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Biomedical subjects

F W Beck

Publications and source records attributed to F W Beck.

At least 55 records · Page 3Linked to original sources
PubMed1983

Effects of bromocriptine on the circadian rhythm of 18-hydroxycorticosterone and cortisol secretion in essential hypertensives.

This study examines the influence of bromocriptine, a dopamine agonist, on circadian secretory patterns of plasma 18-hydroxycorticosterone (18-OHB) and cortisol in essential hypertension. Patients with sustained essential hypertension were studied after they had reached equilibrium on a constant 150 mmol sodium and 80 mmol potassium intake. Plasma 18-OHB and cortisol determinations were made at 30-min intervals over 24 h during a control and bromocriptine treatment period (bromocriptine, 2.5 mg t.i.d. for five days). Circadian patterns for plasma 18-OHB and cortisol were observed in all patients before and after bromocriptine. Although bromocriptine did not affect the circadian rhythm of 18-OHB and cortisol it did decrease mean 24-h recumbent 18-OHB from 23 +/- 42.2 to 14.3 +/- 1.4 ng/dl. These results suggest that there is a circadian rhythm of both 18-OHB and cortisol secretion in patients with essential hypertension as in normotensives. Dopaminergic mechanisms exert an effect on the quantitative secretion of 18-OHB. However, the circadian rhythm for 18-OHB and cortisol does not appear to be dependent on dopaminergic mechanisms.

18-Hydroxycorticosterone↗
PubMed1983

Altered corticosteroid control of the erythrocyte sodium-potassium pump in the spontaneously hypertensive rat.

Recent evidence suggests that corticosteroids may participate in the regulation of erythrocyte Na,K pump activity. To examine the possible role of mineral- and glucocorticoids in the physiological control of Na,K pump in vivo, 10-week-old Sprague-Dawley (SD), Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were randomly assigned to four treatment groups (n = 10 for each): (a) sham operation, (b) bilateral adrenalectomy, (c) bilateral adrenalectomy followed by daily intraperitoneal (i.p.) injection of aldosterone, 10 micrograms/kg, (d) bilateral adrenalectomy followed by daily i.p. injections of dexamethasone 60 micrograms/kg. Fourteen days later all rats were sacrificed and the erythrocyte Na,K pump activity was assessed by two different assays: ouabain sensitive ATP hydrolysis in isolated membranes (ATPase) and 86Rb uptake by intact erythrocytes. SHR exhibited reduced Na,K pump activity as measured by ATPase (compared to WKY) and by 86Rb uptake (compared to WKY and SD rats). Adrenalectomy was associated with 22-44% reduction in ATPase in all three rat species (P less than 0.05-0.01). Adrenalectomized aldosterone or dexamethasone treated SHR, WKY and SD rats exhibited ATPase activity that was indistinguishable from the corresponding control groups. Similarly, 86Rb uptake was lower in adrenalectomized SD and WKY rats. This reduction could be at least partially prevented by daily treatment with either aldosterone or dexamethasone. In SHR adrenalectomy had no effect on 86Rb uptake whether accompanied by daily treatment with aldosterone or dexamethasone or not. These results suggest that the erythrocyte sodium potassium pump is corticosteroid dependent in normotensive rats. An abnormal response of the Na,K pump to corticosteroids is observed in SHR, with a dissociation between steroid stimulated enzymatic ATP hydrolysis and actual transmembrane pumping as measured by 86Rb uptake.

Adenosine Triphosphatases↗
PubMed1983

Effects of metoclopramide on plasma corticosteroid levels in sheep.

This study investigated the role of dopaminergic mechanisms in modulation of corticosteroid secretion in sheep. Administration of the dopamine antagonist metoclopramide (200 micrograms/kg iv) in six mature sheep resulted in rapid and parallel rises in plasma cortisol, corticosterone, 18-hydroxycorticosterone, and aldosterone. Treatment of the sheep with 4 mg dexamethasone im every 6 h for 4 days abolished the response of all four corticosteroids to metoclopramide in the six sheep. These observations suggest that metoclopramide may stimulate corticosteroid secretion in sheep via nonspecific stressor effects.

18-Hydroxycorticosterone↗
PubMed1983

Plasma corticosteroids in hyperreninemic hypoaldosteronism: evidence for diffuse impairment of the zona glomerulosa.

A subgroup of critically ill patients with selective hypoaldosteronism despite hyperreninemia has recently been defined. The mechanism underlying the subnormal response of aldosterone secretion is poorly understood. As cortisol secretion remains intact and the condition usually follows hypotensive episodes, ischemic or functional impairment restricted to the adrenal glomerulosa may be involved. To evaluate the possibility that a specific biosynthetic pathway deficiency exists in hyperreninemic hypoaldosteronism (HH), basal and ACTH-stimulated levels of aldosterone and its immediate precursors 18-hydroxycorticosterone (18-OHB) and corticosterone (B) were determined in eight HH patients, six critically ill subjects with normal aldosterone responsiveness, and nine healthy subjects. Baseline aldosterone (8.2 +/- 3.2 vs. 44.7 +/- 23.6 ng/dl) and 18-OHB (44.7 +/- 13.6 vs. 547.6 +/- 300.4 ng/dl) were lower in HH patients than in Intensive Care Unit controls (both P less than 0.01) despite similarly increased renin concentration and activity. ACTH-stimulated aldosterone and 18-OHB were significantly lower in HH patients, although the percent increase was similar to Intensive Care Unit controls. Plasma B was also lower in HH patients, though not significantly. After ACTH, B was markedly lower than both ICU controls (1764 +/- 576 vs. 6299 +/- 1266 ng/dl, P less than 0.01) and healthy controls (3261 +/- 248 ng/dl, P less than 0.01). All groups had appropriate cortisol responses demonstrating normal zona fasciculata function. Since 18-OHB arises predominantly from the zona glomerulosa, whereas B also derives in part from the zona fasciculata, the data suggest generalized impairment of the adrenal zona glomerulosa probably affecting both early and late pathway corticosteroid biosynthesis.

18-Hydroxycorticosterone↗
PubMed1983

Dopaminergic regulation of 18-hydroxycorticosterone and aldosterone secretion in man.

This study was designed to investigate dopaminergic mechanisms involved in the control of corticosteroid secretion. Plasma renin activity (PRA), prolactin, cortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycorticosterone (18-OHB) and aldosterone responses to metoclopramide 10 mg iv in the presence of a vehicle or dopamine (3 microgram/kg/min) infusions, or domperidone 10 mg iv were evaluated in 10 normal males. Metoclopramide, and the peripheral dopamine antagonist, domperidone both resulted in rises in serum prolactin levels. Metoclopramide, but not domperidone, resulted in parallel rises in plasma 18-OHB and aldosterone levels. Dopamine infusion markedly inhibited prolactin, 18-OHB and aldosterone responses to the central and peripheral dopamine antagonist metoclopramide. Administration of the dopamine agonist, bromocriptine, 2.5 mg three times a day for 4 days suppressed (P less than 0.01) mean 24 h plasma 18-OHB levels from 22.1 +/- 2.1 to 15.8 +/- 1.5 ng/dl. These results suggest that dopaminergic mechanisms modulate the secretion of 18-OHB and aldosterone. The circadian rhythm of 18-OHB secretion is not dependent on dopaminergic mechanisms.

18-Hydroxycorticosterone↗
PubMed1983

Dopaminergic modulation of corticosteroid responses to angiotensin II in man.

This study was designed to investigate dopaminergic mechanisms involved in the control of corticosteroid secretion in man. Plasma cortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycorticosterone (18-OHB), and aldosterone responses to graded doses of angiotensin II and ACTH were evaluated in six healthy male volunteers with and without treatment with the dopamine agonist bromocriptine (BEC). Angiotensin II infusion resulted in parallel responses of 18-OHB and aldosterone without affecting other precursors of the aldosterone biosynthetic pathway. BEC (2.5 mg tid for 6 days) markedly suppressed basal supine plasma 18-OHB levels without affecting basal levels of aldosterone. Basal supine plasma corticosterone levels were increased after BEC treatment. BEC treatment inhibited the 18-OHB and aldosterone responses to graded infusions of angiotensin II. Plasma 18-OHB responses to ACTH infusion were not altered by BEC treatment. Other factors renin activity and serum electrolytes were not altered by BEC administration. These results suggest that angiotensin-mediated 18-OHB and aldosterone secretion is selectively inhibited by dopaminergic mechanisms.

11-Hydroxycorticosteroids↗
PubMed1978

Lymphocyte surface poisons: disulfides and thiolsulfonates.

Eight disulfides (I-VIII) and a thiolsulfonate (IX) were promising blocking agents of lymphocytes in graft-versus-host reactions (GvHR) without comensurate intracellular effects. The blocking effects were assayed through inhibition of the local GvHR after parental lymphocytes had been incubated with agents at suitable concentrations and then inoculated into F1 hybrid offspring. The intracellular effects were assessed beforehand by measuring the inhibition of [6-3H]thymidine incorporation by lymphocytes in the presence of a wide range of concentrations of agents. Concentration levels which induced no greater than approx. 50% inhibition of the [6-3H] thymidine incorporation were considered to reflect sufficiently small intracellular effects and were used for the subsequent GvHR comparisons. Cellular survival always was 90% or more for the GvHR tests (unless stated otherwise), even when inhibition of thymidine incorporation was as high as 50%; hence the thymidine data are useful not only as guides for dose levels in the GvHR but also as leads to new agents that may show immunosuppressive or anti-leukemic activity through intracellular effects. Structural specificity of the active compounds as cell-surface poisons is evidenced by little or no activity (less than 30% inhibition of GvHR) of 28 other disulfides, 2 trisulfides, 2 Bunte salts, and 8 other thiolsulfonates. Active agents may owe this function to replacement of the H of SH in cell-surface thiol receptors by an SR group. Glutathione did not significantly inactivate agents, probably because the products of reaction also are active disulfides. When two agents (III, IX) were given orally or intraperitoneally to F1 hybrid recipients of untreated parental cells, doses of 10--15 mg/kg produced a GvHR inhibition of 17--53%.

Animals↗
PubMed1976

Modifications in the establishment of allergic encephalomyelitis (EAE) in rats; an imporved assay for immunosuppressant drugs.

EAE induced in Lewis rats by guinea-pig spinal cord and such lipid adjuvants as hexadecane or squalene (without the mycobacterial component) is more sensitive to lower doses of cyclophosphamide and some select immunosuppressive agents than the conventional EAE induced using Freund's complete adjuvant. In addition, these animals do not suffer from adjuvant arthritis which may be induced if the bacterial component is present. These modifications in the conventional assay have enhanced its ability to detect new, weaker and/or lower doses of known immunosuppressants.

Adjuvants, Immunologic↗
PubMed1976

Improvements for consistently inducing experimental allergic encephalomyelitis (EAE) in rats: I. without using mycobacterium. II. inoculating encephalitogen into the ear.

Several methods of inducing experimental allergic encephalomyelitis (EAE) in rats were examined using different (i) rat strains, (ii) combinations of encephalitogen with different adjuvants, and (iii) sites of encephalitogen inoculation. The time course and severity of the ensuing diseases were determined and methods delineated for inducing a disease with limited variability and high incidence. Omitting the mycobacterial component from the adjuvant eliminated the complication of adjuvant arthritis, which may develop after the appearance of EAE. Encephalitogenic emulsions prepared with an equal volume of frozen guinea pig spinal cord (GPSC) and hexadecane or squalene, injected into two inguinal nodes or one foot pad of Lewis rats, provided two quick and easy ways to induce EAE. Emulsions of encephalitogen with Freund's complete adjuvant or hexadecane, injected into the ear, also induced EAE but lengthened the time between the antigen inoculation and clinical symptoms which accompany the onset of EAE disease. However, injection into the ear offers an advantage over the Newbould technique (direct instillation of encaphalitogen in pre-exposed lymph nodes), since the animals can be confidently predosed with drugs which may reduce lymphoid mass. Effects of local inflammation on systemic drug metabolism are also minimized when using the ear route.

Adjuvants, Immunologic↗
PubMed1976

Arthritogenicity in rats of cell walls from several streptococci staphylococci and two other bacteria.

Bacterial cell walls from Str. bovis, Str. lactis, Str. mutans, Str. thermophilus, Str. salivarius, and Str. pyogenes were able to produce polyarthritis in rats but Str. faecalis cell walls were nonarthritogenic. S. aureus cell walls produced extremely severe disease. It was also shown that cell walls from S. epidermidis, B. megaterium, and M. lysodeikticus were nonarthritogenic. A close correlation was observed between development of arthritis and the delayed hypersensitivity to bacterial peptidoglycans but not with the PPD hypersensitivity. It was suggested that the adjuvanticity of bacterial cell walls is needed to induce the disease and that arthritogenicity requires a specific antigen in addition to the presence of an adjuvant-inducing agent.

Animals↗
PubMed1975

Irritancy of cyclophosphamide-derived aldehydes (acrolein, chloracetaldehyde) and their effect on lymphocyte distribution in vivo: protective effect of thiols and bisulphite ions1).

(1) A strategy is described for investigating agents such as N-acetylcysteine or penicillamine that might be used as adjuvant therapy with cyclophosphamide, to lessen the toxic side-effects of this latter drug caused by some of its metabolites. (2) The toxic effects of acrolein and chloracetaldehyde were determined by (a) their effects on lymphocyte circulation and (b) their oedemagenic activity in rats. (3) Stable thiols and bisulphite ions antagonised this aldehyde toxicity/irritancy; thiosulphate ions did not. (4) Thiosulphate and bisulphite ions antagonised the irritancy/toxicity of a mustard, mechlorethamine (HN-2). (5) The possible relationship of intrinsic irritancy to anti-inflammatory activity is discussed briefly.

Acetaldehyde↗