摘要:

Alterations in the control of arginine-vasopressin (AVP) secretion have been described in type I diabetes mellitus. In order to gain a better insight into this problem, we examined whether insulin-dependent diabetics in good metabolic conditions and without diabetic complications had an abnormal AVP responsiveness to metoclopramide (MCP), an AVP-stimulating agent with a central site of action. In addition, we tested the AVP response to insulin-induced hypoglycemia in the same subjects. Twenty insulin-dependent diabetic men without neuropathy or other diabetic complications were divided into two groups according to the duration of their illness (10 patients who had been diabetic for less than 10 years, group 1, and 10 patients who had been diabetic for more than 10 years, group 2). Eleven age- and weight-matched normal men participated as controls. All groups were tested with MCP (20 mg in an intravenous bolus) and, on a different occasion, with insulin-induced (0.15 IU/kg) hypoglycemia. Experiments started after optimization of the metabolic status of the diabetic men by 3 days of treatment with continuous subcutaneous insulin infusion. Basal concentrations of AVP were similar in all groups (diabetics of group 1: 2.2 ± 0.2 pmol/l, mean ± SE; group 2: 2.3 ± 0.2 pmol/l; normal controls: 2.2 ± 0.2 pmol/l). Administration of MCP induced a striking elevation of plasma AVP levels in the normal controls and in the diabetic subjects of groups 1 and 2. All subjects showed a mean peak response at 15 min. However, the AVP rise was significantly higher in the diabetic men (peak, mean ± SE: group 1 ≈ 7.3 ± 0.6; group 2 = 6.9 ± 0.3 pmol/l) than in the control subjects (4.9 ± 0.4 pmol/l). There were no significant differences in the AVP response to MCP between groups 1 and 2. Insulin induced a similar hypoglycemic nadir in all subjects at 30 min; however, the diabetic subjects of groups 1 and 2 had a delayed recovery in blood glucose levels. The hypoglycemic pattern was similar in the diabetics of groups 1 and 2. All subjects showed mean AVP peak responses at 30 min, simultaneously with the blood glucose nadir. Hypoglycemia induced a striking AVP increase in the normal controls (peak levels: 4.3 ± 0.4 pmol/l). However, significantly higher AVP responses to hypoglycemia were observed in the diabetic men of groups 1 and 2 (peak levels: 7.1 ± 0.5 and 7.0 ± 0.4 pmol/l, respectively) than in the normal controls. The AVP response to hypoglycemia was similar in groups 1 and 2. These data indicate that a hypothalamic pituitary disorder affects the AVP response to MCP and insulin-induced hypoglycemia in well-controlled type I diabetic men without diabetic complications. Since cholinergic pathways are involved in the mechanisms of action of both MCP and insulin-induced hypoglycemia on AVP, alterations in cholinergic neurotransmission may be supposed to be involved in insulin-dependent

ISSN:1663-2818    

DOI:10.1159/000181521

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The possible mediation of dopaminergic, muscarinic cholinergic and/or serotonergic receptors in the response of ACTH/cortisol to metoclopramide (MCP) was evaluated in 27 normal men. All subjects were tested with MCP (10 mg in an intravenous bolus plus placebo or saline, NaCl 0.9%, control test). For the other tests (experimental tests), the men were divided into three groups of 9 subjects each. One group was tested with MCP in the presence of the dopaminergic agonist bromocriptine (5 mg p.o. 3 h before MCP), another group was tested with MCP plus the M1- and M2-muscarinic-cholinergic antagonist atropine (1.2 mg in an intravenous bolus, just before MCP) or the M1-muscarinic receptor blocker pirenzepine (40 mg in an intravenous bolus 10 min before MCP). The third group was tested with MCP after treatment with the selective 5-HT1-serotonergic receptor blocker metergoline (10 mg/day p.o. in 5 divided doses for 4 days before MCP) or the 5-HT2-serotonergic receptor antagonist ketanserin (10 mg as a slow 3-min intravenous injection, 5 min before MCP). ACTH and cortisol rose by 45 and 55%, respectively, in response to MCP. The basal levels of ACTH and cortisol were not modified by bromocriptine, atropine, pirenzepine, metergoline or ketanserin treatment. Both ACTH and cortisol responses to MCP did not change significantly after bromocriptine, atropine, pirenzepine or ketanserin administration, whereas they were completely abolished by pretreatment with metergoline. Additional experiments were performed in order to evaluate whether the effect of metergoline on the ACTH/cortisol response to MCP depends on the amount of the serotonergic antagonist (dose-response study). For this purpose, 7 additional male subjects were tested with MCP plus metergoline in doses ranging from 2.5 to 10 mg/day p.o. in 5 divided doses for 4 days. The treatment with 2.5 mg/day metergoline was without effects on the ACTH/cortisol response to MCP, whereas 5 mg/day of the drug produced a partial reduction, and 10 mg/day metergoline completely inhibited MCP action. These data indicate that 5-HT1-serotonergic receptors, but not dopaminergic, 5-HT2-serotonergic or M1- or M2-muscarinic cholinergic receptors, mediate MCP-induced ACTH/cortisol release in man.

ISSN:1663-2818    

DOI:10.1159/000181523

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

To identify the effects of acute starvation on endogenous opioids in man, plasma β-endorphin (β-EP) was measured in 17 patients before, during and after fasting. Patients were assigned a posteriori into two groups: group A, comprised of 11 patients able to tolerate 5-7 days of fasting, and group B, comprised of 6 patients able to tolerate 10 days of fasting. Changes in plasma β-EP, serum cortisol, circulating nutritional markers, and their relative levels were assessed on the 5th and 10th days of fasting, and on the 5th and 10th days of the refeeding period. Beta-EP had increased by the 5th day (group A: 4.74 ± 0.42 to 6.91 ± 0.65 pmol/l, p < 0.01; group B: 3.60 ± 0.48 to 5.14 ± 0.22 pmol/l, p < 0.05, and remained at 5.05 ± 0.65 pmol/l on the 10th day (group B: 0.05 < p < 0.1) during fasting. Group B had lower levels of plasma β-EP on the 5th day of fasting than group A (p < 0.05). However, serum cortisol levels changed similarly in both groups. Plasma β-EP showed no significant correlation with either the percentage of body weight lost or the body mass index (kg/m2) over this study period. These findings indicate that plasma β-EP is elevated in the early phase of fasting, while not directly being associated with body weight changes. Plasma β-EP is lower and less activated in subjects who are able to tolerate fasting for lon

ISSN:1663-2818    

DOI:10.1159/000181525

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

This study examined the effect of 17β-estradiol (E2) on basal and luteinizing hormone (LH)-releasing hormone (LHRH)-stimulated gonadotropin secretion in 9 patients with Klinefelter’s syndrome. Intramuscular injection of E2 (10 µg/kg/day during 5 days) induced a rapid decrease in follicle-stimulating hormone (FSH) and LH levels. The maximum suppression was observed on day 7 (D7) for FSH [median 9.7 mlU/ml (range 4.6-37.8) vs. 21.7 mlU/ml (range 12.2-56.9)] and on D2 for LH [median 13.6 mlU/ml (range 6.8-25.2) vs. 21.2 mlU/ml (range 13-54.7)]. E2 concentrations rose and reached their peak values on D3 [median 723 pmol/l (range 517-1,247.8) vs. 110.1 pmol/l (range 68.6-227.5) on DO]. These changes were followed by a subsequent rise in LH on D4 [36.7 mlU/ml (range 19.4-77.7)]. LH response to LHRH was higher during E2 treatment: median value of absolute peaks: 156.3 mlU/ml (range 56.7-188.6) on D4 vs. 64 mlU/ml (range 38.9-131) on DO. These results demonstrate the presence of a positive feedback in patients with Klinefelter’s syn

ISSN:1663-2818    

DOI:10.1159/000181526

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The thymus produces humoral factors that induce the proliferation and differentiation of T cells which are responsible for cell-mediated immunity. Experimental data have suggested that this thymic hormone production is modulated by the neuroendocrine network and, in particular, by growth hormone (GH) and thyroid hormones. To study the role played by GH in thymic endocrine activity in humans, the circulating level of one of the best known thymic peptides, i.e. thymulin (Zn-FTS), has been determined, after a washout period of 2 weeks without GH treatment, in GH-deficient children before and after a single injection of GH. The basal thymulin level is consistently lower in GH-deficient children than in healthy age-matched controls. A single injection of GH induces a significant increment of the thymulin level for at least 48 h. Since thymulin activity may also depend on zinc bioavailability, on thyroid hormone turnover and on the eventual presence of thymulin-inhibitory substances, all these aspects have been checked. No supporting evidence regarding the existence of these kinds of interferences in GH-deficient children has been substantiated. A positive correlation has been found between the serum level of insulin-like growth factor I, but not of GH, and thymulin activity. These data suggest that GH may directly or indirectly modulate the thymic endocrine function in humans. Whether and to what extent such a modulation is relevant to the functioning of the immune system remains to be ascertained.

ISSN:1663-2818    

DOI:10.1159/000181528

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

In this study, we have cultured in vitro purified trophoblastic cells from first-trimester and term human placenta. These cells were obtained by specific enzymatic digestion and centrifugation through a Percoll gradient. Using 2 specific monoclonal antibodies, the pituitary 22-kD growth hormone (GH) and the placental GH variant were assayed in the culture medium by radioimmunoassay. After 48 h of culture, only the placental GH variant was measured in the medium corresponding to first-trimester placenta (3.4 ng/24 h/105 cells). Surprisingly, an immunoactivity pattern of pituitary GH type was found in 3 out of 5 media conditioned with term placenta cells, while GH immunoactivity was very low, around the detection level, in the 2 others. These secretions are not modified with the time in culture and the state of differentiation of the cells from cytotrophoblast to syncytiotrophoblast. Neither in early nor in term placenta does the addition of GH-releasing factor (10-6M in the culture medium) stimulate the secretion of pituitary 22-kD GH or placental GH variant.

ISSN:1663-2818    

DOI:10.1159/000181530

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Neonatal skeletal maturation was assessed by different methods based on the bone centres in the knee and ankle region in 46 infants with true-positive (patients) and 17 infants with false-positive screening tests (controls). The patients and controls did not differ in mean age at X-ray examination and age at the start of treatment (14.5 ± 5.7 days). One of the methods used to score the size of femoral and tibial epiphyses was just as good as the other ones tested, but has the advantage of being the easiest to use and therefore clinically most suitable. Skeletal maturity assessed by this method correlated best with serum T4 (r = 0.62, p < 0.01). Griffiths tests were performed in 37 of the 46 patients at 28-48 months of life. The best correlation obtained between neonatal skeletal maturity and Griffiths global developmental quotient at 3 years of age was r = 0.58 (p < 0.001). Although statistically significant, it was too weak to be of clinical value in identifying individual patients at risk. We conclude that an assessment of skeletal maturation is not useful for the prognosis of psychomotor development in individual patients with congenital hypothyroidism receiving treatment within the first 2 weeks of life

ISSN:1663-2818    

DOI:10.1159/000181532

出版商:S. Karger AG    

年代:1990

数据来源: Karger

ISSN:1663-2818    

DOI:10.1159/000181534

出版商:S. Karger AG    

年代:1990

数据来源: Karger

ISSN:1663-2818    

DOI:10.1159/000181536

出版商:S. Karger AG    

年代:1990

数据来源: Karger

ISSN:1663-2818    

DOI:10.1159/000181520

出版商:S. Karger AG    

年代:1990

数据来源: Karger