Effects of pyridostigmine on spontaneous and growth hormone-releasing hormone stimulated growth hormone secretion in children on daily glucocorticoid therapy after liver transplantation.

OBJECTIVES: We aimed to investigate both nocturnal spontaneous and morning growth hormone (GH)-releasing hormone (GHRH)-induced GH secretion in children on daily glucocorticoid treatment after liver transplantation and to evaluate the effect of pyridostigmine (an acetylcholinesterase inhibitor thought to reduce hypothalamic somatostatin tone) on GH secretion in these patients. DESIGN: We performed a randomized, single-blind, cross-over study. PATIENTS: We studied three male and three female juvenile patients, within a year of orthotopic liver transplantation and under immunosuppressive glucocorticoid therapy (mean dose +/- SEM, 5.92 +/- 0.63 mg/day) and five normal children (four males, one female). MEASUREMENTS: Both nocturnal spontaneous and morning GHRH-induced GH secretion were evaluated after administration of placebo, 1 tablet p.o., or pyridostigmine, 2 mg/kg p.o. RESULTS: Spontaneous GH. Placebo: in liver transplanted children nocturnal GH secretion (mean GH level 10.8 +/- 2.0 mU/l) was not significantly different with respect to normal children (mean GH level 12.8 +/- 1.2 mU/l); pyridostigmine: nocturnal GH secretion was significantly increased as compared to placebo in subjects with liver transplantation but not in normal children. GHRH test. Placebo: liver transplanted patients showed a blunted GH response to GHRH with respect to normal children; pyridostigmine: the GH responses to GHRH (P less than 0.05) increased as compared to placebo and did not differ significantly in the two groups. CONCLUSIONS: Our data suggest a steroid-mediated increase in hypothalamic somatostatin tone in liver transplanted children.

[Effects of acute administration of nifedipine on exercise-induced microalbuminuria in normotensive patients with type 1 diabetes]. / Effetto della somministrazione acuta di nifedipina sulla microalbuminuria da sforzo in pazienti diabetici di tipo 1 normotesi.

The aim of our study was to evaluate the acute effect of nifedipine, a calcium channel blocker, on exercise-induced microalbuminuria in normotensive and normoalbuminuric type 1 diabetic patients. Fifteen normotensive diabetic patients who were normoalbuminuric at rest (8 males and 7 females; age 16-35 years) and 10 normal subjects (6 males and 4 females; age 18-40 years) performed 4 submaximal cycloergometric exercises (90% of theoretical maximum heart rate); the first two exercises were performed in basal condition and the other 2 after 24 h of therapy with nifedipine AR (20 mg/b.i.d.) or placebo (2 cps/die). One hour after exercise in basal condition the microalbuminuria was 78 +/- 17 micrograms/min in diabetic patients vs 16 +/- 4 micrograms/min in normal subjects (p less than 0.001). After placebo no significant changes with respect to basal levels were observed 1 hour after exercise in either diabetic patients (82 +/- 16 microgram/min) or normal subjects (20 +/- 5 micrograms/min). In diabetic patients after nifedipine, systolic blood pressure was reduced both at rest and after exercise (p less than 0.05) with respect to basal condition or placebo. The urinary albumin excretion rate at rest was not modified, but it was significantly reduced 1 hour after exercise: 58 +/- 15 micrograms/min (p less than 0.01 vs placebo). This reduction correlated well with the reduction of exercise blood pressure in diabetic patients (r = 0.91, p less than 0.001). Our results indicate that acute administration of nifedipine reduced exercise-induced microalbuminuria in normotensive diabetic patients, probably by means of a reduction in exercise blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Pyridostigmine blocks the inhibitory effect of glucocorticoids on growth hormone-releasing hormone stimulated growth hormone secretion in normal man.

Glucocorticoids have been shown to inhibit GH secretion in normal man when acutely and chronically administered in pharmacological amounts. Pyridostigmine (PD), an acetylcholinesterase inhibitor, is able to elicit GH secretion when administered alone and to enhance the GH response to GHRH in normal subjects probably via a decrease in the hypothalamic release of somatostatin. The aim of the present study was to investigate the influence of glucocorticoids on the GH response to PD administered either alone or in combination with GHRH in normal adult subjects. Six healthy adult volunteers underwent six experimental protocols. They received 1) human (h) GHRH(1-29)NH2, 100 micrograms injected as an iv bolus; 2) cortisone acetate, 50 mg administered orally (po) 60 min before an hGHRH iv bolus injection; 3) PD, 120 mg administered po, 60 min before an hGHRH iv bolus injection; 4) PD and cortisone acetate, administered po 60 min before an hGHRH iv bolus injection; 5) PD, administered po 60 min before a saline iv bolus injection; 6) PD and cortisone acetate administered po 60 min before a saline iv bolus injection. Mean GH levels, peak GH levels, and GH area under the curves (AUCs) were significantly lower after GHRH + cortisone as compared to GHRH alone. However, these parameters were not significantly different after PD + GHRH + cortisone when compared to PD + GHRH and after PD + cortisone when compared to PD alone. We conclude that acute administration of pharmacological amounts of glucocorticoids cannot inhibit the GH response to PD alone or in combination with GHRH. Thus, we hypothesize that the inhibitory action of glucocorticoids on the GH response to GHRH in man may be mediated by an enhancement of either somatostatin release by the hypothalamus or somatostatin action on the pituitary.

Short-term effect of captopril and nifedipine on micro-albuminuria induced by exercise in hypertensive diabetic patients.

Physical exercise can induce micro-albuminuria, a urinary albumin excretion rate of 20-200 micrograms/min, in diabetics without micro-albuminuria at rest (stage II of diabetic nephropathy). The aim of the present study was to evaluate the acute effects of captopril, an angiotensin converting enzyme (ACE) inhibitor, and nifedipine, a calcium channel blocker, on exercise-induced micro-albuminuria in hypertensive diabetics with stage II nephropathy. Eleven hypertensive World Health Organisation (WHO) stages I-II non-obese diabetics (five insulin-dependent diabetics, six non-insulin dependent diabetics) underwent five submaximal cycloergometric tests, the first two in basal conditions, the other three after 24-h administration of captopril (25 mg twice a day), placebo (1 tablet twice a day) or nifedipine AR (20 mg twice a day) according to a randomized double-blind design. Our results demonstrate that despite a lower reduction in exercise blood pressure, captopril is more effective than nifedipine in blunting diabetic exercise-induced micro-albuminuria.