Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0231530 (twitching)
 2,043 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The basis for the comparative toxicity to parasitic nematodes and their mammalian hosts of the anthelmintics levamisole, pyrantel, and several related analogs on somatic nicotinic cholinergic transmission was examined. Measurements of muscle contractility and membrane potential were made using the isolated hemidiaphragm preparation of the rat and isolated axial muscle segments from the gastrointestinal nematode Haemonchus contortus. Pyrantel caused a dose- and time-dependent reduction of nerve-evoked twitches in the rat diaphragm. These effects were exacerbated by increasing the frequency of phrenic nerve stimulation from 0.5 to 50 Hz. Levamisole was less potent and the onset of its effects slower than pyrantel. Neither drug significantly affected twitches evoked from d-tubocurarine-blocked preparations following direct stimulation of the diaphragm. Twitch depression was reversed by washing, but not by application of physostigmine. In H. contortus, both drugs stimulated a spastic contraction and sustained paralysis in the concentration range of 1-10 microM, mimicking the action of nicotine. Neither nicotinic nor muscarinic antagonists blocked these responses. Moreover, neither nicotinic antagonists nor muscarinic agonists or antagonists had any independent effect on contractility of the parasite muscle segments. The blocking actions of levamisole and pyrantel on H. contortus axial muscle were associated with membrane depolarization at the muscle. In the rat-isolated hemidiaphragm, pyrantel, but not levamisole, depolarized end-plate regions of muscle fibers. d-Tubocurarine blocked the depolarizing action of pyrantel but not levamisole on rat-isolated hemidiaphragm. In axial muscle fibers of H. contortus, d-tubocurarine did not block the depolarizing actions of pyrantel, levamisole, or nicotine. 3-Bromo and 3-amino derivatives of levamisole were equipotent with and mimicked the actions of the parent compound on H. contortus axial muscle contractility. In the rat preparation, the 3-bromo derivative was more potent than levamisole or 3-amino-levamisole. 3-Amino-levamisole, but not 3-bromo-levamisole, depolarized muscle end-plate membrane in the rat diaphragm. Results of the present study are consistent with the following conclusions: (a) both levamisole and pyrantel block contractility of nematode axial muscle by causing sustained depolarization of the muscle membrane; (b) both drugs block neuromuscular transmission at the mammalian neuromuscular junction but their mechanisms appear to differ; (c) levamisole and pyrantel are more potent blockers of neuromuscular transmission in H. contortus than in the rat. These results suggest that potentially important pharmacological differences exist between nematode and mammalian somatic nicotinic receptors.
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PMID:Comparative neuromuscular blocking actions of levamisole and pyrantel-type anthelmintics on rat and gastrointestinal nematode somatic muscle. 131 Jan 65

Neuromuscular blocking and circulatory actions of pipecuronium bromide (PPB) were evaluated in patients under halothane-nitrous oxide-oxygen anesthesia in comparison with those of pancuronium bromide (PCB) in a multi-center cooperative study. Twitch tension of the adductor pollicis muscle was elicited by supramaximal stimulation of the ulnar nerve every 10 seconds. The study was performed according to the following 4 steps and the results were obtained. 1) Cumulative administration of 0.01 mg.kg-1 of PPB or PCB resulted in the potency ratio of 1.3:1.0 and the dose response curves of the two agents paralleled with each other. 2) With PPB 0.05 mg.kg-1 or 0.1 mg.kg-1, almost 100% block of the twitch was obtained. Both duration of action and the recovery time were shorter with 0.05 mg.kg-1 group. 3) After the first dose of 0.04 mg.kg-1 when the twitch recovered to 25% of the initial height 0.02 mg.kg-1 was given and this was repeated. Intervals between the doses showed large individual differences and no significant change was observed with repeated doses. 4) Safety of the drug. No significant change in heart rate or blood pressure was observed with PPB but with PCB a significant increase in heart rate was observed. The study revealed that PPB is slightly more potent than PCB and the duration of action is longer, but it has no untoward cardiovascular action in man under halothane anesthesia.
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PMID:[Evaluation of the action of pipecuronium bromide in patients under halothane anesthesia--a comparison with pancuronium bromide regarding their neuromuscular blocking and cardiovascular effects]. 216 Oct 58

The muscle-relaxation reactions of Ca-antagonist (nifedipine) pretreated patients and a control group (5 in each group) were observed after administration of vecuronium bromide using the "priming principle." Twitch depression induced by the "priming dose" of vecuronium bromide (20 micrograms/kg body weight and T4/T1 ratio in the Ca-antagonist-treated patients (35 +/- 13% and 0.42 +/- 0.14%, respectively), was significantly different (P less than 0.01) when compared with the control group (1.2 +/- 2.7% and 0.75 +/- 0.15%). Similarly, the onset time to maximum blockade after the intubating dose of vecuronium bromide (60 micrograms/kg body wt.) was significantly shorter in the nifedipine group (40 +/- 21 s) when compared with the controls (100 +/- 17 s). The duration of the effect observed clinically (until 25% recovery) in the nifedipine group 32.9 +/- 7.3 min versus 25 +/- 8.15 min was enhanced; however, the difference between the treated group and the control group was not significant.
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PMID:[Nifedipine and vecuronium bromide. How does a patient treated with calcium antagonists react to nondepolarizing muscle relaxants? Brief scientific communication]. 286 76

1. Single barnacle muscle fibres from Megabalanus psittacus (Darwin) were internally perfused with a number of K salt solutions (200 mM) which were made isotonic to the barnacle saline with sucrose.2. 200 mM-K acetate solution, in general, was found to be more effective than other solutions of K salts in generating and maintaining stable resting membrane potential of -56.0 +/- 0.7 mV (all potentials are referred to the external solutions as ground). The various K salts, on the basis of the magnitude of the resting potential they generated in the muscle fibres, followed the sequence, acetate > isethionate > aspartate > glutamate > fluoride > monohydrogen phosphate > succinate > citrate > sulphate > oxalate > iodobenzoate > ferrocyanide > chlorate > nitrate > chloride > thiocyanate > iodide > bromide > cyanide.3. The resting potential in muscle fibres perfused with solutions of acetate, aspartate and glutamate increased linearly with the logarithm of the K concentration (slope = 30.4 mV for K acetate and 27.4 for K aspartate and glutamate) when the ionic strength of the solutions was progressively increased from 50 to 650 mM. On the other hand, similar increase of ionic strength beyond 200 mM of solutions of K isethionate, fluoride, monohydrogen phosphate, succinate and citrate depolarized the muscle fibres.4. Perfusion of acetate solutions of other alkali metal ions gave low values for the resting potential and followed the sequence K > Na > Rb > Li > Cs. Also NH(4) and Tris ions gave low values for the resting potential which underwent oscillations associated with the twitching of the fibre and occasionally became positive in value (action potential).5. Addition of tetraethyl ammonium chloride (TEA-Cl), 20-100 mM, to K acetate solutions (200 mM) depolarized the fibre membrane and the consequent reduction of resting potential varied linearly with the logarithm of TEA concentration.6. Replacement of chloride ion by acetate or isethionate in the external solution did not change significantly the resting potential although the values were consistently lower by about 2 mV.7. Complete elimination of K in the external solution and reduction of its ionic strength using sucrose depolarized the muscle fibres by about 27 mV when Na was changed from 475 to 1 mM. Under these conditions, external solutions completely in acetate form gave resting potentials which were more positive than those observed in completely chloride solutions by 6-8 mV.8. Replacement of Na by Li, Tris, choline, tetramethyl or tetraethyl ammonium ion in the external solution made the values of the resting potential more positive (depolarization). Similarly increasing the concentration of K (or Cs or Rb in place of K) by correspondingly decreasing the concentration of Na in the outside solution depolarized the fibres and the resting potential became zero at a concentration of 280 mM (or 308 or 1500 mM for Rb or Cs, respectively) on extrapolation.
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PMID:Effects of anions and cations on the resting membrane potential of internally perfused barnacle muscle fibres. 475 74

CM-Sephadex C-25 column chromatography profile of Indian cobra (Naja naja) venom from eastern region showed a distinct and a dominant phospholipase peak, peak-10, while it was not seen in either southern or western venom samples. Peak-10 was subjected to CM-Sephadex C-25 and Sephadex G-50 column chromatography to isolate NN-X-PLA(2). NN-X-PLA(2) is a single chain protein with the relative molecular weight of 10kDa by SDS-PAGE. It was toxic to mice with an LD(50) value 0.098 mg/kg body weight (i.p.) and the mice exhibited acute neurotoxic symptoms. Upon indirect stimulation, it inhibited the twitching of frog's gastrocnemius muscle in a dose dependent manner. NN-X-PLA(2) was weakly anticoagulant and devoid of cytotoxicity, myotoxicity, hemorrhage, edema inducing, and directlytic activities and effects on platelet aggregation process. Upon chemical modification independently with p-bromophenacyl bromide and acetic anhydride, NN-X-PLA(2) lost both enzymatic and toxic properties.
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PMID:A neurotoxic phospholipase A2 variant: isolation and characterization from eastern regional Indian cobra (Naja naja) venom. 1657 78

To determine a management strategy for the epilepsy in children with bilateral cortical malformations, clinical data of 23 patients (age, 3-23 years, M:F=7:16) were retrospectively reviewed. Among these patients, 15 were bedridden and 16 were profoundly retarded and could not even smile. The patients were categorized into the following five groups based on the findings of neuroimaging, seizure types, and electroencephalographic patterns. Group 1: Diffuse cortical malformation with epileptic spasms and secondarily generalized tonic seizures, group 2: diffuse cortical malformation with erratic twitches, group 3: bilaterally extended but not diffuse cortical malformations, group 4: bilateral polymicrogyria with persistent epileptic spasms (Aicardi syndrome), and group 5: bilateral cortical malformation with drop attacks (subcortical band heterotopia and congenital bilateral perisylvian syndrome). Eleven patients suffered from infantile spasms; adrenocorticotropic hormone was effective in group 1 but ineffective in group 4. Treatment of tonic seizures in groups 1-3 and erratic twitching in group 3 with phenobarbital, zonisamide and potassium bromide was beneficial. Epileptic spasms and tonic seizures were prominent in group 4 and were refractory to medical treatment, except that zonisamide, clobazam, and a ketogenic diet were partially or transiently effective. Complex partial and astatic/atonic seizures in group 5 were refractory to medications other than that carbamazepine and clobazam provided limited benefits. Total callosotomy resulted in better seizure control for three patients in group 5, and functional hemispherectomy was effective for one patient in group 4. These results provide the basis for the appropriate choice of medical and surgical treatment for managing bilateral, widespread cortical malformations.
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PMID:Treatment of epilepsy in severely disabled children with bilateral brain malformations. 1903 89

A girl with mild psychomotor developmental delay developed right or left hemiclonic convulsion at 10months of age. One month later, clusters of hemiclonic or bilateral tonic seizures with eyelid twitching emerged, resulting in status epilepticus. Treatment with phenobarbital and potassium bromide completely terminated the seizures within 10days. Ictal electroencephalography revealed a migrating focus of rhythmic 3-4Hz waves from the right temporal to right frontal regions and then to the left frontal regions. Genetic analysis was conducted based on the characteristic facial appearance of the patient, which identified a 2.1-Mb terminal deletion on chromosome 4p. This is the first case of Wolf-Hirschhorn syndrome complicated by epilepsy with migrating partial seizures.
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PMID:Successful treatment of migrating partial seizures in Wolf-Hirschhorn syndrome with bromide. 2837 51