Screening of selected ethnomedicinal plants from South Africa for larvicidal activity against the mosquito Anopheles arabiensis.

BACKGROUND: This study was initiated to establish whether any South African ethnomedicinal plants (indigenous or exotic), that have been reported to be used traditionally to repel or kill mosquitoes, exhibit effective mosquito larvicidal properties. METHODS: Extracts of a selection of plant taxa sourced in South Africa were tested for larvicidal properties in an applicable assay. Thirty 3rd instar Anopheles arabiensis larvae were exposed to various extract types (dichloromethane, dichloromethane/methanol) (1:1), methanol and purified water) of each species investigated. Mortality was evaluated relative to the positive control Temephos (Mostop; Agrivo), an effective emulsifiable concentrate larvicide. RESULTS: Preliminary screening of crude extracts revealed substantial variation in toxicity with 24 of the 381 samples displaying 100% larval mortality within the seven day exposure period. Four of the high activity plants were selected and subjected to bioassay guided fractionation. The results of the testing of the fractions generated identified one fraction of the plant, Toddalia asiatica as being very potent against the An. arabiensis larvae. CONCLUSION: The present study has successfully identified a plant with superior larvicidal activity at both the crude and semi pure fractions generated through bio-assay guided fractionation. These results have initiated further research into isolating the active compound and developing a malaria vector control tool.

Screening for adulticidal bioactivity of South African plants against Anopheles arabiensis.

BACKGROUND: This study was conducted to evaluate whether a selection of South African ethnomedicinal plants included in this study displayed insecticidal properties when screened against adult stages of the mosquito. METHODS: 381 crude extracts of 80 plant taxa in 42 families were sprayed onto ceramic tiles and screened using the cone bio-assay method for insecticide efficacy testing. Blood-fed, female Anopheles arabiensis mosquitoes were exposed to the treated tiles for a period of sixty minutes. Mosquito mortality was monitored for twenty-four hours. RESULTS: Of all the extracts analysed, the highest activity was observed in Ptaeroxylon obliquum (Ptaeroxylaceae) and Pittosporum viridiflorum (Pittosporaceae), a single extract from each, exhibiting more than 50% mortality. A large proportion (81.63%) of the extracts tested displayed low levels of mosquitocidal activity. The remainder of the extracts (17.85%) exhibited no bioactivity (0% mortality). CONCLUSIONS: The screening results have shown that in accordance with WHO standards, none of the crude extracts tested had exhibited greater than 60% mortality against the adult stages of the malaria vector Anopheles arabiensis.

Evaluation of selected South African ethnomedicinal plants as mosquito repellents against the Anopheles arabiensis mosquito in a rodent model.

BACKGROUND: This study was initiated to establish whether any South African ethnomedicinal plants (indigenous or exotic), that have been reported to be used traditionally to repel or kill mosquitoes, exhibit effective mosquito repellent properties. METHODS: Extracts of a selection of South African taxa were tested for repellency properties in an applicable mosquito feeding-probing assay using unfed female Anopheles arabiensis. RESULTS: Although a water extract of the roots of Chenopodium opulifolium was found to be 97% as effective as DEET after 2 mins, time lag studies revealed a substantial reduction in efficacy (to 30%) within two hours. CONCLUSIONS: None of the plant extracts investigated exhibited residual repellencies >60% after three hours.

Rifampin levels, interferon-gamma release and outcome in complicated pulmonary tuberculosis.

Factors that relate to medium-term outcome in patients with pulmonary tuberculosis (PTB) who have completed the 2-month intensive phase of treatment are incompletely understood. The relationship between in vitro production of interferon-gamma (IFN-gamma), interleukins (ILs)-5 and -10 and drug levels determined after 2 months of drug therapy, to outcome at 24 months was studied prospectively. Cytokine concentrations were determined from culture supernatants after stimulation of whole blood with purified protein derivative (PPD) of Mycobacterium tuberculosis. Plasma concentrations of rifampin, isoniazid, pyrazinamide and ethambutol were determined by high-performance liquid chromatography. The treatment failure and relapse free survival probability was 0.54 (95% CI: 0.40-0.67) at 24 months. In multivariate analysis of parameters at 2 months the strongest positive associations with disease free survival were IFN-gamma response to PPD (p=0.002) and serum creatinine (p=0.001). Drug concentrations were not associated with outcome although rifampin exposure correlated with IFN-gamma response to PPD (p=0.0132). These data suggest that the ability to mount a recall immune response to M. tuberculosis may influence treatment outcome. The data support the idea to identify persons at risk of a poor treatment outcome by monitoring of the in vitro response to tuberculosis antigens.

Combination of tunicamycin with anticancer drugs synergistically enhances their toxicity in multidrug-resistant human ovarian cystadenocarcinoma cells.

BACKGROUND: The pharmacologic modulatory effects of the antibiotic, tunicamycin (TM), on multidrug-resistant human UWOV2 ovarian cancer cells are reported. The UWOV2 cell line was derived from a cystadenocarcinoma in a patient refractory to combination chemotherapy with actinomycin D, vincristine (VCR), cis-diaminedichloroplatinum (II) (CDDP) and doxorubicin (DXR). In an attempt to explain drug resistance in this cell line, we examined the effects of TM on their sensitivity to various anticancer drugs, the uptake, efflux and retention of [3H]VCR, and their ability to bind [14C]DXR and [3H]azidopine (AZD), a photoaffinity label of the multidrug transporter, P-glycoprotein (Pgp). RESULTS: TM effectively decreased the EC50 for DXR, EXR, VCR and CDDP, thus enhancing their cytotoxicity. The antibiotic also prolonged the intracellular retention time of [3H]VCR and increased the binding of both [14C]DXR and [3H]AZD to the cells. CONCLUSION: It is concluded that the pharmacomodulatory effects of TM in these cells are mediated by global inhibition of protein and glycoprotein synthesis and synergistic interaction with antineoplastic drugs. The ability of TM to enhance the sensitivity of drug resistant tumour cells may have impact on the design and optimization of novel resistance modifiers to improve the efficacy of combination treatment of intractable neoplasms.

The Effects of Cyclophosphamide on Alkaline Phosphatase Activity and on in vitro Post-Implantation Murine Blastocyst Development† : (preimplantation embryo/cyclophosphamide/teratogenicity/alkaline phosphatase/differentiation).

Cyclophosphamide, administered in doses of 20 and 40 mg/kg body weight to pregnant inbred CBA mice on the third day of gestation (60 h after the estimated time of ovulation) reduced the activity of non-specific alkaline phosphatase (E.C. 3.1.3.1.) in 84 h-old blastocysts in a dose-related fashion compared with controls (p < 0.02 in each case; comparison of groups by Kruskal Wallis analysis of variance). This effect was not demonstrated with 4 mg/kg body weight (p < 0.1). Forty mg/kg body weight, but not the lower doses of cyclophosphamide, significantly retarded the hatching of embryos from the zona pellucida, attachment to the culture dish, and the formation of trophoblast outgrowths when the blastocysts were subsequently cultured in vitro for 120 h. The growth of an expanded inner cell mass was impaired in the 20 and 40 mg/kg groups. The differentiation of the inner cell mass into endoderm and ectoderm was significantly affected in the 4 mg, 20 mg and 40 mg/kg groups (p < 0.05, p < 0.01 and p < 0.001 respectively). The possible relationships of these various findings are discussed in the text. These results suggest that alkaline phosphatase may be a useful indicator of impaired growth and differentiation of the inner cell mass after exposure of preimplantation embryos to teratogens.

In vitro antiplasmodial activity of medicinal plants native to or naturalised in South Africa.

The increasing prevalence and distribution of malaria has been attributed to a number of factors, one of them being the emergence and spread of drug resistant parasites. Efforts are now being directed towards the discovery and development of new chemically diverse antimalarial agents. The present study reports on the in vitro antiplasmodial activity of 134 plant taxa native to or naturalised in South Africa, representing 54 families, which were selected semi-quantitatively using weighted criteria. The plant extracts were tested for in vitro activity against a Plasmodium falciparum strain D10 using the parasite lactate dehydrogenase (pLDH) assay. Of the 134 species assayed, 49% showed promising antiplasmodial activity (IC(50)< or = 10 microg/ml), while 17% were found to be highly active (IC(50)< or = 5 microg/ml). Several plant species and genera were shown for the first time to possess in vitro antiplasmodial activity. These results support a rational rather than random approach to the selection of antiplasmodial screening candidates, and identify a number of promising taxa for further investigation as plant-based antimalarial agents.

Determinants of rifampin, isoniazid, pyrazinamide, and ethambutol pharmacokinetics in a cohort of tuberculosis patients.

Evaluation of sources of pharmacokinetic variation can facilitate optimization of tuberculosis treatment regimens by identification of avoidable sources of variation and of risk factors for low or high drug concentrations in patients. Our objective was to describe the pharmacokinetics of rifampin, isoniazid, pyrazinamide, and ethambutol in a cohort of tuberculosis patients established on first-line treatment regimens and to evaluate the determinants of pharmacokinetic variation. Plasma concentration-time profiles were determined for each of the drugs in 142 patients with drug-sensitive pulmonary tuberculosis after 2 months of daily treatment in hospital. Pharmacokinetic measures were described by noncompartmental analysis. Multiple linear regression was used to evaluate the patient and the treatment factors associated with variation of the area under the concentration-time curve from 0 to 8 h. Several factors independently associated with variations in antituberculosis drug concentrations were identified: human immunodeficiency virus infection was associated with 39% and 27% reductions for rifampin and ethambutol, respectively; formulation factors were determinants of rifampin and isoniazid bioavailability; female patients had increased rifampin and isoniazid concentrations but reduced ethambutol concentrations; older patients had higher levels of isoniazid and ethambutol; patients with a history of previous antituberculosis treatment had lower ethambutol concentrations; and the dose per kilogram of body weight was associated with the concentrations of all four agents. Further studies are required to assess the implications of variations in antituberculosis drug concentrations for efficacy and safety before decisions are made to change the dosing strategy in patients at risk.

A global perspective on vaccine safety and public health: the Global Advisory Committee on Vaccine Safety.

Established in 1999, the Global Advisory Committee on Vaccine Safety advises the World Health Organization (WHO) on vaccine-related safety issues and enables WHO to respond promptly, efficiently, and with scientific rigor to issues of vaccine safety with potential global importance. The committee also assesses the implications of vaccine safety for practice worldwide and for WHO policies. We describe the principles on which the committee was established, its modus operandi, and the scope of the work undertaken, both present and future. We highlight its recent recommendations on major issues, including the purported link between the measles-mumps-rubella vaccine and autism and the safety of the mumps, influenza, yellow fever, BCG, and smallpox vaccines as well as that of thiomersal-containing vaccines.