Infliximab treatment prevents hyperglycemia and the intensification of hepatic gluconeogenesis in an animal model of high fat diet-induced liver glucose overproduction

The effect of infliximab on gluconeogenesis in an animal model of diet-induced liver glucose overproduction was investigated. The mice were treated with standard diet (SD group) or high fat diet (HFD group). HFD group were randomly divided and treated either with saline (100 µl/dose, ip, twice a day) or infliximab (10 µg in 100 µl saline per dose, ip, twice a day, i.e., 0.5 mg/kg per day). SD group also received saline. The treatment with infliximab or saline started on the first day of the introduction of the HFD and was maintained during two weeks. After this period, the mice were fasted (15 h) and anesthetized. After laparotomy, blood was collected for glucose determination followed by liver perfusion in which L-alanine (5 mM) was used as gluconeogenic substrate. HFD group treated with saline showed higher (p < 0.05) liver glucose production from L-alanine and fasting hyperglycemia. However, these metabolic changes were prevented by infliximab treatment. Therefore, this study suggested that infliximab could prevent the glucose overproduction and hyperglycemia related with glucose intolerance and type 2 diabetes

Efficacious Treatment of Non-Dermatophyte Mould Onychomycosis with Topical Amphotericin B

BACKGROUND: Dermatophytes are the main cause of onychomycosis, but various non-dermatophyte moulds (NDMs) are often the infectious agents in abnormal nails. In particular, Fusarium spp. and other NDMs are mostly insensitive to standard onychomycosis treatment with topical agents as well as with oral terbinafine and itraconazole.¦OBJECTIVE: The aim of this work is to report the efficacy of a topical amphotericin B solution on NDM onychomycosis in a series of 8 patients resistant to multiple conventional topical and systemic treatments.¦METHODS: Treatment consisted in the application of an optimized amphotericin B solution once daily to the affected nails and surrounding tissue. No mechanical debridement or medications were allowed except for trimming excessively long nails or in some cases occasionally applying urea-based cream to soften thickened nail plates.¦RESULTS: Onychomycosis was clinically cured in all patients after a 12-month treatment. Mycological cure was obtained in all but 1 patient.¦CONCLUSIONS: Topical amphotericin B is an efficacious, safe, cheap and easy-to-apply treatment which should be considered as first-line therapy for NDM onychomycosis

Resposta in vitro de fungos agentes de micoses cutâneas frente aos antifúngicos sistêmicos mais utilizados na dermatologia In vitro response of cutaneous mycosis fungal agents to the most widely used systemic antifungals in dermatology

FUNDAMENTOS - A alta frequência das micoses cutâneas justifica a necessidade de avaliar a possível contribuição da determinação do perfil de susceptibilidade aos antifúngicos in vitro. OBJETIVO - Avaliar se existe variabilidade nos isolados fúngicos quanto à susceptibilidade in vitro de fungos filamentosos, previamente isolados de micoses cutâneas, frente aos antifúngicos fluconazol, cetoconazol, itraconazol e terbinafina. MÉTODOS - Os fungos foram isolados e identificados por meio da metodologia clássica e o teste de susceptibilidade aos antifúngicos foi realizado segundo o método de microdiluição em caldo, de acordo com protocolo preconizado pelo Clinical Laboratory Standards Institute (CLSI), documento M38-A. RESULTADOS - Das 80 amostras de fungos filamentosos identificadas, o gênero Trichophyton representou 81%. As quatro drogas analisadas apresentaram grande variação nos gêneros Trichophyton e Microsporum. O gênero Fusarium foi resistente a todas as drogas testadas. A terbinafina foi o antimicótico mais eficaz contra a maioria dos isolados fúngicos. CONCLUSÃO - Houve uma grande variabilidade nos perfis de resposta aos antifúngicos testados. O estabelecimento de um método-teste de referência permitirá ao clínico maior objetividade na escolha de uma terapia adequada.<br>BACKGROUND - The high frequency of cutaneous mycosis justify the need to evaluate the possible contribution of in vitro profile of susceptibility to antifungal agents. OBJECTIVE - To evaluate whether there is variability in in vitro susceptibility by filamentous fungi, previously isolated from cutaneous mycosis, to fluconazole, ketoconazole, itraconazole and terbinafine. METHODS - Fungi were isolated and identified by classical methods and the antifungal susceptibility test was performed using the method of broth microdilution, according to a protocol recommended by the Clinical Laboratory Standards Institute (CLSI), through M38-A document. RESULTS - Amongst the 80 filamentous fungi identified, Trichophyton genus represented 81%. The four examined drugs showed great variation for Trichophyton spp and Microsporum spp. Fusarium spp was resistant to all tested drugs. Terbinafine was the most effective drug against the majority of the isolated fungi. CONCLUSION - There was great variability in response profiles to the tested antifungals. The definition of a reference test method will offer higher objectivity for physicians to choose the appropriate therapy