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Objectives: We hypothesized that exercise-related periodic breathing (EPB) would be associated with poor prognosis in advanced chronic heart failure (CHF).Background: Patients with CHF might present instability of the ventilatory control system characterized by cyclic waxing and waning of tidal volume (periodic breathing [PB]). This condition is associated with several deleterious circulatory and neuro-endocrine responses; in fact, PB in awake and asleep patients has been identified as an independent risk factor for cardiac death. During exercise, however, the prognostic value of PB is still unknown in CHF patients awaiting heart transplantation.Methods: Eighty-four patients with established CHF (65 male, 19 female) were submitted to clinical evaluation, echocardiogram, ventricular scintigraphy, determination of resting serum norepinephrine levels, and an incremental cardiopulmonary exercise test on cycle ergometer. Patients were followed for up to 49.7 months (median = 15.3), and 26 patients (30.9%) died during this period.Results: Twenty-five of 84 patients presented EPB (29.7%). The following variables were related to mortality according to Kaplan-Meier and univariate Cox regression analysis: EPB (p = 0.004), New York Heart Association class (p = 0.04), serum norepinephrine (p = 0.06), peak oxygen uptake (ml.min(-1).kg(-1) and % predicted; p = 0.085 and p = 0.10, respectively), slope of the ratio of change in minute ventilation to change in carbon dioxide output during exercise (p = 0.10), and scintigraphic left ventricular ejection fraction (p = 0.10). Cox multivariate analysis identified EPB as the only independent variable for cardiac death prediction (p = 0.007). Therefore, EPB alone was associated with a 2.97-fold increase in risk of death in this population (95% confidence interval = 1.34 to 6.54).Conclusions: Exercise-related periodic breathing independently predicts cardiac mortality in CHF patients considered for heart transplantation. [ABSTRACT FROM AUTHOR]

The objective of this study was to establish the phenotypical and molecular patterns of clinical isolates of Trichophyton tonsurans circulating in the state of Ceará, northeastern Brazil. For this purpose, 25 T. tonsurans strains isolated from independent cases of tinea capitis in children were phenotypically evaluated regarding their macro- and micro-morphological characteristics, vitamin requirements, urease production, and antifungal susceptibility. The molecular characterization was carried out with random amplified polymorphic DNA molecular markers and M13 fingerprinting. The presence of the genes CarbM14, Sub2, CER, URE, ASP, PBL, and LAC, which encode enzymes related to fungal virulence, was also evaluated. Finally, melanin production was assessed through specific staining. The data obtained demonstrated that these T. tonsurans strains have considerable phenotypical variation, although they showed a low degree of genetic polymorphism according to the markers used. The genes CarbM14, Sub2, CER, and URE were detected in all the analyzed strains. The gene LAC was also identified in all the strains, and melanin synthesis was phenotypically confirmed. The strains were susceptible to antifungals, especially itraconazole (GM = 0.06 μg/mL) and ketoconazole (GM = 0.24 μg/mL). Therefore, T. tonsurans strains can present great phenotypical heterogeneity, even in genetically similar isolates. Moreover, the presence of the LAC gene indicates the possible participation of melanin in the pathogenesis of these dermatophytes.

Coccidioidomycosis is a systemic mycosis caused by the dimorphic fungi Coccidioides spp. The treatment for chronic and/or disseminated coccidioidomycosis can be prolonged and complicated. Therefore, the search for new drugs is necessary. Farnesol is a precursor in the sterol biosynthesis pathway that has been shown to present antifungal activity. Thus, the objective of this study was to evaluate the in vitro antifungal activity of farnesol alone and in combination with antifungal agents against clinical and environmental strains of Coccidioides posadasii as well as to determine their effect on the synthesis of ergosterol and on cell permeability. This study employed the broth macrodilution method to determine the MIC of farnesol against 18 strains of C. posadasii. Quantification of ergosterol was performed with 10 strains of C. posadasii after exposure to subinhibitory concentrations of farnesol. Finally, the activity of farnesol was evaluated in the presence of osmotic stress, induced by the addition of NaCl to the culture medium, during the susceptibility tests. The results showed that farnesol exhibited low MICs (ranging from 0.00171 to 0.01369 mg/liter) against all tested strains. The combination of farnesol with the antifungals showed synergistic effects (fractional inhibitory concentration index [FICI] ≤ 0.5). As for the ergosterol quantification, it was observed that exposure to subinhibitory concentrations of farnesol decreased the amount of ergosterol extracted from the fungal cells. Furthermore, farnesol also showed lower MIC values when the strains were subjected to osmotic stress, indicating the action of this compound on the fungal membrane. Thus, due to the high in vitro antifungal activity, this work brings perspectives for the performance of in vivo studies to further elucidate the effects of farnesol on the host cells.

The objective of this study was to evaluate the antifungal activity of farnesol and its interaction with traditional antifungals against drug-resistant strains of Candida species. To do so, we studied the minimum in vitro inhibitory concentration (MIC) of amphotericin B (AMB), fluconazole (FLC), itraconazole (ITC), caspofungin (CAS) and farnesol against 45 isolates of Candida spp., i.e., 24 C. albicans, 16 C. parapsilosis and 5 C. tropicalis through the use of the broth microdilution method. Then, the isolates were tested with the combination of farnesol plus drugs to which they were previously found to be resistant. Additionally, the strains were pre-incubated at sub-inhibitory farnesol concentrations and their antifungal susceptibilities were re-evaluated. We found the MIC values for farnesol varied from 4.68-150 µM for Candida spp., with 19 isolates having a MIC > 1 mg/l, 18 a MIC ≥ 64 mg/l, 35 having a MIC ≥ 1 mg/l and 6 isolates a MIC ≥ 2 mg/l or were resistant to AMB, FLC, ITC and CAS, respectively. Significant MIC reductions were observed when farnesol and antifungal drugs were combined (P < 0.05) and when Candida strains were incubated with farnesol (P < 0.05). We conclude that the in vitro effects of farnesol improved the activity of traditional antifungals to which the Candida spp. isolates were resistant. These results support further investigation of the role of farnesol in the balance of the sterol biosynthetic pathway and how it interferes with cell viability.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. It is known for its great disfiguring capacity and is considered an extremely serious disease to public health worldwide. The state of Ceará ranks 13th in number of cases of leprosy in Brazil, and fourth in Northeastern region, with an average of 2,149 new cases diagnosed every year. This study aimed to evaluate the knowledge of leprosy patients regarding treatment, and to assess the level of treatment adherence and its possible barriers. The study was conducted in the reference center for dermatology, from September 2010 to October 2010, in Fortaleza, Ceará. The study data were collected by means of a structured interview, along with the Morisky-Green test, in order to assess treatment adherence and barriers to adherence. A total of 70 patients were interviewed, out of whom 66 were new cases. The majority of patients were between 42 and 50 years old, and 37 (52.9%) were male. Most patients were clinically classified as presenting multibacillary leprosy (80%), and 78.6% of them were from Fortaleza, Brazil. The Morisky-Green test indicated that 62.9% of patients presented a low level of adherence (p<0.005), despite claiming to aware of the disease risks. However, it was observed that 57.1% of the patients had no difficulty adhering to treatment, while 38.6% reported little difficulty. This study shows that despite the patients claiming to be familiar with leprosy and its treatment, the Morisky-Green test clearly demonstrated that they actually were not aware of the principles of therapy, which is evidenced by the low degree of treatment adherence., (Copyright © 2012 Elsevier Editora Ltda. All rights reserved.)

The effects of the protease inhibitors saquinavir, darunavir, ritonavir, and indinavir on growth inhibition, protease and phospholipase activities, as well as capsule thickness of Cryptococcus neoformans were investigated. Viral protease inhibitors did not reduce fungal growth when tested in concentrations ranging from 0.001 to 1.000 mg/L. A tendency toward increasing phospholipase activity was observed with the highest tested drug concentration in a strain-specific pattern. However, these drugs reduced protease activity as well as capsule production. Our results confirm a previous finding that antiretroviral drugs affect the production of important virulence factors of C. neoformans.

This study aimed to evaluate the in vitro combination of farnesol and β-lactams against Burkholderia pseudomallei. A total of 12 β-lactamase-positive strains were tested according to CLSI standards. All strains were inhibited by farnesol, with MICs ranging from 75 to 150 μM. The combination of this compound with β-lactams resulted in statistically significant β-lactam MIC reduction (P ≤ 0.05). This study provides new perspectives for the use of farnesol combined with β-lactam antibiotics against strains of B. pseudomallei.

In the present study, it was sought to compare yeast microbiota of wild and captive Macrobrachium amazonicum and evaluate the antifungal susceptibility and production of virulence factors by the recovered isolates of Candida spp. Additionally, cultivation water was monitored for the presence of fungi. Overall, 26 yeast isolates belonging to three genera and seven species were obtained, out of which 24 were Candida spp., with Candida famata as the most prevalent species for both wild and captive prawns. From cultivation water, 28 isolates of filamentous fungi were obtained, with Penicillium spp., Cladosporium spp. and Aspergillus spp. as the most frequent genera. Eight out of 24 Candida spp. isolates were resistant to azole derivatives, out of which four were recovered from wild-harvested prawns. As for production of virulence factors, three (12.5%) and eight (33.3%) isolates presented phospholipase and protease activity, respectively. This is the first comparative study between wild and captive prawns and the first report on yeast microbiota of M. amazonicum. The most relevant finding was the high percentage of resistant Candida spp., including from wild individuals, which suggests the occurrence of an environmental imbalance in the area where these prawns were captured., (© 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.)

The present study had the aim of testing the hexane and methanol extracts of avocado seeds, in order to determine their toxicity towards Artemia salina, evaluate their larvicidal activity towards Aedes aegypti and investigate their in vitro antifungal potential against strains of Candida spp, Cryptococcus neoformans and Malassezia pachydermatis through the microdilution technique. In toxicity tests on Artemia salina, the hexane and methanol extracts from avocado seeds showed LC50 values of 2.37 and 24.13 mg mL-1 respectively. Against Aedes aegypti larvae, the LC50 results obtained were 16.7 mg mL-1 for hexane extract and 8.87 mg mL-1 for methanol extract from avocado seeds. The extracts tested were also active against all the yeast strains tested in vitro, with differing results such that the minimum inhibitory concentration of the hexane extract ranged from 0.625 to 1.25mg L-(1), from 0.312 to 0.625 mg mL-1 and from 0.031 to 0.625 mg mL-1, for the strains of Candida spp, Cryptococcus neoformans and Malassezia pachydermatis, respectively. The minimal inhibitory concentration for the methanol extract ranged from 0.125 to 0.625 mg mL-1, from 0.08 to 0.156 mg mL-1 and from 0.312 to 0.625 mg mL-1, for the strains of Candida spp., Cryptococcus neoformans and Malassezia pachydermatis, respectively.

The main aim of this study was to verify the efficacy of subculture on potato dextrose agar (PDA) as a complement to the in vitro susceptibility test for Malassezia pachydermatis strains by a broth microdilution method, as well as to determine the MIC and MFC of azole derivatives, amphotericin B and caspofungin. The microdilution assay was performed in 96-well plates using a modified RPMI 1640 medium. The M. pachydermatis strains were resistant to caspofungin. All strains (n=50) had shown MIC values of <0.03, <0.03, 2.0, 4.0 and 4.0 microg/ml for itraconazole, ketoconazole, voriconazole, fluconazole and amphotericin B, respectively. Thus, the subculture on PDA improved the analysis of the in vitro antifungal susceptibility of M. pachydermatis.

Background: Patients with chronic obstructive pulmonary disease (COPD) present abnormal respiratory mechanics, but its relation to ventilation variables at rest is not fully understood., Methods: We evaluated breathing pattern, thoracoabdominal motion, and ventilation in moderate and severe COPD patients by means of respiratory inductive plethysmograph and analysis of respiratory metabolism in semirecumbent position at rest. Diaphragmatic movement was measured using radiographs., Results: COPD patients showed an increase in mean inspiratory flow, minute ventilation, dead space ventilation, oxygen and carbon dioxide ventilatory equivalents and reduction of respiratory times and pulse oxymetry. These findings were more pronounced in severe COPD. Changes in ventilatory efficiency were correlated with decreased respiratory times, reduced diaphragmatic movement, and lower oxygen uptake., Conclusions: Rapid shallow breathing and reduced diaphragmatic movement have led to ventilatory inefficiency without changes in thoracoabdominal motion.

The effects of 12 months of therapy were evaluated in 47 mildly symptomatic patients with moderate to severe mitral valve regurgitation; 26 patients received enalapril and 21 received a placebo. Enalapril was associated with a significant reduction in left ventricular diameter and mitral regurgitation volume, with no evidence of change in systolic function indexes. However, enalapril did not hinder progressive aerobic impairment to effort.

Purpose: To evaluate the cardiopulmonary exercise testing (CPX) for the diagnosis of myopathies., Methods: 27 patients with myopathy were submitted to CPX testing (symptom limited bike protocol)., Results: Dystrophic patients and patients with mitochondrial disease, compared with controls, showed significant differences for the power of work perfomed (watt) and the maximum oxygen consumption (VO2 max). Patients with mitochondrial disease presented significantly lower values of anaerobic threshold when compared to controls and elevation of exercise peak respiratory exchange ratio (RER) values when compared to the others groups., Conclusions: CPX testing may be useful in evaluating degree of physical limitation of patients with myopathy at inicial stage as well on follow-up examinations. Power of work performed, VO2 max, anaerobic threshold and RER at exercise peak may suggest the diagnosis of myopathy and its sub-types and therefore exclude psychologic causes of limitation.

Objective: To evaluate the onset of exercise-induced interstitial pulmonary edema in cardiac patients by high-resolution CT (HRCT)., Design: Prospective, normal controlled., Participants: Thirty subjects divided into three groups: group 1--10 outpatients with chronic congestive heart failure (CCHF), New York Heart Association (NYHA) class I; group 2--10 outpatients with CCHF, NYHA class II/III; and group 3 (control)--10 normal subjects., Method: HRCT scans were obtained at rest and 4, 8, 12, 16, and 20 min after progressive treadmill exercise test., Results: The following HRCT findings consistent with interstitial edema were significantly different (p<0.05) in group 2 when compared with groups 1 and 3: artery/bronchus ratio > 1 in the upper lobes, peripheral increase in the vascular markings, interlobular septal thickening, and peribronchial "cuffing." These differences were maximal at 12 min after exercise and returned to normal values after 20 min., Conclusion: Interstitial pulmonary edema was present immediately after exercise in CCHF patients. It may be important in the genesis of dyspnea of these patients.

Athletes tend to have lower hemoglobin (Hb) concentrations than sedentary counterparts. Sports anemia is used to describe both pseudodilutional anemia and the true anemia of athletes. Pseudodilutional anemia is a beneficial adaptation to endurance training; the two most common causes of true anemia are iron deficiency and intravascular hemolysis. We used questionnaires, physical examination and laboratory investigation to study 19 highly trained hockey athletes and laboratory investigation to study 32 outpatients without hematological diseases. One athlete had anemia (Hb 10.5 g/ dL; 5.44 million red cells/mL; serum iron-13 micrograms/dL; without parasites in the stools); the athletes had Hb = 14.88 +/- 1.33 g/dL and the outpatients had 15.24 +/- 0.74 g/dL; the maximal oxygen uptake of the athletes was 54.0 +/- 6.03 ml/kg/min (112.15 +/- 14.35% of the predicted values). The maximal oxygen uptake of the anemic athlete was 86% of the predicted value. The three athletes with the best maximal uptake had a mean Hb = 15.8 g/dL. In São Paulo-Brazil anemia is uncommon among males but elite athletes are in a borderline anemic state, that may impair the physical fitness.

Stimulated skeletal muscle grafts have been proposed as a means to reinforce ventricular wall in the treatment of severe myocardial failure. Latissimus dorsi cardiomyoplasty was performed in 11 patients with advanced heart failure due to cardiomyopathy who were in New York Heart Association (NYHA) class III or IV despite maximal medical therapy. There were no operative deaths. Eight patients were followed for a mean of 10.8 months. Two patients remain in muscle conditioning protocol. One patient died with latissimus dorsi ischemia and congestive heart failure. Four of the eight patients in long-term follow-up are in NYHA class I, three in class II, and one in class III. At 3 months of follow-up, rest radioisotopic left ventricular ejection fraction increased from 20.5 +/- 3.6% to 26.8 +/- 8.1% (p less than 0.01). Doppler-echocardiography demonstrated that left ventricular segmental wall shortening improved from 11.3 +/- 2.5% to 16.5 +/- 3.9% (p less than 0.01) and left ventricular stroke volume from 22.9 +/- 4.6 to 33.1 +/- 10 ml (p less than 0.01). Cardiopulmonary exercise test showed that maximal oxygen consumption during treadmill test increased from 14.8 +/- 3.7 to 18.2 +/- 3.3 ml/kg.min (p less than 0.05). At 6 months of follow-up, all the above values remained essentially unchanged. Furthermore, nonsustained ventricular tachycardia was abolished without specific medical therapy in four patients. Thus, cardiomyoplasty improves left ventricular function, reverses congestive heart failure, and may improve long-term survival in severe cardiomyopathies.

The effect of methylprednisolone on the distribution of myocardial flow during ischemia and after reperfusion was determined in 10 treated and 11 control dogs. Methylprednisolone, 30 mg/kg, was administered iv after occlusion. Transmural blood flow and the endo/epicardial ratio in the normal and ischemic zones was measured by injecting 141Ce- and 85Sr-labelled microspheres after 90 min of ischemia and 30 min after reperfusion, respectively. During ischemia, transmural blood flow (ml g-1 min-1) in the ischemic zone was higher in treated animals than in controls (0.25 +/- 0.04 vs 0.15 +/- 0.03; P less than 0.05) but not different in the normal zone for both groups (1.36 +/- 0.14 vs 1.15 +/- 0.10; P greater than 0.05). The endo/epicardial ratio of the ischemic zone was low but similar for both groups during ischemia (0.43 +/- 0.07 vs 0.40 +/- 0.09; P greater than 0.05). After reperfusion, transmural blood flow increased significantly in treated (0.25 +/- 0.13 vs 1.36 +/- 0.13; P less than 0.0005) as well as in control animals (0.15 +/- 0.03 vs 1.63 +/- 0.14; P greater than 0.0005), reaching similar values (1.36 +/- 0.13 vs 1.63 +/- 0.14; P greater than 0.05). The endo/epicardial ratio also increased during reperfusion in both treated (0.43 +/- 0.07 vs 1.12 +/- 0.12; P less than 0.0005) and control animals (0.40 +/- 0.90 vs 1.03 +/- 0.19; P less than 0.025). These data show that although methylprednisolone-treated dogs had higher myocardial blood flow during ischemia, after reperfusion the increase in flow in the ischemic zone of treated and control dogs was of the same magnitude.