ABSTRACT
Akinetic crisis (AC) is akin to neuroleptic malignant syndrome (NMS) and is the most severe and possibly lethal complication of parkinsonism. Diagnosis is today based only on clinical assessments yet is often marred by concomitant precipitating factors. Our purpose is to evidence that AC and NMS can be reliably evidenced by FP/CIT single-photon emission computerized tomography (SPECT) performed during the crisis. Prospective cohort evaluation in 6 patients. In 5 patients, affected by Parkinson disease or Lewy body dementia, the crisis was categorized as AC. One was diagnosed as having NMS because of exposure to risperidone. In all FP/CIT, SPECT was performed in the acute phase. SPECT was repeated 3 to 6 months after the acute event in 5 patients. Visual assessments and semiquantitative evaluations of binding potentials (BPs) were used. To exclude the interference of emergency treatments, FP/CIT BP was also evaluated in 4 patients currently treated with apomorphine. During AC or NMS, BP values in caudate and putamen were reduced by 95% to 80%, to noise level with a nearly complete loss of striatum dopamine transporter-binding, corresponding to the "burst striatum" pattern. The follow-up re-evaluation in surviving patients showed a recovery of values to the range expected for Parkinsonisms of same disease duration. No binding effects of apomorphine were observed. By showing the outstanding binding reduction, presynaptic dopamine transporter ligand can provide instrumental evidence of AC in Parkinsonism and NMS.
Subject(s)
Dopamine Plasma Membrane Transport Proteins/metabolism , Lewy Body Disease/diagnosis , Neuroleptic Malignant Syndrome/diagnosis , Parkinson Disease/diagnosis , Aged , Apomorphine/pharmacology , Dopamine Agonists/pharmacology , Dopamine Plasma Membrane Transport Proteins/drug effects , Female , Humans , Lewy Body Disease/pathology , Male , Neuroleptic Malignant Syndrome/pathology , Parkinson Disease/pathology , Prospective Studies , Tomography, Emission-Computed, Single-PhotonABSTRACT
Cysteinyl leukotrienes (i.e. LTC4, LTD4), produced by activated leukocytes or by transcellular metabolism may act at different levels on vascular smooth muscle cells (VSMC) during inflammatory process or atherosclerosis. We studied the effect of LTC4, LTD4, and LTE4 on the in vitro proliferation of rat VSMC, measured by [3H]-thymidine incorporation and cell count. LTD4 had a stronger stimulatory effect on [3H]-thymidine incorporation than LTC4, whereas LTE4 was inactive. The effect of LTD4 on [3H]-thymidine incorporation was dose-dependent, with the maximal activity at 10(-6) M. The stimulatory activity of LTD4 was inhibited in a dose-dependent manner by MK-571, a specific LTD4 receptor antagonist. In addition, MK-571 (1 mg/kg/day) given for at least 1 day after injury in a model of balloon catheter injury of rat carotid artery, provided effective inhibition of myointimal VSMC proliferation, with a 58% reduction of 5-bromo-2'-deoxyuridine (BrdU) uptake in the neointima and 69% reduction of neointimal thickening. Our data support the importance of inflammatory mechanisms in the pathogenesis of atherosclerosis and suggest a possible role for cysteinyl leukotrienes, specifically LTD4, in the control of VSMC proliferation.
Subject(s)
Leukotriene D4/pharmacology , Membrane Proteins , Muscle, Smooth, Vascular/pathology , Receptors, Leukotriene , Tunica Intima/pathology , Animals , Cell Division/drug effects , Cells, Cultured , Hyperplasia , Leukotriene Antagonists , Muscle, Smooth, Vascular/drug effects , Propionates/pharmacology , Quinolines/pharmacology , Rats , Tunica Intima/drug effectsABSTRACT
The aortic wall structure of genetically determined hypercholesterolaemic (Yoshida) and control (Brown-Norway) rats was investigated by transmission and scanning electron and light microscopy. Leucocyte adherence mostly at branch sites and irregular protrusive structures were observed on the endothelial surface of the thoracic aorta of Yoshida, but not of Brown-Norway rats. The subendothelial space of the aortic wall of Yoshida rats was characterized by intimal cushions consisting of smooth muscle cells of 'synthetic phenotype' associated with adhering leucocytes and lipid droplets. Lipid infiltration of the cytoplasm of medial smooth muscle cells was observed on the inner part of the aortic arch and on the lateral parts of the large branches of Yoshida rats. This model of spontaneously hyperlipidaemic Yoshida rats is an appropriate 'moderate' injury system, which may be useful for studies of multiple risk factors for atherogenesis.
Subject(s)
Aorta, Thoracic/ultrastructure , Arteriosclerosis/pathology , Hypercholesterolemia/pathology , Animals , Endothelium, Vascular/ultrastructure , Inclusion Bodies/ultrastructure , Male , Microscopy, Electron , Microscopy, Electron, Scanning , Rats , Rats, Inbred BN , Rats, Mutant Strains , Tunica Media/ultrastructureABSTRACT
Hypercholesterolemia is a predisposing factor for atherosclerosis. We studied the response to damage of vascular smooth muscle cells (SMC) from normocholesterolemic Brown Norway (BN) and from spontaneously hyper-cholesterolemic Yoshida (YOS) rats (16-24 month old). The regrowth rate of SMC from BN and YOS rats after freeze-induced damage was similar in the presence of fetal calf serum and of serum derived from normocholesterolemic rats, while it was reduced in the presence of serum from hypercholesterolemic rats. Freeze-injury of the abdominal aorta was followed by reduced neointima formation in YOS rats, as compared to BN rats, confirming the impaired response of vascular cells from hypercholesterolemic rats to injury. This defect may be due either to lipids or to unknown factors present in the hyperlypidemic serum.
