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Biomedical subjects

L Gianotti

Publications and source records attributed to L Gianotti.

At least 19 recordsLinked to original sources
PubMed2005

Hormonal and metabolic responses to acute ghrelin administration in patients with bulimia nervosa.

Ghrelin is generally influenced by energy balance status and is inversely associated with body mass index (BMI), being reduced in simple obesity, notable exception being Prader Willi syndrome, and elevated in several conditions of undernutrition, including anorexia nervosa (AN). Interestingly, ghrelin levels have also been found elevated in patients with bulimia nervosa (BN) in spite of normal BMI. In humans, intravenous (iv) ghrelin administration induces endocrine (increase in GH, PRL, ACTH and cortisol) and metabolic (increase in glucose and decrease in insulin) effects as well as an increase in appetite and food intake. In AN, ghrelin administration surprisingly leads to a decreased GH response and absence of glycemic variations but normal PRL, ACTH and insulin response. This pattern would reflect a decrease in sensitivity to ghrelin or, alternatively, the metabolic status of AN. To further clarify the function of ghrelin in eating disorders, the endocrine and metabolic response to acute iv ghrelin (1.0 microg/kg) was studied in seven young women with purging BN (BW, BMI, mean+/-SEM: 20.3+/-0.5 kg/m2). Circulating total ghrelin levels were also measured. The results in BW were compared to those recorded in a group of nine healthy women (HW; BMI 22.3+/-2.5 kg/m2). The GH response to ghrelin in BW overlapped with that in HW. Ghrelin administration also led to a similar increase in PRL, ACTH, cortisol and glucose levels in the two groups. Insulin levels were not significantly modified by ghrelin administration in either group. The overlapping endocrine and metabolic response to ghrelin in the two groups occurred with regard to circulating total ghrelin levels which were higher in BW than in HW. In conclusion, BN, a condition of ghrelin hypersecretion, is connoted by a normal endocrine and metabolic response to exogenous ghrelin administration.

Adrenocorticotropic Hormone↗
PubMed2004

The adrenal sensitivity to ACTH stimulation is preserved in anorexia nervosa.

Hyperactivity of hypothalamus-pituitary-adrenal (HPA) axis in anorexia nervosa (AN) has been demonstrated and is likely to reflect a central nervous system (CNS)-mediated effect of starvation. Alterations in the adrenal response to ACTH in AN have also been reported by some authors. In order to define the adrenal sensitivity to ACTH in this condition, we studied cortisol (F), aldosterone (A) and DHEA responses to the sequential administration of low and supramaximal ACTH 1-24 doses (0.06 microg/m2 ACTH 1-24 iv at 0 min and 250 microg ACTH 1-24 iv at +60 min, respectively) in 10 young women with AN [ANW, age 21.2 +/- 0.9 yr, body mass index (BMI) 15.7 +/- 0.6 kg/m2]. The results in this group were compared with those recorded in 10 healthy normal women (HW, 23.4 +/- 1.1 yr, 21.9 +/- 0.9 kg/m2). In ANW urinary F levels were similar to those in HW. Basal serum F, A and DHEA levels in ANW were not significantly different from those in HW. In HW the lowest ACTH dose induced a significant (p<0.05) increase of F, A and DHEA. The maximal ACTH dose induced F, A and DHEA increases greater (p<0.05) than those induced by the lowest ACTH dose. In ANW both ACTH doses induced significant (p<0.05) F and DHEA increases which were not significantly different from those in HW, though a trend toward a lower cortisol response after ACTH 0.06 microg/m2 in ANW was present. Like in HW, in ANW the maximal ACTH dose induced F and DHEA increases greater (p<0.01) than those induced by the lowest dose. Unlike HW, in ANW A levels did not increase after the lowest ACTH dose while they increased after the maximal one overlapping the response in HW. In conclusion, the cortisol and DHEA responses to a very low and a supra-maximal ACTH dose in patients with AN were similar to those in healthy subjects, indicating that the sensitivity to ACTH of the fasciculata and reticularis adrenal zones is preserved in this condition. On the other hand, a reduced sensitivity to ACTH of the glomerularis adrenal zone in patients with AN is suggested by the lack of aldosterone response to the lowest corticotropin dose.

Adolescent↗
PubMed2004

The psychopharmacotherapy of anorexia nervosa: clinical, neuroendocrine and metabolic aspects.

Anorexia nervosa (AN) is a complex mental disorder presenting psychiatric and physical symptoms. Literature recognizes the role of several factors in the pathogenesis of this disorder, according to the biopsychosocial model. Many mechanisms are still partly unclear. Endocrine and metabolic alterations usually occur in AN, probably having a role in its pathogenesis and in the disorder perseverance. In consideration of the multifactorial pathogenesis, a multidisciplinary approach is needed in the treatment of anorexic patients. Up-to-date psychotherapy, psychopharmacological, endocrine and nutritional treatments are considered effective in improving AN. Literature does not however provide evidence of a single validated psychopharmacotherapy for anorexic patients. It is known that psychopharmacotherapy can influence hormonal and metabolic states in some conditions, but for the moment few data are present about these effects in AN. This article aims to review the data about the psychopharmacotherapy role in AN, focusing on the endocrine and metabolic effects of anti-depressants (AD) and novel antipsychotic drugs which seem to be the most effective in AN. Scant data are however available and further research should provide more evidence about these effects and also assess whether the severity of the neuroendocrine, hormonal and metabolic impairments can predict the lack of response to the psychopharmacological treatment with AD and neuroleptics.

Anorexia Nervosa↗
PubMed2004

Obese patients with obstructive sleep apnoea syndrome show a peculiar alteration of the corticotroph but not of the thyrotroph and lactotroph function.

OBJECTIVE: Obstructive sleep apnoea syndrome (OSAS) is strongly associated with obesity (OB) and is characterized by several changes in endocrine functions, e.g. GH/IGF-I axis, adrenal and thyroid activity. It is still unclear whether these alterations simply reflect overweight or include peculiar hypoxia-induced hormonal alterations. Hormonal evaluations have been generally performed in basal conditions but we have recently reported that OSAS is characterized by a more severe reduction of the GH releasable pool in comparison to simple obesity. We aimed to extend our evaluation of anterior pituitary function to corticotroph, thyrotroph and lactotroph secretion under dynamic testing in OSAS in comparison with simply obese and normal subjects. SUBJECTS AND METHODS: In 15 male patients with OSAS [age, mean +/- SEM 43.5 +/- 1.6 years; body mass index (BMI) 39.2 +/- 3.1 kg/m2; apnoea/hypopnoea index, (AHI) 53.4 +/- 8.7], 15 male patients with simple obesity (OB, age 39.7 +/- 1.2 years; BMI 41.2 +/- 2.0 kg/m2; AHI 3.1 +/- 1.2 events/h of sleep) and in 15 normal lean male subjects (NS, age 38.2 +/- 1.4 years; BMI 21.2 +/- 0.8 kg/m2; AHI 1.9 +/- 0.8 events/h of sleep) we evaluated: (a) the ACTH and cortisol responses to CRH [2 microg/kg intravenously (i.v.)] and basal 24 h UFC levels; (b) the TSH and PRL responses to TRH (5 microg/kg iv) as well as FT3 and FT4 levels. RESULTS: Twenty-four-hour UFC levels in OSAS and OB were similar and within the normal range. Basal ACTH and cortisol levels were similar in all groups. However, the ACTH response to CRH in OSAS (Deltapeak: 30.3 +/- 3.8 pmol/l; DeltaAUC: 682.8 +/- 128.4 pmol*h/l) was markedly higher (P < 0.001) than in OB (Deltapeak: 9.3 +/- 1.4 pmol/l; DeltaAUC 471.5 +/- 97.3 pmol*h/l), which, in turn, was higher (P < 0.05) than in NS (Deltapeak: 3.3 +/- 0.9 pmol/l; DeltaAUC 94.7 +/- 76.7 pmol*h/l). On the other hand, the cortisol response to CRH was not significantly different in the three groups. Basal FT3 and FT4 levels as well as the TSH response to TRH were similar in all groups. Similarly, both basal PRL levels and the PRL response to TRH were similar in the three groups. CONCLUSIONS: With respect to patients with simple abdominal obesity, obese patients with OSAS show a more remarkable enhancement of the ACTH response to CRH but a preserved TSH and PRL responsiveness to TRH. These findings indicate the existence of a peculiarly exaggerated ACTH hyper-responsiveness to CRH that would reflect hypoxia- and/or sleep-induced alterations of the neural control of corticotroph function; this further alteration is coupled to the previously described, peculiar reduction of somatotroph function.

Adrenocorticotropic Hormone↗
PubMed2004

The endocrine response to acute ghrelin administration is blunted in patients with anorexia nervosa, a ghrelin hypersecretory state.

OBJECTIVE: Ghrelin, a gastric-derived natural ligand of the GH secretagogue (GHS)-receptor (GHS-R), strongly stimulates GH secretion but also possesses other neuroendocrine actions, stimulates food intake and modulates the endocrine pancreas and energy homeostasis. Ghrelin secretion is negatively modulated by food intake. Similarly, glucose and also insulin probably exert an inhibitory effect on ghrelin secretion. Fasting ghrelin levels are reduced in obesity, elevated in anorexia nervosa and restored by weight recovery. The chronic elevation of circulating ghrelin levels in anorexia suggested the hypothesis of an alteration of the sensitivity to the orexigenic action of ghrelin in this condition. The aim of this study was to define the endocrine actions of ghrelin in patients with anorexia nervosa. DESIGN: We enrolled nine women with anorexia nervosa of restricter type [AN; age (mean +/- SEM) 24.2 +/- 1.8 years; body mass index (BMI) 14.7 +/- 0.4 kg/m2] and seven normal young women in their early follicular phase as control group (NW; age 30.6 +/- 3.1 years; BMI 20.3 +/- 0.5 kg/m2). MEASUREMENTS: In all the subjects we studied the GH, PRL, ACTH, cortisol, insulin and glucose responses to acute ghrelin administration (1.0 microg/kg as i.v. bolus). The GH response to GHRH (1.0 microg/kg as i.v. bolus) and basal ghrelin and IGF-I levels were also evaluated in all the subjects. RESULTS: Basal morning ghrelin and GH levels in AN (643.6 +/- 21.3 ng/l and 10.4 +/- 0.5 microg/l, respectively) were higher (P < 0.05) than in NW (233.5 +/- 14.2 ng/l and 0.7 +/- 0.7 microg/l, respectively). However, IGF-I levels in AN (145.3 +/- 10.9 microg/l) were lower (P < 0.05) than in NW (325.4 +/- 12.6 microg/l). The GH response to GHRH in AN was higher (P < 0.05) than that in NW, but in AN the GH response to ghrelin was lower (P < 0.05) than that in NW. In AN and NW ghrelin also induced similar increases (P < 0.05) in PRL, ACTH and cortisol levels. Ghrelin administration was followed by significant increase in glucose levels in NW (P < 0.05) but not in AN. CONCLUSIONS: This study demonstrates that anorexia nervosa, a clinical condition of ghrelin hypersecretion, shows a specific reduction in the GH response to ghrelin, despite the hyper-responsiveness to GHRH administration. The impaired GH response to ghrelin in anorexia nervosa agrees with previous evidence of blunted GH response to synthetic GH secretagogues and could reflect desensitization of the GHS receptor induced by the chronic elevation of ghrelin levels in this pathological state.

Adrenocorticotropic Hormone↗
PubMed2003

Acute goserelin administration inhibits gonadotropin and androgen secretion in post-menopausal women with ovarian hyperandrogenism.

The aim of this study was to verify the effect of goserelin, a GnRH agonist, in women with post-menopausal virilization. Six patients with post-menopausal virilization and increase in 17-hydroxyprogesterone (17-OHP), total (TT) and free testosterone (FT) levels underwent single subcutaneous administration of goserelin, 3.6 mg. Serum 17-OHP, TT, FT, LH, FSH, E2, delta4 and 3alpha-andro-stanediol glucuronide levels were measured before and 4, 8 and 18 days after goserelin administration. Goserelin administration was followed by progressive inhibition of FSH and LH, which fell to premenopausal levels on day 18, and progressive normalization of androgen parameters. The low E2 levels recorded at baseline were further reduced by goserelin administration. Four patients then underwent ovariectomy while in two patients, rejecting surgical treatment, goserelin treatment was protracted up to 6 and 12 months, respectively, with remission of hyperandrogenism. This study shows that in post-menopausal patients with virilization GnRH agonist allows to confirm the diagnosis of gonadotropin-dependent ovarian hyperandrogenism: its administration induces inhibition of gonadotropin levels, normalization of androgen parameters, and remission of virilization when the treatment is protracted in patients waiting for surgery.

Adrenocorticotropic Hormone↗
PubMed2003

Prolonged treatment with glycerophosphocholine, an acetylcholine precursor, does not disclose the potentiating effect of cholinesterase inhibitors on GHRH-induced somatotroph secretion in anorexia nervosa.

Unlike normal subjects, in patients with anorexia nervosa (AN) the GH response to GHRH is refractory to the increasing and inhibitory effect of cholinergic agonists and antagonists, respectively. This cholinergic impairment could reflect malnutrition-induced exhaustion of acetylcholine (Ach) precursors. We studied whether treatment with glycerophosphocholine (GLY), an Ach precursor, could disclose the potentiating effect of pyridostigmine (PD) on the GH response to GHRH in AN. In 6 young women with AN (AW) we studied the GH response to iv GHRH (1.0 microg/kg) alone and combined with oral PD (120 mg) before and after 1 month of oral treatment with GLY (400 mg thrice daily). Eight age-matched normal women (NW) were studied as controls. Before GLY, basal GH levels in AW were higher (p < 0.05) than in NW. The GH response to GHRH in AW was higher (p < 0.05) than in NW. PD failed to modify the GHRH-induced GH rise in AW, while it enhanced it in NW (p < 0.05). One month treatment with GLY in AW did not modify the GH response to GHRH either alone or combined with PD. This study shows the existence of a derangement in the cholinergic control of somatotroph function in AN and indicates that treatment with Ach precursors does not exert any effect on this impairment. This could reflect primary alterations of cholinergic neurons, though the effectiveness of more prolonged treatment and/or higher doses of cholinergic precursors needs to be verified.

Acetylcholine↗
PubMed2003

Ageing, growth hormone and physical performance.

Human ageing is associated to a declining activity of the GH/IGF-I axis and to several changes in body composition, function and metabolism which show strict similarities with those of younger adults with pathological GH deficiency. The age-related changes of the GH/IGF-I axis activity are mainly dependent on age-related variations in the hypothalamic control of somatotroph function, which is also affected by changes in peripheral hormones and metabolic input. The term "somatopause" indicates the potential link between the age-related decline in GH and IGF-I levels and changes in body composition, structural functions and metabolism which characterise ageing. Physical exercise is an important environmental regulator of the GH/IGF-I axis activity. Increased physical fitness and regular training increase GH production in adults, while the GH response to aerobic or resistance exercise is reduced with age. In older subjects regular exercise has the potential to improve overall fitness and quality of life and is also associated to decreased morbidity and increased longevity. Similar effects are seen following GH therapy in adult deficiency. This assumption led to clinical trials focusing on rhGH and/or rhlGF-I as potential anabolic drug interventions in elderly subjects. To restore the activity of GH/IGF-I axis with anabolic, anti-ageing purposes, attention has been also paid to GH-releasing molecules such as GHRH, orally active synthetic GH-secretagogues (GHS) and, more recently, to the endogenous natural GHS, ghrelin, which exerts several important biological actions, including the regulation of metabolic balance and orexigenic effects. At present, however, there is no definite evidence that "frail" elderly subjects really benefit from restoring GH and IGF-I levels within the young adult range by treatment with rhGH, rhlGF-I, GHRH or GHS. In this article the alteration of the GH/IGF-I axis activity during ageing is revised taking into account the role of physical activity as a regulator of the axis function and considering the effects of the restoration of GH and IGF-I circulating levels on body composition and physical performance.

Adult↗
PubMed2003

Suppression and recovery of LH secretion by a potent and selective GnRH-receptor antagonist peptide in healthy early follicular-phase women are mediated via selective control of LH secretory burst mass.

AIM: GnRH antagonists are competitive inhibitors of GnRH receptors. Their administration induces prompt suppression of the gonadal axis. In animals, GnRH antagonists upregulate the activity of GnRH-secreting neurones, which could cause gonadotrophin rebound following inhibition. The aim of this study was to evaluate the effects of a potent GnRH antagonist, Teverelix (TEV), on the gonadal axis in healthy young women. SUBJECTS AND MEASUREMENTS: In nine women [20-35 years old, body mass index (BMI) 19-25 kg/m2] in the early follicular phase, serum LH and FSH levels were evaluated every 10 min from 08.00 to 12.00 h before, and 24 h and 96 h after TEV injection (2.5 mg in 1 ml subcutaneously on day 0). Serum gonadotrophin and oestradiol levels were also evaluated at baseline and at 6, 8, 12, 48, 72 h after TEV. RESULTS: The antagonist reduced both serum LH and FSH concentrations; LH levels were significantly and promptly reduced at +6 h (nadir at +8 h) until +48 h and recovered at +72 h, while FSH levels were reduced (P<0.05) 24 h after the antagonist and normalized at +48 h. LH (but not FSH) concentrations at +96 h exceeded baseline (P<0.05). TEV suppressed oestradiol concentrations (P<0.05) with a nadir at +24 h, comparable reduction at +48 h and recovery to baseline at +72 h. Deconvolution analysis showed that the antagonist peptide suppressed (P<0.02) the pulsatile production rate, burst mass and amplitude of LH on day 1. Pulsatile FSH secretion also fell at this time (P<0.05). LH and FSH pulse frequency were not modified by TEV. At +96 h, LH pulsatility did not significantly differ from that at baseline. Suppression of mean LH or FSH concentrations did not affect the relative pattern regularity (approximate entropy) of LH and FSH secretion. CONCLUSIONS: This study demonstrates that the acute administration of a potent GnRH antagonist induces prompt inhibition of the gonadal axis lasting for 2 days in women due to mechanistically specific suppression of LH secretory burst mass and the mean FSH secretion rate. The trend toward rebound release of LH following the end of the pharmacological effect of the antagonist could reflect a rise in endogenous GnRH activity.

Adult↗
PubMed2003

Abnormal 5-HT1D receptor function in cluster headache: a neuroendocrine study with sumatriptan.

The purpose of this study was to assess the sensitivity of 5-HT(1D) receptors in patients with episodic cluster headache using sumatriptan as a pharmacological probe. The drug, a selective 5-HT(1B/1D) agonist, stimulates the secretion of growth hormone and inhibits the release of prolactin, adrenocorticotropic hormone (ACTH) and cortisol. These effects may be used to explore the function of serotonergic systems in vivo. We administered subcutaneous sumatriptan and placebo to 20 patients with cluster headache (10 in the active phase and 10 in the remission period) and to 12 controls. The sumatriptan-induced increase of growth hormone concentrations was significantly (P < 0.05) blunted in patients with active cluster headache. Prolactin and ACTH responses to the drug were significantly (P < 0.05) reduced in patients with cluster headache, both in the active and in the remission period. Our results suggest that cerebral serotonergic functions mediated by 5-HT(1D) receptors are altered in patients with episodic cluster headache.

Adult↗
PubMed2003

[Endocrine abnormalities in anorexia nervosa].

Anorexia nervosa is a syndrome with multifactorial etiology in which several genetic, biologic, psychological and social factors are involved. Patients affected by anorexia nervosa (AN) may develop multiple endocrine abnormalities, e.g. amenorrhea, hypothalamus-pituitary-adrenal axis hyperactivity, low T3 syndrome and peculiar changes of somatotroph axis function. These endocrine abnormalities are also found after prolonged starvation and may represent an adaptive response developed in order to save energy and proteins. It is still a matter of debate whether these endocrine changes are etiologic or secondary. In fact, several evidences suggest the existence in AN of hypothalamus functional alterations, which may be involved in the development and maintenance of the food intake disorder; on the other hand, the increased CRH secretion seems to be secondary to malnutrition as well as GH hypersecretion coupled to low IGF-I levels; the latter is a common finding in AN, as well as in other undernutrition and malabsorption conditions, type 1 diabetes mellitus, liver cirrhosis and catabolic states. Hypothalamic amenorrhea, which is one of the diagnostic criteria for AN, is not linked only to the reduction of body weight but reflects also deep alterations of gonadotropin secretory pattern. Low T3 syndrome is frequently found in AN; on the other hand, an iodide-induced hypothyroidism is quite uncommon. T3 reduction in AN seems to be an adaptive response to prolonged starvation; however the presence of a simultaneous central dysregulation cannot be excluded. Finally, AN patients frequently show defects in urinary concentration or dilution with inappropriate secretion of antidiuretic hormone, which may be due to intrinsic defects in the neurohypophysis or to abnormalities of its regulatory afferent neurons.

Animals↗
PubMed2003

[Nutritional therapy in surgical patients: an update].

Patients undergoing major gastrointestinal surgery, often require an adequate artificial nutritional (AN) support for a pre-existing state of malnutrition and/or to overcome forced periods of postoperative starvation and/or for complications that alter the host metabolic response. When an indication to AN is given, enteral feeding should be preferred to parenteral nutrition because more physiological and less expensive. Moreover, recent data showed that patients fed enterally, rather than parenterally, in the postoperative period, have a significant better outcome with a reduction of morbidity and hospitalisation. The supplementation of standard feeds with key nutrients having immunomodulatory properties, such as arginine, omega-3 fatty acids and glutamine (pharmaconutrients), allows to control effectively the surgery-induced immunosuppression and hyperinflammation. An analysis on the principles of evidence-based medicine, supports the hypothesis that the pre-perioperative use of formulas enriched with pharmaconutrients, significantly reduces the rate of infectious complications and saves health care resources.

Enteral Nutrition↗
PubMed2002

Activity of GH/IGF-1 axis in burn patients: comparison with normal subjects and patients with GH deficiency.

The aim of this study was to clarify the activity of GH/IGF-1 axis as well as the variations of nutritional parameters following a thermal injury in man. To this goal, in 22 patients with burn [BURN, age (mean+/-SE): 46.5+/-3.4 yr, BMI: 25.0+/-0.8 kg/m2, % burn surface area: 26.0+/-3.0%, ROI score: 0.22+/-0.1] we evaluated IGF-1, IGF binding protein (IGFBP-3), GH, GH binding protein (GHBP), pre-albumin (pre-A), albumin (A) and transferrin (TRA) levels on days 1, 3, 7, 14 and 28 after intensive care unit (ICU) admission. IGF-1, IGFBP-3, GH and GHBP levels were also assayed basally in 29 normal subjects (Ns) (Ns, age: 47.5+/-2.8 yr, BMI: 22.0+/-1.4 kg/m2) and in 34 panhypopituitary patients with severe GH deficiency (GHD, age: 42.7+/-2.5 yr, BMI: 25.6+/-0.8 kg/m2). On ICU day 1, IGF-1 and IGFBP-3 in BURN were higher than those in GHD (p<0.05 for both, respectively) and lower than those in Ns (p<0.05) while GH levels in BURN did not differ from those in Ns and higher than GHD (p<0.01). In BURN, IGF-I and IGFBP-3 levels showed a progressive decline (p<0.05) with nadir on day 14, when they overlapped those in GHD, and then an increase on day 28, though persisting lower than in Ns, while GH levels did not vary during ICU stay. IGF-I levels were associated neither to burn extension nor to ROI score. On ICU day 1 pre-A, A and TRA levels were similar to those in Ns, but underwent a progressive decrease with nadir on day 7 (p<0.001) for pre-A and TRA, and later, on day 14 (p<0.05) for A; pre-A and TRA but not A showed a rebound increase (p<0.01) on day 14, though persistingly lower than in Ns. In conclusion, our present data firstly show the time course variation of IGF-I levels in burn patients as function of nutritional and hormonal variables. It has to be emphasized that in the most critical phase after burn injuries, IGF-1 levels are as low as in hypopituitary patients with severe GHD. The physiological basis which leads to the impairment of this endogenous anabolic drive in this phase is, however, not clear yet.

Adult↗
PubMed2002

Activity of GH/IGF-I axis in trauma and septic patients during artificial nutrition: different behavior patterns?

The aim of this study was to compare several parameters of GH/IGF-I axis activity in septic and trauma patients during Intensive Care Unit (ICU) stay. To this goal, 13 patients with sepsis (SEP) and 16 with trauma (TRA) were studied. Thirty-three adult subjects (AS) were studied as controls. Serum IGF-I and -II, IGFBP-1, -2 and -3, GH and GHBP levels were studied on day 1, 3, 5 and 7 after ICU admission, during comparable artificial nutrition in SEP and TRA and basally in AS. In 5 patients with SEP and 6 with TRA, the GH response to GHRH was evaluated on day 3. On ICU day 1, IGF-I and -II and IGFBP-3 in SEP were lower (p<0.05) than in TRA which, in turn, were lower (p<0.01) than in AS. IGF-I increased (p<0.05) both in SEP and TRA, but, on ICU day 7, those in SEP persisted lower than in TRA, which became similar to those in AS. IGF-II levels increased (p<0.05) in SEP only, persisting lower (p<0.05) than in TRA. On ICU day 1, GH in SEP and TRA were similar and did not vary until day 7, overlapping those in AS. The GH response to GHRH in SEP and TRA was similar and lower (p<0.01) than in AS. These findings indicate that IGF-I activity is impaired more in septic than in trauma patients. Reduced IGF-I activity probably reflects peripheral GH resistance though basal and GHRH-induced GH levels were not increased in these conditions.

Adult↗
PubMed2002

Alprazolam, a benzodiazepine, does not modify the ACTH and cortisol response to hCRH and AVP, but blunts the cortisol response to ACTH in humans.

Alprazolam (AL), a benzodiazepine which activates gamma-amino butyrric acid (GABA)-ergic receptors, exerts a clear inhibitory effect on the activity of the hypothalamo-pituitary-adrenal (HPA) axis and is able to markedly reduce the ACTH response to metyrapone-induced inhibition of glucocorticoid feedback. It has been suggested that its inhibitory action could be regulated by CRH or AVP mediated mechanisms. However, the effect of benzodiazepines on the HPA response to CRH or AVP is contradictory. It has been shown that benzodiazepines have specific receptors on the adrenal gland but it is unclear if they mediate biological effects in humans. In order to further clarify the mechanisms underlying the inhibitory effect of benzodiazepine on HPA axis in humans, we studied the effect of AL (0.02 mg/kg po at -90 min) or placebo in 7 healthy young volunteers (7 female, age: 26-34 yr; wt: 50-58 kg, BMI 20-22 kg/m2) on: 1) the ACTH and cortisol responses to hCRH (2.0 microg/kg iv at 0 min) or AVP (0.17 U/kg im at 0 min); 2) the cortisol, aldosterone and DHEA responses to ACTH 1-24 (0.06 and 250 microg iv at 0 and 60 min, respectively). After placebo, the ACTH and cortisol responses to hCRH (peaks, mean+/-SE: 29.8+/-4.4 pg/ml and 199.3+/-19.6 microg/l) were similar to those recorded after AVP (31.7+/-6.5 pg/ml and 164.8+/-18.0 microg/l); the cortisol response to 0.06 microg ACTH (190.4+/-11.8 microg/l) was similar to that recorded after hCRH and AVP but lower (p<0.01) than that after 250 microg ACTH (260.6+/-17.4 microg/l). AL did not modify the ACTH response to both hCRH (42.5+/-7.1 pg/ml) and AVP (33.3+/-2.7 pg/ml), which even showed a trend toward increase. AL also failed to significantly modify the cortisol response to both hCRH (156.3+/-12.7 microg/l) and AVP (119.4+/-14.5 microg/l), which, on the other hand, showed a trend toward decrease. The cortisol peaks after 0.06 microg ACTH were significantly reduced (p<0.02) by AL pre-treatment (115.0+/-7.7 microg/l) which, in turn, did not modify the cortisol response to the subsequent ACTH bolus (214.7+/-16.6 microg/l). The DHEA and aldosterone responses to all the ACTH doses were not significantly modified by AL. In conclusion, these data show that the HPA response to AVP as well as to hCRH is refractory to the inhibitory effect of AL which, in turn, blunts the cortisol response to low ACTH dose. These findings suggest that both CRH- and AVP-mediated mechanisms could underlie the CNS-mediated inhibitory effect of AL on HPA axis; in the meantime, these results suggest that benzodiazepines could also act on adrenal gland by blunting the sensitivity of the fasciculata zone to ACTH.

Adrenocorticotropic Hormone↗
PubMed2002

Decreased sensitivity of 5-HT1D receptors in chronic tension-type headache.

OBJECTIVE: To assess the sensitivity of 5-HT1D receptors in chronic tension-type headache using sumatriptan as a pharmacological probe. BACKGROUND: Previous studies have suggested involvement of serotonergic systems in chronic tension-type headache (CTTH), but relevant experimental data are limited. Sumatriptan, a 5-HT1B/1D receptor agonist, stimulates the release of growth hormone (GH) and inhibits the release of ACTH, cortisol, and prolactin. These effects may be used to explore the function of serotonergic systems in vivo. METHODS: We measured GH, ACTH, cortisol and prolactin (PRL) plasma concentrations in 15 patients with chronic tension-type headache and in 18 healthy controls after subcutaneous administration of sumatriptan (6 mg) or placebo. RESULTS: Placebo administration had no effect on hormone concentrations. GH and PRL secretion after sumatriptan administration was significantly (P<0.01 and <0.05) altered in CTTH patients in comparison with controls. CONCLUSION: Our results suggest that cerebral serotonergic functions mediated by 5-HT1D receptors are altered in CTTH.

Adult↗
PubMed2002

Feeding the gut early after digestive surgery: results of a nine-year experience.

BACKGROUND AND AIMS: Early enteral nutrition (EEN) after surgery should be preferred to parenteral feeding, but its clinical use is limited for concerns about possible gastrointestinal (GI) adverse effects and feeding tube-related complications. Thus we evaluated our experience focusing on safety and tolerance of early postoperative jejunal feeding and possible risk factors for gastrointestinal adverse effects. METHODS: 650 subjects treated with EEN after major digestive surgery for cancer were prospectively studied. EEN was started within 12 hours after operation via a naso-jejunal (NJ) feeding tube or a catheter-feeding jejunostomy. The rate of infusion was progressively increased to reach the nutritional goal (25 kcal/kg/day) within the 4th postoperative day. Rigorous treatment protocols for diet delivery and EEN-related GI adverse effects were applied. RESULTS: 402 patients had a jejunostomy and 248 patients a NJ tube. EEN-related GI adverse effects were observed in 194/650 patients (29.8%). In 136/194 patients, these events were successfully handled by treatment protocols. Overall the nutritional goal was achieved in 592/650 patients (91.1%). Fifty-eight (8.9%) subjects had to be switched to parenteral feeding because of refractory intolerance to EEN. Intra-abdominal surgical complications and low serum albumin (<30 g/L) were the two major factors affecting tolerance. Severe jejunostomy-related complications occurred in 7/402 (1.7%) patients. EEN-related mortality was 0.1% (1/650). CONCLUSIONS: The use of the gut early after surgery is safe and well-tolerated and it should represent the first choice for nutritional support in this type of patients.

Digestive System Surgical Procedures↗