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)

Administration of phorbol 12-myristate,13-acetate (PMA, 10 fmol-10 nmol) or phorbol 12,13-dibutyrate (PDB, 0.2-495 nmol) (i.c.v.) to mice induced: hindlimb scratching, tremor, myoclonic jerks, hyperlocomotion, clonic seizure, followed by death or recovery. CD50 values for clonic seizures for PMA and PDB were 1.0 pmol and 1.2 nmol. 4-alpha-Phorbol (68-686 nmol) was inactive. The effects of PDB (24-247 nmol) were reduced by pretreatment with staurosporine (30 nmol, i.c.v.). Protein kinase C activators are potent convulsants in vivo.
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PMID:The protein kinase C activators, phorbol 12-myristate,13-acetate and phorbol 12,13-dibutyrate, are convulsant in the pico-nanomolar range in mice. 149 48

Gamma interferon from genetic recombination (IFN) has been found to have an optimal pH at about 7. An increase in IFN concentration may cause a decrease in solution clarity. A proper selection of isotonizing agent, as well as the addition of sugars, is effective in improving the clarity. The amount of IFN adsorbed on filter membranes varies with the membrane materials: cellulose acetate adsorbs much IFN, 2-fluorovinylidene is the next, followed by polysulfon, and polycarbonate adsorbs it least of all materials tested. Stainless steel adsorbs little IFN, and the level can be lowered even more by electropolishing. Silicone coating can decrease the amount adsorbed to about 1 microgram per vial of 10 ml. The effect of pressure given to the IFN solution during filtration is negligible. Transfer of IFN solution through pipings of conventional shape may result in partial deactivation by bubbling. At around pH 7, a lower pH of IFN solution causes a higher moisture level of the freeze-dried product. Moisture levels up to 3% have no effect on IFN stability. Upon reconstitution of freeze-dried IFN by vigorous shaking with distilled water, filtration of the solution may become difficult because polymers might have been formed during vigorous shaking. The addition of L-cysteine, maltose, and human serum albumin, has been found to be as effective in preventing such unfavorable reactions. Fatty acids in human serum albumin, which is effective in stabilizing IFN, has been found to participate in preventing denaturation of human serum albumin upon freezing and freeze-drying; however, the denaturation prevention mechanisms are not clear yet.
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PMID:Freeze-drying and quality evaluation of protein drugs. 159 81

Systemic beta-blockade after single doses of ophthalmic beta-blockers (one drop in each eye) was investigated in healthy volunteers in two randomized, double-blind, crossover, placebo-controlled studies. beta-Blockade was evaluated by displacement of the bronchodilator (specific airway conductance), positive chronotropic (heart rate), and tremorogenic (finger tremor amplitude) dose-response curve for inhaled isoproterenol. In study 1, 0.5% betaxolol, 0.6% metipranolol, and 0.5% timolol were tested in 16 subjects. Compared with placebo, all beta-blockers resulted in a significant systemic beta-blockade (p greater than 0.05); the increasing order of potency was betaxolol, metipranolol, and timolol. In study 2, 2% butylamino-phenoxy-propanol-acetate (BPPA; a noncardioselective but topically oculoselective drug) and 1% timolol were investigated in 12 subjects. Placebo and BPPA showed no differences (p greater than 0.05), whereas timolol resulted in a significant beta-blockade (p less than 0.05). Topical oculoselectivity is an important aspect of drug safety of beta-blocking eyedrops. Measure of tremor is appropriate to evaluate beta 2-blockade.
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PMID:Assessment of systemic effects of different ophthalmic beta-blockers in healthy volunteers. 167 58

According to an opinion shared by many, human axillary and inguinal odour is related to short-chain fatty acids produced by gram-positive bacteria. Especially coryneform bacteria are said to produce these odiferous substances. After sampling 22 different strains of coryneform bacteria we cultured them for 48 h in a rich medium. Short-chain fatty acids were extracted afterwards by shaking the liquid medium with ether. Gas chromatography was used for detection. Only one of the tested bacteria produced propionic acid. Acetic acid, (iso)butyric acid or (iso)valeric acid could never be detected. The production of substances of the short-chain fatty acid type might, however, be a consequence of the particular substrate found under physiologic conditions by these organisms in human apocrine sweat. The theory that the metabolism of these skin bacteria necessarily produces short-chain fatty acids could not be supported. Another explanation might be that unspecific secreted enzymes of the bacteria are responsible for the production of short-chain fatty acids by a cleavage of skin surface lipids.
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PMID:Do cutaneous coryneform bacteria produce short-chain fatty acids in vitro? 190 53

As a possible preventive measure for brain dysfunction in Menkes disease, prenatal treatment by maternal administration of zinc, vitamin E and copper was examined in brindled mutant mice. During pregnancy and lactation, female heterozygous mice received 20 ppm zinc or 0.004% alpha-tocopherol acetate (vitamin E) throughout and 6 ppm copper from gestational day 13 in the drinking fluid, ad libitum. The maternal administration of zinc and vitamin E, as antioxidants, or copper resulted in decreased fetal and neonatal death of offspring, especially those of hemizygous males, as compared with the administration of water only. When offspring did not grow, maternal abnormal movements, which comprised rotatory movements of high speed with tremor and ataxia, were frequently observed. In the heterozygotes with abnormal movements, the level of lipid peroxidation in cerebrum and the concentration of copper in kidney were much higher than those in the heterozygotes with normal movement. Morphologically, in cerebellum of the heterozygotes with abnormal movements, the loss of Purkinje cells, abundance of lipofuscin granules and abnormal mitochondria or degenerative bodies of high electron density were frequently observed, as compared with heterozygotes with normal movement. These findings suggest that the development of hemizygous male mice may be influenced by both copper and oxygen radical metabolism.
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PMID:Abnormal movements in brindled mutant mouse heterozygotes: as related to the development of their offspring--biochemical and morphological studies. 216 11

The hypothesis that placental secretion of progesterone (P4) and ovine placental lactogen (oPL) are controlled through different mechanisms was tested. Placental tissue was obtained at days 133-138 of pregnancy, and explant incubations were established using 200 mg tissue per flask in 5 ml O2-saturated DMEM containing 24 mM HEPES and lacking phenol red (pH 7.4). Following a 30-min preincubation, and a 15-min control period, test substances were added and incubations continued, with periodic gassing, for 4 h at 37 degrees C in a shaking water bath. Dopamine (DA), norepinephrine (NE) and epinephrine significantly stimulated P4 production (P less than 0.05). The enhancement of placental P4 production was mimicked by the addition of 8-bromo-cyclic adenosine monophosphate and forskolin (P less than 0.05). The response to catecholamines was abolished by the addition of propranolol (P less than 0.05) but not by phentolamine (P greater than 0.05). Inclusion of a membrane-permeant substrate for P4 synthesis, 25-hydroxycholesterol, increased basal (P less than 0.05) but did not enhance agonist-induced P4 production (P greater than 0.05). High performance liquid chromatographic analysis of placental tissue demonstrated the presence of DA (80.8 +/- 7.07 pg/mg) and NE (48.8 +/- 5.77 pg/mg), as well as catecholamine metabolites. Addition of 1,2-dioctanoyl-sn-glycerol (DAG) or phorbol 12-myristate-13-acetate (PMA) enhanced oPL secretion (P less than 0.05) without affecting P4 production. The response to DAG and PMA, representing the release of considerably more oPL than can be detected by extracting the tissue, was not influenced by treatment with cycloheximide (P greater than 0.05) indicating that secretion of preformed oPL is regulated by the protein kinase C pathway. These results support the hypothesis that the secretion of oPL and the production of P4 are controlled by different mechanisms.
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PMID:Differential control of placental lactogen release and progesterone production by ovine placental tissue in vitro. 223 15

Sibling cases of familial vitamin E deficiency accompanied by ataxia, polyneuropathy and mental retardation were reported. Case 1 was a 37-year-old male who developed progressive gait disturbance, deformity of the feet and head tremor from childhood, after normal delivery and development of early childhood. On physical examination, he had cataract, high arched palate and pes cavus. Neurological examination revealed mental retardation (WAIS 68), scanning speech, muscular atrophy of the face and extremities with predominance in the lower limbs, absent Achilles tendon reflex, disturbance of superficial and deep sensation predominant in distal limbs, and marked gait ataxia. Ataxia was both cerebellar and sensory in nature. Laboratory data of the blood showed no significant abnormalities including blood glucose and vitamin B12 except a markedly low level of serum vitamin E. The brain CT scan revealed severe cerebellar atrophy and marked dilatation of the cisterna magna and the subarachnoid space around the cerebellum. Motor nerve conduction velocity in the leg was decreased. Biopsy specimen from the quadriceps muscle showed neurogenic atrophy. Sural nerve biopsy revealed decrease in large myelinated fibers with axonal degeneration and regeneration. Oral administration of alpha-tocopherol acetate, 600 mg per day, diminished ataxia significantly. Based on lysosomal enzyme activity in leukocytes, clinical and laboratory examination, lipidosis or spinocerebellar degeneration was excluded. Chronic lipid malabsorption or beta lipoprotein deficiency which can cause decrease in vitamin E absorption, was not recognized. On oral loading with 2 g of alpha-tocopherol acetate, the decrease rate of serum vitamin E was normal. Consequently the low vitamin E was considered to have resulted from selective impairment of vitamin E absorption.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Familial idiopathic vitamin E deficiency associated with cerebellar atrophy]. 226 7

In 1988 the fourth Joint National Committee (JNC IV) issued new guidelines for the detection, evaluation, and treatment of hypertension. Pharmacologic along with nonpharmacologic therapy is indicated for hypertensive patients whose diastolic blood pressures average greater than or equal to 95 mmHg over a period of time and for patients who have a diastolic blood pressure of 90 mmHg to 94 mmHg with evidence of target organ disease and/or other major risk factors. In the absence of target organ disease and/or other major risk factors, a trial of nonpharmacologic treatment is recommended for patients with a diastolic blood pressure of 90 mmHg to 94 mmHg. The JNC IV report recommends initiating pharmacologic treatment with any one of the following classes of drugs: diuretics, beta blockers, calcium channel blockers, or ACE inhibitors. In general, diuretics and calcium channel blockers are especially indicated for elderly and black patients and beta blockers and ACE inhibitors for young and white patients, but there are many exceptions. In selecting the appropriate step-one agent for a given patient, the therapeutic "two-for-one" concept is emphasized whereby one antihypertensive drug may also be beneficial for a coexisting condition. Examples are: diuretics or ACE inhibitors in congestive heart failure; calcium channel blocking drugs or beta blockers in angina pectoris or paroxysmal supraventricular tachycardia; and beta blockers for migraine headache or senile tremor.
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PMID:Mild hypertension: critical analysis of different therapeutic approaches. 266 23

A method was developed for susceptibility testing with spherule-endospore-phase Coccidioides immitis by using a microtiter format. Isolated endospores were used to inoculate wells containing modified Converse medium with various concentrations of azole or nikkomycin antifungal substances which then were sealed with an acetate film. The plate was incubated at 37 degrees C with shaking for 96 h, after which the control wells had visible turbidity and endpoints were discernible. Microscopic examination revealed that both control and treatment wells maintained cells predominantly in the spherule-endospore phase of growth.
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PMID:Microtiter method for MIC testing with spherule-endospore-phase Coccidioides immitis. 323 Jan 42

Methods have been developed for the removal of retinol from human plasma retinol-binding protein (RBP), so as to form the retinol-free apoprotein, and for the recombination of apo-RBP with retinol to again form the holoprotein. Retinol is removed from RBP by gently shaking a solution of RBP with heptane under controlled conditions. During the shaking, retinol is gradually extracted from the RBP and into the heptane phase. The reassociation of apo-RBP with retinol is achieved by exposing a solution of apo-RBP to Celite coated with a thin film of retinol, followed by isolation of the RBP by gel filtration on Sephadex G-100. This procedure results in the recombination of apo-RBP with an amount of retinol almost identical with that previously removed by extraction. The two-phase extraction procedure was used to explore some of the factors which affect the interaction of retinol with RBP. The retinol-RBP complex was most stable in the lower portion of the pH range 5.6 to 10. The rate of removal of retinol from the RBP-prealbumin complex (the form in which RBP normally circulates in plasma) was markedly less than the rate of its removal from RBP alone. The interaction of retinol with RBP appears to be stabilized by the formation of the RBP-prealbumin complex. The recombination procedure was employed to examine the specificity of the binding of retinol to RBP, by determining whether compounds other than all-trans-retinol would effectively bind to apo-RBP. Apo-RBP did not bind cholesterol, but displayed a slight affinity for phytol. The affinity of RBP for beta-carotene was minimal, whereas both retinyl acetate and retinal were bound about one-third as effectively as all-trans-retinol. In contrast, retinoic acid bound to apo-RBP almost as effectively as did retinol. Each of two isomers of retinol, 13-cis and 11,13-di-cis-retinol, bound to apo-RBP to some extent. The 13-cis isomer appeared to bind somewhat less effectively than did the 11,13-di-cis isomer. The binding of retinol to RBP is highly but not absolutely specific.
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PMID:Extraction and recombination studies of the interaction of retinol with human plasma retinol-binding protein. 433 54


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