Modulation of Antioxidant Enzyme Expression and Activity by Paraquat in Renal Epithelial NRK-52E Cells

Renal toxicity produced by paraquat involves the generation of reactive oxygen species (ROS) which can overwhelm antioxidant defences, leading to oxidant injury. However, there are conflicting reports regarding the activity and/or expression of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) during oxidative stress injury. This study investigated the activity and expression of these enzymes in a renal epithelial cell line following exposure to paraquat. Confluent NRK-52E cells were incubated with increasing concentrations of paraquat (1-100mM) for up to 24 hours. Renal cell death was determined by measurement of lactate dehydrogenase release. Oxidant damage was determined via measurement of malondialdehyde formation and DNA strand breaks. The effects of paraquat on DNA and de novo protein synthesis were determined using radio-labelled thymidine and leucine respectively. ROS generation (superoxide anion and hydroxyl radical formation) was measured using nitro-bluetetrazolium and deoxyribose assays. Antioxidant enzyme activities and expression were measured using established biochemical assays and Western blot analysis. Exposure of confluent NRK-52E cells to paraquat resulted in significant cell death involving increased lipid peroxidation, DNA damage and inhibition of DNA and de novo protein synthesis. Renal cell injury and death were secondary to increased ROS generation. Incubation with paraquat reduced SOD and CAT activities; in contrast, GSH-Px activity increased significantly. Although SOD expression was significantly reduced, catalase expression was unaffected. These results indicate that paraquat mediates renal toxicity via oxidative stress involving both an increase in ROS generation and reductions in SOD and CAT activities with a concomitant reduction in SOD expression

Novel Superoxide Dismutase Mimetics for Protection against Paraquat-induced Acute Renal Injury

Paraquat-induced nephrotoxicity involves severe renal damage caused by reactive oxygen species (ROS), specifically by increasing superoxide (O2●-) generation in the kidney. While proven to be of benefit in animal models of organ injury involving O2●-, superoxide dismutase (SOD) and superoxide dismutase mimetics (SODm) can suffer problems regarding their bioavailability and toxicity. Since ROS has been incriminated in the pathogenesis of several disease conditions including acute kidney injury, the search for ideal SODm therefore continues unabated. Thus, the current study aims at investigating the therapeutic potential of Manganese (II) complexes of ethylenebis (oxyethylenenitrilo) tetraacetic acid (EGTA) and ethylenebis hydroxyphenylglycine (EHPG), novel SODm, against paraquat-induced nephrotoxicity using an in vivo rodent model. Administration of a single intraperitoneal dose of 10-50 or 100 mg/kg paraquat to male Wistar rats (200-250g) produced acute kidney injury within 48 and 24 hours respectively; as evidenced by a significant increase in serum creatinine, fractional excretion of sodium and a reduction in creatinine clearance. Unlike Mn (II)-EGTA (2mg/kg), Mn (II)-EHPG (4mg/kg) was able to significantly attenuate the acute kidney injury induced by 10-50 mg/kg paraquat. These complexes were not toxic at the doses examined unlike SOD or conventional SODm which can display pro-oxidant actions at higher concentrations. Since the clinical toxicity profiles of EGTA and EHPG are already known, these novel SODm particularly Mn (II)-EHPG could be beneficial in attenuating disease conditions involving ROS generation. Keywords: Acute kidney injury, Oxidative stress, Paraquat, Superoxide anion, Superoxide dismutase mimetic

Prevalence of Tobacco Use and Physical Activity among Adult Sierra Leonean Population

The current burden of non-communicable diseases (NCDs) and their risk factors such as tobacco use and physical inactivity remain largely unknown in Sierra Leone. Thus, this study was conducted to document the prevalence of tobacco use and physical activity among the adult Sierra Leonean population with a specific objective of determining the sex and age prevalence. A cross sectional population based survey utilising the multi-stage cluster sampling strategy was used. A total of 5,483 individuals aged 25-64 years of both sexes were recruited into the survey. The World Health Organisation (WHO) STEPwise approach to surveillance instrument was adapted and questionnaire was administered to one individual in selected household. The data was analysed and graphed using Epi-Info software version 3.4.3 and graph pad prism version 5.1 respectively. The analyses showed that 34% of the respondents use tobacco products with 26% engaged in smoking tobacco products and 8% were smokeless tobacco users at the time of this study. The average age of commencing tobacco smoking was 21 years; with 92% and 96% of the male and female daily smokers smoking at least six manufactured tobacco respectively. Seventy four percent (74%) and 69% of the non-smoking respondents were exposed to environmental tobacco smoke (ETS) at home and workplace respectively. The study further revealed that 15%, 23% and 87% of the total respondents reported no work-, transport- or recreational- related physical activity respectively; and were therefore classified as physically inactive. The lowest level of physical activity was reported in the recreation domain. Even those who reported moderate physical activity at work or from travel, their median metabolic equivalent (MET) was not sufficient to achieve a level of physical activity that is beneficial to their health. In conclusion, a significant proportion of the population is exposed either directly or indirectly to tobacco smoke, and a large proportion of the adult population is physically inactivity. Thus, NCD prevention policy addressing lifestyle changes such as no smoking should not be limited to work places but should be population based. Keywords: Non-communicable diseases, Physical activity, Risk factors, Sierra Leone, Tobacc

ACUTE TOXICITY STUDIES AND ANTIDOTAL THERAPY OF ETHANOL EXTRACT OF JATROPHA CURCAS SEEDS IN EXPERIMENTAL ANIMALS

In spite of the myriad of ethno medical uses and agro-feed potential of Jatropha curcas (JC) seeds and the potential for production of biodiesel, toxic properties have been adduced to the plant, especially the seeds. Thus, the current study was done with the aim of investigating the toxicity of the ethanol seed extract of JC in rats, mice, and chicks; and also to use conventional antidotes to treat intoxication in rats due to JC poisoning.The LD50 of the ethanol extract of the JC seed was determined by the method initially described by Lorke. In addition, acute behavioral and CNS toxicity studies of JC including antidotal therapy against JC poisoning were done. The data was analysed using SPSS and results were expressed as mean ± SEM. p < 0.05 was considered significant.The LD50 of IPJC extract ranged from 177.48 to 288.53 mg/kg (moderately toxic) for the adult female rat, adult male mouse, and young male rat. For the adult male rats, the LD50 values were 565.69 mg/kg (IP, slightly toxic) and >5000 mg/kg (oral, slightly toxic) and the LD50 of the JC extract for the chicks was 28.28 mg/kg (IP, highly toxic). JC produced a fairly dose-dependent behavioral and CNS depressant effects which were reduced by atropine, EDTA and a combination of atropine, sodium nitrite & sodium thiosulphate, and EDTA. Also, these antidotes either singly or in combination reduced mortality among the rats by 25-50%.In conclusion, the ethanol extract of JC seeds produces behavioral changes in experimental animals possibly in part by CNS depression which were ameliorated by atropine or EDTA and a combination of antidotes. Thus, these antidotes particularly atropine, may be exploited in the management of JC poisoning

A cross-sectional study on caregivers' perspective of the quality of life and adherence of paediatric HIV patients to highly active antiretroviral therapy.

BACKGROUND:Poor compliance to highly active antiretroviral therapy (HAART) can result in the poor quality of life in children living with Human immunodeficiency virus/Acquired immunodeficiency syndrome (HIV/AIDS) because of low plasma drug concentration and the possibility of drug resistance. This study evaluates the response of caregivers for determination of adherence and the four quality of life domains in children (aged 14 years and under) on HAART. METHODS:We conducted a cross-sectional study of 188 children, each accompanied by their caregivers at Ola During Children's Hospital and Makeni Government Hospital between September and November 2016. Adherence to HAART and Quality of life was assessed using the WHO Quality of life summary questionnaire (WHOQOL-BREF). We obtained ethical approval from the Sierra Leone Ethics and Scientific Review Committee. RESULTS:The study revealed 5.9% adherence amongst paediatric patients, and a strong association of adherent patients(p = 0.019*) to the physical health domain (mean = 64.61 SD = 8.1). Caregiver HIV status showed a strong association with the physical (mean = 58.3, SD = 11.7 and p = 0.024*), and psychological health domains (mean = 68.2, SD = 14.7 and p = 0.001). Caregiver type (mother/father/sibling) accompanying child to hospital also showed strong associated with the physical (mean = 58.0, SD = 10.6, p <  0.001), psychological (mean 68.2 SD = 14.81 p <  0.001) and environmental health domains (mean = 59.7, SD = 13.47, p <  0.001). Further regression analysis showed a strong association with physical health domain for HIV positive caregivers (p = 0.014) and adherent paediatric patients (p = 0.005). Nuclear family also showed a strong association with psychological (p <  0.001) and environmental (p = 0.001) health domains. CONCLUSION:This study showed a strong association between the quality of life domains and the involvement of nuclear family caregiver, HIV-positive caregiver and adherence to HAART. Our study suggests that the involvement of any member of the nuclear family, HIV positive parents and patient adherence to therapy can improve the quality of life of paediatric HIV/AIDS patients on highly active antiretroviral therapy in the two hospitals

What adaptation to research is needed following crises: a comparative, qualitative study of the health workforce in Sierra Leone and Nepal

Background: Health workers are critical to the performance of health systems; yet, evidence about their coping strategies and support needs during and post crisis is lacking. There is very limited discussion about how research teams should respond when unexpected crises occur during on-going research. This paper critically presents the approaches and findings of two health systems research projects that explored and evaluated health worker performance and were adapted during crises, and provides lessons learnt on re-orientating research when the unexpected occurs. Methods: Health systems research was adapted post crisis to assess health workers’ experiences and coping strategies. Qualitative in-depth interviews were conducted with 14 health workers in a heavily affected earthquake district in Nepal and 25 frontline health workers in four districts in Ebola-affected Sierra Leone. All data were transcribed and analysed using the framework approach, which included developing coding frameworks for each study, applying the frameworks, developing charts and describing the themes. A second layer of analysis included analysis across the two contexts, whereas a third layer involved the research teams reflecting on the approaches used to adapt the research during these crises and what was learned as individuals and research teams. Results: In Sierra Leone, health workers were heavily stigmatised by the epidemic, leading to a breakdown of trust. Coping strategies included finding renewed purpose in continuing to serve their community, peer and family support (in some cases), and religion. In Nepal, individual determination, a sense of responsibility to the community and professional duty compelled staff to stay or return to their workplace. The research teams had trusting relationships with policy-makers and practitioners, which brought credibility and legitimacy to the change of research direction as well as the relationships to maximise the opportunity for findings to inform practice. Conclusions: In both contexts, health workers demonstrated considerable resilience in continuing to provide services despite limited support. Embedded researchers and institutions are arguably best placed to navigate emerging ethical and social justice challenges and are strategically positioned to support the co-production of knowledge and ensure research findings have impact

COVID-19 Vaccine Hesitancy among Healthcare Workers and Trainees in Freetown, Sierra Leone: A Cross-Sectional Study.

Despite having safe and efficacious vaccines against COVID-19, vaccine hesitancy is widespread. Although a trusted source of information, vaccine hesitancy has been reported among healthcare professionals, yet few studies have explored this phenomenon in sub-Saharan Africa. We conducted a cross-sectional survey of healthcare professionals in Sierra Leone from January to March 2022. Measures included sociodemographic/health-related information and COVID-19-related concerns. From the responses, we constructed a hesitancy (VAX) score, with higher scores implying negative attitudes or unwillingness to vaccinate. Multivariate linear regression was used to access factors associated with vaccine hesitancy. Overall, 592 participants submitted responses (67.2% female, mean age 29 years, 5.6% physicians/pharmacists, 44.3% medical students, 29.2% nurses, 20.9% nursing students). The mean VAX score was 43.27 ± 8.77, with 60.1% of respondents classified as vaccine hesitant (&gt;50th percentile) and 13.8% as highly hesitant (&gt;75th percentile). Worries about unforeseen future effects (76.3%), a preference for natural immunity (59.5%), and profiteering/mistrust of health authorities (53.1%) were the most common concerns. Being a medical student (β = 0.105, p = 0.011) and previously refusing a recommended vaccine (β = 0.177, p &lt; 0.001) were predictors of COVID-19 vaccine hesitancy. Our findings call for addressing vaccine hesitancy among healthcare professionals as an essential component of strategies aimed at increasing COVID-19 vaccine uptake in this setting

Recognition of fishes in rivers and basin of Qom

This study was carried out on rivers, basins & qanat of Qom region during the 1376-1378and Fish samples were taken from 2 permanent rivers (Qomrood ,Ghara_chag)& from some seasonal ones (Tagharood, Zavarian, Vesva, Biraghan). Also local fishes was followed in 100 qanats in the region and Random fish sampling was done in permanent river extension out of province. This study aimed to recognize different fish species in the province water reservoir and estimating the fisheries potential in the province. For fish sampling nets such as mashk, salik, hook and hand tailored were used. Electroshoker was not used at all. Results of fish recognition showed that fish samples belong to 12 species & 4 family of "cyprinidae", "Balitoridae", "cyprinodontidae" and "poecilidae".The qanat fishes of the montain (kahak, Khagestan) and pastora area (Ghanavat,jafarabad) included by two families of "cyprinid", "Balitoridea".In some qanat which were connected to rivers more species of fish and anotherAquatic animal were observed & sampled.At the and map of geographical distribution of local fishes was planned

An association between TRP64ARG polymorphism of the B3 adrenoreceptor gene and some metabolic disturbances

<p>Abstract</p> <p>Backgrounds</p> <p>B3 adrenoreceptors (ADRB3) are abundant in adipose tissue and play the role in its metabolism and lipolysis. Some variants of the ADRB3 gene may predispose subjects for the development obesity and metabolic abnormalities in the setting of modern sedentary lifestyle. ADRB3 gene polymorphism association with metabolic disturbances has never been studied before in the ethnic Kyrgyz population.</p> <p>Aim</p> <p>To study an association between Trp64Arg polymorphism of the ADRB3 and metabolic syndrome (MS) components in an ethnic Kyrgyz group.</p> <p>Materials and methods</p> <p>213 Ethnic Kyrgyz volunteers over the age of 30 were enrolled in the study. The assessment plan for each individual comprised of general physical and anthropometric exams as well as laboratory tests (glucose, lipid panel, insulin) and genotyping by Trp64Arg polymorphism of the ADRB3. MS diagnosis was consistent with modified ATP III criteria (2005). Logistic regression analysis was performed to test the potential independent association between Arg64 allele with obesity, abdominal obesity (AO) and arterial hypertension (AH).</p> <p>Results</p> <p>Trp64Arg polymorphism of the ADRB3 was assessed in 213 individuals (145 men, 68 women) aged 30-73 (mean age 50.7 ± 7.6). Arg64 allele frequency was 0.239; ADRB3 genotype distribution among participants was: Trp64 homozygotes 54.5%, Trp64Arg 43.2% and Arg64 homozygotes 2.3%. There was an association between Trp64Arg и Arg64Arg genotypes and higher BMI, WC and obesity frequency (p < 0.00009), AO (p < 0.01), type 2 diabetes mellitus (DM) (p < 0.005) and lower high density cholesterol (HDL-C) level (p < 0.03). The logistic regression analysis showed the correlation of the Arg64 allele with obesity (OR 3.159; 95% CI 1.789-5.577) and AO (OR 1.973; 95% CI 1.118-3.481). The association between Arg64 allele and AH lost its significance after adjustment for obesity.</p> <p>Conclusion</p> <p>Arg64 allele of the ADRB3 gene in the studied group has an association with MS components such as obesity, AO and decreased HDL-C level.</p

Association of dietary magnesium intake with radiographic knee osteoarthritis: Results from a population-based study

To examine the cross-sectional association between dietary magnesium (Mg) intake and the radiographic knee osteoarthritis (OA) among African-American and Caucasian men and women