Peroxisome proliferator-activated receptor γ agonist reduces the severity of post-ERCP pancreatitis in rats

AIM:To determine the effects of prophylactic peroxisome proliferator-activated receptor (PPARγ) agonist administration in an experimental model of postendoscopic retrograde cholangiopancreatography (postERCP) acute pancreatitis.METHODS: Post-ERCP pancreatitis was induced in male Wistar rats by infusion of contrast medium into the pancreatic duct. In additional group, rosiglitazone, a PPARγ agonist, was administered 1 h before infusion of contrast medium. Plasma and pancreas samples were obtained 6 h after the infusion.RESULTS: Infusion of contrast medium into the pancreatic duct resulted in an inflammatory process characterized by increased lipase levels in plasma, and edema and myeloperoxidase activity (MPO) in pancreas.This result correlated with the activation of nuclear factor κB (NFκB) and the inducible NO synthase (iNOS)expression in pancreatic cells. Rosiglitazone reduced the increase in lipase and the level of edema and the increase in myeloperoxidase as well as the activation of NFκB and iNOS expression.CONCLUSION: A single oral dose of rosiglitazone, given 1 h before post-ERCP pancreatitis induction is effective in reducing the severity of the subsequent inflammatory process. The protective effect of rosiglitazone was associated with NFκB inhibition and the blockage of leukocyte infiltration in pancreas.     

Effect of ligand troglitazone on peroxisome proliferator-activated receptor γ expression and cellular growth in human colon cancer cells

INTRODUCTION Nowadays, there is increasing interest in the use of specif ic agonists of peroxisome proliferator-activated receptor γ (PPARγ) as a new antineoplastic approach. PPARγ is a member of the nuclear receptor superfamily of ligand- dependent tr…     

Peroxisome proliferator-activated receptor γ agonist reduces the severity of post-ERCP pancreatitis in rats

INTRODUCTIONAcute pancreatitis is one of the major and serious complications after diagnostic or therapeutic endoscopic retrograde cholangiopancreatography(ERCP).Despite the technical improvements of recent years and the experience of endoscopists,the inc…     

Peroxisome proliferator-activated receptor-γ 34C>G polymorphism and colorectal cancer risk: A meta-analysis

AIM: To investigate the association between peroxisome proliferator-activated receptor-γ (PPAR-γ ) gene polymorphism 34 C>G and colorectal cancer (CRC),a meta-analysis review was performed in this report.METHODS: A systematic literature search and selection of eligible relevant studies were carried out.Nine independent studies with a total number of 4533 cases and 6483 controls were included in the meta-analysis on the association between polymorphism 34 C>G and CRC.RESULTS: There was no evidence for the as...     

Peroxisome proliferator-activated receptor-γ 34C>G polymorphism and colorectal cancer risk: A meta-analysis

AIM: To investigate the association between peroxisome proliferator-activated receptor-γ (PPAR-γ ) gene polymorphism 34 C>G and colorectal cancer (CRC),a meta-analysis review was performed in this report.METHODS: A systematic literature search and selection of eligible relevant studies were carried out.Nine independent studies with a total number of 4533 cases and 6483 controls were included in the meta-analysis on the association between polymorphism 34 C>G and CRC.RESULTS: There was no evidence for the as...     

Novel insights into the mechanisms whereby isoflavones protect against fatty liver disease

Fatty liver disease(FLD) is a growing public health problem worldwide. There is an urgent requirement for alternative and natural medicine to treat this disease. As phytochemicals, isoflavones have attracted considerable attention for the prevention of FLD. Numerous studies have revealed that isoflavones protect against FLD through various pathways which modulate fatty acid β-oxidation, lipid synthesis, and oxidative stress. Recently, the aldose reductase(AR)/polyol pathwayhas been reported to be involved in the development of FLD by modulating hepatic fructose production, peroxisome proliferator-activated receptor(PPAR)α activity, cytochrome P450(CYP)2E1 expression, and gut bacterial endotoxin-induced cytokine release. It has been reported that some isoflavones are potent AR inhibitors. Here, we review the anti-FLD actions of isoflavones and the proposed mechanism whereby isoflavones protect against FLD, with regard to the AR/polyol pathway. We propose that isoflavones block the AR/polyol pathway and in turn reduce fructose production and subsequent fat accumulation in the liver in diabetic or high-glucose-diet mice. In addition, in rodents with alcoholic liver disease or nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, inhibition of AR by isoflavones may improve PPARα-mediated fatty acid oxidation, reduce hepatic steatosis, and attenuate CYP2E1-mediated oxidative stress or AR/gut bacterial endotoxin-mediated cytokine overproduction, to alleviate progression of FLD.     

Decreased hepatic peroxisome proliferator-activated receptor-γ contributes to increased sensitivity to endotoxin in obstructive jaundice

AIM: To investigate the role of hepatic peroxisome proliferator-activated receptor-γ (PPAR-γ) in increased susceptibility to endotoxin-induced toxicity in rats with bile duct ligation during endotoxemia.METHODS: Male Sprague-Dawley rats were subjected to bile duct ligation (BDL). Sham-operated animals served as controls. DNA binding were determined by polymerase chain reaction, Western blotting analysis,and electrophoretic mobility shift assay, respectively.BDL and sham-operated rats received a non-lethal d...     

Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 in patients with fatty liver diseases

AIM:To test the occurrence of the Pro12Ala mutation of the peroxisome proliferator-activated receptor-γ (PPARγ)2-gene in patients with non-alcoholic fatty liver disease (NAFLD) or alcoholic fatty liver disease (AFLD).METHODS:DNA from a total of 622 specimens including 259 blood samples of healthy blood donors and 363 histologically categorized liver biopsies of patients with NAFLD (n=263) and AFLD (n=100) were analyzed by Real-time polymerase chain reaction using allele-specific probes.RESULTS:In the NAFLD and the AFLD collective,3% of the patients showed homozygous occurrence of the Ala12 PPARγ2-allele,differing from only 1.5% cases in the healthy population.In NAFLD patients,a high incidence of the Ala12 mutant was not associated with the progression of fatty liver disease.However,we observed a significantly higher risk (odds ratio=2.50,CI:1.05-5.90,P=0.028) in AFLD patients carrying the mutated Ala12 allele to develop inflammatory alterations.The linkage of the malfunctioning Ala12-positive PPARγ2 isoform to an increased risk in patients with AFLD to develop severe steatohepatitis and fibrosis indicates a more prominent anti-inflammatory impact of PPARγ2 in progression of AFLD than of NAFLD.CONCLUSION:In AFLD patients,the Pro12Ala single nuclear polymorphism should be studied more extensively in order to serve as a novel candidate in biomarker screening for improved prognosis.     

The Future of TZD,from Lab Bench to Bedside

The metabolic syndrome is strongly associated with insulin resistance and consists of a constellation of factors such as hypertension and hyperlipidemia that raise the risk for cardiovascular disease (CVD) and diabetes mellitus. Emerging data suggest that peroxisome proliferator-activated receptor-γ(PPARγ) is a critical determinant that may provide functional links between diabetes and CVD.     

Research on Autoantibodies Against Myocardial β1-adrenergic and M2 Cholinergic Receptors in Patients With Chronic Keshan Disease

Objectives To explore the relationship between serum autoantibodies against myocardialβ1-adrenergic, M2-cholinergic receptors and chronic Keshan disease (CKD). Methods The second extracellular loops ofβ1 and M2 receptors on human cardiomyocytes were used as the antigens. Enzyme linked immunosorbent assay (ELISA) was applied to determine serum autoantibodies against myocardialβ1 and M2 receptors in 32 CKD patients. 31 healthy subjects from endemic area were selected as the control. Results Positive rate of autoantibodies against myocardialβ1 adrenergic (51.3%, 17/32) and M2 cholinergic (56.3% , 18/32) receptors were significantly higher than those in the control (9.7%, 3/ 31; 12.9%, 4/31) (both P< 0.01). Both positive rate and liters of above autoantibodies in NYHAⅡ-ⅢCKD patients were significantly higher than those in NYHAⅣ, demonstrating an apparently positive correlation between serum antibodies against myocardialβ1 and M2 receptors (r=0.95). Conclusions Autoantibodies against myocardialβ1 and M2 receptors were found in sera of CKD patients; distribution of positive rate and liters of the auloanlibodies in CKD patients in various NYHA classes of cardiac function are significantly different.     

Expression of Interleukin-11 and Interleukin-11 receptor in human colorectal adenocarcinoma; Immunohistochemical analyses and correlation with clinicopathological factors

AIM: There is strong evidence that interleukin-11 (IL-11)is involved in the regulation of tumor progression, cellular growth and differentiation. Recently, interleukin-11receptor (IL-11R) has been detected on some cancer cells. In this study, we investigated the expression of IL-11 and IL-11R in colorectal adenocarcinoma.METHODS: To elucidate the involvement of IL-11 and IL-11Rα in human intestinal adenocarcinomas, we examined 115 cases of surgically resected human colonic adenocarcinoma and 11 cases of adenoma by immunohistochemistry and Western blotting.RESULTS: Among 115 cases of adenocarcinoma, 100cases (87.0%) showed positive staining in the cytoplasm of carcinoma cells for the IL-11, and 87 cases (75.6%)were positive for the IL-11Rα. Six cases (54.5%) and four cases (36.4%) of 11 adenomas were positive for IL-11 and IL-11Rα, respectively. The expression of IL-11Rα correlated with the histological differentiation (P =0.033503), the depth of tumor invasion (P= 0.006395),Dukes classification (P= 0.015648) and lymphatic invasion (P=0.003865). However, the expression of IL-11Rα was not correlated with the venous invasion and the presence of lymph node metastasis. The expression of IL-11 was not correlated with any clinicopathological factors. In Western blot analysis, two human colorectal carcinoma cell lines and four tissues of surgically resected human carcinoma expressed both IL-11 and IL-11Rαproteins.CONCLUSION: IL-11 and IL-11Rα are highly expressed in human colorectal adenocarcinoma and the IL-11Rα expression is correlated with clinicopathological factors.These findings suggest that the expression of IL-11Rα is an important factor for the invasion of human colorectal adenocarcinoma.     

Renin and cardiovascular disease: Worn-out path, or new direction

Inhibition of the renin angiotensin system has beneficial effects in cardiovascular prevention and treatment. The advent of orally active direct renin inhibitors adds a novel approach to antagonism of the renin-angiotensin system.Inhibition of the first and rate-limiting step of the renin angiotensin cascade offers theoretical advantages over downstream blockade.However,the recent discovery of the(pro)renin receptor which binds both renin and prorenin,and which can not only augment catalytic activity of both renin and prorenin in converting angiotensinogen to angiotensinⅠ,but also signal intracellularly via various pathways to modulate gene expression,adds a significant level of complexity to the field.In this review,we will examine the basic and clinical data on renin and its inhibition in the context of cardiovascular pathophysiology.     

Exploitation of the nicotinic anti-inflammatory pathway for the treatment of epithelial inflammatory diseases

INTRODUCTION Tobacco smoke appears to affect susceptibility to and theseverity of various skin and mucosal diseases differently. For example, tobacco smoking is associated with an increased incidence and clinical severity of psoriasis[1-3] and Crohn’s di…     

Effects on the pouch of different digestive tract reconstruction modes assessed by radionuclide scintigraphy

AIM: To determine the effect of three digestive tract reconstruction procedures on pouch function, after radical surgery undertaken because of gastric cancer, as assessed by radionuclide dynamic imaging. METHODS: As a measure of the reservoir function, with a designed diet containing technetium-99m (99mTc), the emptying time of the gastric substitute was evaluated using a 99mTc-labeled solid test meal. Immediately after the meal, the patient was placed in front of a γ camera in a supine position and the rad...     

Effects of AT1 receptor antagonist, Iosartan, on rat hepatic fibrosis induced by CCl4

AIM To investigate effect of Iosartan, an AT1 receptor antagonist, on hepatic fibrosis induced by CCI4; and to determine whether or not AT1 receptors are expressed on hepatic stellate cells. M~THODS AND RESULTS Fifty male SpragueDawley rats, weighing (180 ± 20) g, were randomized into five groups (control group, model group, and three Iosartan treated groups ), in which all rats were given the subcutaneous injection of 40% CCl4 (every 3 days for 6 weeks) except for rats of control group. Rats of Iosartantreated groups were treated with Iosartan (20 mg/ kg, 10 mg/kg, 5 mg/kg, daily gavage). After 6 weeks liver tissue and serum samples of all rats were examined. Serum hyaluronic acid (HA), procollagen type Ⅲ (PC Ⅲ ) were detected by radioimmunoassays. van Giesion collagen staining was used to evaluate the extracellular matrix of rats with liver fibrosis. The expression of AT1 receptors, transforming growth factor-beta (TGFβ), and alpha-smooth muscle actin (α-SMA) in liver tissue were determined by immunohistochemical techniques. Compared with model group, serum ALT and AST of Iosartantreated groups were significantly reduced (t = 4.20, P < 0.01 and t = 4.57, P < 0.01 ). Serum HA and PC Ⅲ also had significant differences (t = 3.53, P<0.01 and t=2.20, P<0.05). The degree of fibrosis was improved by Iosartan and correlated with the expressions of AT1 receptors, TGF-β, and α-SMA in liver tissue. CONCLUSION AT1 receptor antagonist, Iosartan, could limit the progression of the hepatic fibrosis induced by CCl4. The mechanism may be related to the decrease in the expression of AT1 receptors and TGF-β, ameliorating the injury of hepatocytes; activation of local renin-angiotensin system might relate to hepatic fibrosis; and during progression of fibrosis, activated hepatic stellate cells might express AT1 receptors.     

CCR5△32 mutation does not influence the susceptibility to HCV infection, severity of liver disease and response to therapy in patients with chronic hepatitis C

AIM: To study whether CCR5△32 mutation was associated with viral infection and severity of liver disease.METHODS: Two hundred and fifty two histologically proven, chronic HCV patients (mean age: 41 ± 14 years;M/F: 164/88) were genotyped. PCR based genotyping of 32 bp deletion at the CCR5 locus was done. Fourhundred and eight matched healthy controls were studied to assess susceptibility to HCV infection. To assess correlation of immune gene polymorphism with severity of HCV related liver disease, patients with chronic HCV infection were divided into those with a fibrosis score of ≤ 2 (mild) or ＞ 2 (severe) and histological activity index (HAI) of ≤ 5 or ＞ 5. For correlation between CCR5△32 mutations and response to therapy, 129 patients who completed therapy were evaluated.RESULTS: The majority (89.4%) of the patients were infected with genotype 3. The frequency of homozygous CCR5△32 mutants was comparable to HCV patients as compared to the healthy controls (0.7% vs 0%, P = 0.1).Further more, the frequency of CCR5△32 mutation was comparable in patients with mild or severe liver disease.(P = NS). There was also no association observed with response to therapy and CCR5△32 mutation.CONCLUSION: CCR5△32 mutation does not have a role in disease susceptibility, severity or response to therapy in patients with chronic hepatitis C infection.