RESUMO
Maladaptive remodelling of the arterial wall after mechanical injury (e. g. angioplasty) is characterised by inflammation, neointima formation and media hypertrophy, resulting in narrowing of the affected artery. Moreover, mechanical injury of the arterial wall causes loss of the vessel protecting endothelial cell monolayer. Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2), a major downstream target of p38 MAPK, regulates inflammation, cell migration and proliferation, essential processes for vascular remodelling and re-endothelialisation. Therefore, we investigated the role of MK2 in remodelling and re-endothelialisation after arterial injury in genetically modified mice in vivo. Hypercholesterolaemic low-density-lipoprotein-receptor-deficient mice (ldlr-/-) were subjected to wire injury of the common carotid artery. MK2-deficiency (ldlr-/-/mk2-/-) nearly completely prevented neointima formation, media hypertrophy, and lumen loss after injury. This was accompanied by reduced proliferation and migration of MK2-deficient smooth muscle cells. In addition, MK2-deficiency severely reduced monocyte adhesion to the arterial wall (day 3 after injury, intravital microscopy), which may be attributed to reduced expression of the chemokine ligands CCL2 and CCL5. In line, MK2-deficiency significantly reduced the content of monocytes, neutrophiles and lymphocytes of the arterial wall (day 7 after injury, flow cytometry). In conclusion, in a model of endothelial injury (electric injury), MK2-deficiency strongly increased proliferation of endothelial cells and improved re-endothelialisation of the arterial wall after injury. Deficiency of MK2 prevents adverse remodelling and promotes endothelial healing of the arterial wall after injury, suggesting that MK2-inhibition is a very attractive intervention to prevent restenosis after percutaneous therapeutic angioplasty.
Assuntos
Lesões das Artérias Carótidas/enzimologia , Artéria Carótida Primitiva/enzimologia , Endotélio Vascular/enzimologia , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Proteínas Serina-Treonina Quinases/deficiência , Remodelação Vascular , Cicatrização , Animais , Lesões das Artérias Carótidas/genética , Lesões das Artérias Carótidas/patologia , Artéria Carótida Primitiva/patologia , Adesão Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Quimiocina CCL2/metabolismo , Quimiocina CCL5/metabolismo , Modelos Animais de Doenças , Endotélio Vascular/lesões , Endotélio Vascular/patologia , Hipercolesterolemia/complicações , Hipercolesterolemia/genética , Hipercolesterolemia/metabolismo , Hiperplasia , Inflamação/enzimologia , Inflamação/patologia , Inflamação/prevenção & controle , Peptídeos e Proteínas de Sinalização Intracelular/genética , Leucócitos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Neointima , Proteínas Serina-Treonina Quinases/genética , Reepitelização , Receptores de LDLAssuntos
Goma de Mascar , Haloperidol/uso terapêutico , Nicotina/análogos & derivados , Ácidos Polimetacrílicos/uso terapêutico , Polivinil/uso terapêutico , Síndrome de Tourette/tratamento farmacológico , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Nicotina/administração & dosagem , Nicotina/uso terapêutico , Ácidos Polimetacrílicos/administração & dosagem , Polivinil/administração & dosagem , Projetos de Pesquisa/normas , Dispositivos para o Abandono do Uso de TabacoRESUMO
This study investigates the clinical use of haloperidol within a general hospital. Patients who were prescribed haloperidol were often elderly, seriously ill, and stayed in the hospital longer than average. Only 23% received a psychiatric consultation. Of the patients under study, 80% were prescribed haloperidol on a PRN basis. The most common reason for neuroleptic treatment was to symptomatically manage severe agitation. Organic mental syndromes were rarely documented. Mental status exams were generally absent; the neuroleptic's effect was often omitted, and its use was rarely noted in the discharge summary. It is recommended that more education regarding the use of neuroleptic medication is indicated.
Assuntos
Haloperidol/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Encaminhamento e Consulta , Papel do Doente , Idoso , Feminino , Haloperidol/efeitos adversos , Hospitais Gerais , Humanos , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Transtornos Neurocognitivos/tratamento farmacológico , Fatores de RiscoRESUMO
The relationship of depression and the severity of medical illness to alexithymia was investigated in 75 medically ill patients seen in psychiatric consultation. Both depression and living alone predicted alexithymia but severity of medical illness was not related to an individual's alexithymic characteristics measured by the revised Schalling-Sifneos Scale. The implications of the findings are discussed in relationship to previous data regarding alexithymia in a psychiatric consultation population.