Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factor-alpha (TNF alpha) is postulated to be a mediator of the systemic complications associated with acute pancreatitis. Neutralization of TNF alpha with monoclonal antibody ameliorates the morbidity and mortality associated with acute pancreatitis in a rat model. Although high levels of TNF alpha are measurable in peripheral blood in acute pancreatitis, specific sites of TNF alpha production in this disease have not been described. In this study we show that induction of pancreatitis causes up-regulation of TNF alpha messenger RNA (mRNA) at a distant organ site, the spleen. Hemisplenectomies were performed in male Sprague-Dawley rats prior to induction of pancreatitis by pancreatic duct infusion of artificial bile. Completion hemisplenectomies were then performed at 30 min, 1 hr, and 2 hr after pancreatitis induction. Quantitation of TNF alpha mRNA in the hemispleens before and after pancreatitis using a semiquantitative reverse transcriptase-polymerase chain reaction method revealed an 80-fold increase in amount of TNF alpha mRNA by 2 hr after induction of pancreatitis. By contrast, control rats receiving a sham operation showed no significant increase in TNF alpha mRNA expression after infusion of the pancreatic duct with saline. The increase in TNF alpha mRNA production was associated with increased serum TNF alpha product levels and was independent of endotoxin. We conclude that severe acute pancreatitis in the rat model is associated with significant up-regulation of TNF alpha mRNA in splenic mononuclear cells. These data provide evidence that the local events of acute pancreatitis can induce up-regulation of TNF alpha mRNA at a distant site and suggest a possible mechanism of pathogenesis of the systemic manifestations of this disease.
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PMID:Up-regulation of TNF alpha mRNA in the rat spleen following induction of acute pancreatitis. 853 66

Protease inhibitor treatment has dramatically improved rates of morbidity and mortality in HIV-infected patients. However, it has recently been shown that this medication is associated with long-term side effects characterized by metabolic, clinical and biological alterations. These modifications have been described in patients treated with highly active antiretroviral therapy (HAART), including nucleoside analogue reverse transcriptase inhibitors (NRTI) and generally (but not always) protease inhibitors (PI). Clinical alterations are characterised by a body fat redistribution syndrome or lipodystrophy, with peripheral lipoatrophy and/or central fat accumulation. They are often associated with biological alterations, i.e. insulin resistance, hyperglycaemia and dyslipidaemia, which can also be observed alone. The pathophysiology of these alterations is presently unknown. The deleterious effect of PI on adipose tissue could be direct or indirect, and is probably modulated by genetic or environmental factors. NRTI could also be involved because of their mitochondrial toxicity. The purpose of the treatment is to control metabolic disturbances in order to prevent immediate complications such as acute pancreatitis and limit possible cardiovascular and diabetic complications at longer term. Studies are in progress to evaluate the possibility of therapeutic alternatives to PI when major metabolic disturbances are present.
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PMID:Adverse metabolic disorders during highly active antiretroviral treatments (HAART) of HIV disease. 1059 60

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

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

Treating Hepatitis C among HIV patients under antiretroviral drug therapy requires a high degree of vigilance and continuous monitoring because of frequent problems with intolerance and/or drug interactions. Recent studies, including three therapeutic trials, on Ribavic, APRICOT, and ACTG A5671, have given some insights on following these patients up. The adverse effects are relatively similar in HCV-HIV-co-infected patients and patients infected by HCV only. Their frequency is, on the other hand, higher among HCV-HIV-Co-infected patients. The adverse-effects are consistent, in a non-exhaustive way, with pseudo influenza-like symptoms, fever, myalgia, cephalgia, with psychiatric disorders (irritability, depression, etc.); endocrine disorders (thyroid dysfunction, diabetes...); and with hematological anomalies especially anemia and leucopenia. But the percentage of lymphocyte T CD4 is not modified, therefore there is no risk of opportunistic infection. Pharmacokinetic interactions between antiretroviral drugs and treatment for HCV infection including ribavirin plus interferon alpha (IFN-alpha) or pegylated IFN are described. They are almost exclusively due to the combination of ribavirin and of nucleoside analogue reverse transcriptase inhibitors. One of the principal consequences is the emergence of mitochondrial toxicity defined by the occurrence of hyperlactatemia, or acute pancreatitis). Thus, some combinations should be avoided such as ddI+ribavirin and ddI+d4T+ribavirin. The d4T+ribavirin combination must also be used with caution.
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PMID:[Intolerance to and/or drug interactions of anti-HIV and anti-HVC therapy]. 1591 Nov 83

Acute pancreatitis (AP) is a well-known adverse effect of nucleoside reverse transcriptase inhibitors (NRTIs). Therefore, we performed a prospective, cohort study to examine the incidence rates (IRs) and rate ratios (RRs) of AP for each NRTI. A total of 116 HIV patients were included in the final analysis comprising 445.6 person-years of follow-up. Twelve cases of AP were recorded. The lowest IR for AP was for didanosine (ddI) (IR=0.03 per 100 person-years, 95% confidence interval [CI] = 0.01-0.05), and the highest for ddI + stavudine (d4T) (IR = 0.08, 95% CI = 0.07-012). Compared with ddI alone, the RR of AP was 2.21 (95% CI = 1.32-9.31) for d4T, and 3.13 (95% CI = 1.43-12.56) for ddI + d4T. Other risk factors for AP were CD4 cell count <200 cells/mm(3) and female sex. Our results suggest that the use of d4T alone or combined with ddI should not be used as first-line therapy, especially in women or patients with CD4-cell count <200 cells/mm(3).
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PMID:Incidence of acute pancreatitis and nucleoside reverse transcriptase inhibitors usage. 1596 77

To assess the incidence of and risk factors for acute pancreatitis in HIV-infected patients in the contemporary highly active antiretroviral therapy (HAART) era, we evaluated all cases of acute pancreatitis requiring hospitalization between 1996 and 2006 in patients followed at Johns Hopkins Hospital's HIV clinic. A nested, case-control analysis was employed for initial episodes of acute pancreatitis, and conditional logistic regression was used to assess risk factors. Of 5970 patients followed for 23,460 person-years (PYs), there were 85 episodes of acute pancreatitis (incidence: 3.6 events/1000 PYs). The incidence of pancreatitis from 1996 to 2000 was 2.6 events/1000 PYs; the incidence from 2001 to 2006 was 5.1 events/1000 PYs (p = 0.0014, comparing rates in two time periods). In multivariate regression, factors associated with pancreatitis included female gender (adjusted odds ratio [AOR] 2.96 [1.69, 5.19]; p < 0.001); stavudine use (AOR 2.19 [1.16, 4.15]; p = 0.016); aerosolized pentamidine use (OR 6.27; [1.42, 27.63]; p = 0.015); and CD4 count less than 50 cells/mm(3) (AOR 10.47 [3.33, 32.90]; p < 0.001). Race/ethnicity, HIV risk factor, HIV-1 RNA, and newer non-nucleoside reverse transcriptase inhibitors (NNRTI)- and protease inhibitor (PI)-based HAART regimens were not associated with an increased risk of pancreatitis after adjustment for the above factors. Pancreatitis remains a significant cause of morbidity in the HIV population in the HAART era. Acute pancreatitis is associated with female gender, severe immunosuppression, and stavudine and aerosolized pentamidine usage. Of note, newer antiretrovirals, particularly atazanavir, lopinivir/ritonavir, tenofovir, abacavir, and efavirenz, were not associated with an increased risk of pancreatitis.
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PMID:A ten-year analysis of the incidence and risk factors for acute pancreatitis requiring hospitalization in an urban HIV clinical cohort. 1826 Aug 2

Pancreatitis-associated protein (PAP) is a secretory protein that is not only expressed during acute pancreatitis but also in pancreatic adenocarcinoma, gastric carcinoma, hepatocellular carcinoma, and colorectal carcinoma. Expression in carcinoma might be another characteristic of PAP. The aim of our study was to assess, in 27 patients undergoing surgery for colorectal carcinoma, the expression of the PAP mRNA and to evaluate its association with DNA ploidy and proliferative activity (S-phase fraction, SPF) by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometric analysis (FCM). PAP mRNA was expressed in 29.6% (8 of 27) of the patients with colorectal carcinoma. DNA aneuploid and high SPF were found in 87.5% (7 of 8) of patients with PAP mRNA positive colorectal carcinoma. The serum PAP level was significantly elevated in patients with colorectal carcinoma when compared with the healthy subjects. Twelve of the 27 patients with colorectal carcinoma had high serum PAP concentrations (>25 ng/mL) and the mean SPF was 17.82% +/- 8.02%, which was significantly higher compared with the normal colorectal tissue group (7.33% +/- 3.18%, P < 0.05). The mean serum PAP concentration of DNA aneuploidy colorectal carcinomas was 46.67 +/- 17.58 ng/mL, which was significantly different when compared with the DNA diploidy group (19.18 +/- 8.89 ng/mL, P < 0.05). PAP mRNA expression and serum PAP levels are closely related to neoplastic proliferative activity in patients with colorectal carcinoma. No significant differences are observed between PAP mRNA expression and clinicopathologic parameters (P > 0.05).
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PMID:Pancreatitis-associated protein is related closely to neoplastic proliferative activity in patients with colorectal carcinoma. 1905 Dec 57

Background and aims Reg4 is a recently discovered member of the regenerating gene family with distinctive expression profiles in primary cancers. To date, the physiological function of Reg4 is poorly understood. Previously, the authors found that Reg4 was markedly upregulated during acute pancreatitis (AP). The aim of this study was to investigate the role of Reg4 in experimental pancreatitis. Methods AP was induced in C57BL/6 mice by administration of either l-arginine or caerulein, and Reg4 expression was assessed by immunofluorescence, reverse transcriptase (RT)-PCR and western blot analyses. Recombinant human Reg4 protein (rReg4), heat-inactivated Reg4, neutralising antibody and vehicle were also administered to mice by subcutaneous injection. The severity of AP was determined by measuring amylase and lipase activities in the serum and histological grading. The effect of rReg4 on cell death was examined and epidermal growth factor receptor (EGFR), p-EGFR, Akt, p-Akt, Bcl-2 and Bcl-xL expression were assessed by western blot analysis of isolated murine acinar cells treated with l-arginine. Results Reg4 mRNA and protein were markedly upregulated during arginine-induced pancreatitis. Reg4 was widely expressed in residual acinar cells around the islets and regenerating metaplastic epithelium. rReg4 could protect against arginine-induced necrosis of acinar cells both in vivo and in vitro. This protective effect was also confirmed in the caerulein-induced murine model of AP. It was shown that arginine induced expression of Bcl-2 and Bcl-xL, while rReg4 upregulated Bcl-2 and Bcl-xL expression by activating the EGFR/Akt pathway. The upregulation of Bcl-xL correlated inversely with cell necrosis in isolated pancreatic acinar cells. Conclusions The data suggest that Reg4 may protect against acinar cell necrosis in experimental pancreatitis by enhancing the expression of Bcl-2 and Bcl-xL via activation of the EGFR/Akt signalling pathway.
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PMID:Reg4 protects against acinar cell necrosis in experimental pancreatitis. 2119 57

Based on the function of chemokine fractalkine (FKN), acting as both adhesion and chemoattractant, FKN plays a role in acute inflammatory response. In this study, we investigated the mechanism of FKN mediated upregulation inflammation in severe acute pancreatitis (SAP) rat models. Western blot, reverse transcriptase-polymerase chain reaction, and immunofluorescence demonstrated that FKN and its receptor CX3CR1 were overexpressed in cerulein-stimulated AR42J cells. AG490 and FKN-siRNA inhibited activation of Janus kinase/signal transducers and activators of transcription (Jak/Stat) in cerulein-stimulated AR42J cells. Following exposure AG490 and FKN-siRNA inhibited tumor necrosis factor-alpha expression by enzyme-linked immunosorbent assay and immunohistochemistry in vivo the SAP rat models. These results showed FKN and CX3CR1 were involved inflammatory response in cerulein-stimulated AR42J cells. FKN upregulates inflammation through CX3CR1 and the Jak/Stat pathway in SAP rat models.
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PMID:Fractalkine upregulates inflammation through CX3CR1 and the Jak-Stat pathway in severe acute pancreatitis rat model. 2221 34


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