Intravenous Infusion Of Somatostatin Research Articles

The Case Number 112 of Congenital Chylous Ascites and Its Successful Treatment

Background:Congenital chylous ascites is a very rare condition that has been well recognized as early as the 1950s, and was mostly called “Congenital chyloperitoneum” during that time. Few cases have been reported during the 1960s, and in 1967, Craven et al attributed the development of congenital chylous ascites to obstruction of the cisterna chyli and chylous reflux into the peritoneal space and small intestine and they demonstrated lymphangiographically. Patients and methods: The use of a unique dietary therapy for the treatment of congenital chylous ascites is briefly described and the relevant literature is described. Results:An infant with congenital chylous ascites was seen at about the age of two and half months. He was initially treated with intravenous somatostatin infusion, and thereafter by repeated paracentesis, and continued to receive breast and bottle milk feedings. However, when he was first seen, ultrasound was still showing moderate ascites. The boy was successfully treated a combination of a unique form of very low-fat diet and octreotide acetate subcutaneous injections. Treatment was not associated with a negative effect on growth or development, and no evidence of nutritional deficiency was observed. Conclusion: The case number 112 of congenital chylous ascites is reported and its unique therapeutic approach is described.

Evaluation of postoperative ascites after somatostatin infusion following hepatectomy for hepatocellular carcinoma by laparotomy: a multicenter randomized double-blind controlled trial (SOMAPROTECT)

BackgroundThe majority of patients undergoing hepatectomy for hepatocellular carcinoma (HCC) suffer from underlying liver disease and are exposed to the risk of postoperative ascites, which is favored by an imbalance between portal venous inflow and a diminished hepatic volume. Finding a reversible, non-invasive method for modulating the portal inflow would be of interest as it could be used temporarily during the early postoperative course. Somatostatin, a well-known drug already used in several indications, may limit the risk of postoperative ascites and liver failure by decreasing portal pressure after hepatectomy for HCC in patients with underlying liver disease. We aimed to evaluate the impact of somatostatin postoperative infusion on the incidence of ascites following hepatectomy by laparotomy for HCC in patients with underlying liver disease.Methods/designThe SOMAPROTECT study is a multicenter randomized double-blind placebo controlled phase III trial comparing two arms of patients with underlying liver disease undergoing hepatectomy for HCC by open approach. All patients will have primary abdominal drainage before closure. Patients in the experimental arm will receive a postoperative intravenous infusion of somatostatin during 6 days. Patients in the control group will receive a placebo infusion for the same duration. The primary endpoint will be the presence or absence of postoperative ascites occurring during the 90-day postoperative course, defined as ≥500 ml/24 h of fluid in the drains during at least 3 days or any ascites requiring an invasive procedure comprising percutaneous puncture or drainage. Secondary endpoints will be duration and total volume of ascites, postoperative 90-day mortality and morbidity, liver failure, acute renal failure, length of stay in intensive care unit and hospital stay. The total number of patients to be enrolled was calculated to be 152.DiscussionPostoperative ascites remains a major issue after hepatectomy for HCC as it is associated with increased morbidity, liver and renal failure, the need for specific treatments and prolonged hospital stay. This study represents the first randomized controlled trial to assess the benefits of somatostatin on the risk of postoperative ascites after surgery for HCC.Trial registrationNCT02799212 (ClinicalTrials.gov identifier). Registered prior to conducting the research on 9 June 2016.

Effect of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on C-peptide kinetics.

Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves indices of β-cell function estimated based on circulating C-peptide and glucose concentrations (e.g., Homeostasis Model Assessment [HOMA2-%B], meal tolerance test-based indices). However, use of these β-cell function indices assumes C-peptide kinetics are not altered by canagliflozin. This 2-period crossover study assessed the effect of a single canagliflozin 300-mg dose on C-peptide kinetics in 10 healthy participants. Two hours after receiving canagliflozin or placebo, participants received intravenous somatostatin infusion to suppress endogenous C-peptide secretion and 1 hour later received a bolus injection of synthetic human C-peptide 150 µg. Serum C-peptide was measured over 3 hours and urinary glucose and C-peptide excretion were measured. C-peptide kinetic parameters, including total clearance (CLtotal ) and renal clearance (CLrenal ), were calculated. Serum C-peptide profiles were similar following canagliflozin or placebo treatment. C-peptide CLtotal was slightly lower with canagliflozin versus placebo (mean (SD) of 190 (37) vs. 197 (30) mL/min; canagliflozin/placebo ratio [90% CI] = 96.1% [93.0%; 99.3%]). Other kinetic parameters, including CLrenal , were generally similar between treatments. Results indicate canagliflozin 300 mg does not meaningfully alter C-peptide clearance or other kinetic parameters; therefore, C-peptide-based measurements of insulin secretion are appropriate for assessing β-cell function in canagliflozin-treated participants.

Randomized, Placebo-Controlled, Double-Blind Study of the Efficacy of Lanreotide 30 mg PR in the Treatment of Pancreatic and Enterocutaneous Fistulae

Continuous intravenous infusion of somatostatin improves the natural course of digestive fistulae. Lanreotide 30 mg PR is a synthetic analogue of somatostatin with pharmacological activity extending to at least 10 days after intramuscular administration. Its effectiveness was assessed in patients with simple externalized digestive fistulae in a randomized, doubleblind, placebo-controlled study. Patients demonstrating a reduction of at least 50% of fistula output within 72 hours after a first double-blind intramuscular injection of lanreotide or placebo were considered to be responders (primary end point) and continued the double-blind treatment to a maximum of 6 injections at 10-day intervals. Other endpoints included fistula closure rate and time to closure. Blind was lifted for nonresponders, and those initially on placebo were then treated with open-label lanreotide. Following the first double-blind injection, 35 of 54 patients (64.8%) on lanreotide were responders versus 20 of 53 (37.7%) on placebo, ie, a 3.1 times higher response likelihood on lanreotide compared with placebo (P = 0.006). Group mean reduction of fistula output at 72 hours was 45.1% and 8.9%, respectively (P = 0.005). Lanreotide compared with placebo had no effect on closure rate which averaged 77% but median time to fistula closure was shorter on lanreotide, based on Kaplan-Meier analysis, although no statistical significance was achieved. Compared with placebo, intramuscular lanreotide 30 mg PR significantly decreases digestive fistulae output at Day 3 and shortens time to fistula closure by 9 days. ClinicalTrials.gov registration number: NCT00729313.

Adult presentation of a congenital duodenal diaphragm

1. Neoptolemos JP, London NJM, Carr-Locke DL. Assessment of the main pancreatic duct integrity by endoscopic retrograde pancreatography in patients with acute pancreatitis. Br J Surg 1993;80:94-9. 2. Kozarek RA, Ball TJ, Patterson DJ, et al. Endoscopic transpapillary therapy for disrupted pancreatic duct and peripancreatic fluid collections. Gastroenterology 1991;100:1362-70. 3. Thomas H, Madanur M, Bartlett A, et al. Pancreatic traumad12-year experience from a tertiary center. Pancreas 2009;38:113-6. 4. Varadarajulu S, Noone TC, Tutuian R, et al. Predictors of outcome in pancreatic duct disruption managed by endoscopic transpapillary stent placement. Gastrointest Endosc 2005;61:568-75. 5. Huckfeldt R, Agee C, Nichols WK, et al. Nonoperative treatment of traumatic pancreatic duct disruption using an endoscopically placed stent. J Trauma 1996;41:143-4. 6. Pederzoli P, Bassi C, Falconi M, et al. Conservative treatment of external pancreatic fistulas with parenteral nutrition alone or in combination with continuous intravenous infusion of somatostatin, glucagon or calcitonin. Surg Gynecol Obstet 1986;163:428-32.

Assessment of splanchnic blood flow using magnetic resonance imaging

The splanchnic circulation has an important function in the body under both physiological and pathophysiological conditions. Despite its importance, no reliable noninvasive procedures for estimating splanchnic circulation have been established. The aim of this study was to evaluate MRI as a tool for assessing intra-abdominal blood flows of the aorta, portal vein (VPO) and the major intestinal and hepatic vessels. In nine healthy volunteers, the proximal aorta (AOP) and distal abdominal aorta (AOD), superior mesenteric artery (SAM), celiac trunk (CTR), hepatic arteries (common and proper hepatic arteries, AHC and AHP, respectively), and VPO were localized on contrast-enhanced magnetic resonance angiography images. Volumetric flow was measured using a two-dimensional cine echocardiogram-gated phase contrast technique. Measurements were taken before and 30 min after continuous intravenous infusion of somatostatin (250 microg/h) and were independently evaluated by two investigators. Blood flow measured by MRI in the VPO, SAM, AOP, AHP, and CTR significantly decreased after drug infusion. Flows in the AOD and AHC showed a tendency to decrease (P>0.05). Interrater agreement on flows in MRI was very good for large vessels (VPO, AOP, and AOD), with a concordance correlation coefficient of 0.94, as well as for smaller vessels such as the CTR, AHC, AHP, and SAM (concordance correlation coefficient =0.78). Somatostatin-induced blood flow changes in the splanchnic region were reliably detected by MRI. MRI may be useful for the noninvasive assessment of blood flow changes in the splanchnic region.

Microinjection of exogenous somatostatin in the dorsal vagal complex inhibits pancreatic secretion via somatostatin receptor-2 in rats

Previous studies have suggested that somatostatin inhibits pancreatic secretion at a central vagal site, and the dorsal vagal complex (DVC) is involved in central feedback inhibition of the exocrine pancreas. The aim of this study was to investigate the effect of exogenous somatostatin in the DVC on pancreatic secretion and the somatostatin receptor subtype(s) responsible for the effect. The effects of somatostatin microinjected into the DVC on pancreatic secretion stimulated by cholecystokinin octapeptide (CCK-8) or 2-deoxy-d-glucose (2-DG) were examined in anesthetized rats. To investigate the somatostatin inhibitory action site, a somatostatin receptor antagonist [SRA; cyclo(7-aminoheptanoyl-Phe-d-Trp-Lys-Thr)] was microinjected into the DVC before intravenous infusion of somatostatin and CCK-8/2-DG. The effects of injection of a somatostatin receptor-2 agonist (seglitide) and combined injection of somatostatin and a somatostatin receptor-2 antagonist (CYN 154806) in the DVC on the pancreatic secretion were also investigated. Somatostatin injected into the DVC significantly inhibited pancreatic secretion evoked by CCK-8 or 2-DG in a dose-dependent manner. SRA injected into the DVC completely reversed the inhibitory effect of intravenous administration of somatostatin. Seglitide injected into the DVC also inhibited CCK-8/2-DG-induced pancreatic protein secretion. However, combined injection of somatostatin and CYN 154806 did not affect the CCK-8/2-DG-induced pancreatic secretion. Somatostatin in the DVC inhibits pancreatic secretion via somatostatin receptor-2, and the DVC is the action site of somatostatin for its inhibitory effect.

Sleep-dependent surges in growth hormone do not contribute to sleep-dependent memory consolidation

In the search for the mechanisms that mediate the effects of sleep on the consolidation of memories, growth hormone (GH) recently became of interest, because in humans it is released mainly during slow-wave sleep (SWS), a period of enhanced declarative memory consolidation. In addition, recent studies showed that GH is involved in proper memory function in GH deficient and elderly humans and this effect has been linked to regulatory influences of GH on hippocampal NMDA receptors. Here, we blocked GH secretion by intravenous infusion of somatostatin in healthy young subjects during the first 3 h of sleep, which contain mainly SWS. Declarative and procedural memory consolidation was tested across this period, using a word pair association task and a mirror tracing task, respectively. Although GH was effectively suppressed, memory performance as well as sleep were entirely unaffected by this suppression. Whereas GH may in the long run generally support brain systems required for maintaining proper memory function, our data exclude a necessary contribution of the nocturnal surge in pituitary GH secretion to the acute processing and formation of specific memories during sleep.

Early HVPG measurement and TIPS for acute variceal hemorrhage: Is sooner really better?

Early HVPG measurement and TIPS for acute variceal hemorrhage: Is sooner really better?

Somatostatin for intractable postoperative chylothorax in a premature infant

A premature infant of 31 weeks' gestation underwent repair of an oesophageal atresia, distal tracheo-oesophageal fistula and anal stenosis. A lymphatic leak was noted at the time of surgery. Chylous drainage persisted and an intravenous infusion of somatostatin was begun. The volume of chyle drained fell dramatically within the first 24 h and was negligible by the 5th day of treatment. No reaccumulation of the chylothorax was seen after the cessation of somatostatin. To our knowledge this is the youngest reported child in whom somatostatin has been used successfully in treating a postoperative chylothorax.

Somatostatin for Postoperative Chylothorax after Surgery for Children with Congenital Heart Disease

Chylothorax is a rare but serious postoperative condition with a high rate of morbidity that may lead to death of children with congenital heart disease. Here we reviewed nine consecutive cases with chylothorax in infants and children following cardiac surgery from March 2002 to February 2003. Somatostatin was added to conservative treatment proctocol to increase effectiveness of therapy in all cases. The duration of somatostatin therapy varied from 7 to 32 days. All cases of chylothorax were successfully treated with intravenous infusion of somatostatin as an adjunctive treatment. Even though two cases showed rebound phenomena, we avoided any surgical procedure in the nine patients who treated with conservative management combined with somatostatin. No significant side effects of somatostatin were observed. It seems that somatostatin is effective, noninvasive and safe therapeutic modality. It can be used as an adjunctive treatment to conservative management to control postoperative chylothorax in children with congenital heart disease.

Effect of somatostatin versus octreotide on portal haemodynamics in patients with cirrhosis and portal hypertension

Elevated portal inflow is part of the pathogenesis of portal hypertension in patients with cirrhosis. Vasoactive substances appear to play a primary role in the regulation of portal flow. The aim of this study was to investigate the effects of somatostatin and octreotide on portal pressure and plasma levels of insulin-like growth factor (IGF-1), nitric oxide (NO), endothelin-1 (ET-1) and glucagon (GLU). Portal pressures of 14 cirrhotic patients with portal hypertension who underwent transjugular intrahepatic portosystemic shunt (TIPS) were directly measured via a catheter placed in the portal vein. Portal pressure and IGF-1, NO, ET-1 and GLU plasma levels were determined at baseline, and at 8 h and 24 h after administration of somatostatin or octreotide via portal vein catheter in a randomized, double-blind, cross-over design. The average decrease in portal pressure after intravenous infusion of somatostatin and octreotide was 9.4 +/- 1.0 cmH2O and 5.0 +/- 1.0 cmH2O, respectively (P < 0.01). Plasma levels of GLU and IGF-1 decreased significantly 8 and 24 h after somatostatin and octreotide infusion (P < 0.05). However, there were no significant decreases in plasma NO or ET-1 levels. There was a significant difference between somatostatin and octreotide groups (P < 0.01). Both somatostatin and octreotide can significantly reduce portal pressure, although somatostatin is more potent than octreotide. The underlying mechanisms may involve inhibition of the secretion of GLU, IGF-1 and other hormones as well as a decrease in hepatic metabolism and portal inflow leading to a reduction in portal pressure.

The Endocrine and Pancreatic Unit at the University of Verona, Italy

The Endocrine and Pancreatic Unit at the University of Verona, Italy

Gabexate or somatostatin administration before ERCP in patients at high risk for post-ERCP pancreatitis: A multicenter, placebo-controlled, randomized clinical trial

Background: ERCP is frequently complicated by pancreatitis. The aims of this study were to assess the efficacy of somatostatin and gabexate for prevention of post-ERCP pancreatitis in high-risk patients and to determine predisposing factors for post-ERCP pancreatitis. A meta-analysis was conducted of all published studies on the use of somatostatin or gabexate for prevention of post-ERCP pancreatitis. Methods: A double blind, multicenter, placebo-controlled trial was conducted in patients at high risk for post-ERCP pancreatitis. Patients were randomized to receive an intravenous infusion of somatostatin (750 mg), gabexate (500 mg), or placebo that was started 30 minutes before endoscopy and continued for 2 hours afterward. Patients were evaluated clinically and serum amylase levels determined at 4 and 24 hours after endoscopy. Results: No significant difference in the occurrence of pancreatitis, hyperamylasemia, or abdominal pain was observed among placebo-, gabexate-, and somatostatin-treated patients. A sphincterotomy longer than 2 cm ( p = 0.0001), more than 3 pancreatic injections ( p = 0.0001), and unsuccessful cannulation ( p = 0.008) were predictive of post-ERCP pancreatitis. Hyperamylasemia was predicted by more than 3 pancreatic injections ( p = 0.0001) and sphincterotomy ( p = 0.02). The meta-analysis of trials of short-term infusion of gabexate or somatostatin did not show efficacy for either drug. Conclusions: Short-term administration of gabexate or somatostatin in patients at high risk for pancreatitis is ineffective for prevention of ERCP-induced pancreatitis. Pancreatic injury is related to maneuvers used to obtain biliary access rather than to any patient characteristic or endoscopist experience. (Gastrointest Endosc 2002;56:488-95.)

Inhibitory Effect of Somatostatin on Cholecystokinin Release Is Independent of Luminal Cholecystokinin-Releasing Factor Content in Conscious Rats

Exclusion of bile-pancreatic juice from the intestine increases pancreatic secretion via cholecystokinin (CCK) release in conscious rats. Luminal CCK-releasing factor (LCRF), purified from rat intestinal secretions, is an intraluminal regulator of CCK secretion during bile-pancreatic juice diversion. Because somatostatin is a potent inhibitor of CCK release and pancreatic secretion, the inhibitory effect of somatostatin on LCRF was examined. Rats were prepared with bile and pancreatic cannulae and two duodenal cannulae and with an external jugular vein cannula. The experiments were conducted without anesthesia. After 1.5-hour basal collection of pancreatic juice with bile-pancreatic juice return, bile-pancreatic juice was diverted for 2 hours, during which time somatostatin (2, 10 nmol/kg/h) was infused intravenously. The rats were killed before and 1 and 2 hours after bile-pancreatic juice diversion. To examine the effect of luminal somatostatin, 50 or 200 nmol/kg/h of somatostatin was infused into the duodenum. The plasma CCK and luminal content of LCRF were measured by specific radioimmunoassays. Bile-pancreatic juice diversion significantly increased pancreatic secretion, plasma CCK, and LCRF levels. Intravenous infusion of somatostatin inhibited CCK release and pancreatic secretion, but not LCRF content. Luminal administration of somatostatin did not show any effect. Inhibitory effect of circulating somatostatin on CCK release and pancreatic secretion is independent of LCRF content.

Validation of color Doppler EUS for azygos blood flow measurement in patients with cirrhosis: Application to the acute hemodynamic effects of somatostatin, octreotide, or placebo

Background: Color Doppler EUS (CD-EUS) allows minimally invasive measurement of azygos blood flow (AzBF) in portal hypertension, but further validation of the method is needed. Because a limited number of patients has been studied, the acute hemodynamic effects of somatostatin and octreotide on AzBF and gastric mucosal perfusion are poorly defined in portal hypertension. Methods: A double-blind hemodynamic study was designed to assess rapid changes in AzBF over a 60-minute period after intravenous administration of somatostatin, octreotide, and placebo in 30 stable patients with biopsy-proven cirrhosis. AzBF was measured by using both CD-EUS and the invasive thermal dilution technique in the first 10 patients (phase 1). Then, with CD-EUS alone, the hemodynamic study was extended to a further 20 patients (phase 2). In addition, gastric mucosal perfusion changes were assessed by using laser Doppler flowmetry at endoscopy. Results: In phase 1, the 2 methods for AzBF measurement showed significant correlations both for baseline values (r = 0.685) and for AzBF changes over 60 minutes after drug administration (r = 0.733). In phase 2, a reduction was observed in AzBF 10 minutes after octreotide or somatostatin administration (−47% and −23%, p < 0.0001 vs. placebo, p = 0.058 vs. placebo, respectively). After 60 minutes of somatostatin infusion, AzBF increased 27% over placebo values (p < 0.04). Gastric mucosal perfusion was transiently reduced 5 minutes after octreotide or somatostatin (−21% and −32%, respectively, p < 0.02 vs. placebo). Conclusions: This is the first study to validate CD-EUS AzBF measurement with reference to the invasive thermodilution technique in cirrhosis. It confirmed the transient effects of somatostatin and octreotide on both AzBF and gastric mucosal perfusion. In addition, a significant rebound phenomenon after 60 minutes of continuous intravenous somatostatin infusion was observed. (Gastrointest Endosc 2001;54:24-30.)

Endoscopic pancreatic stent insertion for treatment of pseudocyst after distal pancreatectomy

Pancreatic fistula and pseudocyst are common complications of pancreatic resection. 1 Ridgeway MG Stabile B. Surgical management and treatment of pancreatic fistulas. Surg Clin North Am. 1996; 76: 1159-1173 Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar , 2 Bassi C Falconi M Pederzoli P Pancreatic fistula. in: 3rd ed. Surgical diseases of the pancreas. : Williams & Wilkins, Baltimore1998: 827-834 Google Scholar Such complications prolong hospitalization and may lead to abscess formation, sepsis, and hemorrhage. 1 Ridgeway MG Stabile B. Surgical management and treatment of pancreatic fistulas. Surg Clin North Am. 1996; 76: 1159-1173 Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar , 2 Bassi C Falconi M Pederzoli P Pancreatic fistula. in: 3rd ed. Surgical diseases of the pancreas. : Williams & Wilkins, Baltimore1998: 827-834 Google Scholar Most fistulas and pseudocysts resolve spontaneously, albeit over lengthy periods, with conservative treatment including pancreatic rest (no oral intake with total parenteral nutrition or octreotide administration) and adequate drainage (drains placed during the initial operation or postoperatively via the percutaneous approach). 1 Ridgeway MG Stabile B. Surgical management and treatment of pancreatic fistulas. Surg Clin North Am. 1996; 76: 1159-1173 Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar , 2 Bassi C Falconi M Pederzoli P Pancreatic fistula. in: 3rd ed. Surgical diseases of the pancreas. : Williams & Wilkins, Baltimore1998: 827-834 Google Scholar , 3 Pederzoli P Bassi C Falconi M Albrigo R Vantini I Micciolo R. Conservative treatment of external pancreatic fistulas with parenteral nutrition alone or in combination with continuous intravenous infusion of somatostatin, glucagon or calcitonin. Surg Gynecol Obstet. 1986; 163: 428-432 PubMed Google Scholar , 4 Prinz RA Pickleman J Hoffman JP. Treatment of pancreatic cutaneous fistulas with a somatostatin analog. Am J Surg. 1988; 155: 36-42 Abstract Full Text PDF PubMed Scopus (139) Google Scholar For pancreatic fistulas and pseudocysts refractory to conservative treatment, surgical intervention is indicated but is often technically difficult and associated with a high morbidity rate (13%). 5 Lipsett PA Cameron JL. Internal pancreatic fistula. Am J Surg. 1992; 163: 216-220 Abstract Full Text PDF PubMed Scopus (121) Google Scholar Only a few reports have described endoscopic pancreatic stent placement for treatment of pancreatic duct leakage after pancreatic resection. 6 Saeed ZA Ramirez FC Hepps KS. Endoscopic stent placement for internal and external pancreatic fistulas. Gastroenterology. 1993; 105: 1213-1217 PubMed Google Scholar , 7 Sarzen CD. Endoscopic management of pancreatic duct leak complicated by retrogastric abscess. Am J Gastroenterol. 1995; 90: 2039-2041 PubMed Google Scholar Herein is described a case in which endoscopic transpapillary placement of a pancreatic stent was effective treatment for a pancreatic pseudocyst that developed after distal pancreatectomy.

Somatostatin plus isosorbide 5-mononitrate versus somatostatin in the control of acute gastro-oesophageal variceal bleeding: a double blind, randomised, placebo controlled clinical trial

BACKGROUNDVariceal bleeding is a severe complication of portal hypertension. Somatostatin reduces portal pressure by decreasing splanchnic blood flow, and nitrates by diminishing intrahepatic resistance. Experimental studies have shown that the...

Immunoreactive growth hormone-releasing hormone (IR-GHRH) in the feto-placental circulation and differential effects of L-dopa, L-arginine and somatostatin-14 on the plasma levels of IR-GHRH in normal adults.

The relation of the physiological releases of growth hormone-releasing hormone (GHRH) and growth hormone (GH) into the circulation in various conditions was investigated using a sensitive and specific radioimmunoassay for plasma GHRH. The mean fasting plasma level of immunoreactive (IR)-GHRH in 72 normal adults was 10.3 +/- 0.5 (mean +/- SEM) pg/ml and there was no significant sex difference in the level. The concentrations of IR-GHRH in plasma from the umbilical artery and umbilical vein were 107.3 +/- 20.5 pg/ml and 33.6 +/- 3.8 pg/ml, respectively, and a marked arterio-venous gradient was observed in all 12 individuals examined. The plasma level of IR-GHRH in the maternal vein was significantly lower than that in the cord blood, but was similar to that in non-pregnant women. In normal adults, although there was no apparent fluctuation in the level of plasma IR-GHRH or of plasma GH during bed rest, a significant increase of plasma IR-GHRH was detected followed by, or synchronized with the surge of plasma GH after oral administration of L-dopa. In contrast, on L-arginine infusion, no proportional elevation of plasma IR-GHRH with increase in plasma GH was observed. During and after intravenous infusion of somatostatin, the circulating IR-GHRH level did not increase, but on stopping the infusion there was an immediate and marked rebound surge of GH. We conclude that 1) the elevated IR-GHRH in the cord blood plasma originates from the fetus and may have a primary role in enhancing secretion of GH which promotes growth in early human life, and 2) the participations of GHRH in the mechanisms of GH secretion seen after administrations of L-dopa, L-arginine and somatostatin are different.

Inhibition of acid secretion by electrical acupuncture is mediated via beta-endorphin and somatostatin.

Electroacupuncture (EAP) was shown to inhibit basal gastric acid secretion in dogs and sham feeding-stimulated acid secretion in humans. However, its effect on a meal-stimulated acid secretion in dogs and the mechanisms involved remain unclear. In five dogs prepared with gastric cannulas, gastric acid secretion was determined by a dye-dilution technique for 60 min after intragastric administration of 200 ml of 4% mixed amino acid meal in six different experiments: study 1, no acupuncture; study 2, sham acupuncture (SAP); study 3, EAP; study 4, EAP plus naloxone; study 5, naloxone alone; and study 6, intravenous infusion of somatostatin (SS) and vasoactive intestinal peptide (VIP) at doses of 0.5 and 1.0 micrograms.kg-1.h-1, respectively. EAP was performed on three different points including Pishu, ZusanLi, and Neiguan. Biphasic electrical pulse (25-100 Hz, 12-16 mA) was applied continuously via needles for 75 min starting 15 min before meal. SAP on nonacupoints in hind- and forelegs was performed with the same electrical pulse. Plasma SS, VIP, beta-endorphin, and gastrin were determined by specific radioimmunoassays. EAP significantly inhibited acid secretion (75%; P < 0.01), which coincided with significant increases in plasma SS, VIP, and beta-endorphin and a significant decrease in plasma gastrin. Naloxone completely reversed EAP-induced inhibition of acid secretion and changes in plasma concentration of peptides. SAP also significantly suppressed acid output (30%; P < 0.05), with a modest but significant increase in plasma beta-endorphin. However, the inhibition by EAP on the acid output was significantly greater than that by SAP (P < 0.01). Furthermore, exogenous SS (0.5 microgram.kg-1.h-1) significantly inhibited acid output (78%), whereas VIP failed to inhibit gastric acid secretion. We conclude that, in dogs, EAP significantly inhibits meal-stimulated acid secretion. This acid inhibition is mediated by the release of beta-endorphin and somatostatin, and an endogenous opiate or opiates appear to play an important role in the release of SS, VIP, and beta-endorphin.