Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Carcinoma, Hepatocellular/therapy , Embolization, Therapeutic , Epirubicin/administration & dosage , Iodized Oil/administration & dosage , Liver Neoplasms/therapy , Aged , Carcinoma, Hepatocellular/blood supply , Embolization, Therapeutic/methods , Gallbladder/blood supply , Humans , Liver Neoplasms/blood supply , MaleABSTRACT
ER-30346 is a novel oral triazole with a broad spectrum of potent activity against a wide range of fungi. In the present study, we investigated the therapeutic effects of oral ER-30346 on experimental local infections caused by Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans and compared them with those of itraconazole and fluconazole. In experimental murine models of pulmonary aspergillosis, candidiasis, and cryptococcosis, ER-30346 reduced the numbers of CFU in the lungs significantly compared with the numbers of CFU in the lungs of the controls (P < 0.05). ER-30346 was as effective as or more effective than itraconazole against pulmonary aspergillosis. Against pulmonary candidiasis and cryptococcosis, ER-30346 was more effective than itraconazole and was as effective as fluconazole. ER-30346 was also effective against pulmonary candidiasis caused by fluconazole-resistant C. albicans. In mice with intracranial cryptococcosis, ER-30346 reduced the numbers of CFU in the brains significantly compared with the numbers of CFU in the brains of the controls (P < 0.05) and was more effective than itraconazole and as effective as fluconazole. In an experimental model of oral candidiasis in rats, ER-30346 reduced the numbers of CFU in oral swabs significantly compared with the numbers of CFU in oral swabs from the controls (P < 0.05) and was more effective than itraconazole and as effective as fluconazole. Thus, ER-30346 shows efficacy in murine aspergillosis, candidiasis, and cryptococcosis models. Further studies are needed to determine the potential of ER-30346 for use in the treatment of these infections.
Subject(s)
Antifungal Agents/therapeutic use , Aspergillosis/drug therapy , Candidiasis/drug therapy , Cryptococcosis/drug therapy , Thiazoles/therapeutic use , Triazoles/therapeutic use , Animals , Antifungal Agents/pharmacology , Aspergillosis/microbiology , Brain Diseases/drug therapy , Brain Diseases/microbiology , Candidiasis/microbiology , Candidiasis, Oral/drug therapy , Candidiasis, Oral/microbiology , Cryptococcosis/microbiology , Female , Fluconazole/therapeutic use , Lung Diseases, Fungal/drug therapy , Lung Diseases, Fungal/microbiology , Mice , Mice, Inbred ICR , Microbial Sensitivity Tests , Rats , Rats, Sprague-Dawley , Thiazoles/pharmacology , Triazoles/pharmacologyABSTRACT
The effect of a chemically synthesized polyprenol derivative, dihydroheptaprenol (DHP), on the non-specific resistance of mice to Sendai virus infection was investigated. The mice that received 200 micrograms of DHP intranasally twice, at 3 days and 1 day before the infection, showed a significant protection against Sendai virus infection. Treatment of mice twice even with as much as 2000 micrograms of DHP through the subcutaneous route, however, had no protective effect against infection. Excess interferon and tumour necrosis factor production in intranasally DHP-treated mice was seen 1 day after the infection when compared with Sendai virus alone controls or with DHP alone controls. Variance analysis of these findings indicates a prophylactic activity of DHP in pulmonary viral infections.
Subject(s)
Paramyxoviridae Infections/prevention & control , Terpenes/therapeutic use , Administration, Intranasal , Animals , Dose-Response Relationship, Drug , Female , Immunity, Innate/drug effects , Interferons/biosynthesis , Mice , Mice, Inbred Strains , Parainfluenza Virus 1, Human , Paramyxoviridae Infections/immunology , Paramyxoviridae Infections/metabolism , Pseudomonas Infections/drug therapy , Pseudomonas Infections/immunology , Pseudomonas Infections/metabolism , Terpenes/administration & dosage , Terpenes/immunology , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
E-0702, a new cephalosporin with a potent antipseudomonal action, was synthesized. In the study of the mode of action of this antibiotic in Escherichia coli, it was found that mutants which acquired resistance to E-0702 were isolated spontaneously and could be shown to be susceptible to its closely related derivatives, E-0702-060 and E-0702-061, and other representative beta-lactam antibiotics. In these mutants, no increased production of beta-lactamase was detectable. No apparent differences between the resistant mutants and the parental strains were observed in the affinity of E-0702 for penicillin-binding proteins. Furthermore, no significant reduction in or loss of both OmpF and OmpC porin proteins in the outer membrane was observed. The mutation was mapped to the tonB gene, which is known to be essential for the iron transport system of bacteria. The bactericidal action of E-0702 was rapidly expressed against iron-starved cells in which the iron transport system was induced, whereas the bactericidal action against iron-supplemented cells was ineffective. It is suggested that E-0702 is incorporated into bacterial cells as a chelator of iron via the tonB-dependent iron transport system, after which its strong and rapid bactericidal action is manifested.