Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The acute GH release stimulated by the synthetic hexapeptide, His-DTrp-Ala-Trp-DPhe-Lys-NH2 [GH releasing peptide (GHRP)], was determined in 18 normal men and compared with the effects of GH-releasing hormone, GHRH-(1-44)-NH2. Specificity of effect was assessed by measurement of serum PRL, LH, TSH, and cortisol. GHRP was administered at doses of 0.1, 0.3, and 1.0 microgram/kg by iv bolus. GHRH at a dose of 1.0 microgram/kg was administered alone and together with various does of GHRP. No adverse clinical effects of laboratory abnormalities were observed in response to GHRP. A side-effect of mild facial flushing of 1- to 3-min duration occurred in 16 of the 18 subjects who received GHRH-(1-44)-NH2. Mean (+/- SEM) peak serum GH levels after injection of placebo and 0.1, 0.3, and 1.0 microgram/kg GHRP were 1.2 +/- 0.3, 7.6 +/- 2.5, 16.5 +/- 4.1, and 68.7 +/- 15.5 micrograms/L, respectively. The submaximal dosages of 0.1 and 0.3 microgram/kg GHRP plus 1 microgram/kg GHRH stimulated GH release synergistically. Serum PRL and cortisol levels rose about 2-fold above basal levels only at the 1 microgram/kg dose of GHRP, and there were no changes in serum LH and TSH over the first hour after administration of the peptide(s). GHRP is a potent secretagogue of GH in normal men. Since GHRP and GHRH together stimulate GH release synergistically, these results suggest that GHRP and GHRH act independently. This supports our hypothesis that the GH-releasing activity of GHRP reflects a new physiological system in need of further characterization in animals and man.
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PMID:Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. 210 87

We performed phase I study of FK 435, a new antiestrogen, in 30 patients with advanced breast cancer. Slight to moderate adverse reactions were noted as follows. Single-dose study: anorexia, nausea, lassitude in one patient (80 mg), decreased serum calcium in one (160 mg), redness, tenderness in one, facial flushing, hot flushes, headache in one (320 mg). Repeated-dose study: anorexia, nausea in one patient (40 mg/day), anorexia, diarrhea, increased FSH in one, increased PRL in one (80 mg/day). FK 435 was well tolerated. Tmax was 3-5 hours, T1/2 about 25 hours. Most of FK 435 was excreted into urine as glucuronide.
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PMID:[Phase I study of FK 435]. 219 79

Synthetic analogs of growth hormone-releasing hormone, GHRH(1-29)-NH2 and D-Ala2 GHRH(1-29)-NH2 were administered as a bolus intravenous injection to five normal men in a dose range of 0.015 to 0.5 micrograms/kg body weight. Vehicle only was administered in a control study. Peak responses to GHRH analogs occurred at 15 or 30 min. An increase in the integrated plasma growth hormone (GH) response was observed at each dose. The dose-response curve of GHRH(1-29)-NH2 indicated that it has a similar molar potency to GHRH(1-40) and GHRH(1-44). The potency of D-Ala2 GHRH(1-29)-NH2 was approximately twice that of GHRH(1-29)-NH2. Neither analog affected blood levels of PRL, TSH, LH, FSH, ACTH, insulin, glucagon, glucose, cortisol, free thyroxine, and free triiodothyronine. No side effects were noted other than transient flushing with the highest dose administered. The findings demonstrate GHRH(1-29)-NH2 and its D-Ala2 analog are potent stimulators of GH release and have potential application in clinical medicine.
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PMID:Growth hormone responses to growth hormone-releasing hormone (1-29)-NH2 and a D-Ala2 analog in normal men. 286 96

Human GRF-(1-44)-NH2 (GRF-44) was administered iv in graded doses of 0.01-10 micrograms/kg to 35 normal young adult men and 38 women. GRF-44 stimulated the release of GH in a dose-dependent fashion, although the individual responses varied widely. The ED50 values for this effect were 0.4 micrograms/kg in men and 0.2 micrograms/kg in women in the midfollicular phase of the menstrual cycle. Maximal responses in men and women were not significantly different, and a dose of 1 micrograms/kg was sufficient to produce a maximal response. There was, likewise, no difference between responses of women tested in the midfollicular and midluteal phases of the cycle. There were no changes in PRL, LH, FSH, TSH, ACTH, beta-endorphin, or cortisol at doses up to 1 microgram/kg; at 10 micrograms/kg, PRL increased by an average of 7.6 ng/ml in the women. Side effects occurred in approximately 20% of both men and women at 1 microgram/kg and in nearly all subjects given 10 micrograms/kg; these consisted primarily of flushing and a sense of warmth. Thus, a dose of 1 microgram/kg GRF-44 is safe and effective, and would appear to be a reasonable choice for use in studying GH responses in normal subjects of other ages and in patients with disorders of GH secretion.
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PMID:Dose-response relationships for the effects of growth hormone-releasing factor-(1-44)-NH2 in young adult men and women. 633 Jan 51

The effects of the 44-amino acid growth hormone releasing factor (GRF-44) were tested in normal adult men and women. At a dose of 1 microgram/kg, intravenous boluses of GRF-44 stimulated prompt elevations of plasma GH, which in 5 men reached maximum levels of 34 +/- 28 (S.D.) ng/ml, and in 3 women in the mid-follicular phase, 53 +/- 10 ng/ml. The action of GRF was highly selective; there were no changes in plasma PRL, LH, FSH, TSH, or cortisol at this dose level. Side effects, mostly flushing and a sense of warmth of the face and chest, were mild and occurred only in a minority of subjects.
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PMID:Effects of a growth hormone releasing factor in man. 640 18

Human pancreatic GRF (hpGRF-40; 1 microgram/kg, iv) selectively stimulates GH release in normal men (9). We now report the effects of graded doses of hpGRF-40 on GH release in 12 normal men. Mean peak increments in serum GH after vehicle and the various doses of hpGRF-40 were 1.13, 11.40, 14.60, 17.01, 14.45, and 15.60 ng/ml after vehicle and 0.1, 0.33, 1.0, 3.3, and 10 micrograms/kg hpGRF-40 (iv bolus), respectively. Peak values were observed 30-60 min after hpGRF-40 treatment. There was considerable variability of responsiveness among individual subjects, and no dose-response relationship between the doses and maximal GH values was found. However, the higher doses of 3.3 and 10.0 micrograms/kg resulted in a more prolonged and biphasic pattern of GH release. A side effect of facial flushing of less than 5-min duration occurred in 4 or 6 subjects who received 3.3 micrograms/kg and in all 5 who received 10 micrograms/kg of hpGRF-40. No changes in serum glucose, LH, TSH, PRL, plasma cortisol, or 8 enteropancreatic hormones occurred after hpGRF-40 treatment. There were small increases in serum somatomedin C levels 24 h after the administration of various doses of hpGRF-40 in 11 of 13 studies. Plasma immunoreactive GRF levels measured 5 min after injection were 0.09, 2.0, 4.9, 23.9, and 66.6 ng/ml after 0.1, 0.33, 1.0, 3.3, and 10 micrograms/kg hpGRF-40, respectively. Serum GH responses after insulin-induced hypoglycemia were compared to GH responses after hpGRF-40. Comparable peak GH stimulation occurred with both provocative tests. Mean +/- SEM peak GH was 20.2 +/- 1.0 ng/ml after insulin and 20.9 +/- 3.2 after hpGRF-40 treatment. hpGRF-40 selectively stimulates GH release in normal men over a dose range of 0.1-10 micrograms/kg and is an effective probe to investigate the dynamics of GH release.
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PMID:Human pancreatic tumor growth hormone-releasing factor: dose-response relationships in normal man. 642 60

Human pancreatic tumor GH-releasing factor-40 (hpGRF-40) selectively stimulates GH secretion in normal men and in some adults with GH deficiency. To study its effects in women, we administered hpGRF-40 (3.33 micrograms/kg) or an equivalent volume of vehicle as an iv bolus at 0900 h to 10 normal women during the early follicular, late follicular, and midluteal phases of the menstrual cycle. Serum concentrations of GH, PRL, LH, and FSH were measured at intervals between 0800-1100 h. Serum somatomedin-C concentrations were measured before and 24 h after the administration of vehicle of hpGRF-40. Within 1-3 min after the injection of hpGRF-40 all women described warmth localized to the head and neck and exhibited facial flushing. No changes in pulse rate or blood pressure were noted. When expressed as change from baseline and compared to control values, peak levels of serum GH (nanograms per ml; mean +/- SEM) were higher after hpGRF-40 treatment during the early follicular (5.4 +/- 3.2 vs. 34.9 +/- 8.3; control vs. test day; P = 0.011), late follicular (5.6 +/- 1.5 vs. 25.2 +/- 6.8; P = 0.014), and luteal (0.8 +/- 1.0 vs. 32.7 +/- 12.8; P = 0.033) phases of the menstrual cycle. Similarly, integrated serum GH levels (nanograms per ml/h) were higher after hpGRF-40 administration during the early follicular (0.72 vs. 16.1; P = 0.011), late follicular (0.83 vs. 9.9; P = 0.037), and luteal (-1.54 vs. 17.0; P = 0.036) phases of the cycle. When the increases in serum GH after hpGRF-40 treatment were compared among the phases of the menstrual cycle, however, no differences were found. Serum somatomedin-C values 24 h after hpGRF-40 treatment were higher than those 24 h after vehicle at all stages of the menstrual cycle. hpGRF-40 did not stimulate the release of PRL, LH, or FSH. We conclude that hpGRF-40 stimulates the release of GH, but that in response to the dose used, hpGRF-40-stimulated GH release does not vary during the menstrual cycle.
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PMID:Effects of human pancreatic growth hormone-releasing factor-40 on serum growth hormone, prolactin, luteinizing hormone, follicle-stimulating hormone, and somatomedin-C concentrations in normal women throughout the menstrual cycle. 643 83

L-692,429 (L), a novel nonpeptide mimic of GH-releasing peptide (GHRP), is a potent GH secretagogue in animals and young men. To assess the safety and efficacy of L in stimulating GH release in healthy older men and women, 16 subjects were admitted to a randomized, double blind, cross-over comparison of i.v. administered placebo, GH-releasing hormone [GHRH-(1-29)-NH2; 1 microgram/kg] and two doses of L (0.2 and 0.75 mg/kg). Blood samples were obtained at 5-min intervals for 60 min before and 240 min after each dose for measurement of GH; cortisol, PRL, and insulin-like growth factor-I (IGF-I) were measured less frequently. Peak and integrated GH concentrations increased significantly after L in a dose-dependent manner. Responses to L at either dose were significantly greater than the response to GHRH: peak GH responses in older men and women were (mean +/- SE; micrograms per L): after placebo, 1.2 +/- 0.2; L (0.2 mg/kg), 16.5 +/- 1.8; L (0.75 mg/kg), 32.2 +/- 3.9; and GHRH, 7.6 +/- 1.3 (P < 0.05, L vs. placebo or GHRH). Serum cortisol and PRL concentrations increased after both doses of L, but to values within the respective normal ranges. Serum IGF-I values did not change consistently in any group. The GH responses to GHRH and L (0.75 mg/kg) were highly correlated (r2 = 0.61; P < 0.0004). Deconvolution analysis demonstrated that the increase in serum GH concentrations stimulated by L and GHRH resulted from enhanced GH secretion rates, with no change in the half-life of GH disappearance. Amplitudes of GH secretory pulses were increased 11-, 18-, and 4-fold after L (0.2 mg/kg), L (0.75 mg/kg), and GHRH treatments, respectively. The number of GH secretory pulses was significantly increased by L (0.75 mg/kg; 4.6 +/- 0.4) and GHRH (4.4 +/- 0.3) compared to placebo (2.6 +/- 0.5), but the interval between pulses was shorter after L (0.75 mg/kg; 28.6 +/- 3.6 min) than after GHRH (50.7 +/- 7.7 min; P < 0.05). Adverse experiences were limited to brief episodes of flushing or a warm sensation about the upper body. L-692,429 is a potent GH secretagogue that is well tolerated in healthy older men and women. At the doses employed in this study, L elicited greater increases in GH secretion rates and serum GH concentrations than GHRH. L-692,429 may have therapeutic advantages over peptide GH secretagogues to restore endogenous GH secretion in GH deficiency states or the hyposomatotropism of aging.
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PMID:Neuroendocrine responses to a novel growth hormone secretagogue, L-692,429, in healthy older subjects. 796 1

L-692,429, a substituted benzolactam, is a novel nonpeptide mimic of the GH secretagogue, GH-releasing peptide-6. The safety and GH secretory activity of L-692,429 (0.001-1.0 mg/kg, i.v.) were investigated in 24 healthy nonobese young (18-26 yr old) male volunteers who demonstrated a GH response of 7 micrograms/L or more after 1 microgram/kg, i.v. GH-releasing hormone [GH-releasing hormone-(1-29)NH2]. L-692,429 was administered as a 15-min iv infusion in an incremental dose, double blind, placebo-controlled, alternating panel fashion to 3 panels of 8 subjects each. Dose-dependent GH secretion was observed with a threshold dose of 0.05 mg/kg (4 of 6 subjects responded with peak GH > 7 micrograms/L), and 0.2 mg/kg produced a response in all 14 subjects tested (mean +/- SE peak GH, 41.0 +/- 6.3 micrograms/L). The maximum dose of 1.0 mg/kg L-692,429 resulted in a pronounced GH response (peak GH, 82.5 +/- 14.9 micrograms/L; n = 8). The GH peak was seen 30-45 min after initiation of the infusion. Small transient increases in cortical and PRL were observed (increases in cortical averaged 182.1 +/- 33.1 nmol/L and peak PRL was 21 +/- 2.6 micrograms/L after 1.0 mg/kg L-692,429, respectively), whereas no significant changes occurred in LH, FSH, TSH, insulin, or glucose concentrations. Plasma pharmacokinetic analysis revealed dose-related increases in plasma concentrations of L-692,429 and a half-life of 3.8 +/- 0.2 (+/- SE) h, a plasma clearance of 214 +/- 67 mL/min, and a steady state volume of distribution of 14.2 +/- 4.8 L. Facial flushing or a warm sensation were reported in 4 subjects, primarily at dose levels of 0.2 mg/kg L-692,429 or more, but no other clinical or laboratory adverse experiences appeared related to drug treatment. L-692,429, synthesized as a specific nonpeptide mimic of GH-releasing peptide-6, is thus a well tolerated, highly effective, and selective GH secretagogue in man.
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PMID:Growth hormone response in man to L-692,429, a novel nonpeptide mimic of growth hormone-releasing peptide-6. 807 39