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)

We systematically reviewed the literature on gastroesophageal reflux disease (GERD) related to Helicobacter pylori therapy, and classified the GERD according to various aspects. Preexisting GERD is active GERD before H. pylori therapy, and a substantial proportion of the GERD patients improve after successful H. pylori therapy. If the GERD does not persist or recur after cessation of acid-suppressive therapy combined with H. pylori therapy, it may have been cured (cured GERD). If it recurs, it may have been masked by acid-suppressive therapy and unmasked with cessation of the therapy (pharmacologically masked and unmasked GERD). Newly developed GERD after successful H. pylori therapy is a kind of unmasked GERD arising after cure of infection (de novo unmasked GERD). The possible mechanism of the improvement of cured GERD is normalized hyperacidity associated with an improved cytokine-somatostatin-gastrin system followed by normalized G-cell activity and parietal cell mass. Preexisting GERD is not a reason to avoid eradication therapy. De novo unmasked GERD develops in a substantial proportion of patients with cured infection. The possible mechanism is increased acid exposure in the esophagus due to gastric acid increase, which is caused by a loss of neutralizing effect by ammonia, normalized cytokine-acid suppression and improvement of corpus atrophy. De novo unmasked GERD is important because GERD is recurrent and may induce adenocarcinoma of the esophagus. However, it is expected that cure of infection lowers gastric cancer incidence. Eradication therapy is recommended irrespective of the possibility that de novo unmasked GERD may have a slight increase of the risk of esophageal adenocarcinoma.
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PMID:Active and inactive gastroesophageal reflux diseases related to Helicobacter pylori therapy. 1295 Jun

Fifty percent of the world's population is infected with Helicobacter pylori; however, treatment has been insufficient to eradicate the organisms due to rising antibiotic resistance. Helicobacter infection is characterized by induction of a T helper 1 lymphocyte (Th1) immune response, hypergastrinemia, and suppressed tissue somatostatin (SOM) levels. However, the mechanism by which the immune response regulates acid secretion is not known. We show here that treatment with IFN-gamma, a Th1 cytokine, was sufficient to induce gastritis, increase gastrin, and decrease SOM levels within 7 days. In contrast, the T helper 2 lymphocyte cytokine IL-4 increased SOM levels and effectively suppressed gastrin expression and secretion. This result demonstrated reciprocal regulation of acid regulatory peptides by immune modulators. IL-4 pretreatment prevented gastritis in infected wild-type but not in SOM null mice. Thus, the ability of IL-4 to oppose a Th1-mediated infection required SOM. Immunofluorescence was used to document the presence of IL-4 receptors on the gastric SOM-secreting cell (D cell). Moreover, IL-4 stimulated SOM release from primary D cell cultures. Treatment of mice chronically infected with Helicobacter felis for 2 mo with the SOM analogue octreotide resolved the inflammation. Thus, a mechanism by which IL-4 resolves inflammation in the stomach is by stimulating the release of SOM from gastric D cells.
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PMID:Treatment of Helicobacter gastritis with IL-4 requires somatostatin. 1455 68

The somatostatin analog SMS 201-995 inhibits human peripheral blood lymphocytes (PBL) proliferation and here we demonstrate that it induces a significant increase in T cells IL-10 release as is evidenced in double fluorescence experiments. Seizing IL-10 by monoclonal antibody, SMS does not affect lymphocyte proliferation, suggesting that this cytokine is involved in the antiproliferative effect of these analog. We previously demonstrated that SMS inhibits T cells acting on the CD28 rather than the CD3-mediated signal in exactly the same way as does IL-10. Thus SMS inhibits human PBL activation by inducing IL-10 release and the consequent inhibition of the CD28 co-stimulatory pathway providing new perspectives on developing immunosuppressive strategies.
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PMID:Regulation of human peripheral blood lymphocytes IL-10 BY SMS 201-995. 1502 82

Treatment of severe Graves' ophthalmopathy (GO) is a complex therapeutic challenge and, in spite of any efforts, about one third of patients are disappointed with the outcome of treatment. Glucocorticoids (GC), orbital radiotherapy (RT), or a combination of both, are most frequently used for their immunosuppressive effects. Novel immunosuppressive treatment procedures (or novel modalities of established treatments) are reviewed in the present article. GC has recently been used by the i.v. route and this treatment modality has been shown to be more effective and better tolerated than the oral route. Promising preliminary results have been reported by some authors with somatostatin analogs, octreotide and lanreotide. The number of patients treated so far is limited, most of the results have been obtained in nonrandomized or uncontrolled studies, and comparison with other validated methods of treatment is also needed. Because of the pathogenic role of cytokines, cytokine antagonists, currently evaluated in other autoimmune diseases, have been tested with positive results also in a small series of GO patients. The use of antioxidants might also be envisioned in the future, since in vitro studies have shown that oxygen free radicals might be involved in GO. Based on the shared antigen(s) theory, total thyroid ablation, by removing the bulk of shared antigens(s), might be beneficial for the course of GO. New data on recently performed placebo-controlled studies on orbital radiotherapy are discussed, together with studies on long-term safety of orbital radiotherapy.
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PMID:Novel aspects of immunosuppressive and radiotherapy management of Graves' ophthalmopathy. 1516 4

Graves' ophthalmopathy (GO) is an autoimmune orbital disorder most commonly associated with Graves' disease. Recent studies have underscored the role that orbital cells, particularly fibroblasts and adipocytes, play in causing the increase in orbital content responsible for clinical manifestations of the disease. GO seems to be related to autoimmune reactions triggered by autoreactive T lymphocytes of thyroid origin, which recognize antigen(s) shared by thyroid and orbit. The nature of the antigen (or antigens) involved is not fully understood, but TSH receptor is likely to be involved. Cytokines secreted by T lymphocytes, macrophages and fibroblasts play an essential role in perpetuating the disease. Animal models of GO have been developed, but results have not clarified GO pathogenesis yet. Progress in the management of the ophthalmopathy has been very limited, and glucocorticoids, orbital radiotherapy and orbital decompression remain the mainstays in GO treatment. Novel treatments, such as somatostatin analogues, antioxidants, cytokine antagonists are currently under investigation, as well as the effects of total thyroid ablation. Cessation of smoking currently represents the only form of GO (secondary and tertiary) prevention.
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PMID:Graves' ophthalmopathy: state of the art and perspectives. 1516 7

Signal transducers and activators of transcription (STATs) are a family of transcription factors linked to class I cytokine receptors. In the present study, we investigated whether their distribution in the hypothalamus reflects the feedback regulation by growth hormone and what role they might play in the functioning of target neurones. We demonstrate that each of the seven known STATs has a distinct distribution in the hypothalamus. Notably, the STAT5 proteins, that are important in growth hormone (GH) and prolactin signalling in peripheral tissues, were expressed in somatostatin neurones of the periventricular nucleus and dopamine neurones of the arcuate nucleus. Because somatostatin neurones are regulated by feedback from circulating GH, we investigated the importance of STAT5 in these neurones. We demonstrate that STAT5b protein expression, similar to somatostatin mRNA, is sexually dimorphic in the periventricular nucleus of rats and mice. Furthermore, chronic infusion of male dwarf rats with GH increased the expression of STAT5b, while a single injection of GH into similar rats induced the phosphorylation of STAT5 proteins. The cellular abundance of somatostatin mRNA in STAT5b-deficient mice was significantly reduced in the periventricular nucleus, effectively reducing the sexually dimorphic expression. These results are consistent with the hypothesis that STAT5 proteins are involved in the feedback regulation of somatostatin neurones by GH, and that these neurones may respond to patterned GH secretion to reinforce sexual dimorphism in the GH axis.
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PMID:Hypothalamic STAT proteins: regulation of somatostatin neurones by growth hormone via STAT5b. 1579 71

Developing an understanding of factors that regulate development of the nervous system is important if we hope to be able to repair the nervous system after injury or disease. Suppressor of cytokine signaling-2 (SOCS2) is an intracellular regulator of cytokine signaling that blocks the inhibitory effects of growth hormone on neuronal differentiation and promotes neurogenesis. Here we examine the effect of SOCS2 over-expression on brain development by assessing density and soma size of different neuronal populations in the somatosensory cortex and striatum of SOCS2 transgenic mice compared with wildtype C57BL/6 mice. There were no significant differences in brain weight, cortical thickness or striatal area between mice of either genotype. Analysis of NeuN positive neuronal cell density showed a modest but significant 9% increase across layers 2-6 of SOCS2 transgenic cortex, while cortical interneuron subpopulations were variably affected. In the cortex, parvalbumin and somatostatin expressing neuron densities were unaffected, while calretinin and calbindin positive neuronal densities increased by 48% and 45% respectively. There was no apparent difference in glial fibrillary acidic protein positive astrocyte numbers in layers 1 or 6b of cortex. Furthermore, soma sizes of calretinin and calbindin positive cortical neurons were significantly smaller than wildtype, although there was no difference in size of Cresyl Violet-stained layer 5 projection neurons nor of parvalbumin or somatostatin positive cortical neurons. Additionally, synaptic density and dendritic branching were found to be increased in SOCS2 transgenic cortex. These effects on calretinin and calbindin positive cortical neurons and cortical neuronal circuitry were not observed in the striatum of SOCS2-Tg brains. However, striatal cholinergic interneurons were significantly smaller in SOCS2-Tg brains. At embryonic day 14.5, proliferation and apoptosis in the developing telencephalon were similar in each genotype. Therefore, over-expression of SOCS2 variably affects different cortical regions and neuronal populations, with the predominant effect appearing to be on interneurons and neuronal connectivity in the cortex.
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PMID:Analysis of neuronal subpopulations in mice over-expressing suppressor of cytokine signaling-2. 1583 29

Somatostatin (somatotropin release inhibitory factor; SRIF) peptides are widely distributed throughout the mammalian body and act through a family of genetically distinct, guanine nucleotide regulatory protein coupled (G-protein-coupled), cell surface receptors (sst(1-5)). Compelling evidence shows that SRIF and SRIF peptidyl analogs modulate vascular function, with actions upon smooth muscle and endothelium. SRIF receptors are known to exist in the carotid endothelium, a principal target for the pro-inflammatory cascade that accompanies coronary artery disease. SRIF-14 and SRIF analogs are anti-inflammatory but the molecular mechanism involved remains unclear. Since crucial steps in the endothelial inflammation response include endothelial activation by cytokines, adhesion molecule expression and cell-monocyte interactions, peptide agents that inhibit these steps might provide a novel strategy for reducing vascular inflammation. SRIF, acting through its cognate receptors, modulates a variety of intracellular effectors that are linked to inflammation including phosphotyrosine phosphatases, the extracellular regulated protein kinase 1 and 2 (ERK1/2) cascade, adenylyl cyclase and endothelial nitric oxide synthase. Directly or indirectly, SRIF also functions to inhibit endothelial cell proliferation and induce apoptosis. A detailed understanding of SRIF actions could provide a rational basis for using SRIF ligands in controlling vascular inflammation and inhibiting cytokine signaling, critical events in atherogenesis.
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PMID:Somatostatin: a hormone for the heart? 1585 32

Pancreatic cancer is a devastating disease because of the lack of early detection markers and effective treatments. It is the fourth leading cause of cancer-related death in western countries, including the United States. The mechanisms of pancreatic cancer progression remain unknown. Transforming growth factor beta (TGF-beta), a multifunctional cytokine, regulates cell growth and differentiation in healthy tissues, yet fails to do so in pancreatic cancer. Alterations of the TGF-beta and TGF-beta receptor/Smad signal transduction pathway have been implicated in pancreatic cancer. Furthermore, both the TGF-beta receptor and Smad proteins interact with a variety of cellular signal pathways, such as the somatostatin receptors (SSTRs), ERK1/2, and Wnt signal transduction cascades. This suggests that pancreatic cancer is a multi-gene-controlled malignancy and that effective treatments for pancreatic cancer should be aimed at multiple targets. In this review, we summarized the major signal intermediates involved in pancreatic cancer signal transduction pathways and specifically discussed how alterations in the regulatory functions of TGF-beta and Smad proteins allow for pancreatic carcinogenesis.
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PMID:Signal transduction in human pancreatic cancer: roles of transforming growth factor beta, somatostatin receptors, and other signal intermediates. 1631 22

Cortistatin is a recently discovered cyclic neuropeptide related to somatostatin that has emerged as a potential endogenous antiinflammatory factor based on its production by and binding to immune cells. Because human septic shock involves excessive inflammatory cytokine production, we investigated the effect of cortistatin on the production of inflammatory mediators and its therapeutic action in various murine models of endotoxemia. Cortistatin down-regulated the production of inflammatory mediators by endotoxin-activated macrophages. The administration of cortistatin protected against lethality after cecal ligation and puncture, or injection of bacterial endotoxin or Escherichia coli, and prevented the septic shock-associated histopathology, such as infiltration of inflammatory cells and intravascular disseminated coagulation in various target organs. The therapeutic effect of cortistatin was mediated by decreasing the local and systemic levels of a wide spectrum of inflammatory mediators, including cytokines, chemokines, and acute phase proteins. The combined use of cortistatin and other antiinflammatory peptides was very efficient treating murine septic shock. This work provides the first evidence of cortistatin as a new immunomodulatory factor with the capacity to deactivate the inflammatory response. Cortistatin represents a potential multistep therapeutic agent for human septic shock, to be used in combination with other immunomodulatory agents or as a complement to other therapies.
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PMID:Cortistatin, a new antiinflammatory peptide with therapeutic effect on lethal endotoxemia. 1649 2


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