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Formula | C58H73N13O21S2 |
Molar mass | 1352.41 g·mol−1 |
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Ceruletide (INN), also known as cerulein or caerulein, is a ten amino acid oligopeptide that stimulates smooth muscle and increases digestive secretions. Ceruletide is similar in action and composition to cholecystokinin. It stimulates gastric, biliary, and pancreatic secretion; and certain smooth muscle. It is used in paralytic ileus and as diagnostic aid in pancreatic malfunction. It is used to induce pancreatitis in experimental animal models.
Ceruletide was discovered and its structure elucidated in 1967 by Australian and Italian scientists from dried skins of the Australian green tree frog (Ranoidea caerulea, formerly Hyla caerulea). Its amino acid sequence is Pglu-Gln-Asp-Tyr[SO3H]-Thr-Gly-Trp-Met-Asp-Phe-NH2. [1] [2]
Ceruletide upregulates pancreatic acinar cell intercellular adhesion molecule-1 (ICAM-1) proteins through intracellular upregulation of NF-κB. Surface ICAM-1 in turn promotes neutrophil adhesion onto acinar cells enhancing pancreatic inflammation. [3] In addition to promoting the inflammatory cell reaction to acinar cells, ceruletide induces pancreatitis through dysregulation of digestive enzyme production and cytoplasmic vacuolization, leading to acinar cell death and pancreatic edema. Ceruletide also activates NADPH oxidase, a source of reactive oxygen species contributing to inflammation, as well as the Janus kinase/signal transducer, another inflammation inducer. [4]
The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an endocrine and a digestive exocrine function. 99% of the pancreas is exocrine and 1% is endocrine. As an endocrine gland, it functions mostly to regulate blood sugar levels, secreting the hormones insulin, glucagon, somatostatin and pancreatic polypeptide. As a part of the digestive system, it functions as an exocrine gland secreting pancreatic juice into the duodenum through the pancreatic duct. This juice contains bicarbonate, which neutralizes acid entering the duodenum from the stomach; and digestive enzymes, which break down carbohydrates, proteins and fats in food entering the duodenum from the stomach.
Secretin is a hormone that regulates water homeostasis throughout the body and influences the environment of the duodenum by regulating secretions in the stomach, pancreas, and liver. It is a peptide hormone produced in the S cells of the duodenum, which are located in the intestinal glands. In humans, the secretin peptide is encoded by the SCT gene.
An oligopeptide, often just called peptide, consists of two to twenty amino acids and can include dipeptides, tripeptides, tetrapeptides, and pentapeptides. Some of the major classes of naturally occurring oligopeptides include aeruginosins, cyanopeptolins, microcystins, microviridins, microginins, anabaenopeptins, and cyclamides. Microcystins are best studied, because of their potential toxicity impact in drinking water. A review of some oligopeptides found that the largest class are the cyanopeptolins (40.1%), followed by microcystins (13.4%).
Cholecystokinin is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein. Cholecystokinin, formerly called pancreozymin, is synthesized and secreted by enteroendocrine cells in the duodenum, the first segment of the small intestine. Its presence causes the release of digestive enzymes and bile from the pancreas and gallbladder, respectively, and also acts as a hunger suppressant.
Acute pancreatitis (AP) is a sudden inflammation of the pancreas. Causes in order of frequency include: 1) a gallstone impacted in the common bile duct beyond the point where the pancreatic duct joins it; 2) heavy alcohol use; 3) systemic disease; 4) trauma; 5) and, in minors, mumps. Acute pancreatitis may be a single event; it may be recurrent; or it may progress to chronic pancreatitis.
Digestive enzymes are a group of enzymes that break down polymeric macromolecules into their smaller building blocks, in order to facilitate their absorption into the cells of the body. Digestive enzymes are found in the digestive tracts of animals and in the tracts of carnivorous plants, where they aid in the digestion of food, as well as inside cells, especially in their lysosomes, where they function to maintain cellular survival. Digestive enzymes of diverse specificities are found in the saliva secreted by the salivary glands, in the secretions of cells lining the stomach, in the pancreatic juice secreted by pancreatic exocrine cells, and in the secretions of cells lining the small and large intestines.
Gastrointestinal diseases refer to diseases involving the gastrointestinal tract, namely the esophagus, stomach, small intestine, large intestine and rectum, and the accessory organs of digestion, the liver, gallbladder, and pancreas.
In medicine, a pancreatectomy is the surgical removal of all or part of the pancreas. Several types of pancreatectomy exist, including pancreaticoduodenectomy, distal pancreatectomy, segmental pancreatectomy, and total pancreatectomy. In recent years, the TP-IAT has also gained respectable traction within the medical community. These procedures are used in the management of several conditions involving the pancreas, such as benign pancreatic tumors, pancreatic cancer, and pancreatitis.
Interleukin 8 is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells. Endothelial cells store IL-8 in their storage vesicles, the Weibel-Palade bodies. In humans, the interleukin-8 protein is encoded by the CXCL8 gene. IL-8 is initially produced as a precursor peptide of 99 amino acids which then undergoes cleavage to create several active IL-8 isoforms. In culture, a 72 amino acid peptide is the major form secreted by macrophages.
Osteopontin (OPN), also known as bone /sialoprotein I, early T-lymphocyte activation (ETA-1), secreted phosphoprotein 1 (SPP1), 2ar and Rickettsia resistance (Ric), is a protein that in humans is encoded by the SPP1 gene. The murine ortholog is Spp1. Osteopontin is a SIBLING (glycoprotein) that was first identified in 1986 in osteoblasts.
Pancreatic juice is a liquid secreted by the pancreas, which contains a number of digestive enzymes, including trypsinogen, chymotrypsinogen, elastase, carboxypeptidase, pancreatic lipase, nucleases and amylase. The pancreas is located in the visceral region, and is a major part of the digestive system required for proper digestion and subsequent assimilation of macronutrient substances required for living.
Exocrine pancreatic insufficiency (EPI) is the inability to properly digest food due to a lack or reduction of digestive enzymes made by the pancreas. EPI can occur in humans and is prevalent in many conditions such as cystic fibrosis, Shwachman–Diamond syndrome, different types of pancreatitis, multiple types of diabetes mellitus, advanced renal disease, older adults, celiac disease, IBS-D, IBD, HIV, alcohol-related liver disease, Sjogren syndrome, tobacco use, and use of somatostatin analogues.
Pancreatic polypeptide (PP) is a polypeptide secreted by PP cells in the endocrine pancreas. It regulates pancreatic secretion activities, and also impacts liver glycogen storage and gastrointestinal secretion. Its secretion may be impacted by certain endocrine tumours.
ICAM-1 also known as CD54 is a protein that in humans is encoded by the ICAM1 gene. This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system. It binds to integrins of type CD11a / CD18, or CD11b / CD18 and is also exploited by rhinovirus as a receptor for entry into respiratory epithelium.
Pancreatic diseases are diseases that affect the pancreas, an organ in most vertebrates and in humans and other mammals located in the abdomen. The pancreas plays a role in the digestive and endocrine system, producing enzymes which aid the digestion process and the hormone insulin, which regulates blood sugar levels. The most common pancreatic disease is pancreatitis, an inflammation of the pancreas which could come in acute or chronic form. Other pancreatic diseases include diabetes mellitus, exocrine pancreatic insufficiency, cystic fibrosis, pseudocysts, cysts, congenital malformations, tumors including pancreatic cancer, and hemosuccus pancreaticus.
The biliary tract refers to the liver, gallbladder and bile ducts, and how they work together to make, store and secrete bile. Bile consists of water, electrolytes, bile acids, cholesterol, phospholipids and conjugated bilirubin. Some components are synthesized by hepatocytes ; the rest are extracted from the blood by the liver.
Ulinastatin, as an urinary trypsin inhibitor (UTI), is a glycoprotein that is isolated from healthy human urine or synthetically produced and has molecular weight of 25 - 40kDa. Highly purified ulinastatin has been clinically used for the treatment of acute pancreatitis, chronic pancreatitis, Stevens–Johnson syndrome, burns, septic shock, and toxic epidermal necrolysis (TEN).
Tricetin is a flavone, a type of flavonoid. It is a rare aglycone found in the pollen of members of the Myrtaceae, subfamily Leptospermoideae, such as Eucalyptus globulus. This compound shows anticancer effects on human breast adenocarcinoma MCF-7 cells. Moreover. a potent anti-inflammatory effect of tricetin has also been demonstrated in a model of acute pancreatitis. This observation was explained by the compound's radical scavenging effects, its inhibitory effect on the DNA damage sensor enzyme poly (ADP-ribose) polymerase-1 (PARP1) and PARP1-mediated cell death and suppression of inflammatory gene expression.
Canine pancreatitis is inflammation of the pancreas that can occur in two very different forms. Acute pancreatitis is sudden, while chronic pancreatitis is characterized by recurring or persistent form of pancreatic inflammation. Cases of both can be considered mild or severe.
Ductal cells refer to the epithelial cell lining of the pancreatic duct that deliver enzymes from the acinar cells to the duodenum. They have the essential function of producing bicarbonate-rich (HCO3-) secretion to neutralize stomach acidity. The hormone secretin stimulates ductal cells and is responsible for maintaining the duodenal pH and preventing duodenal injury from acidic chyme. Ductal cells mix their production with acinar cells to make up the pancreatic juice.