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

The heterogeneity of muscarinic receptors has been well supported by differential characteristics between pirenzepine and atropine both in receptor binding and in whole tissue pharmacology studies. Under these conditions pirenzepine has been classified as a selective receptor antagonist with high affinity for M1 receptors. The antisecretory properties of pirenzepine on gastric acid and pepsin secretion may be attributed to the antagonistic activity of the drug on muscarinic M1 receptors of gastric intramural plexuses, whereas the effect on parietal muscarinic M2 receptors seems of less importance. Additional inhibitory mechanisms on gastric secretion may be represented by pirenzepine-induced increase in somatostatin release from gastrointestinal system. Significant cytoprotective properties of pirenzepine have been observed on a variety of experimentally induced peptic ulcerations. This protective activity may be due to pirenzepine-induced increase in gastric mucosal blood flow as well as to the increase in gastric transmural electric potential difference. In accordance with this pharmacodynamic profile of pirenzepine, numerous clinical studies have revealed its efficacy in the treatment of both duodenal and gastric ulcerations. In addition to this, the clinical usefulness of the drug has been demonstrated in Zollinger-Ellison syndrome, in stress ulceration, in acute gastrointestinal bleeding as well as in gastritis, duodenitis and non-ulcer dyspepsia. In most of the studies pirenzepine has been found to be well tolerated with a low incidence of antimuscarinic effects which may occur at salivary, ocular, cardiac and urinary sites. The clinical use of pirenzepine alone or in association with H2 blockers is recommended in the treatment of peptic ulcer patients, in the case of acute gastrointestinal haemorrhage and in patients non responders to H2 antagonists.
 ...
PMID:[A selective antimuscarinic agent: pirenzepine. Review of its pharmacologic and clinical properties]. 257 37

The treatment of patients with Zollinger-Ellison syndrome (ZES) has undergone dramatic evolution during the past decade. Although initially regarded as an incurable tumor, resection of gastrinoma for potential cure has been reported in 30% to 40% of selected patients in recent series. Conversely, although definitive control of acid hypersecretion is achieved by total gastrectomy, histamine (H2)-receptor antagonists and the newly introduced agents omeprazole and somatostatin analogues allow effective medical therapy of gastric acid overproduction. Confirmation of the diagnosis is best achieved with the I.V. secretin stimulation test, and tumor localization techniques are mandatory to identify candidates for operative tumor resection. Intraoperative sonography and careful exploration are required for tumor removal; successful tumor resection is associated with prolonged survival. The majority of patients (60%) are still found to have malignant disease at the time of diagnosis, but 10-year overall survival commonly exceeds 40%. The presence of multiple endocrine neoplasia type I (MEN-I) is seen in 10% to 25% of patients; correction of hypercalcemia alone may have therapeutic benefit in some ZES patients, and while gastrinoma resection is rarely possible, MEN-I patients demonstrate prolonged survival. The choice of medical rather than surgical therapy for acid hypersecretion depends on the suitability of each patient for careful and repeated endoscopic and chemical studies, versus the likelihood of a successful postoperative outcome. Socioeconomic, geographic, and related medical factors in each case may dictate the form of long-term antisecretory therapy. Exploration for possible tumor resection is indicated for virtually all patients who have no documented metastatic disease.
 ...
PMID:Current diagnosis and management of Zollinger-Ellison syndrome. 268 66

The long-acting somatostatin (SMS) analog, SMS 201-995 has beneficial effects on APUDomas. In two Zollinger-Ellison syndrome (ZES) patients we assessed basal acid output (BAO) and 24-h pH under SMS and compared them to controls. We also assessed total gastrin, gastrin 17, insulin, glucagon, C-peptide, and SMS by radioimmunoassay. In the benign gastrinoma, an acid-controlling action of SMS was shown, elevating the 24-h pH threshold over the pH range 1.5-5 of 55-10% compared with control. A parallel inhibition of the gastrins greater than 90% was apparent. We found no beneficial effect on gastric acid secretion and on tumor gastrin in the malignant gastrinoma despite a fourfold higher plasma SMS level. Non-tumor-related peptides were suppressed by approximately 50% and in contrast to gastrin they again reached pre-SMS levels before the next dose of the drug. We conclude that SMS is more effective in benign than in malignant gastrinomas, and may be exclusively so.
 ...
PMID:Long-acting somatostatin analog controls acid and gastrin secretion in benign, not in malignant, Zollinger-Ellison syndrome. 230 79

Gastrinoma cells from surgical specimens of a primary pancreatic tumor and an hepatic metastasis in two patients with a Zollinger-Ellison syndrome were grown and subcultured for 7 mo. Cultured cells displayed a strong reactivity to heptadecapeptide gastrin antibody and maintained an ultrastructural appearance resembling that of the original tumor cells with the presence of secretory granules of variable size and electron density. Cultured cells also showed the ability to secrete immunoreactive gastrin, and this secretion was further concentration-dependently stimulated by secretin (10(-10)-10(-6) M), carbachol (10(-6) M), and bombesin (10(-10)-10(-6) M). The latter peptide was the more potent stimulant with a maximal effect at 10(-9) M (460 +/- 20% of basal release; P less than 0.05). This stimulation occurred in the absence of extracellular Ca2+ and was potentiated by the addition of dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP; 10(-3) M) into the culture medium. The somatostatin analogue, somatostatin-(201-995), did not alter basal gastrin release but inhibited secretin, carbachol, and bombesin stimulation. Moreover, DBcAMP (10(-3) M) and Ca2+ (1-3 mM) stimulated gastrin release; Ca2+ ionophore A23187 (6 micrograms/ml) enhanced gastrin response to Ca2+ in the early time intervals of incubation. Furthermore the phorbol ester derivative, 12-O-tetradecanoyl phorbol-13-acetate, dramatically stimulated gastrin release (10 times the basal value). We conclude that gastrinoma cells can be cultured over an extended period with maintenance of their capacity to secrete gastrin in response to various hormones and mediators.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Gastrin secretion by gastrinoma cells in long-term culture. 284 43

Acute effects of somatostatin analog (SMS 201-995) on pancreatic hormones were studied in two patients with malignant islet-cell carcinoma. Before and after subcutaneous injection of somatostatin with a doses of 50 micrograms, blood glucose (BG), serum growth hormone (hGH), C-peptide immunoreactivity (CPR), plasma immunoreactive glucagon (IRG) and gastrin were assayed, and changes in elution patterns of IRG and gastrin were also analyzed on Bio-Gel P-30 column chromatography. In Patient 1 with glucagonoma syndrome and hypergastrinemia, a prompt and remarkable decrease in plasma IRG and gastrin was observed after the injection of SMS 201-995 in association with a decrease in blood glucose, and then IRG and gastrin increased gradually. The suppressive effect continued for at least 6 hours. On gel filtration of the plasma obtained before the injection of the analog, three major peaks, greater than 20000, 9000 and 3500 molecular-weight (mol wt) fractions, were seen in IRG fraction. The decrease in plasma IRG observed at 1 hour after the injection was mainly due to a marked decrease in the 3500 molecular weight fraction. In addition, a slight decrease in the 9000 mol wt fraction was seen. At 4 hours after the injection, the 3500 mol wt peak returned to the previous level, while the 9000 mol wt peak decreased further. On the other hand, the gastrin elution pattern of plasma obtained before the injection revealed three major gastrin peaks, greater than 20000, 7000 and 5000 mol wt fraction. The changes in the gastrin elution pattern after the injection were similar to those of the IRG elution pattern. In Patient 2 with Zollinger-Ellison's syndrome, the plasma gastrin level decreased gradually for 5 hours after the injection. On gel filtration of the plasma obtained before the injection, two major gastrin peaks, 7000 and 5000 mol wt fraction, of which the large-molecular fraction was more prominent than the small-molecular fraction, were observed. After the injection, a marked decrease in the small-molecular fraction and a gradual decrease in the large-molecular fraction were observed for 4 hours, accompanied by a decrease in plasma gastrin. At 7 hours after the injection, the smaller fraction was augmented again. The serum CPR and hGH was slightly suppressed after the injection in both patients. The adverse effects of slight nausea and vomiting were noticed only in Patient 1.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Inhibitory effects of somatostatin analog (SMS 201-995) on pancreatic hormones in patients with malignant islet-cell carcinoma]. 285 26

SMS 201-995 is an octapeptide analogue of natural somatostatin characterized by pharmacological properties similar to those of somatostatin itself. In addition, its serum half-life of about 60 minutes after i.v. injection is significantly longer than that of the natural compound. A patient with active bleeding from a peptic ulcer jejuni due to a Zollinger-Ellison syndrome was successfully treated with SMS 201-995. Bleeding stopped after continuous infusion (25 micrograms/h) within the first 24 hours of infusion. The serum gastrin concentration dropped from 3,300 pg/ml to 170 pg/ ml (normal range 40-100 pg/ml). Continuation of the treatment by subcutaneous injections of SMS 201-995 (100 micrograms twice daily) maintained serum gastrin concentrations between 300 to 400 pg/ml over a period of 8 months. Side effects have not been observed. Four subsequent endoscopic examinations have revealed no ulcer relapse.
 ...
PMID:Treatment of relapsing bleeding peptic ulcers with the somatostatin analogue SMS 201 995 in a patient with Zollinger-Ellison syndrome. 286 99

Determination of gastrointestinal hormones by radioimmunoassay in plasma is important for detection of endocrine-active tumours in the gut. Since in most cases multiple endocrine tumours occur, a variety of hormones such as gastrin, vasoactive intestinal polypeptide, glucagon, somatostatin, pancreatic polypeptide and neurotensin should be measured. Gastrin is helpful as a diagnostic tool in differentiating between Zollinger-Ellison syndrome and antral G-cell hyperplasia or hyperfunction. Autonomic neuropathy of the gut (as in diabetics) can be detected by measurements of plasma pancreatic polypeptide. The diagnostic value of measurements of plasma cholecystokinin, secretin and other gut peptide hormones is not yet defined.
 ...
PMID:[Diagnostic significance of gastrointestinal hormones]. 286 23

Twelve duodenal carcinoid tumours are presented, 4 of them located in the ampulla. Symptoms included the Zollinger-Ellison syndrome (4 patients), the carcinoid syndrome (1 patient), mechanical obstruction (3 patients), bleeding (1 patient) and abdominal pain (1 patient). Two further tumours were detected by chance. Three patients with the Zollinger-Ellison syndrome had additional endocrine tumours characteristic of the MEN I syndrome. In 2 of them the duodenal carcinoids were of very small size and were multiple. They were observed in close proximity to focal areas of endocrine cell hyperplasia. Immunohistochemical investigations showed gastrin and somatostatin to be the predominant polypeptide hormones produced by these tumours. No somatostatinoma syndrome was encountered. In half of our cases additional production of insulin, VIP or even calcitonin in smaller amounts was found. Two of our patients had cutaneous manifestations of von Recklinghausen's disease and in both of them the carcinoid was located in the ampulla. One of these patients also had a pheochromocytoma.
 ...
PMID:Duodenal and ampullary carcinoid tumors. A report of 12 cases with pathological characteristics, polypeptide content and relation to the MEN I syndrome and von Recklinghausen's disease (neurofibromatosis). 286 9

The provocation of gastrin release by calcium or secretin is accepted as a method to differentiate the hypergastrinemia of the Zollinger-Ellison syndrome from that of other causes. We have previously shown that calcium and secretin failed to provoke gastrin release from acutely dispersed gastrinoma cells. This disparity between the in vivo and in vitro effects of these two provocative agents suggests that intermediates may be necessary for calcium- or secretin-induced gastrin release. In an acute cell dispersion, serum-free model, two gastrinomas with low levels of endogenous somatostatin (SRIF) and other peptides failed to respond to calcium or secretin provocation. Conversely, a third tumor containing high levels of endogenous SRIF-like peptides and low levels of other gut peptides did respond to calcium, but not to secretin provocation in vitro. We suggest that in vivo, SRIF modulation of gastrin release is a prerequisite for calcium-simulated gastrin secretion.
 ...
PMID:Somatostatin-like peptides alter calcium but not secretin sensitivity of gastrinoma cells. 287 13

Acromegaly is rarely caused by the ectopic secretion of growth hormone releasing factor (GRF) from peripheral neuroendocrine tumours. We evaluated the ability of a recently developed somatostatin analogue (SMS 201-995, Sandoz) to reduce hormone levels and pituitary size in a young woman with acromegaly and Zollinger-Ellison syndrome secondary to a metastatic pancreatic islet cell tumour secreting GRF and gastrin. Gastrin, GRF, and growth hormone (GH) levels declined dramatically following the initiation of therapy with the analogue by continuous iv infusion. Although intermittent sc therapy was not effective in suppressing hormone levels, continuous sc infusion of SMS 201-995 has provided good control of both GRF and GH levels for nine months. Moreover, treatment with SMS 201-995 was associated with a substantial reduction in pituitary enlargement and an improvement in her gastric symptoms. Continuous sc infusion of SMS 201-995 may be useful in treating enlarged pituitaries resistant to other modes of therapy.
 ...
PMID:Reduction of pituitary size by the somatostatin analogue SMS 201-995 in a patient with an islet cell tumour secreting growth hormone releasing factor. 287 70


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>