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Biomedical subjects

E Comoy

Publications and source records attributed to E Comoy.

At least 37 records · Page 2Linked to original sources

Palatability of a meal influences release of beta-endorphin, and of potential regulators of food intake in healthy human subjects.

The effect of the palatability of a meal was tested on the post-prandial release of several gut hormones or neuropeptides which are known to have an effect on intake and satiety. Hormonal response was determined in plasma during the 3 h after a highly palatable and energy-rich meal or after the same meal served cold in a poorly acceptable form, as well as while fasting. The early post-prandial pancreatic polypeptide and neurotensin response was significantly higher after the highly palatable meal than after the cold one. Later responses differed only for pancreatic polypeptide. No difference was observed in cholecystokinin and neuropeptide Y levels. Post-prandial levels of beta-endorphin were elevated only after the cold meal and were associated with an elevated response of ACTH. We suggest that beta-endorphin might be secreted in response to an aversion towards the non-palatable cold meal. This could, subsequently, inhibit the cephalic phase of pancreatic polypeptide response and the early post-prandial response of neurotensin by a central anticholinergic effect. This study evidences an effect of palatability on the modulation of the digestive hormonal response after a meal.

Adult↗

Screening for adrenal medullary disease in patients with medullary thyroid carcinoma.

Adrenal medullary disease (AMD) is clinically silent in most patients with medullary thyroid carcinoma (MTC). It was screened yearly by urinary measurements of catecholamines and derivates, and by abdominal ultrasonography (US) in a series of 174 patients with MTC. In cases with suspicion of AMD, abdominal computerized tomography and scintigraphy with meta-iodobenzylguanidine were also performed. AMD was discovered in 10 patients (one adrenal medullary hyperplasia and 9 pheochromocytomas). Three patients were already known to belong to a type II multiple endocrine neoplasia (MEN-2a) family and two had a MEN-2b syndrome. In 5 patients previously considered as having either a sporadic (4 cases) or a familial type of isolated MTC (one case), the occurrence of AMD led to diagnose a MEN-2a syndrome. The diagnostic values of the tests were evaluated by a case-control study. Urinary metanephrine plus normetanephrine (MN+N) had an acceptable sensitivity (0.8) and specificity (0.8). The other urinary tests had a high specificity (range: 0.8 to 1) but a poor sensitivity (range: 0.1 to 0.5). US had a high sensitivity (0.8) and a specificity of one. MN+N and US performed yearly constitute a simple and efficient strategy to screen for AMD in patients with MTC.

Adolescent↗

[Recommended methods for the determination of catecholamines and their metabolites in urine. Significance of results in the diagnosis and follow-up of pheochromocytoma and neuroblastoma].

Laboratory investigation of catecholamines is useful for the clinician in the diagnosis and management of phaeochromocytoma and neuroblastoma. This work summarizes current knowledge on catecholamines and their metabolites and discusses the main indications for their determination. It also examines the most practical methods for studying the secretion of these hormones, ie extraction, separation and quantification using high performance liquid chromatography coupled with electrochemical detection. The workshops attended by the members of the catecholamines working party of the French Clinical Biology Society and phaeochromocytoma and neuroblastoma specialists enabled the role of such determinations in the diagnosis and management of these diseases to be clarified.

Adolescent↗

Peripheral blood corticotropin-releasing factor, adrenocorticotropic hormone and cytokine (interleukin beta, interleukin 6, tumor necrosis factor alpha) levels after high- and low-dose total-body irradiation in humans.

Total-body irradiation (TBI) induces an increase in levels of granulocytes and cortisol in blood. To explore the underlying mechanisms, we studied 26 patients who had TBI prior to bone marrow transplantation. Our findings suggest that only a high dose of TBI (10 Gy) was capable of activating the hypothalamo-pituitary area since corticotropin-releasing factor and blood adrenocorticotropic hormone levels increased at the end of the TBI. There was a concomitant increase in the levels of interleukin 6 and tumor necrosis factor in blood, suggesting that these cytokines might activate the hypothalamo-pituitary adrenal axis. Interleukin 1 was not detected. Since vascular injury is common after radiation treatment, it is possible that interleukin 6 was secreted by endothelial cells. The exact mechanisms of the production of cytokines induced by ionizing radiation remain to be determined.

Adrenocorticotropic Hormone↗

Age-related changes of noradrenergic-NPY interaction in rat brain: norepinephrine, NPY levels and alpha-adrenoceptors.

Noradrenergic-neuropeptide Y interaction, which is implicated in different physiological functions, was studied in senescent rats. Norepinephrine (NE) and neuropeptide Y (NPY) levels were measured in brainstem and hypothalamus, and alpha-adrenergic binding was investigated in brainstem in young (4 months) and old (34 months) Wistar rats. NE concentration was the same in senescent rats, whereas NPY concentration was decreased both in brainstem and hypothalamus compared to levels in young rats. [3H]prazosin binding to alpha 1-adrenoceptors was not modified, but [3H]rauwolscine binding to alpha 2-adrenoceptors was altered with age. In fact, the density of alpha 2-adrenoceptors (Bmax) was lower, while the binding affinity (Kd) was increased in old compared to young rats. These results suggest that the decrease of NPY levels could be one of the possible reasons for changes in [3H]rauwolscine binding to alpha 2-adrenoceptors in old rats. The G-protein-adenylate cyclase system, which is impaired in senescent rats, could be involved in the disorganization of noradrenergic-NPY interaction.

Aging↗

Effects of clonidine on plasma catecholamines and neuropeptide Y in hypertensive patients at rest and during stress.

Neuropeptide Y (NPY), a potent vasoconstrictor agent reported to be released, in addition to norepinephrine (NE), by sympathetic nerve endings during stress, may contribute to the pressor response to various stimuli. The objectives of this study were to determine (a) whether plasma NPY concentrations are altered during different types of stress (cold pressor test, mental stress, and active orthostatism) and (b) whether clonidine, via its central sympatholytic effect, affects the stress-induced blood pressure, NPY, and/or catecholamine changes. Eighteen untreated patients with mild essential or borderline hypertension participated in an acute randomized, double-blind, parallel study. The blood pressure and heart rate were recorded during three control periods, each followed by either a cold pressor test (CPT), a mental stress test (MS: mental arithmetic), or active orthostatism (AO), performed in a random order. Venous blood samples for catecholamines and NPY determination were taken at the end of each control and test period. This entire procedure was repeated after oral clonidine (150 micrograms) or placebo. Before treatment, a CPT, MS, or AO increased the blood pressure to the same extent. The stress-induced increase in plasma NE was greater during AO (+99 +/- 23%) than during CPT (+35 +/- 8%) and MS (+55 +/- 12%). The stress-induced increase in plasma epinephrine was only significant during MS (+142 +/- 69%). A small but significant increase in NPY (p < 0.05) was observed during AO only (+10 +/- 7%). Compared to placebo, clonidine significantly decreased the basal blood pressure and the pressor response to CPT, but did not change the pressor response to MS and AO.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A role for neuropeptide-Y, dynorphin, and noradrenaline in the central control of food intake after food deprivation.

A marked increase in food intake is observed in the rat after central injection of neuropeptide-Y (NPY), dynorphin, or noradrenaline (NA). Levels of both NPY and dynorphin are increased in the hypothalamus of food-deprived rats. The aim of this study was to explore the role of NPY, dynorphin, and NA in the central control of feeding after a period of food deprivation. We have investigated the effect of intracerebroventricular injection of a monoclonal antibody to NPY (NPYAb), a potent and selective kappa-opioid receptor antagonist norbinaltorphimine (norBNI), and the alpha-adrenergic antagonist phentolamine on fast-induced food intake. In animals provided with food after a 24-h fast, NPYAb given 10 min before presentation of food reduced food intake by 30% (P < 0.01) compared to that of animals pretreated with an antibody to chloroquine. A similar (34%; P < 0.05) reduction in fast-induced feeding occurred after pretreatment with norBNI. If norBNI was given together with NPYAb, then a reduction of 51% (P < 0.05) was observed. Pretreatment with phentolamine reduced fast-induced food intake by 39% (P < 0.05), with no evidence of an additive effect when phentolamine was given together with NPYAb. These data would support a role for endogenous NPY, dynorphin, and NA in the mediation of fast-induced feeding. NPY would seem to act independently of dynorphin, but through the same mechanism as NA.

Animals↗

Malignant pheochromocytoma: clinical, biological, histologic and therapeutic data in a series of 20 patients with distant metastases.

Twenty patients, 16 males and 4 females, aged 11-76 yr, were treated for a metastatic pheochromocytoma at our institution between 1985 and 1990. A neurofibromatosis was associated in 4. Thirteen patients had a unilateral adrenal tumor, 3 had an extraadrenal retroperitoneal tumor, 2 had a bilateral adrenal pheochromocytoma, one had a unilateral tumor with a contralateral medullary hyperplasia and one an adrenal and an extraadrenal pheochromocytoma. Metastases occurred in all patients, at presentation in 11, 10 to 30 months later in 7, and 9 and 28 yr later, respectively in two. Histology did not afford conclusive evidence for malignancy. Catecholamine hyperproduction was present in all, predominantly affecting norepinephrine. Neuron Specific Enolase level was elevated in 11, Neuro-Peptide Y level in 9 and procalcitonin level in 11/18. High dopamine, methoxytyramine and homovanillic acid excretion levels seemed to correlate with large tumors or terminal stage. MIBG uptake was found in 16 after a diagnostic dose and in 1 only after a therapeutic dose. Surgery was performed on primary tumor in 18 and on distant metastase in 10. Iodine-131 MIBG therapy was performed in 11, among whom 9 were evaluable. Cumulative activity ranged from 100 to 711 mCi, in 1 to 6 courses. Symptomatic improvement occurred in 5 patients, stabilization was observed in 3 and tumor partial response in two, which lasted for 28 and 9 months, respectively terminating in a rapidly progressing disease with bone marrow involvement. Moderate myelosuppression occurred in 4 patients. Chemotherapy gave no response in 7 evaluable patients. Fourteen patients died with a median survival of 16 months from diagnosis of metastases (range 3-60). Response to therapy was poor and warrants further cooperative trials.

3-Iodobenzylguanidine↗

Brain and adrenal monoamines and neuropeptide Y in codeine tolerant rats.

1. Monoamine turnover and neuropeptide Y (NPY) levels were investigated in the central and peripheral nervous systems in adult male rats chronically treated with codeine. 2. An increase in the dopaminergic turnover was observed in the striatum and cortex. The norepinephrine levels and the serotoninergic turnover were unchanged in all the brain areas. 3. Epinephrine levels were decreased in the adrenal glands. 4. In addition, we observed a significant decrease of NPY levels in the hypothalamus, the striatum and the adrenal glands. These observed changes were not found when assessing NPY level in plasma fluid. 5. The implication of these modifications in the induction of codeine dependence are discussed in view of previous results obtained with morphine.

Adrenal Glands↗

Production and characterization of four anti-neuropeptide Y monoclonal antibodies.

Human neuropeptide Y (hNPY) is a potent vasoconstrictor peptide of 36 aminoacid residues. We isolated hybridomas secreting four monoclonal antibodies directed against various epitopes of neuropeptide Y and studied their cross-reactivity with peptide YY (PYY) and the pancreatic polypeptide (PP), two peptides sharing sequence homologies with hNPY (respectively 70% and 50%). The antibody NPY02 is an IgG1 with a Ka of 5.5 x 10(10) liters/mol. It binds to the 11-24 region of NPY (IC50 = 2 x 10(-7)M), does not recognize PP but cross-reacts weakly with PYY. Antibodies NPY03 and NPY05 are IgG2 with respective Ka's of 6.7 x 10(9) and 2.5 x 10(10) liters/mol. They interact with a C-terminal epitope on NPY (NPY 27-34, IC50 = 2 x 10(-9) M for NPY03 and NPY 32-36, IC50 = 1 x 10(-9) M for NPY05). These two antibodies cross-react with PYY whereas only NPY05 binds PP. NPY05 is unable to bind the free acid form of neuropeptide Y. The 32-36 COOH free subpeptide is recognized 50,000 less efficiently by NPY05 than its amidated form. Antibody NPY04 is an IgG3 with a Ka of 3.8 x 10(8) liters/mol. It recognizes a N-terminal epitope between aminoacids 1 and 12 (IC50 = 2.5 x 10(-6) M). NPY04 interacts weakly with PYY but not detectably with PP. These results obtained with 4 different monoclonal antibodies demonstrate the presence of at least four epitopes on hNPY, two of them being continuous. These antibodies will be used to study the interaction of NPY with its receptor and to develop sensitive and specific assays for determination of NPY concentrations in biological fluids.

Amino Acid Sequence↗

Relationship among neuropeptide Y, catecholamines and haemodynamics in congestive heart failure.

The relationship among neuropeptide Y (NPY), catecholamines and haemodynamics was assessed both at baseline and during inotropic intervention in patients with congestive heart failure. Eighteen patients with idiopathic dilated cardiomyopathy (left ventricular ejection fraction (LVEF) = 26 +/- 10%) underwent both right and left catheterization. Haemodynamic parameters were recorded at baseline and during dobutamine infusion. To measure norepinephrine (NE), epinephrine (E) (nmol.l-1: radioenzymatic assay) and NPY (pmol.l-1: immunoradiometric assay) plasma concentrations, blood samples were drawn from the femoral artery and from the coronary sinus, both at baseline and during dobutamine infusion. At baseline, NPY concentration were 2.15 +/- 0.97 pmol.l-1 in the femoral artery and 1.97 +/- 0.63 pmol.l-1 in the coronary sinus. Peripheral concentrations of NPY were, however, no different from those of patients without congestive heart failure: 2.4 +/- 2.7 pmol.l-1. Peripheral NE concentration was correlated to haemodynamic parameters: LVEF (r = -0.65; P less than 0.01), cardiac index (r = -0.54; P less than 0.05), LV end-diastolic pressure (r = +0.59; P less than 0.05), while peripheral NPY and E concentrations were not. Dobutamine improved haemodynamics, since cardiac index increased by 30% and LV end-diastolic pressure decreased by 40% (P less than 0.01). Peripheral NE concentration decreased from 6.48 +/- 4.5 to 4.82 +/- 2.69 nmol.l-1 (P less than 0.05) but there was no change in E (0.99 +/- 0.61 vs 1.04 +/- 0.74 nmol.l-1) or NPY concentrations (2.41 +/- 0.99 pmol.l-1). In the coronary sinus, neither NE nor NPY concentrations changed during dobutamine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effects of chronic administration of morphine on the levels of brain and adrenal catecholamines and neuropeptide Y in rats.

1. Monoamine turnover and neuropeptide Y (NPY) levels were investigated in the central and peripheral nervous systems in adult male rats chronically treated with morphine. 2. The well-recognized biochemical alterations (serotoninergic turnover increased in the hypothalamus, hippocampus and striatum; dopaminergic turnover increased in the striatum and cortex; adrenaline levels decreased in the adrenal glands) were observed. 3. In addition, we observed a significant decrease of the NPY levels in the hypothalamus, the striatum and the adrenal glands. The observed changes were not reflected in plasma. 4. Our results contribute to the evidence that brain and adrenal monoamines and NPY could be involved in the mechanism of morphine tolerance and/or dependence.

Adrenal Glands↗

TRIAC (3,5,3'-triiodothyroacetic acid) has parallel effects at the pituitary and peripheral tissue levels in thyroid cancer patients treated with L-thyroxine.

OBJECTIVE: To investigate whether the addition of 3,5,3'-triiodothyroacetic acid (TRIAC) to thyroxine (T4) treatment can suppress TSH secretion without inducing thyrotoxicosis at the periphery. DESIGN: Thyroid cancer patients were studied with different treatment modalities: T4 at supraphysiologic dose (2.5 +/- 0.3 micrograms/kg/day) and after reduction to a physiologic dose (1.8 +/- 0.3 micrograms/kg/day); then with the addition of TRIAC 500 or 1000 micrograms/day to the physiologic T4 treatment dose. PATIENTS: Twenty-two patients who had total thyroid ablation for differentiated thyroid carcinoma. MEASUREMENTS: Clinical and biological parameters of thyroid hormone action studied included heart rate, serum creatine phosphokinase, testosterone-oestradiol binding globulin, procollagen III and osteocalcin levels. RESULTS: The addition of TRIAC induced a significant and dose-dependent decrease in serum TSH levels and parallel effects on peripheral tissues. Compared to the suppressive T4 treatment dose, the addition of TRIAC to the physiologic T4 dose resulted in greater inhibition of TSH secretion in only 50% of the patients. The effects at the periphery of both treatment modalities were similar for a comparable level of TSH suppression. CONCLUSIONS: Even at low dose and when combined with T4, TRIAC has parallel effects on the pituitary and peripheral tissues. There is no justification for the use of TRIAC as suppressive treatment in thyroid cancer patients.

Depression, Chemical↗

Hemodynamic and catecholamine response to isoflurane versus droperidol in complement to fentanyl anaesthesia.

Droperidol (0.03 mg.kg-1 to 0.25 mg.kg-1) with fentanyl has been reported to be less efficient than volatile agents in the prevention of haemodynamic responses to surgery. The aim of this study was to investigate the use of high-dose droperidol in complement to fentanyl in comparison with isoflurane and fentanyl anaesthesia. Thirty patients undergoing laryngectomy were studied. Systolic blood pressure (SBP), heart rate (HR) and plasma catecholamines were analysed both during anaesthesia and during recovery. During surgery, SBP epinephrine (E) levels did not change in either group. HR was slightly lower during droperidol fentanyl anaesthesia. Norepinephrine (NE) levels were significantly higher in the droperidol group than in the isoflurane group (P less than 0.05). During recovery, in both groups, SBP increased by 20% whereas E levels increased by 65%. NE levels increased post-operatively in both groups, but this rise was significantly higher in the droperidol group (P less than 0.01). It is concluded that the two techniques contribute to the haemodynamic stability during surgery, but do not prevent haemodynamic instability during recovery.

Anesthesia, General↗

Long-term follow-up of ifosfamide renal toxicity in children treated for malignant mesenchymal tumors: an International Society of Pediatric Oncology report.

The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.

Acute Kidney Injury↗

Neuropeptide Y and neuron-specific enolase levels in benign and malignant pheochromocytomas.

Neuron-specific enolase (NSE) is the isoform of enolase, a glycolytic enzyme found in the neuroendocrine system. Neuropeptide Y (NPY) is a peptide recently discovered in the peripheral and central nervous systems. Serum NSE and plasma NPY levels have been reported to be increased in some patients with pheochromocytoma. The authors evaluated whether the measurement of these molecules could help to discriminate between benign and malignant forms of pheochromocytoma. The NSE levels were normal in all patients with benign pheochromocytoma (n = 13) and elevated in one half of those with malignant pheochromocytoma (n = 13). Plasma NPY levels were on the average significantly higher in the malignant (177.1 +/- 38.9 pmol/l, n = 16) than in the benign forms of the disease (15.7 +/- 389 pmol/l, n = 24). However, there was no difference in the percentage of patients with elevated NPY levels. These results show that determination of serum NSE may be useful for distinguishing between malignant and benign pheochromocytoma; the measurement of plasma NPY is not useful for differentiating the two kinds of tumors.

Adrenal Gland Neoplasms↗