Thomas L. Ray

Candida Albicans Acid Proteinase: Characterization and Role in Candidiasis

Candida albicans and related species are medically important yeast-like dimorphic fungi that are responsible, in part, for the rising incidence of serious, life-threatening opportunistic infections seen in immunocompromised and debilitated patients. In addition to minor localized infections of cutaneous, oropharyngeal and vaginal epithelium, Candida spp. produce transient or persistent fungemia that leads to systemic infections of virtually any organ (esp. liver, kidney and lung). Hematologic malignancy and transplant patients with prolonged neutropenia and antibiotic resistant fevers are particularly at risk. C. albicans and C. tropicalis are medically the most important, although other species do cause disease, but less frequently.

Double-blind comparison of itraconazole and placebo in the treatment of tinea corporis and tinea cruris

BACKGROUND Tinea corporis and tinea cruris are usually treated with a topical antifungal agent unless the infection is unresponsive, involves an extensive area, is chronic, or is in a difficult-to-access area. In these cases oral antifungals are frequently used. OBJECTIVE This double-blind study was undertaken to determine whether a 2-week course of oral itraconazole would produce statistically significant clinical and mycologic improvement in the treatment of tinea corporis, tinea cruris, or both, over the results obtained with placebo. A second objective was to determine the safety of itraconazole, through routine measurements of serum chemistry profiles. METHODS Sixty-seven patients were entered into a double-blind, multicenter study to compare the clinical and mycologic effects of itraconazole, 100 mg daily (45 patients), and placebo (22 patients) on tinea corporis and/or tinea cruris. The duration of treatment was 2 weeks. The investigators assessed signs and symptoms and performed a potassium hydroxide examination and culture at baseline, at termination of therapy, and 2 weeks after completion of treatment. RESULTS Twenty-two (96%) of 23 evaluable patients in the itraconazole group had healed or markedly improved lesions, as compared with 5 of 13 (39%) in the placebo group (p < or = 0.01). Similarly, the condition in 13 of 23 patients (57%) in the itraconazole group was mycologically cleared at the end of treatment whereas this result occurred in only 2 (17%) of 12 patients in the placebo group (p = 0.02). The prevalence of adverse side effects was lower for the itraconazole-treated group (20%) than for the placebo-treated group (36%). CONCLUSION Itraconazole 100 mg once daily is an effective agent for the treatment of tinea cruris and tinea corporis.

Structure of Secreted Aspartic Proteinases from Candida

Pathogens of the genus Candida can cause life threatening infections in immunocompromised patients. The three–dimensional structures of two closely related secreted aspartic proteinases from C. albicans complexed with a potent (Ki=0.17 nM) inhibitor, and an analogous enzyme from C. tropicalis reveal variations on the classical aspartic proteinase theme that dramatically alter the specificity of this class of enzymes. The novel fungal proteases present: i) an 8 residue insertion near the first disulfide (Cys45–Cys50, pepsin numbering) that results in a broad flap extending towards the active site; ii) a seven residue deletion replacing helix hN2 (Serll0–Tyrll4), which enlarges the S3 pocket; iii) a short polar connection between the two rigid body domains that alters their relative orientation and provides certain specificity; and iv) an ordered 12 residue addition at the car–boxy terminus. The same inhibitor (A–70450) binds in an extended conformation in the two variants of C albicans protease, and presents a branched structure at the P3 position. However, the conformation of the terminal methylpiperazine ring is different in the two crystals structures. The implications of these findings for the design of potent antifungal agents are discussed.

Technology in dermatology: Meeting the challenge today and tomorrow

If information technology is to enhance dermatology, physicians must adapt to new uses and forms oflanguage previouslyunconsidered and must adopt new methods and standards of communication. The American Academy of Dermatology (AAD) celebrated its fiftieth anniversary by presenting the 1988 Congress on Technology. The Congress focused on three technologic perspectives: educational applications, clinical practice, and medical information systems (medical informatics). This article considers these issues and offers highlights of the AAD Congress on Technology.