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1.
Eur Cell Mater ; 39: 171-182, 2020 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-32301500

RESUMO

Infections are often caused by pathobionts, endogenous bacteria that belong to the microbiota. Trauma and surgical intervention can allow bacteria to overcome host defences, ultimately leading to sepsis if left untreated. One of the main defence strategies of the immune system is the production of highly specific antibodies. In the present proof-of-concept study, plasma antibodies against 9 major pathogens were measured in sepsis patients, as an example of severe systemic infections. The binding of plasma antibodies to bacterial extracellular proteins was quantified using a semi-automated immunoblot assay. Comparison of the pathogen-specific antibody levels before and after infection showed an increase in plasma IgG in 20 out of 37 tested patients. This host-directed approach extended the results of pathogen-oriented microbiological and PCR diagnostics: a specific antibody response to additional bacteria was frequently observed, indicating unrecognised poly-microbial invasion. This might explain some cases of failed, seemingly targeted antibiotic treatment.


Assuntos
Anticorpos/imunologia , Sepse/imunologia , Sepse/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Formação de Anticorpos/imunologia , Estudos de Casos e Controles , Humanos , Imunoglobulina G/sangue , Cinética , Pessoa de Meia-Idade , Sepse/sangue , Especificidade da Espécie
2.
Pediatr Cardiol ; 36(6): 1204-11, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25822459

RESUMO

Products of hemeoxygenase (HO)-1 have anti-inflammatory and antioxidant functions. The HO-1 promoter has a variable number of GT(n) repeats: A low number (n < 23) is associated with high transcriptional activity in response to oxidative stress. We hypothesized that the frequency of GT(n) repeats in pediatric heart failure (HF) reflects plasma biomarkers of different disease processes: the soluble receptor for advance glycation end products (sRAGE, marking cellular activation), oxLDL (oxidative stress), NGAL (impaired renal function), HIF-1α (hypoxia) and hsCRP (inflammation). Sixty HF children [aged 4-14 years, 30 with HF due to idiopathic dilated cardiomyopathy (IDCM), 30 due to chronic renal failure (CRF)] were compared to 20 healthy controls (HC). Leukocyte HO-1 GT(n) repeats were determined by PCR, plasma markers by ELISA or nephelometry. The number of GT(n) repeats in the HF patients was higher than the number of repeats in the controls, with no difference between the patient groups (p < 0.001). sRAGE, oxLDL, HIF-1α, NGAL and hsCRP were higher in both HF groups compared to HC (all p < 0.01). IDCM had higher sRAGEs and HIF-1α compared to CRF patients (p < 0.01). NGAL was higher in CRF compared to IDCM (p < 0.01). None of the plasma/serum markers correlated with the number of GT(n) repeats in any group. The number of HO-1 promoter GT(n) polymorphism is increased in both IDCM and CRF children with HF, but is unrelated to plasma markers of different pathological processes. This casts doubts on the clinical value of the number of GT(n) repeats in pediatric HF.


Assuntos
Sequência de Bases , Predisposição Genética para Doença , Insuficiência Cardíaca/genética , Heme Oxigenase-1/genética , Regiões Promotoras Genéticas , Adolescente , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Cardiomiopatia Dilatada/complicações , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Testes Genéticos/métodos , Insuficiência Cardíaca/etiologia , Humanos , Inflamação , Rim/metabolismo , Falência Renal Crônica/complicações , Leucócitos/metabolismo , Masculino , Nefelometria e Turbidimetria/métodos , Reação em Cadeia da Polimerase
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