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

Abstract This study aimed to evaluate the in vitro antifungal activity of terpinen-4-ol, tyrosol, and β-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 µg/mL, 20-2860 µg/mL, and 40-1420 µg/mL, respectively for terpinen-4-ol; 250-4000 µg/mL, 30-2000 µg/mL, and 10-1000 µg/mL, respectively, for tyrosol; and 0.48-7.8 µg/mL, 0.25-16 µg/mL, and 0.125-4 µg/mL, respectively for β-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.

Cotrimoxazole enhances the in vitro susceptibility of Coccidioides posadasii to antifungals

The aim of the present study was to evaluate the effect of cotrimoxazole on the in vitro susceptibility of Coccidioides posadasii strains to antifungals. A total of 18 strains of C. posadasii isolated in Brazil were evaluated in this study. The assays were performed in accordance with the Clinical and Laboratory Standards Institute guidelines and the combinations were tested using the checkerboard method. The minimum inhibitory concentrations were reduced by 11, 2.4, 4.3 and 3.5 times for amphotericin B, itraconazole, fluconazole and voriconazole, respectively. Moreover, it was seen that cotrimoxazole itself inhibited C. posadasii strains in vitro. The impairment of folic acid synthesis may be a potential antifungal target for C. posadasii.

Actividad física y potencia aeróbica: ¿Cómo influyen sobre los factores de riesgo cardiovascular clásicos y emergentes? / Association between cardiorespiratory fitness and cardiovascular risk factors in healthy individuals

Background: Cardio respiratory fitness (FIT) is associated with a better profile in most modifiable cardiovascular risk factors (RF). In Chile, sedentary lifestyle is highly prevalent, reaching almost 90 percent. Aim: To determine the association between FIT and traditional and emergent RF in a primary prevention population. Material and methods: We prospectively studied 1973 subjects (36 percent women, mean age 56± 13 years) without history of cardiovascular disease and absence of ischemic changes on exercise testing. We assessed cardiovascular RF and determined body mass index (BMI), waist circumference, systolic and diastolic blood pressure, fasting blood lipids, glucose, C-reactive protein (CRP) and fibrinogen. FIT was measured by a Sci f-reported physical activity questionnaire and by a maximal treadmill exercise test, expressed in metabolic equivalents (METs). Results: Subjects in the highest FIT according to the treadmill test had significantly lower BMI, waist circumference, systolic and diastolic blood pressure, total cholesterol, triglycerides, glucose, CRP and fibrinogen, and higher HDL cholesterol (adjusted by age and gender). LDL cholesterol did not show significant changes. The same pattern of RF (including LDL cholesterol) and CRP was observed when using Sci f-reported physical activity as a FIT parameter There was a significant association between both methods to measure FIT (p <0.0001, Chi-square Mantel-Haenszel). Conclusions: Our findings show that a better level off IT, assessed by exercise testing or through Sci f report is associated with improved levels of traditional and emergent RF.