Long-term monotherapy with suplatast tosilate in patients with mild atopic asthma: a pilot comparison with low-dose inhaled fluticasone.

BACKGROUND AND OBJECTIVE: Suplatast tosilate is a Th2 cytokine inhibitor that is effective for controlling persistent asthma. However, the long-term efficacy of suplatast is unknown. We compared the clinical efficacy of long-term monotherapy with suplatast tosilate with a low dose of inhaled steroids in patients with mild atopic asthma. METHODS: A total of 32 patients with mild atopic asthma were randomly assigned to receive suplatast (n=15) or fluticasone (n=17). In the suplatast group, 100 mg of suplatast was given orally 3 times a day (total daily dose = 300 mg) for 2 years. In the fluticasone group, 100 pg of fluticasone was inhaled twice a day (total daily dose = 200 tg) for 2 years. RESULTS: In the suplatast group, the improvements in peak expiratory flow (PEF) rate and forced expiratory volume in 1 second (FEV1) and the changes in the symptom diary scale and frequency of beta2 stimulant inhalation were generally similar to those in the fluticasone group, and efficacy was maintained for 2 years. Improvements in inflammatory indices, such as the sputum eosinophil cationic protein (ECP) level and exhaled nitric oxide concentration, were comparable in the suplatast and fluticasone groups. The improvement in airway hyperresponsiveness was also similar in the 2 groups. The peripheral blood eosinophil percent change, serum ECP level, and total IgE antibody titer improved only in the suplatast group. CONCLUSIONS: Long-term treatment with suplatast significantly improved symptoms and inflammatory indices in patients with mild atopic asthma. Along with fluticasone, suplatast is considered a useful drug for the management of mild atopic asthma.

Anticancer effects of a tertiary sulfonium compound, dimethylsulfoniopropionate, in green sea algae on Ehrlich ascites carcinoma-bearing mice.

The saline and dimethylsulfoniopropionate (DMSP) solutions at 5, 10 and 20 mM were preliminarily injected intraperitoneally every other day into two control and three DMSP groups of mice (n=8) for 2 wk and thereafter Ehrlich ascites-carcinoma (EAC) cells were peritoneally injected to one control and three DMSP groups of mice, leaving one control group without the EAC injection. Then, the body weight and survival time of all mice were examined over a long rearing time up to 300 d. All EAC-bearing mice, especially the carcinoma control and 5 mM DMSP-carcinoma group mice, rapidly increased their body weights early and then died by day 50 and day 90, respectively. In contrast, the administration of 10 and 20 mM DMSP solutions prolonged the lives of EAC-bearing mice at the survival rate of 50 and 63% respectively up to 300 d without any side effects. Furthermore, the administration of 10 mM DMSP solution proved to activate the delayed-type hypersensitivity of EAC bearing-mice, and the DMSP solutions over the concentrations of 5 to 30 mM to slightly reduce the dead cells in EAC cells on the synthetic medium. Accordingly, the preliminary supplementation of 10 and 20 mM DMSP solutions to EAC-bearing mice was proven to maintain their lives at high survival rates without direct damage to EAC cells for a long time, probably due to the activation of the immune system without any side effects.

Suplatast tosilate alters DC1/DC2 balance in peripheral blood in bronchial asthma.

Suplatast tosilate is an antiallergic drug that selectively suppresses Th2-cytokine production and inhibits airway hyperresponsiveness and eosinophilic airway inflammation. This drug has been also shown to improve pulmonary function and symptoms in steroid-dependent asthma, resulting in a decrease in doses of inhaled corticosteroid. However, the precise mechanism by which suplatast tosilate exerts an antiasthmatic effect in vivo remains to be known. Our previous study showed the polarization of circulating type 1 dendritic cells (DC1)/type 2 dendritic cells (DC2) balance toward DC2 in asthma, which might be associated with its Th2-dominant immune response. In the present study, we attempted to clarify the effect of suplatast tosilate on DC1/DC2 balance in asthma. Using multicolor flow cytometry, we enumerated circulating DC1 and DC2 before and 8 weeks after treatment with suplatast tosilate in nine patients with asthma. Before the treatment, the patients with asthma had a significant higher percentage of DC2 together with a significant lower ratio of DC1/DC2 compared with normal subjects. Administration of suplatast tosilate significantly decreased the percentage of DC2, but not that of DC1, resulting in a significant raises of the ratio of DC1/DC2. Concomitantly, intracellular cytokine analysis showed that the percentage of IL-4 producing CD4+ T cells was significantly decreased after the treatment. These data suggest that suplatast tosilate normalizes the polarized DC1/DC2 balance toward DC2 in asthma, which may also alter its Th2-dominant Th1/Th2 balance toward Th1.

Breath malodor in an asthmatic patient caused by side-effects of medication: a case report and review of the literature.

OBJECTIVE: The purpose of this report is to document the presence of dimethyl sulfide in mouth air as the predominant volatile sulfur compound (VSC) in an asthmatic patient who was regularly taking suplatast tosilate. STUDY DESIGN: The patient was a 33-year-old woman who complained of bad breath. She had been diagnosed as having asthma and was receiving periodical medical examinations once a month. VSC in her mouth air were measured with a gas chromatograph. Oral physiotherapy was also carried out to remove any oral malodor of which the source was intraoral. RESULTS: With the improvement in oral hygiene and periodontal conditions, the level of VSC was reduced but dimethyl sulfide still remained as the predominant VSC. CONCLUSIONS: Dimethyl sulfide metabolized from suplatast tosilate may be a potential cause of halitosis.

Thioacetamide-induced hepatic necrosis. I. Involvement of the mixed-function oxidase enzyme system.

Metabolic activation of thioacetamide (CH3CSNH2) to a toxic metabolite which is responsible for its hepatotoxicity and/or its carcinogenicity has been proposed by a number of investigators. In this investigation thioacetamide and one of its metabolites, thioacetamide sulfine (CH3CSONH2), have been compared for their ability to inhibit hepatic mixed-function oxidase enzymes as well as their ability to induce hepatic necrosis. Thioacetamide sulfine was found to decrease aminopyrine N-demethylation and aniline hydroxylation at a lower dose and at an earlier time after administration than was the case with thioacetamide. In addition, at all doses examined, thioacetamide sulfine produced a more severe centrilobular hepatic necrosis than equivalent doses of thioacetamide. To determine whether the hepatic mixed-function oxidase enzyme system was involved in the biotransformation of thioacetamide and/or thioacetamide sulfine to a hepatotoxic compound(s), the severity of liver damage was examined after the administration of an inducer or inhibitors of hepatic mixed-function oxidase enzyme activity. Phenobarbital pretreatment potentiated the hepatic necrosis produced by both thioacetamide and thioacetamide sulfine. In contrast, pyrazole, SKF 525-A, and cobaltous chloride protected against the hepatic necrosis caused by thioacetamide and thioacetamide sulfine. These data suggest that both thioacetamide and thioacetamide sulfine are activated by hepatic mixed-function oxidase enzymes to a hepatotoxic compound(s). These data also suggest that the hepatotoxicity may be mediated by its metabolism to thioacetamide sulfine which, in turn, is metabolized to an ultimate toxic metabolite.