Correlation of clinical symptoms, HVA and 5-HIAA in csf and plasma L-DOPA in Parkinsonian patients treated with L-DOPA and L-DOPA + RO 4-4602.
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Biomedical subjects
Publications and source records attributed to C Cerletti.
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Plasma L-DOPA levels in rats receiving L-DOPA by the oral route were decreased by the concomitant administration of trihexyphenidyl. Following systemic L-DOPA administration no differences were observed between control and trihexyphenidyl-treated rats. Effects similar to those of trihexyphenidyl were observed with atropine. These results indicate that trihexyphenidyl decreases L-DOPA gastrointestinal absorption probably by delaying gastric emptying. The presence in humans of this interaction between the two antiparkinsonian drugs was suggested by similar findings made either in a group of normal volunteers or in a group of parkinsonian patients. These observations suggest that at the clinical level in selected cases the concomitant administration of trihexyphenidyl to patients receiving L-DOPA may decrease the therapeutic efficacy of L-DOPA by reducing its gastrointestinal absorption.
Morphine, administered to Sprague-Dawley rats over a period of 65 hr either by the simultaneous implantation of two 75 mg pellets, or by a series of twice daily 20 or 30 mg/kg injections, produced dependence as indicated by the precipitation of the abstinence syndrome with the antagonist, naloxone. Plasma morphine levels, analyzed fluorometrically at various times during the treatment procedures, revealed peak concentrations that were 3 or 4 fold higher for injected animals than the maximum steady-state level established in the pellet-implanted animals. The calculated plasma concentration of the drug over time was not statistically different for the groups. It is noted that although the 2 methods of morphine administration produce a qualitatively identical dependent state, the pellet implantation technique causes greater weight loss and a higher incidence of jumping and wet-dog shakes during withdrawal.
The conditions under which pretreatment with a calcium salt may prevent the action of reserpine on brain noradrenaline stores in the rat were investigated. The results show that only after subcutaneous administration of reserpine in the same site as a previous CaCl2 injection, was the action of reserpine prevented and reduced levels of this drug were found in the brain. Conversely, the depletion of encephalic noradrenaline following reserpine, as well as the reserpine brain concentration, were not affected by subcutaneously administered calcium chloride, when reserpine was administered either intravenously, or subcutaneously in a site different from that selected for pretreatment with the calcium salt. In essence calcium chloride, a well known irritant, acts accordingly at the site of subcutaneous administration, thus limiting by a non specific mechanism the absorption of reserpine. Under similar conditions, in fact, the absorption of a different drug, i.e. harmaline, was likewise altered. In view of these findings the significance of some studies on calcium-reserpine interaction appearing in the literature requires a reappraisal.
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The aim of our study was to evaluate the effects of diet induced hypercholesterolemia and associated atherosclerosis in rabbits on serum thromboxane B2 levels. We have determined thromboxane B2 in serum of hypercholesterolemic rabbits with atherosclerosis and in normocholesterolemic rabbits without atherosclerosis. Our data show only a mildly higher serum thromboxane levels in hypercholesterolemic rabbits and extensive atherosclerosis than in controls without atherosclerosis. In conclusion, these results show that diet induced hypercholesterolemia was not associated with thromboxane B2 generation, in spite of a diffuse experimental atheromatosis.
Aspirin inhibits thromboxane and prostaglandin formation in platelets and in vascular cells. It prevents platelet aggregation by irreversible acetylation of cyclooxygenase, a key enzyme in arachidonic acid metabolism. On the basis of its antiplatelet effect, aspirin has been assessed during the past two decades in patients with a history of myocardial infarction, stroke, transient ischemic attack or unstable angina. A meta-analysis of randomized controlled trials of long-term aspirin treatment for the secondary prevention of vascular disease indicated that aspirin (300-1500 mg daily) significantly reduced fatal and non-fatal vascular events. More recently aspirin (160 mg daily) produced a significant reduction in hospital vascular mortality and in non-fatal events in patients with suspected acute myocardial infarction. The combination of aspirin and streptokinase was significantly better than either drug alone. On the other hand, two primary prevention trials of aspirin in healthy doctors did not show any modification of vascular mortality despite an overall reduction of non-fatal myocardial infarction. Resolution of some problems related to the mechanism of action of aspirin and to selection of trial populations will possibly increase the benefit/risk ratio of aspirin treatment for the prevention of vascular disease.
The use of the sensitive photoprotein aequorin as a Ca2+ indicator in human polymorphonuclear leukocytes (PMN) not pretreated with cytochalasin B and stimulated with platelet activating factor (PAF) may help cast more light on the relative importance of intracellular and extracellular Ca2+ in PMN function. PAF elicits Ca2+ mobilization in PMN (resuspended in the presence of 1 mM extracellular Ca2+), in a concentration-dependent manner. The Ca2+ chelator ethyleneglycoltetraacetic acid (EGTA) abolishes Ca2+ mobilization, suggesting that almost all Ca2+ mobilized by PAF derives from the external medium. Aggregation and enzymatic release parallel the Ca2+ mobilization triggered by PAF. In contrast PAF appears to be only a weak stimulus of superoxide anion production (compared to the phorbol ester phorbol 12-myristate 13-acetate (PMA] and leukotriene B4 (LTB4) synthesis (compared to the Ca2+ ionophore A23187). The fact that PAF elicits Ca2+ mobilization, aggregation, secretion and LTB4 generation in human PMN supports the role of this phospholipid as a powerful mediator of physiopathological events involving PMN activation.