Atividade enzimática e hemolítica de Candida dubliniensis

Candida dubliniensis is an opportunistic yeast that has been recovered from several body sites in many populations; it is most often recovered from the oral cavities of human immunodeficiency virus-infected patients. Although extensive studies on epidemiology and phylogeny of C. dubliniensis have been performed, little is known about virulence factors such as exoenzymatic and hemolytic activities. In this study we compared proteinase, hyaluronidase, chondroitin sulphatase and hemolytic activities in 18 C. dubliniensis and 30 C. albicans strains isolated from AIDS patients. C. albicans isolates produced higher amounts of proteinase than C. dubliniensis (p ; 0.05). Hemolytic activity was affected by CaCl2; when this component was absent, we did not notice any significant difference between C. albicans and C. dubliniensis hemolytic activities. On the contrary, when we added 2.5 g% CaCl2, the hemolytic activity was reduced on C. dubliniensis and stimulated on C. albicans tested strains (p ; 0,05). Constatou-se que a atividade hemolítica foi influenciada pelo CaCl2; em sua ausência não foram observadas diferenças na atividade hemolítica das duas espécies; todavia, ao se agregar 2,5% de CaCl2, a atividade hemolítica de C. dubliniensis foi reduzida enquanto a de C. albicans, estimulada (p < 0,05)

ESTUDO EPIDEMIOLÓGICO E PERFIL DA SUSCETIBILIDADE DE AMOSTRAS DE CANDIDA ISOLADAS DE MULHERES COM CANDIDIASE VULVOVAGINAL EM FREDERICO WESTPHALEN – RS

As infecções causadas por Candida são micoses oportunistas reconhecidas desde o século V a.C.O gênero Candida é caracterizado como fungo leveduriforme, saprófita e oportunista, que sob determinadas condições multiplica-se, tornando-se patogênico. Células de Candida são encontradas navagina em 20% de mulheres sadias e assintomáticas. A candidíase vaginal ocorre, principalmente,nas mulheres que estão entre a puberdade e a menopausa, sugerindo dependência hormonal nainfecção. No período de agosto de 2004 a junho de 2005 foram realizadas coletas de amostras desecreções vaginais de mulheres com sintomatologia de infecção vulvovaginal atendidas em trêsestabelecimentos de saúde de Frederico Westphalen – RS. As amostras positivas foram identificadase a sensibilidade frente os antifúngicos fluconazol e anfotericina B foi avaliada. Os resultados obtidos demonstram que Candida spp. ocupou o quarto lugar dentre todas as espécies isoladas causando infecções vulvovaginais, sendo que a identificação apontou Candida albicans como espéciemais prevalentemente isolada. Os testes de suscetibilidade revelaram que Candida glabrata foimais sensível do que Candida albicans e Candida tropicalis a anfotericina B. Frente ao fluconazolCandida albicans e Candida tropicalis foram consideradas sensíveis. De acordo com as normas doNCCLS os isolados foram considerados sensíveis a anfotericina B e fluconazol

NÍVEIS BASAIS DE ACETILCOLINESTERASE E BUTIRILCOLINESTERASE EM AGRICULTORES DA REGIÃO DE FREDERICO WESTPHALEN – RS

A elevada utilização de agrotóxicos, sem os devidos cuidados, tem contribuído em muito para oaumento das intoxicações ocupacionais, sendo hoje, um dos principais problemas de saúde pública no meio rural brasileiro. Entre os pesticidas mais utilizados estão os compostos pertencentes acategoria dos organofosforados que são inibidores da acetilcolinesterase e butirilcolinesterase comvariado grau de toxicidade em seres humanos. Intoxicações por esses compostos podem acarretardiversas alterações sendo a principal e de maior risco ao homem a alteração neuropsicológica. Osdados referentes a utilização de compostos dessa categoria ainda são uma realidade extra-oficial;todavia, motivaram a realização deste estudo. Neste contexto, o objetivo deste trabalho foi avaliar aexposição dos agricultores da área rural de Frederico Westphalen – RS a agrotóxicos inibidores dascolinesterases, valendo-se de dados não oficiais quanto ao uso indiscriminado de organofosforadosnessa região. As atividades enzimáticas foram avaliadas segundo método de Ellman (1961) modificado. Após a determinação individual das atividades da butirilcolinesterase plasmáticas eacetilcolinesterase eritrocitária de 60 agricultores, verificou-se que 15 (25%) agricultores apresentaram valores de butirilcolinesterase abaixo dos valores de referência obtidos para o grupo controle, aopasso que, todos os agricultores apresentaram valores de acetilcolinesterase inferiores aos valoresde referência. Estes resultados são indicadores seguros de uma exposição e/ou intoxicação porpesticidas inibidores de colinesterases

Instantaneous Wave-Free Ratio for the Assessment of Intermediate Left Main Coronary Artery Stenosis: Correlations With Fractional Flow Reserve/Intravascular Ultrasound and Prognostic Implications: The iLITRO-EPIC07 Study

Background: There is little information available on agreement between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) in left main coronary artery (LMCA) intermediate stenosis. Besides, several meta-analyses support the use of FFR to guide LMCA revascularization, but limited information is available on iFR in this setting. Our aims were to establish the concordance between FFR and iFR in intermediate LMCA lesions, to evaluate with intravascular ultrasound (IVUS) in cases of FFR/iFR discordance, and to prospectively validate the safety of deferring revascularization based on a hybrid decision-making strategy combining iFR and IVUS. Methods: Prospective, observational, multicenter registry with 300 consecutive patients with intermediate LMCA stenosis who underwent FFR and iFR and, in case of discordance, IVUS and minimal lumen area measurements. Primary clinical end point was a composite of cardiovascular death, LMCA lesion-related nonfatal myocardial infarction, or unplanned LMCA revascularization. Results: FFR and iFR had an agreement of 80% (both positive in 67 and both negative in 167 patients); in case of disagreement (31 FFR+/iFR- and 29 FFR-/iFR+) minimal lumen area was & GE;6 mm(2) in 8.7% of patients with FFR+ and 14.6% with iFR+. Among the 300 patients, 105 (35%) underwent revascularization and 181 (60%) were deferred according to iFR and IVUS. At a median follow-up of 20 months, major adverse cardiac events incidence was 8.3% in the defer group and 13.3% in the revascularization group (hazard ratio, 0.71 [95% CI 0.30-1.72]; P=0.45). Conclusions: In patients with intermediate LMCA stenosis, a physiology-guided treatment decision is feasible either with FFR or iFR with moderate concordance between both indices. In case of disagreement, the use of IVUS may be useful to indicate revascularization. Deferral of revascularization based on iFR appears to be safe in terms of major adverse cardiac events

Rationale and design of the Concordance study between FFR and iFR for the assessment of lesions in the left main coronary artery. The ILITRO-EPIC-07 Trial

Introduction and objectives: Patients with left main coronary artery (LMCA) stenosis have been excluded from the trials that support the non-inferiority of the instantaneous wave-free ratio (iFR) compared to the fractional flow reserve (FFR) in the decision-making process of coronary revascularization. This study proposes to prospectively assess the concordance between the two indices in LMCA lesions and to validate the iFR cut-off value of 0.89 for clinical use. Methods: National, prospective, and observational multicenter registry of 300 consecutive patients with intermediate lesions in the LMCA (angiographic stenosis, 25% to 60%. A pressure gudiewire study and determination of the RFF and the iFR will be performed: in the event of a negative concordant result (FFR > 0.80/iFR > 0.89), no treatment will be performed; in case of a positive concordant result (FFR 0.80/iFR 0.89), an intravascular echocardiography will be performed and revascularization will be delayed if the minimum lumen area is > 6 mm(2). The primary clinical endpoint will be a composite of cardiovascular death, LMCA lesion-related non-fatal infarction or need for revascularization of the LMCA lesion at 12 months. Conclusions: Confirm that an iFR-guided decision-making process in patients with intermediate LMCA stenosis is clinically safe and would have a significant clinical impact. Also, justify its systematic use when prescribing treatment in these potentially high-risk patients

Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature

Primary Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population

Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals