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At least 739 records · Page 41Linked to original sources

A double blind study of the influence of dipropylacetate on behaviour.

The influence of dipropylacetate (D.P.A.) on behaviour was studied in 20 patients using a double blind cross over trial. 5 patients were rated as improved on D.P.A., 6 on placebo, 3 as deteriorated on D.P.A., 3 on placebo, 12 as unchanged on D.P.A. and 11 on placebo. This study gives us no reason to believe that D.P.A. exerts a psychotropic action within 3 weeks which is better than a placebo effect.

Adolescent↗

Sodium valproate in the treatment of resistant epilepsy.

A series of 115 patients was treated with sodium valproate (Epilim) for periods ranging from 6 to 24 months and in dosages ranging from 400 mg to 2400 mg daily. All but six of these patients had intractable epilepsies and had been previously treated unsuccessfully with other anti-epileptic agents. Eighty patients had generalised seizures and 35 had partial seizures which, in 26 cases, were secondarily generalised. Reduction of seizure frequency by over 50 per cent occurred in about 70 per cent of patients with generalised seizures but in only 37 per cent of those with partial seizures. A number of patients reported increased alertness, improvement of mood, increased appetite and improved performance at school. The adverse effects encountered were gastro-intestinal symptoms, weight gain and hair loss.

Adolescent↗

Organic acids or urine in multiple sclerosis.

The urinary excretion of organic acids was examined in 509 cases with multiple sclerosis and in 50 age- and sex-matched controls. The concentrations of the acids were related to creatinine. No differences were found for compounds such as glycolic acid, 2-methyl-3-hydroxybutyric acid, 2-ethylhydracrylic acid, 4-hydroxyphenylacetic acid, suberic acid and many other acids. However, the mean excretion of 2-hydroxy-2-methyl-3-butenoic acid was increased two-fold in the MS group. 2 MS cases had a very high excretion of 3-methylglutaconic acid, and another 6 cases had moderate elevations, which were fairly constant over a time period of several months. Moderate elevations were also noted in 2 healthy controls. 1 MS case had a very high excretion of 3-hydroxyisovaleric acid. 7 MS cases, and none in the control group, had elevated excretion of adipic acid. Differences were also noted for lactic acid, succinic acid, aconitic acid and 3-methyladipic acid. An oral dose of deuterium-labelled acetate was given to one of the patients with high excretion of 3-methylglutaconic acid. Deuterium was incorporated into this metabolite. 3-methylglutaconic acid, 2-hydroxy-2-methyl-3-butenoic acid, 3-hydroxy-isovaleric acid and 3-methyladipic acid are all potential isoprenoid metabolites. A possible defect in the pathway of isoprenoid biosynthesis is discussed.

Aconitic Acid↗

Phenylketonuria: limit in capacity of pre-weanling rats to oxidize beta-phenyllactate and other alpha-hydroxy acids.

In comparison with mature animals, pre-weanling rats have markedly higher and longer lasting serum levels of beta-phenyllactate following the intraperitoneal injection of a moderate dose. A corresponding age-dependent difference in the rate of oxidation of beta-phenyllactate and other alpha-hydroxy acids was observed in experiments with homogenates and supernatant fractions of rat kidney.

Animals↗

Controlled trial of sodium valproate in severe epilepsy.

In a double-blind crossover trial sodium valproate or placebo was added to the existing anticonvulsant treatment of 20 patients with chronic uncontrolled epilepsy. Sodium valproate 1200 mg/day significantly reduced the frequency of both tonic-clonic and minor seizures in these patients. Only mild and transient side effects occurred (drowsiness, ataxia, and nausea), and these may have been due to the effect of adding sodium valproate to existing phenobarbitone or phenytoin treatment. Further controlled trials are needed to assess more fully the efficacy of this drug in various types of epilepsy.

Adult↗

Effect of sodium valproate on plasma protein binding of diphenylhydantoin.

In vivo and in vitro experimental data are presented in support of the hypothesis that sodium valproate displaces diphenylhydantoin (DPH) from plasma protein binding sites. This interaction could have important practical implications in the management of patients on combined therapy with these two drugs. Acute neurological features of DPH intoxication may be precipitated as a result of an increased free (pharmacologically active) fraction, which would not be detected by routine plasma DPH estimations since these reflects largely the bound fraction.

Animals↗

Sodium valproate in the treatment of levodopa-induced dyskinesia.

The effect of sodium valproate 1200 mg daily on the disability of Parkinsonism and on levodopa-induced dyskinesia was assessed in a double-blind crossover trial with matched placebo in 12 patients with Parkinson's disease. No objective change in the severity of Parkinsonism or dyskinesias was noted. However, six out of nine patients who completed the trial noted a slight to moderate improvement in their dyskinesias with no change in their Parkinsonism. Excess salivation improved in four subjects on sodium valproate.

Clinical Trials as Topic↗

Role of fatty acid oxidation in mechanism of action of gastric secretagogues.

The role of beta-oxidation in the mechanism of stimulation of acid secretion was examined in toad gastric mucosa in vitro. The incubation with 4-pentenoate selectively inhibited in a dose-dependent manner the rate of 14CO2 formation from [1-14C]octanoate. Pretreatment with 20 mM 4-pentenoate sharply reduced the respiratory and secretory responses to theophylline and histamine. Tracer studies showed a major utilization of exogenous octanoate over glucose and pyruvate by the in vitro toad gastric mucosa. Theophylline and histamine stimulated by 69% the rate of octanoate oxidation. Over 60% of the increments in oxygen uptake produced by theophylline and histamine accounted for the increments in octanoate oxidation, whereas glucose and pyruvate together accounted for less than 25%. Octanoate-dependent respiration was shown to correlate with octanoate oxidation under both inhibition with 4-pentenoate and stimulation with theophylline. Theophylline stimulated by 25% the rate of octanoate oxidation in Cl--free glucuronate-nutrient solutions. The present work provides further evidence for the primary role of fatty acid oxidation in the mechanism of acid secretion in amphibian.

Animals↗

Mechanism of action of gemfibrozil on lipoprotein metabolism.

Gemfibrozil is a potent lipid regulating drug whose major effects are to increase plasma high density lipoproteins (HDL) and to decrease plasma triglycerides (TG) in a wide variety of primary and secondary dyslipoproteinemias. Its mechanism of action is not clear. Six patients with primary familial endogenous hypertriglyceridemia with fasting chylomicronemia (type V lipoprotein phenotype) with concurrent subnormal HDL cholesterol levels (HDL deficiency) were treated initially by diet and once stabilized, were given gemfibrozil (1,200 mg/d). Each patient was admitted to the Clinical Research Center with metabolic kitchen facilities, for investigation of HDL and TG metabolism immediately before and after 8 wk of gemfibrozil treatment. Gemfibrozil significantly increased plasma HDL cholesterol, apolipoprotein (apo) AI, and apo AII by 36%, 29%, and 38% from base line, respectively. Plasma TG decreased by 54%. Kinetics of apo AI and apo AII metabolism were assessed by analysis of the specific radioactivity decay curves after injection of autologous HDL labeled with 125I. Gemfibrozil increased synthetic rates of apo AI and apo AII by 27% and 34%, respectively, without changing the fractional catabolic rates. Stimulation of apo AI and apo AII synthesis by gemfibrozil was associated with the appearance in plasma of smaller (and heavier) HDL particles as assessed by gradient gel electrophoresis and HDL composition. Postheparin extra-hepatic lipoprotein lipase activity increased significantly by 25% after gemfibrozil, and was associated with the appearance in plasma of smaller very low density lipoprotein particles whose apo CIII:CII ratio was decreased. These data suggest that gemfibrozil increases plasma HDL levels by stimulating their synthesis. Increased transport (turnover) of HDL induced by gemfibrozil may be significant in increasing tissue cholesterol removal in these patients.

Apolipoprotein A-I↗