terbinafine, Lamisil
Inhibition of human vascular endothelial cells proliferation by terbinafine.

Ho PY, Liang YC, Ho YS, Chen CT, Lee WS.

Graduate Institute of Cellular and Molecular Biology, Taipei Medical University, Taipei, Taiwan.

We have demonstrated previously that terbinafine (TB), an oral antifungal agent used in the treatment of superficial mycosis, suppresses proliferation of various cultured human cancer cells in vitro and in vivo by inhibiting DNA synthesis and activating apoptosis. In our study, we further demonstrated that TB at a range of concentrations (0-120 microM) dose-dependently decreased cell number in cultured human umbilical vascular endothelial cells (HUVEC). Terbinafine was not cytotoxic at a concentration of 120 microM, indicating that it may have an inhibitory effect on the cell proliferation in HUVEC. The TB-induced inhibition of cell growth rate is reversible. [(3)H]thymidine incorporation revealed that TB reduced the [(3)H]thymidine incorporation into HUVEC during the S-phase of the cell-cycle. Western blot analysis demonstrated that the protein levels of cyclin A, but not cyclins B, D1, D3, E, CDK2 and CDK4, decreased after TB treatment. The TB-induced cell-cycle arrest in HUVEC occurred when the cyclin-dependent kinase 2 (CDK2) activity was inhibited just as the protein level of p21 was increased and cyclin A was decreased. Pretreatment of HUVEC with a p21 specific antisense oligonucleotide reversed the TB-induced inhibition of [(3)H]thymidine incorporation. Taken together, these results suggest an involvement of the p21-associated signaling pathway in the TB-induced antiproliferation in HUVEC. Capillary-like tube formation and chick embryo chorioallantoic membrane (CAM) assays further demonstrated the anti-angiogenic effect of TB. These findings demonstrate for the first time that TB can inhibit the angiogenesis. Copyright 2004 Wiley-Liss, Inc.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15185342&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
The successful treatment of Trichophyton rubrum nail bed (distal subungual) onychomycosis with intermittent pulse-dosed terbinafine.

Zaias N, Rebell G.

Greater Miami Skin and Laser Center and Mount Sinai Medical Center, Miami Beach, FL 33140, USA. nardozaias aol.com

BACKGROUND: The standard treatment of Trichophyton rubrum nail bed onychomycosis (or distal subungual onychomycosis [DSO]) with daily terbinafine for 12 weeks involves treating for a fixed period shorter than the time required for complete replacement of the nail bed and overlying nail plate by normal growth. The same total amount of terbinafine pulse-dosed for approximately 12 months would treat the patient until normal replacement of the mycotic nail bed has occurred.OBJECTIVES: To determine the effectiveness of intermittent administration of oral terbinafine (250 mg/d for 7 consecutive days every 2-4 months) to cure DSO and to determine the maximum effective treatment interval. DESIGN: A prospective, nonrandomized, open study of sequential groups of office patients. SETTING: A private dermatology practice. METHODS: A sequence of 4 groups of office patients with DSO (n = 10-20 each) were treated with pulse-dosed terbinafine for 7 consecutive days at intervals of 2, 3, and 4 months, respectively. In each group, treatment was continued until the distally advancing new nail bed and nail had completely removed the mycotic defect or failure of fungistasis was detected. MAIN OUTCOME MEASUREMENT: Results were determined by monthly evaluation. Cure was noted as complete replacement of the mycotic nail bed and overlying nail plate (ascertained by monthly metric measurements of the mycosis-free nail bed and overlying nail place distal to the proximal nail fold). Treatment failure was noted when the mycosis-free proximal portion of the nail bed failed to increase in correspondence with the distally directed movement of the nail bed and overlying nail. RESULTS: Thirty-nine (93%) of the 42 patients in the first 3 groups were cured (95% binomial confidence interval, 67%-100%) with no evidence of decrease in efficacy. However, the group of patients who received the 7-day pulse treatment every 4 months experienced significantly more failures (P<.01), and cures dropped to 10 of 17 cases. CONCLUSION: Terbinafine is an effective treatment for DSO when pulse-dosed for 7 days every 3 months but not every 4 months.

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terbinafine, Lamisil
[Analysis of facial lesions on adult type atopic dermatitis with anti-fungus drug (terbinafine hydrochloride) -- analysis of serum anti-Malassezia IgE antibody titers and histamine release test]

[Article in Japanese]

Maejima H, Tokunaga C, Kaneko S, Mukai H, Abe A.

Division of Dermatology, Yokohama rosai Hospital. hm4765 yahoo.ac.jp

Malassezia furfur has been described as an aggravating factor in facial lesions of atopic dermatitis, and oral antifungal agents have been reported to be effective against these lesions. We used terbinafine hydrochloride to treat 15 patients with adult-type atopic dermatitis and evaluated its efficacy by measuring the improvement in facial skin manifestations, serum IgE values, and serum anti-Malassezia IgE antibody titers. A histamine release test (HRT) for Malassezia. was also performed in 6 of the 15 patients. The facial skin manifestations improved in 8 (53.3%) of the 15 patients, and there were significant simultaneous decreases in their serum IgE values. The serum anti-Malassezia IgE antibody titer decreased significantly in all 15 patients. However, no significant correlation was observed between the HRT and the facial skin manifestations. We concluded that oral terbinafine hydrochloride is effective against the facial lesions of atopic dermatitis patients and this is possibly caused by decrease of Malassezia antigen in the facial lesions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15247532&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
In vitro activity of terbinafine and itraconazole against Aspergillus species isolated from otomycosis.

Karaarslan A, Arikan S, Ozcan M, Ozcan KM.

Department of Microbiology and Clinical Microbiology, Ankara University Medical School, Ankara, Turkey. karaars medicine.ankara.edu.tr

The minimum inhibitory concentrations (MIC, microg ml-1) of itraconazole and terbinafine against overall 34 Aspergillus isolates from the external ear canals with otomycosis have been determined with M38-P microdilution method suggested by National Committee for Clinical Laboratory Standards (NCCLS). MIC intervals in 48 h determined by taking MIC-2 value of itraconazole (the lowest drug concentration causing 50% inhibition of visible fungal growth) and MIC-0 value of terbinafine (the lowest drug concentration causing 100% inhibition of visible fungal growth) as a basis have been found as follows: 0.125-1 and 0.06-0.5 microg ml-1 for A. niger (22 strains), 0.06-0.25 and 0.06-0.125 microg ml-1 for A. flavus (10 strains), 0.125 and 0.125-0.5 microg ml-1 for A. terreus (two strains). It has been observed that both of the antifungal agents showed an in vitro activity against all Aspergillus species tested.

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terbinafine, Lamisil
Clinical and histological aspects of toenail onychomycosis caused by Aspergillus spp.: 34 cases treated with weekly intermittent terbinafine.

Gianni C, Romano C.

Department of Dermatology, Scientific Institute, S. Raffaele Hospital, Milan, Italy. claudiagianni tiscali.it

BACKGROUND: Non-dermatophytic onychomycoses represent 1.45-17.6% of all fungal nail infections. Epidemiological studies have shown that Aspergillus spp. are emerging fungal agents of toenail onychomycosis. Indeed, after Scopulariopsis spp. the genus Aspergillus is the second most common agent of non-dermatophytic onychomycosis. The diagnosis and treatment of toenail onychomycosis caused by non-dermatophyte moulds are not always straightforward. OBJECTIVES: The aims of this study were to describe the clinical appearance of toenail onychomycosis due to Aspergillus spp., to investigate the pathogenetic role of these agents and to evaluate the efficacy and safety of weekly intermittent terbinafine (500 mg/day for 1 week each month for 3 months) in the treatment of these patients. PATIENTS AND METHODS: Mycological study of 2,154 patients with onychodystrophy revealed 1,228 onychomycoses (57%) including 71 cases due to non-dermatophytic fungi (5.6%). Non-dermatophytic onychomycosis caused by Aspergillus spp. represented 2.6% of all onychomycoses. The subjects were 34 patients (22 females, 12 males, age range 30-82 years) observed between September 1999 and December 2001, with toenail onychomycosis caused by Aspergillus spp. confirmed by standard techniques (microscopic examination and culture according to the criteria of English), histological examination of nail clippings and scanning electron microscope examination of the cultures whenever necessary. RESULTS: The clinical features suggesting onychomycosis due to Aspergillus spp. are chalky deep white nail, rapid involvement of lamina and painful perionyxis without pus. Standard mycological tests (direct microscopy and fungal culture) and histological examination confirmed the pathogenetic role of Aspergillus spp. in onychomycoses. In particular, the histological examination was positive in 28 cases (82%) and useful in identifying typical aspects of Aspergillus spp. nail infections. At the follow-up, 12 months after the start of therapy with pulsed terbinafine, clinical and mycological recovery was confirmed in 30 of the 34 patients (88%). CONCLUSIONS: Treatment of non-dermatophytic onychomycosis with terbinafine usually requires at least 3 months of continuous systemic therapy. Our study of 34 patients confirms that terbinafine is particularly effective in the treatment of Aspergillus spp. nail infections and that a pulsed regimen is more economical and less demanding.

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terbinafine, Lamisil
Terbinafine resistance mediated by salicylate 1-monooxygenase in Aspergillus nidulans.

Graminha MA, Rocha EM, Prade RA, Martinez-Rossi NM.

Departamento de Genetica, Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, 14049-900 Ribeirao Preto, Sao Paulo, Brazil.

Resistance to antifungal agents is a recurring and growing problem among patients with systemic fungal infections. UV-induced Aspergillus nidulans mutants resistant to terbinafine have been identified, and we report here the characterization of one such gene. A sib-selected, 6.6-kb genomic DNA fragment encodes a salicylate 1-monooxygenase (salA), and a fatty acid synthase subunit (fasC) confers terbinafine resistance upon transformation of a sensitive strain. Subfragments carrying salA but not fasC confer terbinafine resistance. salA is present as a single-copy gene on chromosome VI and encodes a protein of 473 amino acids that is homologous to salicylate 1-monooxygenase, a well-characterized naphthalene-degrading enzyme in bacteria. salA transcript accumulation analysis showed terbinafine-dependent induction in the wild type and the UV-induced mutant Terb7, as well as overexpression in a strain containing the salA subgenomic DNA fragment, probably due to the multicopy effect caused by the transformation event. Additional naphthalene degradation enzyme-coding genes are present in fungal genomes, suggesting that resistance could follow degradation of the naphthalene ring contained in terbinafine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15328121&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
In vitro susceptibilities of isolates of Sporothrix schenckii to itraconazole and terbinafine.

Kohler LM, Monteiro PC, Hahn RC, Hamdan JS.

Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil.

Thirty isolates of the yeast form of Sporothrix schenckii were evaluated for in vitro susceptibility to itraconazole and terbinafine by the recommended NCCLS modified technique (M27-A2). The MICs of itraconazole obtained oscillated between 0.062 and 4.0 microg/ml, and those of terbinafine oscillated between 0.007 and 0.50 microg/ml; therefore, terbinafine showed greater in vitro activity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15365033&dopt=Abstract terbinafine Lamisil