Polyamines in cow's and sow's milk.

There were considerably interspecies, individual, lactation and age related variabilities in the concentration of spermidine and spermine in cow's and sow's milk. Concentration of spermidine was similar in cow's and sow's milk, whereas spermine level was higher in sow's milk. The level of spermine was higher than spermidine throughout the lactation in sow's milk, whereas spermine in cow's milk was secreted only at the beginning of lactation (collostrum and milk of the first month of lactation). The peak of spermidine and spermine concentration occurred in the collostrum and milk between the 1st and 3rd week of lactation in cow and sow, respectively. There was a significant positive relationship between milk yield and spermidine secretion in cow as well as between the number of piglets and milk spermidine concentration in sow.

Polyamines and pyrimidines in blood plasma and urine of dogs bearing mammary tumours.

The blood plasma and urinary pattern of polyamines and pyrimidines in dogs bearing mammary tumours was examined. A large variability of pyrimidines in blood plasma and spermidine, spermine and pseudouridine in urine of healthy and tumour-bearing dogs was observed. The blood plasma level of uracil and uridine as well as urinary concentration of pseudouridine and spermidine/spermine ratio were significantly elevated in dogs with mammary tumours.

Metabolic effect of orotic acid in calves.

Eight calves (males, Black and White crossbred with Holstein-Fresian) were fed milk and milk replacer without (control group) or with potassium orotate (3 mmol./l.) supplementation for 6 weeks after birth. Orotate depressed the biosynthesis of polyamines in mucosa of the gastrointestinal tract (rumen, omasum, abomasum, colon) by decreasing of ornithine decarboxylase activity with a simultaneous compensatory increase of S-adenosyl-methionine decarboxylase activity. A lower concentration of spermidine and spermine in the mucosa of the colon was also noted. The above changes were accompanied by increased urinary excretion of ornithine and arginine. Calf adaptation to a high OA intake was associated with an increased activity of the OA metabolizing enzyme complex (orotate phosphoribosyl transferase and orotidine monophosphate decarboxylase) in the liver, while urinary OA losses diminished with age. Increased concentrations of uracil and uridine in the liver and higher urinary excretion of pseudouridine in OA-fed calves was also observed. Stimulation of pyrimidine metabolism by OA depressed purine synthesis, which was reflected by a decrease of urate, hypoxanthine, and xanthine concentration in the liver. Interestingly OA enhanced urate excretion by the kidneys. OA strongly affected lipid metabolism in calves because total cholesterol, LDL-, and HDL-cholesterol, and triglycerides in blood plasma decreased while triglycerides accumulated in the liver of OA-fed calves. Milk OA in concentrations characteristic of cows with hereditary orotic aciduria exerts an unfavourable effect on the metabolism of polyamines, purines, and lipids in calf tissues.

Blood plasma pseudouridine in patients with malignant proliferative diseases.

The blood plasma concentration of pseudouridine was estimated in 104 healthy adult subjects, and 108 patients suffering from malignant proliferative diseases. The HPLC method for simultaneous determination of pseudouridine and creatinine was applied. The average physiological concentration of pseudouridine in blood plasma was 2.43 +/- 0.97 mumol.l-1 or 29.15 +/- 7.40 mmol.mol-1 creatinine. The physiological urinary excretion of pseudouridine was 14.32 +/- 5.20 mumol.24 h-1.kg-0.75 or 19.60 +/- 5.22 mmol.mol-1 creatinine. Renal clearance of pseudouridine and endogenous creatinine were 4.04 +/- 0.99 and 5.50 +/- 1.46 ml.kg-0.75, respectively. A positive correlation (r = 0.55, P < 0.01) was found between age (in the range 20-92 years) and blood plasma pseudouridine concentration (mumol.l-1). By expressing plasma pseudouridine in relation to plasma creatinine, the apparent influence of non-metabolic factors (age, renal insufficiency, blood dilution) on the plasma pseudouridine concentration were largely excluded. Among haematological proliferative diseases the highest values of plasma pseudouridine concentrations were observed in chronic lymphocytic leukaemia (8.19 mumol.l-1; 54.9 mmol.mol-1 creatinine) and multiple myeloma (7.02 mumol.l-1; 52.5 mmol.mol-1 creatinine). In multiple myeloma, but not in chronic lymphocytic leukaemia, the plasma pseudouridine concentration depended on the clinical stage. A lower, but still significant response in non-Hodgkin's lymphoma was noted (4.03 mumol.l-1; 40.88 mmol.mol-1 creatinine). A significant increase of the plasma pseudouridine concentration was characteristic of adenocarcinomas of the large intestine, and it occurred in the early stages of malignant growth. In patients with lung cancer the plasma pseudouridine concentration was elevated only in advanced cases with metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of urinary neopterin and pseudouridine in patients with malignant proliferative diseases.

The HPLC method for the simultaneous determination of urinary neopterin, pseudouridine, and creatinine allows a rapid evaluation of the activation state of cell-mediated immunity, and the stimulation of whole-body rRNA + tRNA turnover, associated with malignant growth. Urinary neopterin and pseudouridine concentrations in healthy subjects amounted to: 106.6 +/- 34.6 mumol/mol creatinine, and 19.6 +/- 5.2 mmol/mol creatinine (mean +/- SD), respectively. The increase of neopterin excretion in patients with haematological neoplasms ranged from 146% in Hodgkin's disease to 534% in non-Hodgkin's lymphoma, whereas the increase in cancer cases ranged from 95% in adenocarcinoma of the gaster to 741% in hepatocellular carcinoma. The changes in pseudouridine excretion were much less pronounced: 63% in non-Hodgkin's lymphoma and 120% in carcinoma of the urinary bladder. The correlation coefficient between neopterin and pseudouridine was relatively low (r = 0.43), although statistically significant (P < 0.01). In the case of several neoplasms e.g. Hodgkin's disease, polycythaemia vera, and adenocarcinoma of the gaster, neopterin was significantly elevated, whereas pseudouridine remained at a normal concentration. There was a positive relationship between the stage of the disease (primary focus, regional metastases, dissemination) and urinary concentration of pseudouridine in patients with adenocarcinoma of the large intestine. In the same patients the increase of neopterin excretion was noticed both in early and advanced stages, with the highest values in disseminated disease.

Efficiency of hemodialysis of pyrimidine compounds in patients with chronic renal failure.

The accumulation in blood plasma and efficiency of hemodialysis of pyrimidine compounds (orotic acid, orotidine, pseudouridine, uridine, thymine) as well as uric acid and creatinine in 23 patients with chronic renal failure (CRF) was investigated. As a reference, the analysis of the above metabolites in the plasma of 30 healthy volunteers was performed. Among examined compounds, pseudouridine possessed the highest capability of accumulation in blood plasma (25 times higher concentration than physiological). It coincided with the lowest efficiency of pseudouridine hemodialysis (44%) and the longest T1/2 (relative to creatinine) in plasma. A significant linear correlation (r = 0.81, p < 0.001) between efficiency of creatinine and pseudouridine hemodialysis was calculated. The concentration of orotic acid in the blood plasma of patients before hemodialysis exceeded 14 times its level in healthy subjects; the inhibition of uric acid synthesis by allopurinol in dialyzed patients was accompanied by enlargement of orotidine and orotate accumulation in blood plasma. Extremely high plasma concentration of examined pyrimidines remaining elevated after hemodialysis creates an additional hazard for tissue metabolism and health of patients with CRF.

The metabolism and urinary excretion of orotic acid in hyperargininaemic sheep.

The synthesis, blood plasma turnover and urinary excretion of the orotic acid in normo- and hyperargininaemic sheep was investigated. The whole-body orotate formation was evaluated indirectly by the measurement of urinary orotate excretion after blockage of pyrimidine pathway with 6-azauridine (4 hour i.v. infusion of 0.2 mg.kg-1.min-1). Simultaneous infusion of L-arginine (2.5 mumols.kg-1.min-1) significantly elevated the blood plasma arginine, ornithine and urea level, however, it did not significantly influence urinary orotate excretion. In normoargininaemia blood plasma turnover of exogenous orotic acid amounted to 4.9 min and 67% of this compound was eliminated through the kidneys. The renal clearance of orotic acid amounted to 21.7 ml.min-1.kg-0.75. Hyperargininaemia elevated blood plasma turnover to 8.2 min, and diminished the renal clearance of this metabolite to 13.7 ml.min-1.kg-0.75. These results indicate that hyperargininaemia and hyperornithinaemia do not change the whole body synthesis of orotic acid in sheep but they can affect renal excretion of this metabolite, particularly at the rate of tubular secretion close to saturation.

Urinary excretion of purines in sheep with experimental orotic aciduria.

Urinary excretion of uric acid, hypoxanthine, allantoin, and urea was measured in sheep (Polish Merino, about 20 kg b.w.) with experimental orotic aciduria. The 240 min infusion of 6-azauridine solution into the jugular vein induced a highly significant increase of urinary orotic acid, uric acid and hypoxanthine excretion. No differences were found in relation to excretion of allantoin and urea in examined sheep. It was calculated that renal clearance of uric acid and hypoxanthine increased significantly in response to 6-azauridine infusion. Intravenous infusion of sodium orotate evoked a highly significant elevation of renal urate clearance. No significant change in renal urea clearance was observed. The data suggest that competition between the renal transport of orotate and actively transported purine compounds (uric acid and hypoxanthine) occurs.