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Scientific Reports Oct 2022Currently, there is no specific pharmaceutical agent for treating acute pancreatitis (AP). Somatostatin and its analogues have been used to prevent the autolysis of the... (Meta-Analysis)
Meta-Analysis
Currently, there is no specific pharmaceutical agent for treating acute pancreatitis (AP). Somatostatin and its analogues have been used to prevent the autolysis of the pancreas in AP, however, their effectiveness has not been confirmed. This investigation aimed to examine the efficacy of ulinastatin, a protease inhibitor, combined with somatostatin analogues in the treatment of AP. We conducted a systematic database search in 4 databases to identify randomized controlled trials in which the efficacy of ulinastatin in combination with somatostatin analogue was compared to somatostatin analogue alone in patients with AP. Since the patient populations of analysed papers were slightly different, we used random effect models to pool odds ratios (OR) and mean differences (MD) and the corresponding 95% confidence intervals (CI). A total of 9 articles comprising 1037 patients were included in the meta-analysis. The combination therapy significantly reduced the complication rates for acute respiratory distress syndrome, acute kidney injury, and multiple organ dysfunction. Symptoms were relieved threefold with the combination therapy compared to somatostatin alone, and combination therapy significantly shortened the length of hospital stay. The decrease in mortality was not statistically significant..
Topics: Humans; Acute Disease; Pancreatitis; Protease Inhibitors; Randomized Controlled Trials as Topic; Somatostatin
PubMed: 36289288
DOI: 10.1038/s41598-022-22341-7 -
Gut 1994Somatostatin is a 14 amino acid peptide that inhibits pancreatic exocrine and endocrine secretion. Its clinical application has been limited by its very short half life,... (Review)
Review
Somatostatin is a 14 amino acid peptide that inhibits pancreatic exocrine and endocrine secretion. Its clinical application has been limited by its very short half life, necessitating continuous intravenous infusion. Octreotide is an 8 amino acid synthetic analogue of somatostatin that possesses similar pharmacological effects. It has a much longer duration of action, however, and can be given subcutaneously. Both the intravenous and subcutaneous routes of injection of octreotide are well tolerated. Peak serum concentrations occur within 30 minutes after subcutaneous administration and within four minutes of a three minute intravenous infusion. Serum concentration increases linearly with dose. Octreotide is distributed rapidly, mainly in the plasma, where it is 65% protein bound. The elimination half life is about 1.5 hours and about 32% of a subcutaneous dose is excreted in the urine as unchanged octreotide. Octreotide inhibits gastroenteropancreatic secretion, especially of insulin, glucagon, pancreatic polypeptide, gastric inhibitory polypeptide, and gastrin. It also inhibits both release of thyroid stimulating hormone and growth hormone secretion in response to exercise, insulin induced hypoglycaemia, and argenine stimulation. Octreotide reduces splanchnic blood flow in healthy volunteers and hepatic venous pressure in cirrhotic patients. It can accelerate or delay gastric emptying, prolong transit time at moderate to high doses, stimulate motility at low doses, and inhibit gall bladder emptying. Octreotide considerably inhibits pentagastrin stimulated gastric acid secretion and significantly diminishes exocrine pancreatic function (amylase, trypsin, lipase). Octreotide increases intestinal transit time and decreases endogenous fluid secretion in the jejunum and ileum, thus increasing the absorption of water and electrolytes. These pharmacological effects of the analogue point to its therapeutic role in a variety of endocrine and gastrointestinal disorders.
Topics: Amino Acid Sequence; Digestive System; Humans; Molecular Sequence Data; Octreotide; Pancreas; Somatostatin
PubMed: 7911441
DOI: 10.1136/gut.35.3_suppl.s1 -
Mini Reviews in Medicinal Chemistry Jan 2013During the past 40 years, somatostatin (SST) has been a subject of intensive research. Apart from its substantial role in the neuroendocrine system, due to its dense... (Review)
Review
During the past 40 years, somatostatin (SST) has been a subject of intensive research. Apart from its substantial role in the neuroendocrine system, due to its dense localization in various areas in the brain, its functions as a neuromodulator have also been thoroughly investigated. Increasing evidence suggests that SST plays a crucial role in memory and cognition. Synthetic forms, biologically active peptide sequences, SST receptor agonists and SST depleting agents have been applied in animal models and in human studies of a number of neuropsychiatric disorders. The translation of experimental data into clinical use could provide novel therapies in neurodegenerative disorders involving cognitive dysfunctions. However in view of the controversial data reported concerning the different roles of the SST receptor subtypes, and the lack of SST analogs that are able to cross diffusion barriers and act selectively at these receptor subtypes, broader clinical use of SST analogs as cognitive enhancers is limited. This review covers the whole range of available experimental results relating to the behavioral effects of SST, and highlights the potential for further investigations.
Topics: Amino Acid Sequence; Animals; Cognition; Humans; Molecular Sequence Data; Neurodegenerative Diseases; Receptors, Somatostatin; Somatostatin
PubMed: 22876954
DOI: 10.2174/138955713804484794 -
British Medical Journal (Clinical... Aug 1987
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Proceedings of the National Academy of... May 2023Daily and annual changes in light are processed by central clock circuits that control the timing of behavior and physiology. The suprachiasmatic nucleus (SCN) in the...
Daily and annual changes in light are processed by central clock circuits that control the timing of behavior and physiology. The suprachiasmatic nucleus (SCN) in the anterior hypothalamus processes daily photic inputs and encodes changes in day length (i.e., photoperiod), but the SCN circuits that regulate circadian and photoperiodic responses to light remain unclear. Somatostatin (SST) expression in the hypothalamus is modulated by photoperiod, but the role of SST in SCN responses to light has not been examined. Our results indicate that SST signaling regulates daily rhythms in behavior and SCN function in a manner influenced by sex. First, we use cell-fate mapping to provide evidence that SST in the SCN is regulated by light via de novo activation. Next, we demonstrate that mice display enhanced circadian responses to light, with increased behavioral plasticity to photoperiod, jetlag, and constant light conditions. Notably, lack of eliminated sex differences in photic responses due to increased plasticity in males, suggesting that SST interacts with clock circuits that process light differently in each sex. mice also displayed an increase in the number of retinorecipient neurons in the SCN core, which express a type of SST receptor capable of resetting the molecular clock. Last, we show that lack of SST signaling modulates central clock function by influencing SCN photoperiodic encoding, network after-effects, and intercellular synchrony in a sex-specific manner. Collectively, these results provide insight into peptide signaling mechanisms that regulate central clock function and its response to light.
Topics: Mice; Female; Male; Animals; Light; Circadian Rhythm; Suprachiasmatic Nucleus; Somatostatin; Photoperiod; Circadian Clocks
PubMed: 37098068
DOI: 10.1073/pnas.2216820120 -
Somatostatin and somatostatin analogues--are they indicated in the management of acute pancreatitis?Gut Nov 1993Somatostatin was first suggested for the treatment of acute pancreatitis more than 15 years ago but despite many studies, its role in the management of this condition... (Review)
Review
Somatostatin was first suggested for the treatment of acute pancreatitis more than 15 years ago but despite many studies, its role in the management of this condition remains unclear. The experimental and clinical studies are reviewed and the physiological actions of somatostatin, which may influence the course of acute pancreatitis are examined. It is concluded that although some reports suggest a trend towards improved survival and lessened complication rate with somatostatin treatment, insufficient evidence of benefit exists to support the use of somatostatin or its analogue in the treatment or prophylaxis against acute pancreatitis in routine clinical practice.
Topics: Acute Disease; Animals; Clinical Trials as Topic; Disease Models, Animal; Humans; Octreotide; Pancreas; Pancreatitis; Regional Blood Flow; Somatostatin
PubMed: 7902312
DOI: 10.1136/gut.34.11.1622 -
British Journal of Pharmacology Apr 2014The biological actions of somatostatin are mediated by a family of five GPCRs, named sst1 to sst5 . Somatostatin receptors exhibit equally high-binding affinities to... (Review)
Review
The biological actions of somatostatin are mediated by a family of five GPCRs, named sst1 to sst5 . Somatostatin receptors exhibit equally high-binding affinities to their natural ligand somatostatin-14 and largely overlapping distributions. The overexpression of somatostatin receptors in human tumours is the molecular basis for diagnostic and therapeutic application of the stable somatostatin analogues octreotide, lanreotide and pasireotide. The efficiency of somatostatin receptor signalling is tightly regulated and ultimately limited by the coordinated phosphorylation and dephosphorylation of intracellular carboxyl-terminal serine and threonine residues. Here, we review and discuss recent progress in the generation and application of phosphosite-specific antibodies for human sst2 and sst5 receptors. These phosphosite-specific antibodies are unique tools to monitor the spatial and temporal dynamics of receptors phosphorylation and dephosphorylation. Using a combined approach of phosphosite-specific antibodies and siRNA knock-down screening, relevant kinases and phosphatases were identified. Emerging evidence suggests distinct mechanisms of agonist-selective fine-tuning for individual somatostatin receptors. The recently uncovered differences in phosphorylation and dephosphorylation of these receptors may hence be of physiological significance in mediating responses to acute, persistent or repeated stimuli in a variety of target tissues.
Topics: Amino Acid Sequence; Animals; Antibodies; Humans; Ligands; Molecular Sequence Data; Phosphorylation; RNA Interference; Receptors, Somatostatin; Signal Transduction; Somatostatin
PubMed: 24328848
DOI: 10.1111/bph.12551 -
Molecules (Basel, Switzerland) Sep 2020Identified in 1973, somatostatin (SST) is a cyclic hormone peptide with a short biological half-life. Somatostatin receptors (SSTRs) are widely expressed in the whole... (Review)
Review
Identified in 1973, somatostatin (SST) is a cyclic hormone peptide with a short biological half-life. Somatostatin receptors (SSTRs) are widely expressed in the whole body, with five subtypes described. The interaction between SST and its receptors leads to the internalization of the ligand-receptor complex and triggers different cellular signaling pathways. Interestingly, the expression of SSTRs is significantly enhanced in many solid tumors, especially gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). Thus, somatostatin analogs (SSAs) have been developed to improve the stability of the endogenous ligand and so extend its half-life. Radiolabeled analogs have been developed with several radioelements such as indium-111, technetium-99 m, and recently gallium-68, fluorine-18, and copper-64, to visualize the distribution of receptor overexpression in tumors. Internal metabolic radiotherapy is also used as a therapeutic strategy (e.g., using yttrium-90, lutetium-177, and actinium-225). With some radiopharmaceuticals now used in clinical practice, somatostatin analogs developed for imaging and therapy are an example of the concept of personalized medicine with a theranostic approach. Here, we review the development of these analogs, from the well-established and authorized ones to the most recently developed radiotracers, which have better pharmacokinetic properties and demonstrate increased efficacy and safety, as well as the search for new clinical indications.
Topics: Amino Acid Sequence; Animals; Humans; Neoplasms; Peptides; Radiopharmaceuticals; Receptors, Somatostatin; Somatostatin; Tissue Distribution
PubMed: 32887456
DOI: 10.3390/molecules25174012 -
Frontiers in Neural Circuits 2016Cortical inhibitory neurons exhibit remarkable diversity in their morphology, connectivity, and synaptic properties. Here, we review the function of... (Review)
Review
Cortical inhibitory neurons exhibit remarkable diversity in their morphology, connectivity, and synaptic properties. Here, we review the function of somatostatin-expressing (SOM) inhibitory interneurons, focusing largely on sensory cortex. SOM neurons also comprise a number of subpopulations that can be distinguished by their morphology, input and output connectivity, laminar location, firing properties, and expression of molecular markers. Several of these classes of SOM neurons show unique dynamics and characteristics, such as facilitating synapses, specific axonal projections, intralaminar input, and top-down modulation, which suggest possible computational roles. SOM cells can be differentially modulated by behavioral state depending on their class, sensory system, and behavioral paradigm. The functional effects of such modulation have been studied with optogenetic manipulation of SOM cells, which produces effects on learning and memory, task performance, and the integration of cortical activity. Different classes of SOM cells participate in distinct disinhibitory circuits with different inhibitory partners and in different cortical layers. Through these disinhibitory circuits, SOM cells help encode the behavioral relevance of sensory stimuli by regulating the activity of cortical neurons based on subcortical and intracortical modulatory input. Associative learning leads to long-term changes in the strength of connectivity of SOM cells with other neurons, often influencing the strength of inhibitory input they receive. Thus despite their heterogeneity and variability across cortical areas, current evidence shows that SOM neurons perform unique neural computations, forming not only distinct molecular but also functional subclasses of cortical inhibitory interneurons.
Topics: Animals; Cerebral Cortex; Interneurons; Neural Inhibition; Somatostatin
PubMed: 27746722
DOI: 10.3389/fncir.2016.00076 -
Journal of Pain and Symptom Management Dec 2016Somatostatin analogues are commonly used to relieve symptoms in malignant bowel obstruction (MBO) but are more expensive than other antisecretory agents. (Comparative Study)
Comparative Study Review
CONTEXT
Somatostatin analogues are commonly used to relieve symptoms in malignant bowel obstruction (MBO) but are more expensive than other antisecretory agents.
OBJECTIVES
To evaluate the evidence of effectiveness of somatostatin analogues compared with placebo and/or other pharmacologic agents in relieving vomiting in patients with inoperable MBO.
METHODS
MEDLINE, EMBASE, CINAHL, and The Cochrane Controlled Trials Register databases were systematically searched; reference lists of relevant articles were hand searched. Cochrane risk of bias tool was used.
RESULTS
The search identified 420 unique studies. Seven randomized controlled trials (RCTs) met the inclusion criteria (six octreotide studies and one lanreotide); 220 people administered somatostatin analogues and 207 placebo or hyoscine butylbromide. Three RCTs compared a somatostatin analogue with placebo and four with hyoscine butylbromide. Two adequately powered multicenter RCTs with a low Cochrane risk of bias reported no significant difference between somatostatin analogues and placebo in their primary end points. Four RCTs with a high/unclear Cochrane risk of bias reported that somatostatin analogues were more effective than hyoscine butylbromide in reducing vomiting.
CONCLUSION
There is low-level evidence of benefit with somatostatin analogues in the symptomatic treatment of MBO. However, high-level evidence from trials with low risk of bias found no benefit of somatostatin analogues for their primary outcome. There is debate regarding the clinically relevant study end point for symptom control in MBO and when it should be measured. The role of somatostatin analogues in this clinical situation requires further adequately powered, well-designed trials with agreed clinically important end points and measures.
Topics: Gastrointestinal Agents; Humans; Intestinal Obstruction; Somatostatin
PubMed: 27697568
DOI: 10.1016/j.jpainsymman.2016.05.032