RESUMEN
Impaired efferocytosis has been shown to be associated with, and even to contribute to progression of, chronic inflammatory diseases such as atherosclerosis. Enhancing efferocytosis has been proposed as strategy to treat diseases involving inflammation. Here we present the strategy to increase 'eat me' signals on the surface of apoptotic cells by targeting cell surface-expressed phosphatidylserine (PS) with a variant of annexin A5 (Arg-Gly-Asp-annexin A5, RGD-anxA5) that has gained the function to interact with α(v)ß(3) receptors of the phagocyte. We describe design and characterization of RGD-anxA5 and show that introduction of RGD transforms anxA5 from an inhibitor into a stimulator of efferocytosis. RGD-anxA5 enhances engulfment of apoptotic cells by phorbol-12-myristate-13-acetate-stimulated THP-1 (human acute monocytic leukemia cell line) cells in vitro and resident peritoneal mouse macrophages in vivo. In addition, RGD-anxA5 augments secretion of interleukin-10 during efferocytosis in vivo, thereby possibly adding to an anti-inflammatory environment. We conclude that targeting cell surface-expressed PS is an attractive strategy for treatment of inflammatory diseases and that the rationally designed RGD-anxA5 is a promising therapeutic agent.
Asunto(s)
Anexina A5/farmacología , Oligopéptidos/farmacología , Fosfatidilserinas/metabolismo , Animales , Anexina A5/farmacocinética , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Adhesión Celular/fisiología , Línea Celular , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Células Jurkat , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Microscopía Confocal , Terapia Molecular Dirigida , Monocitos/citología , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Oligopéptidos/farmacocinética , Fagocitosis/efectos de los fármacos , Fagocitosis/fisiología , Fosfatidilserinas/biosíntesisRESUMEN
Vitamin K was discovered early last century at the same time as the vitamin K-antagonists. For many years the role of vitamin K was solely ascribed to coagulation and coagulation was thought to be involved only at the venous blood side. This view has dramatically changed with the discovery of vitamin K-dependent proteins outside the coagulation cascade and the role of coagulation factors at the arterial side. Vitamin K-dependent proteins are involved in the regulation of vascular smooth muscle cell migration, apoptosis, and calcification. Vascular calcification has become an important independent predictor of cardiovascular disease. Vitamin K-antagonists induce inactivity of inhibitors of vascular calcification, leading to accelerated calcification. The involvement of vitamin K-dependent proteins such as MGP in vascular calcification make that calcification is amendable for intervention with high intake of vitamin K. This review focuses on the effect of vitamin K-dependent proteins in vascular disease.
Asunto(s)
Anticoagulantes/metabolismo , Arteriopatías Oclusivas/metabolismo , Arterias/metabolismo , Factores de Coagulación Sanguínea/metabolismo , Proteínas Sanguíneas/metabolismo , Calcinosis/metabolismo , Vitamina K/metabolismo , Animales , Humanos , Modelos CardiovascularesRESUMEN
A substantial group of patients with type 1 diabetes has difficulty adhering to the treatment regimen, and as a consequence is at increased risk of developing microvascular complications. Cognitive behavioural interventions may help these patients to cope more effectively with their diabetes. We developed a 4 weeks cognitive behavioural group training (CBGT) for patients with type 1 (insulin-dependent) diabetes in persistent poor glycaemic control, to help them overcome negative beliefs and attitudes towards diabetes and improve their self-care behaviours. Feasibility and efficacy of CBGT were tested in a non-randomised prospective study in 24 poorly-controlled type 1 diabetes patients (mean age 35.2+/-11.1years; 15 female; mean HbA(1c) 9.3% (+/-1.2)), with assessments at 3 and 6 months follow-up. The programme was delivered in small groups (n=6-8), by a team of a diabetes nurse specialist and a psychologist. Primary outcome measures were glycosylated haemoglobin (HbA(1c)), diabetes-related emotional distress (PAID) and psychological well-being (WBQ-12). Changes in diabetes self-care activities (DSCI) were documented, along with perceived barriers in diabetes questionniare (BDQ) and fear of hypoglycaemia survey (HFS). Data were analysed using repeated measures analysis of variance. The CBGT proved to be feasible in this selected group of patients and was well appreciated. Following CBGT, mean HbA(1c) dropped by 0.8% at 6 months from baseline, while emotional well-being was preserved. It is concluded that CBGT is a promising intervention that deserves further evaluation in randomised controlled trials.
Asunto(s)
Terapia Cognitivo-Conductual/normas , Diabetes Mellitus Tipo 1/prevención & control , Diabetes Mellitus Tipo 1/psicología , Cooperación del Paciente/psicología , Educación del Paciente como Asunto/normas , Psicoterapia de Grupo/normas , Adulto , Diabetes Mellitus Tipo 1/metabolismo , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Masculino , Salud Mental , Enfermeras Clínicas/normas , Investigación en Evaluación de Enfermería , Proyectos Piloto , Evaluación de Programas y Proyectos de Salud , Psicología Clínica/normas , Autocuidado/métodos , Autocuidado/psicología , Encuestas y CuestionariosRESUMEN
OBJECTIVE: The primary aim of this study was to investigate the hypothesis that somatoform dissociation would differentiate among specific diagnostic categories after controlling for general psychopathology. METHOD: The Somatoform Dissociation Questionnaire (SDQ-20), the Dissociative Experiences Scale, and the Symptom Checklist-90-R were completed by patients with DSM-IV diagnoses of dissociative disorders (n = 44), somatoform disorders (n = 47), eating disorders (n = 50), bipolar mood disorder (n = 23), and a group of consecutive psychiatric outpatients with other psychiatric disorders (n = 45), mainly including anxiety disorders, depression, and adjustment disorder. RESULTS: The SDQ-20 significantly differentiated among diagnostic groups in the hypothesised order of increasing somatoform dissociation, both before and after statistically controlling for general psychopathology. Somatoform dissociation was extreme in dissociative identity disorder, high in dissociative disorder, not otherwise specified, and increased in somatoform disorders, as well as in a subgroup of patients with eating disorders. In contrast with somatoform dissociation, psychological dissociation did not discriminate between bipolar mood disorder and somatoform disorders. CONCLUSIONS: Somatoform dissociation is a unique construct that discriminates among diagnostic categories. It is highly characteristic of dissociative disorder patients, a core feature in many patients with somatoform disorders, and an important symptom cluster in a subgroup of patients with eating disorders.
Asunto(s)
Trastornos Disociativos/diagnóstico , Trastornos Somatomorfos/diagnóstico , Adulto , Trastornos de Ansiedad/clasificación , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/psicología , Trastorno Bipolar/clasificación , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/psicología , Trastorno Depresivo/clasificación , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/psicología , Diagnóstico Diferencial , Trastornos Disociativos/clasificación , Trastornos Disociativos/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/clasificación , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Psicometría , Psicopatología , Trastornos Somatomorfos/clasificación , Trastornos Somatomorfos/psicologíaRESUMEN
The pneumothorax, and its often invasive treatment, are impressive events in otherwise healthy young patients. The relationship between smoking behaviour and the idiopathic spontaneous pneumothorax (ISP) is explained to the patients. The objective of the study was to analyse whether smoking behaviour of patients is influenced by the ISP (re-) event, and its treatment. Of 145 consecutive ISP patients (1991-1995), 112 were tobacco smokers at time of the first ISP. Of the 112, 106 participated in a confidential telephone questionnaire survey combined with retrospective medical record analysis. Smoking cessation and reduction percentage related to ISP events, and its treatment, were the outcome measurements. All patients (mean age 28.8 years at the first ISP) were aware of the relationship between smoking, and ISP at time of the first ISP. Age, pack years, and different treatment modalities had no influence on smoking cessation or reduction. Some 86.2% of the male and 80.8% of the female patients continued smoking after the first ISP, despite the known relationship between smoking, and contracting spontaneous pneumothorax, and despite its often invasive treatment. In the group of recurrent pneumothorax events 73.3% continued smoking.