Chemoinformatic Design and Profiling of Derivatives of Dasabuvir, Efavirenz, and Tipranavir as Potential Inhibitors of Zika Virus RNA-Dependent RNA Polymerase and Methyltransferase.

Zika virus (ZIKV) infection is one of the mosquito-borne flaviviruses of human importance with more than 2 million suspected cases and more than 1 million people infected in about 30 countries. There are reported inhibitors of the zika virus replication machinery, but no approved effective antiviral therapy including vaccines directed against the virus for treatment or prevention is currently available. The study investigated the chemoinformatic design and profiling of derivatives of dasabuvir, efavirenz, and tipranavir as potential inhibitors of the zika virus RNA-dependent RNA polymerase (RdRP) and/or methyltransferase (MTase). The three-dimensional (3D) coordinates of dasabuvir, efavirenz, and tipranavir were obtained from the PubChem database, and their respective derivatives were designed with DataWarrior-5.2.1 using an evolutionary algorithm. Derivatives that were not mutagenic, tumorigenic, or irritant were selected; docked into RdRP and MTase; and further subjected to absorption, distribution, metabolism, excretion, and toxicity (ADMET) evaluation with Swiss-ADME and pkCSM web tools. Some of the designed compounds are Lipinski's rule-of-five compliant, with good synthetic accessibilities. Compounds 20d, 21d, 22d, and 1e are nontoxic with the only limitation of CYP1A2, CYP2C19, and/or CYP2C9 inhibition. Replacements of -CH3 and -NH- in the methanesulfonamide moiety of dasabuvir with -OH and -CH2- or -CH2CH2-, respectively, improved the safety/toxicity profile. Hepatotoxicity in 5d, 4d, and 18d is likely due to -NH- in their methanesulfonamide/sulfamic acid moieties. These compounds are potent inhibitors of N-7 and 2'-methylation activities of ZIKV methyltransferase and/or RNA synthesis through interactions with amino acid residues in the priming loop/"N-pocket" in the virus RdRP. Synthesis of these compounds and wet laboratory validation against ZIKV are recommended.

Knowledge Attitude and Practice Regarding Obstructive Sleep Apnea among Medical Doctors in Southern Nigeria.

BACKGROUND: Despite the high global burden of Obstructive Sleep Apnea (OSA), doctors' knowledge of OSA was reported to be generally poor. Data on knowledge, attitude and practice of doctors regarding OSA are scarce in Africa. The only Nigerian study providing data on this included few participants and did not assess practice. We assessed the knowledge, attitude and practice of doctors regarding OSA in southern Nigeria with the aim of finding gaps in knowledge and practice. METHODS: We sent out online survey monkey self-administered structured questionnaires to the WhatsApp numbers or e-mails of 1917 eligible medical doctors. The questionnaires were used to collect data on demography of the medical doctors, their professional history and knowledge of OSA symptoms; general facts, risks factors, and treatment regarding OSA; and their attitude and practice in relation to OSA. RESULTS: Data from five hundred and eighty one respondents (mean age, 39.8 ± 8.7) were analyzed. Overall mean knowledge score was 25.3±6.3 (68.6±17.2 percent). The mean knowledge score of Internists, Family Physicians, General practitioners and Surgeons were 28.2±5.0; 25.0±6.9; and 24.5±5.8 and 24.2±6.7 respectively. Only 47% and 51% of the respondents respectively affirmed that hypertension and diabetes mellitus were associated with increased risk of OSA; and 7.2% referred suspected OSA patients for polysomnography. CONCLUSION: The level of knowledge of OSA among participating doctors was poor. Most of them had the right attitude to OSA but their practice and care of OSA patients was suboptimal. We suggest improvement in care through education and provision of diagnostic and treatment facilities.

Impaired Renal Function and its Predictors among Treatment-Naive HIV-seropositive Patients in a Tertiary Institution in South-East Nigeria.

BACKGROUND: Renal impairment is a significant independent risk factor for mortality among HIV-infected patients. Some antiretroviral drugs are nephrotoxic, especially to the tubules, and their dosage need to be modified in the presence of renal impairment to avoid progression to chronic kidney disease. AIM: To determine the prevalence and predictors of renal impairment among treatment-naïve HIV sero-positive patients seen at Federal Medical Centre, Umuahia, Abia state. MATERIALS AND METHODS: This was a cross-sectional study involving 115 HIV-seropositive treatment-naïve cases and 115 seronegative controls. Questionnaires were administered and history regarding health status was obtained. Participants had biophysical profile measured. Blood and urine specimens were analyzed in the laboratory. The re-expressed modification of diet in renal disease (MDRD) was used to determine estimated Glomerular Filtration Rate (eGFR). Factors found to be associated with renal impairment were subjected to binary logistic regression analysis to determine the predictors of renal impairment. RESULTS: The prevalence of renal impairment among the cases was 27.8%. Factors associated with renal impairment included duration of HIV diagnosis of 12 months and above, significant intake of herbal remedies, hypertension, significant proteinuria, WHO clinical stage 3 or 4, anaemia and CD4 count less than 350cells/µL. Predictors of renal impairment were hypertension, WHO clinical stage 3 or 4 disease, significant proteinuria and significant intake of herbal remedies. CONCLUSION: Renal impairment was prevalent in this sample. Concerted efforts should be directed to early diagnosis of renal impairment among these patients. Reno-protective measures need to be instituted early to avoid deleterious outcomes.

Modulation of the Lipid Profile, Hepatic and Renal Antioxidant Activities, and Markers of Hepatic and Renal Dysfunctions in Alloxan-Induced Diabetic Rats by Virgin Coconut Oil.

BACKGROUND: Research studies that holistically investigated the effect of administration of Virgin Coconut Oil (VCO) on diabetic humans or animals are limited in literature. OBJECTIVE: To investigate the effect of administration of VCO on lipid profile, markers of hepatic and renal dysfunction, and hepatic and renal antioxidant activities of alloxan induced diabetic rats. METHODS: Twenty-four male albino rats were used, and they were divided into four groups of six rats each. Group 1 (Normal Control, NC) received distilled water (1 mL/kg); Group 2 (VCO Control) received VCO (5 mL/kg); Group 3 (Diabetic Control, DC) received distilled water (1 mL/kg); Group 4 (Test Group, TG) received 5 ml/kg of VCO. RESULTS: There were no significant differences in blood glucose, body weights, relative liver weights, relative kidney weights, hepatic and renal Superoxide Dismutase (SOD) activities, Malondialdehyde (MDA), albumin, aspartate Amino Transaminase (AST), alanine Amino Transaminase (ALT), Alkaline Phosphatase (ALP), urea, creatinine, uric acid, total cholesterol, triacylglycerol, Very Low Density Lipoprotein cholesterol (VLDL) and Low Density Lipoprotein cholesterol (LDL) concentrations; significant increases in renal Glutathione (GSH), hepatic catalase, Glutathione Peroxidase (GPx) and GSH but significant reduction in renal GPx and catalase activities of VCO control group compared with NC group. There were significant increases in blood glucose, relative liver and kidney weights, hepatic GPx, hepatic and renal MDA concentration, ALP, AST, ALT, urea, creatinine, uric acid, triacylglycerol, total cholesterol, LDL and VLDL concentrations; and significant decreases in body weight, hepatic SOD and GSH activities and albumin concentration but no significant difference in hepatic catalase activity of DC group compared with NC group. Administration of VCO to diabetic rats positively modulated these parameters compared with the diabetic control. CONCLUSION: The study showed the potentials of VCO in the management of hyperlipidemia, renal and hepatic dysfunctions imposed by hyperglycemia and by oxidative stress in diabetic rats.

A survey of asthma management practices and implementation of Global Initiative for Asthma guidelines among doctors in a resource-limited setting in Nigeria.

BACKGROUND: Bronchial asthma is a global health problem that causes significant morbidity and mortality in all age groups. Global Initiative for Asthma (GINA) seeks to standardize the care asthma patients receive. We assessed the knowledge, attitude, and practices of doctors in Umuahia, Southeast Nigeria, regarding asthma and determined the extent to which they abide by GINA guidelines in their management of asthma. METHODOLOGY: It was a descriptive cross-sectional study. A pretested self-administered questionnaire was used to obtain information from the participants regarding knowledge of asthma prevalence, asthma risk factors, and management practices. RESULTS: Out of 142 questionnaires administered, 117 were retrieved giving a response rate of 82%. About 70% were men, and the most common age group was 30-39 years (57.3%). The median duration of medical practice was 6 (3-12) years. About 77% reported asthma prevalence to be on the increase. While 105 (89.7%) respondents had seen a spirometer, only 28 (23.9%) use spirometry in asthma diagnosis. Similarly, 95 (81.2%) had seen a peak flow meter, but only 41 (35.5%) use it in asthma diagnosis. Only 7 (6.0%) respondents reported that their patients keep a peak flow diary. Of 117 respondents, 94 (80.3%) know about GINA guidelines for asthma control, 45 (38.5%) apply GINA guidelines in patient care, 86 (73.5%) regularly review patient inhaler technique, 33 (28.2%) use adult asthma control test while 17 (14.5%) regularly review asthma action plan with patients. CONCLUSION: There is a wide gap between GINA guidelines and the knowledge, attitude, and practices of doctors in Umuahia regarding asthma management. Improvement and standardization of asthma care are recommended.