Genotoxicity, cytotoxicity and chemical profile from Inga laurina (Fabaceae).

This study aimed to evaluate the cytotoxicity and genotoxicity from Inga laurina leaves extracts and fractions and obtain their chemical profile. The chemical profile of the crude extract from I. laurina leaves and its fractions was investigated through 1H NMR, RP-HPLC-PDA by co-injection with authentic standards and HPLC-MS. The quinone reductase induction as a biomarker for cancer chemoprevention was evaluated in murine hepatocellular carcinoma line, whereas the cytotoxicity was evaluated by sulforhodamine B assay (SRB) using HepG2 cell line and genotoxicity was evaluated by comet assay. The phytochemical analysis of the leaves crude extract and its fractions showed the presence of 2-hydroxyethyl-dodecanoate and the phenolic compounds: gallic acid, methyl gallate, p-coumaric acid, cinnamic acid, myricetin-3-O-(2″-O-galoyl)-α-rhamnopyranoside, proanthocyanidin A-2 and myricetrin. All the fractions tested were not considered cytotoxic against the selected human cancer cell lines, they did not cause genotoxic in some concentrations damage and induced the enzyme quinone reductase.

Process and experience of cross-cultural adaptation of a quality of life measure (CHO-KLAT) for boys with haemophilia in Brazil.

Health-related quality of life (HRQoL) is an important outcome from the perspective of boys with haemophilia and their parents. Few studies have captured the HRQoL of boys with haemophilia in developing countries. This article reports on the cross-cultural adaptation of the Canadian Haemophilia Outcomes - Kids Life Assessment Tool (CHO-KLAT) for use in São Paulo, Brazil. The CHO-KLAT(2.0) was translated into Portuguese, and then translated back into English. The original English and back-translation versions were compared by a group of three clinicians, whose first language was Portuguese. The resulting Portuguese version was assessed through a series of cognitive debriefing interviews with children and their parents. This process identified concepts that were not clear and revised items to ensure appropriate understanding through an iterative process. The initial back-translation was not discrepant from the original English version. We made changes to 66% of the CHO-KLAT(2.0) items based on clinical expert review and 26% of the items based on cognitive debriefings. In addition, two new items were added to the final Portuguese version to reflect the local cultural context. The final result had good face validity. This process was found to be extremely valuable in ensuring the items were accurately interpreted by the boys/parents in São Paulo Brazil. The results suggest that professional translators, clinical experts and cognitive debriefing are all required to achieve a culturally appropriate instrument. The Portuguese CHO-KLAT(2.0) is well understood by Sao Paulo boys/parents. The next step will be to test its validity and reliability locally.

Importance of literacy for self-reported health-related quality of life: a study of boys with haemophilia in Brazil.

Psychosocial outcomes are important in the perspective of boys with haemophilia. However, health-related quality of life (HRQoL) is based on self-report, and assumes adequate literacy. Yet, literacy is rarely assessed prior to data collection. This study sought to identify criteria that might indicate the level of literacy of children being recruited for clinical trials and to develop a simple method to prescreen those whose literacy was uncertain. We developed a brief screening tool in the form of two stories, at a grade 3 reading level, followed by comprehension questions. We applied the screening test to a sample of haemophilic boys between the ages of 7 and 13 years to assess their literacy. The data were analysed to determine the best criteria to use in identifying the ability to independently self-report for HRQoL studies. Twenty-four Brazilian boys (7.9-12.8) completed the testing. The results showed that 17 (70.8%) were literate (were able to both read and comprehend), and could complete a questionnaire without assistance. All boys over 11.0 years of age were sufficiently literate. Grade level was not found to be a helpful criterion. We recommend that all children under the age of 11.0 years be prescreened before providing self-reported HRQoL data. Those with limited literacy should be provided assistance to ensure comprehension of the questions. This is important to ensure high-quality data on HRQoL for future clinical trials.

Serum laminin, type IV collagen and hyaluronan as fibrosis markers in non-alcoholic fatty liver disease.

Hepatic fibrosis in patients with non-alcoholic fatty liver disease is associated with progression of the disease. In the present study, we analyzed the discriminative ability of serum laminin, type IV collagen and hyaluronan levels to predict the presence of fibrosis in these patients. In this preliminary report, we studied 30 overweight patients divided into two groups according to the absence (group I, N = 19) or presence (group II, N = 11) of fibrosis in a liver biopsy. Triglycerides, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidade, hyaluronan (noncompetitive fluoroassay), type IV collagen, and laminin (ELISA) were determined. Group II presented significantly higher mean laminin, hyaluronan, type IV collagen, and aspartate aminotransferase values, which were due to the correlation between these parameters and the stage of fibrosis in the biopsy (Spearman's correlation coefficient, rS = 0.65, 0.62, 0.53, and 0.49, respectively). Analysis of the ROC curve showed that laminin values >282 ng/ml were those with the best diagnostic performance, with 87% accuracy. Association of laminin with type IV collagen showed improvement in the positive predictive value (100%), but with reduction in diagnostic sensitivity (64%). When compared with the criteria of Ratziu et al. for the diagnosis of septal fibrosis, laminin values presented a better diagnostic accuracy (83 vs 70%). Determination of extracellular matrix components in serum, especially of laminin, may identify patients with non-alcoholic fatty liver disease and fibrosis and these components may be used as indicators for liver biopsy in these patients.

Serum laminin, type IV collagen and hyaluronan as fibrosis markers in non-alcoholic fatty liver disease

Hepatic fibrosis in patients with non-alcoholic fatty liver disease is associated with progression of the disease. In the present study, we analyzed the discriminative ability of serum laminin, type IV collagen and hyaluronan levels to predict the presence of fibrosis in these patients. In this preliminary report, we studied 30 overweight patients divided into two groups according to the absence (group I, N = 19) or presence (group II, N = 11) of fibrosis in a liver biopsy. Triglycerides, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidade, hyaluronan (noncompetitive fluoroassay), type IV collagen, and laminin (ELISA) were determined. Group II presented significantly higher mean laminin, hyaluronan, type IV collagen, and aspartate aminotransferase values, which were due to the correlation between these parameters and the stage of fibrosis in the biopsy (Spearman's correlation coefficient, rS = 0.65, 0.62, 0.53, and 0.49, respectively). Analysis of the ROC curve showed that laminin values >282 ng/ml were those with the best diagnostic performance, with 87 percent accuracy. Association of laminin with type IV collagen showed improvement in the positive predictive value (100 percent), but with reduction in diagnostic sensitivity (64 percent). When compared with the criteria of Ratziu et al. [Gastroenterology (2000) 118: 1117-1123] for the diagnosis of septal fibrosis, laminin values presented a better diagnostic accuracy (83 vs 70 percent). Determination of extracellular matrix components in serum, especially of laminin, may identify patients with non-alcoholic fatty liver disease and fibrosis and these components may be used as indicators for liver biopsy in these patients.

A randomized double-blind study of the short-time treatment of obese patients with nonalcoholic fatty liver disease with ursodeoxycholic acid.

In order to determine the effect of ursodeoxycholic acid on nonalcoholic fatty liver disease, 30 patients with body mass indices higher than 25, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) or gamma-glutamyltransferase (gamma-GT) at least more than 1.5 times the upper limit of normality, and hepatic steatosis demonstrated by ultrasonography were randomized into two groups of 15 patients to receive placebo or 10 mg kg-1 day-1 ursodeoxycholic acid for three months. Abdominal computed tomography was performed to quantify hepatic fat content, which was significantly correlated with histological grading of steatosis (r s = -0.83, P < 0.01). Patient body mass index remained stable for both groups throughout the study, but a significant reduction in mean ( +/- SEM) serum levels of ALT, AST and gamma-GT was observed only in the treated group (ALT = 81.2 +/- 9.7, 44.8 +/- 7.7, 48.1 +/- 7.7 and 52.2 +/- 6.3 IU/l at the beginning and after the first, second and third months, respectively, N = 14, P < 0.05). For the placebo group ALT values were 66.4 +/- 9.8, 54.5 +/- 7, 60 +/- 7.6 and 43.7 5 IU/l, respectively. No alterations in hepatic lipid content were observed in these patients by computed tomography examination (50.2 +/- 4.2 Hounsfield units (HU) at the beginning versus 51.1 +/- 4.1 HU at the third month). These results show that ursodeoxycholic acid is able to reduce serum levels of hepatic enzymes in patients with nonalcoholic fatty liver disease, but this effect is not related to modifications in liver fat content.

A randomized double-blind study of the short-time treatment of obese patients with nonalcoholic fatty liver disease with ursodeoxycholic acid

In order to determine the effect of ursodeoxycholic acid on nonalcoholic fatty liver disease, 30 patients with body mass indices higher than 25, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) or gamma-glutamyltransferase (gamma-GT) at least more than 1.5 times the upper limit of normality, and hepatic steatosis demonstrated by ultrasonography were randomized into two groups of 15 patients to receive placebo or 10 mg kg-1 day-1 ursodeoxycholic acid for three months. Abdominal computed tomography was performed to quantify hepatic fat content, which was significantly correlated with histological grading of steatosis (r s = -0.83, P < 0.01). Patient body mass index remained stable for both groups throughout the study, but a significant reduction in mean (+ or - SEM) serum levels of ALT, AST and gamma-GT was observed only in the treated group (ALT = 81.2 + or - 9.7, 44.8 + or - 7,7, 48.1 + or - 7.7 and 52.2 + or - 6.3 IU/l at the beginning and after the first, second and third months, respectively, N = 14, P < 0.05). For the placebo group ALT values were 66.4 + or - 9.8, 54.5 + or - 7, 60 + or - 7.6 and 43.7 + or - 5 IU/l, respectively. No alterations in hepatic lipid content were observed in these patients by computed tomography examination (50.2 + or - 4.2 Hounsfield units (HU) at the beginning versus 51.1 + or - 4.1 HU at the third month). These results show that ursodeoxycholic acid is able to reduce serum levels of hepatic enzymes in patients with nonalcoholic fatty liver disease, but this effect is not related to modifications in liver fat content