Identification of the Anti Listerial

Partially purified fractions of the n-hexane extract of Garcinia kola seeds were obtained through column chromatography and their constituents were identified through the use of gas chromatography coupled to mass spectrometry (GC-MS). Three fractions were obtained by elution with benzene as the mobile phase and silica gel 60 as the stationery phase and these were named Benz1, Benz2, and Benz3 in the order of their elution. The antiListerial activities of these fractions were assessed through MIC determination and only Benz2 and Benz3 were found to be active with MIC’s ranging from 0.625 to 2.5 mg/mL. The results of the GC-MS analysis showed Benz2 to have 9 compounds whilst Benz3 had 7 compounds, with the major compounds in both fractions being 9,19-Cyclolanost-24-en-3-ol, (3.β.) and 9,19-Cyclolanostan-3-ol,24-methylene-, (3.β.). The Benz2 fraction was found to have mainly indifferent interactions with ampicillin and penicillin G whilst mainly additive interactions were observed with ciprofloxacin. The Benz3 fraction’s interactions were found to be 50% synergistic with penicillin G and 25% synergistic with ciprofloxacin and ampicillin. A commercially available 9,19-Cyclolanost-24-en-3-ol, (3.β.) was found not to exhibit any antiListerial activities at maximum test concentrations of 5 mg/mL, suggesting that the compound could be acting in synergy with the other compounds in the eluted fractions of Garcinia kola seeds

The bacteria profiles of wounds in diabetic patients hospitalized in northern Kwazulu-Natal, South Africa

Diabetic wound infections still remain a health concern such that correct identification of bacteria is essential in monitoring the spread of the infections as well as in the administration of the correct treatment. This study therefore focuses on isolating and identifying bacteria present in diabetic wounds of hospitalized patients in northern KwaZulu-Natal and assessing their distribution.The wound specimen were collected and swabbed onto selective and differential media. The bacteria identities were presumptively ascertained through biochemical characterization (Gram-stain, catalase test, oxidase test and API) and then confirmed through 16S rDNA sequencing.A total of 42 isolates were recovered from 83% of the patients sampled from the three participating hospitals (X, Y, and Z). Gram-negative bacilli from Enterobacteriaceaewere predominant followed by Staphylococci spp and Enterococcus faecaliswith 43% polymicrobial cases from hospital Z and 29% from hospital X. Distribution of some opportunistic pathogens and nosocomially-acquired pathogens were also observed across the patients with five bacterial identities distributed among hospital X and Z. The adverse effects associated with the recovered bacteria in diabetic wounds pose a serious health concern and preventive measure should be taken.Keywords: Diabetes mellitus, wounds, bacteria, infectio

Effect of Moringa oleifera Lam. leaf powder on the pharmacokinetics of nevirapine in HIV-infected adults: a one sequence cross-over study

Moringa oleifera Lam., an herb commonly consumed by HIV-infected people on antiretroviral therapy, inhibits cytochrome P450 3A4, 1A2 and 2D6 activity in vitro; and may alter the pharmacokinetics (PK) of antiretroviral drugs metabolized via the same pathways. However, in vitro drug interaction activity may not translate to a clinically significant effect. Therefore, the effect of moringa leaf powder on the PK of nevirapine in HIV-infected people was investigated. Adult patients at steady-state dosing with nevirapine were admitted for 12-h intensive PK sampling following a 21-day herbal medicine washout. Blood sampling was repeated after 14 days of nevirapine and moringa (1.85 g leaf powder/day) co-administration. Nevirapine plasma concentrations were determined by liquid chromatography-tandem mass spectrometry. To assess the effect of moringa on nevirapine PK, the change in nevirapine area under the plasma concentration–time curve (AUC) was determined. The mean difference in pre- and post-moringa nevirapine, maximum concentration (Cmax) and concentration at 12 h (C12h) were also calculated. The PK parameters were compared by assessing the post/pre geometric mean ratios (GMRs) and associated 90% confidence intervals (CIs). Pharmacokinetics analyses were performed on the results from 11 participants for whom complete data were obtained. The post/pre GMRs and associated 90% CIs for nevirapine were 1.07 (1.00–1.14) for the AUC; 1.06 (0.98–1.16) for Cmax and 1.03 (0.92–1.16) for C12h. Co-administration of Moringa oleifera Lam. leaf powder at the traditional dose did not significantly alter the steady-state PK of nevirapine. Trial registration number NCT01410058 (ClinicalTrials.gov

THE ANTIBACTERIAL ACTIVITIES OF SOME PLANT DERIVED TRITERPENES

Background: The increase in the prevalence of multi-drug resistant bacteria has necessitated the search for new antimicrobials from alternative sources such as traditional medicinal plants. Materials and Methods: The agar well diffusion method was employed to determine the susceptibilities of four plant derived triterpenes namely, 3β-hydroxylanosta-9, 24-dien-21-oic acid (RA5), and methyl-3β-hydroxylanosta-9, 24-dien-21oate (RA3), a mixture of oleanolic acid and betulinic acid (SF1) and a mixture of 3β-acetonyloleanolic acid and 3β-acetonylbetulinic acid (SF2), at a concentration of 10 mg/ml against seven Escherichia coli, one Bacillus cereus, five Enterococcus and nine Vibrio bacteria. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined through the micro-broth dilution assay. The checkerboard method was used to determine the antibiotictriterpene interactions while the cytosolic lactate dehydrogenase test was used to determine the membrane damaging potentials of the triterpenes in comparison to 3% Triton X-100. Results: The triterpenes RA3, RA5, SF1 and SF2 had activities against 86.4%, 54.6%, 22.7% and 9.09% of the test bacteria respectively. SF1 had the lowest MIC values ranging 0.625-10 mg/ml with lower MIC values being noted against Gram negative bacteria in comparison to Gram positive bacteria; this trend was also noted among the activities of RA3 and RA5 although they had higher MIC value ranges of 1.25-10 mg/ml and 5- 10 mg/ml respectively. MBC studies proved the triterpenes to be mostly bacteriostatic. The interaction studies with ciprofloxacin were mainly ranging between indifference and antagonism. RA3 alone showed minimal membrane damaging potential with the levels of cytosolic lactate dehydrogenase released ranging from 1-36% in comparison to 3%Triton X-100 against E.coli (DSM-8695) and V. vulnificus (AL 042). Conclusion: The results hereby show the potential that the test triterpenes have as antibacterial agents, especially against the Gram negative bacteria namely E. coli and Vibrio bacteri

The bacteria profiles of wounds in diabetic patients hospitalized in northern Kwazulu-Natal, South Africa

Diabetic wound infections still remain a health concern such that correct identification of bacteria is essential in monitoring the spread of the infections as well as in the administration of the correct treatment. This study therefore focuses on isolating and identifying bacteria present in diabetic wounds of hospitalized patients in northern KwaZulu-Natal and assessing their distribution.The wound specimen were collected and swabbed onto selective and differential media. The bacteria identities were presumptively ascertained through biochemical characterization (Gram-stain, catalase test, oxidase test and API) and then confirmed through 16S rDNA sequencing.A total of 42 isolates were recovered from 83% of the patients sampled from the three participating hospitals (X, Y, and Z). Gram-negative bacilli from Enterobacteriaceaewere predominant followed by Staphylococci spp and Enterococcus faecaliswith 43% polymicrobial cases from hospital Z and 29% from hospital X. Distribution of some opportunistic pathogens and nosocomially-acquired pathogens were also observed across the patients with five bacterial identities distributed among hospital X and Z. The adverse effects associated with the recovered bacteria in diabetic wounds pose a serious health concern and preventive measure should be taken.Keywords: Diabetes mellitus, wounds, bacteria, infectio

Quality and labeling information of Moringa oleifera products marketed for HIV-infected people in Zimbabwe

Labeling information and quality of marketed Moringa oleifera products were assessed. Personnel in 60 pharmacies and 11 herbal shops were interviewed about the sources, dosages, indications and counseling information of Moringa oleifera products. Content analysis of written information provided on Moringa oleifera products was also done. Three samples of Moringa from popular sources were acquired to determine heavy metal content and microbial contamination. The results were compared to specified limits in the European and Chinese pharmacopeia, World Health Organization guidelines and Bureau of Indian Standards. Moringa was available as capsules or powder in 73% of the premises. Moringa was recommended for seven different disease conditions. Four different dosage regimens were prescribed. The main references cited for the counseling information were unscientific literature (62%). The selected Moringa samples were contaminated with bacteria and fungi above the European Pharmacopeia specified limits. Escherichia coli and Salmonella species were present in all three samples. All three samples contained arsenic, nickel and cadmium above the permissible limits. Moringa oleifera with variable labeling information and poor microbial and heavy metal quality is widely available in Zimbabwe

In Vivo Antihyperglycemic Activity of a Lanosteryl Triterpene from Protorhus longifolia

Control of postprandial hyperglycemia is crucial in the management of diabetes mellitus. Despite the use of the current hypoglycemic drugs, incidence of diabetes and related diseases continue to increase. This study aimed at evaluating the in vivo antihyperglycemic activity of methyl-3β-hydroxylanosta-9,24-dien-21-oate (RA-3), a lanosteryl triterpene isolated, and characterized from Protorhus longifolia stem bark. Spectroscopic data analysis was used to establish and verify the structure of the triterpene. The antihyperglycemic activity of the triterpene was evaluated in an STZ-induced diabetes rat model. The experimental animals were orally administered with RA-3 (100 mg/kg body weight) daily for 14 days. An oral glucose tolerance test was also performed. The animals were euthanized and biochemical analysis of antioxidant status, some glycolytic enzymes and glycogen content were conducted on serum and liver samples, respectively. RA-3 exhibited hypoglycemic activity by reducing blood glucose levels by 37%. The triterpene also improved glucose tolerance in the diabetic rats. Relatively higher hepatic glycogen content, hexokinase and glucokinase activity with a decrease in glucose-6-phosphatase activity were observed in the triterpene-treated diabetic group when compared with the diabetic control group. The triterpene treatment further increased antioxidant status of the diabetic animals; increased activity of superoxide dismutase and catalase were observed along with a decrease in malondialdehyde content. The results indicate potential pharmaceutical effects of lanosteryl triterpene in the management of diabetes mellitus

Strategic establishment of an International Pharmacology Specialty Laboratory in a resource-limited setting

Background: A growing number of drug development studies that include pharmacokinetic evaluations are conducted in regions lacking a specialised pharmacology laboratory. This necessitated the development of an International Pharmacology Specialty Laboratory (IPSL) in Zimbabwe. Objectives: The aim of this article is to describe the development of an IPSL in Zimbabwe. Methods: The IPSL was developed collaboratively by the University of Zimbabwe and the University at Buffalo Center for Integrated Global Biomedical Sciences. Key stages included infrastructure development, establishment of quality management systems and collaborative mentorship in clinical pharmacology study design and chromatographic assay development and validation. Results: Two high performance liquid chromatography instruments were donated by an instrument manufacturer and a contract research organisation. Laboratory space was acquired through association with the Zimbabwe national drug regulatory authority. Operational policies, standard operating procedures and a document control system were established. Scientists and technicians were trained in aspects relevant to IPSL operations. A highperformance liquid chromatography method for nevirapine was developed with the guidance of the Clinical Pharmacology Quality Assurance programme and approved by the assay method review programme. The University of Zimbabwe IPSL is engaged with the United States National Institute of Allergy and Infectious Diseases Division of AIDS research networks and is poised to begin drug assays and pharmacokinetic analyses. Conclusions: An IPSL has been successfully established in a resource-limited setting through the efforts of an external partnership providing technical guidance and motivated internal faculty and staff. Strategic partnerships were beneficial in navigating challenges leading to laboratory development and training new investigators. The IPSL is now engaged in clinical pharmacology research

Effect of Moringa oleifera Lam. leaf powder on the pharmacokinetics of nevirapine in HIV-infected adults: a one sequence cross-over study.

BackgroundMoringa oleifera Lam., an herb commonly consumed by HIV-infected people on antiretroviral therapy, inhibits cytochrome P450 3A4, 1A2 and 2D6 activity in vitro; and may alter the pharmacokinetics (PK) of antiretroviral drugs metabolized via the same pathways. However, in vitro drug interaction activity may not translate to a clinically significant effect. Therefore, the effect of moringa leaf powder on the PK of nevirapine in HIV-infected people was investigated.MethodsAdult patients at steady-state dosing with nevirapine were admitted for 12-h intensive PK sampling following a 21-day herbal medicine washout. Blood sampling was repeated after 14 days of nevirapine and moringa (1.85 g leaf powder/day) co-administration. Nevirapine plasma concentrations were determined by liquid chromatography-tandem mass spectrometry. To assess the effect of moringa on nevirapine PK, the change in nevirapine area under the plasma concentration-time curve (AUC) was determined. The mean difference in pre- and post-moringa nevirapine, maximum concentration (Cmax) and concentration at 12 h (C12h) were also calculated. The PK parameters were compared by assessing the post/pre geometric mean ratios (GMRs) and associated 90% confidence intervals (CIs).ResultsPharmacokinetics analyses were performed on the results from 11 participants for whom complete data were obtained. The post/pre GMRs and associated 90% CIs for nevirapine were 1.07 (1.00-1.14) for the AUC; 1.06 (0.98-1.16) for Cmax and 1.03 (0.92-1.16) for C12h.ConclusionCo-administration of Moringa oleifera Lam. leaf powder at the traditional dose did not significantly alter the steady-state PK of nevirapine. Trial registration number NCT01410058 (ClinicalTrials.gov)

Proximal renal tubular function in HIV-infected children on tenofovir disoproxil fumarate for treatment of HIV infection at two tertiary hospitals in Harare, Zimbabwe.

BACKGROUND:Renal abnormalities in HIV infected children may be due to the HIV infection or treatment among other factors. Tenofovir disoproxil fumarate (TDF) is associated with proximal renal tubular dysfunction, proteinuria and decrease in glomerular function. Studies in developed countries have shown variable prevalence of proximal renal tubular dysfunction in children on TDF. There are no known studies in developing countries, including Zimbabwe, documenting the proximal tubular function in HIV infected children on TDF. The aim of this study was to assess renal and proximal renal tubular function in HIV infected children receiving TDF and determine factors associated with proximal tubular dysfunction. METHODS:A descriptive cross-sectional study was conducted in HIV infected patients below 18 years of age attending outpatient clinics at two tertiary hospitals in Harare, who received a TDF-containing antiretroviral regimen for at least six months. Dipstick protein and glucose, serum and urine phosphate and creatinine levels were measured. Fractional excretion of phosphate was calculated. Estimated glomerular filtration rate (eGFR) was calculated using the Schwartz formula. Tubular dysfunction was defined by at least two of the following characteristics: normoglycaemic glycosuria, hypophosphatemia and fractional excretion of phosphate > 18%. FINDINGS:One hundred and ninety-eight children below 18 years of age were recruited over a period of six months. The prevalence of tubular dysfunction was 0.5%. Normoglycaemic glycosuria occurred in 1 (0.5%), fractional excretion of phosphate >18% in 4 (2%), and hypophosphatemia in 22 [11.1%] patients. Severe stunting was associated with increased risk of hypophosphatemia (OR 9.31 CI (1.18, 80.68) p = 0.03). Reduction in estimated glomerular filtration rate (eGFR) < 90ml/min/1.73m2 and proteinuria was evident in 35.9% and 32.8% of children, respectively. Concurrent TDF and HIV-1 protease inhibitor-based regimen was the only independent factor associated with reduction in GFR (OR 4.43 CI (1.32; 4.89) p = 0.016). CONCLUSION:Tubular dysfunction was uncommon in Zimbabwean children on a TDF-based ART regimen. Hypophosphatemia, proteinuria and reduction in eGFR were common. Reassessing renal function using more sensitive biomarkers is needed to examine the long-term tolerance of TDF