Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001339 (acute pancreatitis)
 10,593 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammatory mediators play a key role in acute pancreatitis and the resultant multiple organ dysfunction syndrome, which is the primary cause of death in this condition. Recent studies have confirmed the critical role played by inflammatory mediators such as TNF-alpha, IL-1beta, IL-6, IL-8, PAF, IL-10, C5a, ICAM-1, and substance P. The systemic effects of acute pancreatitis have many similarities to those of other conditions such as septicaemia, severe burns, and trauma. The delay between the onset of inflammation in the pancreas and the development of the systemic response makes acute pancreatitis an ideal experimental and clinical model with which to study the role of inflammatory mediators and to test novel therapies. Elucidation of the key mediators involved in the pathogenesis of acute pancreatitis will facilitate the development of clinically effective anti-inflammatory therapy.
 ...
PMID:Inflammatory mediators in acute pancreatitis. 1065 8

P-selectin and circulating xanthine oxidase are involved in the process of neutrophil infiltration into the lung associated with acute pancreatitis. This study investigated the mediators that trigger the upregulation of P-selectin in this process. Pancreatitis was induced in rats by intraductal administration of 5% sodium taurocholate. P-selectin expression was measured using radiolabeled antibodies. Neutrophil infiltration and PAF levels were also evaluated. The role of superoxide radical, H(2)O(2), or the enzyme poly (ADP-ribose) synthetase (PARS) on these processes was determined in groups of animals treated with the corresponding inhibitors. Pancreatitis was associated with an increase in P-selectin expression in the lung. Inhibition of PARS or H(2)O(2) abrogated P-selectin upregulation, PAF generation, and neutrophil recruitment. Superoxide dismutation prevented neutrophil recruitment and PAF generation, but had no effect on P-selectin expression. We conclude that during acute pancreatitis, upregulation of P-selectin in the pulmonary endothelium is triggered by H(2)O(2) and PARS activity.
 ...
PMID:H(2)O(2) and PARS mediate lung P-selectin upregulation in acute pancreatitis. 1088 59

The activation of pulmonary alveolar macrophages (PAM's), might play an important role in severe complications of acute pancreatitis. The aim of our study was to assess the labilization of macrophage lysosomal membranes and release of lysosomal cathepsin B (CB) and N-acetyl-beta-D-hexosaminidase (NAH) into bronchoalveolar lavage fluid (BALF) during taurocholate acute pancreatitis (AP) in rats treated with PAF-antagonist--BN 52021. Total activity of CB increased by 374% after 6 h and by 237% after 12 h of AP in lysosomal enriched fraction of PAM's. Fractional free activity of CB increased to 40% after 6 h and to 38% after 12 h of AP. Free activity of CB was increased 5 fold in the supernatant of macrophage homogenate, and 10 fold in the supernatant of BALF after 6 h of AP. The values of NAH activity roughly paralleled that of CB. Treatment with BN 52021 (5 mg x kg(-1) every 6 h i.v.) partially normalized the measured parameters. Our results indicate that the PAF-antagonist BN 52021 reduced the increase of total and free activity of lysosomal hydrolases of PAM's and partly prevented the labilization of their lysosomal membranes. Therefore, an important mechanism of BN 52021 beneficial effect in pulmonary complications of acute pancreatitis could be dependent on the stabilization of PAM's lysosomes.
 ...
PMID:Lysosomal activity of pulmonary alveolar macrophages in acute experimental pancreatitis in rats with reference to positive PAF-antagonist (BN 52021) effect. 1096 85

Multi-organ dysfunction syndrome (MODS) is the primary cause of morbidity and mortality in acute pancreatitis. Recent studies have established the critical role played by inflammatory mediators such as TNFalpha, IL-1beta, IL-6, IL-8, CINC/GROalpha, PAF, IL-10, C5a, ICAM-1 and substance P in acute pancreatitis and the resultant MODS. Potentially, there is a therapeutic window between symptom onset and the development of distant organ damage, when anti-inflammatory therapy may be of use. Elucidation of the key mediators in acute pancreatitis coupled with the discovery of specific inhibitors may make it possible to develop clinically effective anti-inflammatory therapy.
 ...
PMID:Inflammatory mediators as therapeutic targets in acute pancreatitis. 1156 5

Acute pancreatitis is a common clinical condition. The exact mechanisms by which diverse etiological factors induce an attack are unclear but once the disease process is initiated, common inflammatory and repair pathways are invoked. Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction; if marked, this leads to a systemic inflammatory response syndrome (SIRS). An excessive SIRS leads to distant organ damage and multiple organ dysfunction syndrome (MODS). MODS associated with acute pancreatitis is the primary cause of morbidity and mortality in this condition. The systemic effects of acute pancreatitis have many similarities to those of other conditions such as septicemia, severe burns and trauma. Potentially, there is a therapeutic window between symptom onset and the development of distant organ damage in acute pancreatitis, when anti-inflammatory therapy may be of use. Recent studies conducted by us and other investigators have established the critical role played by inflammatory mediators such as TNF-alpha, IL-1beta, IL-6, IL-8, CINC/GRO-alpha, MCP-1, PAF, IL-10, CD40L, C5a, ICAM-1, and Substance P in acute pancreatitis and the resultant MODS. It is reasonable to speculate that elucidation of the key mediators in acute pancreatitis coupled with the discovery of specific inhibitors will make it possible to develop a clinically effective anti-inflammatory therapy.
 ...
PMID:Novel therapeutic targets for acute pancreatitis and associated multiple organ dysfunction syndrome. 1456 Nov 81

Although many factors such as histamine, bradykinin, TNFalpha, IL-1, FDP, thrombin, and PAF are involved in the increase of the vascular permeability, neutrophil infiltration is a major cause of microcirculatory impairment and organ failure in acute pancreatitis. Vasospasm and microthrombi formation due to hypercoagulability are also other cause of deterioration of the microcirculation of the pancreas leading to pancreatic necrosis.
 ...
PMID:[Role of increase in permeability and circulatory failure in the development of organ dysfunction in severe acute pancreatitis]. 1555 80

Acute pancreatitis is an inflammatory disorder, and inflammation not only affects the pathogenesis but also the course of the disease. Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction; if marked this leads to a systemic inflammatory response syndrome (SIRS). An excessive SIRS leads to distant organ damage and multiple organ dysfunction syndrome (MODS). MODS associated with acute pancreatitis is the primary cause of morbidity and mortality in this condition. Recent studies by us and other investigators have established the critical role played by inflammatory mediators such as TNF-alpha, IL-1beta, IL-6, IL-8, CINC/GRO-alpha, MCP-1, PAF, IL-10, CD40L, C5a, ICAM-1, MIP1-alpha, RANTES, substance P, and hydrogen sulfide in acute pancreatitis and the resultant MODS. This review intends to present an overview of the inflammatory response that takes place following pancreatic acinar cell injury.
 ...
PMID:Inflammatory response on the pancreatic acinar cell injury. 1611 Oct 89

The clinical presentation of acute pancreatitis varies significantly from mild self-limiting discomfort to a severe life-threatening condition. Once the disease process is initiated, the severity of the disease is largely determined by a complex network of activated inflammatory mediators such as cytokines, proteolytic enzymes, reactive oxygen species, and many more which render the local injury to a systemic disease with multiple organ dysfunction, sepsis, and considerable mortality. Remarkable progress in diagnostic modalities, intensive care technologies, and organ preserving surgical techniques have decreased mortality of severe acute pancreatitis during the past decades. However, the treatment of acute pancreatitis still remains largely supportive and no specific approach exists to prevent evolving complications. A large body of clinical and experimental evidence suggests that cytokines are key factors in the pathomechanism of local and systemic complications of acute pancreatitis. Targeting cytokine activity as therapeutic approach to acute pancreatitis is a challenging concept and the results of modulating activation of TNF-alpha, IL-1beta, IL-2, IL-10, PAF and various chemokines has indeed been promising in the experimental setting even if tested under therapeutic conditions. However, experience from a limited number of clinical trials on anti cytokine strategies in acute pancreatitis has remarkably emphasized that translating successful experimental observations into reproducible clinical associations seems to be difficult.
 ...
PMID:Anti-cytokine strategies in acute pancreatitis: pathophysiological insights and clinical implications. 1635 48

Acute pancreatitis is a common clinical condition. Excessive systemic inflammatory response syndrome (SIRS) in acute pancreatitis leads to distant organ damage and multiple organ dysfunction syndrome (MODS), which is the primary cause of morbidity and mortality in this condition. Development of in vivo experimental models of acute pancreatitis and associated systemic organ damage has enabled us to study the role played by inflammatory mediators in the pathogenesis of acute pancreatitis and associated systemic organ damage. Using these models, recent studies by us and other investigators have established the critical role played by inflammatory mediators such as TNF-a, IL-1b, IL-6, PAF, IL-10, CD40L, C5a, ICAM-1, chemokines, substance P and hydrogen sulfide in acute pancreatitis and the resultant MODS. This chapter intends to present an overview of different experimental animal models of acute pancreatitis and associated MODS and the role of inflammatory mediators in the pathogenesis of this condition.
 ...
PMID:Acute pancreatitis as a model of SIRS. 1927 84

To observe the protecting effects and mechanisms of Dexamethasone and Salviae miltiorrhizae on intestinal mucosa and immune organs (spleen, thymus and lymph node) in rats with severe acute pancreatitis (SAP). The rats were randomly divided into sham-operated, model control, Dexamethasone treated group and Salviae miltiorrhizae treated group. At 3, 6 and 12 h after operation, the mortality rate, pathological changes of intestinal mucosa and immune organs as well as the contents of serum PAF, IL-1 beta and sIL-2R were observed, respectively. The mortality rate and the contents of PAF (at 3 and 6 h), IL-1 beta (at all time points) and sIL-2R (at 3 and 6 h) as well as the pathological scores of thymus (at all time points) and spleen (at 3 h) in Dexamethasone treated group were significantly lower than those in model control groups (P < 0.05). The contents of PAF (at 3 and 12 h), IL-1 beta (at 6 and 12 h) and sIL-2R (at 3 and 6 h) as well as the pathological scores of thymus (at all time points) and spleen (at 3 and 12 h) in Salviae miltiorrhizae treated group were markedly lower than those in model control groups (P < 0.05). Since both Dexamethasone and Salvia miltiorrhizae can reduce the contents of serum PAF, sIL-2R and IL-1 beta, mitigate the pathological changes in the small intestine, spleen and thymus and reduce the mortality rate of SAP rats, they show good therapeutic effects on SAP rats.
 ...
PMID:Effects of dexamethasone and Salvia miltiorrhizae on the small intestine and immune organs of rats with severe acute pancreatitis. 2012 99


<< Previous 1 2