Antiretroviral drugs saquinavir and ritonavir reduce inhibitory concentration values of itraconazole against Histoplasma capsulatum strains in vitro

Recent studies have shown that some drugs that are not routinely used to treat fungal infections have antifungal activity, such as protease inhibitor antiretroviral drugs. This study investigated the in vitro susceptibility of Histoplasma capsulatum var. capsulatum to saquinavir and ritonavir, and its combination with the antifungal itraconazole. The susceptibility assay was performed according to Clinical and Laboratory Standards Institute guidelines. All strains were inhibited by the protease inhibitor antiretroviral drugs. Saquinavir showed minimum inhibitory concentrations ranging from 0.125 to 1 mu g mL(-1) for both phases, and ritonavir presented minimum inhibitory concentrations ranging from 0.0312 to 4 mu g mL(-1) and from 0.0625 to 1 mu g mL(-1) for filamentous and yeast phase, respectively. Concerning the anti fungal itraconazole, the minimum inhibitory concentration values ranged from 0.0019 to 0.125 mu g mL(-1) and from 0.0039 to 0.0312 mu g mL(-1) for the filamentous and yeast phase, respectively. The combination of saquinavir or ritonavir with itraconazole was synergistic against H. capsulatum, with a significant reduction in the minimum inhibitory concentrations of both drugs against the strains (p < 0.05). These data show an important in vitro synergy between protease inhibitors and itraconazole against the fungus H. capsulatum. (C) 2016 Published by Elsevier Editora Ltda.CNPqCAPESUniv Fed Ceara, Postgrad Program Med Microbiol, Specialized Med Mycol Ctr, Fortaleza, CE, BrazilUniv Fed Ceara, Postgrad Program Med Sci, Fortaleza, CE, BrazilUniv Estadual Ceara UECE, Postgrad Program Vet Sci, Fortaleza, CE, BrazilUniv Fed Ceara, Dept Stat & Appl Math, Fortaleza, CE, BrazilUniv Fed Sao Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, Sao Paulo, SP, BrazilHosp Sao Jose, Fortaleza, CE, BrazilUniv Fed Sao Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, Sao Paulo, SP, BrazilCNPq: 303396/2014-8CNPq: 552161/2011-0CAPES: AE1 - 0052-000630100/11Web of Scienc

Efeito da estimulação auditiva rítmica associada à fisioterapia na mobilidade funcional de idosos sedentários: um ensaio clínico randomizado

A Estimulação Auditiva Rítmica (EAR) tem despertado interesse pelos efeitos positivos durante o envelhecimento sobre os declínios da mobilidade. Objetivo: Avaliar os efeitos de um treinamento com estimulação auditiva rítmica associada à fisioterapia sobre mobilidade funcional em idosos sedentários. Métodos: Neste ensaio clínico randomizado, controlado, simples cego os idosos foram alocados em três grupos: controle (GC), estimulação auditiva rítmica associada à fisioterapia (EAR+FT) e fisioterapia (FT). Os grupos FT e EAR+FT foram submetidos a 12 sessões com o protocolo da fisioterapia (três vezes por semana, 40 min/sessão). Ao grupo EAR+FT eram acrescidos a estimulação auditiva rítmica com música (10-20 min/sessão), fornecidos pelo aplicativo ParkinSONS®. Para a análise dos dados, foi utilizada a ANOVA two-way com medidas repetidas para comparação entre os grupos e o tempo, com o post hoc de Tukey. O tamanho do efeito das intervenções também foi calculado. O nível de significância estabelecido foi de p&lt;0.05. Resultados: Não foi encontrada diferença significativa entre os grupos. Na análise pareada, foi observado que o grupo EAR+FT apresentou resultados significativos e tamanho do efeito benéfico com aumento da velocidade (p= 0.0001), redução do tempo (p= 0.001) e do número de passos (p= 0.0007), redução nos valores do TUG (p= 0.0001), aumento do deslocamento no TAF (p= 0.0001), melhora dos escores no TUG-ABS (p= 0.003) e PAP (p= 0.0001). Conclusão: Verificou-se um efeito positivo do uso da EAR associada à fisioterapia sobre mobilidade funcional de idosos sedentários, repercutindo sobre os parâmetros espaços-temporais, o risco de quedas e a execução de atividades funcionais.Rhythmic Auditory Stimulation (RAS) has aroused interest in the positive effects of aging on mobility declines. Objective: Evaluate the effects of training with rhythmic auditory stimulation associated with physiotherapy on functional mobility in sedentary elderly. Method: In this randomized, controlled, simple-blind clinical trial, the elderly were divided into three groups: control (CG), rhythmic auditory stimulation associated with physiotherapy (RAS+FT) and physiotherapy (FT). The FT and RAS+FT groups were submitted to 12 sessions with the physiotherapy protocol (three times a week, 40 min/session). Rhythmic auditory stimulation with music (10-20 min/session), provided by the ParkinSONS® app, was added to the RAS+FT group. For data analysis, two-way ANOVA with repeated measures was used for comparison between groups and time, with Tukey's post hoc. The effect size of interventions was also calculated. The level of significance established was p&lt;0.05. Results: No significant differences were found between groups. In the paired analysis, it was observed that the RAS+FT group presented significant results and size of the beneficial effects with increased speed (p=0.0001), reduction in time (p= 0.001), number of steps (p= 0.0007), reduction in TUG values (p= 0.0001), increase in displacement in TAF (p= 0.0001), improvement in scores in TUG-ABS (p= 0.003) and PAP (p= 0.0001). Conclusions: There was a positive effect of the use of RAS associated with physiotherapy on the functional mobility of sedentary elderly, reflecting on the spatiotemporal parameters, the risk of falls and the performance of functional activities

Simvastatin inhibits planktonic cells and biofilms of Candida and Cryptococcus species

The antifungal activity of some statins against different fungal species has been reported. Thus, at the first moment, the in vitro antifungal activity of simvastatin, atorvastatin and pravastatin was tested against Candida spp. and Cryptococcus spp. Then, in a second approach, considering that the best results were obtained for simvastatin, this drug was evaluated in combination with antifungal drugs against planktonic growth and tested against biofilms of Candida spp. and Cryptococcus spp. Drug susceptibility testing was performed using the microdilution broth method, as described by the Clinical and Laboratory Standards Institute. The interaction between simvastatin and antifungals against planktonic cells was analyzed by calculating the fractional inhibitory concentration index. Regarding biofilm susceptibility, simvastatin was tested against growing biofilm and mature biofilm of one strain of each tested yeast species. Simvastatin showed inhibitory effect against Candida spp. and Cryptococcus spp. with minimum inhibitory concentration values ranging from 15.6 to 1000 mg L−1 and from 62.5 to 1000 mg L−1, respectively. The combination of simvastatin with itraconazole and fluconazole showed synergism against Candida spp. and Cryptococcus spp., while the combination of simvastatin with amphotericin B was synergistic only against Cryptococcus spp. Concerning the biofilm assays, simvastatin was able to inhibit both growing biofilm and mature biofilm of Candida spp. and Cryptococcus spp. The present study showed that simvastatin inhibits planktonic cells and biofilms of Candida and Cryptococcus species. Keywords: Candida, Cryptococcus, Simvastatin, Antifungal activity, Biofil

Terpinen-4-ol, tyrosol, and beta-lapachone as potential antifungals against dimorphic fungi

This study aimed to evaluate the in vitro antifungal activity of terpinen-4-ol, tyrosol, and beta-lapachone against strains of Coccidioides posadasii in filamentous phase (n=22) and Histoplasma capsulatum in both filamentous (n=40) and yeast phases (n=13), using the broth dilution methods as described by the Clinical and Laboratory Standards Institute, to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of these compounds. The mechanisms of action of these compounds were also investigated by analyzing their effect on cell membrane permeability and ergosterol synthesis. The MIC and MFCf these compounds against C. posadasii, mycelial H. capsulatum, and yeast-like H. capsulatum, were in the following ranges: 350-5720 mu g/mL, 20-2860 mu g/mL, and 40-1420 mu g/mL, respectively for terpinen-4-ol250-4000 mu g/mL, 30-2000 mu g/mL, and 10-1000 mu g/mL, respectively, for tyrosoland 0.48-7.8 mu g/mL, 0.25-16 mu g/mL, and 0.125-4 mu g/mL, respectively for p-lapachone. These compounds showed a decrease in MIC when the samples were subjected to osmotic stress, suggesting that the compounds acted on the fungal membrane. All the compounds were able to reduce the ergosterol content of the fungal strains. Finally, tyrosol was able to cause a leakage of intracellular molecules. (C) 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Ceara, Postgrad Program Med Microbiol, Specialized Med Mycol Ctr, Fortaleza, Ceara, BrazilUniv Fed Ceara, Postgrad Program Med Sci, Fortaleza, Ceara, BrazilUniv Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Cellular Biol Div, Sao Paulo, SP, BrazilUniv Fed Ceara, Dept Stat & Appl Math, Fortaleza, Ceara, BrazilChristus Coll Unichristus, Sch Med, Fortaleza, Ceara, BrazilUniv Estadual Ceara, Postgrad Program Vet Sci, Fortaleza, Ceara, BrazilUniversidade Federal de São Paulo (UNIFESP), Department of Microbiology, Immunology and Parasitology, Cellular Biology Division, São Paulo, SP, BrazilCNPq: 303396/2014-8CNPq: 552161/2011-0CAPES: AE1-0052-000630100/11Web of Scienc