Uremic toxins promote accumulation of oxidized protein and increased sensitivity to hydrogen peroxide in endothelial cells by impairing the autophagic flux.

Chronic kidney disease (CKD) is associated with high mortality rates, mainly due to cardiovascular diseases (CVD). Uremia has been considered a relevant risk factor for CVD in CKD patients, since uremic toxins (UTs) promote systemic and vascular inflammation, oxidative stress and senescence. Here, we demonstrate that uremic toxins indoxyl sulfate (IxS), p-cresyl sulfate (pCS) and indole acetic acid (IAA) are incorporated by human endothelial cells and inhibit the autophagic flux, demonstrated by cellular p62 accumulation. Moreover, isolated and mixed UTs impair the lysosomal stage of autophagy, as determined by cell imaging of the mRFP-GFP-LC3 protein. Endothelial cells exposed to UTs display accumulation of carbonylated proteins and increased sensitivity to hydrogen peroxide. Rapamycin, an autophagy activator which induces both autophagosome formation and clearance, prevented these effects. Collectively, our findings demonstrate that accumulation of oxidized proteins and enhanced cell sensitivity to hydrogen peroxide are consequences of impaired autophagic flux. These data provide evidence that UTs-induced impaired autophagy may be a novel contributor to endothelial dysfunction.

Spectrographic Vocal Characteristics in Female Teachers: Finger Kazoo Intensive Short-term Vocal Therapy.

OBJECTIVE: Verify the results from intensive short-term vocal therapy using the Finger Kazoo technique about the spectrographic vocal measurements of teachers. METHODS: Controlled and randomized trial. Spectrographic vocal assessment was performed by judges before and after intensive short-term vocal therapy with Finger Kazoo. Sample was composed of 41 female teachers. There were two study groups (with vocal nodules and without structural affection of the vocal folds) and the respective control groups. For the statistical analysis of the data, nonparametric tests were used (Mann-Whitney test and Wilcoxon test). RESULTS: After intensive short-term vocal therapy with Finger Kazoo, improvement in voice spectral parameters, such as improvement in tracing (color intensity and regularity), greater definition of formants and harmonics, increased replacement of harmonics by noise, and a greater number of harmonics, mainly in the group without structural affection of the vocal folds. CONCLUSION: There was an improvement in the spectrographic vocal parameters, showing greater stability, quality, and projection of the emission, especially in female teachers without structural affection of the vocal folds.

SULT1A1 genetic polymorphisms and the association between smoking and oral cancer in a case-control study in Brazil.

INTRODUCTION: Oral cancer is a public health problem worldwide, being tobacco and alcohol consumption their main risk factors. Sulfotransferase (SULT) 1A1 (encoded by SULT1A1) is involved in procarcinogens metabolism, such as polycyclic aromatic hydrocarbons (PAHs) present in tobacco smoke. OBJECTIVE: The aim of this study was to explore the magnitude of association between SULT1A1 gene Arg(213)His polymorphism and oral cancer, and to explore the interaction between such polymorphism and smoking. METHODS: A hospital-based case-control study was carried out in Rio de Janeiro, Brazil, during 1999-2002. Epidemiological data and biological samples were obtained from 202 oral cancer patients and 196 sex and age-frequency matched controls without cancer antecedents. RESULTS: No association was observed between Arg(213)His SULT1A1 polymorphism and oral cancer risk in overall analysis (OR = 1.06, 95% CI = 0.71-1.57). The magnitude of association between cigarette smoking and oral cancer was higher in individuals with a SULT1A1(*)1 isoform (wild type, genotype Arg/Arg) (OR = 10.19, 95% CI = 3.90-26.61) than in those with at least one SULT1A1(*)2 allele (genotypes Arg/His + His/His) (OR = 4.50, 95% CI =2.09-9.69). CONCLUSION: Our results suggest that Arg(213)His SULT1A1 polymorphism may modulate the association between smoking and oral cancer. However, this association needs to be replicated in other studies: due to modest number of cases and controls, the role of chance in the observed association cannot be ruled out.