[Fluorometric determination of 11-hydroxycorticosteroids in the blood].
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Cinchophen injected into the cerebral ventricle reacted with the hypothalamus somewhere in the vicinity ventricle, and produced a release of ACTH as indicated by a rise in peripheral plasma 11-OHCS concentration in the dog. The amount of cinchophen injected into the ventricle corresponds to about 1/600 of the dose required to produce the same effect by the intravenous route. Repeated intraventricular injections of cinchophen were effective in producing gastric erosions and ulcers at smaller doses than the intravenous one (1/100 and 1/400). Damage to the gastric wall might be due to a mechanism involving a localized portion of the hypothalamus and/or via a cerebral ventricle. Bilateral truncal vagotomy did not have any effect on chronic ulcer production. The cinchophen ulcerations were accompanied by an increase in plasma corticosteroids. The new experimental technique for producing peptic ulcer in dogs via a central neurohumoral mechanism is described.
An intraventricular administration of sulpiride suppressed the experimental cinchophen ulcer, thereby the effect of repeated administration of the material on cinchophen ulcerogenesis is evident, whereas intermittent administration lacked this effect. Such an effect as reducing experimental cinchophen ulceration, which is due to central neurohumoral mechanism, following intraventricular infusion of sulpiride appears to be ascribable to a chemical blockage of the hypothalamic structure. It can thus be concluded that sulpiride acts principally at the level of hypothalamus. Its inhibitory action on cinchophen gastric ulcer development is probably exerted via the hypothalomo-pituitary-adrenal axis, which is essential to the occurrence of an ulcer, and may be regarded as favoring the central neurohumoral theory of cinchophen ulcerogenesis.
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In two experiments the effects were investigated of MSH-inhibiting factor-I (MIF-I) and of Melatonin on step-down latencies, defection, plasma 11-OHCS levels, whole brain DA and whole brain NE concentrations on Days 1, 3 and 5 of novelty exposure. Treatment with MIF-I led to a significant habituation of novelty-induced defecation over 5 days, whereas plasma 11-OHCS level was reduced only on Day 1. The concentrations of whole brain DA and whole brain NE also showed a significant increase over days of MIF-I and novelty treatment. Melatonin treatment, on the other hand, significantly inhibited novelty-induced defecation and reduced plasma 11-OHCS level on Day 5 of novelty exposure. Melatonin treatment led to a significant increase of whole brain DA in animals exposed to novelty for 5 days. Neither MIF-I nor Melatonin was found to significantly affect the step-down activity of treated animals. The overall results suggested a possible relationship between novelty-induced defecation and brain DA levels of MIF-I and Melatonin treated animals.
Qualitative and quantitative effects of classical reactions on steroids observed by gas-liquid chromatography (GLC) under standardized conditions, including the double internal-standard technique, are reported. Simple procedures applicable to nanogram amounts of reactants which afford excellent yields of the major products are described. Reactions studied include the Wolff-Kishner removal of keto groups, their conversion into hydroxyl groups with sodium-ethanol or sodium borohydride and into dioxolone derivatives with ethylene glycol; the conversion of hydroxyl into keto groups with chromium trioxide and to trimethylsilyl (TMS) ethers by hexamethyldisilazane; the hydrolysis of dioxolone and TMS derivatives by H+. Gas-liquid chromatograms of reaction mixtures of single- and multistep reactions readily provide information on the effects on the 11alpha-hydroxy and other functional groups at positions 3 and 17 (androstane series) and positions 3 and 20 (pregnane series), and the retention times of many steroids unavailable from commercial or other sources. GLC data analysis provides relationships between steroid structure and retention time from which methods for the computation of retention times and for steroid identification are designed. The accuracy of the calculation methods is demonstrated.
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The increase in plasma-fluorogenic-corticosteroids in response to a single injection of tetracosactrin depot was measured in eleven patients with suspected acute renal insufficiency who were treated simultaneously with prednisolone and deoxycorticosterone acetate (D.O.C.A.). Acute adrenal insufficiency was excluded in seven patients within 24 hours. There was no response in the remaining four patients, and prolonged corticotrophin stimulation tests confirmed the diagnosis of Addison's disease.
Bromocriptine (CB-154, Sandoz) has been given to 21 acromegalic patients (11 female, 10 male) for a period of 6-10 months. The mean serum growth-hormone (G.H.) levels ranged from 10 mug/1 to 512 mug/1 before therapy. Bromocriptine suppressed G.H. values to 5 mug/1 or less in 4 patients and to less than 10 mug/1 in a further 8 patients, but in 2 patients G.H. levels did not show any significant reduction. Bromocriptine did not block stress-induced G.H. secretion. It did not distrub pituitary function other than secretion of prolactin and had negligible side-effects. Its effect on tumour size is uncertain and it is therefore unsuitable for patients with suprasellar extension of the tumour. Otherwise it seems reasonable to offer a trial of bromocriptine to all patients with acromegaly where therapy is deemed necessary. In those who show a full response of G.H. levels with a dose of 20-40 mg of bromocriptine per day, external radiation to the pituitary can be used to prevent tumour expansion and bromocriptine withdrawn at intervals to assess the effect of the radiation. In patients with a partial response to bromocriptine, the decision to offer alternative therapy depends on the extent of the response and on the age and medical condition of the patient. In patients who fail to respond to bromocriptine, particularly those younger patients with active disease, more definitive local treatment (e.g., trans-sphenoidal removal of the tumour or yttrium-90 implantation) would be indicated. Bromocriptine may also be used with benefit in the large number of patients who have shown a partial response to other forms of therapy.
Heparin and the heparinoid Ro 1-8307 inhibited the secretory rate of aldosterone in physiological or pathological aldosteronism to the level found in normal subjects on liberal sodium intake. In addition, these compounds inhibited corticosterone biosynthesis, although less markedly than that of aldosterone. Indications of interference with cortisol production have not been found. During drug treatment angiotensin, in doses of 5-10 ng/kg b.wt./min, did not stimulate aldosterone secretion. ACTH responsiveness of the adrenals--indicated by the fractional increases of both aldosterone and corticosterone secretory rates--remained unchanged. In two studies heparin had no consistent effect on plasma renin activity.
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In the course of investigations of gamma-oryzanol in rats, circadian rhythms in antiulcerogenic action on gamma-oryzanol were observed. Circadian rhythms in several other parameters were investigated and correlated with the antiulcerogenic action. Pretreatment of rats with gamma-oryzanol 100 mg/kg, s.c., for 5 days tended to decrease serum gastrin levels and gastric secretion, and to increase serum 11-OHCS. Suppresive patterns of serum gastrin and gastric secretion following the pretreatment with gamma-oryzanol corresponded to the circadian rhythms in antiulcerogenic action of gamma-oryzanol. A complication of our results suggests that increment of catecholamines in rat brain after gamma-oryzanol plays a role in the above mentioned actions.
Seven urinary metabolites of tryptophan-kynurenine pathway were measured in riboflavin-deficient, pyridoxine-deficient, pair-fed and natural diet baboons. The most significant changes in the pyridoxine-deficient baboons was a mean sevenfold increase in the excretion of xanthurenic acid and a threefold decrease in 3-hydroxy anthranilic acid. The riboflavin-deficient baboons showed a twelvefold increase in the excretion of anthranilic acid, and a tenfold decrease in 3-hydroxy kynurenine. Red blood-cell pyridine nucleotides decreased only in the pyridoxine-deficient baboons, while plasma 11-hydroxy corticosteroids increased only in the riboflavin-deficient baboons. These results are discussed in relation to enzymatic changes that may be expected during these deficiencies.
Mechanisms of integration in the neuroendocrine system in the regimens of physiological rhythm (oestral cycle) and of isolated effect upon one link of the system (metapyrone administration) were studied with the aid of qualitative histoenzymological analysis of adenohypohysis and adrenal cortex, estimating the comoplex reorganization of various structural components of adenohypophysis and adrenal cortex in response to specific depression of glycocorticoid synthesis. The role of the so called unspecific reorganization in the maintenance of functional response to isolated effects upon certain endocrine functions is discussed along with the necessity of further studies on the principles of interaction in the endocrine system using morphofunctional analysis.
The effect of a changed atmosphere, hypoxia, hypercapnia, their combinations and different motor activities on the adrenocortical function was studied in 36 test subjects kept in an 8 m3 altitude chamber. Human adaptation to the environmental changes developed with an active involvement of the adrenal cortex. The level and direction of the changes depended on both the force of the influences and on the initial state of the test subjects.
The concentration of the fractions of corticosteroids, aldosterone, catecholamines, and cyclic nucleotides (cAMP and cGMP) in blood of the adrenal veins and the activity of renin in blood of the renal veins were studied in 22 patients with stages IIA and IIB hypertensive disease. At the same time the content of these substances in the peripheral blood was determined and compared with the level of steroid and catecholamine excretion in the daily urine. An increase in the content of free 11 OCS and F fractions in the peripheral blood and blood of the adrenal veins was revealed in all patients examined.
The authors studied the functional interrelations between the adrenal glands and the thyroid gland of female albino rats of various age groups. Blood content of 11-oxycorticosteroids and protein-bound iodine was determined. Analogous determinations were carried out in partial exclusion of the adrenal gland function (metapyron block) and of the thyroid gland function (6-methyluracil block). It is supposed that in the young sexually-mature female albino rats the functions of the adrenal glands and the thyroid gland were in direct relationship irrespective of the cyclic variations in the sex steroid secretion; with the advance of age this association became deranged.