RESUMO
Intravenous delivery of adenoviruses is the optimal route for many gene therapy applications. Once in the blood, coagulation factor X (FX) binds to the adenovirus capsid and protects the virion from natural antibody and classical complement-mediated neutralisation in mice. However, to date, no studies have examined the relevance of this FX/viral immune protective mechanism in human samples. In this study, we assessed the effects of blocking FX on adenovirus type 5 (Ad5) activity in the presence of human serum. FX prevented human IgM binding directly to the virus. In individual human sera samples (n=25), approximately half of those screened inhibited adenovirus transduction only when the Ad5-FX interaction was blocked, demonstrating that FX protected the virus from neutralising components in a large proportion of human sera. In contrast, the remainder of sera tested had no inhibitory effects on Ad5 transduction and FX armament was not required for effective gene transfer. In human sera in which FX had a protective role, Ad5 induced lower levels of complement activation in the presence of FX. We therefore demonstrate for the first time the importance of Ad-FX protection in human samples and highlight subject variability and species-specific differences as key considerations for adenoviral gene therapy.
Assuntos
Adenoviridae/imunologia , Fator X/imunologia , Técnicas de Transferência de Genes , Terapia Genética/métodos , Adenoviridae/genética , Linhagem Celular Tumoral , Vetores Genéticos/sangue , Vetores Genéticos/genética , Vetores Genéticos/imunologia , Células HEK293 , Humanos , Imunoglobulina M/imunologia , Injeções Intravenosas/métodosRESUMO
We report a case of severe sand aspiration in association with near-drowning, which led to respiratory failure secondary to the acute respiratory distress syndrome, necessitating mechanical ventilation, repeated therapeutic bronchoscopic lavage, and a stay in the intensive care unit that exceeded one month.
Assuntos
Afogamento Iminente/complicações , Aspiração Respiratória/etiologia , Dióxido de Silício , Adulto , Dióxido de Carbono/sangue , Feminino , Humanos , Oxigênio/sangue , Pressão Parcial , Aspiração Respiratória/diagnóstico por imagem , Aspiração Respiratória/terapia , Insuficiência Respiratória/diagnóstico por imagem , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Tomografia Computadorizada por Raios XRESUMO
Acute respiratory distress syndrome is a severe form of respiratory failure characterized by acute onset of significant hypoxaemia (PaO2:FiO2<200mmHg) with diffuse bilateral pulmonary air-space shadowing on chest X-ray, without clinical signs of heart failure (Bernard et al, 1994). It has a heterogeneous aetiology with wide-ranging pulmonary and extra-pulmonary causes.
Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Síndrome do Desconforto Respiratório/terapia , Oxigenação por Membrana Extracorpórea/efeitos adversos , HumanosRESUMO
A 17-month-old toddler became critically ill after an accidental overdose with 'Ecstasy'. A single tablet was quickly retrieved intact from under her tongue, but within 5 min the child developed generalised tonic-clonic seizures requiring immediate transfer to hospital. She also had hyperthermia (38.5 degrees C), tachycardia (150 beats.min(-1)) and hypertension. Treatment to terminate the seizures necessitated intubation and ventilation, and cooling measures brought the temperature within normal limits. The child was admitted to the intensive care unit and made a rapid recovery. She was discharged to the ward 12 h later, and had no long-term sequelae.