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Biomedical subjects

A L Sherwin

Publications and source records attributed to A L Sherwin.

At least 37 records · Page 2Linked to original sources
PubMed1977

Brain isoenzyme of creatine kinase. I. Purification of rabbit enzyme and production of specific antibodies.

Creatine kinase (EC 2.7.3.2) of rabbit brain (BB) was purified to hemogeneity as judged by sedimentation velocity analysis in the ultracentrifuge. Nevertheless, the purified enzyme contained as many as seven extraneous protein species when examined by disc electrophoresis in polyacrylamide gel. The purified preparation also showed antigenic heterogeneity when it reacted in agar gel double immunodiffusion analysis with antibodies produced against it in the rooster. At least some of the extraneous proteins appeared to arise from BB during storage. Subsequently BB was purified to hemogeneity by disc electrophoresis in polyacrylamide gel. It was excised from the gel and injected repeatedly with Freund's complete adjuvant into roosters. A single immunoprecipitin line was noted in agar gel double immunodiffusion analysis when partially pure enzyme reacted with the antibodies raised to the electrophoretically pure protein. These antibodies inhibited the enzymatic activity of BB in both soluble and insoluble immune complexes. They did not, however, form immunoprecipitates with or inhibit rabbit muscle (MM) or rabbit hybrid (MB) creatine kinases. The antibodies were therefore specific for BB and did not react with MM or MB.

Animals↗
PubMed1977

Brain isoenzyme of creatine kinase. II. Species specificity of enzyme and presence of inactive form in striated muscle of rabbit and man.

Antibodies specific for the brain isoenzymes (BB) of creatine kinase were prepared by the injection of the highly purified rabbit enzyme into roosters. The antibodies were found to cross-react only partially with BB of rat, guinea pig, sheep, monkey, and man, demonstrating that these proteins are not entirely identical with respect to their antigenic sites. A greater degree of species specificity seems to exist for BB than for the muscle isoenzyme (MM) suggesting that BB may have undergone considerable evolutionary modification. Developmentally mature rabbit cardiac and skeletal muscles contained large quantites of an enzymatically inactive BB which can be detected immunochemically. It is antigenically identical with active rabbit BB but the two proteins can be separated by DEAE-cellulose chromatography. Enzymatically inactive BB is also present in human skeletal muscle. The presence of MM in muscle provides sufficient catalytic function and may have permitted the evolution of inactive BB in an additional (noncatalytic) metabolic role.

Animals↗
PubMed1977

Brain isoenzyme of creatine kinase. III. Active and inactive forms in dystrophic muscle of vitamin E-dificient rabbit.

Rabbits were fed a vitamin E-deficient diet for 7 weeks. Control rabbits, paired for weight, were pair-fed an identical diet supplemented with vitamin E. After 3 weeks the expermental animals showed a rise in serum creatin kinase activity which was attributable to the muscle isoenzyme (MM). No rise in creatine kinase activity or appearance of MM was noted in the serum of the control rabbits. Total creatine kinase activity and MM activity were reduced in the gastrocnemii of the experimental animals while the activities of the brain (BB) and hybird (MB) isoenzymes were increased. The specific activity of BB based on immunochemically determined BB protein was not different from normal in either the experimental or control group. Activation of pre-existing inactive BB is probably not the explanation for increased BB activity in the gastroncnemii of the experimental group.

Animals↗
PubMed1977

Salivary levels of anticonvulsants: a practical approach to drug monitoring.

Phenobarbital, phenytoin, carbamazepine, primidone, and ethosuximide were measured in saliva and plasma obtained simultaneoulsy from 115 patients. A method to correct for the effect of salivary pH on phenobarbital concentration of saliva was developed. Salivary concentrations of these drugs were found to be equivalent to the plasma free drug and to correlate closely with the total plasma levels. Expressed as percent of total plasma drug, the salivary (S) and plasma free (P) concentrations were: phenytoin, S 11.1 +/- 2.0 percent (mean +/- SD), P 10.1 +/- 2.4 percent (r = 0.97); carbamazepine, S 26.0 +/- 2.4 percent, P 25.9 +/- 3.4 percent (r = 0.97); phenobarbital, S 43.1 +/- 5.2 percent, P 40.8 +/- 7.9 percent (r = 0.91); primidone, S 75.4 +/- 24.9 percent, P 66.4 +/- 8.8 percent (r = 0.76). Ethosuximide was not bound by plasma proteins, and its plasma and salivary levels were equal.

Anticonvulsants↗
PubMed1977

Distribution of anticonvulsant drugs in gray and white matter of human brain.

Gray and white matter were obtained during neurosurgical therapy of focal epilepsy from 17 patients. In 10 patients, receiving only phenobarbital, the drug was uniformly distributed between gray and white matter. Phenytoin concentrations averaged 1.4-fold greater in white matter than in gray matter when expressed per gram wet weight of tissue. The gray matter/plasma ratio of phenytoin was approximately 2-fold greater than that of phenobarbital. Carbamazepine levels were also slightly greater in white matter. The data revealed wide differences between drugs in the relative concentrations in gray and white matter, which must be taken into account in any quantitative studies of anticonvulsant drug levels in the brain.

Anticonvulsants↗
PubMed1977

Anticonvulsant activity of phenobarbital and phenytoin in combination.

The anticonvulsant properties of phenobarbital and phenytoin given individually or in various combinations were determined by the maximal electroshock seizure test in rats 2 hours after subcutaneous administration. Drug concentrations in brain and plasma obtained immediately after maximal electroshock seizure were measured by gas-liquid chromatography. Total brain anticonvulsant drug concentrations required to abolish the hindlimb extensor component of maximal electroshock seizure were similar when these drugs were employed singly or in combinations. The median effective brain concentrations (EC50) were: phenobarbital, 12.2 micronmol/kg; phenytoin 12.3 micronmol/kg; and phenobarbital plus phenytoin, 14.8 micronmol/kg. Brain/plasma concentration ratios of these drugs were not affected by concomitant administration of the other agent: phenobarbital alone, 0.73; phenobarbital in the presence of phenytoin 0.77; phenytoin, 1.21; and phenytoin in the presence of phenobarbital, 1.22. Brain and plasma concentrations of phenytoin relative to the dose employed were significantly higher (P less than .001) when phenobarbital was administered concurrently than when phenytoin was given alone. This resulted in an apparent potentiation of anticonvulsant activity at 2 hours when these drugs were administered simultaneously. The anticonvulsant activity of the two combinations could be accounted for by the sum of the concentrations of the individual drugs in brain.

Animals↗
PubMed1976

Correlation between red cell and free plasma phenytoin levels in renal disease.

Free phenytoin levels were determined in a group of patients with renal disease treated by hemodialysis or transplantation and in epileptic patients who were otherwise healthy. A highly significant correlation was observed between free drug levels and the phenytoin content of red blood cells in both groups. Considerable fluctuation in free phenytoin levels was observed during long-term maintenance hemodialysis. After transplantation, the degree of abnormality in plasma protein binding was not related to the functional adequacy of the cadaveric allografts. Free phenytoin levels must be monitored in patients with renal disease.

Adult↗
PubMed1975

Biochemical observations following administration of taurine to patients with epilepsy.

Amino acid analysis of plasma and urine obtained from 12 patients with epilepsy indicated that the plasma concentrations of taurine and glutamic acid were much higher than might have been expected. Glutamic acid in urine was also increased in these patients. Oral administration of taurine did not appreciably affect the levels of amino acids in plasma or urine with the exception of that of glutamic acid. In patients with an abnormal plasma concentration of glutamic acid, the administration of taurine caused glutamic acid levels to change in the direction of normal values along with a decrease in the urinary excretion of this amino acid. This action of taurine was independent of either its initial or final plasma concentration. Amino acid concentrations in the CSF were within normal range and were not influenced by taurine administration. The selective elevation of both taurine and glutamic acid in the plasma, combined with previous findings of a deficiency of these same amino acids in human and experimental epileptogenic brain, implies that some patients with epilepsy may suffer from an aberration in taurine and glutamic acid metabolism. Taurine administration appears to partially correct these biochemical abnormalities. Theoretically, such normalization of the amino acid profile in epileptogenic brain may be beneficial, but clinical signs of improvement may only become apparent after a long delay. The present study was designed to determine only the biochemical parameters implicated in taurine administration and no definite conclusions can be drawn as to the clinical efficacy of the amino acid in epilepsy. However, this study suggests that in future clinical trials investigating the potential use of taurine as an antiepileptic agent, the oral dose of taurine should not exceed 1.0 g/day and optimal doses may be as low as 0.1-0.5 g/day. In one patient who received 2.0-2.5 g of taurine/day for 2 weeks, a generalized amino aciduria occurred.

Adolescent↗
PubMed1975

Response of generalized penicillin epilepsy in the cat to ethosuximide and diphenylhydantoin.

The effects of ethosuximide and diphenylhydantoin sodium on feline generalized penicillin epilepsy, a model of human generalized corticoreticular (centreccephalic) epilepsy, were significantly reduced following administration of ethosuximide with plasma levels of 60 mug per milliliter, and there was a linear correlation between the plasma level and antiephilepileptic effect (p less than 0.01). Diphenylhydantoin produced a lesser reduction in epileptic activity, and there was no correlation between the plasma level and effect. Four cats that received both drugs successively responded well to ethosuximide, while only two responded to diphenylhdantoin. The good response to ethosuximide is in accord with clinical experience in human generalized corticoreticular epilepsy.

Animals↗