Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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1. Normal subjects showed a highly reproducible, rapid increase in plasma adenosine 3':5'-cyclic monophosphate (cyclic AMP) after an intravenous injection of 200 MRC units of highly purified bovine parathyroid hormone. 2. No significant increase in plasma cyclic AMP was observed after administration of bovine parathyroid hormone to patients with severe chronic renal failure. 3. Even when renal function was not impaired, some patients with primary hyperparathyroidism, who had high concentrations of endogenous parathyroid hormone, showed resistance to bovine parathyroid hormone and when this was injected intravenously it caused only a small increase in plasma cyclic AMP. This resistance was reversible since there was marked improvement in the response after parathyroidectomy, when endogenous parathyroid hormone concentration had fallen. 4. It was possible to reproduce this resistance to the hormone by intravenous infusion of bovine parathyroid hormone into normal subjects. When the hormone (1000 MRC units) was infused over 2 h, after an initial increase there was a progressive decline in plasma cyclic AMP concentration and a fall in urinary cyclic AMP excretion. The response to a standard test stimulus (200 MRC units of bovine parathyroid hormone given as a rapid intravenous injection) was examined at intervals after 1000 units of bovine parathyroid hormone had been infused. Initially, the response was severely impaired; at 4 h, partial recovery had occurred and, 24 h after the infusion, recovery of the response was complete. The resistance was therefore reversible. Infusion of the amino-terminal peptide, fragment 1-34, gave the same effect as infusion of intact hormone. Region-specific assays for the hormone were used to show that the concentration of immuno-assayable hormone remained high during the infusions. 5. The mechanism of this reversible resistance to parathyroid hormone remains to be elucidated; it seems unlikely that circulating hormone fragments could account for the prolonged impairment in the responsiveness to the intact hormone. It is possible that alteration in the formation, intracellular degradation or, perhaps, release of cyclic AMP from the cells, is the cause. Changes in the characteristics of the hormone receptor sites might also explain the phenomenon.
Clin Sci Mol Med 1976 Jul
PMID:Reversible resistance to the renal action of parathyroid hormone in man. 18 Nov 94

Isolated pituitary cells prepared from adrenalectomized rats secrete ACTH in response to CRF, and this response is inhibited by corticosterone. Both the stimulation of release by CRF and the inhibition of release by corticosterone are antagonized by cordycepin (3'-deoxyadenosine). Inhibition of CRF-stimulated secretion by cordycepin is apparently not related to inhibition of RNA synthesis, since high doses of actinomycin D do not affect ACTH secretion. More likely, cordycepin's inhibition of secretion stems from its inhibition of adenylate cyclase activity. Inhibition of corticosterone action by cordycepin is qualitatively similar to that previously reported actinomycin D. This effect of both drugs is probably due to inhibition of RNA synthesis. Significantly, a low dose of cordycepin has a greater inhibitory effect on corticosterone action than on total cellular RNA synthesis. Cordycepin is reported to preferentially inhibit messenger RNA synthesis, and low dose preferentially inhibits appearance of cytoplasmic RNA in pituitary cells. These data suggest that corticosterone-induced RNA is a cytoplasmic (messenger) RNA.
Mol Cell Endocrinol 1978 Jan
PMID:Effect of cordycepin on CRF stimulation and steroid inhibition of ACTH secretion by rat pituitary cells. 20 1

1. The pharmacokinetics of intravenous and oral pindolol were determined in 24 hypertensive patients with normal or impaired renal function. 2. In patients with normal renal function, the total clearance of the drug was the sum of both the renal and non-renal clearances in equal parts. The non-renal clearance was found to equal the hepatic clearance directly measured from the hepatic extraction ratio and hepatic blood flow. 3. Compared with patients with normal renal function, patients with chronic renal failure exhibited (i) unchanged transfer rate constants and distribution volumes, (ii) decreased total body clearance with decreased renal clearance and unchanged non-renal clearance. 4. Analysis of data obtained after oral administration of the drug by the Loo-Riegelman method showed that the pindolol absorption kinetic was non-linear. Compared with patients with normal renal function, patients with chronic renal failure exhibited (i) a significantly decreased fraction of dose effectively absorbed, (ii) an increased initial rate of absorption. The initial rate of absorption was inversely correlated with creatinine clearance. 5. The study provided evidence that in patients with renal insufficiency, (i) no increase in the metabolism of the drug accompanied the decrease in renal function, and (ii) decreased bio-availability was associated with a reduced fraction of the dose effectively absorbed and an increased rate of absorption.
Clin Sci Mol Med Suppl 1978 Dec
PMID:Pharmacokinetics of intravenous and oral pindolol in hypertensive patients with chronic renal failure. 28 67

1. Plasma concentrations of human calcitonin were measured in groups of patients with chronic renal failure, treated either conservatively or by haemodialysis, and compared with a normal group of persons. 2. Plasma calcitonin was statistically significantly elevated in both groups with renal failure. 3. When the data from the three groups were pooled, plasma calcitonin was found to be inversely correlated with total calcium and directly correlated with plasma creatinine.
Clin Sci Mol Med 1977 Jun
PMID:Plasma calcitonin in chronic renal failure: relation to other factors of importance in bivalent ion metabolism. 32 18

1. To evaluate potential alterations in hepatic metabolism of drugs occurring in patients with renal insufficiency the fate of aminopyrine was studied in 17 patients with chronic renal failure and in 27 normal subjects. 2. Although patients with chronic renal failure exhibited large variations, their aminopyrine plasma disappearance times (mean 0.62 +/- SD 0.24 h-1) were significantly higher than those found in normal subjects (0.30 +/- 0.07 h-1, P less than 0.002). 3. 14CO2 derived from [dimethylamine-14C]aminopyrine disappeared from breath more rapidly in patients with chronic renal failure and a history of analgesic abuse (0.40 +/- 0.04 h-1) than in control subjects (0.22 +/- 0.03 h-1, P less than 0.01) and in other patients with chronic renal failure (0.24 +/- 0.04 h-1). 4. Dialysis treatment and serum creatinine concentrations were not correlated with the rates of aminopyrine metabolism. Two additional patients, however, with combined renal and hepatic disease, exhibited markedly slowed rates of aminopyrine demethylation. 5. Although chronic renal failure by itself might not alter microsomal drug metabolism it is concluded that, in patients with a history of abuse of phenacetin-containing analgesics, marked acceleration in aminopyrine N-demethylation may be observed.
Clin Sci Mol Med 1978 Feb
PMID:Hepatic metabolism of aminopyrine in patients with chronic renal failure. 62 May 2

1. Five patients with the osteomalacia of chronic renal failure were given 50--100 nmol of 25-hydroxy vitamin D3 intravenously per day for 24--28 days. 2. In all five patients, during administration of 25-hydroxy vitamin D3 there was a substantial rise in the plasma concentration of 25-hydroxy vitamin D from initially abnormally low values. 3. Significant improvement in bone mineralization, intestinal calcium absorption and muscle strength occurred in the three patients with the greatest rise in plasma 25-hydroxy vitamin D.
Clin Sci Mol Med 1977 May
PMID:The effect of 25-hydroxy vitamin D3 in the osteomalacia of chronic renal failure. 86 43

1. One-year-old male rats were injected intravenously with 200 pmol of 25-hydroxy[26(27)-methyl-3H]cholecalciferol per 100 g body weight and the presence of this metabolite of vitamin D, as well as other metabolites, produced during the following 8 h was examined in serum, urine and bile. 2. The chromatography data indicated an excretion of 25-hydroxycholecalciferol both in bile and urine and, in urine, also of 1,25-dihydroxycholecalciferol. In bile, fractions of labelled substances were also obtained which, according to their elution positions, might represent cholecalciferol and conjugated metabolites. 3. The excretion of active metabolites of vitamin D in normal urine might be elevated in chronic renal failure and, in conjunction with a reduced synthesis, contribute to the occurrence of renal osteodystrophy.
Clin Sci Mol Med 1977 Oct
PMID:Excretion of active metabolites of vitamin D in urine and bile of the adult rat. 91 62

1. Five normal subjects were given 100 ml of aluminium hydroxide gel per day for 28 days. 2. The phosphorus balance became more positive in one subject, less negative in two and changed from negative to positive in the other two subjects. This was accompanied by a rise in the concentration of the fasting morning plasma phosphorus. Calcium balance did not change. 3. The normal subjects absorbed 0-3-3-6 mmol of aluminium/day, which is significantly less than that absorbed by five patients with chronic renal failure, three of whom were studied before, and two after, the observations on the normal subjects had been completed. 4. In a further five normal subjects on 100 ml of aluminium hydroxide gel/day the 08.00 hours concentration of plasma phosphorus did not fall, though there was a fall at 11.00, 14.00 and 17.00 hours.
Clin Sci Mol Med 1976 Oct
PMID:The effect of aluminium hydroxide orally on calcium, phosphorus and aluminium metabolism in normal subjects. 97 81

1. The anti-hypertensive effect of converting enzyme inhibition was evaluated in twenty-three hypertensive patients (seven renovascular, four essential, four malignant, one scleroderma, three chronic renal failure, four primary or idiopathic aldosteronism). 2. In sixteen patients a single injection (1--4 mg/kg) of the inhibitor produced an immediate anti-hypertensive effect, which lasted up to 16 h. In six patients the anti-hypertensive effect of the inhibitor was significantly improved after sodium depletion. 3. Plasma renin activities increased and plasma aldosterone concentrations decreased consistently except in idiopathic aldosteronism. 4. Converting enzyme inhibition provides a direct way of defining the degree of renin-dependency of the hypertension. Accordingly, it can be used diagnostically and for planning appropriate therapy. Therapeutically, it could be advantageous in hypertensive emergencies because of its safety, specificity and capacity to reduce aldosterone secretion.
Clin Sci Mol Med Suppl 1975 Jun
PMID:The use of angiotensin-converting enzyme inhibitor in the diagnosis and treatment of hypertension. 107 92

1. The relation between endogenous urea metabolism and albumin synthesis has been studied in ten patients with chronic renal failure and in four normal subjects, after single intravenous injections of [14-C]urea,[15-N]urea and 125-I-labelled albumin. 2. The rate of urea synthesis was determined from the dynamics of plasma [14-C]urea specific radioactivity and the rate of urea metabolism was estimated from the relative rates of urea synthesis and urea appearance in urine and body water. Deconvolution analysis of plasma [15N]albumin enrichmevt and 125-i-labelled albumin radioactivity yielded the cumulative incorporation of 15-N into total exchangeable albumin and enabled calculation of the absolute rate of urema nitrogen utilization for albumin synthesis. 3. Although the mean absolute rate of urea degradation in uraemic patients (3-7 mmol/h) was higher than in normal subjects (2-3 mmol/h) there was no significant positive correlation between urea degradation and plasma urea concentration. 4. In uraemic subjects, there was a significant positive correlation between urea synthetic rate and urea degration rate. 5. The rate of utilization of urea nitrogen for albumin synthesis was low, but was very much higher in uraemic subjects (mean 83-8 mumol/h) compared with normal subjects (mean 6-4 mumol/h), as was the provision by urea of the nitrogen required for albumin synthesis in uraemic subjects (2-37%) compared with normal subjects (0-13%). 6. The efficiency of utilization of urea nitrogen for albumin synthesis was higher in the uraemic patients (1-3%) than the normal subjects (0-2%), and was higher in those patients with chronic renal failure who received a 30 g protein diet than those on 70 g of protein. A significant negative correlation was noted between efficiency of urea nitrogen utilization and the rate of synthesis of albumin. 7. These studies suggest the presence of a mechanism for the conservation of urea nitrogen in chronic renal failure which is unrelated to the extent of urea degradation, and which can only be partly explained by the higher proportion of intraluminal gut nitrogen derived from urea.
Clin Sci Mol Med 1975 May
PMID:Efficiency of utilization of urea nitrogen for albumin synthesis by chronically uraemic and normal man. 112 30


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