Oxypurine excretion,urinary

The urinary uric acid excretion and the urinary oxypurine excretion were measured up to 180 minutes after the start of the fructose infusion (Figure 4). A mean increase in the urinary uric acid excretion to 144% of control values and in urinary oxypurine excretion to 397% of control values occurred in the first hour after infusion. The marked rise in urinary oxypurines resulted primarily from a rise in hypoxanthine excretion. A striking increase in the excretion of inosine was also noted. No change was observed in the fractional clearance of uric acid. Pretreatment with allopurinol enhanced the absolute increase in urinary oxypurine excretion. These observations suggest that fructose-induced hyperuricemia is related to stimulation of uric... 

ALLOPURINOL AND THIOPURINOL EFFECT IN VIVO ON URINARY OXYPURINE EXCRETION AND RATE OF SYNTHESIS OF THEIR RIBONUCLEOTIDES IN DIFFERENT ENZYMATIC DEFICIENCIES. 

In patients with nearly complete deficiency of erythrocyte HGPRT activity (either Gout or LESH NYHAN syndrome) thiopurinol has no effect on plasma and urinary excretion of uric acid (DELBARRE et al. 1970), while in the same patients treated with allopurinol there is a rapid andimportant decrease of uric acid balanced by nearly stochiometric increase of oxypurines. Gouty patients with HGPRT deficiency have higher urinary oxypurine excretion with a more important contribution of hypoxanthine (H/X = 2,36) than... 

Ill - EFFECT OF ALLO AND THIOPURINOL ON URINARY OXYPURINE EXCRETION AND THEIR RATE OF SYNTHESIS IN VITRO OF RIBONUCLEOTIDE IN ENZYMATIC DEFICIENCIES (table IV)... 

We have shown that allopurinol and thiopurinol (about 200 mg per day) have no significant effet on the decrease of total urinary oxypurine excretion and on the ratio hypoxanthine to xanthine, either after prolonged period administration or after a single dose. It is well known that thiopurinol like allopurinol reduces the synthesis of uric acid in non xanthinuric subjects this effect needs normal activity of HGPRT. 

Allopurinol and Thiopurinol Effect in vivo on Urinary Oxypurine Excretion and Rate of Synthesis of Their Ribonucleotides in Different Enzymatic Deficiencies C. Auscher, N. Mercier, C. Pasquier, and F. Delbarre... 

UNSTABLE HPRTase IN SUBJECTS WITH ABNORMAL URINARY OXYPURINE EXCRETION... 

An initial screen of the six siblings was performed on an ad libitum diet measuring serum uric acid, 24-hourly excretion of urinary uric acid and oxypurine excretion. Containers with 10 cc phenol as preservative were sent by mail. Two patients had moderately or only minimally elevated oxypurines, but normal serum and urinary uric acid. Therefore, repeat urine samples were obtained from these patients and their children while on a meat free diet for two days, avoiding coffee and tea during the collection period. 

There were two subjects who clearly had primary xanthinuria (Table I), (Fig 1). P.J. and E.S. had 24-hour urinary excretion of uric acid of 36 and 19 mg/24 hr respectively and their serum uric acids were 1.1 and 0.7. After being on three days of a meat free diet their urinary uric acid values were 32 and 6.5 mg/24 hr, and their serum uric acid levels were 0.5 and 0.7 mg percent. In P.J. oxypurine excretion was unchanged by altering dietary urate being 409 and 407 mg/24 hr. In E.S. however oxypurine excretion fell from 263 mg/24 hr to 198 mg on a restricted diet. 

Most kindreds reported in the literature and our data are most consistent with an incompletely recessive mode of inheritance. If that is true the children of Il4,7 are obligate heterozygotes. They are identified as HIlO-12 18-20 none of them had any abnormality of urinary oxypurine excretion or uric acid excretion. 

As close as can be calculated 36 of these should have been heterozygotes based on an autosomal recessive inheritance. It can be readily appreciated that in no case was an abnormality of serum or urinary uric acid perceived. Only one other patient besides our series was reportedly tested for increased urinary oxypurine and it was elevated. Tobias states in his review that oxypurine excretion was elevated in the children of two siblings with xanthinuria from Johannesburg although no data is available (5). Three of the 15 patients at risk in our kindred had elevated oxypurine on a low meat diet. 

The mode of inheritance of xanthinuria is one of the major concerns of this study. The fact that two siblings are involved and there is no vertical transmission make an autosomal recessive inheritance likely. Patient II3 could have been recessive with incomplete penetrance or a heterozygote. His son (III5) is almost certainly a heterozygote with virtually the same expression as his father i.e. normal serum urate (6.0 mg percent), urinary urate (609 mg/24 hr) and elevated oxypurine excretion. This makes it likely that II3 is a heterozygote and is strong evidence that the heterozygote can be identified at least in some cases. 

The initial plasma urate concentration (Table 1) was disproportionately high levels greater than 0.6-0.9mmol/l in cases of acute renal failure are rare. The plasma urate concentration remained high when renal function had returned to normal 115 ml/min) However, the urinary uric acid, hypoxanthine and xanthine were nomnal for age, as was the excretion of total oxypurines in relation to creatinine excretion on a millimolar basis. Only after clinical gout appeared two years later was purine overproduction demonstrated, with plasma and urinary urate increased, as were hypoxanthine and xanthine excretion. The oxypurine/creatinine ratio was raised. 

The supernatants were concentrated with CF 25 cone, washed twice with 1.0 ml buffer, and reacted with a reaction mixture containing 0.5 n mol/I hypoxanthine at 37°C for 30 minutes. Uric acid product was determined by the rate of increased absorption of 293 nm at 37°C measured in a Gilford 2400 type recording spectrophotometer. Protein concentration of the specimens was determined by the Lowry method. Urinary oxypurines were assayed by HPLC as follows. One to two ml of urine samples from 24 hours total excretion were diluted 5-10 times with 0.9% NaCl and filtrated by a 0.45 pm Millipore filter. Three quarters of ml of this sample with 0.25 ml of 0.1 N NaOH and 1.0 ml of ethyo-acetate n- Butanol =2 1 solution were mixed for one minute. 

Fig. 4. Effect of fructose on serum urate and urinary excretion of uric acid and oxypurines. (From Fox and Kelley, 1972).

Since ATP normally inhibits 5 -nucleotidase and inorganic phosphate inhibits AMP deaminase, these changes would be expected to stimulate the catabolism of AMP to inosine. This hypothesis would most readily account for the rapid rise in serum urate concentration, the increased urinary excretion of inosine, oxypurines and uric acid, and the lack of an increase in intracellular PP-ribose-P levels following fructose infusion. 

At the present time, we just report some experimental results of a study on the mechanism of action of allopurinol (U-hydroxy-pyrazolo (3, -d ) pyrimidine) and thiopurinol k thiopyrazolo (3, d) pyrimidine) on de novo biosynthesis of uric acid. In this present work, we have compared effect of alio and thiopurinol on oxypurine (xanthine and hypoxanthine) urinary excretion with their rate of synthesis of ribonucleotides in vitro by erythrocyte hemolysate in some particular enzymatic deficiencies (hypoxanthine-guanine phosphoribosyltransferase HGPRT, adenine phosphoribosyl-transferase APRT and xanthinuria). 

In gout with normal renal function and normal HGPRT activity, we have shown that thiopurinol like allopurinol reduces uric acid synthesis. However, while allopurinol reduces urinary uric acid excretion with partly balanced increase of oxypurine, thiopurinol has no significant effect after prolonged period administration on urinary excretion and plasma oxypurines (DELBARRE et al 1967,1972). 

URINARY EXCRETION OF 6 HYDROXYLATED METABOLITE AND OXYPURINES IN A XANTHINURIC MAN GIVEN ALLOPURINOL OR THIOPURINOL... 

Xanthinuria is characterized by a large urinary excretion of oxypurine (xanthine + hypoxanthine) which replaces uric acid at the end product of purine metabolism. Patients with xanthinuria are very deficient in xanthine oxidase activity. This rare metabolic disorder may be of interest for both information ... 

The clinical case of this xanthinuric man has been reported by DELBARRE in a previous paper (to be published). This man is a pastry cook since he could not be in the hospital more than one or two days, most determinations were done without control diet. This explains the great difference of daily urinary oxypurine values that were found. This patient has normal renal function (creatinine clearance = 99 ml/min). His averaged uric acid and oxypurines (xanthine and hypoxanthine) plasma concentration were 1.2 and 0.58 mg per 100 ml. His 95 % range ( mean + 2s) urinary excretion of uric acid is 7 to 27 mg per day and of oxypurine 310 to 618 mg... 

The amount of urinary excretion of each PP and its 6-hydroxy-lated metabolite as well as the concomitant excretion of oxypurine were determined 1) in daily urine after prolonged period of oral administration. 2) in the hours following a single dose of oral administration. The same experiment was carried out in a non-xanthinuric man with normal renal function. 

We have found no modification of urinary excretion amount of oxypurines or of the ratio of hypoxanthine to xanthine after 3,7 and 57 days allopurinol (200 mg/days) and 3,5,1 and 25 days of thiopurinol(500 mg/days) administration, nor during the 2h hours following administration of a single dose of every PP. All the values found were in the 95 % range limits of the mean values obtained without treatment. 

Four of the subjects with neoplastic disease were studied in more detail (Table 3 and Table 4). In each subject, the ratio of urate creatinine found to be increased (Table 3). There was no evidence of renal glucosuria, hyperphosphaturia, or bicarbonate wasting, which would suggest a generalized defect of tubular transport in these patients (Table 4). One patient, however, patient W.G., had a generalized amino aciduria and another, patient A.H., had an increase in alanine excretion. Two of the patients, J.L. and W.G., with neoplastic disease and an increased Curate/ creatinine ratio had evidence of obstructive jaundice, with plasma bilirubin levels of 15 and 20 mg/100 ml, respectively. In these same two patients with extensive hepatic involvement there was also an increase in the urinary excretion of oxypurines (Table 4). 

Urinary Excretion of 6 Hydroxylated Metabolite and Oxypurines in a Xanthinuric Man Given Allopurinol or Thiopurinol. ... 

The urinary excretion data of uric acid and oxypurine in conjunction with the extremely low serum urate speak strongly for this. However, we have not measured the xanthine oxidase levels in the tissue of these patients leaving some small measure of doubt as to the true etiology of these deranged values. 

Drugs affecting purine metabolism act aberrantly in the Lesch-Nyhan syndrome [127]. Azathioprine and 6-mercapto-purine do not affect purine synthesis allopurinol reduces uric acid production but causes an equivalent increase in oxypurines probenecid increases urinary excretion of uric acid and... 

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