Potent growth inhibitory activity of zidovudine on cultured human breast cancer cells and rat mammary tumors.

Originally designed as an antitumor agent, zidovudine (AZT) has exhibited only marginal tumor growth inhibitory activity. Recently, three abstracts have described positive clinical outcomes for a small number of patients with advanced breast cancer treated with weekly infusions of either methotrexate or cisplatin and AZT. Consequently, we conducted a preclinical study of the anti-breast cancer and anti-mammary tumor activity of AZT. Here we have demonstrated that AZT, alone, has a preferential in vitro and in vivo effect on breast and mammary cancer cells. It is 1000 times as potent as an inhibitor of the in vitro growth of the human breast cancer cell line MCF-7 (IC50 = 10 +/- 5 nM) than of the growth of the T-cell leukemia cell line CEM (IC50 = 14 +/- 2 microM). A novel mechanism for this preferential effect on growth is indicated by the 3-4-fold increase in production of phosphorylated AZT (mono-, di-, and triphosphate) in MCF-7 relative to CEM. We extended these in vitro observations to in vivo studies in rats and found that AZT is a potent in vivo inhibitor of the growth of methylnitrosourea-induced rat mammary tumors without any apparent toxic effects on internal organs. These preclinical results demonstrate, for the first time, that AZT has significant anti-breast cancer activity and strongly suggest that the clinical usefulness of this drug is worthy of investigation.

Influence of sundrying on the chemical composition, aflatoxin content and fungal counts of two pepper varieties--Capsicum annum and Capsicum frutescens.

Samples of sundried, matured red pepper, Capsicum annum with a moisture content (MC) of 12.7-26.8 percent had on dry weight basis, vitamin C, 5.0-6.4 mg/100 g; crude protein, 0.8-1.2 percent; total soluble solids, 3.3-4.1 percent, and fungal counts of log 4.4-4.5/g. Ordinary matured red C. annum had MC, 75.7-78.2 percent vitamin C, 36.1-38.5 mg/100 g; crude protein, 2.4-2.8 percent; total soluble solids, 9.3-9.9 percent and fungal count of log 3.32-3.39/g. Sundried matured red C. frutescens had corresponding values of 9.4-18.7 percent; 5.8-6.3 mg/100 g; 0.8-1.1 percent; 0.9-2.6 percent and log 3.2-3.4/g. No aflatoxins were detected in sundried, matured red C. frutescens, but aflatoxin B1 values obtained from C. annum varied from non-detectable to 2.2 micrograms/kg. Dominant fungi isolated from C. annum and C. frutescens were Rhizopus oryzaze, Aspergillus niger, A. flavus, Geotrichum candidum and Saccharomyces spp.

Bioequivalence of pyrantel pamoate dosage forms in healthy human subjects.

Drugs that are largely restricted to the gastro-intestinal tract (GIT) for their therapeutic efficacy and that are not substantially absorbed into the body are usually inadequately studied in terms of systemic bioavailability. The possibility of systemic effects requires that bioavailabilities be studied to ensure against enhanced toxicity resulting from formulation differences. Pyrantel pamoate falls into this category. High-performance liquid chromatography was employed in this study to determine plasma levels of pyrantel in nine healthy human subjects after administration of tablet and suspension dosage forms. Mean peak plasma concentrations of 37.56 +/- 9.37, 35.89 +/- 8.94, and 36.22 +/- 10.10 ng mL-1 were obtained following administration of 750 mg pyrantel pamoate in three different formulations. The mean tmax values were 2.02 +/- 0.12, 2.05 +/- 0.356, and 2.05 +/- 0.339 h respectively for the above dosage forms; the respective AUC0-9 values were 81.01 +/- 12.97, 94.59 +/- 17.18, and 101.47 +/- 19.59 h ng mL-1. There was no statistically significant difference between the bioavailabilities of the dosage forms tested. Large inter-subject variations were observed. One subject experienced abdominal discomfort and one experienced dizziness. It was not possible to clearly correlate individual variations in absorption with the observed adverse effect because the number of incidents was low (two out of 27 treatments).

Influence of grain quality, heat, and processing time on the reduction of aflatoxin B1 levels in 'tuwo' and 'ogi': two cereal-based products.

During the production of 'tuwo' from laboratory-contaminated corn (AFB1:150 mcg/kg) and sorghum (AFB1:87.5 mcg/kg) grains, reductions in the aflatoxin-B1 levels of pastes boiled for 30 min and 60 min were found to be 68.0% and 80.8%, respectively. In the preparation of 'ogi' from contaminated corn and sorghum grains, reductions of about 72.5% and 71.4%, respectively, were obtained after fermentation at ambient conditions. Reconstitution of 'ogi' paste into a porridge (akamu) considerably reduced the AFB level.

Effect of processing on the mycoflora and aflatoxin B1 level of a cassava-based product.

Cassava bread was prepared by pre-gelling, battering and baking cassava flour to which were added, in moderate amounts, sugar, yeast solution and edible oil. Baking was at 215 degrees C for 40 min. No mould was isolated from the cassava bread and the mean value of aflatoxin B1 (AFB1) for the three subsamples of cassava bread was 0.03 microgram/kg. The cassava tuber (Manihot esculenta Crantz), which was used for the production of cassava bread had an initial AFB1 level of 1.91 micrograms/kg and the dominant mycoflora were Penicillium oxalicum, Aspergillus flavus, Fusarium spp and some unidentified fungi.

Determination of ampicillin in the presence of cloxacillin.

A spectrophotometric method is described for the assay of ampicillin in the presence of cloxacillin in pharmaceutical preparations. It involves the reaction of hydrolysed ampicillin with formaldehyde in an acidic phosphate buffer (pH 2.5) and measurement of the absorbance of the product at 373 nm after dilution with 2 M sulphuric acid. The method is selective for ampicillin in the presence of cloxacillin. The absorbance had a linear relationship with concentration for the range studied (5-35 micrograms ml-1). By this method the ampicillin content of combined preparations of ampicillin and cloxacillin has been successfully determined in capsules, injections and a syrup.

Effects of sodium metabisulphite, hydrogen peroxide and heat on aflatoxin B1 in lafun and gari--two cassava products.

Sodium metabisulphite and hydrogen peroxide alone or in combination with heat (50-70 degrees C) were found to be effective in degrading aflatoxin B1 (AFB1) in lafun and gari. Hydrogen peroxide (H2O2) at a concentration of 3% in the aqueous phase gave a 12.5% degradation of aflatoxin B1 in lafun and at 50 degrees C, degradation levels of 25% and 50% were obtained with 6.0 and 9.0% H2O2, respectively. When sodium metabisulphite was applied during the production of gari (a fermented cassava product heated to 50-70 degrees C during production) AFB1 degradation levels were found to be 65.8%, 60.9%, 41.5% and 36.6%, respectively, for sodium metabisulphite levels of 1.0%, 0.8%, 0.5% and 0.3%.

Comparative in-vitro antibacterial activity of two brands of antibiotics against clinical isolates of some bacterial genera.

Six brands of ampicillin and four of gentamicin were compared for their in-vitro antibacterial activity against clinical isolates of Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. The minimum inhibitory concentrations obtained for each brand against each bacterial isolate compared very well with one another, and the kinetics of bactericidal activity showed that the brands of each antibiotic possessed similar activity against the clinical isolates tested.

Comparative bioavailability studies on some brands of ampicillin capsules.

The bioequivalence of two generics of Ampicillin capsules, hitherto untested, were assessed using Penbritin capsules, the innovator's brand, as the reference product. The bioavailability study was carried out in nine healthy volunteers given one capsule (250 mg) of ampicillin in a completely randomized cross-over design. Statistical analysis (ANOVA) of the results indicated that one of the products tested, designated ampicillin (X), was significantly different (p less than 0.05) in its bioavailability compared to Penbritin while the other product, ampicillin (Helm), was not.