Effects of Caffeoylquinic Acid Derivatives and C-Flavonoid from Lychnophora ericoides on in vitro Inflammatory Mediator Production

In this study we aimed at evaluating the effect of the major polar constituents of the medicinal plant Lychnophora ericoides on the production of inflammatory mediators produced by LPS-stimulated U-937 cells. The 6,8-di-C-beta-glucosylapigenin (vicenin-2) presented no effect on tumor necrosis factor (TNF)-alpha production, but inhibited, in a dose-dependent manner, the production of prostaglandin (PG) E(2) without altering the expression of cyclooxygenase (COX) -2 protein. 3,5-Dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid, at lower concentrations, had small but significant effects on reducing PG E, levels; at higher doses these compounds stimulated PGE(2) and also TNF-alpha production by the cells. All the caffeoylquinic acid derivatives, in a dose-dependent fashion, were able to inhibit monocyte chemoattractant protein-3 synthesis/release, with 4,5-DCQ being the most potent at the highest tested concentration. These results add important information on the effects of plant natural polyphenols, namely vicenin-2 and caffeoylquinic acid derivatives, on the production of inflammatory mediators by cultured cells.

Bursts of transposition from non-long terminal repeat retrotransposon families of the RTE clade in Schistosoma mansoni

The genus Schistosoma is composed of blood flukes that infect vertebrates, from which three species are major causative agents of human schistosomiasis, a tropical disease that affects more than 200 million people. Current models of the recent evolution of Schistosoma indicate multiple events of migration and speciation from an Asian ancestral species. Transposable elements are important drivers of genome evolution and have been hypothesised to have an important role in speciation. In this work, we describe a comprehensive inventory of Schistosoma mansoni and Schistosoma japonicum retrotransposons, based on their recently published genomic data. We find a considerable difference in retrotransposon representation between the two species (22% and 13%, respectively). A large part of this difference can be attributed to higher representation of two previously described families of S. mansoni retrotransposons (SR2 and Perere-3/SR3), compared with the representation of their closest relative families in S. japonicum. A more detailed analysis suggests that these two S. mansoni families were the subject of recent bursts of transposition that were not paralleled by their S. japonicum counterparts. We hypothesise that these bursts could be a consequence of the evolutionary pressure resulting from migration of Schistosoma from Asia to Africa and their establishment in this new environment, helping both speciation and adaptation. (C) 2009 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

The Genome Sequence of Taurine Cattle: A Window to Ruminant Biology and Evolution

To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.

Do psychiatric comorbidities predict postoperative seizure outcome in temporal lobe epilepsy surgery?

Clinical and demographic presurgical variables may be associated with unfavorable postsurgical neurological outcome in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). However, few reports include preoperative psychiatric disorders as a factor predictive of long-term post-surgical MTLE-HS neurological Outcome. We used Engel`s criteria to follow 186 postsurgical patients with MTLE-HS for an average of 6 years. DSM-IV criteria and psychiatric comorbidity criteria specific to epilepsy (interictal dysphoric disorder, postictal and interictal psychosis) were used to assess presurgical psychiatric disorders. Kaplan-Meier event-free Survival and adjusted hazard ratios were estimated with unconditional logistic regression. Seventy-seven (41.4%) patients had a preoperative Axis I psychiatric diagnosis. Thirty-six patients had depression, I I interictal dysphoric disorder, 14 interictal psychosis, 6 postictal psychosis, and 10 anxiety disorders. Twenty-three (12.4%) patients had Axis 11 personality disorders. Regarding seizure outcome, preoperative anxiety disorders (P = 0.009) and personality disorders (P = 0.003) were positively Correlated with Engel class I B (remaining auras) or higher. These findings emphasize the importance of presurgical psychiatric evaluation, counseling, and Postsurgical follow-up of patients with epilepsy and psychiatric disorders. (C) 2009 Elsevier Inc. All rights reserved.

Loss of samples in the tissue microarray technique: comparison between slides using adhesive tape and silanized slides

The tissue microarray (TMA) technique allows multiple tissue samples in a single block. Commercial adhesive tape is used to avoid the loss of tissue samples during the immunostaining process. Few reports exist in the literature comparing the use of these adhesive tapes to other adhesive techniques. The objective of this study was to compare loss of sections adhered to slides using commercial adhesive tapes versus using silanized only slides. TMA was constructed with varying tissues using a fixed-base device (Beecher Instruments), placing 108 cylinders of 1 mm diameter in duplicate, spaced 1.2 mm apart. Section of 4 mu m were cut from the TMA block and adhered to 30 silanized slides and 30 commercial glass slides using adhesive tape, according to manufacturer`s recommendations. Vimentin immunoexpression was evaluated by immunohistochemistry. Antigenic recovery was realized in citrate buffer using a microwave oven. Cylinder loss in the immunohistochemical process was quantified and expressed as: total (>80%), almost complete (75-79%), or partial (50-74%). The commercial adhesive tape group presented lesser total loss (1.1 versus 6.4%), almost complete loss (2.2 versus 3.5%), and partial loss (2.1 versus 3.8%) than the silanized slide group (ANOVA, P < 0.05). The sum of total and almost complete losses in the silanized slide group was 9.9%, greater than the losses in slides using commercial adhesive tapes (3.3%) and less than reported and considered acceptable in the literature (10-30%). In conclusion, the use of silanized only slides presents very satisfactory results, requires less training, and reduces costs significantly, thus justifying their use in research.

Current developments on Schistosoma proteomics

Several papers on Schistosoma mansoni and Schistosoma japonicum proteomes have been published worldwide in the past few years, representing an emerging field of study. Knowledge of the schistosome proteome may greatly enhance our understanding of schistosome physiological processes at the molecular level, and may provide new models for development of vaccines or drugs. Despite the importance of this approach. schistosome proteomic research in Brazil is still incipient. Here we review the development of schistosome proteomic research around the world and provide an appreciation on the future opportunities in Brazil. (c) 2008 Elsevier B.V. All rights reserved

Cannabis use before age 15 and subsequent executive functioning

Background Many studies have suggested that adolescence is a period of particular vulnerability to neurocognitive effects associated with substance misuse. However, few large studies have measured differences in cognitive performance between chronic cannabis users who started in early adolescence (before age 15) with those who started later. Aims To examine the executive functioning of individuals who started chronic cannabis use before age 15 compared with those who started chronic cannabis use after 15 and controls. Method We evaluated the performance of 104 chronic cannabis users (49 early-onset users and 55 late-onset users) and 44 controls who undertook neuropsychological tasks, with a focus on executive functioning. Comparisons involving neuropsychological measures were performed using generalised linear model analysis of variance (ANOVA). Results The early-onset group showed significantly poorer performance compared with the controls and the late-onset group on tasks assessing sustained attention, impulse control and executive functioning. Conclusions Early-onset chronic cannabis users exhibited poorer cognitive performance than controls and late-onset users in executive functioning. Chronic cannabis use, when started before age 15, may have more deleterious effects on neurocognitive functioning.

Panretinal photocoagulation versus PRP plus intravitreal bevacizumab for high-risk proliferative diabetic retinopathy (IBeHi study)

Purpose: To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal bevacizumab on best corrected visual acuity (BCVA) and total area of fluorescein leakage from active new vessels (NVs) in patients with high-risk proliferative diabetic retinopathy (PDR). Methods: We carried out a prospective study of patients with high-risk PDR and no prior laser treatment who were randomly assigned to receive PRP (PRP group) or PRP plus intravitreal injection of 1.5 mg of bevacizumab (PRP-plus group). In all patients, the PRP was administered at two time-points (weeks 1 and 3), with the intravitreal bevacizumab delivered at the end of the second laser episode in the PRP-plus group. Standardized ophthalmic evaluation including Early Treatment Diabetic Retinopathy Study BCVA as well as stereoscopic fundus photography and fluorescein angiography were performed at baseline and at weeks 4, 9 (+/- 1) and 16 (+/- 2). Main outcome measures included changes in BCVA and in total area of fluorescein leakage from active NVs. Results: Twenty-two (n = 30 eyes) consecutive patients completed the 16-week follow-up. There was no significant difference between the PRP and PRP-plus groups with respect to age, gender, type or duration of diabetes, area of fluorescein leakage from active NVs or BCVA. No significant difference in BCVA was observed between the groups throughout the study period. However, the total area of actively leaking NVs was significantly reduced in the PRP-plus group compared with the PRP group at weeks 4, 9 and 16 (p < 0.001). No major adverse events were identified. Conclusions: In the short-term, the adjunctive use of intravitreal bevacizumab with PRP was associated with a greater reduction in the area of active leaking NVs than PRP alone in patients with high-risk PDR.

Influence of aging, tidal volume, and respiratory rate on Doppler echocardiographic indices of diastolic function in normal male subjects: A quantitative evaluation

Background: Although the influence of respiration on ventricular filling, as evaluated by Doppler technique, and the evaluation of diastolic velocities of mitral valve annulus (MVA), as measured by Doppler tissue imaging (DTI), can provide valuable information for the study of left ventricular (LV) diastolic function, the concomitant effects of aging, tidal volume (TV), and respiratory rate (RR) on these velocities have not been quantitatively investigated. Methods: We evaluated 12 normal male volunteers (Group I) aged 20-26 years (mean: 22.8) and 8 normal subjects aged 41 to 54 years old (mean: 45.9) (Group II). Using DTI we measured peak early (E-a) and late (A(a)) velocities of longitudinal axis expansion at lateral and medial MVA. Doppler mitral and tricuspid flow velocities were measured: peak early (E) and late (A) inflow velocity, early (E-i) and late (A(i)) flow integral, and deceleration time of peak early mitral flow velocity (DT). Respiratory cycles were simultaneously recorded at RR of 9, 12, 15, and 18 cycles/min and TV of 600 and 900 mL during respiration (RESP). Results and conclusions: (1) E, A, and A(i) in MV had negligible change during respiration, but E-i was significantly reduced during inspiration; (2) DT reduced slightly with inspiration, but the change was significant only with TV of 900 mL; (3) an important increase of E in right ventricular flow was observed during inspiration; (4) variations of RR and TV did not significantly influence right and left ventricular inflow in normal subjects, in the conditions of this investigation; (5) a significant increase of E-a at medial MVA was documented during inspiration only in young subjects; (6) a significant decrease of A(a) at medial MVA was observed during inspiration in both groups of volunteers; (7) RR and TV did not influence MVA velocities in young and adult subjects; (8) a consistent reduction in E-a and a significant increase in A(a) were observed with increasing age; (9) these changes were more conspicuous and consistent than those documented in ventricular filling when young and middle-age men are compared, suggesting that the DTI is more sensitive to detect changes in diastolic function; and (10) in addition, these data suggest that, for evaluation of diastolic function, in clinical context, it is not necessary to control rigorously RR or TV.

Addressing overtreatment in patients with refractory epilepsy at a tertiary referral centre in Brazil

Background. Patients with refractory epilepsy often have impaired quality of life (QOL) as a consequence of seizures and adverse effects of antiepileptic drugs. We assessed the impact of adverse effects on QOL and the utility of a structured instrument to help the physician manage adverse effects in patients with refractory epilepsy. Methods. Clinical characteristics, drug treatment and adverse effects were evaluated in 102 patients with refractory epilepsy at a single tertiary referral centre. The Adverse Events Profile (AEP) and Quality of Life in Epilepsy-31 (QOLIE-31) questionnaires were completed at baseline and after six months. At baseline, patients with a high burden of adverse effects (AEP scores >= 45) were randomized to an intervention or control group. AEP scores in the intervention group were available to the physician as an instrument to help to reduce adverse effects. Results. Ninety-five patients (93.1%) were on polytherapy. Sixty-six completed the questionnaires and, of these, 43 (65.1%) had a high AE burden and were randomized to the intervention and control group. QOLIE-31 scores were inversely correlated with AEP scores at both visits. Among randomized patients, AEP scores tended to decrease between the baseline and the final visit without significant differences between groups (intervention group: 54.1 +/- 6.1 vs 51.1 +/- 9.1; control group: 55.8 +/- 5.8 vs 50.5 +/- 12.2). QOLIE-31 scores did not change substantially between visits (intervention group: 45.9 +/- 17.4 vs 48.4 +/- 14; control group: 47.5 +/- 15.7 vs 45.2 +/- 18.9). Conclusion. A significant proportion of patients had a high toxicity burden which had an impact on their QOL. Reduction of over-treatment is a difficult challenge which cannot be addressed solely by providing a structured assessment of adverse effects, but requires a more comprehensive approach aimed at optimizing the many components of the management strategy.

Tunicamycin inhibition of N-glycosylation of alpha-glucosidase from Aspergillus niveus: partial influence on biochemical properties

Treatment of Aspergillus niveus with 30 mu g tunicamycin/ml did not interfere with alpha-glucosidase production, secretion, or its catalytic properties. Fully- and under-glycosylated forms of the enzyme had similar molecular masses, similar to 56 kDa. Moreover, the absence of N-glycans did not affect either pH optimum (6.0) or temperature optimum (65A degrees C). The K(m) and V(max) values of under- and fully-glycosylated forms of alpha-glucosidase were similar when assessed for hydrolysis of starch (similar to 0.6 mg/ml, similar to 350 mu mol glucose per min per ml), maltose (similar to 0.54 mu mol, similar to 330 mu mol glucose per min per ml) and p-nitrophenyl-alpha-d-glucopyranoside (similar to 0.54 mu mol, similar to 8.28 mu mol p-nitrophenol per min per ml). However, the under-glycosylated form was sensitive to high temperatures probably because, in addition to stabilizing the protein conformation, glycosylation may also prevent unfolded or partially folded proteins from aggregating. Binding assays clearly showed that the under-glycosylated protein did not bind to concanavalin A but has conserve its jacalin-binding property, suggesting that only O-glycans might be intact on the tunicamycin treated form of the enzyme.

The Impact of Preexisting Myocardial Remodeling on Ventricular Function Early after Tetralogy of Fallot Repair

Background: Twenty-three patients (median age 23 months) who underwent Fallot`s tetralogy repair were investigated prospectively to detect a possible association between histopathologic myocardial remodeling and echocardiographic findings of systolic or diastolic ventricular dysfunction. Methods: Intraoperatively resected infundibular bands and subendocardial biopsy samples from the right ventricle (RV) and left ventricle were obtained for histopathologic evaluation. Tissue Doppler echocardiographic interrogation of the ventricles was performed before surgery and in the postoperative period. Results: Histopathologic data revealed hypertrophy of the RV cardiomyocytes and increased interstitial collagen in both ventricles. Mean values of RV isovolumic acceleration decreased significantly at the third evaluation compared with the preoperative values (P = .006). RV myocardial fibrosis greater than 8.3% was associated with a probability of altered E` of at least 0.7 (odds ratio = 2.31). Conclusion: Preoperative histologic myocardial remodeling influenced the postoperative RV function in this group of patients with late repair. Further studies are necessary to evaluate the myocardium in younger patients and to define its influence in the long-term follow-up. (J Am Soc Echocardiogr 2010;23:912-8.)

Curupira-1 and Curupira-2, two novel Mutator-like DNA transposons from the genomes of human parasites Schistosoma mansoni and Schistosoma japonicum

Transposons of the Mutator superfamily have been widely described in plants, but only recently have metazoan organisms been shown to harbour them. In this work we describe novel Mutator superfamily transposons from the genomes of the human parasites Schistosoma mansoni and S. japonicum, which we name Curupira-1 and Curupira-2. Curupira elements do not have Terminal Inverted Repeats (TIRs) at their extremities and generate Target Site Duplications (TSDs) of 9 base pairs. Curupira-2 transposons code for a conserved transposase and SWIM zinc finger domains, while Curupira-1 elements comprise these same domains plus a WRKY zinc finger. Alignment of transcript sequences from both elements back to the genomes indicates that they are subject to splicing to produce mature transcripts. Phylogenetic analyses indicate that these transposons represent a new lineage of metazoan Mutator-like elements with characteristics that are distinct from the recently described Phantom elements. Description of these novel schistosome transposons provides new insights in the evolution of transposable elements in schistosomes.

Number of expressed cancer/testis antigens identifies focal adhesion pathway genes as possible targets for multiple myeloma therapy

Considering that the importance of cancer/testis (CT) antigens in multiple myeloma (MM) biology is still under investigation, the present study aimed to: (1) identify genes differentially expressed in MM using microarray analysis of plasma cell samples, separated according to the number of expressed CTs; (2) examine possible pathways related to MM pathogenesis; (3) validate the expression of candidate genes by quantitative real-time PCR (RQ-PCR). Three samples predominantly positive (>6 expressed), including the U266 cell line, and three samples predominantly negative (0 or 1 expressed CT for the 13 analyzed CT antigens), were submitted for microarray analysis. Validation by RQ-PCR from 24 MM samples showed that the ITGAS gene was downregulated in predominantly positive (>6 expressed CTs, p = 0.0030) and in tumor versus normal plasma cells (p = 0.0182). The RhoD gene was overexpressed in tumor plasma cells when compared to normal plasma cells (p = 0.0339). Results of the microarray analysis corroborate the hypothesis that MM could be separated into predominantly positive and predominantly negative expression. The differential expression of ITGA5 and RhoD suggests disruption of the focal adhesion pathway in MM and offers a new target field to be explored in this disease.

Antimicrobial and Cytotoxic Activity of Fruit Extract from Syzygium cumini (L.) Skeels

The aim of the present study was to evaluate the antimicrobial and cytotoxic activity of the ethanolic extract of S. cumini according to the Clinical and Laboratory Standards Institute reference method (with modifications), determining the minimal inhibitory and lethal concentration. Activity against Gram-positive (Staphylococcus aureus and S. epidermidis), Gram-negative (Pseudomonas aeruginosa) and yeast of Candida sp and Cryptococcus neoformans was evaluated. The effects of the fruit extract were examined in hamster cells ovaries in concentrations ranging from 1250.0 a 4.9 mu g/ml, measuring the reduction of the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium. The extract showed both bactericidal and fungicidal activity among the various microorganisms tested and the MIC ranging from 7.8 to 250 mu g/ml. The MIC, MBC and MFC should values that were similar for all the microorganisms. Cytotoxicity index of the dried extract corresponded to the concentration of 400 mu g/ml. The extract could potentially be used in topical antimicrobial products. Thus, the activity of extract was potent to bacteria and mainly to non-albicans species and C. neoformans.