[Age-specific features of the cyclic nucleotide system in children]. / Vozrastnye osobennosti sistemy tsiklicheskikh nukleotidov u detei.

The content of cyclic nucleotides (cAMP and cGMP) in the plasma and peripheral blood leukocytes, levels of their daily urinary excretion, and the activities of adenylate cyclase and cAMP-dependent phosphodiesterase responsible for the synthesis and degradation of cAMP in the leukocytes were studied in 114 healthy children aged 0 to 15 years. The levels of cyclic nucleotides in the blood plasma and leukocytes were found to gradually increase with age, as well as urinary excretion of cAMP. Both cAMP synthesis and degradation were found intensified with age. The detected age-specific features of cyclic nucleotides are important criteria for the assessment of the development of children and their health status. The findings may be used as reference values in assessment of the status of cyclic nucleotides in children with various diseases.

[Value of several hormone indicators and cyclic nucleotides in the assessment and prognosis of resistance to acute hypoxia during operator activities]. / Informativnost' nekotorykh gormonal'nykh pokazatelei i tsiklicheskikh nukleotidov v otsenke i prognoze ustoichivosti k vozdeistviiu ostroi gipoksii pri operatorskoi deiatel'nosti.

A study was performed in which 16 healthy volunteers, aged 25-40 years, worked in a two-dimensional tracking simulator and breathed a mixture containing 9-12% oxygen. This led to a higher incretion of cortisol, insulin, somatotropin, a greater renal excretion of epinephrine, norepinephrine, and a higher content of cAMP in lymphocytes, plasma and urine. The subjects with a higher insulin in plasma and renal excretion of catecholamines showed a longer time of tolerance to the above exposure which varied from 50 to 120 min. The high tolerance was combined with a greater activity of the sympathoadrenal system, incretion of cortisol and cAMP in lymphocytes. A significant correlation was demonstrated between cAMP in the above environments both before and after exposure.

[Radionuclide studies on the hormonal manifestations of heat stress in cancer patients under controlled total hyperthermia]. / Radionuklidnye issledovaniia gormonal'nykh proiavlenii teplovogo stressa u onkologicheskikh bol'nykh pri obshchei upravliaemoi gipertermii.

The results of the investigations of ACTH, HGH, hydrocortisone, glucagon, C-peptide, insulin in 180 patients with advanced and metastatic melanomas, soft tissue sarcomas, lung cancers and renal cell carcinomas testify to the development of the syndrome of endocrine hyperfunction in patients under whole-body guided hyperthermia as well as of functional pancreas insufficiency. The data presented form a biochemical basis for working out measures to optimally carry out whole-body hyperthermia treatment, aimed at increasing the range of indications for its use in clinical oncology.

Effects of a rice meal on renal hemodynamics and excretory functions in normal subjects.

The nature of renal hemodynamic response to a large carbohydrate-rich meal and the associated renal excretory functions were examined. Seven normal subjects were studied after ingestion of 300 g of rice meal. Five healthy men served as a time control. After eating the test meal, the mean creatinine clearance began to rise and became significantly higher in the 2nd hour compared with the control (118 +/- 7 vs. 91 +/- 3 ml/min/1.73 m2; p less than 0.01). Urinary excretion rates of sodium and chloride after the meal were significantly higher compared with those in the premeal period. Blood glucose concentrations rose significantly following the meal. The postprandial plasma levels of amino acids did not vary significantly compared with the premeal values. These results demonstrate that rice meal ingestion increased glomerular filtration rate via a mechanism(s) different from the protein-induced glomerular hyperfiltration.

Effects of dietary protein intake on vasoactive hormones.

Vasoactive hormonal response to two levels of dietary protein intake was studied in seven healthy adult volunteers. The subjects were randomly placed on a 2-g.kg-1.day-1 (high) or 0.55-g.kg-1.day-1 (low) diet using a crossover design and were studied on the morning of the 5th day and again after 24 h of indomethacin treatment. Plasma renin activity (PRA), aldosterone, vasopressin, and urinary excretion of 6-ketoprostaglandin F1 alpha (PGF1 alpha) were significantly higher on the high-protein diet despite constancy of body weight, blood pressure, pulse, urinary sodium and potassium excretion, and plasma amino acid levels. After treatment with cyclooxygenase inhibitor indomethacin, 6-keto-PGF1 alpha excretion was equalized, but the elevated PRA and aldosterone levels persisted on the high-protein diet, suggesting that PRA and aldosterone elevations do not depend entirely on prostanoid release. We conclude that chronic augmentation of dietary protein intake is accompanied by alterations of vasoactive hormones, which persist for up to 10 h postprandially and are independent of elevated plasma amino acid levels. Such hormonal alterations may mediate some of the dietary protein-mediated changes in renal hemodynamics.

[Excretion of cyclic nucleotides during prolonged gamma irradiation of rats]. / Eksrektsiia tsiklicheskikh nukleotidov pri dlitel'nom gamma-obluchenii krys.

Excretion of cGMP in urine was significantly increased and cAMP/cGMP ratio decreased in rats subjected to long-term repeated gamma irradiation with cumulative doses of 15 to 20 Gy.

Urinary excretion of cyclic nucleotides, creatinine prostaglandin E2 and thromboxane B2 from mice exposed to whole-body irradiation from an enhanced neutron field.

Urine volume and excretion of cyclic AMP, cyclic GMP, prostaglandin E2 (PGE2), thromboxane B2 (TxB2) and creatinine were evaluated as potential indicators of radiation damage in mice given 2-5 Gy to the whole body from an enhanced neutron field. In general, urinary cyclic AMP, cyclic GMP, creatinine and urine volumes were positively correlated across time postexposure, for each radiation dose. TxB2 levels positively correlated with urine volume and cyclic AMP excretion only in animals given 2.0 Gy. None of these parameters suggests their use as a prognostic indicator of the extent of radiation damage. Urinary excretion of PGE2 was negatively correlated with other urinary parameters. Biphasic increases in urinary PGE2 were also observed. The initial transient elevation 2-3 days postexposure was not correlated with the dose (2-5 Gy). The second elevation of PGE2 excretion occurred at 6-10 days. The magnitude of the latter increase suggests that urinary PGE2 excretion may be a useful indicator of whole-body or kidney exposure to neutron fields.

Human renal response to meat meal.

Glomerular filtration rate (GFR) increases after a meat meal in several species. The mechanism of this phenomenon is unknown and the excretory and metabolic responses largely unexplored. We examined in humans the nature of the hemodynamic response to a meat meal, the role of salt and water load in this response, and the associated renal excretory responses. Ten normal volunteers were studied after eating an average of 3.5 g/kg body wt of lean cooked beef steak and, on a separate day, after ingesting an amount of sodium and water equivalent to that in the steak. Average GFR increased by 28% for the entire 3 h after the meat meal compared with the same time period after the control salt solution (90 +/- 8 vs. 114 +/- 6 ml X min-1 X 1.73 M-2, mean +/- SE, P less than 0.05) and by 15% compared with the base-line periods, although this difference was not of statistical significance. However, not all subjects demonstrated an increase, and in those eight who did the degree was variable from 5 to 46% for the 3-h mean above the basal value. During the hour of peak GFR, the increment was associated with a nearly proportional increase in renal plasma flow and renal blood flow (all P less than 0.05). The increase in renal blood flow was entirely due to a significant fall in renal vascular resistance. The vasodilation was not accompanied by any change in prostaglandin E excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma and urine cyclic nucleotide levels in patients with neoplastic diseases.

Plasma and/or urine cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) levels were measured in 67 normal subjects, 55 patients with nonneoplastic diseases, and 324 patients with ten different types of cancer. There were no significant differences in plasma and urine cyclic nucleotide levels between normal subjects and patients with non-neoplastic diseases. In untreated cancer patients, plasma and urine cAMP levels were similar to those of normal subjects, whereas plasma and urine cGMP levels were markedly higher. This pattern was common to all the cancer groups studied. Chemotherapy per se did not seem to influence cyclic nucleotide levels in cancer patients. However, plasma and urine cGMP levels normalized in all patients who attained complete remission. Moreover, in acute leukemia patients who relapsed, plasma cGMP levels increased significantly with respect to the complete remission values, thus suggesting that this parameter may be useful in monitoring the response of cancer patients to treatment.

Comparison of effects of guanfacine and clonidine on blood pressure, heart rate, urinary catecholamines, and cyclic nucleotides during and after administration to patients with mild to moderate hypertension.

In a random trial, the effects of treatment and withdrawal of guanfacine were compared with those of clonidine in 20 uncomplicated hypertensive patients. Elevated blood pressure returned to normal or responded well in all the patients given either guanfacine once daily or clonidine thrice daily. The pulse rate was reduced comparably by both treatments after 12 weeks, but the effect of guanfacine developed more gradually. Both guanfacine and clonidine significantly inhibited urinary noradrenaline, dopamine, and cyclic nucleotide excretion, while urinary adrenaline levels were unaffected. Side effects occurred earlier during treatment with clonidine. After sudden withdrawal, all the parameters tended to increase gradually in the guanfacine group, reaching base line by days 4-6. In the clonidine group the increase was more rapid, with pretreatment values reached within the 2nd day, and sometimes these values were surpassed. After withdrawal of clonidine all the patients had one or more side effects, most of them occurring within 48 h, while only 60% of the patients in the guanfacine group reported the appearance of unwanted symptoms, on days 3-6. It is concluded that there are close similarities between the effects of guanfacine and clonidine on the parameters evaluated, except for dopamine excretion, which was significantly less affected by guanfacine. Marked differences were found after abrupt withdrawal, with guanfacine less likely to produce the "discontinuation syndrome," probably due to its long half-life.

High-performance liquid chromatographic determination of purine and pyrimidine bases, ribonucleosides, deoxyribonucleosides and cyclic ribonucleotides in biological fluids.

A method is presented for the separation and quantitative determination of compounds normally related to purine and pyrimidine metabolism in biological material. The retention behaviour of nucleobases, ribonucleosides, deoxyribonucleosides and cyclic ribonucleotides has been systematically investigated by reversed-phase high-performance liquid chromatography using a non-linear gradient. Ultimately a separation of the purine and pyrimidine compounds was achieved in a 35-min run with an average detection limit of 5-10 pmol per injection. Recoveries of standards added to urine, plasma or serum were 96 +/- 5%.

Urinary excretion of cyclic nucleotides and phosphate in response to parathyroid hormone and calcitonin in man.

The response to parathyroid hormone (PTH) and calcitonin (CT) was studied in eight children with various bone diseases by determining the serum calcium (Ca) and phosphate (P) concentration, urinary phosphate excretion rate, renal phosphate clearance, the percentage of filtered phosphate reabsorbed by the renal tubule (%TRP), creatinine clearance (Ccr), urinary cyclic adenosine 3',5' monophosphate excretion rate (UcGMPV). Administration of PTH caused no significant change in serum Ca and P values, whereas CT produced a decrease in Ca (delta Ca, -1.4 +/- 0.1 mg/100 ml) and P (delta P; -1.1 +/- 0.1 mg/100 ml). There was an increase in UcAMP V (delta UcAMP; 437 +/- 74 nmoles/min/100 ml Ccr) without any significant change in UcGMPV after administration of PTH. Phosphaturia was produced by both PTH (delta TRP, -18 +/- 3%) and CT (delta TRP, -13 +/- 2%). However, CT did not elicit any increase in either UcAMPV or UcGMPV.

Urinary excretion of cyclic nucleotides and principal electrolytes in healthy humans of different ages.

Urinary excretion of cyclic AMP, cyclic GMP, inorganic phosphorus, calcium, sodium, potassium and creatinine was measured in 138 healthy male and 104 healthy female humans from 2 to 68 years old. The range of cyclic nucleotide excretion was as follows: cyclic AMP (mumol/day), 1.01-10.89; cyclic GMP (mumol/day), 0.13-2.00; cyclic AMP (mumol/g creatinine), 1.52-8.93; cyclic GMP (mumol/g creatinine), 0.11-1.87. The 242 volunteers were grouped into seven classes according to age: A, 2-9 years old; B, 10-19; C, 20-29; D, 30-39; E, 40-49; F, 50-59 and G, 60-68. Average excretion (mumol/day) of cyclic AMP in class A (2.62 +/- 0.29 for males and 2.30 +/- 0.18 for females) was significantly smaller than that in other classes (4.59 +/- 0.12 for males and 3.90 +/- 0.13 for females) (p less than 0.01). Such a significant difference was not observed in cyclic GMP excretion. In terms of mumol/g creatinine, however, average excretion of both cyclic AMP and cyclic GMP in class A was greater than that in other classes. The amounts of urinary cyclic AMP and cyclic GMP (mumol/day) were correlated with age in the subjects from 2 to 16 years. A reverse correlation between the amounts of both nucleotides (mumol/g creatinine) and age was found in the young subjects. No correlation between the excretion of either urinary cyclic nucleotide and age was found in adults. A significantly positive correlation between cyclic AMP (mumol/day) and inorganic phosphorus (g/day) was found (r = 0.50 for males and 0.56 for females) (p less than 0.01). This correlation suggests that urinary cyclic AMP might reflect the activity of parathyroid hormone in normal humans. There was no significant correlation between cyclic GMP and electrolytes tested. The above results are considered to provide basic data for clinical evaluation of relevant disorders.

Cyclic nucleotides in rheumatoid arthritis.

Cyclic 3',5'-adenosine monophosphate (cAMP) and cyclic 3',5' guanosine monophosphate (cGMP) may influence important regulatory mechanisms in the rheumatoid inflammatory process. It has been claimed that fasting improves the condition of the patient with rheumatoid arthritis (RA). The present study was designed to measure cAMP in plasma and urine cGMP in urine in medically untreated RA patients. 12 female patients were investigated in a cross-over study during a control and a fasting period. They received no other drugs than analgesics during these periods. Levels of plasma and urinary cAMP found during the control period were somewhat lower than previously reported. However, the ratio cAMP/cGMP in urine was 10 to 1 which is reported to be normal. Clinical and laboratory variables of inflammatory activity were significantly improved during the 7-day fasting period. The ratio of cAMP/cGMP in urine was significantly increased on days 2-4 and coincided in time with the maximum of clinical improvement. Cyclic AMP concentrations were lowered both in plasma and urine during fasting. This is in contrast to fasting in normal and obese subjects reported in previous studies.

Changes in the concentration of cyclic nucleotides dependent on their antibodies in plasma.

In the process of immunization of rabbits with cyclic AMP or cyclic GMP, the plasma concentration of cyclic AMP or cyclic GMP was markedly elevated as the titer of the antiserum increased. The i.v. injection of anti-cyclic AMP or anti-cyclic GMP antiserum into rats or mice also caused a marked increase in the respective cyclic nucleotide in plasma. On the other hand, an injection with the antiserum did not cause any significant increase in urinary cyclic nucleotides. Therefore, the effect of the antiserum seems to be different from that of glucagon or carbamylcholine which increases cyclic AMP or cyclic GMP respectively in both plasma and urine. The injection of the antiserum, but not nephrectomy, caused a significant increase in plasma cyclic nucleotides in adrenalectomized rats. This made it unlikely that the antiserum-induced increase was due to the inhibition of urinary excretion. The plasma cyclic nucleotides, increased by an i.v. injection with the antiserum, servived enzymatic hydrolysis by phosphodiesterase in vitro; most of them proved to be bound to the antibody. It was concluded that the increases in plasma cyclic nucleotides in the process of cyclic nucleotide-immunization were mainly due to decreased metabolic clearance of plasma cyclic nucleotides.