Comparison of impurity profiles of lipiblock® vs. orlistat using HPLC and LC-MS/MS

Comparative HPLC-UV and LC-MS/MS studies of impurity profiles of a reference sample (Xenical®, F. Hoffmann-La Roche Ltd., Switzerland) vs. generic (Lipiblock®, EMS-Sigma Pharma, a generic drug) were carried out with ethanol extracts of commercial samples. The generic formulation contained higher levels of common impurities as well as a considerable number of impurities not found in the reference product. The detected impurity profile of Lipiblock® revealed that it most likely is based on fermentation. Since the effect of the impurities is unknown, at this point fully synthetic Xenical® appears to offer a better safety margin than Lipiblock® which, however, compares quite well to other generic formulations.

Profiles of gene polymorphisms in cytokines and toll-like receptors with higher risk for gastric cancer

Background: Chronic inflammation and gastric carcinogenesis show a close association, so gene polymorphisms that modify the intensity of the inflammatory response may contribute to variations in gastric cancer risk. Aims: The purpose of this study was to investigate the combined effect of the pro- and anti-inflammatory cytokines and toll-like receptors polymorphisms on the chronic gastritis and gastric cancer risk in a Brazilian population sample. Methods: We evaluated 669 DNA samples (200 of gastric cancer [GC], 229 of chronic gastritis [CG], and 240 of healthy individuals [C]). Ten polymorphisms were genotyped: IL-1RN and TLR2 -196 to -174 del using the allele-specific PCR method and TNF-A (rs1800629; rs1799724), TNF-B (rs909253), IL-8 (rs4073; rs2227532), IL-10 (rs1800872) and TLR4 (rs4986790; rs4986791) using PCR-RFLP. Results: Polymorphisms TNF-A-308G/A, IL-8-251A/T, TNF-B + 252A/G and TLR4 + 1196C/T were not associated with risk of any gastric lesion. However, an association with increased risk for GC was observed for polymorphisms IL-1RNL/2 (p < 0.001), TNF-A-857C/T (p = 0.022), IL-8-845T/C (p < 0.001), IL-10-592C/A (p < 0.001), TLR2ins/del (p < 0.001), and TLR4 + 896A/G (p = 0.033). In CG, an association was observed only with polymorphisms IL-1RNL/2 and IL-10-592A/C (p < 0.001 for both). A combined analysis of these six polymorphisms associated with GC revealed a profile with two to four combined genotypes which confer a higher risk of gastric carcinogenesis, with an OR increased 2.95-fold to 50.4-fold, highlighting the combinations IL-1RN2/TNF-A-857T/IL-8-845C, IL-1RN2/IL-8-845C/TLR2del, IL-1RN2/IL-10-592A/TLR4 + 896G, IL-10-592A/TLR2del/ TLR4 + 896G, and IL-1RN2/TNFA-857T/IL8-845C/TLR2del. Conclusions: Our findings evidenced that the combined effect of polymorphisms in genes involved in the inflammatory process may potentiate the risk of gastric cancer, thus emphasizing the importance of evaluating multiple polymorphisms together. © 2012 Springer Science+Business Media New York.

Genomic and phenotypic profiles of two Brazilian breast cancer cell lines derived from primary human tumors

Breast cancer is the most common type of cancer among women worldwide. Research using breast cancer cell lines derived from primary tumors may provide valuable additional knowledge regarding this type of cancer. Therefore, the aim of this study was to investigate the phenotypic profiles of MACL-1 and MGSO-3, the only Brazilian breast cancer cell lines available for comparative studies. We evaluated the presence of hormone receptors, proliferation, differentiation and stem cell markers, using immunohistochemical staining of the primary tumor, cultured cells and xenografts implanted in immunodeficient mice. We also investigated the ability of the cell lines to form colonies and copy number alterations by array comparative genomic hybridization. Histopathological analysis showed that the invasive primary tumor from which the MACL-1 cell line was derived, was a luminal A subtype carcinoma, while the ductal carcinoma in situ (DCIS) that gave rise to the MGSO-3 cell line was a HER2 subtype tumor, both showing different proliferation levels. The cell lines and the tumor xenografts in mice preserved their high proliferative potential, but did not maintain the expression of the other markers assessed. This shift in expression may be due to the selection of an 'establishment' phenotype in vitro. Whole-genome DNA evaluation showed a large amount of copy number alterations (CNAs) in the two cell lines. These findings render MACL-1 and MGSO-3 the first characterized Brazilian breast cancer cell lines to be potentially used for comparative research. © 2013 Spandidos Publications Ltd. All rights reserved.

Effects of active smoking on airway and systemic inflammation profiles in patients with chronic obstructive pulmonary disease

Background: The markers that characterize local and systemic inflammation in chronic obstructive pulmonary disease (COPD) remain unclear, as do their correlations with smoking status and presence of disease. The aim of this study was to assess markers of inflammation in the peripheral blood and airways of current smokers without COPD, of current smokers with COPD and of ex-smokers with COPD. METHODS: In this study, 17 current smokers with COPD (mean age: 58.2 ± 9.6 years; mean forced expiratory volume in 1 second [FEV1]: 56.1 ± 15.9%), 35 ex-smokers with COPD (mean age: 66.3 ± 7.3 years; mean FEV1: 47.9 ± 17.2%) and 20 current smokers without COPD (mean age: 49.1 ± 6.2 years; mean FEV1: 106.5 ± 15.8%) were evaluated. Spirometry findings, body composition and serum/induced sputum concentrations of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-8 and IL-10, together with serum C-reactive protein (CRP) levels, were assessed. RESULTS: Serum TNF-α concentration was higher in all current smokers than in ex-smokers with COPD. In current smokers without COPD, serum CRP level was lower than in ex-smokers with COPD and significantly lower than in current smokers with COPD. Sputum TNF-α concentration was higher in current and ex-smokers with COPD than in current smokers without COPD. Multiple regression analyses showed that serum TNF-α was associated with active smoking, and serum CRP and sputum TNF-α were associated with COPD diagnosis. CONCLUSIONS: Smoking is associated with higher systemic inflammation in patients with COPD. Current findings also support the hypothesis that smoking and COPD have different effects on the regulation of airway and systemic inflammatory processes. © 2013 Lippincott Williams and Wilkins.

Comparison of inflammatory cytokine profiles in plasma of patients undergoing otorhinological surgery with propofol or isoflurane anesthesia

Objective and design: The effects of anesthetics on cytokine release in patients without comorbidities who undergo minor surgery are not well defined. We compared inflammatory cytokine profiles in adult patients undergoing minimally invasive surgery who received isoflurane or propofol anesthesia. Methods: Thirty-four patients without comorbidities undergoing minor surgery were randomly assigned to receive an inhaled anesthetic (isoflurane; n = 16) or an intravenous anesthetic (propofol; n = 18). Blood samples were drawn before premedication and anesthesia (T1), 120 min after anesthesia induction (T2), and on the first post-operative day (T3). Plasma concentrations of interleukins (IL-) 1β, 6, 8, 10 and 12 and tumor necrosis factor (TNF)-α were measured using flow cytometry. Results: The pro-inflammatory cytokine IL-6 was increased in the isoflurane group at T2 and T3 compared to T1 (P < 0.01). In the propofol group, IL-6 and IL-8 were significantly increased at T3 compared to T1. However, there were no significant differences in cytokine concentrations between the isoflurane and propofol groups. Conclusion: An inflammatory response occurred earlier in patients who received an inhaled agent compared with an intravenous anesthetic, but no differences in plasma cytokine profiles were evident between isoflurane and propofol anesthesia in patients without comorbidities undergoing minimally invasive surgeries. © 2013 Springer Basel.

Semen parameters and seminal plasma protein and biochemical profiles of dogs with benign prostatic hyperplasia after botulinum toxin type A intraprostatic injection

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

EGHEP-ISFG collaborative exercise on mixture profiles of autosomal STRs (GHEP-MIX01, GHEP-MIX02 and GHEP-MIX03): Results and evaluation

One of the main objectives of the Spanish and Portuguese-Speaking Group of the International Society for Forensic Genetics (GHEP-ISFG) is to promote and contribute to the development and dissemination of scientific knowledge in the area of forensic genetics. Due to this fact, GHEP-ISFG holds different working commissions that are set up to develop activities in scientific aspects of general interest. One of them, the Mixture Commission of GHEP-ISFG, has organized annually, since 2009, a collaborative exercise on analysis and interpretation of autosomal short tandem repeat (STR) mixture profiles. Until now, three exercises have been organized (GHEP-MIX01, GHEP-MIX02 and GHEP-MIX03), with 32, 24 and 17 participant laboratories respectively. The exercise aims to give a general vision by addressing, through the proposal of mock cases, aspects related to the edition of mixture profiles and the statistical treatment. The main conclusions obtained from these exercises may be summarized as follows. Firstly, the data show an increased tendency of the laboratories toward validation of DNA mixture profiles analysis following international recommendations (ISO/IEC 17025: 2005). Secondly, the majority of discrepancies are mainly encountered in stutters positions (53.4%, 96.0% and 74.9%, respectively for the three editions). On the other hand, the results submitted reveal the importance of performing duplicate analysis by using different kits in order to reduce errors as much as possible. Regarding the statistical aspect (GHEP-MIX02 and 03), all participants employed the likelihood ratio (LR) parameter to evaluate the statistical compatibility and the formulas employed were quite similar. When the hypotheses to evaluate the LR value were locked by the coordinators (GHEP-MIX02) the results revealed a minor number of discrepancies that were mainly due to clerical reasons. However, the GHEP-MIX03 exercise allowed the participants to freely come up with their own hypotheses to calculate the LR value. In this situation the laboratories reported several options to explain the mock cases proposed and therefore significant differences between the final LR values were obtained. Complete information concerning the background of the criminal case is a critical aspect in order to select the adequate hypotheses to calculate the LR value. Although this should be a task for the judicial court to decide, it is important for the expert to account for the different possibilities and scenarios, and also offer this expertise to the judge. In addition, continuing education in the analysis and interpretation of mixture DNA profiles may also be a priority for the vast majority of forensic laboratories. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Effect of lipid sources with different fatty acid profiles on the intake, performance, and methane emissions of feedlot Nellore steers

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Analysis of Toll-Like Receptors, iNOS and Cytokine Profiles in Patients with Pulmonary Tuberculosis during Anti-Tuberculosis Treatment

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Expression profiles of fetal membrane nicotinamide adenine dinucleotide phosphate oxidases (NOX) 2 and 3 differentiates spontaneous preterm birth and pPROM pathophysiologies

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Comprehensive Analysis of Gene Expression Profiles of the Beet Armyworm Spodoptera exigua Larvae Challenged with Bacillus thuringiensis Vip3Aa Toxin

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Dose and temporal effects on gene expression profiles of urothelial cells from rats exposed to diuron

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Frontonasal dysplasia: clinical evaluation on audiological and brainstem electrophysiological profiles

Frontonasal dysplasia (FND) is a rare malformative complex affecting the frontal portion of the face, the eyes and the nose; it may occur singly or associated with other clinical signs. No systematic studies describing hearing in this condition were found. AIM: To evaluate hearing sensitivity and sound stimulus conduction from cochlea to brainstem in patients with clinical signs of FND. METHODS: 21 patients with isolated or syndromic FND were submitted to a clinical (otological/vestibular antecedents and otoscopy) and instrumental (pure tone and speech audiometry, tympanometry and brainstem auditory evoked response) hearing evaluation. DESIGN: A clinical, cross-sectional observational prospective study. RESULTS: Hearing thresholds were normal in 15 (70%) patients, abnormal in 5 (25%), mostly with conductive hearing loss; one patient did not cooperate with testing. The tympanometric curve was type A in 30 (72%) ears, type C in 5 (12%), type As in 4 (9%) and type B in 3 (7%). The auditory brainstem response (ABR) showed no abnormalities. CONCLUSION: Patients with FND showed no abnormalities in the auditory system from cochlea to brainstem in this study. Mild conductive hearing loss found in some is probably related to cleft palate. Further evaluation of hearing pathways at higher levels is recommended.

Changes in gene expression in PBMCs profiles of PPAR alpha target genes in obese and non-obese individuals during fasting

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Profiles of steroid hormones in canine X-Linked muscular dystrophy via stable isotope dilution LC-MS/MS

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)