Repositioning of FDA-approved drugs for the treatment of methicillin-resistant Staphylococcus aureus infection: Structure-based virtual screening and in vitro assay

Background: Computer-aided repositioning of approved drugs is an increasingly popular strategy for the discovery of effective therapies. The potency of the newly repositioned drugs can be optimized using them as a component of an effective drug combination, thereby achieving the desired therapeutic effect at a lower and more tolerable drug concentration. Aim and Objectives: The aim of the study was to perform structure-based virtual screening and repurposing of FDA-approved drugs for the treatment of methicillin resistance by Staphylococcus aureus (SA) and perform an in vitro validation of the prediction. Materials and Methods: Following ethical clearance at the Department of Pharmacology and Therapeutics, College of Health Sciences, Usmanu Danfodiyo University Sokoto, molecular docking was performed against 5 validated protein targets involved in the development of methicillin resistance by SA and an in vitro validation of the prediction was done using 3 of the top-ranking drug candidates against methicillin-resistant vancomycin-susceptible strain of the pathogen (ATCC 43300). Results: Desmopressin and docetaxel, two of the 20 top-ranking repurposed drugs discovered through virtual screening, enhanced the inhibitory effect of oxacillin against the ATCC 43300 SA strain in a ratio-dependent manner, although each of the two drugs singly was only weakly effective against the bacterial strain. The standard drug, vancomycin (also among the top-scoring candidates), alone, was effective against ATCC 43300 strain and in combination with oxacillin, the two drugs produced a ratio-dependent synergistic effect against the bacterial strain. Conclusion: These findings suggest that oxacillin-based combinations with desmopressin, docetaxel, and the standard drug vancomycin, three of the 20 top-ranking drugs, at optimum ratios, may be beneficial in reversing the resistance of the ATCC 43300 SA strain to oxacillin, thus supporting the prediction of the molecular docking results.

Functional Iron Indices and Highly Sensitive CRP Post Single Dose Irradiation with Cobalt60 and the Ameliorating Effects of Single and Combined Doses of Aqueous Extracts of Parquetina nigrescens, Camellia sinensis and Telfairia occidentalis in Guinea Pigs

Background: The relationship between iron, hypoxia, inflammation, and erythropoietin in cellular homeostasis is well documented. Patients on radiotherapy are known with active immune/inflammatory disorders often accompanied with reduced iron uptake or unavailability of circulatory iron and hence, must be adequately evaluated. The present study hypothesized “aqueous extracts of Camellia sinensis, Telfairia occidentalis and Parquetina nigrescens have chemical properties of ameliorating and restoring to normal, functional iron deficiency sequel to Cobalt 60 irradiation effect”. Materials and Methods: Fifty-Five young male guinea-pigs approximately 450 gram in weight were recruited and thirty were randomly assigned to 3 groups (A, B and C) for the study. Groups A and B were further divided into 4 (A1-4 and B1-4) with 3 animals (n=3) per group. Three guinea-pigs were also assigned to group C. Groups A and B belonged to Pre and post-irradiation groups while groups C served as control. Each animal was given 400r (4.0 Gy) whole-body gamma-irradiation under general anaesthesia, using a Co60 therapy unit as a source. Groups A1, A2, A3 and A4 had 1,400 mg/kg C. sinensis, 4000 mg/kg P. nigrescens, 3,500 mg/kg T. occidentalis and Combined dose (1,400 mg/kg C. sinensis + 400 mg/kg P. nigrescens + 3,500 mg/kg T. occidentalis) respectively twice daily 72 hours prior to irradiation and continued throughout the 14 days of the study. Groups B1, B2, B3 and B4 had similar treatment but commenced 24 hours after exposure to radiation and likewise continued throughout the 14 days of the study. Group C were not given any treatment but also had irradiation. Results: Total Iron Binding Capacity, Ferritin, Serum Transferrin receptor and Iron were all increased significantly for all the extracts pre and post irradiation. However, C-reactive protein decreased significantly. Conclusion: Aqueous extracts of Camellia sinensis, Parquetina nigrescens and Telfairia occidentalis leaves have good ameliorating effect on irradiation-induced injuries.

Serum levels of antioxidant vitamins and mineral elements of human immunodeficiency virus positive subjects in Sokoto, Nigeria

Background: Undernourishment and micronutrient deficiencies exacerbate immunosuppression, oxidative stress, acceleration of human immunodeficiency virus (HIV) replication and CD4 T-cell depletion in HIV-infected individuals. Materials and Methods: The current work reports the serum levels of antioxidant vitamins (vitamins A, C and E) and minerals (Zn, Fe, Cu) in 90 HIV positive subjects attending the Usmanu Danfodiyo University Teaching Hospital (UDUTH), Sokoto, Nigeria. The serum levels of the micronutrients were correlated with the CD4 count of the subjects. Results: The results showed that the HIV positive subjects have significantly lower (P < 0.05) levels of vitamins A, C and E. Also, serum Zn, Fe, Cu and CD4 count were also significantly (P < 0.05) lower compared with the HIV negative subjects. Micronutrient deficiencies were more pronounced in HIV positive subjects with CD4 counts less than 200 cell/ìl. The results based on age and sex showed no significant (P > 0.05) difference. Vitamins A, E and C and Zn and Fe showed positive correlation with CD4 count of the HIV positive subjects. Conclusion: The results suggest that the HIV subjects in the study area have lowered serum levels of antioxidant micronutrients and that the levels decrease with increase in the severity of the infection. These may increase the chances of the symptomatic and asymptomatic subjects progressing into full-blown Acquired Immunodeficiency Syndrome

Diagnostic Potentials of the Reactivities of Lectins with whole Cells of Three Bacterial Diarrheagenic Agents : Aeromonas; Plesiomonas and Campylobacter

The reactivities of strains of Plesionmona shigeloides; Campylobater jejuni; Campylobacter coli and Aeromonas species with some lectins namely Soyabean agglutinin (SBA); Ricinus communis agglutinin (RCA); Peanut agllutinin (PNA); Cancanavalin-A (Con-A); Lima bean agglutinin (LMA) and Abrin were investigated using the microtitre plate method. The results obtained show that all stains of A. hydrophila; A. caviae; A. Sobria and P. shigelloides reacted very strongly with PNA and SBA. All strains of C. jejuni studied failed to react with SBA but reacted with PNA Whereas C. coli did not show any reaction towards PNA but reacted very strongly with SBA. All strains of the different organisms were strongly agglutinated by RCA and LMA except A. Hydrophilia and A. sobria which did not react with RCA and LMA respectively. C. jejuni was not agglutinated by Con-A unlike C. coli. Only C. jejuni; C. coli and P. shigelloides reacted with abrin. This study suggests that the reactivities of lectins with the diarrheogenic bacteria studied may be used for their presumptive identifications and for epidemiological purposes

Pericardial effusion associated with minoxidil therapy. [case reports]

Symptomatic pericardial effusion (PE) occured in two patients with chronic renal failure (CRF) who had taken minoxidal for control of their hypertension. One of them died from the effects of cardiogenic shock due to cardiac tamponade. This experience conforms with reports from elsewhere that minoxidil may cause PE. Therefore; patients with CRF who need minoxidil as an anti-hypertensive agent should be examined regularly for clinical evidence of PE