bromochloroacetic-acid and Tinea-Pedis

Terbinafine (Tbf) is a well-established anti-fungal agent used for management of a variety of dermal conditions including ringworm and athlete's foot. Both the biochemical mechanism of Tbf fungicidal action (based on squalene epoxidase inhibition) and the target region for Tbf in vivo (the stratum corneum (SC)) are well determined. However, the biochemical and pharmacokinetic approaches used to evaluate Tbf biochemistry provide no biophysical information about molecular level physical changes in the SC upon Tbf binding. Such information is necessary for improved drug and formulation design. IR spectroscopic methods were used to evaluate the effects of Tbf on keratin structure in environments commonly used in pharmaceutics to mimic those in vivo. The Amide I and II spectral regions (1500-1700 cm

Topics: Filaggrin Proteins; Humans; Intermediate Filament Proteins; Keratins; Protein Conformation, beta-Strand; Skin; Skin Abnormalities; Squalene Monooxygenase; Terbinafine; Tinea; Tinea Pedis

The therapeutic efficacy of KP-103, a triazole derivative, for 10 guinea pigs with interdigital tinea pedis or tinea corporis was investigated. Topical KP-103 solution (0.25 to 1%) was dose-dependently effective in treating both dermatophytoses. A 1% KP-103-treatment rendered all infected skins culture-negative on day-2 posttreatment. A high negative-culture rate was obtained with 1% solutions of butenafine and lanoconazole but not with 1% neticonazole solution. The follow up study performed on day-30 and day-9 posttreatment demonstrated that the relapse rates for 1% KP-103-treated animals with tinea pedis and for those with tinea corporis were 20 and 30%, respectively, and that these values were the same as those for 1% butenafine-treated animals, but lower than those for 1% lanoconazole-treated animals (55 and 80%, respectively). When a single dose of 1% KP-103 was applied to the back skin 48 hr before fungal inoculation, 9 of the 10 animals were protected from the dermatophytosis, suggesting that active KP-103 is retained in skin tissue for at least 48 hr after dosing. Moreover, it was suggested that KP-103 retains a high activity in the horny layer because of its lower keratin-affinity. The effectiveness of KP-103 against dermatophytoses may be due to the favorable pharmacokinetic properties in the skin tissues, together with its potent antifungal activity.

Topics: Animals; Antibiotic Prophylaxis; Antifungal Agents; Aspergillus flavus; Disease Models, Animal; Drug Evaluation, Preclinical; Guinea Pigs; Keratins; Male; Microbial Sensitivity Tests; Secondary Prevention; Tinea; Tinea Pedis; Toes; Treatment Outcome; Triazoles; Trichophyton

A keratinolytic proteinase with enzyme activity at acidic pH was isolated from culture filtrates of Trichophyton mentagrophytes, a major pathogenic fungus of dermatophytosis. The molecular weight of the proteinase was estimated to be 41,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 38,000 by gel filtration. The isoelectric point was determined to be 3.9. The proteinase had a pH optimum of 4.5 for keratin and 5.5 for hemoglobin. This enzyme hydrolyzed the synthetic chymotrypsin substrate Suc-Ala-Ala-Pro-Phe-MCA (Km, 0.59 mM), and its activity was strongly inhibited by chymostatin. Previously reported proteinases from dermatophytes have had enzyme activities in neutral or alkaline pH; however, healthy skin has a weakly acidic pH. Thus, the purified proteinase which has an optimal activity at acidic pH and hydrolyzes skin constituents could be an important virulence factor in dermatophytosis.

Topics: Cations, Divalent; Extracellular Space; Hydrogen-Ion Concentration; Isoelectric Point; Keratins; Kinetics; Molecular Weight; Peptide Hydrolases; Protease Inhibitors; Substrate Specificity; Tinea Pedis; Trichophyton

The amino acid composition of keratin from soles of patients suffering from hereditary palmoplantar keratoderma of the Unna Thost variety was investigated. Patients were divided into two groups: those without dermatophytosis and those whose hereditary palmoplantar keratoderma was complicated with a dermatophyte infection. The amino acid composition of the horny layer was compared to that of control individuals and to a previously performed analysis of mammalian hair. However, no difference was found between the groups nor was any explanation as to why Trichophyton mentagrophytes occurred significantly more often in soles of patients with hereditary palmoplantar keratoderma made apparent.

Topics: Adult; Amino Acids; Female; Humans; Keratins; Keratoderma, Palmoplantar; Male; Middle Aged; Skin; Tinea Pedis

Topics: Arthrodermataceae; Female; Germany, West; Humans; Keratins; Male; Nails; Onychomycosis; Psoriasis; Tinea Pedis

Topics: Adolescent; Ascomycota; Child; Child, Preschool; Dermatomycoses; Female; Fungi; Health Surveys; Humans; India; Keratins; Male; Microsporum; Mitosporic Fungi; Onychomycosis; Rural Population; Seasons; Soil Microbiology; Tinea; Tinea Capitis; Tinea Pedis; Trichophyton; Urban Population