Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is difficult to choose among the many drugs advocated for treating anxiety symptoms. The barbiturates were the most commonly used antianxiety agents until recently but are being superseded by the benzodiazepines. The latter are more effective than the barbiturates as shown in comparative clinical trials, they are safer in overdosage (deliberate or accidental), and they are somewhat less likely to induce dependence. The barbiturates have the additional drawback of interfering with the action of other drugs by inducing liver microsomal (oxidising) drug metabolising enzymes. The major tranquilisers (neuroleptics or antipsychotics) are often of value in low dosage in patients with a previous history of dependence on alcohol, the barbiturates or the benzodiazepines. Tricyclic antidepressants are the treatment of choice in anxious and depressed patients and monoamine oxidase inhibitors may be helpful in phobic patients. The beta-adrenoreceptor blocking agents such as propranolol often ameliorate somatic symptoms such as palpitations and tremor. In the treatment of anxious patients it is important to remove causes for anxiety and to limit any course of drug treatment to a finite period. Both dosage level and dosage interval should be flexible. Benzodiazepines remain the drug treatment of choice.
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PMID:Antianxiety drugs: clinical pharmacology and therapeutic use. 1 Jan 53

Two subcellular fraction, P-1 and P-2, were isolated by differential centrifugation from 0.25 M sucrose muscle homogenates of the parasitic roundworm, Ascaris lumbricoides suum. Morphological studies indicated that P-1 fraction consisted of intact mitochondria, whereas P-2 fraction consisted almost exclusively of vesicular components. The difference spectrum of Ascaris microsomes showed a characteristic b-type cytochrome spectrum with three distinct absorption peaks at 560, 525, and 424 nm. However, the alpha-peak at 560 nm was asymmetric with a shoulder at 555 nm. This microsomal b-type cytochrome was reduced by NADH, which was inhibited by rotenone and HgCl2. The reduced b-type cytochrome was easily reoxidized by shaking. NADH-oxidase activity observed in Ascaris microsomes was inhibited by rotenone, but not by KCN, NaN3, and antimycin A. On the other hand, NADH-cytochrome c and NADH-neotetrazolium (NT) reductase activities in Ascaris microsomes were not inhibited by antimycin A and rotenone, but were inhibited by HgCl2. Further observations indicated that neither HgCl2 nor rotenone inhibited Ascaris microsomal NADH-ferricyanide (FC) reductase activity, but rabbit antibody prepared against the purified NADH-FC reductase inhibited the NADH-cytochrome c reductase activity, the reduction of b-type cytochrome and the NADH-oxidase activity, as well as microsomal NADH-FC reductase activity.
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PMID:Biochemical studies on the muscle microsomes of Ascaris lumbricoides var. suum. I. Biochemical characterization and electron transport of Ascaris microsomes. 42 35

The tremorogenic properties of a series of benzylimidoylurea derivatives are described. The most potent member, N-carbamoyl-2-(2,6-dichlorophenyl) acetamidine hydrochloride (LON-954), produces a reproducible, dose-dependent rest tremor in the mouse with oral doses of 5-100 mg/kg which is also seen in other species (rat, cat, dog, rabbit). The tremor is of constant frequency, rapid onset and short duration. It is not accompanied by akinesia, muscle ridigity, antinociceptive activity, parasympathomimetic effects or marked hypothermia and in these respects differs from tremor produced by oxotremorine. Pretreatment with a microsomal enzyme inhibitor had no effect on the tremor. An LD50 of 165 mg/kg p.o. was calculated in the mouse. After repeated administration both acute and chronic tolerance developed to the tremorogenic effects of LON-954. Evidence for a central site of action is presented, since the tremor could be reproduced following injection of small quantities (50-100 microgram) into the cerebral ventricles of the mouse. Furthermore, the use of spinal, decorticate and and decerebrate rats indicated that although tremor is not of cortical origin, it arises in an area rostral to the inferior colliculi. The mechanism underlying the tremor appears to involve dopaminergic pathways, since the action of LON-954 was antagonised by L-dopa and apomorphine and potentiated by pimozide. Atropine and carbachol were without effect. It is suggested that LON-954 could be used as an alternative to oxotremorine for the detection of anti-Parkinson drugs, particularly those exerting their effects through dopaminergic mechanisms.
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PMID:The pharmacology of N-carbamoyl-2-(2,6-dichlorophenyl)acetamidine hydrochloride (LON-954) a new tremorogenic agent. 58 44

Several brominated androgen derivatives were tested for their ability to inactivate microsomal aromatase from term human placenta. In the experimental protocol, the microsomal homogenate was incubated either with androstenedione or a brominated derivative of androstenedione (16alpha-bromo-6-ketoandrostenedione, 16alpha-bromoandrostenedione, 7alpha-(3'-bromoacetoxypropyl)androstenedione, 6alpha-bromoandrostenedione, or 6beta-bromoandrostenedione) and reduced nicotinamide adenine dinucleotide phosphate in a nitrogen saturated buffer composed of glycerol, ethylenediaminetetraacetic acid, and dithiothreitol in tris(hydroxymethyl)aminomethane hydrochloride (pH 7.4) under nitrogen at 4 degrees C with shaking. After the incubation period, the microsomes were recovered by centrifugation and washed once before determining aromatase specific activity. The brominated androgen derivatives which inactivated aromatase were 7alpha-(3'-bromoacetoxypropyl)androstenedione and 6alpha-bromoandrostenedione. The structures of 6alpha- and 6beta-bromoandrostenedione were unequivocally established by single crystal x-ray diffraction techniques. The extent of the enzyme inactivation by 6alpha-bromoandrostenedione was linearly proportional to the logarithm of its concentration. The evidence that this inactivation occurs at the aromatase active site is that androstenedione, when coincubated with 6alpha-bromoandrostenedione, protected aromatase from this inactivation. Progesterone provided much less protection than androstenedione. Furthermore, both 6alpha- and 6beta-bromoandrostenedione are competitive inhibitors of androstenedione aromatization, as determined by a Lineweaver-Burk plot, and 6alpha-bromoandrostenedione gives the same type I cytochrome P-450 binding spectrum with placental microsomes as androstenedione. These data suggest that 6alpha-bromandrostenedione is effective as an active-site-directed inhibitor of placental microsomal aromatase.
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PMID:Active-site-directed inactivation of aromatase from human placental microsomes by brominated androgen derivatives. 97 87

Sertraline is slowly absorbed after oral administration, with peak plasma concentrations at 6-8 h. Plasma concentrations are linearly related to dose. The elimination half-life is about 32 h; metabolism is by demethylation to an inactive metabolite. Once-daily dosing is recommended, with steady state being reached after about 7 days. The kinetics of sertraline in the elderly and in patients with renal impairment are similar to those in young healthy female volunteers. In young male volunteers, peak plasma concentrations were lower, and elimination half-life shorter, than in elderly men or both groups of women. Nevertheless, no reduction in dosage is recommended for these groups. Sertraline is highly active in animal models of depression, and administration of the drug to healthy human beings causes a selective, dose-related inhibition of 5-hydroxytryptamine (5-HT) uptake into blood platelets. Single doses of sertraline in volunteers caused changes in the quantitative pharmaco-electroencephalogram suggesting antidepressant and anxiolytic actions, with sedative potential evident only at doses of 200 mg or more. Sertraline does not impair psychomotor performance, including simulated car driving, and overall seems neither stimulating nor sedating: an increase in critical flicker fusion threshold suggests a slight alerting effect, whereas subjective tests indicate an increase in perceived sedation at doses of 100 mg or more. No potentiation of the effects of ethanol has been noted in either young or elderly subjects. No adverse effects on the electrocardiogram, blood pressure, or systolic time intervals have been detected, and sertraline lacks anticholinergic action. These studies imply a low probability of adverse central nervous and cardiovascular effects. Sertraline is probably a weak inducer of hepatic microsomal enzyme activity. Sertraline does not affect the clearance of lithium but there may be a pharmacodynamic interaction which leads to increased tremor when the drugs are given together. No clinically relevant effects were noted in the interaction studies with digoxin, atenolol and diazepam. The pharmacokinetics and pharmacodynamics of sertraline are generally favourable. However, caution is needed when sertraline is given to patients receiving lithium or drugs with a low therapeutic ratio, such as corticosteroids, oral hypoglycaemic agents, and warfarin.
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PMID:Clinical implications of the pharmacology of sertraline. 180 26

Groups of Alpk:AP (Wistar-derived) rats were fed diets containing 0, 500, 1000 or 2500 ppm permethrin for 2 years and Swiss-derived mice were maintained for their lifetime (80% mortality) on diets containing 0, 250, 1000, or 2500 ppm permethrin. Changes of toxicological significance were confined to the top dose level of 2500 ppm permethrin in both species. Tremors and hypersensitivity to noise were noted in rats at this dose during the first 2 weeks of study but such signs were not seen in mice. Pathological examination of the central and peripheral nervous systems did not reveal abnormalities attributable to permethrin administration. The effect on mice at 2500 ppm permethrin was shown by decreased body weight gain. Liver hypertrophy, associated with increase in liver weight, microsomal enzyme activity, and proliferation of smooth endoplasmic reticulum occurred in the rat with similar but less marked changes in the mouse. This was considered to be an adaptive response of no toxicological significance. No evidence of a carcinogenic effect was seen in the rat study. In the mouse study a slight elevation in benign lung tumor incidence in males only at 2500 ppm permethrin was observed but was not considered to represent a carcinogenic effect.
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PMID:Chronic toxicity and carcinogenic evaluation of permethrin in rats and mice. 322 Feb 9

Microsomal membranes prepared from Candida lipolytica cells grown at 10 degrees C had a higher lipid content and degree of unsaturation than membranes prepared from cells grown at 25 degrees C. The specific activities of stearoyl-CoA (18:0-CoA), oleoyl-CoA (18:1-CoA), and dioleoyl phosphatidylcholine (18:1-PC) desaturases in microsomes of cells grown at either 25 or 10 degrees C showed maximum values near midlog phase, coinciding with the respective maximum absolute content of linoleic (18:2) in the microsomal preparations. The 18:1-CoA desaturase activity in 10 degrees C cells was nearly double that in 25 degrees C cells, while the 18:0-CoA and 18:1-PC desaturases had considerably lower activities in 10 degrees C cells. An increase in aeration rate (shaking speed, 70 to 130 rpm) resulted in increased proportions of 18:2 (32 to 47%, respectively) in microsomes of cells grown at 25 degrees C and in increased 18:1-CoA desaturase specific activity (83 to 140 pmol X min-1 X mg-1); however, no significant changes occurred in 18:0-CoA or 18:1-PC desaturase activities.
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PMID:Influence of temperature and growth phase on desaturase activity of the mesophilic yeast Candida lipolytica. 613 6

Organic materials were extracted from airborne particles by shaking with different solvent systems including acetone, benzene, cyclohexane, dichloromethane (DCM), methanol, a mixture of acetone and DCM and a combination of benzene, cyclohexane and methanol. The solvent-extracted materials were tested for mutagenic activity with the Ames Salmonella/microsomal assay system. Acetone- and cyclohexane-extracted materials gave the highest and lowest mutagenic activities, respectively. Re-extraction experiments confirmed that most of the mutagenic material from air particles cannot be extracted by cyclohexane. The sequential extraction with acetone followed by DCM gave a better mutagenic response than acetone alone or acetone in combination with DCM. Extraction with varying amounts of solvent indicated that 1 ml of acetone per mg of airborne particles reached the maximum recovery of mutagenic material.
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PMID:Mutagenicity studies of ambient airborne particles. I. Comparison of solvent systems. 635 84

A case of 43-year-old woman with Hashimoto's encephalopathy who experienced three relapses closely associated with the menstrual cycle is reported. In April 1992, she began to experience occasional tremors in her arms. Three months later, she experienced a generalized seizure and was transferred to our hospital. Hashimoto's thyroiditis was diagnosed on the basis of high thyroid microsomal titer and mild hypothyroidism. Neurological findings in admission included action tremor in both hands, myoclonus in all extremities, cerebellar ataxia, confusion, and hyperreflexia. Cerebrospinal fluid showed elevated protein level without pleocytosis. Electroencephalogram showed diffuse slowing and magnetic resonance imaging of brain was normal. Hashimoto's encephalopathy was diagnosed from these findings. These episodes of remission and exacerbation were observed during the admission. Her symptoms started at ovulation, worsened during the luteal phase, and improved when menstruation started. After the third relapse, she was treated with oral thyroxine for hypothyroidism and with an estrogen and progesterone combination to regulate the menstrual cycle. Her thyroid function gradually became euthyroid and she did not experience any subsequent relapses. The relation between the relapsing course and menstrual cycle suggests that the periodic alteration of gonadotrophic and/or gonadal hormones or the menstrual regulating center itself in the brain may be an important factor of pathogenetic mechanism of the disorder.
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PMID:[A case of Hashimoto's encephalopathy with a relapsing course related to menstrual cycle]. 829 82

Various diseases often occur after delivery but the systemic examinations have not been studied before. Thyroid dysfunction frequently (4.4%) occurs after delivery through an immune rebound mechanism. If postpartum women complain of the symptoms caused by thyrotoxicosis (palpitation, weight loss, increased sweating, finger tremor, fatigue) or hypothyroidism (edema, cold intolerance, hoarseness, sleepiness, fatigue), it is essential to examine thyroid hormones, thyroid stimulating hormone, anti-thyroid microsomal antibody (MCHA) and anti-TSH receptor antibody. To predict who will develop postpartum thyroid dysfunction, the measurement of MCHA during pregnancy is useful because 62% of the subjects with positive MCHA show thyroid dysfunction after delivery. The individuals at high risk of postpartum onset of Graves' thyrotoxicosis can be found early in their pregnancy by the detection of thyroid stimulating antibody (TSAb). Other autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, autoimmune hypophysitis and so on, also could develop after delivery. These findings indicate that laboratory tests in the postpartum period are essential to diagnose postpartum onset of autoimmune diseases and the measurement of autoantibodies in early pregnancy is useful for prediction of their onset in the postpartum period.
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PMID:[Postgravid health care and laboratory tests]. 855 72


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