An overview of recently published medical papers in Brazilian scientific journals

A brief review intended as information to the readership of Clinics on papers recently published under various medical headings in Brazilian scientific journals recently indexed or about to be indexed in ISI-THOMSON Journal Citation Reports. Journals covered in this review are Acta Ortopédica Brasileira, Arquivos Brasileiros de Cardiologia, Jornal Brasileiro de Pneumologia, Revista Brasileira de Cirurgia Cardiovascular and Revista da Associação Médica Brasileira.     

Frequency of genetic polymorphisms of PXR gene in the Brazilian population

INTRODUCTION:

PXR polymorphisms have been implicated in modulating CYP3A4 and PXR expression, potentially accounting for interindividual differences in drug metabolism. The prevalence of PXR polymorphisms varies among ethnic groups and data on the allelic distribution in the highly mixed Brazilian population is lacking. The aim of this study was to analyze genetic variations in the PXR gene in Brazilians and to compare the results to other ethnic groups.

METHODS:

DNA samples from 117 healthy Brazilians underwent PCR amplification and sequencing.

RESULTS:

Eleven polymorphisms were identified, 3 of which are highly associated with differences in CYP3A4 expression. We also identified 1 new synonymous variant in 1.3% of the alleles. Among the functional polymorphisms, –25913 C>T and –6994T>C occurred at a higher frequency compared to the African alleles (p < 0.05) but at a lower frequency compared to Caucasian alleles. The 8055 C>T allele was found at a similar frequency to those described in Caucasians and Africans (p > 0.05).

CONCLUSION:

We observed that functional variants of the PXR were frequent in our sample of the Brazilian population. Our results suggest that PXR gene variants may be of interest in pharmacogenetic studies involving Brazilians.     

Unpredictable chronic stress model in zebrafish (Danio rerio): behavioral and physiological responses

Zebrafish (Danio rerio) have emerged as a promising model organism to study development, toxicology, pharmacology, and neuroscience, among other areas. Despite the increasing number of studies using zebrafish, behavioral studies with this species are still elementary when compared to rodents. The aim of this study was to develop a model of unpredictable chronic stress (UCS) in zebrafish. We evaluated the effects of UCS protocol during 7 or 14 days on behavioral and physiological parameters. The effects of stress were evaluated in relation to anxiety and exploratory behavior, memory, expression of corticotrophin-releasing factor (CRF) and glucocorticoid receptor (GR), and cortisol levels. As expected, UCS protocol increased the anxiety levels, impaired cognitive function, and increased CRF while decreased GR expression. Moreover, zebrafish submitted to 7 or 14 days of UCS protocol presented increased cortisol levels. The protocol developed here is a complementary model for studying the neurobiology and the effects of chronic stress in behavioral and physiological parameters. In addition, this protocol is less time consuming than standard rodent models commonly used to study chronic stress. These results confirm UCS in zebrafish as an adequate model to preclinical studies of stress, although further studies are warranted to determine its predictive validity.     

Reference values for the fetal lateral ventricle atrium measurement in the second and third trimesters of pregnancy in a Brazilian population

Objective: To establish reference values for the fetal atrium lateral ventricle measurements in the second and third trimesters of pregnancy in a Brazilian population.

Methods: A retrospective cross-sectional study was performed with low-risk pregnant women who underwent ultrasound examination at 16–41 weeks of gestation. The atrium of lateral ventricle measurement was performed in the transventricular plane at the end of choroid plexus. We assessed reference curves (percentiles 5th, 50th and 95th) for the atrium of lateral ventricle measurement with gestational age (GA), using the best-fit polynomial equation, and determination coefficient (R²) and modeling the variability.

Results: The fetal atrium of lateral ventricle measurements was assessed in 519 singleton pregnancies. However, seven fetuses were excluded because of central nervous system malformations, and therefore data from 512 pregnancies were included in the analysis. The mean?±?standard deviation (range) of the fetal atrium lateral ventricle measurement (mm) was 5.1?±?1.4 (1.6–9.7). A best-fit curve was a first-degree polynomial regression: atrium lateral ventricle?=?6.455???0.049?×?GA (R²?=?0.05).

Conclusion: Reference values for the fetal atrium lateral ventricle measurements in the second and third trimesters of pregnancy in a Brazilian population were established.     

Immunoblot analyses of Brazilian pemphigus foliaceus antigen using different antigen sources

Summary We investigated the Brazilian pemphigus foliaceus (BPf) antigen applying the immunoblotting method to two different antigen sources using 27 patients' sera. Twelve BPf sera reacted specifically with a 150 kD protein in extract of dispase separated human epidermis, while 18 sera yielded a similar protein band in bovine muzzle desmosomal preparation. The diversity of staining intensities between the two samples suggested the heterogeneity of BPf antigens in terms of epitopes. Japanese sporadic pemphigus foliaceus (Pf) sera showed similar results but Japanese pemphigus vulgaris (Pv) sera recognized different antigens of 130 kD or 135 kD, suggesting that BPf is similar to Japanese Pf but is distinct from Pv in respect to the antigenic substance. Furthermore, the present study showed that immunoblot analysis using different antigen sources should be a valuable tool to determine clinical types of pemphigus.This work was supported in part by grant from the Ministry of Health and Welfare of Japan. Dr. Marilia M. Ogawa was an awardee of the Uehara Memorial Foundation Research Fellowship Program (1988)     

Antiproliferative activity and new argininyl bufadienolide esters from the “cururú” toad Rhinella (Bufo) schneideri

Ethnopharmacological relevance

Toads known as “cururú” (Rhinella schneideri) have been used in the Brazilian Pantanal and Paraguayan Chaco wetlands to treat erysipelas and cancer. The aim of the study was to assess the antiproliferative effect of the venom obtained from Rhinella schneideri and to identify its constituents by spectroscopic and spectrometric methods.

Materials and methods

The venom was obtained by gentle pressing the parotid glands of the toads. The dry crude drug was analyzed by HPLC–MS–MS and chromatographed on Sephadex LH-20 to obtain purified compounds and fractions for spectroscopic analysis. The venom and fractions were evaluated for antiproliferative activity towards normal human lung fibroblasts (MRC-5) and four human cancer cell lines: gastric epithelial adenocarcinoma (AGS), lung cancer (SK–MES-1), bladder carcinoma (J82) and promyelocytic leukemia (HL-60).

Results

From the Rhinella schneideri venom, 29 compounds were isolated and/or identified by spectroscopic and spectrometric means. Three known alkaloids and five argininyl diacids were identified in the complex mixture by HPLC–MS–MS. Nine out of fifteen argininyl diacid derivatives of the bufadienolides bufalin, marinobufagin and telocinobufagin are reported for the first time and four argininyl diacids are described for the first time as natural products. The venom and the fractions 9–13 showed a remarkable antiproliferative effect, with IC₅₀ values in the range 0.019–0.022, 0.035–0.040, 0.028–0.064, 0.042–0.056 and 0.044–0.052 µg/mL for MRC-5, AGS, SK-MES-1, J82 and HL-60 cell lines, respectively. Under the same experimental conditions, IC₅₀ values of the reference compound etoposide were 2.296, 0.277, 1.295, 1.884 and 1.059 µg/mL towards MRC-5, AGS, SK-MES-1, J82 and HL-60 cells, respectively.

Conclusions

The venom showed a strong antiproliferative effect towards human cancer cells and presented a high chemical diversity in its constituents, supporting its use as anticancer agent. These findings encourage further work on the chemistry and bioactivity of South American toad venoms.     

Inherited thrombophilias and pre-eclampsia in Brazilian women

OBJECTIVE: The aim of the present study was to compare the distribution of G1691A, G20210A and C677T mutations in pre-eclamptic Brazilian women and in matched control women with an uncomplicated normal pregnancy. STUDY DESIGN: these mutations were investigated by PCR-RFLP in 83 normal pregnancies (control group) and in 30 pre-eclamptic pregnant women (severe form). RESULTS: G1691A mutation was detected neither in the control group nor in pre-eclamsia women. G20210A mutation was detected in heterozygosis in 3 (3.61%) control subjects, but not in pre-eclampsia group. C677T mutation was detected in homozygosis in 6 (7.23%) control subjects and 2 (6.67%) pre-eclamptic women and in heterozygosis in 31 (37.3%) control subjects and 12 (40%) pre-eclamptic women. Differences in the mutation frequencies detected in the two groups were not statistically significant. CONCLUSION: No correlation was observed between pre-eclampsia and presence of G1691A, G20210A and C677T mutations in Brazilian women.     

Anti‐TNF‐α Activity of Brazilian Medicinal Plants and Compounds from Ouratea semiserrata

Several plant species are used in Brazil to treat inflammatory diseases and associated conditions. TNF‐α plays a pivotal role on inflammation, and several plant extracts have been assayed against this target, both in vitro and in vivo. The effect of 11 Brazilian medicinal plants on TNF‐α release by LPS‐activated THP‐1 cells was evaluated. The plant materials were percolated with different solvents to afford 15 crude extracts, whose effect on TNF‐α release was determined by ELISA. Among the evaluated extracts, only Jacaranda caroba (Bignoniaceae) presented strong toxicity to THP‐1 cells. Considering the 14 non‐toxic extracts, TNF‐α release was significantly reduced by seven of them (inhibition > 80%), originating from six plants, namely Cuphea carthagenensis (Lythraceae), Echinodorus grandiflorus (Alismataceae), Mansoa hirsuta (Bignoniaceae), Ouratea semiserrata (Ochnaceae), Ouratea spectabilis and Remijia ferruginea (Rubiaceae). The ethanol extract from O. semiserrata leaves was fractionated over Sephadex LH‐20 and RP‐HPLC to give three compounds previously reported for the species, along with agathisflavone and epicatechin, here described for the first time in the plant. Epicatechin and lanceoloside A elicited significant inhibition of TNF‐α release, indicating that they may account for the effect produced by O. semiserrata crude extract. Copyright © 2015 John Wiley & Sons, Ltd.     

Research of Dynamic Tensile Properties of Five Rocks under Three Loading Modes Based on SHPB Device

The validity of calculating the dynamic tensile strength of rock materials based on dynamic Brazilian tests is problematic. In order to gain a deeper understanding of the effects of three typical loading methods on the damage mechanism of rock specimens in the dynamic Brazilian tests, five different rocks were selected for the study. In the constant incident energy dynamic Brazilian test, the loading modes had a significant effect on the loading rate and dynamic tensile strength of the specimen, with the highest loading rate and tensile strength of the specimens under mode-III loading, followed by mode-I loading and mode-II loading. A high-speed camera and the digital image correlation (DIC) technique were used to successfully capture the rupture process of the Brazilian disc during impact loading. The evolution of the displacement and strain fields of the specimen was obtained by DIC technique, and four typical failure patterns and two rupture characteristics in the dynamic Brazilian test were summarized. The loading mode determined the crack initiation position of the specimen in the dynamic Brazilian test. The results showed that the mode-III loading is the most consistent with the Brazilian test theory, while the mode-II loading violates the test principle.