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

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

Synthetic human GRF (hGRF (1-44) NH2; SM-8144) was administered as an iv bolus to 141 normal children of short stature (NSC), 73 patients with severe idiopathic GH deficiency (IGD; group A), 30 patients with mild idiopathic GH deficiency (IGD; group B), 29 patients with secondary GH deficiency, 3 patients with primary hypothyroidism, 21 patients with Turner's syndrome and 25 patients with various other disease. Their height was below normal for their age and sex, and they were all below 25 years old without obesity. The maximal GH responses (M+SEM) were 39.5 +/- 2.2, 7.2 +/- 0.9, 27.2 +/- 3.7, 5.2 +/- 0.8, 9.7 +/- 4.4, 25.1 +/- 2.8 and 32.3 +/- 4.8 ng/ml, respectively (significance from the NSC, ; p less than 0.05, ; p less than 0.001). The GH responses to hGRF were greater than those elicited by standard pharmacological tests. There was a negative correlation between bone age and peak plasma GH response to hGRF in patients with idiopathic GH deficiency (IGD) but not in normal children (NSC). In twenty-two percent of the patients with IGD in group A the response was above 10 ng/ml and in 57% of the patients with IGD in group B the response was above 20 ng/ml, suggesting that a large percentage of patients with idiopathic GH deficiency lack hypothalamic GRF. The side effect of flushing was observed in 15.2% of all subjects. These results indicate the potential usefulness of hGRF (1-44) NH2 (SM-8144) in inducing GH release from the pituitary.
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PMID:Plasma growth hormone (GH) response to GH-releasing factor (SM-8144) in children of short stature and patients with GH deficiency. 311 40

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

A synthetic replicate of human pancreas growth hormone-releasing factor, hpGRF1-44-NH2, (hpGRF44), a 44-amino acid amidated peptide, was administered to seven normal men. In addition to placebo, 4 subjects received 3 doses of hpGRF44 (0.5 microgram/kg, 5 micrograms/kg, 10 micrograms/kg), while one subject received 2 doses (5 micrograms/kg, 10 micrograms/kg) and 2 subjects received one dose (0.5 microgram/kg or 5 micrograms/kg), each as a rapid intravenous injection. A significant increase in circulating growth hormone (GH) was observed at each dose (0.5 microgram/kg, p = 0.05; 5 micrograms/kg, p less than 0.005; 10 micrograms/kg, p = 0.01) when compared to placebo, with equivalent maximal responses. At all doses studied a rise in plasma GH occurred within 5 min, with a peak response in most patients at 30-45 min. There were no associated changes in any of the other anterior pituitary hormones or insulin. Other than transient flushing and minimal changes in vital signs, no side effects were noted. The results of these studies support the potential usefulness of hpGRF44 for the assessment of GH secretion and reserve, and of this peptide or an analog as a therapeutic agent to stimulate GH release.
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PMID:Synthetic human pancreas growth hormone-releasing factor (hpGRF1-44-NH2) stimulates growth hormone secretion in normal men. 640 19

Ammonia removal from a recirculating dialysate stream is a major challenge in developing a truly portable, regenerable hemodialysis system. Three zeolites, type F, type W, and clinoptilolite, were found to have good ammonia ion exchange capacity with linear equilibrium ion exchange coefficients of 0.908, 0.488, and 0.075 L/g, respectively. The linear equilibrium ion exchange coefficient relates dialysate ammonia concentration (mumol/L) to the amount of ammonia absorbed by zeolite (mumol/g) at equilibrium. Ammonia uptake by zeolite powders was fast, with equilibrium reached within 15 sec. Zeolite ammonia ion exchange and regeneration through multiple cycles was studied using an ion exchange column containing clinoptilolite pellets. Zeolite ion exchange capability was regenerated by flushing the column with 2 mol/L sodium chloride after an ion exchange run. The column maintained ammonia ion exchange capacity through six ion exchange/regeneration cycles, demonstrating multiple dialysis use possibilities. Atomic absorption spectroscopy of the column effluent showed no detectible (< 1 part per million) Si or Al leached from the zeolite.
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PMID:Zeolitic ammonium ion exchange for portable hemodialysis dialysate regeneration. 858 74

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

Nitrogen (N2) may accumulate to unacceptable levels during closed-circuit anesthesia (CCA) when the sampled gases are redirected to the anesthesia circuit, because many gas analyzers entrain air as a reference gas to calibrate for oxygen analysis. Using oxygen instead of air as the reference gas for paramagnetic oxygen analysis could attenuate N2 accumulation. Forty-three adult ASA physical status I-III patients undergoing a variety of peripheral and abdominal procedures were assigned to one of two groups, depending on the reference gas used by a paramagnetic oxygen analyzer, either air (group I, n = 23) or oxygen (group II, n = 20). Gases sampled by the multigas analyzer were redirected to the anesthesia circuit. End-expired N2 (N2Et) was calculated as "balance gas": (100 - %O2 - %anesthetic vapor - %CO2). N2Et after 55 min (N2Et55min) was correlated with the end-expired N2 concentration when the circuit was closed (N2Et0min) and 5 min (N2Et5min) thereafter. In group I, N2Et accumulated almost linearly over time (t, min): N2Et (%) = 2.47 + 0.61 * t (r2 = 0.999). N2Et0min, N2Et5min, and N2Et55min were 1.3+/-0.8, 5.3+/-1.7, and 35.3+/-5.3%, respectively (mean +/- SD). The correlation (r2) between N2Et55min and N2Et0min was 0.19, and between N2Et55min and N2Et5min it was 0.56. In group II, N2Et increased exponentially: N2Et (%) = 1.01 + 11.9 * (1 - e(-t/43.5)) (r2 = 0.99). N2Et0min, N2Et5min, and N2Et55min were 0.87+/-0.93, 2.6+/-1.5, and 10.1+/-2.9%, respectively. The correlation (r2) between N2Et55min and N2Et0min was 0.04, and between N2Et55min and N2Et5min it was 0.40. We conclude that paramagnetic oxygen analyzers that use oxygen as the reference gas significantly attenuate N2 accumulation during CCA, which may reduce the need for frequent flushing of the anesthesia system, may provide more constant oxygen and nitrous oxide concentrations, and may simplify pharmacokinetic studies of potent inhaled anesthetics.
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PMID:Influence of the reference gas of paramagnetic oxygen analyzers on nitrogen concentrations during closed-circuit anesthesia. 1002 34

Nitrogen from the Mississippi River Basin is believed to be at least partly responsible for the large zone of oxygen-depleted water that develops in the Gulf of Mexico each summer. Historical data show that concentrations of nitrate in the Mississippi River and some of its tributaries have increased by factors of 2 to more than 5 since the early 1900s. We have used the historical streamflow and concentration data in regression models to estimate the annual flux of nitrogen (N) to the Gulf of Mexico and to determine where the nitrogen originates within the Mississippi Basin. Results show that for 1980-1996 the mean annual total N flux to the Gulf of Mexico was 1,568,000 t/year. The flux was approximately 61% nitrate as N, 37% organic N, and 2% ammonium as N. The flux of nitrate to the Gulf has approximately tripled in the last 30 years with most of the increase occurring between 1970 and 1983. The mean annual N flux has changed little since the early 1980s, but large year-to-year variations in N flux occur because of variations in precipitation. During wet years the N flux can increase by 50% or more due to flushing of nitrate that has accumulated in the soils and unsaturated zones in the basin. The principal source areas of N are basins in southern Minnesota, Iowa, Illinois, Indiana, and Ohio that drain agricultural land. Basins in this region yield 800 to more than 3100 kg total N/km2 per year to streams, several times the N yield of basins outside this region. Assuming conservative transport of N in the Mississippi River, streams draining Iowa and Illinois contribute on average approximately 35% of the total N discharged by the Mississippi River to the Gulf of Mexico. In years with high precipitation they can contribute a larger percentage.
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PMID:Nitrogen flux and sources in the Mississippi River Basin. 1080 29


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