Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatostatin is present in the gastrointestinal tract in appreciable amounts. The highest concentrations of the polypeptide are found in the stomach, the upper small intestine, and the pancreas. Within the gastrointestinal tract, somatostatin inhibits various functions, including endocrine and exocrine secretion, motility, blood flow, absorption, and growth. The polypeptide regulates these functions by endocrine, paracrine, neurocrine or luminal mechanisms. Abnormalities of endogenous somatostatin have been implicated in several gastrointestinal disorders, including the somatostatinoma syndrome, antroduodenal D-cell hyperplasia, peptic ulcer, obesity, and liver cirrhosis. Because of its potent inhibitory effects, somatostatin or somatostatin-analogues have been used as therapeutic agents in various clinical conditions, such as upper gastrointestinal haemorrhage, endocrine pancreatic tumours, gastrointestinal and pancreatic fistulas, pancreatitis, secretory diarrhoea, and dumping syndrome. The recent availability of the synthetic long-acting somatostatin-analogue SMS 201-995 (Sandostatin) has greatly facilitated the therapeutical application of somatostatin-polypeptides.
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PMID:Clinical and pathophysiological aspects of somatostatin and the gastrointestinal tract. 289 34

A somatostatin analogue, a long-acting octapeptide (SMS 201-995), has been reported to decrease portal pressure, but the mechanism is unclear. To elucidate the effects of this drug on both systemic and splanchnic hemodynamics, it was administered in two conscious rat models of portal hypertension. The dose-response curves showed that the somatostatin analogue significantly decreased portal pressure at a lower dose in rats with cirrhosis than in portal vein-stenosed rats. Calculated ED50 values were significantly different among all groups. Intravenous infusion of 8 micrograms/kg body wt.h of somatostatin analogue significantly decreased cardiac output by approximately 20% in both groups of portal hypertensive rats and increased mean arterial pressure by 7%. Accordingly, systemic vascular resistance markedly increased, indicating vasoconstrictor effects of this drug. The somatostatin analogue also significantly decreased portal tributary blood flow by 18% in portal vein-stenosed rats and 27% in cirrhotic rats. In sham-operated rats, somatostatin analogue had no effect on the systemic or splanchnic circulation. This study shows that somatostatin analogue decreases portal pressure principally by reducing portal tributary blood flow. This reduction may be due to either a direct vasoconstrictive effect or diminution in vasoactive hormone release.
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PMID:Circulatory effects of somatostatin analogue in two conscious rat models of portal hypertension. 289 52

Transmural oesophageal variceal pressure was determined by direct puncture of the varices in 27 patients with liver cirrhosis and oesophageal varices. Variceal pressure was not influenced three to six minutes after somatostatin bolus administration and slightly increased during somatostatin infusion. Thus, potential haemostatic benefits of somatostatin cannot be explained by pressure reductions in the varices.
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PMID:Somatostatin does not reduce oesophageal variceal pressure in liver cirrhotics. 289 36

The aim of this study was to evaluate the contribution of gluconeogenesis from amino acids in the development of fasting and absorptive hyperammonemia in cirrhosis. Somatostatin (SRIF), which is known to inhibit the hepatic disposal of gluconeogenic amino acids, was administered in a continuous infusion (500 micrograms/h) for 90 min before and 5 h after a protein meal (240 g of meat) in 11 overnight fasting patients. Plasma glucagon, insulin, gluconeogenic amino acids (GAA: alanine, serine, glycine, and threonine) and ammonia (NH3) were evaluated before the infusion, immediately before, and at 1, 3, and 5 h after the meal. As control study, the same protocol was randomly repeated in a different day with saline infusion. During the latter, a direct correlation was found between fasting glucagon and ammonia (r = 0.68; p less than 0.05). Fasting glucagon, insulin, and NH3 did not change, whereas alanine (p less than 0.05) and the GAA sum decreased (p less than 0.01). When SRIF was infused, fasting glucagon (p less than 0.05), insulin (p less than 0.05), and NH3 (p less than 0.05) decreased. Alanine did not change, and GAA sum increased (p less than 0.02). No correlations were found by plotting changes in glucagon or GAA sum and NH3. After the meal, SRIF infusion abolished the plasma response of glucagon and markedly reduced that of insulin, so that their area under the curve (AUC0-5) were reduced (p less than 0.005, for both), with respect to control study. Moreover, the AUC0-5 of alanine (p less than 0.005) and GAA sum (p less than 0.005) were increased, suggesting a reduced disposal of these compounds. In spite of this, the meal-induced early increase and the AUC0-5 of plasma NH3 observed during SRIF and saline infusion did not differ. Our results do not confirm the importance of gluconeogenesis from alpha-amino-nitrogens in determining the fasting ammonemia of cirrhosis, and suggest that this metabolic pathway does not significantly influence the protein meal-induced exacerbation of plasma ammonia.
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PMID:Role of gluconeogenesis from amino acids in determining fasting and absorptive levels of plasma ammonia in cirrhosis. 289 85

The present study was undertaken in order to establish the significance of glucagon in glucose intolerance in liver cirrhosis. The plasma glucose response to an oral glucose load (75 g) was determined in 10 control subjects and in 10 cirrhotic patients, after infusions of: glucagon (3 ng.kg-1.min-1) or saline (154 mmol/l); somatostatin (SRIH) (500 micrograms/h); and SRIH plus glucagon (3 ng.kg-1.min-1). Glucagon infusion did not impair glucose tolerance, neither in normal subjects nor in patients with cirrhosis. On the other hand, in both groups glucose tolerance was impaired by SRIH infusion, presumably owing to an absolute insulin deficiency. Both in normal subjects and in cirrhotic patients, SRIH plus glucagon infusion further impaired glucose tolerance, presumably as a result of excess glucagon and concomitant insulin deficiency. In conclusion, our data show that hyperglucagonemia is not an important factor in the development of the glucose intolerance in patients with hepatic cirrhosis.
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PMID:Glucagon and glucose tolerance in liver cirrhosis. 289 68

Patients with cirrhosis of the liver often have insulin resistance and elevated circulating growth hormone levels. This study was undertaken (a) to evaluate glucose intolerance, insulin resistance and abnormal growth hormone secretion and (b) to determine if GH suppression improves insulin resistance. Glucose tolerance tests (GTT), intravenous insulin tolerance tests (IVITT), arginine stimulation tests (AST) and glucose clamp studies before and during GH suppression with somatostatin were performed in a group of patients with alcohol-induced liver cirrhosis. During GTT cirrhotic subjects had a 2-hour plasma glucose of 200 +/- 9.8 ng/dl (N = 14) compared to 128 +/- 8.0 ng/dl in normal controls (N = 15), P less than 0.001. Basal GH was elevated in cirrhotic patients and in response to arginine stimulation reached a peak of 17.0 +/- 5.4 ng/ml (N = 7), compared to a peak of 11.3 +/- 1.8 ng/ml in 5 normal controls (P = NS). During IVITT patients with cirrhosis had a glucose nadir of 60.0 +/- 4.0 mg/dl (N = 9), compared to 29.0 +/- 7.0 mg/dl in controls (N = 5), P less than 0.001. Peak GH levels during IVITT were not significantly different in cirrhotics and controls. Glucose utilization rates in 4 patients with cirrhosis of the liver before somatostatin mediated GH suppression was 3.1 +/- 0.5 mg/kg/min and 6.5 +/- 1.5 mg/kg/min during somatostatin infusion, P less than 0.025. We conclude that patients with alcohol induced cirrhosis have sustained GH elevations resulting in insulin resistance which improves after GH suppression.
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PMID:Growth hormone and carbohydrate intolerance in cirrhosis. 305 69

The effect of the long-acting somatostatin analogue SMS 201-995 on renal function was investigated in nine cirrhotic patients with ascites, low urine output, low serum sodium, and normal serum creatinine. SMS 201-995, infused at 40 micrograms/h for 2 h, produced a significant increase in urine volume, a significant decrease in urine osmolality, and a significant increase in creatinine clearance. These changes, although less pronounced, persisted 24 h after the infusion of the analogue. No significant changes in free water clearance, urinary sodium excretion or serum sodium were noted. The effects of SMS 201-995 might be attributed to an improvement of renal haemodynamics through inhibition of vasoconstrictor systems acting in cirrhosis. It is concluded that SMS 201-995 may have a role in the treatment of the renal abnormalities complicating liver disease.
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PMID:Enhancement of renal function by a long-acting somatostatin analogue in patients with decompensated cirrhosis. 314 15

Circulating forms of somatostatinlike immunoreactivity (SLI) in humans were characterized using several chromatographic techniques. After gelfiltration chromatography on Bio-Gel P-6 columns greater than 90% of circulating SLI was of high molecular weight (MW) and eluted in the void volume. When plasma samples were passed through protein A-Sepharose columns, more than 85% of the high MW SLI was removed, indicating that this form of plasma SLI is mainly due to cross-reacting immunoglobulins. Extraction of 10-ml plasma samples from normal subjects on octadecyl silyl silica cartridges eliminated the high MW material. In addition, this extraction technique concentrated the two lower MW forms of SLI, which coelute on gel filtration chromatography with somatostatin-28 (S-28) and the tetradecapeptide form of somatostatin (S-14), respectively. Extracted plasma SLI was further analyzed by high-pressure liquid chromatography (HPLC). The results confirmed the identity of S-28 and demonstrated that S-14 is converted, in part, to Des-Alasomatostatin (S-13) following secretion into the circulation. At least four forms of SLI are thus present in human plasma: cross-reacting immunoglobulins, S-28, S-14, and S-13. Concentrations of SLI forms in the plasma of normal controls and patients with renal failure or cirrhosis were measured to assess the role of circulating somatostatin in health and disease. High MW SLI was elevated above normal in the plasma of patients with cirrhosis, but was not significantly elevated in patients with chronic renal failure. On the other hand, concentrations of plasma S-28 and S-13/14 (total concentrations of S-13 plus S-14) were elevated in patients with either chronic renal failure or cirrhosis.
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PMID:Circulating forms of somatostatinlike immunoreactivity in human plasma. 396 83

The effects of somatostatin on hepatic and systemic hemodynamics were investigated in 17 patients with chronic liver disease and severe portal hypertension during the hemodynamic assessment before elective portal-systemic shunt surgery. The injection of somatostatin (1.0 microgram/kg) caused a decrease of the wedged hepatic venous pressure, from 19.5 +/- SE 1.3 mmHg to 14.0 +/- 1.0 mmHg (p < 0.001). Injections of 0.5 and 2.0 microgram/kg had similar effects. During somatostatin infusion at a constant rate (7.5 microgram/min) there was a reduction of the wedged hepatic venous pressure (-17.0%, p < 0.001) and estimated hepatic blood flow (-17.5%, p < 0.01) but no significant changes in hepatic vascular resistance, cardiac output, systemic blood pressure, peripheral resistance, or cardiopulmonary pressures. In marked contrast to the selective action of somatostatin on splanchnic hemodynamics, vasopressin infusion (0.3 U/min) in 6 patients caused not only significant falls in the wedged hepatic venous pressure and estimated hepatic blood flow (-28.6% and -31.8%, respectively), but also significant changes in the systemic circulation, including a reduction of the cardiac output (-19.7%, p < 0.01) and heart rate (-12.6%, p < 0.01) and an increase of the arterial pressure (+18.8%, p < 0.01) and peripheral resistance (+46.8%, p < 0.01). These results show that somatostatin effectively reduces hepatic blood flow and portal pressure in patients with cirrhosis and severe portal hypertension, without altering the systemic circulation.
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PMID:Effects of somatostatin on hepatic and systemic hemodynamics in patients with cirrhosis of the liver: comparison with vasopressin. 610 97

The effect of somatostatin on splanchnic hemodynamics was determined in 8 patients with cirrhosis of the liver and in 18 normal subjects using arterial-hepatic-venous catheterization. Estimated hepatic blood flow determined by indocyanine green infusion was 1.36 +/- 0.23 L/min (+/- SEM) in patients with cirrhosis and remained unaffected during 30 min of somatostatin (250 microgram/h) administration. Wedged hepatic venous pressure which was elevated to 23 +/- 1.8 mmHg was also uninfluenced. In contrast to somatostatin, an infusion of vasopressin (12 U/h for 30 min) given to the same patients, lowered estimated blood flow by 28% (p < 0.05) and wedged hepatic venous pressure by 18% (p < 0.02). Arterial gastrin and insulin levels were lowered during somatostatin infusion by 33% (p < 0.02) and by 75% (p < 0.005), respectively. In contrast to the cirrhosis, infusion of 250 microgram/h somatostatin into normal subjects was associated with a decrease of estimated hepatic blood flow from 1.20 +/- 0.16 to 0.88 +/- 0.12 L/min (p < 0.01) representing a 27% decline. Arterial gastrin and insulin concentrations were lower (p < 0.01) than in cirrhosis, but the basal levels were lowered by somatostatin to a similar degree in both groups of patients. A higher dose of somatostatin (500 microgram/h) administered to normal subjects resulted in a similar decrease of gastrin and of estimated hepatic blood flow as that seen with 250 microgram/h, whereas a lower dose (125 microgram/h) decreased gastrin but failed to influence estimated hepatic blood flow. Thus, somatostatin at a dose which has been used in the treatment of acute peptic ulcer hemorrhage (250 microgram/h) failed to influence estimated hepatic blood flow and wegded hepatic venous pressure in patients with cirrhosis but lowered splanchnic blood flow in normal subjects. Assuming that this effect contributes to somatostatin's therapeutic efficacy, these results cast doubt on its potential value in the treatment of upper gastrointestinal bleeding of cirrhotics with portal hypertension.
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PMID:Effect of somatostatin on splanchnic hemodynamics in patients with cirrhosis of the liver and in normal subjects. 610 98


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