specific cause(s) for this observed high prevalence of low 25OH vitamin D levels are not clear and need to be investigated further upon

Firm performance, corporate governance and executive compensation in Pakistan

yesThis study examines the effects of firm performance and corporate governance on chief executive officer (CEO) compensation in an emerging market, Pakistan. Using a more robust Generalized Method of Moments (GMM) estimation approach for a sample of non-financial firms listed at Karachi Stock Exchange (KSE) over the period 2005 to 2012, we find that both current and previous year accounting performance has positive influence on CEO compensation. However, stock market performance does not appear to have a positive impact on executive compensation. We further find that ownership concentration is positively related with CEO compensation, indicating some kind of collusion between management and largest shareholder to get personal benefits. Inconsistent with agency theory, CEO duality appears to have a negative influence, while board size and board independence have no convincing relationship with CEO compensation, indicating board ineffectiveness in reducing CEO entrenchment. The results of dynamic GMM model suggest that CEO pay is highly persistent and takes time to adjust to long-run equilibrium

Prevalence of HCV and HIV infections in 2005-Earthquake-affected areas of Pakistan

<p>Abstract</p> <p>Background</p> <p>On October 8, 2005, an earthquake of magnitude 7.6 hit the Northern parts of Pakistan. In the post-earthquake scenario, overcrowding, improper sewage disposal, contamination of food and drinking water, hasty surgical procedures, and unscreened blood transfusions to earthquake victims most likely promotes the spread of infections already prevalent in the area.</p> <p>Objective</p> <p>The objective of the study reported here was to determine the prevalence of Human Immunodeficiency and Hepatitis C viruses (respectively, HIV and HCV) in the earthquake-affected communities of Pakistan. The samples were analyzed 2 months and then again 11 months after the earthquake to estimate the burden of HIV and HCV in these areas, and to determine any rise in the prevalence of these viral infections as a result of the earthquake.</p> <p>Methods</p> <p>Blood samples were initially collected during December, 2005 to March 2006, from 245 inhabitants of the earthquake-affected areas. These samples were screened for HCV and HIV, using immunochromatography and Enzyme-Linked Immuno-Sorbent Assay (ELISA).</p> <p>Results</p> <p>Out of 245 samples tested, 8 (3.26%) were found positive for HCV, and 0 (0.0%) for HIV, indicating the existence of HCV infection in the earthquake-stricken areas. The same methods were used to analyze the samples collected in the second round of screening in the same area, in September, 2006 – 11 months after the earthquake. This time 290 blood samples were collected, out of which 16 (5.51%) samples were positive for HCV, and 0 for HIV.</p> <p>Conclusion</p> <p>A slightly higher prevalence of HCV was recorded 11 months after the earthquake; this increase, however, was not statistically significant. None of the study participants was found HIV-infected.</p

Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI

Mental distress links with physical activities, sedentary lifestyle, social support, and sleep problems: A Syrian population cross-sectional study

BackgroundMental diseases are very widespread and difficult to treat, affecting around 12% of the global population in 2019. Since social interaction is crucial to human existence and loneliness has been proven to be a significant predictor of depressive symptoms, it stands to reason that social connection problems would also contribute to depression. Physical inactivity seems to weaken and aggravate insulin tolerance alterations, glucose homeostasis, and plasma triglyceride levels, thereby influencing one's mood and happiness. This suggests that physical inactivity may be a significant risk factor for mental illness. This research contributes to our understanding of the mental health situation in Syria by exploring associations between a set of measurable characteristics that may be adjusted.MethodsAn online quantitative cross-sectional study was conducted between March and April 2022 in Syria, using a structured questionnaire that assesses data on behaviors of health, health in general, wellbeing, and adult population quality of life.ResultsAmong 1,224 respondents (371 men and 853 women), women have shown higher levels of mental distress, sleep issues, low engagement in structured activities, and a difficult work environment than men. Women experiencing mental anguish have reported being more sedentary, participating in less scheduled activities, and receiving less social support.ConclusionsThere are observable connections between high sedentary time and women experiencing mental distress. The mental health of Syrian women in distress was associated with a lack of participation in both organized activities and physical exercise in their free time. Furthermore, sleep issues and financial troubles were seen in persons with mental diseases of both males and females