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Biomedical subjects

J P Colombo

Publications and source records attributed to J P Colombo.

28 records · Page 2Linked to original sources
PubMed1977

Enzyme induction and renal function in man.

1. In a previous study in rats, an increased PAH clearance was found following chronic phenobarbitone administration. These results formed the basis for the present study in which fifteen healthy male volunteers were investigated and the parameters of liver microsomal enzyme activity and renal function were measured. 2. As parameters of liver microsomal enzyme activity, the antipyrine elimination in the plasma, the gamma-glutamyl-transpeptidase and the D-glucaric excretion in the urine were measured. Endogenous creatinine clearance, 51Cr-EDTA and 125I-Hippuran clearance were determined as measurements of renal function. 3. No correlation was found between any of the parameters of microsomal enzyme activity and renal function. 4. Of the fifteen volunteers, seven having a mean antipyrine half-life of 13.3 h were given antipyrine (500 mg) daily for 3 weeks. Afterwards all measurements of liver microsomal enzyme activity and renal function were repeated. The antipyrine half-life decreased to 8.5 h, while the antipyrine clearance was increased by about 56%. gamma-glutamyl-transpeptidase and D-glucaric acid were also significantly increased, while renal function remained unchanged. 5. Therefore, an increased PAH-clearance, as found in the rat, is not obtained in man following induction of liver microsomal enzyme activity.

Adult↗
PubMed1977

Enzymes of ammonia detoxication after portacaval shunt in the rat. I. Carbamylphosphate synthetase and aspartate transcarbamylase.

At high systemic blood concentrations ammonia may be partially deviated into the pathway of pyrimidine synthesis, as has been observed in different genetic defects of the urea cycle. The portacaval shunt (PCS) rat presents an animal model to study ammonia detoxication without an underlying enzyme defect in the urea cycle. Since ammonia may induce a deviation into the pyrimidine pathway by influencing enzymatic reactions involved in this pathway, the activity of carbamylphosphate synthetase and aspartate transcarbamylase in liver as well as the excretion of orotic acid in the urine were measured in rats 10, 20 and 30 days after PCS. The results suggest that in this experimental model ammonia may be channeled into the pyrimidine pathway leading to a stimulation of the first enzymatic step and to an increased excretion of orotic acid.

Ammonia↗
PubMed1977

Enzymes of ammonia detoxication after portacaval shunt in the rat. II. Enzymes of glutamate metabolism.

Besides the synthesis of urea, ammonia detoxication at high concentrations can also be effected through enzyme reactions involved in glutamic acid metabolism. These mechanisms are also operative in extrahepatic tissues. Hyperammonemia is also found in the animal model of the portacaval shunt (PCS) rat. This model was chosen to study the activities of glutamate dehydrogenase, glutamine synthetase and glutaminase I in liver, brain and kidney 10, 20 and 30 days after PCS. In brain and kidney ammonia is detoxified mainly by the glutamate dehydrogenase and glutamine synthetase reactions whereas in the liver these enzyme reactions play a minor role.

Ammonia↗
PubMed1977

The defect of uric acid metabolism in Eck-fistula rats.

Because of the discovery of uric acid urolithiasis in rats after end-to-side portacaval anastomosis (PCA), uric acid metabolism was studied in these animals and in appropriate controls. Hyperuricemia and hyperuricosuria were observed in all experimental rats. The fraction of purine catabolites excreted in the urine as uric acid increased from an average of 4.8% to 15.3%. If 14C-uric specifically labeled at position 6 (6-14C-ua) was infused intravenously and the exhalation of 14CO2 was used to calculate a hepatic uric acid clearance, it decreased from 2.14 to 0.97 ml/min/100 gm despite a normal content of hepatic uricase activity as measured in liver homogenates. The fraction of the filtered amount of uric acid excreted in the urine increased from an average of 11% to 30%. Increased supersaturation of the urine with uric acid after PCA may be expected to contribute to the formation of uric acid urolithiasis. This investigation defines a hepatic and renal functional defect in uric acid metabolism which occurs as a result of the PCA.

Allantoin↗
PubMed1976

[The behavior of gamma-glutamyltranspeptidase and other liver enzymes in the plasma during alcohol withdrawal treatments].

90 chronic alcoholics (55 men and 35 women, aged between 20 and 60 years) were investigated to determine how alcohol withdrawal effects the pattern of enzymes in plasma and if changes in this enzyme pattern could be used as criteria for evaluation of the recovery process. Among the different enzymes tested, gamma-glutamyl-transpeptidase (GGTP) and the transamines seemed the most suitable parameters. At the beginning of the alcohol withdrawal course, 79 out of 90 patients (80%) showed elevated values of one of these enzymes in plasma. GOT was elevated in 31 (34%), GPT in 24 (23%) and GGTP in 79 (88%) of the cases. In 49 patients (54%) GGTP was the only enzyme found to be elevated. The values of GGTP were on the average higher than those of GOT and GPT. GGTP has thereforeto be regarded as the most sensitive enzyme since it was elevated in most of the patients. GGTP reacted with 6.8 times more sensitivity than GOT and 6.3 times that of GPT. After withdrawal of alcohol the three enzymes showed a decline in all 79 patients. The transaminases normalized faster than GGTP. GTP fell into the upper normal limit after only 30 days. Among the 90 alcoholics examined, 14 relapsed during the alcohol withdrawal course. After the new excess of alcohol intake, the GGTP in plasma rose immediately. Alcohol abuse was suspected in 50% of the patients due to the increase in this enzyme and was subsequently confirmed by the patients. Acute alcohol loading in normal volunteers did not lead to an increase in GGTP activity. A comparison of the histology of liver biopsy material showed that neither the transaminases nor the alkaline phosphatase and GGTP served to differentiate the various forms of alcoholic liver damage. However, GGTP represents the most sensitive enzymatic parameter for the detection of alcoholic liver disease. This enzyme is useful in evaluating the success of a course of alcohol deprivation. The decreasing values during such treatment, as well as the prompt increase after a relapse, points to the high sensitivity of this enzyme. A further argument is that in 54% of the patients elevation of GGTP only was present. Since no liver damage could be demonstrated in these patients with the aid of the other liver enzymes, the elevation of GGTP may be related to the alcohol intake through an enzyme induction mechanism such as has been demonstrated for this enzyme with certain drugs.

Adult↗
PubMed1976

Gamma-glutamyltranspeptidase in the rat liver after portacaval shunt.

Gamma-Glutamyltranspeptidase (GGTP) activity was studied in livers of rats submitted to an end-to-side portacaval shunt (PCS) and in developing animals. To correlate the evolution of the enzymatic activity measured in vitro, histochemical techniques were used to localize enzyme activity in liver tissue. The GGTP activity in the adult rats was low and amounted to 2.0 +/- 0.1 mumol/min/g. During fetal development the enzyme activity rose beginning on the 15th gestational day from 630 +/- 97 to 1,058 +/- 20 on the first postnatal day. Then the values declined and reached nearly adult values from the 10th postnatal day. After PCS the GGTP activity exhibited a three- to sixfold increase (130 +/- 69 to 371 +/- 131) as compared with unoperated adult controls (53 +/- 13). the highest levels corresponded to those observed between the 3rd and 5th postnatal day in the developing rats. The histochemistry of GTTP in the fetal and newborn liver showed a regular distribution of the enzyme as a fine deposit in the hepatocytes throughout the whole tissue. Ten days after birth the activity was low, at the same level as in the adult rat. In the period after PCS hepatocytes began to show signs of enzymatic activity at the periphery of the hepatic lobules, which subsequently spread through the whole lobules. The increase of GGTP activity after PCS equaled the activity found in fetal animals. That correlated well in both groups with the reappearance of histologically demonstrable enzyme activity in hepatocytes.

Animals↗
PubMed1975

Unsuccessful trial of gene replacement in arginase deficiency.

The Shope virus following cutaneous inoculation produces skin papillomas in rabbits and induces a virus-coded arginase in the squameous epithelium of these papillomas. The only discernible effect of the virus inoculated intravenously in rabbits and other animals was a decrease of the serum arginine concentration. Intravenous injection in 3 hyperargininemic patients, however, did not influence the underlying metabolic disease.

Amino Acid Metabolism, Inborn Errors↗
PubMed1975

Familial hyperargininaemia.

A third case of hyperargininaemia occurring in one family was studied from birth. In cord blood serum arginine concentration was only slightly raised, but arginase activity in red blood cell haemolysates was very low. In the urine on day 2 a typical cystinuria pattern was present. Arginine concentration in serum increased to 158 mumol/100 ml on the 41st day of life. Later determinations of the arginase activity in peripheral blood showed values below the sensitivity of the method. Blood ammonia was consistently high, and cystinuria was present. The enzymatic defect was further displayed by intravenous loading tests with arginine. Serum urea values were predominantly normal or near the lower limit of normal, suggesting the presence of other metabolic pathways of urea synthesis. In urine there was no excretion of guanidinosuccinic acid, while the excretion of other monosubstituted guanidine derivatives was increased, pointing to a connexion with hyperargininaemia. Owing to parental attitude, a low protein diet (1-5 g/kg) was introduced only late. The infant developed severe mental retardation, athetosis, and spasticity.

Amino Acids↗
PubMed1975

Methylmalonic acidaemia and nonketotic hyperglycinaemia. Clinical and biochemical aspects.

The clinical and metabolic data of 2 cases of methylmalonic acidaemia with propionic acidaemia are reported together with those of 3 other patients with nonketotic hyperglycinaemia. Liver enzymatic studies showed decreased activity in vitro of the glycine cleavage enzyme in one patient with methylmalonic acidaemia as well as in 2 unrelated patients with nonketotic hyperglycinaemia, while the activity of the serine hydroxymethylase enzyme was normal. Hyperammonaemia was substantiated in one patient with methylmalonic acidaemia and also in one child with nonketotic hyperglycinaemia. The activity of the enzymes of the urea cycle, determined in the liver of this nonketotic child, was normal except for a decrease of the carbamyl phosphate synthetase enzyme to 15% of normal.

Amino Acid Metabolism, Inborn Errors↗