RESUMO
Clopidogrel and aspirin are the most commonly used medications worldwide for dual antiplatelet therapy after percutaneous coronary intervention. However, clopidogrel hyporesponsiveness related to gene polymorphisms is a concern. Populations with higher degrees of genetic admixture may have increased prevalence of clopidogrel hyporesponsiveness. To assess this, we genotyped CYP2C19, ABCB1, and PON1 in 187 patients who underwent percutaneous coronary intervention. Race was self-defined by patients. We also performed light transmission aggregometry with adenosine diphosphate (ADP) and arachidonic acid during dual antiplatelet therapy. We found a significant difference for presence of the CYP2C19*2 polymorphism between white and non-white patients. Although 7% of patients had platelet resistance to clopidogrel, this did not correlate with any of the tested genetic polymorphisms. We did not find platelet resistance to aspirin in this cohort. Multivariate analysis showed that patients with PON1 and CYP2C19 polymorphisms had higher light transmission after ADP aggregometry than patients with native alleles. There was no preponderance of any race in patients with higher light transmission aggregometry. In brief, PON1 and CYP2C19 polymorphisms were associated with lower clopidogrel responsiveness in this sample. Despite differences in CYP2C19 polymorphisms across white and non-white patients, genetic admixture by itself was not able to identify clopidogrel hyporesponsiveness.
Assuntos
Aspirina/farmacologia , Plaquetas/efeitos dos fármacos , Doença da Artéria Coronariana/tratamento farmacológico , Inibidores da Agregação Plaquetária/farmacologia , Ticlopidina/análogos & derivados , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Alelos , Arildialquilfosfatase/genética , Clopidogrel , Doença da Artéria Coronariana/genética , Citocromo P-450 CYP2C19/genética , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Polimorfismo Genético , Estudos Prospectivos , Ticlopidina/farmacologiaRESUMO
Forty Cryptococcus gattii strains were submitted to antifungal susceptibility testing with fluconazole, itraconazole, amphotericin B and terbinafine. The minimum inhibitory concentration (MIC) ranges were 0.5-64.0 for fluconazole, <0.015-0.25 for itraconazole, 0.015-0.5 for amphotericin B and 0.062-2.0 for terbinafine. A bioassay for the quantitation of fluconazole in murine brain tissue was developed. Swiss mice received daily injections of the antifungal, and their brains were withdrawn at different times over the 14-day study period. The drug concentrations varied from 12.98 to 44.60 µg/mL. This assay was used to evaluate the therapy with fluconazole in a model of infection caused by C. gattii. Swiss mice were infected intracranially and treated with fluconazole for 7, 10 or 14 days. The treatment reduced the fungal burden, but an increase in fungal growth was observed on day 14. The MIC for fluconazole against sequential isolates was 16 µg/mL, except for the isolates obtained from animals treated for 14 days (MIC = 64 µg/mL). The quantitation of cytokines revealed a predominance of IFN-γ and IL-12 in the non-treated group and elevation of IL-4 and IL-10 in the treated group. Our data revealed the possibility of acquired resistance during the antifungal drug therapy.
Assuntos
Antifúngicos/farmacologia , Encéfalo/microbiologia , Infecções Fúngicas do Sistema Nervoso Central/tratamento farmacológico , Criptococose/tratamento farmacológico , Cryptococcus gattii/efeitos dos fármacos , Fluconazol/farmacologia , Animais , Antifúngicos/uso terapêutico , Infecções Fúngicas do Sistema Nervoso Central/microbiologia , Criptococose/microbiologia , Modelos Animais de Doenças , Farmacorresistência Fúngica , Fluconazol/uso terapêutico , Humanos , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Resultado do TratamentoRESUMO
The fate of organochlorine 14C-dicofol in activated sludge process was investigated. Results showed that the major part of radioactivity remained adsorbed on biological sludge. Consequently, its final disposal deserves special attention. The small amounts of dicofol, biotransformed or not, which remained in the treated effluent could contaminate receiving bodies.
Glicoproteínas, glicoesfingolipídios e polissacarídios, expostos nas camadas mais externas da parede celular dos fungos, estão envolvidos em diferentes tipos de interações com o ambiente extracelular. Essas moléculas são componentes essenciais desses organismos, contribuindo para a estrutura, integridade, crescimento celular, diferenciação e sinalização. Alguns são compostos imunologicamente ativos com potencial para regular a patogênese e a resposta imune do hospedeiro, Algumas dessas estruturas podem ser especificamente reconhecidas por anticorpos presentes no soro de pacientes, sugerindo uma possível utilização como ferramenta no diagnóstico das infecções fúngicas.
Assuntos
Humanos , Diferenciação Celular , Crescimento Celular , Parede Celular , Fungos , Glicoconjugados , Imunidade nas Mucosas , Técnicas In Vitro , Micoses , Polissacarídeos , Métodos , Pacientes , Técnicas e Procedimentos DiagnósticosRESUMO
Isolated from the mycelium of Scedosporium prolificans were complex glycoproteins (RMP-Sp), with three structurally related components (HPSEC). RMP-Sp contained 35% protein and 62% carbohydrate with Rha, Ara, Man, Gal, Glc, and GlcNH(2) in a 18:1:24:8:6:5 molar ratio. Methylation analysis showed mainly nonreducing end- of Galp (13%), nonreducing end- (9%), 2-O- (13%), and 3-O-subst. Rhap (7%), nonreducing end- (11%), 2-O- (10%), 3-O- (14%), and 2,6-di-O-subst. Manp units (13%). Mild reductive beta-elimination of RMP-Sp gave alpha-l-Rhap-(1-->2)-alpha-l-Rhap-(1-->3)-alpha-l-Rhap-(1-->3)-alpha-d-Manp-(1-->2)-d-Man-ol, with Man-ol substituted at O-6 with beta-d-Galp units, a related pentasaccharide lacking beta-d-Galp units, and beta-d-Galp-(1-->6)-[alpha-d-Manp-(1-->2)]-d-Man-ol in a 16:3:1w/w ratio. Traces of Man-ol and Rha-ol were detected. ESI-MS showed HexHex-ol and Hex(3-6)Hex-ol components. Three rhamnosyl units were peeled off successively from the penta- and hexasaccharide by ESI-MS-MS. The carbohydrate epitopes of RMP-Sp differ from those of the glycoprotein of Pseudallescheria boydii, a related opportunistic pathogen.
Assuntos
Epitopos/química , Epitopos/imunologia , Glicoproteínas/química , Glicoproteínas/imunologia , Scedosporium/imunologia , Scedosporium/patogenicidade , Sequência de Carboidratos , Espectroscopia de Ressonância Magnética , Oligossacarídeos/química , Scedosporium/química , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Glycoproteins, glycosphingolipids and polysaccharides exposed at the most external layers of the wall are involved in several types of interactions of fungal cells with the exocellular environment. These molecules are fundamental building blocks of organisms, contributing to the structure, integrity, cell growth, differentiation and signaling. Several of them are immunologically active compounds with potential as regulators of pathogenesis and the immune response of the host. Some of these structures can be specifically recognized by antibodies from patients' sera, suggesting that they can be also useful in the diagnosis of fungal infections.
RESUMO
The fate of organochlorine 14C-dicofol in activated sludge process was investigated. Results showed that the major part of radioactivity remained adsorbed on biological sludge. Consequently, its final disposal deserves special attention. The small amounts of dicofol, biotransformed or not, which remained in the treated effluent could contaminate receiving bodies.
Glicoproteínas, glicoesfingolipídios e polissacarídios, expostos nas camadas mais externas da parede celular dos fungos, estão envolvidos em diferentes tipos de interações com o ambiente extracelular. Essas moléculas são componentes essenciais desses organismos, contribuindo para a estrutura, integridade, crescimento celular, diferenciação e sinalização. Alguns são compostos imunologicamente ativos com potencial para regular a patogênese e a resposta imune do hospedeiro, Algumas dessas estruturas podem ser especificamente reconhecidas por anticorpos presentes no soro de pacientes, sugerindo uma possível utilização como ferramenta no diagnóstico das infecções fúngicas.
RESUMO
The purpose of this investigation was to evaluate the rose Bengal plate test (RBPT) for brucellosis serodiagnosis in a Brucella abortus infected buffalo (Bubalus bubalis) herd, comparing the results with those obtained by the mercaptoethanol (MET) and the complement fixation tests (CFT). Serum samples from 90 three-to-five-years-old cows were collected. Animals were unvaccinated against brucellosis. Every serum was tested by the three serological tests, and the results were compared by kappa (k) and the MacNemar chi-square, adopting as cutt-off the titre 25 for the MET and the titre 4 for the CFT. A good agreement was observed among the tests (RBPT versus CFT, k = 0.82; RBPT versus MET, k =0.92; MET versus CFT, k = 0.86), and the chi-square did not show significant difference. The relative sensitivity of the RBPT, when compared with the combination of the results of MET and CFT, was 93.03%, with a confidence interval (95%) ranging from 87.57% to 98.47%. Out of 43 animals considered infected by the combination of the results of the two other tests, three tested negative by the RBPT, suggesting the possibility of occurrence of false-negative results. KEY-WORDS: Brucellosis. Bubalus bubalis. Serodiagnosis. Rose Bengal plate test. Complement fixation test. Mercaptoethanol test.
O trabalho teve por objetivo avaliar a prova do antígeno acidificado tamponado (AAT) para diagnóstico da brucelose em um rebanho bubalino (Bubalus bubalis) do qual foi isolada Brucella abortus, comparando seus resultados com aqueles obtidos na prova do 2-mercaptoetanol (2-ME) e na reação de fixação de complemento (RFC). Foram colhidas amostras de sangue de 90 fêmeas adultas com idade entre três e cinco anos e não vacinadas contra brucelose. Todos os soros foram submetidos às três provas sorológicas, e os resultados foram comparados por meio do indicador kappa e do teste de X2 de MacNemar, adotando-se como ponto de corte o título 25 na 2-ME e o título 4 na RFC. Os três testes apresentaram boa concordância entre si (AAT x RFC, k = 0,82; AAT x 2-ME, k = 0,92; 2-ME x RFC, k = 0,86), e o teste de X2 não apontou diferença significativa entre eles. A sensibilidade relativa da AAT, em comparação com a combinação dos resultados da 2-ME e da RFC, foi de 93,03%, com um intervalo de confiança(95%) de 87,57% a 98,47%. Três animais, de um total de 43 classificados como infectados pela combinação dos resultados do outros dois testes, apresentaram resultado negativo na AAT, indicando a possibilidade de ocorrência de resultado falso-negativo nesse teste.PALAVRAS-CHAVE: Brucelose. Bubalus bubalis. Diagnóstico sorológico. Prova do antígeno acidificado tamponado. Reação de fixação de complemento.
RESUMO
A molecular phylogeographic study of Paragonimus mexicanus collected from Guatemala and Ecuador was performed. Genomic DNA was extracted from individual metacercariae, and two gene regions (partial mitochondrial cytochrome c oxidase subunit 1 (CO1) and the second internal transcribed spacer of the nuclear ribosomal gene repeat (ITS2)) were amplified by the polymerase chain reaction (PCR). Sequences segregated in a phylogenetic tree according to their geographic origins. ITS2 sequences from Ecuador and Guatemala differed at only one site. Pairwise distances among CO1 sequences within a country were always lower than between countries. Nevertheless, genetic distances between countries were less than between geographical forms of P. westermani that have been suggested to be distinct species. This result suggests that populations from Guatemala and Ecuador are genetically differentiated perhaps at the level of subspecies.
Assuntos
DNA de Helmintos/análise , Paragonimus/genética , Animais , Sequência de Bases , Equador , Guatemala , Haplótipos , Larva , Dados de Sequência Molecular , Filogenia , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
Mediante esta pesquisa, estudamos a ramificaçäo e a distribuiçäo das artérias pulmonares em 20 fetos de bovinos azebuados (13 machos e 7 fêmeas), com idades variando entre 6 e 9 meses. As peças foram fixadas em soluçäo aquosa de formol a 10 por cento, e o método de dissecaçäo da abertura da cavidade torácica desses animais, com vistas à individualizaçäo dos vasos arteriais e brônquios. Da artéria pulmonar direita observou-se que, mais comumente, 15 vezes (75 por cento), parte como primeiro colateral o ramo ascendente, seguido do ramo descendente que acompanham os dois brônquios segmentares do brônquio traqueal, os quais irrigam, respectivamente, a porçäo cranial e caudal do lobo cranial do pulmäo. Logo após este arranjo, surgem o ramo lobar acessório e em seguida o ramo lobar médio. O ramo lobar acessório pode emergir duas vezes (10 por cento) depois do ramo lobar médio ou na mesma altura dele, cinco vezes (25 por cento). Uma única vez (5 por cento) aparecem dois ramos lobares médios. Em cinco preparaçöes (25 por cento), os dois primeiros ramos da artéria pulmonar direita säo vistos a nascer em tronco comum, o ramo lobar cranial. Da artéria pulmonar esquerda nascem mais freqüentemente 18 vezes (90 por cento) como 1º e 2º colaterais os ramos ascendente e descendente, e respectivamente duas vezes (10 por cento) estes ramos provêm de um único colateral, o ramo lobar cranial. Em cada lobo caudal (direito e esquerdo), penetra um ramo lobar caudal (direito e esquerdo) que emite número bastente variado do ramos arteriais (6 a 14) do lado direito e (7 a 16) do lado esquerdo