Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Octreotide acetate (Sandostatin), a long-acting somatostatin analogue, has been demonstrated to have an inhibitory effect on exocrine secretion in the neurally intact pancreas. This study was designed to evaluate the effect of this agent on exocrine secretion in the denervated canine pancreas, utilizing animals with pancreatic autografts and functioning pancreaticocystostomies. The rates of secretion of urinary (autograft) amylase (units/min) and bicarbonate (mM/min), over a five-hr interval, were determined in the basal state (group A, n = 10), after a bolus injection of 400 micrograms of Sandostatin (group B, n = 5), after a standard meal (group C, n = 5), or a meal preceded by 400 micrograms of Sandostatin (group D, n = 5). Basal secretion of amylase was decreased for 4 hr following Sandostatin, although this decrease was not significant. Conversely, basal bicarbonate secretion was not inhibited by Sandostatin. When compared with group C (22.4 +/- 3.2), a significant inhibition of meal-stimulated amylase release was demonstrated in group D (5.4 +/- 0.21, P = 0.0006) during the first hour after Sandostatin was given. This inhibition remained significant at 2 hr (group C = 38.5 +/- 5.2 versus group D = 9.4 +/- 0.8; P = 0.0006) and 3 hr (group C = 38.6 +/- 6.3 versus group D = 17.5 +/- 0.9; P = 0.0108) after Sandostatin was given. In addition, meal-stimulated bicarbonate secretion was significantly inhibited for 2 hr following Sandostatin (group C = 0.19 +/- 0.03 versus group D = 0.07 +/- 0.02, P = 0.0096; and group C = 0.23 +/- 0.03 versus group D = 0.10 +/- 0.01, P = 0.0018, respectively). These studies demonstrate that Sandostatin has a profound inhibitory effect on meal-stimulated enzyme and bicarbonate release in a denervated canine autograft model. Although the site of action of this agent remains to be defined, Sandostatin may have therapeutic potential in clinical pancreas transplantation.
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PMID:The effect of octreotide acetate on meal-stimulated exocrine secretion in canine pancreatic autografts. 171 96

Octreotide acetate is a somatostatin analogue that has been shown to ameliorate the side effects of excessive secretion of hormone from benign and malignant tumors. The ability of this drug to inhibit the growth of malignant cells and to control gastrointestinal hemorrhage will prompt additional clinical trials. Because some of these patients may have thrombocytopenia, platelet dysfunction, or a coagulopathy, we studied tests of platelet function and blood coagulation in 15 patients before and after 14 days of therapy with octreotide acetate at a dosage of 500 micrograms three times daily. We found no substantial change in the results of these tests, and no patient experienced bleeding or thrombosis. These results suggest that octreotide acetate does not adversely affect platelet function or the coagulation system in humans.
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PMID:Effect of the somatostatin analogue octreotide acetate on hemostasis in humans. 184 35

Octreotide acetate is a long-acting analogue of the naturally occurring inhibitory gastrointestinal peptide, somatostatin. We tested the efficacy of octreotide in controlling the symptoms of dumping syndrome in response to a provocative meal in a randomized, double-blinded, crossover trial in nine severely affected patients. Pretreatment with octreotide acetate (100 micrograms injected subcutaneously) reduced postprandial dumping symptoms from a mean +/- SEM score of 15.7 +/- 1.6 (placebo treatment day) to 4.6 +/- 1.7. With placebo treatment, all nine patients became symptomatic in response to the meal, whereas with octreotide treatment, symptoms occurred in only two of nine patients. Similarly, all placebo-treated patients showed a postprandial increase in pulse rate to a mean +/- SEM of 105 +/- 6 beats per minute, whereas only one of nine octreotide-treated patients showed an increase in pulse rate (mean +/- SEM, 80 +/- 3 beats per minute). These differences were also statistically significant. While no significant changes were observed in postprandial hematocrit values or osmolality between placebo and octreotide treatments, octreotide prevented hypoglycemia in four affected patients and significantly inhibited insulin release. We conclude that octreotide is a useful tool in the treatment of patients with severe, refractory dumping syndrome.
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PMID:Control of dumping symptoms by somatostatin analogue in patients after gastric surgery. 192 23

Post-resectional hyperplasia is the phenomenon in which residual small bowel increases in size and absorptive capacity after segmental enterectomy. This experiment studied the effect of somatostatin analogue therapy on the development of two structural parameters of post-resectional hyperplasia in rats subjected to 40% proximal small bowel resection. Octreotide acetate-treated rats failed to develop increased villus height (902 +/- 50 microns) relative to saline-treated rats (1,103 +/- 98 microns). Augmentation of residual intestinal weight was also significantly impaired in analogue-treated rats (92 +/- 3 versus 118 +/- 5 mg/cm). We conclude that somatostatin analogue treatment during the early postoperative period does impair the growth of residual bowel in rats. These findings raise concern regarding the use of this drug for postoperative patients who have undergone massive small bowel resection in whom the process of post-resectional adaptation may be critical to allow sustenance with enteral nutrition.
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PMID:Somatostatin analogue treatment inhibits post-resectional adaptation of the small bowel in rats. 198 43

The long acting somatostatin analogue octreotide acetate has been effective in the treatment of early dumping syndrome. We hypothesized that this may be related to its effects on inhibiting gastric emptying and delaying intestinal transit. To study the effect of octreotide acetate on intestinal motility in patients we carried out a randomized, double-blinded study using a subcutaneous injection of either octreotide acetate (100 micrograms) or placebo given 20 min prior to ingestion of a high carbohydrate "dumping" meal in six patients with known severe dumping syndrome. Prior to each study a multilumen polyethylene tube was inserted into the efferent limb to study small intestinal contractions using low compliance pneumo-hydraulic water-perfused manometry. Octreotide acetate prevented dumping symptoms in all six patients and induced the appearance of migrating myoelectric complexes (MMC) characteristic of interdigestive motility. After ingestion of the dumping meal the postprandial "fed" motility pattern lasted for 141 +/- 9 min while after octreotide acetate the fed motility lasted for 29 +/- 5 min (P less than 0.03). The vigor of the fed motility pattern as measured by the motility index (MI = loge (sum of amplitudes X No. of contractions + 1] was lower after octreotide acetate than after placebo (15.1 +/- 0.1 vs 13.4 +/- 0.2, P less than 0.03). The induction of fasting MMC motility pattern and reduction in the duration and vigor of fed motility may explain the symptomatic relief these patients obtained with octreotide acetate. It is not known whether the induction of the MMC is a direct effect of octreotide acetate or secondary to the concomitant inhibition of peptide release (neurotensin, insulin, glucagon, pancreatic polypeptide) that has been demonstrated in earlier studies.
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PMID:Octreotide acetate induces fasting small bowel motility in patients with dumping syndrome. 226 84

Somatostatin and its analogs have been shown to inhibit both pancreatic endocrine and exocrine function. We hypothesized that octreotide acetate (Sandostatin), a somatostatin analog, decreases the pancreatic flow rate through a peptide-mediated mechanism and alters pancreatic fluid composition by inhibiting carbonic anhydrase action and circulating peptide levels. To test this hypothesis, we collected pancreatic fluid from six patients (four with pancreatic fistulas and two with pancreatic drains after pancreatic resection). Pancreatic fluid volume and chloride, sodium, potassium, amylase, lipase, and bicarbonate levels were measured before and after octreotide acetate therapy. Octreotide acetate reduced pancreatic fluid output by a mean of 75 percent (p less than 0.05), increased chloride concentration by 21 percent (p less than 0.05), and reduced bicarbonate content by 45 percent (p less than 0.05). Sodium levels were unchanged, but the potassium concentration was increased by 14 percent (p less than 0.05). Total amylase and lipase production per 24 hours was decreased by 63 percent and 27 percent, respectively (differences not significant). Somatostatin may be useful in the treatment of established pancreatic fistulas and may be a useful prophylactic tool to prevent postoperative fistula formation.
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PMID:Effect of octreotide acetate on pancreatic exocrine function. 246 37

Octreotide acetate (SMS-201-995), a somatostatin analogue, was used to treat an acromegalic patient harboring a growth hormone-secreting pituitary macroadenoma. Intermittent subcutaneous administration of octreotide suppressed growth hormone and insulin-like growth factor-I (IGF-I) levels and ameliorated clinical symptoms. Magnetic resonance imaging performed after 16 weeks revealed a 70% shrinkage of the pituitary mass, with a resultant partially empty sella turcica. To document that this shrinkage occurred as a result of octreotide treatment and not spontaneous tumor infarction, the medication was withdrawn for 4 weeks. A second magnetic resonance image disclosed regrowth of the tumor accompanied by rebound of growth hormone and IGF-I secretion. Subsequent biochemical remission has been sustained with preservation of anterior pituitary function since the drug was reinitiated. These findings suggest that intermittent subcutaneous administration of octreotide may provide potent medical ablation of growth hormone-secreting macroadenomas.
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PMID:Reversible shrinkage of a growth hormone-secreting pituitary adenoma by a long-acting somatostatin analogue, octreotide. 273 Feb 66

Octreotide acetate, a long-acting somatostatin analogue, is effective in controlling and markedly reducing the symptoms of carcinoid crisis. We report a patient with carcinoid syndrome with prolonged survival for 4.5 years with high dose octreotide therapy and survived for 7.5 years after the first flushing, in spite of episodes of severe carcinoid crisis. Dose escalation was required in order to control carcinoid symptoms, and the final dosage was 5,950 micrograms/day. Although administration of such a high dosage of octreotide has never been reported before, we found that octreotide could be used at this dosage safely without inducing serious side effects, and probably prolonged the patient's survival. Our experience with this case indicates that octreotide acetate is an effective drug in controlling carcinoid crisis and prolonging survival without serious side effects.
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PMID:Long-term survival in a patient with malignant carcinoid treated with high-dose octreotide. 751 29

The effect of somatostatin (SS) on adrenocorticotrophic hormone (ACTH) secretion from COR-L103 cells derived from a human small cell lung carcinoma was examined. SS at 1 microM had no effect on ACTH secretion from the cells on either short-term or long-term incubation. Studies by the reverse transcription-polymerase chain reaction (RT-PCR) showed that mRNA transcripts of the somatostatin receptor (SSTR) 2, SSTR3 and SSTR4 genes were present in COR-L103 cells. Extra bands were obtained by PCR-single strand conformation polymorphism (SSCP) analysis of the SSTR2 gene Sequence analysis of the SSTR2 gene demonstrated one point mutation in codon 188 of TGG for tryptophan to TGA for a stop codon causing loss of 182 C-terminal amino acid residues of SSTR2. The nucleotide sequences of the SSTR3 and SSTR4 genes in COR-L103 cells were normal. Binding studies using 125I-Tyr11-SS-14 showed specific affinity binding sites on COR-L103 cells and mouse pituitary tumor AtT-20 cells. Octreotide acetate suppressed the binding of 125I-Tyr11-SS-14 to these two cell lines, but the Kd of COR-L103 cells (160 nM) was 60-fold higher than that of AtT-20 cells (2.6 nM). Affinity cross-linking studies using 125I-Tyr11-SS-14 gave three bands of 72 KDa, 55 KDa and 32 KDa from AtT-20 cells, but only two bands of 55KDa and 32kDa from COR-L103 cells. These findings suggest that SSTR2 is not expressed in the plasma membranes of COR-L103 cells due to a point mutation, but that this may have no influence on the effect of SS on ACTH secretion.
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PMID:Point mutation of the somatostatin receptor 2 gene in the human small cell lung cancer cell line COR-L103. 776 54

Pancreatic pseudocysts in children are rare. A total of 213 cases have been reported in the literature, the majority secondary to trauma (65%). Treatment options range from conservative, non-operative management to operative drainage. Octreotide acetate, a long-acting analog of somatostatin, is a synthetic peptide with a variety of endocrine and gastrointestinal functions. Octreotide has been successfully used following pancreatic surgery to reduce exocrine function and most recently in the management of adult pancreatic pseudocysts. We report the efficacy of octreotide, as an adjunct to treatment, in two children with pancreatic pseudocyst. Each child was treated conservatively with bowel rest, hyperalimentation, and octreotide acetate (2.5 micrograms/kg SQ QD). Complete resolution of the pseudocysts occurred within 5 weeks. We conclude that octreotide acetate is a safe and potentially effective adjunct in the treatment of pediatric pancreatic pseudocyst, and should be added to the management of pseudocyst before drainage procedures.
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PMID:Conservative management of pediatric pancreatic pseudocyst using octreotide acetate. 788 30


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