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)

The pathophysiology and treatment of esophageal varices are reviewed. The cause of esophageal varices is generally thought to be portal hypertension. The most common cause of portal hypertension in the United States is alcoholic liver disease. Other etiologies of portal hypertension include portal vein thrombosis, schistosomiasis, and inferior vena caval obstruction by tumor or thrombus. Although short-term balloon tamponade and vasopressin infusion will control acute variceal hemorrhage, they do not affect the underlying problem and are not indicated for long-term treatment of esophageal varices. Surgical procedures either ablate varices or lower portal vein pressure. Portal-systemic shunts have emerged as the preferred surgical technique, but the superiority of total versus selective shunts is unclear. Pharmacological management can include administration of vasopressin, somatostatin, verapamil, or isosorbide dinitrate for short-term treatment or verapamil, isosorbide dinitrate, or propranolol for prolonged treatment. Use of sclerotherapy for treatment and prevention of hemorrhage from esophageal varices has grown recently. Because there are several sclerosing agents and combinations of agents available for use, assessing their relative safety and efficacy is difficult. Innovative approaches to management of varices include a shunt procedure involving the left lung, use of a tissue adhesive, and laser treatment. Because of its effectiveness and ease of administration, sclerotherapy appears to be a rational method of treatment for acute hemorrhage from esophageal varices.
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PMID:Treatment of esophageal varices. 264 81

Substance P (SP) and somatostatin 1-14 (SOM) have immunoregulatory properties. Cells within the granulomas of murine schistosomiasis mansoni make both. SP enhances, whereas SOM inhibits soluble egg Ag (SEA)-induced, IFN-gamma production. IFN-gamma is important during IgG2a isotype switching. Thus, we investigated whether SP or SOM could affect IgG2a production in murine schistosomiasis. Our results show that SEA and rIFN-gamma stimulate splenic IgG2a secretion in murine schistosomiasis. Moreover, SP at > or = to 10(-10) M substantially increased both polyclonal as well as SEA-specific, IgG2a secretion from spleen cells challenged with SEA. However, cells exposed to SOM at > or = 10(-10)M showed strong inhibition. Also, both SP and SOM modulated the frequency of IgG2a-producing cells. Splenic IgG2a production in response to SEA, SP, and SOM required the presence of Thy 1.2+ cells, whereas, rIFN-gamma- induced IgG2a synthesis did not. Also, experiments using irradiation lymphocytes showed that SP, SOM, or rIFN-gamma modulation of IgG2a release was not dependent on cell proliferation. The highly specific SP receptor antagonist, CP-96,345, completely inhibited the effect of SP but not SOM on IgG2a release. This suggests that SP acted through an authentic NK-1 receptor and that SOM required a different receptor interaction. Granuloma cells secreted IgG2a constitutively. Yet, neither SEA, SP, SOM, rIFN-gamma, nor blocking anti-IFN-gamma mAb could modulate this constitutive IgG2a release during short term culture conditions. Moreover, the IgG2a secretion also continued in the absence of Thy 1.2+ lymphocytes. However, mice treated with CP-96,345 or octreotide (SOM agonist) in vivo produced granulomas that made little or no IgG2a. Spleen cell experiments showed that SEA, SP, SOM, and rIFN-gamma could only affect SEA-induced, IgG2a production during early stages of Ag stimulation. Thus, unlike the spleen, it is probable that the granulomas contain mostly activated B cells that have completed switch recombination.
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PMID:Substance P and somatostatin can modulate the amount of IgG2a secreted in response to schistosome egg antigens in murine schistosomiasis mansoni. 750 19

In murine Schistosomiasis mansoni, granuloma eosinophils make SP. We investigated whether SP affects lymphokine secretion in murine schistosomiasis. SP at > or = 10(-10) M, and other tachykinins at much higher concentrations, substantially increased IFN-gamma secretion from spleen or granuloma inflammatory cells primed in vitro by suboptimal stimulatory concentrations of egg Ag or mitogen. Cells receiving maximal antigenic or mitogenic stimulation were affected marginally. Also, tachykinins induced no IFN-gamma from resting cells receiving no Ag or mitogen stimulation. There are three distinct tachykinin receptors, called NK-1, NK-2 and NK-3. SP binds the NK-1 receptor with highest affinity. Specific NK-1 receptor antagonists blocked all tachykinin-induced, IFN-gamma secretion. An NK-2 receptor inhibitor had no effect. Thus, SP and other tachykinins were acting through an NK-1 receptor. Inflammatory cells from 4-day-old granulomas cultured in vitro secrete IFN-gamma. Yet, there was no measurable IFN-gamma when SP receptor antagonists were added to the cultures. Moreover, animals treated in vivo with the NK-1 receptor antagonist CP-96,345 produced smaller granulomas. This suggested that endogenous SP may be necessary for normal induction of granuloma IFN-gamma secretion and a normal granulomatous response. Granuloma macrophages make somatostatin (SOM) that can decrease IFN-gamma secretion. Yet, IFN-gamma secretion was unaffected when both SP and SOM were in the cell cultures. In conclusion, SP modulates Ag-driven IFN-gamma secretion through a NK-1 receptor. Also, SP and SOM may be components of a natural circuit within inflammation that regulates IFN-gamma production.
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PMID:Substance P modulates antigen-induced, IFN-gamma production in murine Schistosomiasis mansoni. 768 34

The role of somatostatin (SRIF) in controlling the granulomatous inflammatory response to infection with the parasite Schistosoma mansoni was explored in mice. The murine granulomas contain SRIF-14. Immunoreactive SRIF and prepro SRIF localize in the cytoplasmic granules of macrophages within the granulomas. The granulomas contain mRNA for prepro SRIF and are not innervated. The production of SRIF by the inflammatory cells appears to be inducible. The granulomas contain mRNA for the SRIF receptors sst2A and sst2B, which are expressed mainly on CD4- T lymphocytes and bind SRIF-14 with high affinity. Antigens from the schistosome eggs stimulate granuloma T lymphocytes to produce cytokines. Interferon-gamma (IFN-gamma) is one such cytokine made by CD4+ T lymphocytes. SRIF-14 suppresses antigen-induced IFN-gamma production from granuloma cells, and this effect is blocked by anti-sst2 antibody. SRIF was shown to inhibit IFN-gamma-induced immunoglobulin G2a (lgG2a) synthesis in murine schistosomiasis. SRIF also blocks substance P (SP)-stimulated IFN-gamma and lgG2a secretion. Schistosome-infected animals treated with the SRIF analog octreotide form smaller granulomas that secrete substantially less IFN-gamma and lgG2a. Unpublished observations suggest that SRIF does not modulate schistosome egg antigen- or concanavalin A-stimulated granuloma lymphocyte proliferation in murine schistosomiasis. In conclusion, SRIF may be an important factor in the control of the granulomatous inflammatory response in murine schistosomiasis.
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PMID:Granulomas in murine schistosomiasis mansoni have a somatostatin immunoregulatory circuit. 876 93

Murine schistosomiasis mansoni is a parasitic disease in which flukes living in the portal vein of the host produce ova that deposit in the liver and intestines. In these organs, ova release antigens that induce chronic, focal granulomatous inflammation. IFN-gamma is an inflammatory cytokine important in macrophage activation and B-cell differentiation. A substance P (SP)/somatostatin (SOM) neurokine immunoregulatory circuit controls IFN-gamma production in schistosome granulomas. SP stimulates, while SOM inhibits IFN-gamma release, modulating IFN-gamma-dependent circuitry. SP and SOM function through interaction with authentic SP and SOM receptors located on granuloma T cells. Also, the granulomas produce authentic SP and SOM14, as evidenced by the presence of mRNA and product. The granulomas have no nerves. This, and other data suggest that the inflammatory cells make these neurokines. Granuloma macrophages produce SOM. Macrophages from various sources express SOM mRNA in response to LPS, IFN-gamma, IL-10 or several other inflammatory mediators. Thus, the inflammation of murine schistosomiasis has a complete SP/SOM immunoregulatory circuit, which in turn is subject to immunoregulation.
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PMID:The substance P and somatostatin interferon-gamma immunoregulatory circuit. 962 80

Substance P (SP) and somatostatin (SOM) are made at mucosal surfaces and sites of inflammation. There is a SP/SOM immunoregulatory circuit that modulates the IFN-gamma response in murine schistosomiasis. SP enhances, while SOM decreases, IFN-gamma secretion. Various inflammatory mediators induce macrophages to make SOM, but no known factor limits this expression. It was discovered that SP regulates SOM synthesis. Splenocytes from normal, uninfected mice cultured with LPS, IFN-gamma, or IL-10 for 4 h strongly expressed SOM mRNA, but failed to do so in the presence of SP. The inhibition with 10(-9) M SP was > 85% shown by quantitative PCR. Also, splenocyte SOM content decreased from 1048 +/- 275 to < 10 pg/4 x 10(8) cells following SP exposure. Immunohistochemistry identified SOM solely within splenic macrophages following cytokine stimulation. Mice infected with Schistosoma mansoni form granulomas in the liver and intestines resulting from deposition of parasite eggs in these organs. The granulomas contain macrophages that make SOM constitutively. SP at 10(-8) M decreased SOM mRNA expression > 90% in dispersed granuloma cells cultured for 4 h or longer. Specific SP receptor antagonists blocked SP suppression of SOM expression in splenocytes and dispersed granuloma cells, showing that an authentic SP receptor mediated the regulation. Additional studies revealed that IL-4 antagonized the SP effect in the spleen. It is concluded that in granulomas and splenocytes from mice with schistosomiasis and in splenocytes from uninfected animals that 1) SP inhibits macrophage SOM induction and ongoing expression at the mRNA and protein levels acting through the SP receptor, and 2) IL-4 can antagonizes this SP effect.
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PMID:Substance P regulates somatostatin expression in inflammation. 983 21

Somatostatin is part of an immunoregulatory circuit that helps limit interferon-gamma (IFNgamma) production at sites of chronic inflammation. In murine schistosomiasis. parasite eggs induce focal, chronic granulomatous inflammation in the liver and intestines. These granulomas produce somatostatin 1-14 and express somatostatin receptor subtype number 2 (SSTR2), which is the exclusive somatostatin receptor present in this inflammation. Granuloma and splenic macrophages as well as macrophage cell lines make somatostatin. There appears to be no other inflammatory cell source of the peptide. Various inflammatory mediators induce this expression, whereas substance P inhibits somatostatin production. Somatostatin can suppress IFN-gamma secretion from T cells via interaction with the SSTR2 receptor expressed on these cells. Other cells within the granuloma also display SSTR2. The effect of somatostatin on these other cell types remains unknown. The thymus of normal mice has a complete somatostatin regulatory circuit. The thymic epithelial and dendritic cells make somatostatin. Like the granulomas of murine schistosomiasis, the thymus expresses only SSTR2. Somatostatin likely has an important role in thymic T cell education and selection.
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PMID:The somatostatin immunoregulatory circuit present at sites of chronic inflammation. 1106 35

This review explores the possible modulatory role of the neuropeptide somatostatin in the outcome of Schistosoma-caused morbidity in man. Somatostatin could play an important role in Schistosoma mansoni-man interactions via its influence on intersystem signalling; therapeutically, via its direct effect on Schistosoma-caused morbidity (fibrosis, granuloma size, portal hypertension, variceal bleeding); and via immunomodulation of Schistosoma-induced inflammatory responses in the liver and intestines. In schistosomiasis-endemic regions two interesting patterns of infection emerge. First, the intensity of infection is higher in children than in adults; secondly, at any given time, only a fraction of Schistosoma-infected individuals develop Symmer's pipe-stem fibrosis. These morbidity patterns cannot be explained on the basis of acquired immunity alone. Somatostatin has an inhibitory effect on hormone, immune and physiological body functions like growth hormone secretion, Interferon (IFN) gamma production, collagen I and III formation and hepatic stellate cell activation. Levels of somatostatin secreted endogenously by man upon the onset of Schistosoma infection may be one factor regulating the activity of the above, and thereby fibrosis in the host. The neuropeptide hormone somatostatin may determine pre-disposition to Schistosoma-caused morbidity.
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PMID:The role of somatostatin in schistosomiasis: a basis for immunomodulation in host-parasite interactions? 1155 24

A better insight into the mechanisms regulating the human body can lead to improved knowledge of the patho-physiological processes of many diseases. New therapeutic possibilities can be devised at the level of these regulatory mechanisms. Somatostatin is one of the major regulatory hormones in the central nervous system (CNS) and digestive system. Its wide variety of activities means it is implicated in a broad range of conditions. One symptom common to both the acute and chronic stages of schistosomiasis is intestinal pathology characterized by abdominal pain, diarrhoea that is bloody in more chronic stages, nausea and fever. Some chronic patients develop severe hepatosplenic fibrosis, leading to fatal oesophageal variceal bleeding. In this review we assess the therapeutic potential of somatostatin in the treatment of intestinal pathology associated with schistosomiasis. The activity of somatostatin is mediated via binding to specific cell surface receptors. While we are making progress in studies of the expression and regulation of the different somatostatin receptors, the true role and distribution of each receptor subtype is far from fully understood. Animal models will help to define the specific role of individual receptors in physiological and pathological conditions. The regulation of receptor expression as well as receptor internalization can give us insight into the effect of exogenous somatostatin on schistosomiasis-mediated intestinal pathology, as well as its modulation by intrinsically produced somatostatin levels.
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PMID:Somatostatin and intestinal schistosomiasis: therapeutic and neuropathological implications in host-parasite interactions. 1173 38

Neurocysticercosis, a parasitic infection of the human central nervous system caused by Taenia solium, is a leading cause of seizures. Seizures associated with neurocysticercosis are caused mainly by the host inflammatory responses to dying parasites in the brain parenchyma. We previously demonstrated sequential expression of Th1 cytokines in early-stage granulomas, followed by expression of Th2 cytokines in later-stage granulomas in murine cysticercosis. However, the mechanism leading to this shift in cytokine response in the granulomas is unknown. Neuropeptides modulate cytokine responses and granuloma formation in murine schistosomiasis. Substance P (SP) induces Th1 cytokine expression and granuloma formation, whereas somatostatin inhibits the granulomatous response. We hypothesized that neuropeptides might play a role in regulation of the granulomatous response in cysticercosis. To test this hypothesis, we compared expression of SP and expression of somatostatin in murine cysticercal granulomas by using in situ hybridization and immunohistochemistry. We also compared expression with granuloma stage. Expression of SP mRNA was more frequent in the early-stage granulomas than in the late-stage granulomas (34 of 35 early-stage granulomas versus 1 of 13 late-stage granulomas). By contrast, somatostatin was expressed primarily in later-stage granulomas (13 of 14 late-stage granulomas versus 2 of 35 early-stage granulomas). The median light microscope grade of SP mRNA expression in the early-stage granulomas was significantly higher than that in the late-stage granulomas (P = 0.008, as determined by the Wilcoxon signed rank test). By contrast, somatostatin mRNA expression was higher at later stages (P = 0.008, as determined by the Wilcoxon signed rank test). SP and somatostatin are therefore temporally expressed in granulomas associated with murine cysticercosis, which may be related to differential expression of Th1 and Th2 cytokines.
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PMID:Sequential expression of the neuropeptides substance P and somatostatin in granulomas associated with murine cysticercosis. 1211 65


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