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1.
Clin Chim Acta ; 484: 87-90, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29802830

RESUMO

Platelets have various functions and participate in primary hemostasis, inflammation, and immune responses. Human platelet antigens (HPAs) are alloantigens expressed on the platelet membrane. Each HPA represent one of six platelet glycoproteins GPIIb, GPIIIa, GPIa, GPIbα, GPIbß, and CD109, and six biallelic systems are grouped. A single nucleotide polymorphism (SNP) in the gene sequence causes a single amino acid substitution of relevant platelet glycoprotein with the exception of HPA-14bw. High-throughput next-generation sequencing-based method has been developed, which enable accurately identification of HPA polymorphisms. The roles of HPA in disease were reviewed. HPAs mediate platelet-microorganism and platelet-malignant cell interactions, and they also participate in pathogenesis of hemorrhagic fever with renal syndrome and infective endocarditis. The exploration of HPA polymorphisms in association with disease susceptibility of individuals will benefit prevention or management of disease.


Assuntos
Antígenos de Plaquetas Humanas/genética , Endocardite/genética , Febre Hemorrágica com Síndrome Renal/genética , Substituição de Aminoácidos/genética , Humanos , Glicoproteínas da Membrana de Plaquetas/genética , Polimorfismo de Nucleotídeo Único/genética
2.
Biomed Res Int ; 2016: 7923874, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27110570

RESUMO

Infective endocarditis (IE) is a life-threatening disease that is associated with high morbidity and mortality. Its long-term prognosis strongly depends on a timely and optimized antibiotic treatment. Therefore, identification of the causative pathogen is crucial and currently based on blood cultures followed by characterization and susceptibility testing of the isolate. However, antibiotic treatment starting prior to blood sampling or IE caused by fastidious or intracellular microorganisms may cause negative culture results. Here we investigate the additional diagnostic value of broad-range PCR in combination with direct sequencing on resected heart tissue or swabs in patients with tissue or swab culture-negative IE in a routine clinical setting. Sensitivity, specificity, and positive and negative predictive values of broad-range PCR from diagnostic material in our patients were 33.3%, 76.9%, 90.9%, and 14.3%, respectively. We identified a total of 20 patients (21.5%) with tissue or culture-negative IE who profited by the additional application of broad-range PCR. We conclude that broad-range PCR on resected heart tissue or swabs is an important complementary diagnostic approach. It should be seen as an indispensable new tool for both the therapeutic and diagnostic management of culture-negative IE and we thus propose its possible inclusion in Duke's diagnostic classification scheme.


Assuntos
DNA Ribossômico/genética , Endocardite/tratamento farmacológico , Endocardite/genética , RNA Ribossômico 16S/genética , Idoso , Antibacterianos/uso terapêutico , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/patogenicidade , Hemocultura , DNA Ribossômico/isolamento & purificação , Endocardite/microbiologia , Endocardite/cirurgia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miocárdio/patologia , RNA Ribossômico 16S/isolamento & purificação , Cirurgia Torácica
3.
Klin Med (Mosk) ; 94(8): 596-601, 2016.
Artigo em Russo | MEDLINE | ID: mdl-30289676

RESUMO

Infectioue endocarditis (IE) is frequently associated with the use of narcotic drugs, glucocorticosteroids, and cytostatics that are metabolized in the body by enzymes of the xenobiotic detoxification system (XDS). This work was aimed at elucidating association between IE and mononucleotide polymorphisms of genes encoding XDS enzymes. 46 IE patients and 114 subjects without cardiovascular diseases (controls) underwent genotyping for polymorphic loci of cytochrome P450 1A1 gene I462V (CYP1A1), I105VandA114V gene of glutathione-S-transferase Pi1 (GSTP1) using allele-specific PCR. The study revealed association of CYP1A1 I462VandGSTP1 I105V with IE while IE proved unrelated to GSTP1 A114V polymorphism. Combination of homozygous variant I462I of the CYP1A1 gene and heterozygous variant I105V/ of the GSTP1 gene was associated with the 9-fold increase of the risk of IE in the subjects practicing intravenous druginjections or having congenital and acquired heart failure or implanted valve prostheses. These findings suggest the necessity of further studies on the role of XDS in pathogenesis of IE and other infectious diseases.


Assuntos
Citocromo P-450 CYP1A1/genética , Endocardite , Glutationa S-Transferase pi/genética , Adulto , Idoso , Endocardite/etiologia , Endocardite/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético
4.
Arch. Soc. Esp. Oftalmol ; 90(11): 546-548, nov. 2015. ilus
Artigo em Espanhol | IBECS | ID: ibc-145388

RESUMO

Caso clínico: Paciente con amaurosis brusca debido a oclusión de arteria central de la retina (OACR), en el que se objetivó insuficiencia mitral y hemocultivos positivos para Streptococcus viridans. Con el estudio de ecografía transesofágica, se diagnosticó de endocarditis infecciosa subaguda sobre válvula nativa mitral que cursó sin fiebre y con la pérdida de visión como único síntoma. Discusión: La OACR debida a endocarditis infecciosa es muy infrecuente, y hay escasos casos reportados en la literatura médica. La semiología y el estudio sistemático y exhaustivo de los pacientes con esta OACR, ayuda a descubrir enfermedades graves subyacentes. La endocarditis infecciosa tiene formas muy diversas de presentación y con frecuencia se requiere una alta sospecha clínica para llegar a su diagnóstico (AU)


Clinical case: A patient with acute amaurosis due central retinal artery occlusion (CRAO), who had mitral regurgitation and Streptococcus viridans positive blood cultures. Using transesophageal ultrasound, the patient was diagnosed with native valve infective endocarditis without fever, and with loss of vision as the only symptom. Discussion: CRAO due to infective endocarditis is rare and there are few cases reported in the literature. Semiology and a systematic and comprehensive study of patients with this ophthalmological pathology helps uncover serious underlying medical conditions. Infective endocarditis has many different forms of presentation and a high clinical suspicion is often required to reach a diagnosis (AU)


Assuntos
Adulto , Humanos , Masculino , Artéria Retiniana/anormalidades , Artéria Retiniana/metabolismo , Endocardite/genética , Endocardite/metabolismo , Cegueira/metabolismo , Insuficiência da Valva Mitral/congênito , Preparações Farmacêuticas/administração & dosagem , Sopros Sistólicos/genética , Artéria Retiniana/citologia , Artéria Retiniana/lesões , Endocardite/fisiopatologia , Endocardite/reabilitação , Cegueira/patologia , Insuficiência da Valva Mitral/genética , Preparações Farmacêuticas , Sopros Sistólicos/metabolismo
5.
Intern Emerg Med ; 10(5): 587-94, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25711313

RESUMO

The pathogenesis of infective endocarditis (IE) involves activation of the haemostasis system at the site of endocardial defects. Whether prothrombotic conditions are associated with IE by enhancing early vegetation formation is unknown. In this study, we assess the prevalence and clinical significance of two major conditions associated with thrombophilia in patients with IE. Mutations G20210A of the prothrombin (PTH) gene and G1691A of factor V (FV Leiden) gene were studied by means of allele-specific polymerase chain reaction in 203 IE patients, 175 valvular heart disease (VHD) patients and 200 blood donors (BD). IE patients show higher cumulative frequencies of mutated alleles of PTH and FV Leiden [6.4 vs 3.25 %; OR 2.03 (95 % CI 0.97-3.66); p = 0.047] compared to BD, but not VHD. Device-related IE is enriched with FV Leiden, and prosthetic valve IE with PTH mutations (allele frequency 8.3 vs 2.2 % in native valve IE; p = 0.021). Vegetation size and embolic complications are not influenced by the examined thrombophilias. A trend for a higher mortality was observed in IE patients with any of the two thrombophilias studied. Our data do not support a role for factor V Leiden and G20210A prothrombin gene mutations in the susceptibility to IE. Whether any of these genetic polymorphisms play a role in a specific subtype of IE needs to be re-examined in larger studies.


Assuntos
Endocardite/complicações , Endocardite/genética , Fator V/genética , Mutação/genética , Protrombina/genética , Trombofilia/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Trombofilia/genética , Adulto Jovem
6.
Cytokine ; 71(1): 16-21, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25213166

RESUMO

Infective endocarditis (IE) is an inflammatory condition of the lining of the heart chambers and valves, which is generally caused by bacteria. Toll-like receptors (TLRs) and Triggering receptor expressed on myeloid cells (TREMs) are key effectors of the innate system that play a significant role in the recognition of infectious agents, particularly, bacteria. We hypothesised that inherited variation in TLR and TREM-1 genes may affect individual susceptibility to IE. The distribution of genotypes and alleles of the TLR1 (rs5743551, rs5743611), TLR2 (rs3804099, rs5743708), TLR4 (rs4986790, rs4986791), TLR6 (rs3775073, rs5743810), and TREM-1 (rs1817537, rs3804277, rs6910730, rs7768162, rs2234246, rs4711668, rs9471535, rs2234237) gene polymorphisms was investigated in 110 Caucasian (Russian) subjects with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors. Odds ratios with 95% confidence intervals were calculated. We found that C/C genotype of the rs3775073 polymorphism within TLR6 gene was associated with a decreased risk of IE (OR=0.51, 95% CI=0.26-0.97, P=0.032) according to the recessive model; however, we observed no association between the other investigated SNPs within TLR and TREM-1 genes and IE. Further in-depth investigations in this field are necessary to shed the light on the impact of inherited variation within innate immune response genes on the development of IE.


Assuntos
Endocardite/genética , Predisposição Genética para Doença , Glicoproteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Receptores Imunológicos/genética , Receptor 6 Toll-Like/genética , Receptores Toll-Like/genética , Alelos , Endocardite/imunologia , Endocardite/mortalidade , Feminino , Estudos de Associação Genética/estatística & dados numéricos , Genótipo , Voluntários Saudáveis , Humanos , Imunidade Inata/genética , Masculino , Pessoa de Meia-Idade , Razão de Chances , Receptor Gatilho 1 Expresso em Células Mieloides
7.
PLoS One ; 9(10): e110151, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25299518

RESUMO

AIMS: Inflammation in infective endocarditis (IE) is a complex network including interactions of inflammatory cytokines and other components of host response. Certainly, any variation in this network could influence susceptibility or disease progression of IE. In this study, 14 single nucleotide variants (SNVs) in genes coding for interleukin-1ß, interleukin-6, interleukin-10, toll-like receptor-4, tumor necrosis factor-α, selectin E and intercellular adhesion molecule-1 were analyzed for an association with susceptibility to IE and correlated with disease-related laboratory parameters. Furthermore, the occurrence of SNVs was examined to elucidate pathogen-dependent associations. METHODS AND RESULTS: The distribution of SNVs was determined in IE-patients and healthy blood donors by RFLP analysis. White blood cells (WBC) were counted using flow cytometry, concentration of C-reactive protein and procalcitonin was measured immunologically. Interleukin-6 c.471+870G>A genotypes differed significantly between IE patients and controls. The frequency of the heterozygote genotype GA was considerably higher in the patient group (68.9% vs. 43.8%, Pc<0.0003). Interleukin-6 c.-237 minor allele frequency was increased in patients, although not statistically significant. Additionally, we detected a potential relation between interleukin-1ß c.315C>T and IE. Pathogen-dependent analysis showed no significantly associated subgroup in relation to IE susceptibility, but gave hints towards alterations regarding Enterococcus-caused IE cases. Patients with genotype selectin-E c.-19 GT tend to have higher preoperative WBC counts than patients with genotype GG. We further showed an association between two interleukin-1ß SNVs and laboratory biomarkers. CONCLUSION: This study shows genetic predispositions for the establishment of IE. Furthermore, correlation of SNVs with disease-related biomarkers suggests a role of genetic variants regarding the inflammatory response in IE.


Assuntos
Biomarcadores/sangue , Endocardite/genética , Estudos de Associação Genética , Genótipo , Inflamação/genética , Adolescente , Adulto , Idoso , Calcitonina/sangue , Calcitonina/genética , Peptídeo Relacionado com Gene de Calcitonina , Selectina E/sangue , Selectina E/genética , Endocardite/sangue , Endocardite/patologia , Enterococcus/patogenicidade , Feminino , Frequência do Gene , Humanos , Inflamação/sangue , Inflamação/patologia , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão Intercelular/genética , Interleucina-1beta/sangue , Interleucina-1beta/genética , Interleucina-6/sangue , Interleucina-6/genética , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Precursores de Proteínas/sangue , Precursores de Proteínas/genética , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética
9.
PLoS One ; 8(9): e73205, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24086273

RESUMO

Tax1-binding protein 1 (Tax1bp1) negatively regulates NF-κB by editing the ubiquitylation of target molecules by its catalytic partner A20. Genetically engineered TAX1BP1-deficient (KO) mice develop age-dependent inflammatory constitutions in multiple organs manifested as valvulitis or dermatitis and succumb to premature death. Laser capture dissection and gene expression microarray analysis on the mitral valves of TAX1BP1-KO mice (8 and 16 week old) revealed 588 gene transcription alterations from the wild type. SAA3 (serum amyloid A3), CHI3L1, HP, IL1B and SPP1/OPN were induced 1,180-, 361-, 187-, 122- and 101-fold respectively. WIF1 (Wnt inhibitory factor 1) exhibited 11-fold reduction. Intense Saa3 staining and significant I-κBα reduction were reconfirmed and massive infiltration of inflammatory lymphocytes and edema formation were seen in the area. Antibiotics-induced 'germ free' status or the additional MyD88 deficiency significantly ameliorated TAX1BP1-KO mice's inflammatory lesions. These pathological conditions, as we named 'pseudo-infective endocarditis' were boosted by the commensal microbiota who are usually harmless by their nature. This experimental outcome raises a novel mechanistic linkage between endothelial inflammation caused by the ubiquitin remodeling immune regulators and fatal cardiac dysfunction.


Assuntos
Endocardite/microbiologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Microbiota , Proteínas de Neoplasias/genética , Animais , Antibacterianos/uso terapêutico , Sequência de Bases , Doença Crônica , Primers do DNA , Endocardite/tratamento farmacológico , Endocardite/genética , Ensaio de Imunoadsorção Enzimática , Perfilação da Expressão Gênica , Camundongos , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/genética , Reação em Cadeia da Polimerase em Tempo Real
10.
Clin Exp Immunol ; 173(3): 419-29, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23663103

RESUMO

Rheumatic heart disease (RHD) is characterized by the presence of anti-streptococcal group A antibodies and anti-endothelial cell antibodies (AECA). Molecular mimicry between streptococcal antigens and self proteins is a hallmark of the pathogenesis of rheumatic fever. We aimed to identify, in RHD patients, autoantibodies specific to endothelial autoantigens cross-reactive with streptococcal proteins and to evaluate their role in inducing endothelial damage. We used an immunoproteomic approach with endothelial cell-surface membrane proteins in order to identify autoantigens recognized by AECA of 140 RHD patients. Cross-reactivity of purified antibodies with streptococcal proteins was analysed. Homologous peptides recognized by serum cross-reactive antibodies were found through comparing the amino acid sequence of streptococcal antigens with human antigens. To investigate interleukin (IL)-1R-associated kinase (IRAK1) and nuclear factor-κB (NF-κB) activation, we performed a Western blot analysis of whole extracts proteins from unstimulated or stimulated human microvascular cardiac endothelial cells (HMVEC-C). Adhesion molecule expression and release of proinflammatory cytokines and growth factors were studied by multiplex bead based immunoassay kits. We observed anti-vimentin antibodies in sera from 49% RHD AECA-positive patients. Cross-reactivity of purified anti-vimentin antibodies with heat shock protein (HSP)70 and streptopain streptococcal proteins was shown. Comparing the amino acid sequence of streptococcal HSP70 and streptopain with human vimentin, we found two homologous peptides recognized by serum cross-reactive antibodies. These antibodies were able to stimulate HMVEC-C inducing IRAK and NF-κB activation, adhesion molecule expression and release of proinflammatory cytokines and growth factors. In conclusion, streptococcal-vimentin cross-reactive antibodies were able to activate microvascular cardiac endothelium by amplifying the inflammatory response in RHD.


Assuntos
Anticorpos/imunologia , Reações Cruzadas/imunologia , Endocardite/imunologia , Cardiopatia Reumática/imunologia , Vasculite Reumatoide/imunologia , Streptococcus/imunologia , Vimentina/imunologia , Adolescente , Adulto , Sequência de Aminoácidos , Animais , Anticorpos/sangue , Autoanticorpos/sangue , Autoanticorpos/imunologia , Autoantígenos/imunologia , Proteínas de Bactérias/química , Proteínas de Bactérias/imunologia , Criança , Endocardite/genética , Endotélio/imunologia , Endotélio/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Coelhos , Cardiopatia Reumática/genética , Vasculite Reumatoide/genética , Vimentina/química , Vimentina/genética , Adulto Jovem
11.
PLoS One ; 7(2): e31490, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22319637

RESUMO

BACKGROUND: The diagnostic and prognostic assessments of infective endocarditis (IE) are challenging. To investigate the host response during IE and to identify potential biomarkers, we determined the circulating gene expression profile using whole genome microarray analysis. METHODS AND RESULTS: A transcriptomic case-control study was performed on blood samples from patients with native valve IE (n = 39), excluded IE after an initial suspicion (n = 10) at patient's admission, and age-matched healthy controls (n = 10). Whole genome microarray analysis showed that patients with IE exhibited a specific transcriptional program with a predominance of gene categories associated with cell activation as well as innate immune and inflammatory responses. Quantitative real-time RT-PCR performed on a selection of highly modulated genes showed that the expression of the gene encoding S100 calcium binding protein A11 (S100A11) was significantly increased in patients with IE in comparison with controls (P<0.001) and patients with excluded IE (P<0.05). Interestingly, the upregulated expression of the S100A11 gene was more pronounced in staphylococcal IE than in streptococcal IE (P<0.01). These results were confirmed by serum concentrations of the S100A11 protein. Finally, we showed that in patients with IE, the upregulation of the aquaporin-9 gene (AQP9) was significantly associated with the occurrence of acute heart failure (P = 0.02). CONCLUSIONS: Using transcriptional signatures of blood samples, we identified S100A11 as a potential diagnostic marker of IE, and AQP9 as a potential prognostic factor.


Assuntos
Aquaporinas/genética , Proteínas Sanguíneas/genética , Endocardite/diagnóstico , Perfilação da Expressão Gênica , Proteínas S100/genética , Biomarcadores , Estudos de Casos e Controles , Endocardite/complicações , Endocardite/genética , Perfilação da Expressão Gênica/métodos , Insuficiência Cardíaca , Humanos , Regulação para Cima/genética
12.
Univ. odontol ; 30(64): 57-66, ene.-jun. 2011. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-667733

RESUMO

Las cardiopatías congénitas se definen como lesiones anatómicas del corazón y sus componentes que se presentan en el nacimiento y representan un problema de salud pública de primer orden. Los pacientes afectados presentan sintomatología muy diversa y requieren un manejo estomatológico adecuado y de calidad que les permita mantener su salud bucal sin poner en riesgo su salud general. Existe muy poca literatura sobre el manejoestomatológico del paciente pediátrico con cardiopatía congénita, por lo que se realizó una búsqueda sistematizada sobre el tema en las principales bases de datos científicas, así como en revistas especializadas, con el objetivo de analizar la literatura, y basándose en esta proponer pautas para el manejo estomatológico de estos pacientes...


Congenital heart diseases are defined as anatomical lesions of the heart that are presented at birth and represent a first-priority public health problem. Patients affected by this kind ofpathologies show a large variety of symptoms and require proper dental care to maintain a healthy oral and overall status. Literature about dental pediatric care of patients with congenital heart diseases is limited. A systematic search in scientific databases and specialized journals on the subject was carried out with the aim of analyzing the available literature and propose dental guidelines for these patients...


Assuntos
Criança , Endocardite/complicações , Endocardite/congênito , Endocardite/genética , Odontopediatria
13.
Microbes Infect ; 13(3): 216-25, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21044892

RESUMO

Cardiac vegetations result from bacterium-platelet adherence, activation and aggregation, and are associated with increased morbidity and mortality in infective endocarditis. The GPIIb/IIIa and FcγRIIa platelet receptors play a central role in platelet adhesion, activation and aggregation induced by endocarditis pathogens such as Staphylococcus aureus, but the influence of known polymorphisms of these receptors on the pathogenesis of infective endocarditis is unknown. We determined the GPIIIa platelet antigen Pl(A1/A2) and FcγRIIa H131R genotype of healthy volunteers (n = 160) and patients with infective endocarditis (n = 40), and investigated the influence of these polymorphisms on clinical outcome in infective endocarditis and S. aureus-platelet interactions in vitro. Platelet receptor genotype did not correlate with development of infective endocarditis, vegetation characteristics on echocardiogram or the composite clinical end-point of embolism, heart failure, need for surgery or mortality (P > 0.05 for all), even though patients with the GPIIIa Pl(A1/A1) genotype had increased in vivo platelet activation (P = 0.001). Furthermore, neither GPIIIa Pl(A1/A2) nor FcγRIIa H131R genotype influenced S. aureus-induced platelet adhesion, activation or aggregation in vitro (P > 0.05). Taken together, our data suggest that the GPIIIa and FcγRIIa platelet receptor polymorphisms do not influence S. aureus-platelet interactions in vitro or the clinical course of infective endocarditis.


Assuntos
Plaquetas/microbiologia , Endocardite/sangue , Integrina beta3/genética , Receptores de IgG/genética , Infecções Estafilocócicas/sangue , Staphylococcus aureus/fisiologia , Adulto , Idoso , Plaquetas/fisiologia , Endocardite/genética , Endocardite/microbiologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária , Polimorfismo Genético , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/microbiologia , Estatísticas não Paramétricas
14.
Int J Cardiol ; 145(2): 226, 2010 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-19616859

RESUMO

Causative microorganism is not always isolated from blood and infected tissues although some major and minor criteria have been proposed for diagnosis of infective endocarditis (IE). Prophylactic antibiotic regimens are generally used for these culture-negative IE. Further diagnostic tools such as PCR, however, can demonstrate the organism and decrease the ratio of culture-negative IE.


Assuntos
Endocardite/diagnóstico , Infecções Relacionadas à Prótese/diagnóstico , Endocardite/genética , Endocardite/microbiologia , Humanos , Reação em Cadeia da Polimerase/métodos , Infecções Relacionadas à Prótese/genética
15.
Vaccine ; 25(46): 7873-84, 2007 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-17931756

RESUMO

Brucellosis is an important zoonotic disease that causes abortion in cattle and undulant fever, arthritis, endocarditis and meningitis in human. In spite of the fact that immunization could be an efficient measure to control brucellosis, not a single ideal vaccine against this important disease has been developed so far. In order to develop an effective vaccine against Brucella abortus (B. abortus), various protective immunodominant gene/protein products of the pathogen have been studied in combination with different adjuvants. For example, recombinant ribosomal protein L7/L12 (rL7/L12) although an interesting T-cell antigen, normally failed to evoke protective immune response when used in free form. In the present study we have demonstrated that Escherischia coli (E. coli) lipid liposome (escheriosome)-mediated cytosolic delivery of recombinant rL7/L12 protein can elicit strong immunological responses in the Balb/c mice. In contrast, egg PC/Chol liposome entrapped rL7/L12, in a manner similar to its free form, was found to impart relatively poor immune response. Furthermore, escheriosome entrapped rL7/L12 protein elicited high IgG2a isotype response suggestive of its relevance in imparting protection against brucellosis in mice. Altogether the present study is a clear indicative of the possible use of escheriosome-based delivery of rL7/L12 protein to induce protective immune responses against experimental murine brucellosis.


Assuntos
Antígenos de Bactérias/imunologia , Vacina contra Brucelose/imunologia , Brucella abortus/imunologia , Brucelose/prevenção & controle , Escherichia coli/imunologia , Lipossomos/imunologia , Proteínas Recombinantes/imunologia , Proteínas Ribossômicas/imunologia , Aborto Séptico/genética , Aborto Séptico/imunologia , Aborto Séptico/prevenção & controle , Adjuvantes Imunológicos/genética , Adjuvantes Imunológicos/farmacologia , Animais , Antígenos de Bactérias/genética , Antígenos de Bactérias/farmacologia , Artrite/genética , Artrite/imunologia , Artrite/prevenção & controle , Vacina contra Brucelose/genética , Vacina contra Brucelose/farmacologia , Brucella abortus/genética , Brucelose/genética , Brucelose/imunologia , Bovinos , Modelos Animais de Doenças , Endocardite/genética , Endocardite/imunologia , Endocardite/prevenção & controle , Escherichia coli/química , Escherichia coli/genética , Feminino , Febre/genética , Febre/imunologia , Febre/prevenção & controle , Humanos , Lipossomos/química , Lipossomos/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Gravidez , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/farmacologia , Linfócitos T/imunologia , Zoonoses
17.
J Infect Dis ; 186(6): 769-73, 2002 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-12198610

RESUMO

Bacterial adherence to intravenous catheters may be mediated, in part, by adherence to coagulation proteins and platelets. The possibility that catheter infection is associated with gene polymorphisms that cause hypercoagulability or increased platelet stickiness was examined. Among patients with infected catheters, there was no increase in the frequency of polymorphisms that increase coagulability, including factor V Leiden R506G, factor II (prothrombin) G20210A, and methylenetetrahydrofolate reductase C677T, compared with control subjects. The incidence of polymorphisms of the platelet beta(3) integrin among patients with infected catheters was also similar to that among control subjects. The C/D heterozygote of the variable number tandem repeat polymorphism and the C/T heterozygote of the KO polymorphism of glycoprotein Ibalpha were more frequent among patients with infected catheters than they were among control subjects. In a small proportion of patients, a genetic predisposition to platelet stickiness may be associated with infection of intravenous catheters, but in the majority, a recognized genetic tendency to hypercoagulability or platelet stickiness does not underlie infection.


Assuntos
Infecções Bacterianas/genética , Cateterismo Venoso Central , Predisposição Genética para Doença , Adesividade Plaquetária/genética , Agregação Plaquetária/genética , Trombofilia/genética , Antígenos de Plaquetas Humanas/genética , Infecções Bacterianas/microbiologia , Biofilmes , Endocardite/genética , Heterozigoto , Humanos , Polimorfismo Genético
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