Dietary maltitol decreases the incidence of 1,2-dimethylhydrazine-induced cecum and proximal colon tumors in rats.

Maltitol is fermented in the colon due to only partial hydrolysis in the small intestine. In the present study, we examined effects of dietary maltitol on dimethylhydrazine-induced intestinal tumor in rats. In experiment 1, rats were fed a fiber-free diet or diets supplemented with 1 or 5 g/100 g maltitol for 27 wk. Each group of rats was injected with dimethylhydrazine or vehicle alone for the first 14 wk of the experimental period. Maltitol supplementation at 1 g/100 g of the diet significantly reduced tumor incidence in the cecum and the 5% supplement reduced tumor incidence in both the cecum and proximal colon in dimethylhydrazine-treated rats. In experiment 2, we investigated the effect of the 1 g/100 g maltitol diet on the short chain fatty acid concentrations in cecal contents of placebo and dimethylhydrazine-treated rats. Intake of the 1 g/100 g maltitol diet doubled (P < 0.05) the concentration of butyrate but did not affect acetate or propionate in the cecal contents. These results suggest that dietary maltitol has a protective effect against dimethylhydrazine-induced tumors in rat cecum and proximal colon and that butyrate produced by bacterial fermentation of maltitol in the cecum may be involved in the protection.

[Evaluation of clinical efficacy of rifampicin in the treatment of nontuberculous mycobacteriosis from in vitro susceptibility testing].

In vitro susceptibility testing of various mycobacteria (a total of 295 strains) to rifampicin was carried out using Ogawa egg medium and inoculation of 0.02 ml-samples from 10 mg wet weight per ml suspensions, which were prepared from 10 day-old cultures (M. tuberculosis, 21 day-old cultures; M. fortuitum, 3 day-old cultures). The minimal inhibitory concentration (MIC) was determined after incubation at 37 degrees C for 14 days (M. tuberculosis and M. xenopi 21 days and M. fortuitum 5 days). MIC of M. tuberculosis strains, which were isolated from patients who were untreated previously by any antituberculosis drugs, was in the range of 3.13 to 12.5 micrograms/ml, thus the critical concentration of rifampicin, in which the clinical efficacy of rifampicin could be expected, was determined as 12.5 micrograms/ml. The percentage of strains of each species which are susceptible to this critical concentration is shown in Table 1. In M. avium complex strains, 50% of the strains were inhibited by rifampicin equal to or lower than the critical concentration. However, it is considered to be difficult to cure the disease completely even in these cases, because of the lack of other effective combination drugs with rifampicin. Monotherapy with rifampicin or that with less effective combined drugs would result in development of rifampicin-resistant population and failure of treatment. In successive studies, we will try to find out best possible combination drugs. From this study, the highest efficacy of rifampicin treatment was expected in the disease due to M. kanasaii and the lowest efficacy in the disease caused by M. fortuitum.

[Evaluation of cycloserine in the treatment of infections caused by nontuberculous mycobacteria viewed from in vitro experiments].

Evaluation of cycloserine as a drug in the treatment of infections caused by nontuberculous mycobacteria was made from in-vitro studies, in which Mycobacterium tuberculosis strains were used as the standard of the evaluation. The susceptibility testing to cycloserine was made using Ogawa egg medium. Bacterial suspensions, 10 mg wet weight/ml, prepared from 10 day-old cultures (M. tuberculosis, 14 day-old cultures) growing on Ogawa egg medium were used as the source of inoculation. A 0.02 ml-sample of the suspensions was inoculated onto Ogawa egg medium containing cycloserine or containing no drug, and the media inoculated were incubated at 37 degrees C. The minimal inhibitory concentration (MIC) was determined after incubation for 14 days (M. tuberculosis, for 21 days). The MIC was determined as the lowest concentration of the drug, on which the growth of test strains was completely inhibited. However, residual growth was sometimes observed. This was regarded as growth inhibition, because control medium containing no drug showed always abundant, membraneous growth. The results are shown in Fig.. The growth of M. tuberculosis strains was inhibited by the concentrations of 6.25 to 25 micrograms/ml. However, considering our previous observations on the relationship between the cycloserine resistance and the drug efficacy (reference 1), we regarded the MIC 12.5 micrograms/ml as critical concentration for presumable clinical efficacy. The ratios of strains of various mycobacterial species showing the MICs lower than the critical concentration are shown in Table. As seen in this table, clinical efficacy of cycloserine was expected in the treatment of infections caused by Mycobacterium kansasii, M. malmoense, M. simiae, M. scrofulaceum and M. marinum.(ABSTRACT TRUNCATED AT 250 WORDS)

[Sulfadimethoxine as a promising drug in the treatment of infections caused by Mycobacterium kansasii and Mycobacterium xenopi--differentiation between M. kansasii and M. marinum and between M. gordonae and M. scrofulaceum by the susceptibility testing to sulfadimethoxine].

Susceptibility testing to sulfadimethoxine of various mycobacteria was made using Ogawa egg medium containing various concentrations of the drug. Each medium was inoculated by a 0.02 ml-sample of bacterial suspensions (10 mg wet weight per ml) prepared from 10 day-old (M. tuberculosis, 14 day-old) cultures growing on Ogawa egg medium after homogenizing the bacteria by shaking with glass beads. The media inoculated were incubated at 37 degrees C for 14 days (M. marinum, at 28 degrees C). The minimal inhibitory concentration (MIC) was determined as the lowest drug concentration on which the growth of bacteria was completely inhibited. However, residual growth occurred often. This was regarded as negative growth, because control medium containing no drug always exhibited abundant membraneous growth. Of the mycobacteria tested, M. kansasii (MICs, 0.8-3.2 micrograms/ml) and M. xenopi (MICs, 0.2-3.2 micrograms/ml) were most susceptible to this drug. Other mycobacteria showed the MICs higher than 3.2 micrograms/ml. The drug seemed to be useful in the treatment of infections caused by M. kansasii and M. xenopi. Furthermore, the susceptibility testing to sulfadimethoxine was considered to be useful for differentiation between two photochromogens, M. kansasii and M. marinum and for differentiation between two scotochromogens, M. scrofulaceum and M. gordonae (Fig. 3 and 4).

Evidence that antituberculosis drugs are really effective in the treatment of pulmonary infection caused by Mycobacterium avium complex.

Successful chemotherapy of pulmonary disease caused by Mycobacterium avium complex by antituberculosis drugs has been reported by a number of investigators. However, no certain evidence of the efficacy has yet been demonstrated in a controlled clinical trial. The present study has approached this problem in 2 ways: serial analysis of minimal inhibitory concentrations (MIC) during treatment and correlation of response to therapy with initial MIC. It was observed that after administration of antituberculosis drugs (rifampin, isoniazid, kanamycin, enviomycin, and minocycline), MIC values for the M. avium complex strain increased significantly. This change may be considered a result of suppression of relatively susceptible bacteria and as evidence of the efficacy of drugs. Furthermore, a correlation between the MIC values determined before chemotherapy with the conversion of sputum to negative was shown. The M. avium complex strains varied markedly in their susceptibility to antituberculosis drugs, and these susceptibilities were correlated with the chemotherapeutic effect. The fate of patients seemed to be greatly influenced by the susceptibilities of the strains that caused infection.

Antituberculosis activity of ofloxacin (DL 8280) on experimental tuberculosis in mice.

Ofloxacin (DL 8280) is rapidly eliminated from mouse organs. It disappears quickly from the lungs and the spleen and more slowly from the liver and the kidneys. The antituberculosis activity of this agent was shown in mice when the agent was given intraperitoneally at daily doses of 1 mg per mouse (approximately 42 mg/kg). The number of viable bacteria of Mycobacterium tuberculosis strain H37Rv contained in the liver decreased markedly in the mice treated with ofloxacin, and the inhibitory effect of the agent seemed to appear when the tubercle bacilli actively multiplied.