Serum Concentrations Of Enzymes Research Articles

Drugs, coma, and myoglobinuria.

Myoglobinuria was proved in four patients in coma after drug ingestion or injection and was suspected in four others because of the very high serum enzyme concentrations, including creatine phosphokinase, and renal insufficiency. The variety of drugs used suggests that this is not a direct effect of specific drugs but is due to several effects of coma. Pressure upon dependent muscles in immobile individuals is probably primarily responsible, but ischemia, anoxia, hypotension, hypothermia, and acidosis contribute. In five patients there was residual evidence of pressure or traction injury to ulnar, peroneal, and sciatic nerves or to the brachial plexus. The syndrome can be recognized in comatose individuals if dependent limbs are swollen and indurated. In any comatose patient, routine determination of serum enzymes and evaluation of the urine for myoglobin would permit early recognition of this syndrome; forced diuresis might decrease the incidence of renal damage, the most threatening complication of myoglobinuria.

The effect of enzyme concentration and serum concentration on initial rate measurements of serum enzymes.

The correlation between measured enzyme activity and enzyme concentration has been tested for aspartate aminotransferase and creatine kinase. Some conditions where this is non-linear have been described. The correlation was independent of the source of the enzyme: serum enzymes or purified enzyme solutions. By isotope technique a back reaction has been demonstrated for aspartate aminotransferase. Difficulty of measuring true initial reaction rates in manual routine methods has been demonstrated. When methods with a non-linear correlation curve have to be used, the estimation of serum concentration of enzyme must be based on a correlation curve between enzyme concentration and enzyme activity.

Acid and alkaline phosphatase activity in the liver of brown and rainbow trout.

THE susceptibility of the rainbow trout to liver cell tumours following the administration of aflatoxin is well documented1–3, as is the refractory behaviour of brown trout4. The different responses of these two closely related species probably indicate variations in basic metabolism. We decided to investigate histochemically some enzyme systems of the livers from brown, and rainbow trout. Although histologically these livers were similar, the activity and distribution of the acid and alkaline phosphatases showed distinct variations. The activity of alkaline phosphatase was greater in the brown than in the rainbow trout (Fig. 1a and b), while acid phosphatase was more active in the rainbow than in the brown trout (Fig. 1c and d). The distribution of the phosphatases varies throughout the fish kingdom5,6, and the significance of the present findings is uncertain. The metabolic differences in these two species may begin to explain the inverse response to the induction of liver cell tumours. A significant loss of alkaline phosphatase from the livers of ducklings fed aflatoxin has already been reported7, as has the elevation of various serum enzyme concentrations, including alkaline phosphate, in the pig8. We are extending histochemical studies on the effect of aflatoxin at various doses on the two species of trout, and hope to elucidate the different effects, if any, on the enzyme systems in the livers with special reference to the phosphatases.

Cellular immune response during rejection of a liver transplant in man

THE diagnosis of rejection of transplanted organs can be difficult. Function of a renal transplant can be similarly affected by ischaemia, obstruction and rejection. Anorexia, and malaise may be the earliest signs of rejection of a heart transplant1 but are clearly difficult to interpret, and a rise in serum enzyme concentrations may occur too late to be of practical value. Rejection of a liver transplant may be accompanied by a cholestatic jaundice2, but a drug reaction, particularly to azathioprine used in immuno-suppressive therapy, serum hepatitis and extrahepatic-obstruction, can all produce the same picture. First set, rejection of transplanted organs seems to be mediated by cellular immune mechanisms rather than circulating; antibodies3. If alterations in the cellular immune response could be detected in vitro the diagnosis might be made with more certainty and treatment instituted more, rapidly.

Cellular immune response during rejection of a liver transplant in man.

THE diagnosis of rejection of transplanted organs can be difficult. Function of a renal transplant can be similarly affected by ischaemia, obstruction and rejection. Anorexia, and malaise may be the earliest signs of rejection of a heart transplant1 but are clearly difficult to interpret, and a rise in serum enzyme concentrations may occur too late to be of practical value. Rejection of a liver transplant may be accompanied by a cholestatic jaundice2, but a drug reaction, particularly to azathioprine used in immuno-suppressive therapy, serum hepatitis and extrahepatic-obstruction, can all produce the same picture. First set, rejection of transplanted organs seems to be mediated by cellular immune mechanisms rather than circulating; antibodies3. If alterations in the cellular immune response could be detected in vitro the diagnosis might be made with more certainty and treatment instituted more, rapidly.

Development of hepatic lesions in calves fed with ragwort ( Senecio jacobea)

The sequential changes in the livers of 5 calves fed several levels of ragwort ( Senecio jacobea) in their diet were studied by serial biopsy. Parenchymal megalocytosis, hepatic fibrosis and veno-occlusive lesions developed in all the calves. One calf given 1·2 lb. ragwort per day, showed centrilobular hepatic necrosis. Histochemical enzyme studies showed an early and progressive fall in alkaline phosphatase activity in the parenchymal cells, and a late reduction in succinic dehydrogenase and cytochrome oxidase activity. Non-specific esterase activity persisted in the megalocytes at a high level. There was little if any relationship between the progress of the liver changes and the pattern of changes in the serum enzyme concentration. The changes in enzymes and other constituents of serum are reported in detail in a subsequent paper.

Lactic dehydrogenase isoenzymes after electroshock treatment of cardiac arrhythmias

The serum enzyme concentrations measured in this study can be used to differentiate injury of heart muscle, skeletal muscle, lung and liver tissue. Serum lactic dehydrogenase (SLDH) isoenzymes, total SLDH, serum glutamic oxalacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) were measured in 29 patients on the day before, the day of but before and the three days after treatment of atrial fibrillation by D.C. electroshock. All patients selected were men aged 50 or older with some evidence of atherosclerotic heart disease. Identical enzyme measurements were also made concurrently in a control group of 19 untreated subjects who were matched to the treated subjects by sex, age and disease. The SGOT levels increased significantly after D.C. electroshock in a minority of patients. These changes are statistically significant for the group as a whole ( p values < 0.02 and < 0.05). No significant changes occurred in SLDH alpha 1 and 2 and beta isoenzymes, in total SLDH, or in SGPT. No evidence was found that the enzyme changes observed after D.C. electroshock are due to myocardial injury. The statistically significant rise in SGOT appears to originate from tissues other than those of the heart. Reasons are presented for implicating the skeletal muscle of the chest wall as the source of these changes in serum enzyme concentrations.

Serum changes following the feeding of ragwort ( Senecio jacobea) to calves

Five calves were fed ragwort incorporated into the feed at levels of 1·2, 0·8 and 0·4 lb. per day. All the calves died or were killed in a moribund state with severe hepatic lesions. None of them showed a significant alteration in total serum protein concentration. Only 2 calves, one that received 0·8 lb. and one that received 0·4 lb. ragwort per day, showed a fall in serum albumin concentration and a rise in serum globulin. The 3 calves which received the higher doses of ragwort developed a terminal hyperbilirubinaemia. All calves showed an increase in the concentration of the 4 enzymes, G.O.T., G.D., S.D. and O.C.T., in the serum. In the calves dosed at the 2 higher rates, the rises were concurrent. In the 2 calves receiving smaller amounts of ragwort, different enzymes leaked into the serum at different times after the commencement of ragwort feeding. In all animals, structural changes in the liver were minimal at the time of initial enzyme release whereas immediately before death, at which time there were marked liver lesions, serum enzyme concentration was in many instances within the normal range.

Clinical chemistry of staphylococcal enterotoxin poisoning in monkeys.

Clinical chemistry values were examined in 90 monkeys administered a purified preparation of staphylococcal enterotoxin, type B, intravenously. These studies showed an early release of epinephrine accompanied by a mild increase in blood glucose. This was followed by progressively developing prolonged hypoglycemia. An early increase in bloodurea nitrogen occurred, presumably as a result of both prerenal azotemia and functional renal failure seen in association with the observed hypotension. Serum protein, Ca, and Cl concentrations decreased with time. Pi levels increased, whereas Na and K concentrations in serum remained unchanged. Serum enzyme concentrations were unchanged, with the exception of serum glutamic oxaloacetic transaminase, which rose rapidly when compared with prechallenge control observations or with values from sham-challenged monkeys. These changes were statistically significant. These results suggested that enterotoxin administered intravenously produced early change in glucose metabolism, possibly related initially to catecholamine release and later to increased utilization of glucose and metabolic acidosis. Other findings were compatible with tissue breakdown at as yet undetermined locations and with loss of endothelial membrane integrity, as evidenced by loss of protein from the vascular space.

Clinical Chemistry of Staphylococcal Enterotoxin Poisoning in Monkeys

Clinical chemistry values were examined in 90 monkeys administered a purified preparation of staphylococcal enterotoxin, type B, intravenously. These studies showed an early release of epinephrine accompanied by a mild increase in blood glucose. This was followed by progressively developing prolonged hypoglycemia. An early increase in bloodurea nitrogen occurred, presumably as a result of both prerenal azotemia and functional renal failure seen in association with the observed hypotension. Serum protein, Ca, and Cl concentrations decreased with time. Pi levels increased, whereas Na and K concentrations in serum remained unchanged. Serum enzyme concentrations were unchanged, with the exception of serum glutamic oxaloacetic transaminase, which rose rapidly when compared with prechallenge control observations or with values from sham-challenged monkeys. These changes were statistically significant. These results suggested that enterotoxin administered intravenously produced early change in glucose metabolism, possibly related initially to catecholamine release and later to increased utilization of glucose and metabolic acidosis. Other findings were compatible with tissue breakdown at as yet undetermined locations and with loss of endothelial membrane integrity, as evidenced by loss of protein from the vascular space.

THE DIAGNOSTIC VALUE OF SERUM CREATINE KINASE IN NEUROMUSCULAR AND MUSCULAR DISEASE

Serum creatine kinase activity in 200 patients was studied in order to check whether this determination might be of help in differential diagnosis between primary and secondary (neurogenic) myopathies. Elevated CK values are found physiologically in children, pregnant women, and after exercise. In pathological states increased serum enzyme concentrations (probably the expression of a defect in cellular permeability) are constantly present in the Duchenne type of progressive muscular dystrophy. More variable values are encountered in other types of muscular dystrophy and in metabolic disorders like Refsum's syndrome, coproporphyria, and hypothyroidism. In states of necrosis or injury to muscle cells like in polymyositis, dermatomyositis, after burns or trauma, serum CK concentrations vary according partly to the amount of muscle mass involved. Enzyme concentrations can be markedly increased after tetany or epileptic seizures. Normal values or occasionally slightly increased values are found in neurogenic myopathies. High CK values in patients with muscular atrophies should permit the clinician to exclude the differential diagnostic group of neurogenic myopathies. As a diagnostic tool CK proved to be more reliable than transaminases or lactic dehydrogenase because of its higher muscle specificity and a slightly greater sensitivity.

Circadian variation of serum acid phosphatase in prostatic cancer

A circadian variation in total serum acid phosphatase was demonstrated in 5 patients with prostatic carcinoma using the method of Fishman and Lerner. Blood samples were drawn from a polyethylene catheter every hour for 25 hours. The cancer patients all had elevated serum enzyme concentrations and the nocturnal decrease was 25–50 per cent of the highest day-time value. The highest values were usually found from 9 A.M. to 3 P.M. and the lowest from 9 P.M. to 3 A.M. This circadian variation was entirely accounted for by variations in the prostatic (tartrate inhibitable) fraction. Orchiectomy did not obliterate the rhythmical variation. Urinary acid phosphatase did not have a circadian variation in a patient with a definite variation in serum enzyme concentration. Two normal patients did not have a readily detectable rhythm although a minor variation within the normal range would have been obscured by technical variations in the procedure which became important at low enzyme concentrations.

The hypotonic infant: A review

Summary (Table I) I. The factors concerned in maintainingnormal muscle tone have been described in detail as a background to the understanding of the possible sites of pathology which can lead to hypotonia. II. The causes of hypotonia in childrenunder 24 months of age have been discussed from the point of view of the presumed site of pathology. The classification which has evolved from this approach is as follows: A. Hypotonia due to diseases of thecentral nervous system: 1. Atonic diplegia 2. Congenital chorea and athetosis 3. Congenital cerebellar ataxia 4. Kernicterus 5. Mongolism 6. Tay-Sach's diseas B. Hypotonia due to diseases of thespinal cord: 1. Werdnig-Hoffman's disease (infantileprogressive muscular atrophy) 2. Myelopathic arthrogryposis multiplexcongenita 3. Congenital anterior poliomyelitis C. Hypotonia due to diseases of thespinal roots or peripheral nerves: 1. Acute and chronic polyneuropathy D. Hypotonia due to abnormalities of the myoneural junction: 1. Congenital myasthenia gravis 2. Neonatal (transient) myasthenia gravis E. Hypotonia due to diseases of themuscle: 1. Benign congenital hypotonia 2. Universal muscular hypoplasia 3. Congenital infantile muscular dystrophy with or without arthrogryposis multiplex congenita 4. Dystrophica myotonica 5. Central core disease 6. Rod body myopathy 7. Polymyositis 8. Glycogen storage disease III. The value of ancillary aids in thediagnosis of the etiology of hypotonia in infants has been discussed. These have included muscle biopsy, electromyography, measurement of the nerve conduction time, determination of serum enzyme concentrations, urinary creatine and creatinine excretion coefficients, and the assessment of the developmental level of the infant.

Effect of Exercise on Serum Enzyme Levels in Untrained Males

Abstract The purpose of this study was to investigate the effect of increasing the intensity of exercise on serum enzyme levels in untrained males. Subjects exercised on a treadmill at one of four inclines for 15 minutes, and serum enzyme determinations were made before and after exercise. Results showed a greater increase in mean serum enzyme levels after strenuous exercise than after either mild or moderate exercise. Variations in serum enzyme concentrations between subjects, as well as differences in the relative increases of enzymes, were shown to exist.