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)

Using HPLC with electrochemical detection, we found that icv somatostatin (Som) 5 or 10 micrograms increased rat's pain threshold and contents of 5-HT and 5-HIAA in hippocampus, hypothalamus and brainstem, except the 5-HIAA content of brainstem in Som 5 micrograms group. However, the changes of NE among above three areas of brain were different, the NE contents of hypothalamus and brainstem significantly increased while that of hippocampus markedly decreased. After icv Som 20 micrograms, hypoxanthine and xanthine in hippocampus and hypothalamus decreased significantly, but encephaledema occurred. Som 40 micrograms icv caused necrotic changes of neurons in brain.
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PMID:[Effect of intraventricular injection of somatostatin on pain threshold, and contents of the monoamines, xanthine, hypoxanthine in rats brain]. 168 90

In vivo voltammetry involves the electrochemical detection of central oxidisable substances in situ. In association with this technique micro carbon fibre electrodes (CFE) are able to separate ascorbic acid (Peak 1) from 3,4-dihydroxyphenylacetic acid (DOPAC) plus dopamine (DA) (Peak 2) and 5-hydroxyindoleacetic acid (5-HIAAA) plus serotonin (5-HT) (Peak 3) in vitro. In vivo these biosensors detect the amine metabolites, due to their high extracellular concentration (microM) compared to the amines (nM). In addition homovanillic acid (HVA) (or 3-methoxytyramine (3-MT) in pargyline-pretreated mice) (Peak 4) and somatostatin (Peak 5) were also measured in vivo. However, potassium-stimulated release of DA has been directly monitored in pargyline pretreated mice. In addition, low concentrations (nM) of DA and 5-HT can now be selectively monitored in vitro with new biosensors coated with Nafion which repels negatively charged species including acid metabolites. In vivo, the combination of the Nafion-CFE and normal CFE allowed simultaneous measurements of release and metabolism of 5-HT, respectively. This permitted the observation that changes in 5-HT release are not necessarily reflected by changes in 5-HIAA levels. At present we are developing a Nafion biosensor to monitor basal extracellular DA. Electron microscope studies have shown radical modifications in the surface and structure of carbon fibres following chemical and electrical pretreatments, which may be involved in the development of sensitivity and selectivity displayed by the pretreated CFE towards electroactive compounds. A new approach for selective detection of neuroamines is the analysis of their stimulated fluorescence using LASER. In vitro, the fluorescence of 5-HT is in fact clearly distinguishable from that of 5-HIAA. The feasibility of this methodology in vivo using fiber optic probes will be explored.
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PMID:In vivo voltammetry with micro-biosensors for analysis of neurotransmitter release and metabolism. 197 51

The concentrations of arginine vasopressin (AVP), somatostatin (SS), and the primary brain metabolites of norepinephrine (MHPG), serotonin (5-HIAA), and dopamine (HVA) were measured in samples of lumbar CSF obtained from ten amnesics with Korsakoff's psychosis, four patients with a history of Korsakoff's psychosis who had recovered from the amnesic symptoms of this disease, and control subjects. Significant deficits were observed in the amnesic group for AVP and MHPG, but not for the other substances measured. Subjects who had recovered from the amnesic symptoms of Korsakoff's psychosis had increased concentrations of AVP and MHPG, but not of SS or the other monoamine metabolites.
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PMID:Reduced concentrations of arginine vasopressin and MHPG in lumbar CSF of patients with Korsakoff's psychosis. 242 5

CSF samples from ten healthy volunteers and 22 patients with major depression were collected by lumbar puncture at 9 a.m. and the content of monoamine metabolites, corticotropin releasing factor (CRF) and somatostatin (SRIF) was analyzed. Plasma concentrations of TSH following a TRH challenge test (200 micrograms) and plasma cortisol following dexamethasone (1 mg; DST) were also analyzed. No relationships were observed between the CRF or SRIF concentrations and either basal or post-dexamethasone cortisol concentrations. Fourteen of 21 depressed patients were DST nonsuppressors using a plasma cortisol concentration cut off point greater than or equal to 138 nmol/l. If a more conservative cut off point was used (greater than 290 nmol/l) seven out of 21 patients revealed a severity-related cortisol nonsuppression. No significant difference was observed between healthy volunteers and depressed patients with regard to TSH response to TRH. The CSF content of CRF was elevated and the content of SRIF reduced in the depressed patients. In the healthy volunteers an inverse relationship was observed between CSF concentrations of CRF and MHPG (r = -0.72; P = 0.019); no relationship was observed between the concentrations of CRF and 5-HIAA or HVA. In the depressed patients positive correlations were found between CSF concentrations of CRF and 5-HIAA (r = 0.59; P = 0.004) and between CRF and HVA (r = 0.44; P = 0.042). These data are concordant with the view that norepinephrine and serotonin may be involved in the regulation of CRF secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Monoamine metabolites, corticotropin releasing factor and somatostatin as CSF markers in depressed patients. 245 42

Monoamine metabolites, biopterin, acetylcholinesterase (AChE) activity, and somatostatin-like immunoreactivity (SLI) were determined in the lumbar cerebrospinal fluid (CSF) of 24 patients with dementia of the Alzheimer type (DAT) without myoclonus or extrapyramidal signs, in 8 patients with DAT and myoclonus, and in 14 age-matched healthy control subjects. In patients with DAT with myoclonus as compared with both DAT patients without myoclonus and control subjects, the concentrations of homovanillic acid and biopterin were significantly decreased. 5-Hydroxyindoleacetic acid was significantly lower in patients with myoclonic DAT as compared to patients with nonmyoclonic DAT, but not significantly lower than in control subjects. CSF AChE and SLI were significantly reduced in patients with DAT with or without myoclonus, as compared with control subjects, but AChE and SLI were not significantly different between dementia groups. These results suggest that DAT patients with myoclonus represent a distinct clinical and neurochemical DAT subtype.
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PMID:Cerebrospinal fluid neurochemistry in the myoclonic subtype of Alzheimer's disease. 246 3

The increased knowledge of the pathobiology of gastrointestinal carcinoid (neuroendocrine) tumours and the improved therapeutic possibilities have brought a demand for more precise diagnosis. Although the carcinoid tumours can often be tentatively recognized in routinely processed microscopic slides, their more accurate identification requires additional diagnostic procedures. General neuroendocrine markers such as the argyrophil reaction of Grimelius and immunohistochemistry with application of antibodies against chromogranin A and of neuron-specific enolase are discriminatory staining methods which are used to reveal the neuroendocrine origin of almost all highly differentiated carcinoid tumours of the gastrointestinal tract. Mid-gut carcinoids, which predominate among these tumours almost unexceptionally contain serotonin. This biogenic amine can be demonstrated by the argentaffin reaction of Masson, serotonin immunoreactively or by formalin-induced fluorescence. The characteristic staining pattern of mid-gut carcinoids is almost invariably preserved in the metastatic deposits and consequently the staining methods for identifying serotonin can also be used on metastases to reveal a primary mid-gut carcinoid. The enterochromaffin-like (ECL) cell carcinoids of the body and fundic area of the stomach often seen in association with pernicious anaemia are argyrophil with the Sevier-Munger silver stain. Other neuroendocrine tumours, viz. antral, duodenal and rectal carcinoids should be studied by a battery of relevant peptide hormone antisera for adequate diagnosis. During the last decade new peptide hormones have been found in circulation in patients with carcinoid tumours, but serotonin and urinary 5-HIAA are still the most important markers for carcinoids of the mid-gut origin. Other clinically useful tumour markers are chromogranin A + B, pancreatic polypeptide, human chorionic gonadotropin alpha and beta subunits. For localizing procedures, angiography is the most reliable investigative method for primary tumours in the gut, whereas CT-scan and ultrasound investigations are good for detection of liver metastases. During the last five years, the therapy for malignant carcinoid tumours has been considerably improved. Chemotherapy has only revealed objective response rates in about 10-30% of the patients giving median survivals from start of therapy of about 10 months. Recently treatment with alpha interferons and the new somatostatin analogue octreotide have given objective responses in 50-75% of patients with malignant mid-gut carcinoid tumours. These patients have now a median survival from start of therapy of 70 months when treated with alpha interferons. In the future new therapies will come into use such as monoclonal antibodies and perhaps also agents blocking different growth factors.
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PMID:Gastrointestinal carcinoid tumours. Histogenetic, histochemical, immunohistochemical, clinical and therapeutic aspects. 266 60

A review is given on the clinical features of carcinoid syndrome including symptomatology, diagnostics, biochemistry and treatment. We have reviewed the literature on current therapy of carcinoid patients with special emphasis on the use of the somatostatin analogue SMS 20-1995. In addition, we present data on the effects of SMS 201-995 on indices of a clinical, biochemical and tumor growth. Diarrhea is abolished or significantly reduced in 75% of patients, flushing improves in 100%, wheezing in 100% with a decrease in airways resistance, and in one patient myopathy has improved. Blood serotonin is notoriously resistant to intervention and urinary 5-HIAA will decrease in 75% of causes but subsequently rebounds in 38%. Tumors, in general, continue to grow, but this may be slowed or in rare cases tumor growth is arrested. In individual instances the tumor may even infarct, leading to spontaneous cure. Tumors secreting PP, ACTH and calcitonin may be particularly resistant to treatment, whereas VIP secreting tumors appear to be sensitive.
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PMID:Clinical features of carcinoid syndrome and the use of somatostatin analogue in its management. 266 49

Cerebrospinal fluid from 31 normals and two groups of phenomenologically similar schizophrenics (n = 72) were collected by identical methods. Radioimmunoassay of CSF was carried out for somatostatin, bombesin, and cholecystokinin. One group of schizophrenics had increased baseline somatostatin and cholecystokinin, and decreased bombesin. No CSF gradient effect was found for the peptides nor were their levels affected by probenecid or pimozide treatment. An inverse correlation was found between bombesin and psychosis rating. Intercorrelation between the peptides and HVA, 5-HIAA, and MHPG were not significant.
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PMID:Cerebrospinal fluid cholecystokinin, bombesin and somatostatin in schizophrenia and normals. 285 35

Positron emission tomography (PET) makes it possible to study effects of medical treatment in vivo. Carcinoid tumors with liver metastases, especially those of midgut origin, produce serotonin via the precursors tryptophan and 5-hydroxytryptophan (5-HTP) and this overproduction contributes to the clinical symptoms of the carcinoid syndrome. Seven patients with histopathologically verified neuroendocrine tumors and liver metastases, five of whom with ileal carcinoids, one a lung carcinoid and one an endocrine pancreatic tumor, were included in the study. All patients had elevation of urinary 5-HIAA with the exception of one patient with a solitary liver metastasis of midgut origin. After an intravenous injection of 11C-5-HTP, PET was performed and the uptake of radioactivity in tumor tissue, normal liver and plasma were compared. All patients with elevated urinary 5-HIAA and also the patient with a solitary liver metastasis and normal urinary 5-HIAA had high accumulation and signs of a high rate of binding of 5-HTP in the liver metastases. The uptake was relatively homogeneous in midgut carcinoid liver metastases but in large necrotic metastases the radioactivity was localized to the periphery. In three patients PET examination was repeated after 3 months of interferon treatment and in agreement with circulating tumor markers and ultrasonography the uptake of 5-HTP was unchanged. Another patient who received the somatostatin analog somatuline progressed on treatment and accordingly the uptake of 5-HTP also increased. The experience with PET in neuroendocrine gastrointestinal tumors is very limited. Our results so far indicate that 5-HTP can be used to visualize serotonin-producing neuroendocrine tumors and furthermore it might prove to be of value to monitor the effects of treatment, possibly also as an early predictive test of the outcome of treatment.
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PMID:Positron emission tomography (PET) in neuroendocrine gastrointestinal tumors. 768 63

Fifty-five patients with metastatic carcinoid tumor were treated with the long-acting somatostatin analogue octreotide. Nineteen received in addition alpha-interferon when octreotide had failed. During octreotide treatment reduced flush and/or diarrhea was seen in 70% of the patients, 37% showed > 50% decrease in urinary 5-HIAA for a median of 8 months. A further 49% experienced stabilization of their disease and only 14% progressed. One patient showed reduced tumor size. Of the 19 patients given alpha-interferon in combination with octreotide, 72% showed significant reduction in urinary 5-HIAA for a median of 10 months. Twenty-two percent became stabilized and only 6% progressed. A symptomatic improvement was seen in 49%. The combination was well tolerated. Our data confirm previous studies, showing that octreotide is useful for treatment of the carcinoid syndrome. Our results also indicate that the combination of octreotide and alpha-interferon might be of beneficial value for long-term management of this disease.
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PMID:Long-term management of the carcinoid syndrome. Treatment with octreotide alone and in combination with alpha-interferon. 768 65


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