RESUMO
Objectiveto quantitatively assess disturbances of sweet, sour and salty and bitter tastes in a group of young, asymptomatic or oligosymptomatic COVID-19 patients; establish a reliable, sensitive and specific test that can diagnose COVID-19 on the basis of taste disorders and publish the results according to STARD 2015 statement (Standards for Reporting Diagnostic Accuracy). Designcase-control study Settingisolated rooms in the Central Clinical Hospital of the Ministry of the Interior and Administration in Warsaw (which had been transformed into an infectious hospital) and a dormitory in one of Warsaw universities. Participants52 SARS-CoV-2 positive (51 men, mean age 21.7 years) and 36 negative students (34 men, mean age 20.8 years). Main outcome measuresa gustatory function assessment (sweet, salty, sour and bitter taste), with flavour concentrations established previously in healthy subjects was conducted for all subjects. Each participant received one tasteless reference and nine flavour tablets with sucrose concentrations of 40, 80 and 106.4 mg/ml; NaCl at 13.5, 17 and 27 mg/ml; ascorbic acid at 6.25 and 12.5 mg/ml and grapefruit extract at 40 mg/ml. Resultsthe only taste that was impaired significantly more frequently in COVID-19 patients was the sweet taste at the lowest flavour concentration (40 mg/ml, p = 0.002). Different screening and diagnostic models were constructed using the examined variables. The highest accuracy screening test consisted of the positive result of a three-question questionnaire (self-reported loss of taste, self-reported loss of smell, or fever within the last month (positive if at least one present) and/or ageusia of sweet taste at a sucrose concentration of 40 mg/ml. The sensitivity of the model was 94% with a specificity of 55%. The highest accuracy diagnostic test consisted of ageusia of sweet taste at a sucrose concentration of 106.4 mg/ml or/and ageusia of salty taste at an NaCl concentration of 13.5 or 17 mg/ml. The specificity of the test was found to be 100%, and the sensitivity was 34%. Conclusionas the most effective way of controlling the present pandemic involves testing the wider population for symptomatic, oligosymptomatic and asymptomatic carriers of SARSCoV-2 and isolating or hospitalising infected subjects, in the present study, an inexpensive, simple, fast and sensitive (94%) screening test that can be used for such a purpose is proposed. In addition, a specific (100%) diagnostic test that could be used to refer patients to quarantine in the case of limited availability of genetic or serological tests is proposed.
RESUMO
Obesity and diabetes mellitus are the leading causes of renal disease. In this study, we determined the regulation and role of the G protein-coupled bile acid receptor TGR5, previously shown to be regulated by high glucose and/or fatty acids, in obesity-related glomerulopathy (ORG) and diabetic nephropathy (DN). Treatment of diabetic db/db mice with the selective TGR5 agonist INT-777 decreased proteinuria, podocyte injury, mesangial expansion, fibrosis, and CD68 macrophage infiltration in the kidney. INT-777 also induced renal expression of master regulators of mitochondrial biogenesis, inhibitors of oxidative stress, and inducers of fatty acid ß-oxidation, including sirtuin 1 (SIRT1), sirtuin 3 (SIRT3), and Nrf-1. Increased activity of SIRT3 was evidenced by normalization of the increased acetylation of mitochondrial superoxide dismutase 2 (SOD2) and isocitrate dehydrogenase 2 (IDH2) observed in untreated db/db mice. Accordingly, INT-777 decreased mitochondrial H2O2 generation and increased the activity of SOD2, which associated with decreased urinary levels of H2O2 and thiobarbituric acid reactive substances. Furthermore, INT-777 decreased renal lipid accumulation. INT-777 also prevented kidney disease in mice with diet-induced obesity. In human podocytes cultured with high glucose, INT-777 induced mitochondrial biogenesis, decreased oxidative stress, and increased fatty acid ß-oxidation. Compared with normal kidney biopsy specimens, kidney specimens from patients with established ORG or DN expressed significantly less TGR5 mRNA, and levels inversely correlated with disease progression. Our results indicate that TGR5 activation induces mitochondrial biogenesis and prevents renal oxidative stress and lipid accumulation, establishing a role for TGR5 in inhibiting kidney disease in obesity and diabetes.