摘要:

Beside its known hormonal activity, somatostatin exerts cytoprotective action. Thus, its favorable effect on the course of experimental pancreatitis, liver and lung lesions, and gastric ulcerations cannot be explained solely on the basis of hormone-mediated mechanisms. Cytoprotection is only observed when somatostatin is administered prior to toxine exposure or tissue damage, and the structure/activity of the substance is important in determining this effect. Thus, the non-hormonal biological effects of somatostatin can be summarized as follows: (a) Natural somatostatin- 14 has been shown, in addition to its full endocrine effect, to block the uptake of toxic substances into liver cells, (b) Analogues with superactive cytoprotection may be devoid of endocrine activity. In turn, this effect is commonly found in the low-molecular derivatives, (c) Although the mechanism leading to tissue protection has not been clarified, stabilisation of cell membranes may play a role as well as changes in the aminoacid sequence.

ISSN:1663-2818    

DOI:10.1159/000180974

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Biological activity of somatostatin can be altered by modiñcations in the amino acid sequence. Thus, a number of bioassays have been developed in order to measure the potency and specificity of analogues and heterogenous molecular forms of somatostatin. These procedures may assist in the estimation of somatostatin contents of tissue extracts but measurements in blood are limited by the presence of other substances masking the biological response to somatostatin. Recently, radioimmunoassay procedures have been developed and their usefulness in experimental and clinical medicine is reviewed

ISSN:1663-2818    

DOI:10.1159/000180975

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Because of its wide distribution in the organism, natural somatostatin (SRIF) demonstrates an ample spectrum of actions, involving mainly the central neuroendocrine system and the enteropancreatic area. In the former, this peptide may find its field of application in conditions characterized by excessive GH, TSH or ACTH secretion, depending on the central or peripheral cause of the inappropriate hormone control. The inhibitory effect of SRIF on gastrointestinal and pancreatic hormones may be useful in the management of tumors originating in this system and also in the treatment of inflammatory processes such as pancreatitis, in malignant diarrhea, and in gastrointestinal bleeding. A complex action of SRIF and its derivative on insulin release and glucose homeostasis may offer some advantages in the control of unstable diabetes. Dampening of organic functions in the upper digestive tract may also render SRIF and its analogues useful in the exploration of the gallbladder, gastric and pancreatic functions. The effect of such peptides on tissue growth and on the regulation of blood pressure are the subject of present investigations. Cytoprotection, an interesting aspect of SRIF application, is discussed elsewhere in this compendium. Finally, some comments on the possible use of SRIF as an additive to the conventional treatment of burns and sepsis close this review.

ISSN:1663-2818    

DOI:10.1159/000180976

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The infusion of natural somatostatin (SRIF) has been able to partially correct postprandial hyperglycemic reactions in insulin-dependent diabetes mellitus (IDDM). SMS 201-995 (Sandostatin) is a long-acting derivative with a growth hormone-suppressive effect 10-60 times more potent than the native peptide. The effect of SMS 201-995 (50 µg s.c.) on glucose control by exogenous insulin has been documented in a series of type I diabetics after stabilization of blood sugar by an artificial pancreas. Inhibition of counterregulatory mechanisms significantly diminished the postprandial hyperglycemia, and insulin requirements, both total and 2 h after meals, were markedly decreased. Also the effect of a single s.c. injection of 100 µg SMS 201-995 on the dawn phenomenon in a patient with poorly adjustable diabetes was investigated. The glucose escape observed during the control night was blocked by SMS 201-995. Thus, the stabilizing action of this peptide on postprandial and nocturnal hyperglycemia in unstable diabetes warrants further studie

ISSN:1663-2818    

DOI:10.1159/000180977

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

L363,586 is a potent, long-acting, somatostatin derivative. Intravenous and intranasal administration to diabetic subjects was effective in reducing both fasting and postprandial hyperglycemia. Also in patients stabilized on a closed-loop insulin infusion device, the intranasal administration of L363,586 was able to improve the glucose imbalance known as dawn phenomenon. Therefore, this analogue associated to standard insulin replacement could be useful in the control of unstable diabetes.

ISSN:1663-2818    

DOI:10.1159/000180978

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Portal hypertension is a common complication of chronic liver disease. Conventional therapy consists of surgery and palliative measures for the hemodynamic problem. It has been recently reported that somatostatin may reduce portal pressure without altering the systemic circulation and so reducing hepatic blood flow. This peptide also causes a significant fall in azygos circulation in patients with esophageal varices. The mechanism of this effect is unclear although suppression of intestinal vasodilating hormones and of glucagon have been claimed to play a role. Comparative clinical studies have shown somatostatin to be superior to the standard vasopressin treatment. Recent findings suggest that the efficacy of somatostatin can be increased by administering this peptide in repeated intravenous bolus injections. New derivatives, specially long-acting peptides, may eventually prove beneficial in the chronic treatment of this complication.

ISSN:1663-2818    

DOI:10.1159/000180979

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Stress ulcers are characterized by difficult management and poor prognosis. They currently represent a complication in the clinical course of other conditions, mainly shock states. The pathogenesis of stress ulcers is not well understood although the role of hypovolemia leading to energetic deprivation and instauration of anaerobic cellular metabolism have been carefully studied. Somatostatin has been found to reduce the incidence of experimental stress ulcers. In the clinic, patients with duodenal ulcers were found to exhibit a low number of antral D cells and a significant decrease in tissue somatostatin. In a multicenter trial, patients with bleeding peptic or stress ulcers were treated with somatostatin or cimetidine plus pirenzepine. Results were favorable to the former substance on account of the time required to stop the hemorrhage and the demands for blood replacement. Thus, medical management of bleeding ulcers with somatostatin may represent an alternative to more radical surgical intervention.

ISSN:1663-2818    

DOI:10.1159/000180980

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Mild pancreatitis is a common complication of endoscopic retrograde cholangio-pancreatography (ERCP) and endoscopic sphincterotomy. Knowing that a bolus injection of natural somatostatin (SRIF) dramatically reduces pancratic secretion, a study was conducted in 33 subjects undergoing invasive diagnostic procedures. A placebo (n = 16) or SRIF (n = 17; 4 µg/kg) were injected before cannulation. Enzymatic rise was observed in 16 (94 %) subjects receiving placebo and in 8 (50%) injected previously with SRIF. In the former group 65% reported abdominal pain whereas only 19% had this complaint in the SRIF series. Results suggest that a bolus injection of SRIF may attenuate pancreatic irritation caused by diagnostic procedures or sphincterotomy

ISSN:1663-2818    

DOI:10.1159/000180981

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

A 46-year-old woman with acromegaly and marked hyperprolactinemia was treated chronically with sandostatin (50 µg b.i.d. up to 100 µg t.i.d.). Plasma growth hormone (GH) was reduced by 90% of basal values and prolactin (PRL) dropped from initially 204 to 74 ng/ml. Serial CAT scans detected a volume reduction of the pituitary adenoma of 46.7%, but discontinuation of therapy was followed by re-expansion of the tumor. Tissue collected at transsphenoidal adenomectomy was examined by immunohistology and found positive for both GH and PRL. This characteristic would explain the dual hormonal response to the specific GH inhibitor sandostati

ISSN:1663-2818    

DOI:10.1159/000180982

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The present report illustrates the effectiveness of a long-acting somatostatin analog, SMS 201–995 (Sandostatin), in the chronic treatment of acromegaly. Daily doses of 50-300 µg were administered subcutaneously to 37 patients. Gradual dose increments induced a progressive GH decrease accompanied by a parallel reduction in plasma somatomedin C concentrations. There was a concomitant amelioration of clinical signs and symptoms throughout the investigational period. No escape phenomenon or tachyphylaxis was observed. It is concluded that chronic therapy with SMS 201–995 represents a promising medical alternative for the treatment of active acrome

ISSN:1663-2818    

DOI:10.1159/000180983

出版商:S. Karger AG    

年代:1988

数据来源: Karger