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)

Growth hormone (GH) hypersecretion is well documented in insulin-dependent diabetes mellitus (IDDM). Somatostatin inhibits GH in acromegalics and healthy subjects although data on its inhibitory effects on high GH levels in IDDM patients are controversial. The effect of treatment with the somatostatin analogue octreotide ("Sandostatin") on GH secretion, IGF1 levels and metabolic control was investigated in insulin-dependent diabetics. Growth hormone and blood glucose were measured at hourly intervals whilst IGF-I was measured every 6 hours during the 24-h period before and after 7 days' treatment with octreotide (200 micrograms subcutaneously three times daily) in 10 C-peptide negative diabetics. Octreotide significantly reduced mean 24 h GH profile (7.2 +/- 0.7 mU/L before; 5.2 +/- 0.5 mU/L on octreotide, p less than 0.01), IGF-I levels (0.62 +/- 0.06 before; 0.47 +/- 0.05 on octreotide, p less than 0.005) mean 24 h blood glucose (14.4 +/- 0.5 mmol/L before; 12.6 +/- 0.4 mmol/L on octreotide, p less than 0.001) and daily insulin requirements (44.8 +/- 3.0 IU before; 37.2 +/- 3.0 IU on octreotide, p less than 0.02). The shape of 24 h GH profile curve changed significantly on octreotide treatment (p less than 0.05) when it consisted of three nadirs and three peaks closely linked with the time of octreotide administration. Moderate (abdominal discomfort) to severe hypoglycaemia) transient side effects have been observed in all treated patients. The results of this study showed that short-term treatment with octreotide given s. c. every eight hours modulates the pattern of GH secretion in C-peptide negative insulin-dependent patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of the somatostatin analogue octreotide on growth hormone secretion in insulin-dependent diabetics without residual insulin secretion. 151 89

Ten patients (seven women, three men) with active acromegaly, five previously treated and five newly diagnosed, were included in an open-label prospective trial of 3 daily subcutaneous injections of the long-acting somatostatin analogue SMS 201-995 (Sandostatin) at increasing doses in order to obtain maximum growth hormone (GH) suppression. Four patients had received surgery, radiotherapy or bromocriptine. SMS 201-995 doses were increased in a stepwise fashion from 100 micrograms every 8 h (three times daily) to 200, 300 and finally 500 micrograms three times daily at monthly intervals if mean serum GH values failed to decrease to undetectable levels in over 75% of the samples. The optimal dose was maintained for up to 28 months. Significant clinical improvement of headache, soft tissue swelling, facial features, hyperhidrosis and paraesthesia occurred in all patients. Mean 12-h GH levels were significantly suppressed in four patients and fell to normal values in four. Suppression of GH levels was not achieved in two patients. Comparison of the mean interindividual GH values shows that the optimal efficacious dose is 100 micrograms t.i.d. in 7/10 patients. Somatomedin-C (SM-C) was also significantly reduced to below 50% of pretreatment levels in nine patients in whom it was measured. The subsequent increments of SMS 201-995 up to 500 micrograms three times daily did not produce further clinically relevant GH or SM-C suppression. Pituitary tumour shrinkage occurred in five patients. Thyroid function remained normal. Impaired glucose tolerance occurred in four patients. Side-effects (diarrhoea, abdominal discomfort) were mild and transient. Asymptomatic gallstones occurred in three patients on 1500 micrograms/day and one patient on 600 micrograms/day after 6-12 months treatment. This dose-finding study shows that 100 micrograms three times daily SMS 201-995 is an effective therapy for most of the acromegalic patients we treated.
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PMID:Clinical and biochemical effects of incremental doses of the long-acting somatostatin analogue SMS 201-995 in ten acromegalic patients. 220 Jun 20

To determine whether sc injections of a somatostatin analog (SMS 201-995) every 2 h (q2h) is more effective than sc injections every 8 h (q8h) in achieving a constant suppression of GH levels and a more satisfactory clinical response, we studied 10 patients with acromegaly (4 newly diagnosed and 6 previously treated with bromocriptine/pituitary irradiation/transfrontal hypophysectomy). The dose of SMS 201-995 was increased from 300 micrograms/day to a maximum of 600 micrograms/day when the mean serum GH (hourly samples for 12 h) failed to be suppressed to undetectable levels in over 75% of the samples. Five patients received a 200-micrograms sc injection q8h (600 micrograms/day), and the other 5 received sc injections q2h [418 +/- 46 micrograms/day (mean +/- SE); range, 288-504 micrograms/day]. In the group receiving q2h sc SMS 201-995 there was a marked suppression of mean GH from a basal level of 77.3 +/- 24.7 mU/L to less than 5 mU/L in all five subjects. In the group receiving q8h sc SMS 201-995, mean GH was suppressed from a basal level of 82.2 +/- 21.7 to 15.4 +/- 3.3 mU/L after 6 months of therapy, and none of the patients had a mean GH level consistently less than 5 mU/L. Despite the difference in the level of GH suppression, mean serum somatomedin-C levels were decreased promptly in both groups of subjects. Associated with the decrease in somatomedin-C levels there was a marked clinical response in both groups, but improvement in clinical features and decreases in hand volumes and ring size occurred earlier in the group receiving SMS 201-995 q2h. Significant tumor shrinkage (25% to greater than 50% reduction) was observed in two patients receiving q2h injections, while a 25-50% reduction in tumor size was noted in another patient receiving q8h injections. Because of the small doses of SMS 201-995 used side-effects of abdominal discomfort and flatulence were mild and rapidly disappeared. Our results show that increasing the frequency of sc administration of the somatostatin analog from q8h to q2h leads to more marked and consistent suppression of GH levels and more rapid improvement of clinical signs. Increasing the frequency of delivery of SMS 201-995 may be an alternative to increasing the dose in some patients with acromegaly.
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PMID:Comparison of the effectiveness of 2-hourly versus 8-hourly subcutaneous injections of a somatostatin analog (SMS 201-995) in the treatment of acromegaly. 266 25

Nine acromegalic patients, six previously untreated, were studied before and after 3-15 months of treatment with a long-acting somatostatin analogue (SMS 201-995; 100 micrograms injected s.c. three times daily). During treatment, the mean (+/- SEM) 24-h GH concentration fell from 82 +/- 22 mIU/l to 33 +/- 7 mIU/l (P less than 0.001), and eight of the 9 patients showed a reduction of at least 50% in GH levels in the fasting state and/or during a glucose tolerance test. There was a significant 30% fall in serum concentrations of insulin-like growth factor (IGF-1) with SMS. All patients showed rapid clinical improvement, with diminished sweating and headaches, and reduction in skinfold thickness, hand volumes and finger size. Computer tomographic scanning of the pituitary in eight patients showed no change in the size of the pituitary tumour during treatment. The only side-effects of SMS noted were transient abdominal discomfort and loose stools in two patients on initiating therapy. Although fasting plasma glucose concentration did not change during treatment (5.4 +/- 0.3 vs 5.5 +/- 0.3 mmol/l), mean 24-h plasma glucose concentration was higher with SMS (6.6 +/- 0.5 mmol/l vs 6.0 +/- 0.4 mmol/l; P less than 0.02). Mean 24-h plasma insulin concentration fell from 87 +/- 11 mIU/l before treatment to 39 +/- 6 mIU/l during treatment (P less than 0.005). No change in other anterior pituitary hormones was observed. SMS appears to be a safe, rapidly effective, long-term treatment for certain patients with acromegaly.
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PMID:Effective long-term treatment of acromegaly with a long-acting somatostatin analogue (SMS 201-995). 287 56

One hundred and three acromegalic patients from 14 medical centers were enrolled in this study to determine the efficacy and safety of the somatostatin analog, octreotide acetate, during long term treatment. Seventy percent of the patients had undergone previous surgery or radiation treatment. Octreotide was initiated at a dose of 100 micrograms, sc, every 8 h and gradually increased to a maximum of 1500 micrograms daily depending upon the individual patient's clinical and biochemical response [GH and insulin-like growth factor I (IGF-I) reduction]. The mean duration of treatment was 24 months (range, 3-30 months). However, most patients were treated for a mean of 30 months, because this study took place after an initial 6-month study previously reported. Mean serum GH fell from 30.9 micrograms/L (range, 2.7-350) to 5.7 micrograms/L (range, 0.6-59) at the 3 months visit and remained suppressed (P < 0.001). Plasma IGF-I concentrations were also significantly reduced and remained in the normal range for at least half of the treatment visits in 56 of 87 patients (64%) treated for 12-30 months. Patients with higher initial GH concentrations were less likely to normalize IGF-I concentrations during treatment (P < 0.001). There was no evidence of drug tachyphylaxis in those patients who continued taking stable doses of medication. With some exceptions, dose increments above 800 micrograms daily in 31 patients did not provide additional benefit in terms of GH and IGF-I reduction. Headache, excessive perspiration, fatigue, and joint pain were ameliorated in 83-95% of patients. Mean finger circumference was decreased significantly at the 12 month visit (P < 0.05). The most common adverse events reported were diarrhea, abdominal discomfort, loose stools, and nausea; these symptoms usually disappeared within 3 months of treatment. Five patients discontinued octreotide because of adverse events. Of 102 patients with normal baseline ultrasound examinations of the gallbladder, 24 patients (23.5%) developed gallstones (usually during the first year of treatment), and 21 patients developed sludge alone. Gallstone formation was not related to the dose of octreotide. Most patients with cholelithiasis were asymptomatic, and none developed cholecystitis. These observations suggest that octreotide is a valuable long term medical treatment for acromegaly.
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PMID:Safety and efficacy of long-term octreotide therapy of acromegaly: results of a multicenter trial in 103 patients--a clinical research center study. 767 22

Changes in immunoreactive (ir)-somatostatin, substance P, and calcitonin gene-related peptide concentrations of the human gastric mucosa were examined in subjects with nonulcer dyspepsia (NUD) and peptic ulcer to clarify the relationship between these peptides and dyspeptic symptoms. Fifty-six patients with NUD were divided into two subject subgroups as follows: 22 patients with upper abdominal discomfort, nausea, and/or vomiting (motility disorder group) and 34 patients complaining of upper abdominal pain [ulcer-like disorder (UD) group]. These patients were compared with either an age- and sex-matched group of asymptomatic outpatients without any organic disease (control group: n = 51), or to a group with peptic ulcer (PU group: n = 30). Ir-somatostatin concentrations of the gastric mucosa were significantly higher in UD group than in PU, motility disorder, or control group, and ir-substance P concentrations in the UD group were higher than in the PU group. No difference in ir-calcitonin gene-related peptide concentrations was observed among the four groups. These results indicate that there may be two distinct subgroups in NUD, and that NUD is not just a stage within the spectrum of peptic ulcer disease from the viewpoint of several gastrointestinal-hormone concentrations of the human gastric mucosa.
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PMID:Immunoreactive-somatostatin, substance P, and calcitonin gene-related peptide concentrations of the human gastric mucosa in patients with nonulcer dyspepsia and peptic ulcer disease. 768 83

Unresectable meningioma is the cause of a serious clinical problem, for whom no satisfactory mode of treatment is currently available. Meningiomas are known to have receptors for diverse hormones. In this sense, somatostatin receptors were found in every meningioma specimen studied in a recent report. In addition, somatostatin has been able to inhibit meningioma cell proliferation in vitro. A brief report of clinical use of somatostatin long-life analogue octreoctide upon three patients diagnosed of unresectable meningioma is here presented. Doses used were gradually increased up to 1000, 900 and 1500 micrograms/24 h during 16, 6 and 7 weeks, respectively. There was an almost perfect tolerance to the drug (in one case a mild and transient abdominal discomfort and diarrhea could be observed). An important alleviation of headaches in 2 cases, and a transient but objective improvement in ocular movements and signs in 1 case were noticed. No change (neither growth nor shrinkage) was observed by CT scan at the end of treatment course in the three cases studied. In 1 case a partial resection was performed and tissue specimen was found to contain somatostatin receptors. Although in our very limited experience no brilliant results are presented, duration of treatment or doses used could have been insufficient. Data herein presented seem to support recently reported findings in which no growth inhibition of meningioma cells cultured in vitro by adding octreoctide to the medium was observed. So, in our opinion, clinical use of octreoctide on unresectable meningioma deserves further experience, that must be carried out with great caution.
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PMID:Clinical use of octreotide in unresectable meningiomas. A report of three cases. 793 48

Immunoreactive-somatostatin (ir-SS) concentrations of the gastric mucosa and mood state in patients with functional dyspepsia were examined. The subjects were 12 patients with upper abdominal discomfort, nausea and/or vomiting (motility disorder group) and 14 patients complaining of upper abdominal pain (ulcer-like disorder group) for more than a month without any organic upper-gastrointestinal tract disease proven by endoscopy. These patients were compared with either an age- and sex-matched group of asymptomatic outpatients without any organic disease (control group: n = 26) or to a group of patients with peptic ulcer (n = 19). Somatostatin concentrations of the stomach were measured by radio-immunoassay, and the mood state of each subject was assessed by Manifest Anxiety Scale (MAS) and Self-rating Depression Scale test. Immunoreactive-somatostatin concentrations of the gastric mucosa were significantly higher in the ulcer-like disorder group than in the peptic ulcer, motility disorder or control group, and gastric juice levels were higher in the ulcer-like disorder group. The psychometric tests showed that the motility disorder group was more depressive than the ulcer-like disorder group, but there were no differences between the motility disorder, ulcer-like disorder and peptic ulcer group in MAS scores or environmental factors. These results indicate that there may be two different subgroups in functional dyspepsia influenced by both ir-SS concentration of the stomach and/or mood state.
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PMID:Immunoreactive-somatostatin concentrations of the human stomach and mood state in patients with functional dyspepsia: a preliminary case-control study. 810 48

Small cell carcinoma (SCC) of the pancreas is a rare malignancy with an extremely poor prognosis. We present the case of a 74-year-old man with a 2-month history of upper abdominal discomfort who was diagnosed with SCC of the pancreas tail, involvement of peripancreatic and mesenteric lymph nodes and multiple liver metastases (extended disease). A CT scan and a positive somatostatin receptor scintigraphy showed no evidence of a primary lung tumour. The diagnosis of a SCC was confirmed by biopsy. Local tumour control could be achieved by gemcitabine once a week and a long-acting somatostatin analogue once a month, but liver metastasis showed progress. Thus, 5-fluorouracil on a weekly basis was started. The patient died 8 months after diagnosis and had not been hospitalised in the meantime.
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PMID:Poorly differentiated small cell carcinoma of the pancreas. A case report and review of the literature. 1533 3

Pasireotide (SOM-230) is a small somatostatin (SST) analog that is being developed by Novartis Pharma AG for the potential treatment of acromegaly, Cushing's disease and neuroendocrine tumors; the compound is currently in phase III clinical trials for Cushing's disease. Pasireotide exhibits high binding affinity to four of the five human (h)SST receptor subtypes, with IC50 values for hSST5 > hSST2 > hSST3 > hSST1; the compound displays no affinity for hSST4. The affinity profile of pasireotide resembles the profile of endogenous SSTs--a feature that is favorable given that different tumors exhibit differing SST receptor expression profiles. Pasireotide also exhibits a longer half-life than the clinically available SST analogs octreotide or lanreotide. Thus, this compound may be a better therapeutic agent than other analogs. In phase II clinical trials, pasireotide inhibited growth hormone (GH) secretion from GH-secreting pituitary tumors, controlled symptoms associated with metastatic carcinoid tumors, and inhibited adrenocorticotropic hormone secretion in Cushing's disease. However, a major advantage for pasireotide compared with octreotide was not demonstrated. Commonly encountered side effects for the compound included mild to moderate gastrointestinal events (diarrhea, abdominal discomfort, nausea and vomiting). The efficacy of pasireotide and any potential advantage over current therapies will need to be tested or validated in larger phase III clinical trials.
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PMID:Pasireotide--a somatostatin analog for the potential treatment of acromegaly, neuroendocrine tumors and Cushing's disease. 1804 87


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