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Biomedical subjects

W Jubiz

Publications and source records attributed to W Jubiz.

At least 37 records · Page 2Linked to original sources
PubMed1980

Prostaglandins activation of erythropoietin production and erythroid progenitor cells.

A model is presented postulating a role for prostaglandins E and prostacyclin in kidney generation of erythropoietin and the activation of the erythroid progenitor cell (CFU-E) compartment by erythropoietin (Ep). Several criteria have been met to prove that prostanoids mediate erythropoiesis: 1) several E-type prostaglandins (PGE2, 15-methyl prostaglandin E2, 16,16-dimethyl E2, 6-keto-E1 and PGE1) produced a significant increase in radioiron incorporation in red cells of exhypoxic polycythemic mice; 2) prostaglandin E2 increased kidney production of erythropoietin in the isolated perfused dog kidney; 3) arachidonic acid, a precursor for all bisenoic prostaglandins, increased kidney production of erythropoietin in the isolated perfused dog kidney which was blocked by pretreatment with the cyclo-oxygenase inhibitor drug indomethacin; 4) hypoxemic perfusion of the isolated perfused dog kidney increased kidney production of erythropoietin and produced an elevation in prostacyclin in the perfusates; 5) albuterol, a beta-2 adrenergic agonist, produced a significant increase in perfusate levels of erythropoietin and PGE in the isolated perfused dog kidney; 6) renal ischemia increased Ep and PGE levels in renal venous plasma which was blocked by pretreatment with indomethacin; 7) prostaglandin E2 and arachidonic acid produced a significant increase in erythroid colonies (CFU-E) in vitro in normal mouse bone marrow; 8) E-type prostaglandins (15-methyl E2) increased in vivo erythroid colony (CFU-E) formation in bone marrows of post-hypoxic polycythemic mice; and 9) injections of 15-methyl E2 daily for six weeks in normal and hypoxic mice produced a significant elevation in the total circulating red cell mass. These studies indicate that hypoxic stimulation of kidney production of erythropoietin may be related to the generation of prostacyclin (PGI2). On the other hand, albuterol and ischemic (reduction in renal blood flow) stimulation of kidney production of erythropoietin involves prostaglandins of the E type. In addition, E-type prostaglandins were found to enhance the effects of erythropoietin in activating erythroid progenitor cells (CFU-E) in the bone marrow. We postulate from our model that prostaglandins E and prostacyclins are involved in the mechanism of kidney production of erythropoietin as well as the activation of the Ep-responsive cell (ERC) compartment.

Albuterol↗
PubMed1980

Albuterol-induced erythropoietin production and prostaglandins release in the isolated perfused dog kidney.

The present study was designed to attempt to clarify the mechanism by which the specific beta-2 adrenergic agonist albuterol causes an enhancement of erythropoietin (Ep) production in the isolated perfused dog kidney. We have postulated previously that prostaglandins (PG) release is an early event in initiating a cascade which leads to enhanced kidney production of Ep. In the present study, the posthypoxic dog kidney was perfused for 5 hr with blood containing 500 microgram/l of albuterol. A significant (P<.001) increase in prostaglandin E (PGE) concentration was seen as early as 1 hr and continued to rise over the 5-hr perfusion period. This microgram increase in PGE was correlated with a significant (P<.05) increase in Ep titers in the perfusates after 3 and 5 hr perfusion. The addition of the PG cyclooxygenase inhibitor meclofenamate (1000 micrograms/l) to the perfusate together with albuterol completely abolished the albuterol-induced increase in PGE and Ep generation in the isolated perfused kidney. No significant increase in PGE or Ep titers in the perfusates occurred during the 5-hr perfusion period in the saline and albuterol plus meclofenamate perfused groups. These data suggest that beta-2 adrenergic activation of Ep production is correlated with an increase in PGE production by the kidney which may be related to the mechanism by which beta-2 agonists enhance kidney production of Ep.

Albuterol↗
PubMed1979

Metyrapone test with adrenocorticotrophic levels. Separating primary from secondary adrenal insufficiency.

Basal plasma adrenocorticotrophic hormone (ACTH) and cortisol concentrations as well as plasma ACTH and 11-deoxycortisol responses to the administration of a single dose of metyrapone were evaluated in 104 patients with intact pituitary-adrenal axis, in 20 patients with secondary adrenal insufficiency, and in seven patients with primary adrenal insufficiency. In patients with primary adrenal insufficiency, baseline ACTH levels were high. Following metyrapone administration, 11-deoxycortisol concentrations were low and ACTH levels did not change. In patients with secondary adrenal insufficiency, baseline plasma ACTH levels were normal, but neither 11-deoxycortisol nor ACTH levels increased in response to metyrapone. The metyrapone test is not only useful to screen for adrenal insufficiency, it is also useful to differentiate a primary from a secondary cause.

Adrenal Insufficiency↗
PubMed1979

Alterations of glucocorticoid actions by other drugs and disease states.

Glucocorticoids are used in physiological and pharmacological amounts in the management of a variety of clinical conditions. Concomitant utilisation of other drugs or the presence of some diseases may affect the physiological action of the steroid in the tissues. Phenytoin, phenobarbitone, ephedrine and rifampicin accelerate the metabolism of glucocorticoids thereby decreasing their biological activity. A similar phenomenon occurs in patients with hyperthyroidism. In contrast, glucocorticoid action is enhanced in hypothyroid patients and in those with hepatic damage as the result of a defect in the clearance of the hormone from blood. In turn, glucocorticoids antagonise the effects of cholinesterase inhibitors and ganglion blocking agents. The above mentioned effects should be kept in mind whenever glucocorticoids are utilised in the diagnosis and management of endocrine or non-endocrine conditions.

Anticonvulsants↗
PubMed1979

Inhibitory effect of prostaglandin F2 alpha on the growth of a hormone-dependent rat mammary tumor.

Growth of the rat hormone-dependent mammary adenocarcinoma MTW-9 was inhibited by prostaglandin F2alpha (PGF2alpha) This inhibition of tumor growth was associated with a marked reduction in serum progesterone concentrations. The inhibitory effect of PGF2alpha on tumor growth was abolished by concomitant injections of progesterone. The growth rates of coimplanted prolactin-secreting pituitary tumor MtTW-5 and plasma concentrations of prolactin and estradiol were not affected significantly by PGF2alpha. Our data imply that the effect of PGF2alpha on growth of rat mammary adenocarcinoma is mediated by progesterone.

Adenocarcinoma↗
PubMed1979

Serum C-peptide in renal failure patients following stimulation of pancreatic secretion.

We have demonstrated persistently elevated serum C-peptide concentrations in patients with chronic renal failure on chronic hemodialysis. A blunted serum C-peptide response to intravenous glucose, glucagon and tolbutamide was also found. However, the response to oral glucose stimulation was greater and more prolonged than in control subjects, probably related to the magnitude of hyperglycemia found in patients with chronic renal failure. These observations suggest the existence of a defect in the renal clearance of C-peptide although an abnormality in C-peptide secretion cannot be excluded.

Adult↗
PubMed1978

The effect of prednisone on serum thyrotropin, thyroxine and triiodothyronine concentrations in hypothyroid patients.

The effect of exogenous prednisone on serum thyrotropin (TSH), thyroxine (T4), and triiodothyronine (T3) concentrations was investigated in four patients with non-functioning thyroid glands receiving T4 replacement therapy. Orally administered prednisone, in a dose of 20 mg each day for nine days, resulted in a significant decrease in mean serum TSH levels (p less than 0.01) without significant changes in levels of serum T4, T3, and thyroxine binding globulin (TBG). These findings suggest an inhibitory action of relatively low pharmacologic doses of prednisone on TSH release without changes in circulating thyroid hormone concentrations or inhibition of the peripheral conversion of T4 to T3.

Adult↗
PubMed1978

A concept for the control of kidney production of erythropoietin involving prostaglandins and cyclic nucleotides.

Our hypothesis is that PGs released within the kidney play a role in the modulation of kidney production of Ep. PGs release probably at medullary and/or cortical sites following erythropoietic stimuli such as hypoxic hypoxia, anemic hypoxia, and ischemic hypoxia induced by renal artery constriction increase kidney production of Ep. PGs which are released probably activate a renal cortical adenylate cyclase thereby enhancing the production of intracellular cAMP. This initiates the cascade of events resulting in the production and/or secretion of Ep by the kidney. The endoperoxide analogs and PGE2 have been found to produce a dose-related and Ep-dependent increase in radioiron incorporation into newly formed red blood cells of exhypoxic polycythemic mice. Indomethacin, a potent PG cyclo-oxygenase inhibitior, attenuates Ep production and the appearance of PGE in the renal venous effluent of animals exposed to hypoxic hypoxia and renal artery constriction. Arachidonic acid (C20:4) and PGE2 infusion into the posthypoxic isolated perfused dog kidney produced a significant elevation in Ep titers in the perfusate. The increase in Ep production caused by arachidonate is blocked by indomethacin. It has been previously reported that PGs of the E series stimulate cAMP formation in several tissues. We have found that not only are renal cortical cAMP levels significantly elevated in rats following exposure to hypobaric hypoxia but that dibutyryl cAMP administration produces an increase in hematocrit and circulating red cell mass in normal mice. Our data thus far strongly support the hypothesis that the renal PGs and the cyclic nucleotides are intimately involved in the pharmacologic and/or pathophysiologic control of Ep production. Further work is necessary to determine whether the PGs and cyclic nucleotides are involved in the day-to-day control of Ep production by the mammalian kidney.

Animals↗
PubMed1978

Effect of indomethacin on the hypothalamic-pituitary-adrenal axis in man.

The effect of the cyclo-oxygenase inhibitor, indomethacin, on hypothalamic-pituitary-adrenal function was investigated in five normal males. Baseline 0800 and 1600 h plasma ACTH and cortisol, plasma ACTH and 11-deoxycortisol responses to metyrapone, and plasma cortisol responses to dexamethasone and exogenous ACTH were not affected by indomethacin. However, the area under the curve for plasma ACTH after iv injection of regular insulin (0.1 U/kg) was significantly decreased during indomethacin administration (control, 88.0 +/- 32.6 cm2, mean +/- sd; indomethacin, 47.6 +/- 23.1, P less than 0.01). Plasma cortisol levels were decreased only at 30 min. Our results support the hypothesis that prostaglandins or any of their precursors play a role in the hypothalamic control of ACTH secretion and indicate that evaluation of hypophyseal ACTH secretory capacity by means of insulin-induced hypoglycemia may yield abnormal results in patients receiving indomethacin.

Adrenal Glands↗
PubMed1978

N-Ethylmaleimide prevents destruction of corticotropin (ACTH) in plasma.

Addition of N-ethylmaleimide, an inhibitor of proteolytic enzymes, to samples for plasma corticotropin determinations prevents destruction of the hormone at room temperature for at least 72 h. A concentration of 125 mg per liter of blood is effective. N-Ethylmaleimide is not so effective in preventing corticotropin degradation in whole blood. Use of the inhibitor should make plasma corticotropin determinations more practical and reliable.

Adrenocorticotropic Hormone↗
PubMed1978

Abnormalities in the regulation of growth hormone in chronic renal failure.

Carbohydrate intolerance is a common abnormality in patients with chronic renal failure. In this group of patients we investigated the interrelation among glucose, insulin, and growth hormone and confirmed the presence of carbohydrate intolerance and hyperinsulinemia. In addition we demonstrated alterations in growth hormone regulation, characterized by (1) the lack of suppression of growth hormone by orally induced hyperglycemia and paradoxical increase in serum levels of growth hormone after the administration of intravenous glucose or glucagon; (2) lack of release of growth hormone with induced hypoglycemia and an exaggerated response to levodopa administration. Furthermore, thyrotrophin-releasing hormone stimulated growth hormone release, a phenomenon not observed in the control population. Our studies show an impaired hypothalamic regulation of growth hormones secretion in patients with renal failure undergoing long-term hemodialysis.

Adult↗
PubMed1977

Tissue lipoprotein lipase in the hyperthyroid rat. Effect of growth and aging.

The hydrolysis of lipoprotein triglycerides is catalyzed by lipoprotein lipase (LPL), an enzyme found in many tissues. We have examined tissue LPL activity (LPLA) in rats with experimentally-induced hyperthyroidism. In younger, lighter rats, hyperthyroidism was accompanied by a decrease in LPL in adipose tissue whereas heart and diaphragm muscle LPL activities were increased. These changes are consistent with the hypothesis that the hypercatabolism and increased beta-adrenergic activity of hyperthyroidism result in characteristic changes in tissue LPLA. In older, heavier hyperthyroid animals, however, adipose tissue LPLA was increased and heart and diaphragmatic LPLA were similar to control activities. Propranolol feeding abolished the thyroxine-induced increase in adipose tissue LPLA. In euthyroid animals of similar size the response of muscle LPLA to short-term starvation was also attenuated. These changes in tissue LPLA may provide a mechanism for shunting triglyceride fatty acids away from adipose tissue for utilization by muscle in the hyperthyroid state. During growth and aging, these adaptations are modified.

Adipose Tissue↗
PubMed1977

Potassium-renin-aldosterone relationships during the first year of life.

In order to gain insight into factors controlling aldosterone secretion during the first year of life, we studied the relationships between PRA, serum potassium, sodium, and serum aldosterone levels. While we found a dissociation during the early neonatal period, there was a high degree of correlation between serum aldosteron, PRA, and serum potassium by 3 to 12 months of age. This suggests that aldosterone secretion in the 3- to 12-month-old child, as in adults, is regulated by the circulating levels of potassium and angiotensin II.

Aldosterone↗
PubMed1977

Plasma prostaglandin E concentrations from birth through childhood.

The prostaglandins are synthesized in a variety of tissues and participate in an extensive number of physiologic processes. As prostaglandin concentrations have not been reported in infants and children, we measured PGE levels from birth through childhood. PGE levels in cord blood were significantly higher than those in adults. By 48 to 72 hours of age, however, they had fallen to levels that were significantly lower than those in adults. Although PGE concentrations increased with age, they remained significantly lower than did adult levels. These low levels may be related to some of the functional pecularities of the immature kidney.

Adolescent↗
PubMed1977

The role of iodine in the pathogenesis of thyroid enlargement in rats with chronic renal failure.

In rats with mild renal failure produced by a 2/3 nephrectomy on one side followed by a total nephrectomy on the other, ingestion of a high (10 mg/kg) iodine diet for two months resulted in thyromegaly, high serum iodine levels and a good correlation between thyroid weight and serum iodine (r = 0.75, P less than 0.01) or thyroid weight and blood urea nitrogen (r = 0.745, P less than 0.01). Iodine may potentiate the effects of unidentified gointrogens that accumulate in rats with renal failure. Since the serum iodine levels were higher in the animals with renal failure, it is also possible that iodine alone may have been responsible for the observed differences in thyroid weight.

Animals↗
PubMed1977

Serum thyrotropin and thyroid hormone levels in humans receiving chronic potassium iodide.

Serum thyroxine (T4), triiodothyronine (T3) and thyrotropin (TSH) concentrations were measured in 13 patients with chronic obstructive pulmonary disease receiving saturated solution of potassium iodide (SSKI). All had a low serum T4 and a high serum TSH concentration. However, serum T3 levels were normal in eight. Recovery of normal thyroid function was observed in each of the seven patients in whom the iodide was discontinued. The same hormones were measured in four normal subjects who received 30 drops of SSKI daily for 11 weeks. An increase in serum TSH levels was preceded by a fall in serum concentrations of T4 and to some extent, T3. Upon SSKI withdrawal subsequent increases in the serum concentrations of both thyroid hormones, but particularly T3, resulted in the return of serum TSH to baseline levels. None of the subjects developed clinical hypothyroidism. It is not apparent why the normal subjects did not exhibit clinical or laboratory evidence of hypothyroidism while the patients with chronic pulmonary disease did. A younger age and the shorter duration of iodide administration in the normal subjects may have played a role.

Adult↗
PubMed1977

Plasma 1,25-dihydroxyvitamin D levels in patients receiving anticonvulsant drugs.

Recent evidence has linked altered plasma vitamin D metabolite levels to the reported occurrence of hypocalcemia and other metabolic abnormalities in patients receiving anticonvulsant drugs. We have measured plasma levels of 25-hydroxyvitamin D (25-(OH)D) and 1,25-dihydroxyvitamin D (1,25-(OH)2D) in institutionalized patients on diphenylhydantoin (Dilantin) and/or phenobarbital therapy. Values were compared with those obtained in institutionalized patients receiving no drugs and with normal ambulatory subjects. Although plasma 25-(OH)D levels were lower in the patients on drugs, a deficiency of 1,25-(OH)2D, the tissue active metabolite of vitamin D, was not present. These results indicate that in patients taking anticonvulsant drugs, the serum calcium, phosphorus, alkaline phosphatase and parathyroid hormone (PTH) abnormalities are not caused by a defective formation of 1,25-(OH)2D.

Adult↗