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Biomedical subjects

W Gröbner

Publications and source records attributed to W Gröbner.

At least 55 records · Page 3Linked to original sources
PubMed1979

[Time course of oxipurinol levels in plasma following single dose and chronic administration of allopurinol in different pharmaceutical preparations (author's transl)].

Oxipurinol plasma levels and plasma elimination half-life were investigated in five healthy volunteers after oral administration of 300 mg allopurinol in customary (A 300) and in slow-release preparation (A ret) in a double blind cross-over study. After a single oral dose of 300 mg allopurinol in customary preparation maximum oxipurinol plasma levels were 5.24 microgram/ml. After allopurinol in slow-release preparation maximum oxipurinol levels were 2.22 microgram/ml. 24-h oxipurinol plasma levels were 3.78 microgram/ml after A 300 and 2.08 microgram/ml after A ret, respectively. Chronic oral administration of a daily dose of 300 mg allopurinol resulted in accumulation of oxipurinol until day 8. 24-h steady-state levels of oxipurinol were found to be 9.98 microgram/ml after A 300 and 7.14 microgram/ml after A ret. All oxipurinol plasma levels on A 300 exceeded those on A ret. The time course of oxipurinol plasma levels after a single oral dose of allopurinol suggests that oxipurinol elimination from plasma follows an exponential function (first-order elimination). Plasma elimination half-life of oxipurinol was 42.65 h after administration of A 300 and 49.91 h after administration of A ret. The difference between the elimination half-lives is statistically not significant.

Adult↗
PubMed1978

[Juvenile gout with decreased activity of hypoxanthine-guanine-phosphoribosyl transferase and pheochromocytoma: partial persistence of tophi despite uric-acid reducing treatment for 12 years (author's transl)].

A now 45-year-old man with marked chronic tophous gout and recurrent nephrolithiasis has been followed for 12 years. First gouty symptoms appeared at age 18. Uric-acid reducing treatment freed the patient of symptoms, and bony and soft-tissue tophi in part regressed. The early onset and high urinary uric-acid excretion indicated increased uric-acid production. Decreased activity of the enzyme hypo-xanthine-guanine-phosphoribosyl transferase was demonstrated to be the cause of the hyperuricaemia, which led to an excessive purine synthesis. An almost complete loss of activity of this enzyme is the basis of the Lesch-Nyhan syndrome. In the described patient all of the neurological and behavioural disorders of the Lesch-Nyhan syndrome were absent. A pheochromocytoma was found to be the cause of malignant hypertension, which had been present for many years.

Adrenal Gland Neoplasms↗
PubMed1978

[The influence of allopurinol on purine- and pyrimidinesynthesis (author's transl)].

Allopurinol inhibits xanthinoxydase. This results in a decrease of the serum and urinary uric acid. Simultaneously the renal excretion of hypoxanthine and xanthine increases. In most patients, however, the decrease of urinary uric acid is not completely replaced by the increase of oxypurines. This is attributed to an additional inhibition of de novo purine biosynthesis. The different effect of allopurinol on the endogenous and exogenous urates offers an alternative approach to explain the "purine deficit". The effect of allopurinol on the pyrimidine metabolism is due to an inhibition of orotidylic decarboxylase by the ribonucleotides of allopurinol, xanthine and oxipurinol. This inhibition is followed by an increase in the urinary excretion of orotidine and orotic acid. The additional administration of ribonucleic acid leads to a striking decrease of the allopurinol induced orotaciduria. The continuous administration of allopurinol also produces an increase in the activity of orotate phosphoribosyltransferase and orotidylic decarboxylase. At this time the mechanism of this increase in activity is not completely understood. Allopurinol is metabolized rapidly. Only 3-10% of an administered dose are excreted unchanged in the urine. Most of the allopurinol is oxidized to oxipurinol. A small portion is converted to the ribonucleosides and ribonucleotides1 of allopurinol and oxipurinol.

Allopurinol↗
PubMed1977

Dietary feedback regulation of purine and pyrimidine biosynthesis in man.

Ten days after a healthy person has consumed a purine-free isoenergetic diet, the excretion of (endogenous) uric acid reaches a minimum and remains constant thereafter. Purines are absorbed in different degrees from various biochemical sources added to such a diet--little from DNA, nearly all from ribomononucleotides--presumably owing to different rates of hydrolysis. There is always a linear relationship between dietary purine content and uric acid excretion, independent of the source of purine. The findings suggest that dietary purines play a minor role (if any) in the regulation of purine synthesis, contrary to the conclusions of other workers. The demonstration that oral administration of uridine diminishes the oroticaciduria in patients with hereditary oroticaciduria suggested dietary feedback regulation of pyrimidine biosynthesis by pyrimidine nucleosides in the diet. The reduction of allopurinol-induced oroticaciduria by dietary RNA pointed in the same direction. Closer analysis with RNA hydrolysate and isolated purine as well as pyrimidine nucleotides, however, revealed that not only pyrimidine derivatives but also purine mononucleotides diminish oroticaciduria. The nucleotides had no influence on the change in the activity of orotidine-5'-phosphate decarboxylase (EC 4.1.1.23), induced by allopurinol; this makes an effect on the decarboxylase unlikely. The feedback regulation is assumed to act by inhibition of an earlier step.

Allopurinol↗
PubMed1977

The influence of dietary purines and pyrimidines on purine.

Allopurinol-induced orotaciduria is reduced by dietary ribonucleic acid (RNA), RNA hydrolysate and different nucleotides. These findings are compatible with feedback regulation of pyrimidine biosynthesis by dietary nucleotides. Serum uric acid and urinary uric acid excretion on a purine-free isoenergetic diet reach a minimum after about 10 days and remain constant thereafter. When purines from different biochemical sources are added to such a diet there is always a linear relationship between dietary purines and serum uric acid level and urinary uric acid excretion. The findings suggest that dietary purines play a minor role if any in the regulation of purine biosynthesis in man.

Adenosine Monophosphate↗
PubMed1977

The influence of dietary purines and pyrimidines on purine and pyrimidine biosynthesis in man.

Allopurinol-induced orotaciduria is reduced by dietary ribonucleic acid (RNA), RNA hydrolysate and different nucleotides. These findings are compatible with feedback regulation of pyrimidine biosynthesis by dietary nucleotides. Serum uric acid and urinary uric acid excretion on a purine-free isoenergetic diet reach a minimum after about 10 days and remain constant thereafter. When purines from different biochemical sources are added to such a diet there is always a linear relationship between dietary purines and serum uric acid level and urinary uric acid excretion. The findings suggest that dietary purines play a minor role if any in the regulation of purine biosynthesis in man.

Animals↗
PubMed1975

[Disorders of human pyrimidine metabolism (author's transl)].

Pyrimidine synthesis and its regulation are presented. Among the disorders of human pyrimidine metabolism, hereditary orotic aciduria and that produced by drugs play the principal role. A rise in renal excretion of orotic acis is also observed when ornithine transcarbamylase activity is lacking. The importance of "orotic aciduria with partial response to folic acid" in pyrimidine metabolism is still not clear. Close relationship between the formation of pyrimidine and purine nucleotides must be assumed, because both enter into the synthesis of nucleic acid, for the greatest part in approximately equimolecular amounts. Possibly 5-phosphoribosyl-1-pyrophosphate plays an important part.

Allopurinol↗