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Biomedical subjects

E Mazza

Publications and source records attributed to E Mazza.

At least 73 records · Page 4Linked to original sources
PubMed1990

Effects of alpha- and beta-adrenergic agonists and antagonists on growth hormone secretion in man.

The adrenergic system is involved in the neural control of GH secretion with both stimulatory and inhibitory influences mainly mediated via GHRH and/or somatostatin modulation. To throw further light on adrenergic neuroregulation of somatotrophic function in man, the effect of various catecholamine agonists and antagonists on basal or GHRH-stimulated GH secretion was studied. Twenty-one adult males aged 20-30 years underwent the following studies: 1. clonidine (CLON), alpha 2-agonist, (15 micrograms/min infused i.v. from 0 to +10 min) alone and preceded by yohimbine (YOH), alpha 2-antagonist, (30 mg orally at -50 min); 2. GHRH (GHRH 44, 1 microgram/kg i.v. bolus at 0 min) alone and preceded by YOH; 3. CLON alone and combined with methoxamine (METHOX), alpha 1-agonist, (1 mg/min infused i.v. from -10 to +10 min); 4. GHRH alone and combined with i.v. infusion of phentolamine (PHEN), alpha 1/alpha 2-antagonist, (0.5 mg/min from -60 to +30 min); 5. GHRH alone and combined with i.v. infusion of salbutamol (SAL), beta 2-agonist, (10 micrograms/min from -5 to +15 min). The GH response to CLON was inhibited by YOH (area under the response curve, mean +/- S.E.: 672.6 +/- 143.0 vs. 219.6 +/- 16.7 micrograms/l/h, P less than 0.05) but was not modified by METHOX (278.4 +/- 94.1 vs. 216.7 +/- 115.5 micrograms/l/h). On the other hand, YOH was unable to affect the GH response to GHRH (339.3 +/- 19.1 vs. 518 +/- 172.8 micrograms/l/h).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1989

Acute administration of pyridostigmine and clonidine has an additive stimulatory effect on GH release in normal children.

It has been shown in humans that both alpha 2-adrenoceptor activation by clonidine (CLON) and cholinergic enhancement by pyridostigmine (PD) have a clear-cut stimulatory effect on GH release. As this effect is probably mediated by two different mechanisms, i.e. via increased endogenous GHRH for CLON and via inhibition of endogenous somatostatin for PD, in 8 normal children we studied the effect of both single and combined acute oral administration of CLON (150 micrograms/m2) and PD (60 mg). When administered alone, CLON and PD induced a similar GH increase (peak, mean +/- SE: 14.6 +/- 2.4 vs 14.2 +/- 3.1 ng/ml; area under curve, AUC: 376.9 +/- 57.6 vs 390.0 +/- 74.3 ng/ml/h). Combined administration of CLON and PD had an additive effect on GH release (peak: 27.5 +/- 4.5 ng/ml; AUC: 920.8 +/- 153.3 ng/ml/h; p less than 0.005 vs CLON and PD alone). In conclusion, presented data show that: i) CLON and PD have similar GH-releasing effect in normal children; ii) The additive stimulatory effect on GH release exerted by acute combined administration of CLON and PD agrees with the hypothesized different mechanism of action of these two drugs; iii) A therapeutic association of CLON and PD may be envisaged in the treatment of some children of short stature.

Adolescent↗
PubMed1989

Effect of the potentiation of cholinergic activity on the variability in individual GH response to GH-releasing hormone.

In man the GH response to GHRH is highly variable and some normal subjects may be completely unresponsive to the neuropeptide. On the other hand, the potentiation of cholinergic activity by pyridostigmine (PD), a cholinesterase inhibitor, increases the GH response to GHRH, probably by inhibiting somatostatin release. The aim of this study was to assess the existence of intraindividual variability in the GH response to GHRH and verify the effects of PD treatment on inter- and intraindividual variability. Twenty normal adults (17 M and 3 F) and 10 normal prepubertal children (9 M and 1 F) underwent 2-5 administrations of 1 micrograms/kg GHRH on different days. Seven adults and all children also underwent 1-5 other tests in which GHRH was preceded (60 min before) by oral PD (120 mg in adults and 60 mg in children). The GH responses to GHRH were highly variable, not only within subjects but also in the same subject on different occasions (peak range; adults: 0.4-49.0 ng/ml; children: 2.4-50.0 ng/ml). PD always markedly increased the GH response to GHRH, even unmasking this response in 3 adults and 4 children hyporesponsive to the neuropeptide alone. However, the variability in the GH response was still present (adults: 27.2-108.5 ng/ml; children: 25.0-144.0 ng/ml), though reduced (adults: p = 0.0005; children: p = 0.0204). These data indicate that: i. A great inter- and intraindividual variability in the GH response to GHRH is present.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Effect of cholinergic enhancement by pyridostigmine on growth hormone secretion in obese adults and children.

In obesity the reduced growth hormone (GH) responses to several provocative stimuli including growth hormone-releasing hormone (GHRH) indicate a diminished somatotroph responsiveness but do not distinguish between primary pituitary and hypothalamic pathogenesis. However, it has been shown that the cholinergic system positively influences Gh secretion likely by modulating somatostatin release in a negative way. Thus, the effect of cholinergic activity enhancement by pyridostigmine (PD), an acetylcholinesterase inhibitor, on both basal and GHRH-induced GH secretion was studied in 14 obese subjects (eight adults and six children). Eighteen nonobese subjects (seven adults and 11 children) were studied as controls. In obese subjects the GHRH-induced GH increase was lower than in controls (peak, mean +/- SEM, adults, 9.2 +/- 2.7 v 16.8 +/- 5.7 ng/mL; children, 8.0 +/- 0.8 v 20.3 +/- 4.6 ng/mL) attaining statistical significance only in children group (P less than .02). The PD-induced GH response in the two obese groups was similar to that observed in relative controls (adults, 5.3 +/- 1.0 v 7.4 +/- 1.7 ng/mL; children, 9.6 +/- 1.6 v 13.3 +/- 1.4 ng/mL). PD clearly potentiated the GH response to GHRH in obese subjects, both adults (P less than .05 v GHRH alone) and children (P less than .0005 v GHRH alone). However, the GH responses to PD + GHRH was significantly reduced in obese subjects compared with controls (adults, 18.1 +/- 2.2 v 42.7 +/- 10.7 ng/mL, P less than .05; children, 28.3 +/- 4.5 v 58.2 +/- 7.7 ng/mL, P less than .01). In conclusion, PD is able to potentiate the blunted GH responses to GHRH in obese adults and children, inducing a GH increase similar to that observed after GHRH alone in normal subjects. This finding suggests that an alteration of somatostatinergic tone could be involved in the reduced GH secretion in obesity.

Adult↗
PubMed1989

Cholinergic enhancement of pyridostigmine potentiates spontaneous diurnal but not nocturnal growth hormone secretion in short children.

It has been shown that enhanced cholinergic tone induced by pyridostigmine (PD) increases both basal and GHRH-stimulated GH levels in both adults and children. In this study the effects of PD (60 mg orally) on GH secretion were studied both in the morning (from 8.00 to 12.00) and in the night (from 23.00 to 3.00) in 7 short children previously shown as having a normal spontaneous nocturnal GH secretion. In the morning, PD induced a GH increase higher than saline (peak, mean +/- SEM: 17.4 +/- 3.4 vs. 5.5 +/- 3.0 ng/ml, p less than 0.02; area under curve (AUC): 360.8 +/- 71.4 vs. 109.4 +/- 44.7 ng/ml/h, p less than 0.01). In the night, no difference was observed between GH secretion after PD (peak: 16.7 +/- 2.4 ng/ml; AUC: 468.2 +/- 95.5 ng/ml/h) and saline (peak: 16.0 +/- 2.7 ng/ml; AUC: 409.1 +/- 97.7 ng/ml/h). Spontaneous GH secretion was higher during the night than in the morning (p less than 0.02) whereas nocturnal GH secretion overlapped with that in the morning after PD. The ability of PD to increase GH secretion during the morning but not GH hypersecretion occurring at night implies that the cholinergic tone in the central nervous system areas controlling GH secretion is already maximally stimulated at night. Since, reportedly, the cholinergic system negatively modulates somatostatin secretion, presence of a physiologically reduced somatostatinergic tone may be envisaged at night.

Adolescent↗
PubMed1989

Repeated GH-releasing hormone administration unravels different GH secretory patterns in normal adults and children.

In normal adults, repeated GHRH administration leads to progressively decreasing somatotrope responses. To verify whether this GH secretory pattern also connotes normal growing children, we have studied the effects of two consecutive (every 120 min) 1 microgram/kg iv GHRH boluses on GH release in normal adults (N = 7, age 23.2-30.6 years) children (N = 6, age 10.4-13.2 years). In the adults, the GH response to the second GHRH bolus (peak, mean +/- SEM; 2.9 +/- 0.8 micrograms/l) was lower (P less than 0.02) than that to the first bolus (15.9 +/- 2.4 micrograms/l). Conversely, in children the GH response to the second GHRH bolus (25.6 +/- 6.3 micrograms/l) overrode the first one (13.6 +/- 6.5 micrograms/l), but this difference did not attain statistical significance. In adults cholinergic enhancement by pyridostigmine, a cholinesterase inhibitor, was previously shown to re-instate, even to potentiate somatotrope responsiveness to consecutive GHRH boluses. Thus, in 5 children GH response to repeated GHRH boluses was retested administering pyridostigmine (60 mg orally) 30 min before the second GHRH bolus. In these subjects, pyridostigmine failed significantly to potentiate the GH responsiveness to the second GHRH bolus (30.3 +/- 4.6 vs 25.0 +/- 7.6 micrograms/l). These data indicate that differently from in adults, in children repeated GHRH administration does not reduce somatotrope responsiveness and that cholinergic enhancement fails to potentiate GH responsiveness to the second GHRH bolus.

Adolescent↗
PubMed1987

Long term treatment with oral single administration of bromocriptine in patients with hyperprolactinemia.

In the treatment of hyperprolactinemia bromocriptine is generally administered in 3 daily doses during the day. Due to the limited compliance of patients under this long term regimen, in 16 hyperprolactinemic patients we investigated the efficacy and tolerability of the treatment with this dopaminergic drug administered as a single evening dose. This dose was the same which the patients had been assuming previously on a tid basis. Chronic treatment (4-12 months) with an oral single evening dose of bromocriptine is able to control plasma PRL at least as well as the traditional tid regimen (2.8-21.6 ng/ml vs 1.2-31.8 ng/ml). Furthermore, during this single dose regimen the side effects were of lesser intensity and extent. Since the compliance of the patients with the single dose regimen was very good and the efficacy the same in reducing plasma PRL and controlling the clinical manifestations with a lower rate of side effects, we suggest to extend this regimen to all patients with hyperprolactinemia treated with bromocriptine after successful reduction of plasma PRL levels is obtained.

Administration, Oral↗
PubMed1987

Effects of a new long-acting form of bromocriptine on tumorous hyperprolactinemia.

Recently, a new long-acting form of bromocriptine (Parlodel LA, Sandoz) has been developed and it has already been found to be effective in lowering plasma PRL levels in normal volunteers and postpartum women. This work reports the clinical, hormonal and radiological effects of a single 50 mg dose of long-acting bromocriptine in 10 patients with tumorous hyperprolactinemia (2 microprolactinomas, 6 macroprolactinomas, 1 acromegaly and 1 nonsecreting macroadenoma). A rapid and long-lasting (28 days) normalization of PRL levels was observed in patients with microprolactinoma, acromegaly and nonsecreting adenoma. None of the 6 patients with macroprolactinoma underwent normalization of plasma PRL, but the latter was markedly reduced (61-80% of basal levels). A second injection of the drug in 5 macroprolactinoma patients induced a further reduction of plasma PRL levels in 2 of them. No changes in the tumor size were observed either after the first or the second injection of long-acting bromocriptine in any of the patients. This injectable form of bromocriptine induced nausea and/or mild hypotension lasting a few h in 4 of the 10 patients and was better tolerated than the oral form as regards both the duration and intensity of the side effects. Thus, as this drug has proved to be efficacious and well tolerated by the patients, this long-acting form of bromocriptine may be a valid therapeutical approach for initiating medical treatment of patients with prolactinoma.

Acromegaly↗
PubMed1987

Growth hormone responses to pyridostigmine in normal adults and in normal and short children.

There is evidence indicating that the cholinergic system positively modulates GH release probably by inhibiting somatostatinergic tone. In the present study, the effects of cholinergic enhancement by pyridostigmine, (PD), a cholinesterases inhibitor, on GH release in normal adults (n = 14) (NA) and in both normal (n = 5) (NC) and short children (n = 19) (SC) with familial short stature (n = 7) or constitutional growth delay (n = 12) were studied. In SC the insulin hypoglycaemia (IH)-induced GH increase was also studied. In both NC and SC 60 mg orally PD induced a significant GH increase with mean peak at 90 min (mean +/- SEM 11.0 +/- 2.2 ng/ml in NC and 11.2 +/- 2.3 ng/ml in SC). The GH areas under response curve (AUC) were 379.3 +/- 76.6 and 327.8 +/- 43.2 ng/ml/h in NC and SC respectively. In NA 120 mg orally PD induced a significant GH increase with mean peak at 120 min (5.1 +/- 1.1 ng/ml) which was significantly lower (P less than 0.05) than that observed in both NC and SC. This statistical difference was strengthened by evaluating AUC (NA:205.6 +/- 33.7 ng/ml/h, P less than 0.05 vs NC and SC). The correlation of drug dosage with body area ruled out that this difference could be related to the different PD dose in adults and children. In SC, IH induced a GH increase significantly lower than that observed after PD (GH peak 7.8 +/- 0.6 vs 16.4 +/- 1.9 ng/ml P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Enhancement of cholinergic tone by pyridostigmine promotes both basal and growth hormone (GH)-releasing hormone-induced GH secretion in children of short stature.

Increased cholinergic tone induced by pyridostigmine (PD) increases basal plasma GH levels and potentiates the GH response to GHRH in normal adults. In this study the effects of PD (60 mg, orally) on both basal and GHRH (1 microgram/kg)-induced GH secretion in seven children with familial short stature (FSS), six with GH deficiency (GHD) and 10 with constitutional growth delay (CGD) were studied and compared with results obtained by stimulation with insulin-induced hypoglycemia (IH) and GHRH alone. The mean peak plasma GH levels were variable, but individual values were frequently low in all groups after both IH [FSS, 9.7 +/- 1.3 (+/- SEM) ng/mL; GHD, 1.6 +/- 0.4 ng/mL; CGD, 7.0 +/- 0.8 ng/mL] and GHRH (FSS, 23.8 +/- 6.6 ng/mL; GHD, 11.1 +/- 5.8 ng/mL; CGD, 15.1 +/- 4.5 ng/mL) administration. PD induced GH responses (FSS, 14.5 +/- 1.6 ng/mL; GHD, 3.8 +/- 0.8 ng/mL; CGD, 18.3 +/- 3.2 ng/mL) that in many children in the FSS and CGD groups were higher than those after IH and GHRH treatment. PD clearly increased the GH response to GHRH in all children [FSS, 69.5 +/- 9.4 ng/mL (P less than 0.01 vs. other stimuli); GHD, 18.0 +/- 7.5 ng/mL; CGD, 50.0 +/- 8.5 ng/mL (P less than 0.01 vs. other stimuli)]. We conclude that in children with short stature, as in adults, enhancement of cholinergic tone increases both basal and GHRH-induced GH secretion, and that PD plus GHRH is the best provocative stimulus for evaluating the somatotroph response.

Adolescent↗
PubMed1987

Prophylactic plasma exchange in burn treatment.

The first cause of death in burned patients is still sepsis. A great number of studies point out a serious immunodeficiency due to several circulating mediators. Nowadays early excision and plasma exchange appear to be the most efficient procedures in order to remove from the patient these circulating agents. Therefore in this study the authors have treated 8 patients (average age 25 years), who presented an average of total burned surface of 49%, with plasma exchange performed early after injury. The results of PMN and lymphocyte function tests showed a significant therapeutic correction of these parameters in patients treated with plasma exchange. The clinical observations agreed with the results: in 7 patients with positive outcome, no invasive infections were recorded. The positive results obtained warrant further investigation with this procedure.

Adolescent↗
PubMed1986

Cholinergic involvement in the growth hormone releasing hormone-induced growth hormone release: studies in normal and acromegalic subjects.

To throw light onto the mechanism(s) by which the cholinergic system influences growth hormone (GH) release, the effects of two muscarinic receptor blockers, pirenzepine and atropine, and of an acetylcholinesterase inhibitor, pyridostigmine bromide, on the GH response to GHRH-44 were studied in 19 normal volunteers. Moreover, the effects of pirenzepine administration on plasma GH levels both in basal conditions and after stimulation by GHRH-44 and TRH were studied in 9 acromegalics. Both pirenzepine (0.6 mg/kg i.v., 5 min before GHRH) and atropine (1 mg i.m., 15 min before GHRH) blunted the GH response to GHRH (1 microgram/kg i.v. bolus) (area under the response curve, AUC: 81.3 +/- 17.3 vs. 481.2 +/- 211.3 ng/ml/h for pirenzepine and 100.2 +/- 27.0 vs. 364.7 +/- 81.0 ng/ml/h for atropine; p less than 0.01). Pyridostigmine (120 mg orally, 30 min before GHRH) induced a variable but significant (p less than 0.02) rise in basal plasma GH levels and, furthermore, an unequivocal potentiation of the GH response to GHRH (AUC: 1044.6 +/- 245.3 vs. 481.2 +/- 211.3 ng/ml/h; p less than 0.01). In all but one acromegalics 0.6 mg/kg i.v. pirenzepine was unable to modify the basal GH levels whilst it showed a variable inhibitory effect on the GH response to GHRH. The GH response to TRH (200 micrograms i.v. bolus) was instead unmodified by pirenzepine. In conclusion, muscarinic receptor blockade inhibits while cholinergic potentiation seems to positively modulate the GH response to GHRH. Therefore, the cholinergic system seems to positively modulate the GHRH effect on somatotrophs.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1986

Potentiation of cholinergic tone by pyridostigmine bromide re-instates and potentiates the growth hormone responsiveness to intermittent administration of growth hormone-releasing factor in man.

It is known that in normal subjects repeated administration of the growth hormone-releasing factor (GRF) induces a state of partial refractoriness of the somatotropes to GRF. Studies were conducted to verify whether the cholinergic system plays a role in the mechanism(s) underlying the reduced GH responsiveness to the neuropeptide. In five healthy men, the GH response to three consecutive injections of GRF (50 micrograms iv), administered at 2 h intervals, was considerably blunted after the second and third GRF bolus. Administration of the inhibitor of cholinesterase, pyridostigmine bromide (120 mg orally) 30 min before the second GRF bolus, not only restored but greatly potentiated the GH responsiveness to the second GRF bolus. The GH response to the third GRF bolus was not apparently influenced by pre-treatment with pyridostigmine. These data reinforce the view that cholinergic neurotransmission plays an important role in the control of GH secretion in human.

Adult↗