ABSTRACT
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.
Subject(s)
Carotid Artery Injuries/enzymology , Carotid Artery, Common/enzymology , Endothelium, Vascular/enzymology , Intracellular Signaling Peptides and Proteins/deficiency , Protein Serine-Threonine Kinases/deficiency , Vascular Remodeling , Wound Healing , Animals , Carotid Artery Injuries/genetics , Carotid Artery Injuries/pathology , Carotid Artery, Common/pathology , Cell Adhesion , Cell Movement , Cell Proliferation , Cells, Cultured , Chemokine CCL2/metabolism , Chemokine CCL5/metabolism , Disease Models, Animal , Endothelium, Vascular/injuries , Endothelium, Vascular/pathology , Hypercholesterolemia/complications , Hypercholesterolemia/genetics , Hypercholesterolemia/metabolism , Hyperplasia , Inflammation/enzymology , Inflammation/pathology , Inflammation/prevention & control , Intracellular Signaling Peptides and Proteins/genetics , Leukocytes/metabolism , Mice, Inbred C57BL , Mice, Knockout , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology , Neointima , Protein Serine-Threonine Kinases/genetics , Re-Epithelialization , Receptors, LDLSubject(s)
Chewing Gum , Haloperidol/therapeutic use , Nicotine/analogs & derivatives , Polymethacrylic Acids/therapeutic use , Polyvinyls/therapeutic use , Tourette Syndrome/drug therapy , Drug Synergism , Drug Therapy, Combination , Humans , Nicotine/administration & dosage , Nicotine/therapeutic use , Polymethacrylic Acids/administration & dosage , Polyvinyls/administration & dosage , Research Design/standards , Tobacco Use Cessation DevicesABSTRACT
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.
Subject(s)
Haloperidol/therapeutic use , Mental Disorders/drug therapy , Referral and Consultation , Sick Role , Aged , Female , Haloperidol/adverse effects , Hospitals, General , Humans , Male , Mental Disorders/psychology , Middle Aged , Neurocognitive Disorders/drug therapy , Risk FactorsABSTRACT
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.
