Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is thought that tumor necrosis factor (TNF) plays an important role in pathogenesis of acute lung injury or ARDS. So we want to get insight into the relationship between intrapulmonary expression of TNF-alpha gene and lung injury during acute necrotizing pancreatitis (ANP). In our study, acute edematous pancreatitis (AEP) and ANP were induced in rats by caerulein and sodium taurocholate respectively. After acute pancreatitis was induced, serum TNF-alpha was assessed by ELISA assay while endotoxin was assessed by limulus lysate test. Intrapulmonary expression of TNF-alpha mRNA was detected by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) technique. Moreover, content of pulmonary lesion was investigated and graded with microscope. It was found that TNF-alpha concentration in blood elevated markedly after acute pancreatitis was induced, especially in ANP group. Results of RT-PCR revealed that no TNF-alpha mRNA could be detected in lung tissue from those rats undergoing sham-operation, but marked expression appeared 1 hour after AEP or ANP was induced. Upregulation of expression of TNF-alpha gene in the early 3 hours was similar in the two groups with pancreatitis, and since then expression of TNF-alpha mRNA in ANP group was stronger than that in AEP group. Serum endotoxin increased significantly 6 hours after ANP was induced, with a higher level at 12 hour. However, there was no marked change of endotoxin level in AEP group and control group. It is noted that intrapulmonary expression of TNF-alpha gene in ANP group reached its peak as soon as serum endotoxin increased markedly. Lung damage in ANP group was more serious than that in AEP group significantly. Score of lung injury correlated well with TNF-alpha concentration in blood and expression of its gene in lung tissue in either AEP group or ANP group, as well as with serum endotoxin in ANP group. So overwhelm expression of some harmful cytokines like TNF-alpha in lung tissue may be the main cause of lung injury during acute necrotizing pancreatitis, and stimulation of endotoxiemia can at least partly explain the upregulation of expression of TNF-alpha gene.
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PMID:[Intrapulmonary expression of tumor necrosis factor alpha mRNA and its significance in rats with acute pancreatitis]. 1138 45

Because bacterial translocation from the gut is one of the important sources of bacterial infection in acute necrotizing pancreatitis (ANP) and growth hormone (GH) has the ability to promote the intestinal epithelial proliferation, we investigated the effects of GH on bacterial translocation in a rat ANP model. ANP was induced in rats by injection of 5% sodium taurocholate into the biliopancreatic duct. The rats with ANP were treated with either human recombinant GH or placebo. Laparotomized animals without induction of ANP (sham operation [SO]) served as controls. At 24 hours after operation, blood was drawn for bacterial culture and determination of amylase, lipase, and endotoxin. Peritoneal fluid and specimens of mesenteric lymph nodes (MLN), liver, pancreas, and spleen were taken for bacterial culture by standard techniques. Intestinal mucosal permeability was assessed by measuring the movement of 125I-labeled albumin from blood to intestinal lumen. Insulin-like growth factor-1 (IGF-1) mRNA was detected in the liver and ileum by reverse transcriptase-polymerase chain reaction (RT-PCR). Morphologic changes of pancreas and ileum were also analyzed. Administration of GH significantly decreased the serum amylase, lipase activities, plasma endotoxin level, and incidence of bacterial translocation. Moreover, the survival rate of ANP rats was improved. The severity of inflammation in pancreas and ileum was alleviated by GH treatment. Ileal mucosal thickness, villus height, and crypt depth in GH treatment rats were obviously increased compared with those of ANP rats. The intestinal permeability was markedly improved in the GH group versus the ANP group. GH treatment resulted in up-regulation of IGF-1 mRNA expression in ileum, but not in liver. These results suggested that exogenous GH had beneficial effects in maintaining the integrity of intestinal mucosal barrier and reducing the incidence of bacterial translocation in rats with ANP. One of the mechanisms might be the up-regulation of IGF-1 mRNA in intestine by GH treatment.
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PMID:Beneficial effects of growth hormone on bacterial translocation during the course of acute necrotizing pancreatitis in rats. 1148 17

Since the adoption of highly active antiretroviral therapy (HAART) in the mid-1990s, certain metabolic toxicities have been increasingly recognized. These include a fat redistribution syndrome (lipohypertrophy, lipoatrophy), hyperlipidaemia, altered glucose metabolism and insulin resistance, mitochondrial toxicity (presenting as anaemia, myopathy, pancreatitis, neuropathy, hepatic steatosis and lactic acidosis), and bone density abnormalities (osteoporosis and osteonecrosis). Metabolic complications are principally reported with protease inhibitors and nucleoside reverse transcriptase inhibitors, but may be seen with all classes of antiretroviral therapy. In this review, we summarize the epidemiology, pathogenesis and management of these various toxicities.
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PMID:The metabolic toxicities of antiretroviral therapy. 1151 63

Nucleoside reverse transcriptase inhibitors result in a wide range of toxic side effects. These include lactic acidosis syndrome, myopathy, cardiomyopathy, pancreatitis, peripheral neuropathy, and possibly lipodystrophy. Despite the seemingly diverse nature of these side effects, all of these toxicities may be mediated by a common pathophysiologic mechanism, namely, mitochondrial toxicity resulting from nucleoside reverse transcriptase inhibitor-induced inhibition of DNA polymerase g. This article reviews the relevant mitochondrial biology and mechanism underlying nucleoside reverse transcriptase inhibitor-induced mitochondrial toxicity. Clinical manifestations of this toxicity are reviewed followed by a discussion of clinical management.
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PMID:Mitochondrial Toxicity Associated with Nucleoside Reverse Transcriptase Inhibitor Therapy. 1172 14

For the last several years, the combination of ddI (didanosine, Videx) and d4T (stavudine, Zerit) as a backbone of three-drug therapy has been popular both in treatment and in research. Together, the two nucleoside analog reverse transcriptase inhibitor (NARTI) drugs offered relatively high strength and fairly simple use. Despite this, some researchers have long questioned the wisdom of the combination as it violates one of the key rules of combining drugs: combine only drugs with different side effect profiles. Both drugs are associated with the development of peripheral neuropathy and pancreatitis. Pancreatitis is more commonly seen with ddI and neuropathy with d4T, but both occur to a significant degree with each drug and to a higher degree than was seen with other drugs of their class. However, few if any studies were run comparing the ddI/d4T combination to alternatives such as AZT/3TC (Combivir) or even 3TC/d4T. Both ddI and d4T come from the same company, Bristol Myers Squibb.
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PMID:New questions about an old combination--ddI + d4T. 1264 75

HAART has resulted in dramatic declines in morbidity and mortality among patients infected with HIV. Increased experience with HAART has led to the detection of drug related toxicities that may compromise adherence and necessitate discontinuation of treatment and alteration of otherwise effective regimens. This article considers the major long-term complications associated with nucleoside reverse transcriptase inhibitor (NRTI) use--hyperlactatemia and lactic acidosis/hepatic steatosis, other hepatotoxicities, pancreatitis, lipodystrophy, lipoatrophy, neuropathy, and hematologic toxicities. Mechanisms by which NRTIs may produce these effects are discussed, as are differential effects of agents in this class and management options.
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PMID:Long-term complications of nucleoside reverse transcriptase inhibitor therapy. 1274 68

Data from basic science and clinical studies suggest that hydroxyurea (hydroxycarbamide)-based regimens are effective treatment options for patients with HIV at various stages of disease. In vitro studies of HIV-infected lymphocytes have shown that hydroxyurea: (i) inhibits viral DNA synthesis; (ii) synergistically interacts with nucleoside reverse transcriptase inhibitors (NRTI); and (iii) increases the antiviral activity of didanosine. Clinical studies have confirmed that hydroxyurea in combination with didanosine produces potent and sustained viral suppression in patients with HIV infection. However, some concerns have been recently raised on the use of hydroxyurea in association with NRTI. Hydroxyurea can cause myelosuppression, skin toxicities, mild gastrointestinal toxicity, and abnormalities of renal and liver functions. In addition, hydroxyurea may accentuate the toxic effects of nucleoside analogues. In fact, some clinical data seem to indicate an increased risk of pancreatitis and neuropathy when hydroxyurea is combined with didanosine and stavudine. Since hydroxyurea-related toxicity is dose dependent, a systematic study of hydroxyurea optimal dosage and schedule was initiated to monitor patients for possible nucleoside toxicity. In the Research Institute for Genetic and Human Therapy (RIGHT) 702 study it was shown that a low, well-tolerated hydroxyurea dose (600 mg daily) achieved better antiretroviral activity than higher doses, together with better CD4+ cell count increase and fewer adverse effects. In this paper the effects of hydroxyurea as salvage therapy for heavily pretreated patients with advanced HIV disease are presented. These studies have shown that some patients with extensive pretreatment experience and advanced disease can respond substantially to the addition of hydroxyurea. The addition of hydroxyurea to didanosine does not prevent the emergence of resistance to didanosine; nonetheless, the efficacy of this therapeutic regimen may not be attenuated by the presence of didanosine-resistant HIV mutants. Since CD4 T lymphocyte activation is essential for virus replication and CD8 T lymphocyte activation may contribute to pathogenesis, the combination of hydroxyurea with other drugs may lead to the inhibition of HIV, by blocking the 'cell activation-virus production-pathogenesis' cycle. Clinical data indicate that hydroxyurea may play a role in attenuation of viral rebound and immune reconstitution by decreasing CD4 T cell proliferation, as well as preventing the exhaustion of CD8 T cell populations that may result from excessive activation during HIV infection. While the combination of hydroxyurea with didanosine has provided hope, future studies including those that evaluate optimal dosing and long-term toxicity are needed to define the role for this agent in the treatment of HIV infection.
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PMID:Hydroxyurea in the treatment of HIV infection: clinical efficacy and safety concerns. 1281 30

Antiretroviral regimens are complicated and difficult for patients to follow, and they can have serious side effects, such as osteonecrosis and bone demineralization. Protease inhibitor therapy has been associated with hyperlipidemia, hyperglycemia, gastrointestinal symptoms, and body-fat distribution abnormalities. Nonnucleoside reverse transcriptase inhibitors can cause rashes and hepatotoxicity, and nucleoside reverse transcriptase inhibitors can cause lactic acidosis, hypersensitivity reactions, neuropathies, pancreatitis, anemia, and neutropenia. Malabsorption can occur if antiretroviral agents are taken improperly with regard to meals or if they are taken with certain other drugs or herbal remedies. Some commonly prescribed drugs can cause dangerous drug toxicities if they are taken by patients who are also taking certain antiretroviral medications. Suboptimal exposure to antiretrovirals because of noncompliance or malabsorption can result in viral resistance and loss of future treatment options.
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PMID:Managing issues related to antiretroviral therapy. 1295 84

Hepatocyte growth factor (HGF) overexpression is observed in experimental and clinical acute pancreatitis. Moreover, previous studies have shown that administration of HGF reduces pancreatic damage in experimental pancreatitis. The aim of our studies was to determine the role of cyclooxygenase-1 and cyclooxygenase-2 in the protective effect of HGF administration against caerulein-induced pancreatitis. Acute pancreatitis was induced in rats by infusion of caerulein. HGF was administered twice at the dose 10 microg/kg s.c. The activity of cyclooxygenase-1 and cyclooxygenase-2 was inhibited by resveratrol and rofecoxib, respectively (10 mg/kg). Immediately after cessation of caerulein or saline infusion, pancreatic blood flow, pancreatic cell proliferation, pancreatic prostaglandin E(2) generation, plasma lipase activity, plasma interleukin-1 beta and interleukin-10 concentration were measured and morphological signs of pancreatitis were examined. Expression of cyclooxygenase-1 and cyclooxygenase-2 mRNA transcripts was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Cyclooxygenase protein production was analyzed by Western blot. Administration of HGF or caerulein alone, or their combination, was without effect on cyclooxygenase-1 mRNA expression in pancreatic tissue. Expression of cyclooxygenase-2 mRNA was increased by HGF and caerulein. The maximal increase in cyclooxygenase-2 mRNA expression was observed when HGF administration was combined with caerulein infusion. A similar effect was observed when we studied the influence of HGF and caerulein on pancreatic cyclooxygenase-2 production, as determined by Western blot. Administration of HGF without induction of acute pancreatitis increased pancreatic prostaglandin E(2) generation and plasma interleukin-10, and this effect was abolished by the cyclooxygenase-2 inhibitor, rofecoxib. Treatment with HGF, during the development of pancreatitis, increased the plasma interleukin-10 concentration and attenuated pancreatic damage, as evidenced by: (a) histological improvement of pancreatic integrity; (b) the partial reversal of the decrease in DNA synthesis and pancreatic blood flow; (c) the reduction in pancreatitis-evoked increase in plasma lipase and interleukin-1 beta. Administration of resveratrol and rofecoxib alone was without effect on the development of pancreatitis. Combination of rofecoxib with HGF reduced the HGF-evoked increase in plasma interleukin-10 concentration and pancreatic prostaglandin E(2) generation, and abolished the protective effect of HGF against pancreatic damage in pancreatitis. Resveratrol did not affect the protective effect of HGF. We conclude that: (1) HGF induces cyclooxygenase-2 but not cyclooxygenase-1 expression; (2) inhibition of cyclooxygenase-2 in HGF-treated rats decreases the release of anti-inflammatory interleukin-10, increases the production of pro-inflammatory interleukin-1 beta and reduces pancreatic blood flow; (3) cyclooxygenase-2 activity is necessary for the protective effect of HGF in acute pancreatitis.
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PMID:Inhibition of cyclooxygenase-2 reduces the protective effect of hepatocyte growth factor in experimental pancreatitis. 1475 15

Mitochondrial toxicity has been implicated in the development of a variety of nucleoside reverse transcriptase inhibitor-associated syndromes. Mitochondrial damage and decreases in mitochondrial DNA levels have been demonstrated in various tissues of patients treated with NRTIs, especially in conjunction with exposure to stavudine. Clinical syndromes that may be mediated by mitochondrial toxicity include hyperlactatemia and lactic acidosis, hepatic steatosis, lipoatrophy, peripheral neuropathy, HIV-associated neuromuscular weakness syndrome, pancreatitis, skeletal myopathies, and cardiomyopathy. Early recognition of these syndromes in their mild forms involves close monitoring and a high index of suspicion. This may allow prompt discontinuation of the causative agent(s) and initiation of appropriate therapeutic measures, thereby increasing the chances of reversibility of the syndrome.
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PMID:Mitochondrial dysfunction: patient monitoring and toxicity management. 1531 67


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