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Biomedical subjects

R Deghenghi

Publications and source records attributed to R Deghenghi.

At least 127 records · Page 7Linked to original sources
PubMed1994

Arginine and growth hormone-releasing hormone restore the blunted growth hormone-releasing activity of hexarelin in elderly subjects.

Although both spontaneous and stimulated GH secretion undergo an age-related decline, the secretory capacity of somatotrope cells is preserved in human aging. In the present study we compared the GH responses to hexarelin, GHRH, and the combined administration of hexarelin and GHRH or arginine in young and elderly subjects. Thirteen young (24- to 30-yr-old) and 16 elderly (65- to 84-yr-old) normal males were divided into 2 groups. The first group (7 young and 8 elderly subjects) received the following as single iv injections during 3 different treatment sessions: hexarelin (2 micrograms/kg), GHRH (2 micrograms/kg), or hexarelin (2 micrograms/kg) plus GHRH (2 micrograms/kg). The second group (6 young and 8 elderly subjects) was administered single iv injections of hexarelin (2 micrograms/kg) or hexarelin (2 micrograms/kg) plus arginine (0.5 g/kg) during 2 different treatment sessions. In both groups basal IGF-I levels in the elderly were lower than those in young subjects (114.5 +/- 18.7 vs. 211.5 +/- 19.1 micrograms/L; P < 0.001). In the first group the GH response to hexarelin was greater in young compared to elderly subjects (area under the curve from 0-120 = 4849 +/- 601 vs. 2112 +/- 683 micrograms.min/L; P < 0.001). GHRH elicited a lower GH response than that induced by hexarelin in both young (1455 +/- 102 micrograms/h.L; P < 0.02) and elderly subjects (563 +/- 87 micrograms/min.L; P < 0.02). GHRH potentiated the somatotrope response to hexarelin in both young (7725 +/- 503 micrograms/min.L; P < 0.02) and elderly subjects (3895 +/- 612 micrograms/min.L; P < 0.02), but to a lesser extent in the latter (P < 0.001). In the second group, the GH response induced by hexarelin was also higher in young subjects than in elderly subjects (4819 +/- 668 vs. 1649 +/- 459 micrograms/min.L; P < 0.001). The GH response to hexarelin was potentiated by arginine in elderly (4139 +/- 1057 micrograms/min. L; P < 0.001), but not in young subjects (4743 +/- 774 micrograms/min.L). This study shows that the maximal effective dose of hexarelin releases more GH than the maximal effective dose of GHRH in both normal young and elderly subjects. The effect of hexarelin on GH secretion is age dependent, and the GH response to the combined administration of hexarelin and GHRH was significantly higher in young subjects compared to elderly subjects. Arginine does not potentiate the GH response to hexarelin in young subjects, whereas it significantly enhances it in elderly subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Antarelix (EP 24332) a novel water soluble LHRH antagonist.

A novel water soluble LHRH antagonist (EP 24332-Antarelix) is described. Its activity in vitro and in vivo in several animal models is given. Antarelix (Ac-D-Nal, D-Cpa, D-Pal, Ser, Tyr, D-Hci, Leu, Lys-(iPr), Pro, D-Ala-NH2) in view of its potency, modest histamine-liberating activity and high water solubility has been selected for further development.

Animals↗
PubMed1990

Effects of dextronatrin on blood pressure, hematocrit, urinary sodium excretion and sympathetic nerve activity of rats.

The purpose of this investigation was to study in unanesthetized rats the blood pressure, renal and hematocrit responses to dextronatrin, a structural analogue of atrial natriuretic peptides (ANP). The peptide was infused intravenously for 20 min at doses of either 1 or 20 micrograms/min in binephrectomized rats as well as in rats with intact kidneys. The experiments were started 2 h after preparation of the rats under ether anesthesia. In binephrectomized rats, the small dose of dextronatrin lowered blood pressure and raised hematocrit. In those rats, the larger dose of the investigational peptide had no blood pressure lowering effect, but still increased hematocrit. Dextronatrin had no effect on heart rate, both in rats with and without kidneys. Dextronatrin given at the 1 microgram/min dose to normal rats caused a significant increase in urinary Na excretion. The large dose, however, did not modify this parameter. The effect of dextronatrin (1 microgram/min for 20 min) on splanchnic nerve activity was evaluated in other normal rats after a recovery period of 24 h from surgical procedure. Integrated nerve activity was found to significantly increase in parallel with heart rate while blood pressure was reduced. Taken together, these results show that a low dose of dextronatrin lowers blood pressure and induces an increase in urinary Na excretion and hematocrit. They also indicate that the blood pressure and renal effects of the peptide are abolished when a high dose is administered. In addition, it appears that the shift of fluid from the intra- to the extravascular compartment, reflected in binephrectomized rats by an increase in hematocrit, does not depend on the level of systemic blood pressure. Finally, the present observations suggest that the blood pressure lowering effect of dextronatrin is accompanied in the conscious rat by a stimulation of the sympathetic nervous system.

Amino Acid Sequence↗
PubMed1988

Somatostatin analogues in the treatment of the carcinoid syndrome.

Somatostatin analogs have been found useful in a variety of endocrine-related diseases. In particular, patients with malignant carcinoid syndrome benefit from their administration. A review of published data and a rationale for their use is hereby presented.

Carcinoid Tumor↗
PubMed1986

[p-[(Thienylcarbonyl)amino]phenoxy]propanolamines derivatives as diuretic and beta-adrenergic receptor blocking agents.

The synthesis of [[(thienylcarbonyl)amino]phenoxy]propanolamines and their beta-adrenergic blocking and diuretic activity are described. Structure-activity relationships demonstrated that ortho substitution of the phenoxy ring with an hydrogen or an ester function leads to compounds possessing both activities. Ethyl 2-[3-[(1,1-dimethylethyl) amino]-2-hydroxypropoxy]-5-[(2-thienylcarbonyl)amino]benzoate (3d) was selected as the most active compound for further investigation.

Animals↗
PubMed1986

[Atriopeptides, hormones of the heart].

Since their discovery in 1981, atrial natriuretic peptides have taken an important place in cardiovascular research and have defined the heart as a hormone-producing endocrine gland.

Animals↗
PubMed1985

Effect of rat and beta-human interferons on hyperacute experimental allergic encephalomyelitis in rats.

Human interferon-beta (human IFN-beta) and rat interferon (rat IFN) were evaluated on experimental allergic encephalomyelitis (EAE) in rats, a delayed cellular reaction resembling human multiple sclerosis (MS). Rat IFN was active by intravenous and intracerebroventricular routes. It decreased the severity of clinical symptoms of paralysis during the 22 days of the assay. Human IFN-beta, on the contrary, had no effect when similarly tested in this rat model. Cyclophosphamide delayed the onset of paralysis, but levamisole enhanced the severity of the EAE.

Animals↗
PubMed1983

Effects of calcium-antagonists on passive cutaneous anaphylaxis in the rat.

The actions of four Ca2+-antagonists (nifedipine, verapamil, diltiazem and D 600) were compared with those of four substances that are used clinically in treating asthma (theophylline, isoproterenol, disodium cromoglycate and clemastine), using the passive cutaneous anaphylaxis (PCA) reaction in the rat. Nifedipine, verapamil and diltiazem produced a partial, but dose-related inhibition of the PCA reaction. A slight, but significant inhibitory effect was also observed with D 600. Isoproterenol, theophylline and disodium cromoglycate also produced dose-related inhibition of the PCA reaction, their maximum effects being greater than those of the Ca2+-antagonists. As the histamine H1-antagonist clemastine was about as active as nifedipine, verapamil or diltiazem in inhibiting the PCA reaction, it seems possible that certain Ca2+-antagonists might be of value in treating allergic disorders in man.

Animals↗
PubMed1982

Effects of an extract of Ginkgo biloba on rabbit isolated aorta.

1. Extract of Ginkgo biloba (Gb) provoked a dose-dependent contraction of spirally-cut rabbit aortic strips (EC50 congruent to 1.0 mg/ml) by an action that was antagonized by phentolamine (10(-7) M). 2. Inhibitors of catecholamine re-uptake, cocaine (10(-5) M) and desipramine (10(-7) M) potentiated the contractile effect of norepinephrine (NE), but inhibited the contractile effects of Gb and tyramine. 3. A comparison of the actions of Gb, NE and tyramine using aortic strips prepared from control and reserpine-treated rabbits revealed that reserpine treatment increased the response to NE but decreased the response to Gb and tyramine. 4. The contractile action of Gb on rabbit isolated aorta involves, at least in part, a release of catecholamines from endogenous tissue stores.

Animals↗
PubMedDate not supplied

There are no acute cardiac effects of a single iv dose of human ghrelin in severe growth hormone deficient patients.

It has previously been suggested that ghrelin mediates GH-independent biologic activities on the heart. We investigated the acute effects on cardiac contraction of a single iv administration of human ghrelin (in a dose of 1 microg/kg) in severe untreated GH deficient subjects. Prior to the ghrelin infusion, an echocardiographic examination was performed at rest (baseline), after physiologic saline and during dobutamine stress echocardiography (DSE) to exclude a preexisting (subclinical) myocardial dysfunction. To evaluate the acute cardiac effect of infusion and during DSE the velocity of left ventricular (LV) wall contraction was measured continuously by echocardiography. Despite severe GH deficiency we observed in all subjects a normal cardiac function at rest after physiologic saline and during DSE. No acute changes in cardiac performance or cardiac parameters could be observed after a single iv dose of ghrelin. Also, no important increase in GH secretion was detected after ghrelin administration. Our study suggests that, in contrast to hexarelin, a single iv administration of ghrelin in a physiological dose has no acute effects on cardiac function in severe GH deficiency. This suggests that GH-independent effects of ghrelin play no important role in the acute regulation of cardiac function in man.

Adult↗
PubMedDate not supplied

Short term effect of intranasal administration of hexarelin--a synthetic growth hormone-releasing peptide. Preliminary communication.

Twice or three times daily intranasal administration of the hexapeptide hexarelin for 7 days to children with short stature and normal growth hormone (GH) secretion evoked a significant rise in serum levels of insulin-like growth factor-1 (IGF-1) and alkaline phosphatase. There was also a significant, within normal limits, rise of thyroid stimulating hormone (TSH) without evidence of thyroxine suppression.

Administration, Intranasal↗
PubMedDate not supplied

Small peptides as potent releasers of growth hormone.

Newly synthesized peptides are described which release growth hormone in the infant rat and their biological activity is compared with known GHRPs. Some of these peptides are the most potent GHRPs reported to date.

Amino Acid Sequence↗
PubMedDate not supplied

Growth hormone release by the novel GH releasing peptide hexarelin in patients with homozygous beta-thalassemia.

Patients with beta-thalassemia often present with abnormalities in growth and other endocrine functions. Growth hormone (GH) secretion is controlled via somatostatin and growth hormone releasing hormone (GHRH). Recently, Hexarelin, a new potent GH secretagogue (His-D-2-Methyl-Trp-Ala-Trp-D-Phe-Lys-NH2), was synthesized. Our study was designed to assess and compare its efficacy as a GH secretagogue to GHRH 1-29 in beta-thalassemia. Eighteen patients, regularly transfused and chelated, were studied; 11 were short statured. None had diabetes mellitus, hypothyroidism, hypopara-thyroidism or major organ failure. We measured GH at 0, 30, 60, 90, 120 min after GHRH 1-29 or Hexarelin administration. Hexarelin p.o. or i.v. evoked a brisk rise of serum GH which was significantly higher (p < 0.01) than that induced by GHRH 1-29 i.v. In conclusion, Hexarelin has greater GH releasing capacity than GHRH 1-29 at 1 microgram/kg i.v. and can thus be viewed as a potential therapeutic agent in GH deficient states.

Adolescent↗