RESUMEN
AIMS: Functions of the gut hormone cholecystokinin (CCK) include an important role in the regulation of gastric emptying, postprandial glucose homeostasis, and postmeal satiety. Postprandial CCK responses are significantly blunted in type 2 diabetic patients by unknown mechanisms. We hypothesized that hyperinsulinemia and lipid infusion influence circulating levels of biologically active CCK. METHODS: Eleven healthy subjects were studied in a cross-over design after 10-h overnight fasts, using euglycemic-hyperinsulinemic clamps for 443 min, with an additional infusion of lipid-heparin (1.25 ml.min(-1)) or saline (1.25 ml.min(-1)) for the last 300 min after constant plasma glucose levels were achieved. RESULTS: Euglycemic-hyperinsulinemia resulted in a sustained, up to 5-fold increase of plasma CCK (P < 0.001). When adding lipid infusion instead of saline, CCK concentrations rapidly declined and returned to baseline levels (CCK(300 min) 1.1 +/- 0.2 vs. 3.3 +/- 0.3 pmol/liter, P < 0.001). Partial intraclass correlation showed an independent correlation of plasma CCK with free fatty acids (r(ic) = -0.377, P < 0.001) but not with serum insulin (r(ic) = 0.077, P = 0.32). Whole-body insulin sensitivity decreased in lipid-exposed subjects (M value 7.1 +/- 0.7 vs. 5.6 +/- 0.9 mg.kg.min(-1), P = 0.017) but was not independently correlated with CCK (r(ic) = 0.040, P = 0.61). CONCLUSIONS: We report novel findings showing that circulating CCK markedly increased in the euglycemic-hyperinsulinemic state, possibly as a result of near-complete suppression of circulating free fatty acids. Moreover, raising blood lipids even moderately by lipid infusion rapidly and significantly interfered with this effect, suggesting that a negative feedback mechanism of blood lipids on circulating CCK might exist.
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Colecistoquinina/sangre , Técnica de Clampeo de la Glucosa , Hiperinsulinismo/sangre , Hiperinsulinismo/inducido químicamente , Lípidos/farmacología , Estudios Cruzados , Femenino , Humanos , Hiperlipidemias/sangre , Hiperlipidemias/inducido químicamente , Bombas de Infusión , Insulina/sangre , Insulina/farmacología , Resistencia a la Insulina/fisiología , Lípidos/administración & dosificación , Masculino , Persona de Mediana EdadRESUMEN
UNLABELLED: mu-Opiate receptor agonists, such as loperamide, influence biliary excretion and suppress cholecystokinin (CCK)-induced gallbladder contraction. Loperamide decreases cholinergic mechanisms, like pancreatic polypeptide (PP) release, while muscarinic agonist (bethanechol)-induced PP release remains unaffected. The effects of loperamide on gallbladder contraction and peptide release were performed to resolve this discrepancy. METHODS: Six subjects (27.6 +/- 2.0 years) received bethanechol (12.5, 25 and 50 microg kg(-1) h(-1) continuously over 40 min) after oral 16 mg loperamide (vs placebo) in a crossover design. Gallbladder volume and plasma levels of CCK, PP, motilin, gastrin, neurotensin, cholylglycine were measured regularly. RESULTS: Bethanechol significantly reduced gallbladder volume (26.7 +/- 1.9 to a nadir of 15.3 +/- 2.2 mL, P < or = 0.05), and this action was inhibited by loperamide. Basal CCK levels increased significantly after loperamide. Incremental integrated CCK release after bethanechol was higher under loperamide (P < or = 0.05), as placebo CCK release was significantly decreased under bethanechol (2.0 +/- 0.4-0.8 +/- 0.3 pmol L(-1)). In both settings, PP levels were significantly increased after bethanechol, while release of neurotensin, motilin, gastrin and cholylglycine was unaffected. CONCLUSION: The mu-opiate receptor agonist loperamide inhibits bethanechol-induced gallbladder contraction. This effect is not mediated by inhibition of CCK release, as loperamide even enhances basal CCK plasma levels. As cholinergic mechanisms, like bethanechol-induced incremental PP release, were unaffected, mu-opiate agonists might influence gallbladder contraction via vagal-cholinergic pathways.
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Betanecol/farmacología , Colecistoquinina/sangre , Vesícula Biliar/fisiología , Loperamida/farmacología , Contracción Muscular/efectos de los fármacos , Receptores Opioides mu/agonistas , Adulto , Estudios Cruzados , Vesícula Biliar/efectos de los fármacos , Humanos , Masculino , Contracción Muscular/fisiología , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiología , Polipéptido Pancreático/sangre , Polipéptido Pancreático/metabolismo , PlacebosRESUMEN
OBJECTIVE: Ghrelin is a new gastric hormone that has been identified as an endogenous ligand for the growth hormone (GH) secretagogue receptor subtype 1a (GHS-R1a). Ghrelin administration however not only stimulates GH secretion but also induces adiposity in rodents by increasing food intake and decreasing fat utilization. We hypothesized that impaired ghrelin secretion in anorexia nervosa may be involved in the pathogenesis of this eating disorder. To examine this hypothesis and to further investigate the role for ghrelin in regulating energy homeostasis, we analyzed circulating ghrelin levels in patients with anorexia nervosa and examined possible correlations with clinical parameters before and after weight gain. METHODS: Plasma ghrelin levels were measured in overnight fasting plasma samples from 36 female patients with anorexia nervosa (age: 25.0+/-1.2 years, BMI: 15.2+/-0.2 kg/m(2)) before and after weight gain following psychotherapeutic treatment intervention in a psychosomatic institution. Plasma ghrelin levels were also measured in fasting plasma samples from 24 age-matched female controls (31+/-1.4 years, BMI: 22.9+/-0.45 kg/m(2)). For quantification of ghrelin levels a commercially available radioimmunoassay (Phoenix Pharmaceuticals, USA) was used. RESULTS: Fasting plasma ghrelin levels in anorectic patients were significantly higher (1057+/-95 pg/ml) than in normal age-matched female controls (514+/-63 pg/ml n=24, P=0.02). Therapeutic intervention in a psychosomatic institution caused an BMI increase of 14% (P<0.001) leading to a significant decrease in circulating ghrelin levels of 25%, (P=0.001). A significant negative correlation between Deltaghrelin and DeltaBMI was observed (correlation coefficient: -0.47, P=0.005, n=36). CONCLUSION: We show for the first time that fasting plasma levels of the novel appetite-modulating hormone ghrelin are elevated in anorexia nervosa and return to normal levels after partial weight recovery. These observations suggest the possible existence of ghrelin resistance in cachectic states such as caused by eating disorders. Future studies are necessary to investigate putative mechanisms of ghrelin resistance such as a possible impairment of intracellular ghrelin receptor signaling in pathophysiological states presenting with cachexia.
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Anorexia Nerviosa/sangre , Hormonas Peptídicas , Péptidos/sangre , Aumento de Peso/fisiología , Adolescente , Adulto , Anorexia Nerviosa/terapia , Índice de Masa Corporal , Femenino , Ghrelina , Humanos , Persona de Mediana Edad , Psicoterapia , Valores de ReferenciaRESUMEN
The aim of this study was to investigate the relationship between postprandial release of cholecystokinin (CCK) and pancreatic polypeptide (PP) in healthy subjects and patients with chronic pancreatitis (CP). 14 patients with CP and 14 age-matched healthy subjects were studied. Diagnosis of CP was confirmed by standardized imaging modalities (ERCP and CT). Exocrine pancreatic function was assessed in all 28 subjects using the pancreolauryl serum test (PLT). An oral test meal was administered to stimulate endogenous hormone release. Plasma samples were taken before and at several time points after the test meal. CCK and PP plasma levels were measured by specific radioimmunoassays. Basal CCK and PP plasma levels were not different between patients with CP and controls, and were not correlated in either group. However, a direct linear correlation between integrated postprandial release of CCK and PP was found in healthy subjects (r = 0.74, P < 0.005). This postprandial coupling was not evident in patients with CP (r = 0.16; n.s.). Peak fluorescein serum concentration in patients with CP and steatorrhea (SCP) (n = 6) was < 2.5 micrograms/ml, and CCK and PP responses to the meal were significantly impaired (CCK response = 61 +/- 14 pmol/l/120 min in SCP vs. 110 +/- 14 in controls, P < 0.05; PP response = 3920 +/- 1773 pg/ml/120 min in SCP vs. 13418 +/- 3299 in controls, P < 0.05). In patients with mild/moderate exocrine insufficiency, CCK and PP responses varied greatly and were not different from controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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Colecistoquinina/sangre , Ingestión de Alimentos , Polipéptido Pancreático/sangre , Pancreatitis/sangre , Adulto , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , RadioinmunoensayoRESUMEN
Intraduodenal (i.d.) application of bile or Na-taurodeoxycholate (TDC) dose dependently enhances basal exocrine pancreatic secretion. The hydrokinetic effect is mediated at least in part by secretin. This study should show, whether vasoactive intestinal polypeptide (VIP), a partial agonist of secretin, may also be involved in the mediation of the hydrokinetic effect. Furthermore, plasma concentrations of somatostatin-like immunoreactivity (SLI) were measured in order to check whether this counterregulating hormone is also released by bile and TDC. Twenty investigations were carried out on 10 fasting healthy volunteers provided with a double-lumen Dreiling tube. Bile and TDC were intraduodenally applied in doses of 2-6 g and 200-600 mg, respectively, at 65-min intervals. Plasma samples were withdrawn at defined intervals for radioimmunological determination of VIP and SLI. Duodenal juice was collected in 10-min fractions and analyzed for volume, pH, bicarbonate, lipase, trypsin, and amylase. I.d. application of bile or TDC dose dependently stimulated hydrokinetic and ecbolic pancreatic secretion. Bile exerted a slightly stronger effect than TDC. Pancreatic response was simultaneously accompanied by a significant increase of plasma VIP and SLI concentrations. The effect of bile on integrated plasma VIP and SLI concentrations seems to be dose dependent; the effect of TDC on integrated SLI, too. For the increase of integrated plasma VIP concentrations after TDC no dose-response relation could be established. We conclude that VIP may be a further mediator of bile-induced volume and bicarbonate secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Bilis/fisiología , Duodeno/efectos de los fármacos , Páncreas/metabolismo , Somatostatina/sangre , Ácido Taurodesoxicólico/farmacología , Péptido Intestinal Vasoactivo/sangre , Amilasas/metabolismo , Bicarbonatos/metabolismo , Humanos , Cinética , Lipasa/metabolismo , Páncreas/efectos de los fármacos , Tripsina/metabolismoRESUMEN
In six conscious dogs with chronic gastric and pancreatic fistulas we compared the action of different doses (20.25 to 81.0 nmol/kg/h) of the muscarinic M1-receptor antagonist telenzepine, the cholecystokinin (CCK) antagonist loxiglumide (2.5 to 10.0 mg/kg/h) and several combinations of both drugs on the pancreatic secretory response to intraduodenal perfusion of graded loads of tryptophan (0.37-10.0 mmol/h) given against a background of secretin (20.5 pmol/kg/h i.v.). Except for 20.25 nmol/kg/h telenzepine, all tested doses of telenzepine and/or loxiglumide decreased the 180-min integrated bicarbonate response to tryptophan by 55 to 119%. Except of 20.25 nmol/kg/h telenzepine and/or 2.5 mg/kg/h loxiglumide, all tested doses of telezepine and/or loxiglumide inhibited the tryptophan stimulated integrated pancreatic protein responses by 54 to 88%. While telenzepine mainly inhibited the bicarbonate and protein response to the lower loads of tryptophan (0.37-1.1 mmol/h), loxiglumide decreased the response to all loads of tryptophan. The inhibition evoked by the combinations of telenzepine and loxiglumide was not significantly greater than that by single infusion of either drug. The CCK plasma levels basally and in response to tryptophan were not significantly altered by telenzepine and/or loxiglumide. These findings indicate that (1) both enteropancreatic cholinergic reflexes and the hormone CCK are mediators of the protein response to intraduodenal trytophan (2) enteropancreatic cholinergic reflexes are probably the dominant mediators of the response to low amounts of tryptophan, whereas CCK is the major mediator of the response to high loads of tryptophan, (3) the two mediators seem to act independently of each other, and (4) the release of CCK by intestinal trytophan is not influenced by telenzepine or loxiglumide.
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Antagonistas Muscarínicos/farmacología , Páncreas/metabolismo , Pirenzepina/análogos & derivados , Proglumida/análogos & derivados , Receptores de Colecistoquinina/antagonistas & inhibidores , Triptófano/farmacología , Animales , Bicarbonatos/metabolismo , Perros , Duodeno/efectos de los fármacos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Páncreas/efectos de los fármacos , Pirenzepina/farmacología , Proglumida/farmacología , Proteínas/metabolismo , Receptores de Colecistoquinina/fisiología , Receptores Muscarínicos/fisiología , Secretina/farmacología , Triptófano/administración & dosificaciónRESUMEN
BACKGROUND: Neuropathy of the enteric nervous system and hyperglycaemia are regarded as the main causes of diabetic gastroparesis. PATIENTS AND METHODS: In ten patients with Type-1 diabetes mellitus and sensomotoric neuropathy gastric emptying half times were compared with ten healthy controls by employing the 13C-octanoic acid and the 13C-sodiumacetate breath test, resp., following the intake of equally composed and isocaloric liquid and solid meals. Plasma glucose concentrations were controlled by permanent intravenous administration of insulin. RESULTS: In diabetes mellitus gastric emptying half times after the intake of the liquid meal (p < 0.05) but not after ingestion of the solid meal were slightly prolonged. Gastric emptying half times in patients and controls were not different when liquid and solid meals were compared. CONCLUSIONS: Acute hyperglycaemia appears to be more important than the neuropathy of the enteric nervous system in the pathophysiology of diabetic gastroparesis. The rate of gastric emptying is obviously not dependent on the phase of a meal, but rather on the composition and the caloric content.
Asunto(s)
Glucemia/análisis , Diabetes Mellitus Tipo 1/fisiopatología , Vaciamiento Gástrico , Adulto , Estudios de Casos y Controles , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/complicaciones , Neuropatías Diabéticas/etiología , Neuropatías Diabéticas/fisiopatología , Sistema Nervioso Entérico/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
BACKGROUND: After pylorus-preserving Whipple (PPW), delayed gastric emptying (DGE) is reported in up to 50% of these patients. We analyzed gastric emptying and hormonal adaptation of cholecystokinin (CCK), pancreatic polypeptide (PP), and gastrin following two surgical procedures for chronic pancreatitis (CP): the PPW and the duodenum-preserving pancreatic head resection (DPPHR). METHODS: Ten patients underwent DPPHR and 10 underwent PPW for CP. Preoperatively and 10 days and 6 months postoperatively, gastric emptying (paracetamol absorption test) and CCK, gastrin, and PP were measured using a test meal stimulation. RESULTS: The area under the serum paracetamol time curve for 0 to 120 minutes (AUC) showed no preoperative difference. Ten days postoperatively, the AUC was significantly reduced (P <0.05) after PPW but not after DPPHR. Six months postoperatively, AUC was comparable with the preoperative findings in DPPHR and PPW. The integrated 180-minute PP release was significantly reduced 10 days and 6 months postoperatively in both groups. The integrated 180-minute CCK release was decreased 10 days after PPW, but failed to be significant (P = 0.053). Gastrin levels were postoperatively unchanged. CONCLUSION: Following DPPHR we found no delay in gastric emptying. In contrast, DGE occurs early after PPW. Our data may help explain the slower recovery in PPW patients with regard to weight gain and relief from pain, which may be due to the functional alteration of gastric emptying and motility after this type of surgery.
Asunto(s)
Vaciamiento Gástrico , Pancreaticoduodenectomía/métodos , Pancreatitis/fisiopatología , Pancreatitis/cirugía , Complicaciones Posoperatorias/fisiopatología , Acetaminofén/sangre , Adulto , Colecistoquinina/sangre , Enfermedad Crónica , Femenino , Gastrinas/sangre , Humanos , Masculino , Persona de Mediana Edad , Polipéptido Pancreático/sangre , Pancreatitis/sangre , Complicaciones Posoperatorias/sangreRESUMEN
OBJECTIVE: To examine the effects of chronic treatment and a single high-dose application of anthranoids and sodium picosulphate on the neuropeptide content of the rat colon. DESIGN AND METHODS: Over a 6-month period, eight groups of rats were each given one of the following: sennosides or sodium picosulphate in low daily doses (10 and 2.5 mg/kg/day, respectively), in high daily doses (40 and 10 mg/kg/day, respectively), and in high twice-weekly doses (30 and 7.5 mg/kg/day, respectively); high daily doses of danthron (500 mg/kg/day); and vehicle (tragacanth 0.5%) only. Four further groups of rats each received a single dose of vehicle or a high dose of one of the three laxatives. All rats were killed 48 h after the last dose. The ascending and descending colon were removed and separated into mucosa, submucosa, and muscularis externa. Vasoactive intestinal polypeptide (VIP), somatostatin, and substance P were extracted by boiling and homogenizing the tissue in acetic acid, and their levels were determined using validated radioimmunoassays. RESULTS: After long-term treatment with high doses of sennosides and danthron, but not after a single high-dose administration, there was a significant reduction in mucosal levels of VIP and somatostatin and in submucosal levels of somatostatin of both colonic segments, as well as in the level of VIP in the muscularis externa of the descending colon. Substance P levels remained unaffected. Sodium picosulphate had no effect. CONCLUSIONS: Chronic treatment with anthranoids in high doses, but not with sodium picosulphate, reduces VIP and somatostatin levels in the rat colon. This may represent damage to the enteric nervous tissue or a pharmacological effect of the anthranoids, causing decreased synthesis or increased breakdown of these peptides.
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Antraquinonas/farmacología , Catárticos/farmacología , Colon/metabolismo , Neuropéptidos/metabolismo , Picolinas/farmacología , Extracto de Senna/farmacología , Animales , Citratos , Femenino , Compuestos Organometálicos , Radioinmunoensayo , Ratas , Ratas Wistar , Somatostatina/metabolismo , Sustancia P/metabolismo , Péptido Intestinal Vasoactivo/metabolismoRESUMEN
OBJECTIVE: Previous studies in patients with chronic constipation found abnormalities in the nervous tissue of the large intestine, predominantly in the muscularis externa. Since there is evidence that the nervous system of mucosa and submucosa is also involved in the control of colonic motility we investigated the contents of vasoactive intestinal polypeptide (VIP), somatostatin and substance P in rectal biopsies of patients with slow colonic transit constipation. DESIGN AND METHODS: Twenty-two patients (17 females, 5 males) with chronic slow transit constipation (oro-anal transit with radio-opaque markers on high fibre diet > 70 h) and long-term use of laxatives, and 20 controls (12 females, 8 males) with no history of constipation, were included in this study. Large rectal biopsy specimens including the submucosa were obtained from 5 cm above the dentate line and frozen in liquid nitrogen. After microdissection of the biopsies into mucosa and submucosa the neuropeptides were extracted by boiling and homogenizing the tissue in acetic acid and determined using validated radioimmunoassays. RESULTS: Patients with slow transit constipation showed, compared to healthy controls, significantly lower levels of the excitatory neurotransmitter substance P in the mucosa and submucosa of rectal biopsies. There was no difference between the two groups concerning the levels of the inhibitory neurotransmitters, VIP and somatostatin. CONCLUSION: Slow transit constipation is associated with abnormalities of the substance P content of the enteric nervous system of mucosa and submucosa. This seems not to be related to chronic laxative use, since anthranoids cause a reduction in the levels of inhibitory neurotransmitters (VIP, somatostatin), but not of substance P, in the rat colon.
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Estreñimiento/patología , Sistema Nervioso Entérico/metabolismo , Recto/patología , Sustancia P/análisis , Biopsia , Estudios de Casos y Controles , Estreñimiento/metabolismo , Estreñimiento/fisiopatología , Sistema Nervioso Entérico/fisiopatología , Femenino , Tránsito Gastrointestinal/fisiología , Humanos , Mucosa Intestinal/química , Mucosa Intestinal/patología , Masculino , Persona de Mediana Edad , Radioinmunoensayo , Recto/química , Somatostatina/análisis , Péptido Intestinal Vasoactivo/análisisRESUMEN
Intraduodenally applied bile salts and essential amino acids are known to stimulate exocrine pancreatic secretion. There are contradictory reports, however, about an interaction of both stimuli with respect to pancreatic function. The intention of the study was to compare the effects of equimolar amounts of taurodeoxycholate and L-phenylalanine used singularly and combined on pancreatic secretion and on gastroenteropancreatic peptide release. In 12 healthy subjects, 0.8 mmol of Na-taurodeoxycholate (410 mg) and L-phenylalanine (130 mg) were separately and combined applied into the duodenum in a randomized order. Volume, bicarbonate, trypsin, lipase, and amylase secretion as well as cholecystokinin, pancreatic polypeptide, and somatostatin plasma levels were measured. Volume and bicarbonate secretion was significantly enhanced by taurodeoxycholate. The effect was stronger compared to L-phenylalanine. The increase of enzyme secretion was comparable. After combined application, the ecbolic effect was insignificantly smaller, whereas the hydrokinetic effect was between those of the single stimuli. Plasma levels of cholecystokinin, pancreatic polypeptide, and somatostatin rose concomitantly with the pancreatic response. On an equimolar basis taurodeoxycholate results in a stronger hydrokinetic effect than L-phenylalanine. Their ecbolic effects, however, are comparable. In addition to cholinergic mechanisms, as indicated by the PP release observed, cholecystokinin may also act as a mediator. In combined application, the stimuli interfere with each other. Somatostatin and pancreatic polypeptide are not responsible for this mutual inhibition.
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Duodeno/fisiología , Hormonas Gastrointestinales/metabolismo , Páncreas/metabolismo , Fenilalanina/farmacología , Ácido Taurodesoxicólico/farmacología , Amilasas/metabolismo , Bicarbonatos/metabolismo , Colecistoquinina/metabolismo , Nutrición Enteral , Hormonas Gastrointestinales/sangre , Humanos , Lipasa/metabolismo , Páncreas/efectos de los fármacos , Páncreas/enzimología , Polipéptido Pancreático/sangre , Polipéptido Pancreático/metabolismo , Fenilalanina/administración & dosificación , Valores de Referencia , Somatostatina/sangre , Somatostatina/metabolismo , Ácido Taurodesoxicólico/administración & dosificación , Tripsina/metabolismoRESUMEN
The aim of the study was to investigate whether cholecystokinin, neurotensin, and cholinergic mechanisms act as mediators of bile salt-stimulated exocrine pancreatic secretion. Ten fasting healthy subjects provided with a double-lumen tube received 2, 4, and 6 g cattle bile and 200, 400, and 600 mg Na-taurodeoxycholate (TDC) into the duodenum at 65-min intervals, respectively. The application of TDC was repeated in another 10 subjects after intravenous bolus injection of 2.5 micrograms/kg b.w. atropine followed by continuous infusion of 5 micrograms/kg.h. Secretions of volume, bicarbonate, trypsin, and lipase were determined in 10-min fractions of duodenal juice. Plasma samples were analysed for cholecystokinin-like immunoreactivity (CCK-LI) and neurotensin with radioimmunoassays. Volume, bicarbonate, trypsin, and lipase secretion rates were significantly increased by 4 g and 6 g bile and by all doses of TDC. Incremental volume and bicarbonate output was dose-dependently enhanced by bile and TDC, and trypsin and lipase output by bile. Atropine significantly decreased the baseline values and all responses to TDC. Plasma concentrations and integrated CCK-LI and neurotensin significantly increased after 4 and 6 g bile and after 400 and 600 mg TDC. Atropine did not significantly influence peptide release. It is concluded that both hydrokinetic and ecbolic pancreatic secretion stimulated by intraduodenal bile and TDC are dependent on a cholinergic tone. CCK and probably also neurotensin act as further mediators of the ecbolic effect.
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Bilis/fisiología , Colecistoquinina/sangre , Duodeno/fisiología , Lipasa/metabolismo , Páncreas/metabolismo , Ácido Taurodesoxicólico/farmacología , Tripsina/metabolismo , Animales , Atropina/administración & dosificación , Atropina/farmacología , Bicarbonatos/metabolismo , Bovinos , Ayuno , Humanos , Infusiones Intravenosas , Inyecciones Intravenosas , Neurotensina/sangre , Páncreas/efectos de los fármacos , Páncreas/enzimología , Valores de Referencia , Análisis de Regresión , Ácido Taurodesoxicólico/administración & dosificación , Factores de TiempoRESUMEN
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder, characterized by progressive loss of motor neurons. However, ALS has been recognized to involve several non-motor systems, subclinically. Cardiac and sudomotor autonomic involvement in ALS has been described. Recently, delayed gastric emptying was reported. The aim of this study was to assess colonic transit time in patients with ALS. Therefore, measurement of total and segmental colonic transit times using radio-opaque markers was performed in 14 patients with ALS and 14 healthy age-matched volunteers. Multiple-ingestion, single-radiograph technique was used. Segmental and colonic transit times were calculated from the number of retained markers. Nine of 14 patients with ALS showed markedly delayed colonic transit times if compared to healthy controls. Colonic transit in ALS patients was significantly delayed in the right and left colon; the rectosigmoid transit did not show major delay. The colonic transit times did not correlate with bulbar involvement, Norris score, walking disability or duration of the disease. In summary, colonic dysfunction in ALS may be a result of inactivity or inadequate fiber intake. However, it also may represent a gastrointestinal autonomic involvement due to nerval degeneration. Considering ALS as a multisystem disorder including the autonomic nervous system may have implications for research into pathogenesis and therapy of neurodegenerative disease.
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Esclerosis Amiotrófica Lateral/fisiopatología , Bario , Motilidad Gastrointestinal , Dolor Abdominal/etiología , Adulto , Anciano , Esclerosis Amiotrófica Lateral/complicaciones , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , RadiografíaRESUMEN
Twenty-two different humoral parameters including stress-, gastrointestinal- and volume-regulating hormones were measured before and within 45 min after parabolic flight maneuvers of twenty healthy adult subjects. We compared hormonal data of motion sickness-affected participants with those unaffected. Changes in cortisol and vasoactive intestinal peptide plasma levels were significantly different (p less than 0.002 and p less than 0.004) between the two groups with increasing plasma levels of both hormones during motion sickness but decreasing levels within the control group. Growth hormone and prolactin plasma levels increased by 400% and 115% within the motion sickness-affected group and to a smaller degree (120% and 40% increases, respectively) within the control group, while ACTH levels were almost unchanged within both groups. Pancreatic polypeptide and gastrin plasma levels as well as plasma levels of insulin and C-peptide were significantly decreased within both groups after the parabolic flight. Plasma renin, aldosterone, atrial natriuretic peptide and cyclic GMP levels were unchanged within the control group. Within the motion sickness-affected group, plasma renin and aldosterone levels were decreased and atrial natriuretic peptide levels increased after the flight. Humoral parameters of the thyroid gland were neither changed within the groups nor different between the groups. The present data confirm previous results that increases in plasma levels of certain stress hormones participate in motion sickness. Furthermore, increases in vasoactive intestinal peptide levels participate in motion sickness. These increases could explain some of the gastrointestinal symptoms in motion sickness and might serve as markers for a discrimination between regular stress and motion sickness.
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Hormonas/sangre , Mareo por Movimiento/etiología , Vuelo Espacial , Estrés Fisiológico/sangre , Femenino , Gravitación , Hormonas/fisiología , Humanos , Masculino , Mareo por Movimiento/sangre , Mareo por Movimiento/fisiopatología , Náusea/sangre , Náusea/etiología , Náusea/fisiopatologíaRESUMEN
The aim of our study was to identify diurnal variation of perception of rectal distension and the release of gastroenteropancreatic hormones. In 12 healthy male volunteers (25 years, range 22-32), a rectal balloon distension was performed. Rectal perception thresholds (minimal, urge and pain) and rectal compliance were double-measured with a computer-controlled barostat at seven standardized time points during the day (from 16.00 to 14.00 hours the following day). Blood samples were taken 30 min before and after each rectal distension procedure to determine plasma levels of cholecystokinin (CCK), pancreatic polypeptide (PP) and motilin. Sensory thresholds for urge and pain varied significantly with the time of day, with higher threshold levels in the evening than in the morning hours. Bowel wall compliance showed as well-significant variance at pain threshold and was higher during daytime than in the evening or at night. In contrast to motilin, release of CCK and PP also showed a significant variation depending on daytime. Perception of rectal distension stimuli as well as compliance was independent of intake of food and peptide hormone levels, but CCK and PP levels increased with food, and PP levels decreased with rectal distension. Significant differences in the perception of rectal distension stimuli for urge and pain depending on daytime were found, but the release of gastrointestinal peptides seemed not to be involved. This circadian variation needs to be taken into account in patients and volunteer studies.
Asunto(s)
Ritmo Circadiano/fisiología , Hormonas Gastrointestinales/sangre , Recto/fisiología , Umbral Sensorial/fisiología , Adulto , Colecistoquinina/sangre , Adaptabilidad/fisiología , Humanos , Masculino , Manometría , Motilina/sangre , Polipéptido Pancreático/sangreRESUMEN
Fasting and postprandial levels of human peptide YY (PYY) were recently found to be lower in obesity. To investigate whether PYY levels are correspondingly high in patients with anorexia nervosa, PYY concentrations were analyzed under basal conditions and in response to a liquid meal. We investigated PYY plasma levels in 16 female anorectic (BMI 15.2+/-0.3 kg/m2) and seven lean subjects (BMI 21.3+/-0.6 kg/m2) before and after ingestion of a liquid meal (250 kcal; 15% protein, 55% carbohydrates, and 30% fat). PYY levels were analyzed using PYY ELISA (DSL, USA). Values are given as mean+/-SEM. Basal PYY levels in anorectic patients (89.0+/-14.4 pg/mL) were not significantly different from lean subjects (64.1+/-12.1 pg/mL). Postprandial PYY levels in healthy volunteers increased significantly after 20 and 60 min (80.4+/-12.7 and 96.0+/-19.9 pg/mL, respectively). In anorectic women PYY was increased at 20 min (137.9+/-19.5 pg/mL) and at 60 min (151.3+/-19.2 pg/mL). No difference was found between both groups. We conclude that basal and postprandial PYY levels in normal weight women are not different from anorectic patients. We could not confirm the recently published blunted postprandial PYY response in anorexia, a finding that merits further study.
Asunto(s)
Anorexia Nerviosa/sangre , Péptido YY/sangre , Delgadez/sangre , Adulto , Anorexia Nerviosa/metabolismo , Índice de Masa Corporal , Ingestión de Alimentos/fisiología , Ayuno/sangre , Femenino , Humanos , Péptido YY/metabolismo , Periodo Posprandial , Delgadez/metabolismoRESUMEN
Under basal conditions, bile and bile salts applied intraduodenally influence plasma levels of several gastroenteropancreatic peptides. Besides those with stimulatory effects on exocrine pancreatic secretion, others with inhibitory or no effects are released as well. Furthermore, cholinergic and peptidergic neural mechanisms may also be activated. Secretin seems to be the most important mediator of bile- or bile salt-induced water and bicarbonate secretion. In addition, VIP released from peptidergic nerve endings in the pancreas may also be involved in the mediation of the hydrokinetic effect. With regard to water and bicarbonate secretion, cholinergic mechanisms probably are of minor importance. Cholinergic mechanisms, however, seem to be the most important mediator of bile- or bile salt-induced pancreatic enzyme secretion. CCK may act as an additional mediator of the ecbolic effect. This statement, however, is based on few results only and has to be confirmed by further studies. Gastroenteropancreatic peptides with an inhibitory action on the exocrine pancreas were also released by intraduodenal bile or bile salts. Somatostatin is released in physiologically relevant amounts to bring about a counter-regulation. Plasma PP levels are also enhanced by bile and bile salts. The amounts of PP released, however, are below those observed postprandially. In contrast to their stimulatory action on basal pancreatic secretion, bile and bile salts have no or even an inhibitory effect on pancreatic secretion stimulated by intraluminal nutrients. Accordingly, the release of gastroenteropancreatic peptides is not influenced (for example, secretin) or even reduced (for example, CCK) when bile or bile salts are added to intraluminal nutrients.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Ácidos y Sales Biliares , Bilis , Hormonas Gastrointestinales/fisiología , Páncreas/fisiología , Animales , Humanos , Neurotensina/fisiología , Polipéptido Pancreático/fisiología , Somatostatina/fisiologíaRESUMEN
About 50% of patients with progressive systemic sclerosis develop significant clinical involvement of the alimentary tract. In decreasing order of frequency esophagus (75%), anorectum (50-70%), small bowel (50%), colon (40%) and stomach (40%) can exhibit characteristic morphological or functional features. Typical symptoms of reluxesophagitis and severe constipation are often reported. Beside this, diarrhea, steatorrhea and malnutrition are common complaints. Manometric and electrophysiological studies brought evidence of a neuropathy of the enteric nervous system in the early stages of the disease, resulting in disturbances of the digestive and interdigestive peristalsis and therefore e.g. leading to gastroparesis, bacterial overgrowth of the small intestine or constipation. In late PSS collagen deposition and atrophy of the smooth muscle layer of the bowel wall cause loss of function of sphincters as the lower esophageal sphincter or the anal sphincter and marked atony of parts of the intestine. The diagnostic procedures consist of esophageal manometry, 24-h pH-metry, esophageal and gastric radionuclide transit studies, H2-breath tests, barium enemas, anorectal manometry and endoscopy. Therapeutic options include H2-antagonists, proton-pump inhibitors, prokinetic drugs, octreotides and antibiotics. Nutritional supplementation and surgical interventions are often of limited therapeutic value. Finally in some cases long-term total parenteral nutrition is warranted.
Asunto(s)
Enfermedades Gastrointestinales/diagnóstico , Esclerodermia Sistémica/diagnóstico , Sistema Digestivo/fisiopatología , Sistema Nervioso Entérico/fisiopatología , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/fisiopatología , Reflujo Gastroesofágico/terapia , Enfermedades Gastrointestinales/fisiopatología , Enfermedades Gastrointestinales/terapia , Tránsito Gastrointestinal/fisiología , Humanos , Seudoobstrucción Intestinal/diagnóstico , Seudoobstrucción Intestinal/fisiopatología , Seudoobstrucción Intestinal/terapia , Manometría , Valores de Referencia , Esclerodermia Sistémica/fisiopatología , Esclerodermia Sistémica/terapiaRESUMEN
A previously healthy 17-year-old Greek boy suddenly developed jaundice of sclerae and skin. In addition, physical examination revealed a pale appearance. He also reported feeling tired and weak. The haemoglobin level was 9.6 g/dl, lactate dehydrogenase activity 335 U/l, bilirubin concentration 3.2 mg/dl (direct bilirubin 0.7 mg/dl, indirect bilirubin 2.5 mg/dl), haptoglobin concentration 48.8 mg/dl. As haemolytic anaemia was assumed, direct questioning elicited the fact that the patient had, for the first time in his life, eaten 300 g of broad beans (Vicia faba) on each of two days, namely 3 and 2 days before the appearance of jaundice. Absence of glucose-6-phosphate dehydrogenase activity in the red blood corpuscles confirmed the diagnosis of favism. On symptomatic treatment both the enzyme activities and the bilirubin level fell to normal within one week, and the haemoglobin level was 15.7 g/dl after 4 weeks.
Asunto(s)
Favismo/sangre , Enfermedad Aguda , Adolescente , Diagnóstico Diferencial , Favismo/complicaciones , Deficiencia de Glucosafosfato Deshidrogenasa/sangre , Hepatitis Viral Humana/diagnóstico , Humanos , Ictericia/etiología , MasculinoRESUMEN
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder, characterized by progressive loss of motor neurons. However, ALS has been recognized to involve several non-motor systems. Subclinical involvement of the autonomic system (i.e. of cardial or sudomotor regulation) has been described in ALS. Gastrointestinal motor dysfunction can occur in amyotrophic lateral sclerosis, even if patients do not complain of gastrointestinal symptoms. New techniques in non-invasive evaluation of gastrointestinal function showed delayed gastric emptying and delayed colonic transit times in patients with ALS.