Revisão sistemática e metanálise de testes diagnósticos: o uso da razão proteinúria/creatininúria em amostra para avaliação de proteinúria de 24 horas na pré-eclâmpsia

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Pregnane X receptor and constitutive androstane receptor modulate differently CYP3A-mediated metabolism in earlyand late-stage cholestasis

AIM: To ascertain whether cholestasis affects the expression of two CYP3A isoforms (CYP3A1 and CYP3A2) and of pregnane X receptor (PXR) and constitutive androstane receptor (CAR). METHODS: Cholestasis was induced by bile duct ligation in 16 male Wistar rats; whereas 8 sham-operated rats were used as controls. Severity of cholestasis was assessed on histological examination of liver sections, and serum concentrations of albumin, AST, ALT, GGT, ALPK and bilirubin. Gene and protein expressions of PXR, CAR, CYP3A1 and CYP3A2 were assessed by means of qRT-PCR and Western blot, respectively. Alterations in CYP3A activity were measured by calculating the kinetic parameters of 4-OH and 1'-OH-midazolam hydroxylation, marker reactions for CYP3A enzymes. RESULTS: The mRNA and protein expression of CYP3A1 increased significantly in mild cholestasis (P < 0.01). At variance, mRNA and protein expression of CYP3A2 didn't change in mild cholestasis, whereas the expression and activity of both CYP3A1 and CYP3A2 decreased dramatically when cholestasis became severe. Consistently with these observations, the nuclear expression of both PXR and CAR, which was measured because they both translocate into the cell nucleus after their activation, virtually disappeared in the late stage of cholestatic injury, after an initial increase. These results indicate that early- and late-stage cholestasis affects CYP3A-mediated drug metabolism differently, probably as consequence of the different activation of PXR and CAR. CONCLUSION: Early- and late-stage cholestasis affects CYP3A-mediated drug metabolism differently. PXR and CAR might be targeted therapeutically to promote CYP3A-mediated liver detoxification

Acurácia diagnóstica da razão proteinúria/creatininúria em pacientes com suspeita de síndrome de pré-eclâmpsia: revisão sistemática e metanálise de estudos diagnósticos

Background: The laboratory gold standard test for identification of proteinuria in pregnant women is its measurement in a 24-hour urine sample. Urine protein-to-creatinine ratio in an isolated sample has been suggested as an option to a 24-hour urine collection. Proteinuria is a key feature of the preeclampsia syndrome. The current study aims at estimating the diagnostic accuracy of urine protein-to-creatinine ratio in comparison to 24 hours proteinuria determination in women with suspected preeclampsia syndrome. Methods: Systematic review and meta-analysis was used in comparing the accuracy of the protein-to-creatinine ratio in isolated urine samples with 24-hour urine protein excretion from Medline and LILACS electronic databases (to Feb/10) as data source. Results: The review included 14 studies with a total of 2,255 patients. Inclusion of a LILACS database search added one new paper to the sample. All the studies but two were cross-sectional in design. The method of urinary protein excretion evaluation differed among studies and was not mentioned in three. All the studies demonstrated significant correlation between protein-to-creatinine ratio and 24-hour proteinuria, with a coefficient greater than 0. 500. Proteinuria-to-creatininuria ratio combined sensibility and specificity estimates were 86. 6% (95% CI: 84. 3-88. 6) and 90. 1% (95% CI: 88. 2-91. 7), respectively. Conclusion: The pooled estimate suggests that protein-to-creatinine ratio in isolated urine samples may be used for diagnosis and follow-up of patients with suspected preeclampsia syndrome.INTRODUÇÃO: O teste de laboratório padrão-ouro para identificação de proteinúria em mulheres grávidas é a sua medição em amostra de urina de 24 horas. A razão de proteínas e creatinina na urina em amostra isolada tem sido sugerida como uma opção para uma coleta de urina de 24 horas. Proteinúria é uma característica diagnóstica da síndrome pré-eclâmpsia. O presente estudo visa estimar a precisão do diagnóstico pela relação de proteínas e creatinina na urina, em comparação a determinação de proteinúria em 24 horas de mulheres com suspeita de síndrome pré-eclâmpsia.MÉTODOS: revisão sistemática e meta-análise foram empregadas na comparação da precisão da relação proteína-creatinina em amostras de urina isolada, com a proteína urinária excretada em 24 horas. A consulta utilizou as bases de dados Medline e LILACS eletrônico (a Fev/10) como fonte de dados. RESULTADOS: A revisão incluiu 14 estudos com um total de 2. 255 pacientes. A inclusão do banco de dados LILACS adicionou um novo artigo à amostra. O método de avaliação da excreção urinária de proteína diferiu entre os estudos e não foi mencionado em três. Todos os estudos demonstraram correlação significativa entre a proteína e creatinina e proteinúria de 24 horas, com um coeficiente maior que 0,500. O índice proteinúria-creatininúria apresentou sensibilidade e especificidade estimada de 86,6% (IC 95%: 84,3-88,6) e 90,1% (IC 95%: 88,2-91,7), respectivamente. CONCLUSÃO: A estimativa combinada sugere que a razão de proteína e creatinina em amostras de urina isolada pode ser usada para o diagnóstico e acompanhamento de pacientes com suspeita de síndrome pré-eclâmpsia

GENETIC DIVERSITY OF LACTOBACILLI ISOLATED FROM HUMAN INFANT FECES*

Seventy-five strains isolated from fecal samples of six children were studied for their morphology and biochemical properties. Genetic diversity of 30 strains was analyzed by using Random Amplified Polymorphic DNA (RAPD). The intestinal isolates were grouped into four clusters. Some strains in group I were 100% similar (Lactobacillus reuteri) while high degree of genetic diversity was found in groups II (standard species), III and IV. Eight strains of group I and group III were identified through biochemical identification, as Lactobacillus reuteri, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus casei and Lactobacillus salivarius, and showed low genetic similarity with type strains. The findings in this study provide a strong basis for exploring the potential of these eight selected lactobacilli strains for use in fermented-milk based products.

Multimodality imaging and functional assessment in patients with systemic right ventricle and biventricular physiology: a retrospective single-center study

Systemic right ventricle (sRV) dysfunction is frequent in patients with congenitally corrected transposition of great arteries (cc-TGA) and those with dextro-transposition of great arteries (D-TGA) after Mustard/Senning operations. This condition should be identified promptly. We aimed to compare echocardiographic parameters with cardiac magnetic resonance (CMR)-derived parameters in patients with sRV and to evaluate their correlation with clinical variables and exercise capacity. Patients with cc-TGA and D-TGA after Mustard/Senning who underwent standard and advanced (speckle tracking and 3D) echocardiography and CMR (including feature-speckle tracking) were included. Clinical and imaging parameters were collected. Echocardiographic-derived right ventricle end-diastolic area and end-systolic area correlated with 3D echocardiographic-derived right ventricle end-diastolic and end-systolic volume (r=0.6, p=0.006 and r=0.8, p=0.002). 3D ejection fraction (EF) correlated with fractional area change and tricuspid annular plane systolic excursion (TAPSE) (r=0.8, p=0.001 and r=0.7, p=0.03). sRV global longitudinal strain correlated with systemic atrial strain (sAS) (r=-0.6, p=0.01). CMR-derived EF correlated with CMR-derived global longitudinal strain (GLS) both endocardial and myocardial (r=-0.7, p=0.007 and r=-0.6, p=0.005). sRV areas as assessed by echo correlated with CMR-derived volumes (r=0.9, p=0.0001 for diastole and r=0.8, p=0.0001 for systole). Similarly, a correlation was found between sRV echo-derived GLS and CMR-derived GLS, both endocardial and myocardial (r=0.8, p=0.001 and r=0.7, p=0.01). The only imaging parameter which correlated with peak V02 was sAS (r=0.55, p=0.04). When comparing cc-TGA and D-TGA, the former showed better GLS-derived values as assessed by CMR (CMR-derived right ventricle endocardial longitudinal strain -23.2% versus -17.2%, p=0.002; CMR-derived right ventricle myocardial longitudinal strain -21.2% versus -16.7%; p=0.05), bigger systemic atrial area (20.2 cm2/m2 versus 8.4 cm2/m2, p=0.005) and higher TAPSE values (16.2 mm versus 12.2 mm, p=0.04). Echocardiography is valid to screen for sRV dilatation and function and to guide the timing for CMR. The investigation of atrial deformation imaging may help to better understand diastolic function. Patients with cc-TGA show better cardiac function compared to patients after atrial switch. Further investigations are needed to identify imaging parameters linked to exercise capacity

Covid-19 em crianças e adolescentes brasileiros: registros de 21 hospitais

Introduction:Children and adolescents with Covid-19 have been shown lower mortality less intense symptoms when compared to adults, but studies in Brazil have been based on the compulsory notifying system only. Objective: To analyse clinical, laboratory, radiological characteristics and outcomes of hospitalized patients under 20 years with Covid-19. Methods: Cases series of hospitalized patients with confirmed Covid-19 under 20 years, obtained from a cohort study in 21 hospitals from five states of Brazil.Results: From 36 patients, 20 (55.5%) were adolescentes, 20 (55.5%) were male, 18 (50.0%) had comorbidities, 2 were pregnant and in 7 (19.4%), initial symptoms occurred during hospitalization for other causes, of whom 3 were possibly infected in the hospital. Fever (61.1%), dyspnea (33.3%) and neurological symptoms (33.0%) were the most common complaints. C-reactive protein was higher than 50mg/L in 16.7% and D-dimer was above the reference limit in 22.2%. Chest X-rays were performed in 20 (55.5%) patients, 9 had abnormalities, and chest tomography in 5. Hospital length of stay ranged from 1-40 days (median 5 [interquartile range 3-10]), 16 (44.4%) needed intensive therapy, 6 (16.7%) required mechanical ventilation and one patient (2.8%) died. Conclusion: In case series patients under 20 years from hospitals from 5 states of Brazil, comorbidities were frequent, and most common symptoms were fever, dyspnea and neurological symptoms. Forty-four percent required intensive therapy, showing that the disease was not as mild as it was expected, and one patient died

Sulfonamidas derivadas de 8-hidroxiquinolina, processo de síntese, composição farmacêutica e uso

Universidade Federal do Rio Grande do SulCiências Básicas da SaúdeQuímicaFarmáciaDepositad

ABC₂-SPH risk score for in-hospital mortality in COVID-19 patients:development, external validation and comparison with other available scores

Objectives: The majority of available scores to assess mortality risk of coronavirus disease 2019 (COVID-19) patients in the emergency department have high risk of bias. Therefore, this cohort aimed to develop and validate a score at hospital admission for predicting in-hospital mortality in COVID-19 patients and to compare this score with other existing ones. Methods: Consecutive patients (≥ 18 years) with confirmed COVID-19 admitted to the participating hospitals were included. Logistic regression analysis was performed to develop a prediction model for in-hospital mortality, based on the 3978 patients admitted between March–July, 2020. The model was validated in the 1054 patients admitted during August–September, as well as in an external cohort of 474 Spanish patients. Results: Median (25–75th percentile) age of the model-derivation cohort was 60 (48–72) years, and in-hospital mortality was 20.3%. The validation cohorts had similar age distribution and in-hospital mortality. Seven significant variables were included in the risk score: age, blood urea nitrogen, number of comorbidities, C-reactive protein, SpO2/FiO2 ratio, platelet count, and heart rate. The model had high discriminatory value (AUROC 0.844, 95% CI 0.829–0.859), which was confirmed in the Brazilian (0.859 [95% CI 0.833–0.885]) and Spanish (0.894 [95% CI 0.870–0.919]) validation cohorts, and displayed better discrimination ability than other existing scores. It is implemented in a freely available online risk calculator (https://abc2sph.com/). Conclusions: An easy-to-use rapid scoring system based on characteristics of COVID-19 patients commonly available at hospital presentation was designed and validated for early stratification of in-hospital mortality risk of patients with COVID-19.</p