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)

Natural somatostatin and two synthetic derivatives (octreotide, 008) were tested for their ability to prevent hypoxic ischemic cell injury of the isolated perfused rat liver. The cyclic octapeptide octreotide is known to have endocrine and cytoprotective activities, whereas the cyclic hexapeptide 008 exerts protective actions without any endocrine effects. In isolated perfused rat livers flow rate was reduced and oxygen supply interrupted for 180 min. Then the livers were normoxically reperfused for 30 min. LDH and GLDH activity as well as Ca2+ concentration was determined in the effluent. Hypoxic ischemia led to a substantial enzyme release from the liver and to a strong Ca2+ influx. Pretreatment with somatostatin, octreotide and 008 significantly reduced LDH and GLDH release (P < 0.001). The somatostatins significantly increased the Ca(2+)-influx into the hypoxic, ischemic perfused rat liver (P < 0.001). Ca(2+)-influx is known to be an essential factor in the final common pathway of cell death induced by hypoxic ischemia. Even though the administration of the somatostatins was associated with an enhanced Ca(2+)-influx, the somatostatins reduced hypoxic ischemic liver injury.
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PMID:Rat liver injury induced by hypoxic ischemia and reperfusion: protective action by somatostatin and two derivatives. 809 90

We retrospectively studied 22 patients with hepatopulmonary syndrome (HPS) evaluated at the Mayo Medical Center from 1984 to 1991. All patients had hepatic cirrhosis with clinical evidence of portal hypertension; 13 (59 percent) had severe hypoxemia while breathing room air in the supine position (PaO2 < 60 mm Hg), and 14 of 16 (88 percent) had orthodeoxia breathing room air. On the basis of angiographic observations, we defined type 1 and type 2 patterns of pulmonary vascular abnormalities in HPS. Response to 100 percent oxygen and therapeutic regimens may differ in the angiographic patterns. Substantial deterioration in PaO2 associated with clinically stable hepatic dysfunction was documented in five of seven patients studied with sequential arterial blood gas testing; four subsequently died within 48 months. Overall mortality was 41 percent, occurring a mean of 2.5 years after diagnosis. In 7 of the 22 patients, we prospectively studied the effect of somatostatin analogue given subcutaneously for 4 consecutive days. No significant improvement in PaO2 was documented while breathing room air or 100 percent oxygen (p < 0.05). We conclude that in selected patients with clinically stable hepatic dysfunction and deteriorating oxygenation, the prognosis is poor. Our data in combination with recent surgical reports suggest that liver transplantation may be the treatment of choice in patients with HPS and worsening oxygenation.
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PMID:Hepatopulmonary syndrome. Clinical observations and lack of therapeutic response to somatostatin analogue. 810 97

We studied the effects of the 36-amino acid peptide, neuropeptide Y (NPY), on salt secretion by the rectal gland of Squalus acanthias. We used three preparations: whole isolated perfused glands, freshly prepared separated rectal gland tubules, and confluent monolayers of cultured rectal gland cells. In perfused glands NPY inhibited secretion stimulated by vasoactive intestinal peptide (VIP), forskolin, or adenosine 3',5'-cyclic monophosphate (cAMP) and theophylline. Maximal inhibition of 63 +/- 3.4% was seen at 3 x 10(-8) M NPY, with half-maximal effect at 3 x 10(-9) M. NPY did not inhibit the basal activity of rectal gland adenylate cyclase or that stimulated by VIP. The inhibitory action of NPY was not prevented by procaine, nifedipine, or diltiazem, suggesting that it was not secondary to the release of somatostatin or other unknown neurotransmitters from rectal gland nerves. In confirmation, somatostatin was not detected in the venous effluent after administration of NPY. NPY also inhibited transport-related oxygen consumption in separated rectal gland tubules and inhibited short-circuit current generated by confluent monolayers of primary cultures of rectal gland cells. The results indicate that NPY inhibits chloride secretion by a direct action on cells of the shark rectal gland at a site distal to the generation of cAMP.
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PMID:Neuropeptide Y inhibits chloride secretion in the shark rectal gland. 810 43

Intrapulmonary shunts producing basal resting hypoxemia and necessitating the continual use of supplemental oxygen by two cirrhotic men were closed prior to liver transplantation with octreotide acetate, a somatostatin analogue. The closure of these shunts was monitored by serial blood gas determinations and shunt estimations using two different techniques. Partial closure of the shunts with preoperative octreotide acetate administration allowed liver transplantation to proceed with successful engraftment and eventual permanent closure of the shunts. Currently, both patients are alive and well with normal liver function and blood gases and, most important, have no requirement for supplemental oxygen.
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PMID:Liver transplantation following preoperative closure of intrapulmonary shunts. 815 44

The aim of this study was to evaluate the effects of octreotide, a long-acting somatostatin analogue, on canine gastric mucosal blood flow and hemodynamics. We hypothesized that octreotide might decrease gastric mucosal blood flow without causing adverse hemodynamic effects. Two groups of dogs were anesthetized (six normal dogs and six dogs with prehepatic portal hypertension), and each dog was administered intravenous octreotide, normal saline solution, and vasopressin for 30 minutes on separate days in a blinded, randomized fashion. Vasopressin was included as treatment for a positive control. Gastric mucosal blood flow was assessed at the fundus, corpus, and antrum by endoscopic reflectance spectrophotometry. A femoral arterial catheter monitored systemic blood pressure and heart rate. Treatment responses for all observations were calculated for each dog as a percentage of baseline values. For mucosal blood flow, treatment responses did not differ significantly over time or between animal group or gastric location. Octreotide significantly decreased indices of hemoglobin concentration (-19%, p = 0.01) and oxygen saturation (-17%, p = 0.0002) compared to saline (-9% and -7%, respectively). The mean arterial pressure was increased after octreotide compared to saline (+23% versus +7%, p = 0.01), but octrotide had no effect on heart rate (+2% versus +1%). Vasopressin also decreased the indices of hemoglobin concentration (-34%) and oxygen saturation (-82%) significantly more than saline (p = 0.001). Vasopressin increased mean arterial pressure (+55%), but also caused reflex bradycardia (-22%) significantly more than saline (p = 0.001). We conclude that octreotide decreases canine gastric mucosal blood flow and appears to cause minimal hemodynamic changes.
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PMID:Octreotide decreases canine gastric mucosal blood flow: a controlled assessment by endoscopic reflectance spectrophotometry. 816 36

Chronic rejection is a major threat towards the long-term function and survival of transplanted hearts and kidneys. It is characterized by a proliferative remodelling of the graft vessels along with structural changes of the parenchyma and gradual deterioration of graft function. The pathogenesis is complex and multifactorial. Since grafts with chronic rejection are also subjected to a more or less intense invasion of immunoreactive cells, an important primary objective is to optimize the immunosuppressive treatment. There is no established means of prevention or treatment of chronic rejection. Pharmacological agents interfering with prostaglandin metabolism have been tried most frequently and preliminary results are also available from the use of polyunsaturated fatty acids of the omega-3 series and of heparin derivatives. Based on experimental studies the somatostatin analogue angiopeptin seems very promising today. There will certainly be an increased interest in the use of lipid-reducing agents in the future as well as antioxidant agents acting against the effects of reactive oxygen radicals and oxidative modification of LDL fractions. A strong novel candidate is carvedilol, exerting both antihypertensive, antioxidant and antiproliferative properties.
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PMID:Pathogenesis and treatment perspectives of chronic graft rejection (CVR). 822 76

Anesthetic management of a 75-year-old female with carcinoid syndrome is reported. She had a tumor on the ileum and multiple metastatic tumors in the both lobes of the liver. Levels of both plasma serotonin and urinary 5-hydroxyindole acetic acid (5-HIAA) were significantly elevated before the operation. Although she was treated with somatostatin-analogue percutaneously, the levels of these hormones did not decrease significantly. The partial resection of the small intestine was scheduled under general anesthesia. Before induction of general anesthesia, hydrocortisone and ulinastatin were administered intravenously to prevent the release of chemical mediators. Anesthesia was induced with ketamine, diazepam, and vecuronium, and maintained with nitrous oxide, oxygen and enflurane. There was mild bronchospasm at the beginning of the surgery and the blood pressure was unstable during the operation, but anesthetic course was relatively uneventful. Although the patient recovered from anesthesia smoothly, she developed respiratory acidosis 45 minutes after extubation. She was intubated again and ventilated artificially with pressure support ventilation whose support level was 15 cmH2O for only three hours. We conclude that we should pay much attention not only during anesthesia but also after surgery, especially to respiratory system in patients with carcinoid syndrome.
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PMID:[Anesthetic management of a patient with carcinoid syndrome]. 835 Apr 72

The health promoting, anabolic effects of physical activity may be mediated, in part, by an exercise-associated increase in GH. However, little is known about the acute effects of diet on exercise-induced GH release. We hypothesized that a single meal could attenuate the GH response to exercise by modulating substances like somatostatin, insulin, or glucose. Eleven healthy young adults performed 10 min of high intensity, standardized cycle ergometry in the morning following an overnight fast. On separate days they ingested a noncaloric placebo liquid meal or an isovolemic, isocaloric liquid meal high in either fat or glucose. Venous blood samples were obtained before and for 90 min after exercise began, whereas gas exchange data were measured breath by breath. Peak mean oxygen consumption (VO2) was, on average, 9-fold greater than preexercise levels in all groups. Although there was no difference in preexercise GH levels, mean peak, postexercise GH was 54% lower after the high-fat meal compared with placebo (P < 0.01). Modest decreases in GH response to exercise after the high-glucose meal were not statistically significant. Mean serum somatostatin was significantly higher after the high-fat meal compared with both high glucose and placebo meals. This study demonstrates that exercise-induced GH release can be significantly attenuated by the contents of a single preexercise meal. The high fat meal increased circulating somatostatin and was associated with an inhibition of the GH secretion. The data provide a possible specific mechanism to explain how diet can acutely modulate the anabolic effects of exercise.
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PMID:Acute effects of high fat and high glucose meals on the growth hormone response to exercise. 850 Nov 45

We have demonstrated that adenosine enhances insulin-stimulated myocardial glucose uptake in situ. In the present study we determined the role of adrenergic influences and myocardial work on insulin-stimulated myocardial glucose uptake while varying intracoronary adenosine concentrations. Under pentobarbital anesthesia we instrumented mongrel dogs to obtain blood pressure, heart rate, and arterial and coronary sinus blood samples for measuring oxygen and glucose concentrations. An electromagnetic blood flow probe around the circumflex coronary artery allowed determinations of blood flow, and calculation of myocardial oxygen (MVO2) and glucose (MGU) uptakes. Somatostatin was infused i.v. (0.8 microgram/kg.min-1) along with 10 mU/kg.min-1 regular insulin, and variable quantities of glucose to maintain euglycemia. Adenosine was infused at logarithmic incremental rates (0, 0.01, 0.1, 1.0, and 10 mumoles.min-1) for 30 min each into the main left coronary arteries. Adrenergic blockade was achieved with i.v. propranolol (70 micrograms/kg bolus followed by 5 micrograms/kg.min-1 infusion), and phentolamine (95 micrograms/kg bolus followed by 9.5 micrograms/kg.min-1 infusion). Insulin infusion significantly increased MGU. Adenosine increased the maximal value for insulin-stimulated glucose uptake. Adrenergic blockade alone did not alter insulin-stimulated MGU, but reduced heart rate and MVO2. When evaluated relative to MVO2 1.0 mumoles/ml adenosine infusion increased MGU independent of work-related changes in the presence or absence of adrenergic blockade. With an adenosine infusion rate of 10 mumoles/ml myocardial glucose uptake returned to baseline. These data also support our earlier speculation that the MGU response to adenosine may be biphasic. These results suggest that antagonism of adrenergic effects by adenosine cannot account for adenosine's ability to enhance insulin's effects on glucose uptake in the heart, but that work-related influences should be accounted for in interpreting results of this kind.
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PMID:Adrenergic, insulin, and work interactions with adenosine's effects on in situ myocardial glucose uptake. 876 98

In addition to its functions as a neuronal messenger molecule, nitric oxide (NO) has also been implicated in playing a major role in ischemic damage and glutamate neurotoxicity. Using primary cortical cultures from transgenic neuronal NO synthase (NOS) null (nNOS-) mice, we definitively establish NO as a mediator of NMDA and hypoxic neurotoxicity. Neurotoxicity elicited by NMDA is markedly attenuated in nNOS- cortical cultures compared with wild-type cultures. The NOS inhibitor nitro-L-arginine is neuroprotective in wild-type but not nNOS-cultures, confirming the role of nNOS-derived NO in glutamate neurotoxicity. Confirming that the nNOS- cultures lack NMDA-stimulated nNOS activity, NMDA did not stimulate the formation of cGMP in nNOS- cultures, but markedly elevates cGMP in wild-type cultures. Both wild-type and nNOS- cultures are sensitive to toxicity induced by NO donors, indicating that pathways stimulated by NO that result in neuronal cell death are still intact in the transgenic mice. Superoxide dismutase is neuroprotective against NMDA and NO neurotoxicity in both wild-type and nNOS- cultures, highlighting the importance of superoxide anion in subsequent neuronal damage. The unknown cellular factors that endow differential resistance to NMDA neurotoxicity and differential susceptibility to quisqualate neurotoxicity remain intact in the nNOS- cultures, because the response of somatostatin-immunopositive neurons in nNOS- cultures to high-dose NMDA and low-dose quisqualate is identical to the response of NOS-immunopositive neurons in the wild-type cultures. There is no difference in susceptibility to kainate neurotoxicity between nNOS- and wild-type cultures and only a modest resistance to quisqualate neurotoxicity, confirming observations that NO-mediated neurotoxicity is associated primarily with activation of the NMDA receptor. The nNOS- cultures are markedly protected from 60 min of combined oxygen-glucose deprivation neurotoxicity compared with wild-type cultures. Wild-type cultures are protected from neuronal cell death by the NMDA receptor antagonist MK-801 and the NOS inhibitor L-nitroarginine methyl ester, but not its inactive stereoisomer D-nitroarginine methyl ester. nNOS- cultures were not additionally protected. These data confirm that activation of NMDA receptors and production of NO are primary mediators of neuronal damage after ischemic insult.
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PMID:Resistance to neurotoxicity in cortical cultures from neuronal nitric oxide synthase-deficient mice. 878 24


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