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Biomedical subjects

J P Colombo

Publications and source records attributed to J P Colombo.

At least 55 records · Page 3Linked to original sources
PubMed1991

[Therapy of hyperammonemia in carbamyl phosphate synthase deficiency with peritoneal dialysis and venovenous hemofiltration].

Inborn errors of metabolism with hyperammonaemia cause emergency situations with unconsciousness, convulsion, hyperpnoea and hyperpyrexia. Therefore hyperammonaemia has to be treated immediately after diagnosis to avoid irreversible damage. Two newborns with carbamylphosphates synthetase deficiency are described. Both, continuous peritoneal dialysis and venovenous haemofiltration have proved to be effective methods to reduce serum ammonia concentration to values of less than 300 mu/l. Because of the severity of the enzyme defect in both cases, (carbamylphosphate synthetase was not detectable in liver tissue), treatment finally had to be stopped, and both patients died.

Amino Acid Metabolism, Inborn Errors↗
PubMed1991

[Macrocephaly and dystonic cerebral palsy in a child with type I glutaric aciduria].

In a male infant with macrocephaly and dystonic cerebral palsy glutaric aciduria type I was detected by analysis of urine for organic acids. Glutaric aciduria type I is an inherited metabolic disorder of organic acids due to a defect of glutaryl-CoA-dehydrogenase in the intermediate metabolic step of lysine and tryptophan degradation. In the urine glutaric acid is usually accompanied by 3-hydroxy-glutaric acid in abnormal quantities. The enzyme defect in our patient was proved in cultured fibroblasts. In the cerebral computer tomography marked atrophy of bilateral frontotemporal regions could be demonstrated. The amount of urinary glutarat excretion decreased after protein but especially after lysine and tryptophan restriction in the diet. The administration of carnitine improved carnitine levels in blood and urine. Although the progression of neurological impairment could be stopped, dystonia and dyskinesis remained nearly unaltered. In spite of severe motor retardation, recognition and vocalisation were established. In the two year old patient mental retardation is relatively mild comparing with motor retardation. The administration of 100 or 200 mg Riboflavin/day was stopped, as it did not alter clinical symptoms or excretion of glutarat. Baclofen, an analogue of gamma-amino-butyric acid, was orally given (2 mg/kg/day) and improved dystonia, but did not influence organic aciduria. The neurological manifestations may be due in part to inhibition of neuronal glutamat decarboxylase by glutaric acid with decreased gamma-amino-butyric acid biosynthesis. The characteristic clinical symptoms with macrocephaly and dystonia and the very typical pattern of organic acids in urine are a challenge for rapid diagnosis and therapy.

Amino Acid Metabolism, Inborn Errors↗
PubMed1990

The regulation of N-acetylglutamate synthetase in rat liver by protein intake.

Urea cycle enzymes are subjected to regulation by dietary proteins. We have shown that this is also the case for N-acetylglutamate synthetase (EC 2.3.1.1.) (NAGS). Four different groups (n = 7) of male Wistar rats received either a low protein (8.7%) or a high (32% and 51%) protein diet and a control diet of 17% protein. The NAGS-activity in the liver, assayed after 15 days of feeding the different diets, increased from 25 +/- 7 (controls, 17% protein) to 31 +/- 5 (32% protein) and to 52 +/- 17 (51% protein) nmoles.min-1.g-1 wet weight. It decreased in the group with low protein diet (8.7%) to 5 +/- 3. The ratio of the arginine stimulated to the unstimulated enzyme activity remained constant over the range of protein intake. Similar changes were observed for carbamylphosphate synthetase, ornithine carbamyltransferase and arginase. As it is known for these enzymes adaptive mechanisms in relation to variations in dietary protein consumption also could be demonstrated for the enzyme NAGS.

Acetyltransferases↗
PubMed1990

Brain development: 1H magnetic resonance spectroscopy of rat brain extracts compared with chromatographic methods.

We compared in vitro 1H magnetic resonance spectroscopy (MRS) measurements of rat brain extracts (rats: 2-56 days old) with chromatographic measurements and in a further step also with results of in vitro MRS. The following substances can be reliably measured in brain extracts by in vitro MRS: N-acetylaspartate (NAA), total creatine (Cr), phosphorylethanoloamine (PE), taurine (Tau), glutamate (Glu), glutamine (Gln), gamma-aminobutyrate (GABA) and alanine (Ala). Two different methods of MRS data evaluation compared with chromatographic data on Cr and NAA are shown. During development of the rat from day 2-56 brain concentrations of PE, Tau and Ala decrease, those of NAA, Cr, Glu and Gln increase, while GABA does not change. The developmental patterns of these substances are the same, whether measured by in vitro MRS or by chromatographic methods. Quantification of NAA, Cr, Tau, GABA and PE leads to the same results with both methods, while Glu, Gln and Ala concentrations determined by in vitro MRS are apparently lower than those measured chemically. The NAA/Cr ratios of 7 to 35-day-old rats were determined by in vivo 1H MRS. These results correlate with chromatographic and in vitro data. Using appropriate methods in the in vivo and in vitro MR-technique, the obtained data compare well with the chromatographic results.

Aging↗
PubMed1990

Early diagnosis and treatment of neonatal medium-chain acyl-CoA dehydrogenase deficiency: report of two siblings.

Two siblings are reported who were symptomatic in the neonatal period. The first died suddenly at 4 days of age after regurgitating a meal. The postmortem examination showed steatosis of the liver, kidney and muscle. In the second, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency was diagnosed at 3 days of age with muscular hypotonia, vomiting, hyperammonaemia and mild acidosis. Thus disorders of fatty acid oxidation should also be considered in newborns. The biochemical work up indicates that in neonates, analysis of serum medium-chain fatty acids and of acyl and free carnitine are more likely to lead to a diagnosis than determining dicarboxylic acids alone in urine. Long-term treatment was effective and monitored by the acyl/free carnitine ratio.

Acid-Base Equilibrium↗
PubMed1990

Late-onset form of partial N-acetylglutamate synthetase deficiency.

A 13-month-old female presented with neurological deterioration of 1 month duration and hyperammonaemia. N-acetylglutamate synthetase activity in the liver was reduced to 33% of the control. A male cousin and a female sister had died following a similar clinical course. This is the first report of late-onset N-acetylglutamate synthetase deficiency. An autosomal-recessive mode of inheritance is suggested.

Acetyltransferases↗
PubMed1990

[Ultrasound, computed tomography and magnetic resonance tomography in a child with macrocephaly and glutaric aciduria type I].

The rare case of glutaric aciduria type I (GA Type I) is described. Its characteristics are discussed and compared with cases in the literature. This disease is basically due to a lack of glutaryl-CoA-dehydrogenase with increased excretion of glutaric acid. Most authors describe frontotemporal cerebral atrophy. In the majority of cases macrocephaly is also present. This sign was also seen in our case and was the reason for performing an ultrasound examination, CT and MR. Ultrasound and CT showed a large insular cistern with incomplete formation of the opercula and frontal atrophy. In addition MR revealed hyperintensity of the basal ganglia and the periventricular white matter. To our knowledge this is the first publication of radiological findings in GA Type I in the German language.

Amino Acid Metabolism, Inborn Errors↗
PubMed1990

Guanidino compound analysis as a complementary diagnostic parameter for hyperargininemia: follow-up of guanidino compound levels during therapy.

The aim of this collaborative study was to investigate whether guanidino compound analyses in the biologic fluids can be used as a complementary diagnostic parameter for hyperargininemia. Guanidino compounds were determined in the biologic fluids of all known living hyperargininemic patients using a cation exchange chromatographic system with a fluorescence detection method. The serum arginine, homoarginine, alpha-keto-delta-guanidino-valeric acid, argininic acid, and N-alpha-acetylarginine levels of all the hyperargininemic patients are higher than the normal range. Similar increases were seen for the urinary excretion of alpha-keto-delta-guanidinovaleric acid and argininic acid. Untreated hyperargininemic patients have the highest guanidino compound levels in cerebrospinal fluid. However, even under therapy, the arginine, homoarginine, alpha-keto-delta-guanidinovaleric acid, and argininic acid levels in cerebrospinal fluid are still increased. Protein restriction alone is not sufficient to normalize the hyperargininemia, but protein restriction together with supplementation of essential amino acids with or without sodium benzoate decreases further the arginine levels. However, whereas the argininemia can be normalized, the catabolites of arginine are still increased. We conclude that the urinary amino acid levels may remain normal in hyperargininemia, whereas consistent increases of the guanidino compounds are observed. Thus, guanidino compound analyses can be used as a complementary biochemical diagnostic parameter for hyperargininemia. Although the argininemia can be normalized by therapy, the levels of the catabolites of arginine are still elevated.

Adolescent↗
PubMed1990

Proton NMR observation of phenylalanine and an aromatic metabolite in the rabbit brain in vivo.

1H nuclear magnetic resonance (NMR) was used to detect directly the signal from the aromatic protons of phenylalanine (phe) in the brains of rabbits made hyperphenylalaninemic by administration of a diet high in phe and containing 0.4% alpha-methylphenylalanine. In addition to those resonances found in the region between 6.5 and 8.5 ppm in the 1H NMR spectra of control rabbits, a resonance centered at 7.37 ppm was observed in the spectra obtained from the brains of hyperphenylalaninemic rabbits in vivo or in situ postmortem. The chemical shift of this additional resonance was that expected for protons of the phenyl ring of phe. Its intensity correlated well with measurements of brain phe levels made on postmortem samples by amino acid analyzer. Both of these measurements correlated poorly with amino acid analyzer measurements of serum phe, especially at high values of the latter. High-resolution 1H NMR spectra of the brain extracts showed that in most animals an unidentified aromatic compound, possibly gamma-glutamyl-phe, was present in addition to phe. This study demonstrates the feasibility of measuring the concentration of brain phenyl and its metabolites noninvasively by 1H NMR. The method can be used for similar measurements in human brain.

Animals↗
PubMed1990

[Late diagnosis of congenital argininemia during administration of sodium valproate].

Congenital hyperargininaemia is a rare condition transmitted as an autosomal dominant trait. Following a one-year free interval, repeated vomiting, psychomotor regression and spastic paraparesis with talipes equinus progressively develop. The diagnosis, confirmed by arginine assays in blood and urine, is probably often missed. We report a case of homozygous arginase deficiency belatedly diagnosed at the age of 18 years, when treatment with sodium valproate (VPA) was instituted. This female patient presented with psychomotor regression since the age of 15 months and with paraparesis since she was 3 years' old. These symptoms rapidly became worse. At the age of 18 years, when she was bed-ridden, she was hospitalized for subintrant tonic seizures. EEG showed generalized, continuous spike-wave discharges at the rate of 3.5 c/s. Treatment with VPA was instituted. Five days later, she went into a state of stupor. Blood ammonia level was elevated at 362 mumol/l. VPA was discontinued, and this was followed by a regression of disturbances of consciousness and by a decrease in arterial ammoniaemia, although the ammonia levels remained high, fluctuating between 40 and 100 mumol/l. Several months after VPA treatment was interrupted, the patient had a second episode of stupor, and her ammoniaemia was 500 mumol/l. Serum amino acid chromatography showed hyperargininaemia at 501 mumol/l (N = 30-150 mumol/l). The diagnosis of arginase deficiency was confirmed by the rise of arginine in red cells, cerebrospinal fluid and urine and, above all, by the finding of a deeply depressed arginase activity in erythrocytes. In all cases of intolerance to VPA, arterial ammoniaemia should be measured after withdrawal of VPA, some time after the acute episode.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

[Determination of fructosamine in chronic kidney diseases (dialysis-dependent patients)].

The serum fructosamine normal range was confirmed. Correction to protein or albumin did not significantly affect the results. Therefore, correction of fructosamine values from patients with normal protein and albumin values would not improve the clinical significance of fructosamine. Fructosamine concentrations of heparin plasma from non-diabetics also fell within the serum fructosamine normal range. The fructosamine concentration from non-diabetic dialysis patients was significantly higher and more widely distributed than that of the reference collective despite normal blood glucose concentration. Relating fructosamine to protein had no substantial effect, whereas the differences were even increased when fructosamine was related to albumin. On the present stage of knowledge it might be considered to establish a reference interval for dialysis patients. It appears that the fructosamine estimation may then be successfully applied also to dialysis patients. Although dialysis resulted in hemoconcentration, the fructosamine concentration remained virtually unchanged. Referencing both values before and after dialysis to protein or albumin improved the correlation, but substantial differences were introduced as well. However, none of several parameters measured in parallel interfered to a degree which might explain such differences. In order to find a reasonable explanation for these findings further experiments are necessary.

Adult↗
PubMed1989

Benzoate stimulates glutamate release from perfused rat liver.

In isolated perfused rat liver, benzoate addition to the influent perfusate led to a dose-dependent, rapid and reversible stimulation of glutamate output from the liver. This was accompanied by a decrease in glutamate and 2-oxoglutarate tissue levels and a net K+ release from the liver; withdrawal of benzoate was followed by re-uptake of K+. Benzoate-induced glutamate efflux from the liver was not dependent on the concentration (0-1 mM) of ammonia (NH3 + NH4+) in the influent perfusate, but was significantly increased after inhibition of glutamine synthetase by methionine sulphoximine or during the metabolism of added glutamine (5 mM). Maximal rates of benzoate-stimulated glutamate efflux were 0.8-0.9 mumol/min per g, and the effect of benzoate was half-maximal (K0.5) at 0.8 mM. Similar Vmax. values of glutamate efflux were obtained with 4-methyl-2-oxopentanoate, ketomethionine (4-methylthio-2-oxobutyrate) and phenylpyruvate; their respective K0.5 values were 1.2 mM, 3.0 mM and 3.8 mM. Benzoate decreased hepatic net ammonia uptake and synthesis of both urea and glutamine from added NH4Cl. Accordingly, the benzoate-induced shift of detoxication from urea and glutamine synthesis to glutamate formation and release was accompanied by a decreased hepatic ammonia uptake. The data show that benzoate exerts profound effects on hepatic glutamate and ammonia metabolism, providing a new insight into benzoate action in the treatment of hyperammonaemic syndromes.

Ammonium Chloride↗
PubMed1989

In vivo 31P NMR spectroscopy of energy rich phosphates in the brain of the hyperammonemic rat.

Hyperammonemia is a major contributing factor to the neurological abnormalities observed in hepatic encephalopathy and in congenital defects of ammonia detoxication. In rats variable changes in labile energy rich phosphates in the brain have been observed in hyperammonemia using biochemical methods. Using 31P-NMR spectroscopy however no significant changes of the relative concentrations of the energy rich phosphates alpha, beta and gamma-ATP, phosphocreatine, inorganic phosphate and the pH were found in the fronto parietal cortex of the urease treated hyperammonemic rat. Alterations in the metabolites of these compounds do not appear to be a major pathomechanism of ammonia toxicity in this brain area.

Ammonia↗
PubMed1989

[Excretion of N-acetyl-beta-D-glucosaminidase in the urine of children with type I juvenile diabetes mellitus and of patients treated with the aminoglycoside amikacin].

N-acetyl-beta-D-glucosaminidase activity, alpha 1-microglobulin, albumin, and creatinine were determined in urine specimens of healthy children, age 4 months up to 15 years, and of children with type I diabetes and of juvenile patients receiving amikacin, an aminoglycoside antibiotic, during severe systemic infections. All resulting values were expressed per g of creatinine. beta-Glucosaminidase activity was determined colorimetrically using 3-cresolsulfonphthaleinyl-N-acetyl-beta-D-glucosaminide as a substrate. Creatinine was determined by a modified Jaffé reaction. alpha 1-microglobulin and albumin were measured by immunodiffusion. In normal urine beta-glucosaminidase activity showed a log-normal distribution with an upper limit 97.5 percentile of 3.61 U/g creatinine. In patients receiving amikacin for up to 3 weeks beta-glucosaminidase and alpha 1-microglobulin significantly rose to very high values (6-10 times) during the course of the treatment. Urinary albumin values was only doubled. All values returned to normal, days or occasionally weeks after discontinuation of the therapy. 3 groups of diabetic children could be distinguished using urinary beta-glucosaminidase as a discriminator a) children with repeatedly normal activities, b) children with intermittently elevated activities and c) children with repeatedly elevated activities. While alpha 1-microglobulin concentrations followed the same pattern, the excretion of albumin did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗
PubMed1988

Determination of medium chain fatty acids in serum.

The determination of medium chain fatty acids in serum is a useful approach of the diagnosis of medium chain acyl-CoA dehydrogenase deficiency, an increasingly recognized cause of Reye-like syndrome in infants. A reliable and practical method requiring 0.5 ml of serum is presented by which results are obtained within 2.5 h. The preparation of the samples is done by solid phase extraction on reverse phase cartridges, the separation and quantitation by gas chromatography. Reference values for children (n = 24) and adults (n = 40) are given for octanoic, decanoic and dodecanoic acids.

Acyl-CoA Dehydrogenase↗
PubMed1988

Mitochondrial urea cycle enzymes in rats treated with sodium benzoate.

Since sodium benzoate, which is widely used to treat hyperammonemia its effect on mitochondrial urea cycle enzymes was investigated. its effect on mitochondrial urea cycle enzymes was investigated. Sodium benzoate was administered to urease treated hyperammonemic rats and controls. In both groups no interference with the activity of carbamylphosphate synthetase, ornithine carbamyltransferase and N-acetylglutamate synthetase in the liver could be observed at concentrations of benzoate in plasma found in hyperammonemic patients. Careful monitoring of plasma levels reduces benzoate toxicity as shown in a patient with argininosuccinic aciduria.

Acetyltransferases↗
PubMed1988

Lethal osteogenesis imperfecta: abnormal collagen metabolism and biochemical characteristics of hypophosphatasia.

We have examined collagen from a patient with the rare type IIC form of perinatally lethal osteogenesis imperfecta, in whom biochemical characteristics of hypophosphatasia were also apparent. In addition to normal alpha 1(I) and alpha 2(I) chains, there were chains overmodified along their lengths. Unexpectedly, the thermal stability of molecules containing these chains was normal. This suggests the existence of a structural mutation causing delayed triple helix formation, situated in either the alpha 1(I) or alpha 2(I) C-terminal propeptide. Since collagen synthesised by fibroblasts from each of the patient's parents was normal, the mutation was probably newly arising and dominant. In contrast to other reported cases of lethal osteogenesis imperfecta, not only was the secretion of collagen by cultured fibroblasts considerably retarded, but that of non-collagenous proteins was also severely impaired.

Alkaline Phosphatase↗