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 medical literature was reviewed from 1968-2002 using Medline and the key words "intra-articular" and "osteoarthritis" to determine the various intra-articular therapies used in the treatment of osteoarthritis. Corticosteroids and hyaluronic acid are the most frequently used intra-articular therapies in osteoarthritis. Other intra-articular substances such as orgotein, radiation synovectomy, dextrose prolotherapy, silicone, saline lavage, saline injection without lavage, analgesic agents, non-steroidal anti-inflammatory drugs, glucosamine, somatostatin, sodium pentosan polysulfate, chloroquine, mucopolysaccharide polysulfuric acid ester, lactic acid solution, and thiotepa cytostatica have been investigated as potentially therapeutic in the treatment of arthritic joints. Despite the lack of strong, convincing, and reproducible evidence that any of the intra-articular therapies significantly alters the progression of osteoarthritis, corticosteroids and hyaluronic acid are widely used in patients who have failed other therapeutic modalities for lack of efficacy or toxicity. As a practical approach for a knee with effusion, steroid injections should be considered while the presence of symptomatic "dry" knees may favour the hyaluronic acid approach. The virtual absence of serious side effects, coupled with the perceived benefits, make these approaches attractive.
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PMID:Intra-articular therapy in osteoarthritis. 1295 56

2-[18F]fluoro-2-deoxy-D-glucose (FDG) is currently the only fluorinated tracer used in routine clinical positron emission tomography (PET). Fluorine-18 is considered the ideal radioisotope for PET imaging owing to the low positron energy (0.64 MeV), which not only limits the dose rate to the patient but also results in a relatively short range of emission in tissue, thereby providing high-resolution images. Further, the 110-min physical half-life allows for high-yield radiosynthesis, transport from the production site to the imaging site and imaging protocols that may span hours, which permits dynamic studies and assessment of potentially fairly slow metabolic processes. The synthesis of fluorinated tracers as an alternative to FDG was initially tested using nucleophilic fluorination of the molecule, as performed when radiolabelling with iodine-124 or bromide-76. However, in addition to being long, with multiple steps, this procedure is not recommended for bioactive molecules containing reactive groups such as amine or thiol groups. Radiochemical yields are also often low. More recently, radiosynthesis from prosthetic group precursors, which allows easier radiolabelling of biomolecules, has led to the development of numerous fluorinated tracers. Given the wide availability of 18F, such tracers may well develop into important routine tracers. This article is a review of the literature concerning fluorinated radiotracers recently developed and under investigation for possible PET imaging in cancer patients. Two groups can be distinguished. The first includes "generalist" tracers, i.e. tracers amenable to use in a wide variety of tumours and indications, very similar in this respect to FDG. These are tracers for non-specific cell metabolism, such as protein synthesis, amino acid transport, nucleic acid synthesis or membrane component synthesis. The second group consists of "specific" tracers for receptor expression (i.e. oestrogens or somatostatin), cell hypoxia or bone metabolism.
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PMID:Fluorinated tracers for imaging cancer with positron emission tomography. 1524 31

Novel information was recently provided concerning the reciprocal effects of D-glucose and D-fructose upon their respective metabolism in rat pancreatic islets. In the light of such findings, this study aims at comparing the effects of D-glucose and D-fructose on insulin, somatostatin, and glucagon release from the isolated perfused rat pancreas. A rise in D-glucose concentration from 3.3 to 5.0 or 7.3 mM or the administration of D-fructose (17 and 40 mM) in the presence of 3.3 mM D-glucose stimulated insulin release in a concentration-related manner, but failed to affect somatostatin output. The secretion of glucagon was decreased in all cases. The secretory response to L-arginine (5 mM), 25 min after restoring the basal concentration of D-glucose, was more markedly affected, in terms of potentiation of insulin and somatostatin release and reduction of glucagon output, after prior administration of D-fructose than after a prior increase in D-glucose concentration. These findings argue against any major role for a paracrine regulation of hormonal release and, instead, are consistent with a causal link between metabolic and secretory events in the islet cells. Nevertheless, the present results emphasize differences in the response of distinct pancreatic endocrine cell types to the same or distinct hexoses.
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PMID:Immediate and delayed effects of D-fructose upon insulin, somatostatin, and glucagon release by the perfused rat pancreas. 1524 6

[reaction: see text] The synthesis of four bioactive analogues of the somatostatin (SRIF-14) mimetic, beta-d-glucoside (+)-2, in which the C1 indole side chain is replaced with indole surrogates, has been achieved. These congeners, possessing the naphthyl, benzothiophene, benzyl, and benzofuran substituents, were predicted to satisfy the electrostatic requirements of the tryptophan binding pocket of SRIF. Unlike the previously described C4 picolyl and pyrazinyl congeners, these ligands bind the hSST4 receptor.
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PMID:Synthesis and binding affinities of novel SRIF-mimicking beta-D-glucosides satisfying the requirement for a pi-cloud at C1. 1576 Jan 54

Worldwide, ocular cataracts are a major cause of human blindness. A key goal of cataract-related research is to identify simple, cost-efficient but effective ways to prevent cataract formation or progression. Genistein is a naturally occurring dietary isoflavone with well-documented estrogenic, antioxidant, and protein tyrosine kinase inhibitor activity, which in turn modulates the activity of several enzymes involved in cell signaling and proliferation. Furthermore, many isoflavones have been shown to be potent inhibitors of aldose reductase, which is an important rate-limiting enzyme in the process of cataract induction in the metabolic disease galactosemia. In order to assess the potential for genistein to mitigate cataract formation, we have studied its effects in the animal model of dietary galactose-induced cataracts in adult male rats. Our experimental hypothesis was that dietary genistein would prevent or delay the progression of cataracts induced by high dietary intake of galactose. Our results show that the isoflavone genistein was not able to completely prevent galactose-induced cataract formation, but genistein did delay the progression of cataracts induced by dietary galactose. In addition, we found that dietary galactose decreased concentrations of serum somatostatin, while adding genistein decreased the serum glucose level but increased the serum testosterone level. As an initial inquiry into the mechanisms by which the partial protective effect of genistein could be mediated, we found that genistein increased the expression of connexin (Cx) 43 in the lens but did not affect the expression of soluble guanylyl cyclase (sGC) subunits. This finding suggests that the partial protective effect of genistein on cataract induction appears to be unrelated to sGC but may be mediated by enhanced expression of Cx43 and changed metabolic state.
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PMID:Effect of the isoflavone genistein against galactose-induced cataracts in rats. 1720 92

Melatonin and resistance exercise alone have been shown to increase the levels of growth hormone (GH). The purpose of this study was to determine the effects of ingestion of a single dose of melatonin and heavy resistance exercise on serum GH, somatostatin (SST), and other hormones of the GH/insulin-like growth factor 1 (IGF-1) axis. Physically active males (n = 30) and females (n = 30) were randomly assigned to ingest either a melatonin supplement at 0.5 mg or 5.0 mg, or 1.0 mg of dextrose placebo. After a baseline blood sample, participants ingested the supplement and underwent blood sampling every 15 min for 60 min, at which point they underwent a single bout of resistance exercise with the leg press for 7 sets of 7 reps at 85% 1-RM. After exercise, participants provided additional blood samples every 15 min for a total of 120 min. Serum free GH, SST, IGF-1, IGFBP-1, and IGFBP-3 were determined with ELISA. Data were evaluated as the peak pre- and post-exercise values subtracted from baseline and the delta values analyzed with separate three-way ANOVA (p < 0.05). In males, when compared to placebo, 5.0 mg melatonin caused GH to increase (p = 0.017) and SST to decrease prior to exercise (p = 0.031), whereas both 0.5 and 5.0 mg melatonin were greater than placebo after exercise (p = 0.045) and less than placebo for SST. No significant differences occurred for IGF-1; however, males were shown to have higher levels of IGFBP-1 independent of supplementation (p = 0.004). The 5.0 mg melatonin dose resulted in higher IGFBP-3 in males (p = 0.017). In conclusion, for males 5.0 mg melatonin appears to increase serum GH while concomitantly lowering SST levels; however, when combined with resistance exercise both melatonin doses positively impacts GH levels in a manner not entirely dependent on SST.
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PMID:Effects of a single dose of N-Acetyl-5-methoxytryptamine (Melatonin) and resistance exercise on the growth hormone/IGF-1 axis in young males and females. 1795 23

In this review, we focus on the oncological applications of positron emission tomography (PET) tracers other than [(18)F]fluoro-2-deoxy-D-glucose (FDG) and the novel quantitative approaches in PET imaging. Oncological non-FDG PET tracers can be broadly categorized into 3 groups: those labeled with (18)F, (11)C and other non-FDG tracers. Fluorine-18 and (11)C are labeled with different amino acids, substrates involved in fatty acid synthesis, protein synthesis, amino acid transport substrate and tracers linked to nucleic acid synthesis. These tracers are also labeled with specific ligands for receptor imaging (i.e. estrogens, dihydrotestosterone or somatostatin). The other non-FDG radiotracers can be labeled with (68)Ga, (60)Cu, (64)Cu, etc. and are aimed to detect cell hypoxia, bone metabolism and receptor. Many of these have shown promising results in the management of various cancers where FDG has limited role. These radiotracers have more specific mechanism of uptake and is likely be investigated in the near future. In the era of fusion imaging, novel approaches for accurate quantitative analysis include partial volume correction for measured values in small lesions, dual-time point and delayed PET imaging, and global metabolic activity for assessment of various stages of disease. Major changes are likely to occur in the future that may overcome deficiencies that are associated with the current quantitative (standardized uptake value) techniques.
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PMID:Oncologic PET tracers beyond [(18)F]FDG and the novel quantitative approaches in PET imaging. 1823 21

Abstract Increasing concentrations of D-glucose (1 to 25 mM) inhibited somatostatin, thyrotrophin-releasing hormone (TRH) and growth hormone-releasing hormone (GHRH) release from incubated adult rat hypothalami in a stereospecific manner. In contrast, the effects of D- and L-glucose on luteinizing hormone-releasing hormone release were virtually identical. Increasing concentrations of D-glucose also inhibited somatostatin release following depolarization with high K(+), but had no obvious effect on depolarization-induced TRH or GHRH release when compared with L-glucose. In conclusion, D-glucose exerts a potent, dose-related modulatory action on the release of rat hypothalamic TRH and GHRH as well as somatostatin in vitro. Further studies are required to establish any physiological relevance of glucose in the modulation of these hypothalamic neuropeptides.
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PMID:Effects of Glucose on Thyrotrophin-Releasing Hormone, Growth Hormone-Releasing Hormone, Somatostatin and Luteinizing Hormone-Releasing Hormone Release from Rat Hypothalamus in vitro. 1921 Apr 14

Treatment of gastropod mollusks of pond snail Lymnaea stagnalis and orb snail Coretus corneus with streptozotocin was followed by an increase in hexose content in the hemolymph and development of the diabetic state (day 1 after treatment). Functional activity of the hormone-sensitive adenylate cyclase system significantly decreased in the muscles and hepatopancreas of mollusks with diabetes. We revealed a decrease in the regulatory effects of biogenic amines and peptide hormones that were realized via stimulatory (octopamine, dopamine, serotonin, tryptamine, and relaxin) and inhibitory G proteins (somatostatin). Disturbances in the hepatopancreas were more pronounced than in the muscle. The severity of disorders in the adenylate cyclase system reached maximum 1 day after streptozotocin treatment. The sensitivity of this system to hormonal and nonhormonal agents was partially restored on days 3 and 5. Hexose content in the hemolymph was elevated after streptozotocin treatment, but returned to normal on day 3. Our results indicate that hyperglycemia is one of the key factors for dysfunction of the adenylate cyclase system in mollusks with the diabetic state.
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PMID:Variations in functional activity of the hormone-sensitive adenylate cyclase system in tissues of gastropod mollusks with streptozotocin-induced diabetes. 1948 11

Activity and selectivity are typically the first considerations when designing a drug. However, absorption, distribution, metabolism, excretion, and toxicity (ADMET) are equally important considerations. Peptides can provide a combination of potent binding and exquisite selectivity, as evidenced by their pervasive use as enzymes, hormones, and signaling agents within living systems. In particular, peptidic turn motifs are key elements of molecular recognition. They may be found at the exposed surfaces of globular proteins, where they are available for binding interactions with other peptides and small molecules. However, despite these advantages, peptides often make poor drugs. The amide backbone is subject to rapid enzymatic proteolysis, resulting in short half-lives. Furthermore, the ability of the amide backbone to hydrogen bond with water restricts its ability to cross membranes and, consequentially, results in poor oral bioavailability. Accordingly, the development of nonpeptidic scaffolds that mimic peptidic turn motifs represents a promising means of converting peptidic agents into more drugable molecules. In this Account, we describe the design and synthesis of beta-turn mimetics that use a beta-D-glucose scaffold, the first use of a sugar scaffold for this purpose. Somatostatin (SRIF) is a small protein (14 amino acid residues) human hormone; a shorter (6 amino acid residues) synthetic peptide, L-363,301, is a fully peptidal agonist. These two cyclic peptides share the beta-turn motif comprising Phe(7)-Trp(8)-Lys(9)-Thr(10) (d-Trp(8) in the case of L-363,301), of which the tryptophan and lysine residues in the i + 1 and i + 2 positions, respectively, are critical for binding. In 1988, we initiated a program that tested and validated the then-novel proposition that the beta-D-glucose scaffold can mimic the beta-turn in L-363,301. The beta-D-glucose scaffold proved to be an attractive mimic of a beta-turn in part because it permits the convenient attachment of amino acid side chains via facile etherification reactions, rather than carbon-carbon bond formations; it is also an inexpensive starting material with well-defined stereochemistry. From the beginning, biological assays were used alongside physical measurements to assess the relevance of the design. Our first two synthetic targets, compounds 6 and 7, bound the SRIF receptors on benchmark (AtT-20) cells, albeit weakly, consistent with the objective of the design. Subsequently, a better ligand (8) and two congeners were found to be agonists at the SRIF receptors, providing convincing evidence that the peptide backbone is not required for receptor binding or signal transduction. The unexpectedly high level of receptor affinity of selected analogs, as well as the fortuitous discovery that our peptidomimetics were active against several chemically distinct receptors, led us to hypothesize that these monosaccharides could access multiple potential binding modes. Our later studies of this sugar scaffold confirmed this property, which we termed pseudosymmetry, whereby multiple similar but nonidentical motifs are displayed within a single analog. We propose the presence of pseudosymmetry to be an element of privilege and an advantage for lead discovery.
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PMID:The beta-D-glucose scaffold as a beta-turn mimetic. 1962 54


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