Comparison of the hemolytic activity between C. albicans and non-albicans Candida species

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

Supplementation and therapeutic use of vitamin D in patients with multiple sclerosis: Consensus of the Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology

A esclerose múltipla (EM) é uma doença inflamatória, autoimune, desmielinizante e degenerativa do sistema nervoso central. Estudos epidemiológicos têm identificado associações de hipovitaminose D com doenças autoimunes. O principal objetivo desta revisão é responder se há evid��ncias que indiquem o uso terapêutico de vitamina D em monoterapia para pacientes com EM. Por meio dos sites PUBMED, EMBASE, LILACS e Scielo foram realizadas buscas usando os descritores “vitamin D���, e “multiple sclerosis” até 12/09/2013. Estudos clínicos randomizados, controlados e duplo-cegos foram selecionados para avaliar a resposta terapêutica da vitamina D na EM. Não foram encontradas evid��ncias científicas que justifiquem o uso da vitamina D em monoterapia no tratamento da EM, na prática clínica.

Inflammatory response of endothelial cells to hepatitis C virus recombinant envelope glycoprotein 2 protein exposure

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

Caracterização mineralógica, petrológica e química da sulfetação nos reef's da mina Canavieiras, Jacobina, Bahia

In the Serra de Jacobina, localized in the North Central portion of the state of Bahia, occours the Jacobina Group. It’s a sedimentary basin and the gold deposit is stocked on the basal portion, which consist on quartzites intercalated with oligomítico metaconglomerates of Serra do Córrego Formation. There are controversies about the origin of the gold mineralization, but the currently most accepted hypothesis corresponds to a paleoplacer deposit with subsequent ore remobilization and concentration by hydrothermal process. The sulphidation is one of the main results of hydrothermal process, which was more detail characterized, besides identifying if there was more than one sulfides phase generation and its relationship with gold mineralization. The analyzes were performed from the main reef's (metaconglomerates mineralized levels) of Mine Canavieiras: Maneira, Holandez, Liberino, Piritoso, MU and LU. Chemical analyzes semi-quantitative were developed with EDS in MEV and also petrographics analyses. The main sulfide is pyrite, followed by chalcopyrite. Six groups of pyrite were classified according with chemical composition, however they show similarities in their habit and occurrence. Were identified four types of chlorite, labeled A, B, C, D. Gold occurs in free form, associate to pyrites, to Fe-Ti-Muscovite, to chlorite type B and to microfractures with iron hydroxide. Gold presents three different compositions: pure, with Ag or associated with U-Zr. The results of chemical analysis showed that the hydrothermal process have as their main source, ultramafic rocks present in the Jacobina Basin

Characterization of the phosphatidylinositol-specific phospholipase C-released form of rat osseous plate alkaline phosphatase and its possible significance on endochondral ossification

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

Associations of vitamin D deficiency with postoperative gait and mortality among patients with fractures of the proximal femur

To assess whether serum vitamin D concentration is associated with gait status and mortality among patients with fractures of the proximal femur, six months after suffering the fracture. Consecutive patients aged ≥65 years with fractures of the proximal femur, who were admitted to the orthopedics and traumatology ward of our service between January and December 2011, were prospectively evaluated. Clinical, radiological, epidemiological and laboratory analyses were performed, including vitamin D. The patients underwent surgery and were followed up as outpatients, with return visits 15, 30, 60 and 180 days after discharge, at which the outcomes of gait and mortality were evaluated. Eighty-eight patients were evaluated. Two of them were excluded because they presented oncological fractures. Thus, 86 patients of mean age 80.2 ± 7.3 years were studied. In relation to serum vitamin D, the mean was 27.8 ± 14.5 ng/mL, and 33.7% of the patients presented deficiency of this vitamin. In relation to gait, univariate and multivariate logistic regression showed that vitamin D deficiency was not associated with gait recovery, even after adjustment for gender, age and type of fracture (OR: 1.463; 95% CI: 0.524-4.088; p = 0.469). Regarding mortality, Cox regression analysis showed that vitamin D deficiency was not related to its occurrence within six months, even in multivariate analysis (HR: 0.627; 95% CI: 0.180-2.191; p = 0.465). Serum vitamin D concentration was not related to gait status and/or mortality among patients with fractures of the proximal femur, six months after suffering the fracture.

Involvement of AMPK, IKβα-NFκB and eNOS in the sildenafil anti-inflammatory mechanism in a demyelination model

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Integration of R&D and new product development: case studies of Brazilian high-tech firms

One of the aspects that influence good performance of new product development (NPD) at high-tech companies is the integration of research and development (R&D) and the other functions involved with NPD. The objective of this paper is to examine why Brazilian medium and large sized high-tech companies are different with respect to the integration of R&D with NPD. An analysis of case studies was conducted at five Brazilian high-tech firms. Among the results, collectivism, which is characteristic of the Brazilian organisational culture, was seen to manifest itself in companies through the adoption of cross-functional teams; the valorisation of personal relations, which is stimulated by physical proximity; and project managers’ ample participation in different functions involving NPD.

Immature stages of Calycopis bellera (Hewitson) and C-janeirica (Felder) (Lepidoptera, Lycaenidae, Theclinae, Eumaeini): Taxonomic significance and new evidence for detritivory

Details of egg, larval, and pupal morphology are described and illustrated for Calycopis bellera (Hewitson) and C. janeirica (Felder), with a special emphasis on larval chaetotaxy. Wild-caught Calycopis females laid eggs on dead leaves in the laboratory, and the caterpillars successfully completed development on an artificial agar diet to which no leaves were added. Males and females of the sexually dimorphic C. bellera had been previously placed in different genera or different species groups. Calycopis janeirica had been chronically misidentified (and misspelled C. jeneirica). Males and females of this species appear to be correctly associated for the first time. Whereas C. bellera has five larval instars-as reported previously for C. caulonia-C. janeirica has four. Morphological characters of the immatures of C. bellera and C. janeirica are summarized in a table and compared with those of other reared Calycopis species.

In Vitro Schistosomicidal Activity of Balsaminol F and Karavilagenin C

Five cucurbitane-type triterpenes (1-5), previously isolated from the African medicinal plant Momordica balsamina, along with five ester derivatives (6-10) of karavilagenin C (2), were evaluated for their potential schistosomicidal activity against Schistosoma mansoni adult worms. The natural compounds were isolated from the ethyl acetate-soluble fraction of the methanol extract of the aerial parts of M. balsamina. In a preliminary study, a significant schistosomicidal activity was observed for both the crude methanol extract and the ethyl acetate fraction. The compounds responsible for the activity were found to be balsaminol F (1) and karavilagenin C (2) with LC50 values of 14.7 +/- 1.5 and 28.9 +/- 1.8 mu M, respectively, after 24 h of incubation (positive control praziquantel, LC50 = 1.2 +/- 0.1 mu M). Both compounds (1, 2), at 10-50 mu M, induced significant reductions in the motor activity of the worms and significantly decreased the egg production. Furthermore, they were able (at 10-100 mu M) to separate the adult worm pairs into male and female after 24 h. Compounds 3-5, bearing a sugar moiety as a substituent, and the acylated derivatives of karavilagenin C (6-10) were inactive, suggesting that the presence of free hydroxyl groups in the tetracyclic skeleton might be important for the activity. A correlation between activity and the molecular volume/weight of compounds was also found.

The contribution of HGAL/GCET2 in immunohistological algorithms: a comparative study in 424 cases of nodal diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma can be subclassified into at least two molecular subgroups by gene expression profiling: germinal center B-cell like and activated B-cell like diffuse large B-cell lymphoma. Several immunohistological algorithms have been proposed as surrogates to gene expression profiling at the level of protein expression, but their reliability has been an issue of controversy. Furthermore, the proportion of misclassified cases of germinal center B-cell subgroup by immunohistochemistry, in all reported algorithms, is higher compared with germinal center B-cell cases defined by gene expression profiling. We analyzed 424 cases of nodal diffuse large B-cell lymphoma with the panel of markers included in the three previously described algorithms: Hans, Choi, and Tally. To test whether the sensitivity of detecting germinal center B-cell cases could be improved, the germinal center B-cell marker HGAL/GCET2 was also added to all three algorithms. Our results show that the inclusion of HGAL/GCET2 significantly increased the detection of germinal center B-cell cases in all three algorithms (P<0.001). The proportions of germinal center B-cell cases in the original algorithms were 27%, 34%, and 19% for Hans, Choi, and Tally, respectively. In the modified algorithms, with the inclusion of HGAL/GCET2, the frequencies of germinal center B-cell cases were increased to 38%, 48%, and 35%, respectively. Therefore, HGAL/GCET2 protein expression may function as a marker for germinal center B-cell type diffuse large B-cell lymphoma. Consideration should be given to the inclusion of HGAL/GCET2 analysis in algorithms to better predict the cell of origin. These findings bear further validation, from comparison to gene expression profiles and from clinical/therapeutic data. Modern Pathology (2012) 25, 1439-1445; doi: 10.1038/modpathol.2012.119; published online 29 June 2012

Plasma corticosterone elevation inhibits the activation of nuclear factor kappa B (NFKB) in the Syrian hamster pineal gland

We evaluated how the mild stress-induced increase in endogenous corticosterone affected the pineal gland in Syrian hamsters (Mesocricetus auratus). The animals were maintained under constant light for 1 day, instead of a cycle of 14:10-h, to increase the circulating corticosterone levels during the daytime. The nuclear translocation of nuclear factor kappa B (NFKB), which is the pivotal transcription factor for stress and injury, presented a daily rhythm in normal animals. NFKB nuclear content increased linearly from the onset of light [Zeitgeber Time 0 (ZT0)] until ZT11 and decreased after ZT12 when the plasma corticosterone peak was detected in normal animals. However, the 24-h profiles of the two curves were different, and they did not clearly support an exclusive relationship between corticosterone levels and NFKB content. Therefore, we tested the effect of increased endogenous corticosterone through inducing mild stress by maintaining daytime illumination for one night. This stressful condition, which increased daytime corticosterone levels, resulted in a daytime decrease in NFKB nuclear content, and this was inhibited by mifepristone. Overall, this study shows that NFKB has a daily rhythm in Syrian hamster pineal glands and, by increasing endogenous corticosterone with a stressful condition, NFKB activity is regulated. Therefore, this study suggests that the pineal gland in the Syrian hamster is a sensor of stressful conditions.

Detection of the Epstein-Barr virus in blood and bone marrow mononuclear cells of patients with aggressive B-cell non-Hodgkin's lymphoma is not associated with prognosis

The Epstein-Barr virus (EBV) is associated with a large spectrum of lymphoproliferative diseases. Traditional methods of EBV detection include the immunohistochemical identification of viral proteins and DNA probes to the viral genome in tumoral tissue. The present study explored the detection of the EBV genome, using the BALF5 gene, in the bone marrow or blood mononuclear cells of patients with diffuse large B-cell lymphomas (DLBCL) and related its presence to the clinical variables and risk factors. The results show that EBV detection in 21.5% of patients is not associated with age, gender, staging, B symptoms, international prognostic index scores or any analytical parameters, including lactate dehydrogenase (LDH) or beta-2 microglobulin (B2M). The majority of patients were treated with R-CHOP-like (rituximab. cyclophosphamide, doxorubicin, vincristine and prednisolone or an equivalent combination) and some with CHOP-like chemotherapy. Response rates [complete response (CR) + partial response (PR)] were not significantly different between EBV-negative and -positive cases, with 93.2 and 88.9%, respectively. The survival rate was also similar in the two groups, with 5-year overall survival (OS) rates of 64.3 and 76.7%, respectively. However, when analyzing the treatment groups separately there was a trend in EBV-positive patients for a worse prognosis in patients treated with CHOP-like regimens that was not identified in patients treated with R-CHOP-like regimens. We conclude that EBV detection in the bone marrow and blood mononuclear cells of DLBC patients has the same frequency of EBV detection on tumoral lymphoma tissue but is not associated with the risk factors, response rate and survival in patients treated mainly with immunochemotherapy plus rituximab. These results also suggest that the addition of rituximab to chemotherapy improves the prognosis associated with EBV detection in DLBCL.

Microbial transformation of the sesquiterpene lactone tagitinin C by the fungus Aspergillus terreus

The biotransformation of the sesquiterpene lactone tagitinin C by the fungus Aspergillus terreus MT 5.3 yielded a rare derivative that was elucidated by spectrometric methods. The fungus led to the formation of a different product through an unusual epoxidation reaction between C4 and C5, formation of a C3,C10 ether bridge, and a methoxylation of the C1 of tagitinin C. The chemical structure of the product, namely 1 beta-methoxy-3 alpha-hydroxy-3,10 beta-4,5 alpha-diepoxy-8 beta-isobutyroyloxygermacr-11(13)-en-6 alpha,12-olide, is the same as that of a derivative that was recently isolated from the flowers of a Brazilian population of Mexican sunflower (Tithonia diversifolia), which is the source of the substrate tagitinin C. The in vitro cytotoxic activity of the substrate and the biotransformed product were evaluated in HL-60 cells using an MTT assay, and both compounds were found to be cytotoxic. We show that soil fungi may be useful in the biotransformation of sesquiterpene lactones, thereby leading to unusual changes in their chemical structures that may preserve or alter their biological activities, and may also mimic plant biosynthetic pathways for production of secondary metabolites.

Prevalence of the BRCA1 founder mutation c.5266dupin Brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome

About 5-10% of breast and ovarian carcinomas are hereditary and most of these result from germline mutations in the BRCA1 and BRCA2 genes. In women of Ashkenazi Jewish ascendance, up to 30% of breast and ovarian carcinomas may be attributable to mutations in these genes, where 3 founder mutations, c.68_69del (185delAG) and c.5266dup (5382insC) in BRCA1 and c.5946del (6174delT) in BRCA2, are commonly encountered. It has been suggested by some authors that screening for founder mutations should be undertaken in all Brazilian women with breast cancer. Thus, the goal of this study was to determine the prevalence of three founder mutations, commonly identified in Ashkenazi individuals in a sample of non-Ashkenazi cancer-affected Brazilian women with clearly defined risk factors for hereditary breast and ovarian cancer (HBOC) syndrome. Among 137 unrelated Brazilian women from HBOC families, the BRCA1c.5266dup mutation was identified in seven individuals (5%). This prevalence is similar to that encountered in non-Ashkenazi HBOC families in other populations. However, among patients with bilateral breast cancer, the frequency of c.5266dup was significantly higher when compared to patients with unilateral breast tumors (12.1% vs 1.2%, p = 0.023). The BRCA1 c.68_69del and BRCA2 c.5946del mutations did not occur in this sample. We conclude that screening non-Ashkenazi breast cancer-affected women from the ethnically heterogeneous Brazilian populations for the BRCA1 c.68_69del and BRCA2 c.5946del is not justified, and that screening for BRCA1c.5266dup should be considered in high risk patients, given its prevalence as a single mutation. In high-risk patients, a negative screening result should always be followed by comprehensive BRCA gene testing. The finding of a significantly higher frequency of BRCA1 c.5266dup in women with bilateral breast cancer, as well as existence of other as yet unidentified founder mutations in this population, should be further assessed in a larger well characterized high-risk cohort.