Acute pancreatitis is an inflammatory disorder of the pancreas that may cause life-threatening complications.Etiologies of pancreatitis vary,with gallstones accounting for the majority of all cases,followed by alcohol...Acute pancreatitis is an inflammatory disorder of the pancreas that may cause life-threatening complications.Etiologies of pancreatitis vary,with gallstones accounting for the majority of all cases,followed by alcohol.Other causes of pancreatitis include trauma,ischemia,mechanical obstruction,infections,autoimmune,hereditary,and drugs.The main events occurring in the pancreatic acinar cell that initiate and propagate acute pancreatitis include inhibition of secretion,intracellular activation of proteases,and generation of inflammatory mediators.Small cytokines known as chemokines are released from damaged pancreatic cells and attract inflammatory cells,whose systemic action ultimately determined the severity of the disease.Indeed,severe forms of pancreatitis may result in systemic inflammatory response syndrome and multiorgan dysfunction syndrome,characterized by a progressive physiologic failure of several interdependent organ systems.Stress occurs when homeostasis is threatened,and stressors can include physical or mental forces,or combinations of both.Depending on the timing and duration,stress can result in beneficial or harmful consequences.While it is well established that a previous acute-short-term stress decreases the severity of experimentally-induced pancreatitis,the worsening effects of chronic stress on the exocrine pancreas have received relatively little attention.This review will focus on the influence of both prior acute-short-term and chronic stress in acute pancreatitis.展开更多
AIM To study the effects of aminoguanidine(AG) and two L-arginine analogues Nω-nitro-L-arginine methyl ester (L-NAME) and Nω-nitro-L-arginine (L-NNA) on nitric oxide (NO) productioninduced by cytokines (TNF-α, IL-1...AIM To study the effects of aminoguanidine(AG) and two L-arginine analogues Nω-nitro-L-arginine methyl ester (L-NAME) and Nω-nitro-L-arginine (L-NNA) on nitric oxide (NO) productioninduced by cytokines (TNF-α, IL-11β, and IFN-γ)and bacterial lipopolysaccharide (LPS) mixture(CM) in the cultured rat hepatocytes, andexamine their mechanisms action.METHODS Rat hepatocytes were incubatedwith AG, L-NAME, L-NNA, Actinomycin D (ActD)and dexamethasene in a medium containing CM(LPS plus TNF-α, IL-1β, and IFN-γ) for 24 h. NOproduction in the cultured supernatant wasmeasured with the Griese reaction. IntracellularcGMP level was detected with radioimmunoasey.RESULTS NO production was markedlyblocked by AG and L-NAME in a dose-dependentmanner under inflammatory stimuli conditiontriggered by CM in vitro. The rate of themaximum inhibitory effects of L-NAME (38.9%)was less potent than that obtained with AG(53.7%, P<0.05). There was no significantdifference between the inhibitory effects of AGand two L-arginine analogues on intracellularcGMP accumulation in rat cultured hepatocytes.Non-specific NOS expression inhibitordexamethasone ( DEX ) and iNOS mRNAtranscriptional inhibitor ActD also significantlyinhibited CM-induced NO production. AG(0.1mmol.L-1) and ActD (0.2ng@Lt) wereequipotent in decreasing NO production inducedby inflammatory stimuli in vitro, and botheffects were more potent than that induced bynon-selectivity NOS activity inhibitor L-NAME(0. 1 mmol@ L- 1) under similar stimuli conditions(P＜O.O1).CONCLUSION AG is a potent selectiveinhibitor of inducible isoform of NOS, and themechanism of action may be not onlycompetitive inhibition in the substrate level, butalso the gene expression level in rathepatocytes .展开更多
AIM:To determine the effect of non-selective cyclooxygenase (COX) inhibitors,selective COX-2 inhibitors and nitric oxide (NO)-releasing aspirin in the healing of ulcerative colitis.METHODS:Rats with 2,4,6 trinitrobenz...AIM:To determine the effect of non-selective cyclooxygenase (COX) inhibitors,selective COX-2 inhibitors and nitric oxide (NO)-releasing aspirin in the healing of ulcerative colitis.METHODS:Rats with 2,4,6 trinitrobenzenesulfonic acid (TNBS)-induced colitis received intragastric (ig) treatment with vehicle,aspirin (ASA) (a nonselective COX inhibitor),celecoxib (a selective COX-2 inhibitor) or NO-releasing ASA for a period of ten days.The area of colonic lesions,colonic blood flow (CBF),myeloperoxidase (MPO) activity and expression of proinflammatory markers COX-2,inducible form of nitric oxide synthase (iNOS),IL-1β and tumor necrosis factor (TNF)-α were assessed.The effects of glyceryl trinitrate (GTN),a NO donor,and 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide,onopotassium salt (carboxy-PTIO),a NO scavenger,administered without and with ASA or NO-ASA,and the involvement of capsaicin-sensitive afferent nerves in the mechanism of healing the experimental colitis was also determined.RESULTS:Rats with colitis developed macroscopic and microscopic colonic lesions accompanied by a significant decrease in the CBF,a significant rise in colonic weight,MPO activity and plasma IL-1β and TNF-α levels.These effects were aggravated by ASA and 5-(4-chlorophenyl)-1-(4-methoxyphenyl)3-(trifluoromethyl)-1H-pyrazole (SC-560),but not celecoxib and counteracted by concurrent treatment with a synthetic prostaglandin E 2 (PGE 2) analog.Treatment with NO-ASA dose-dependently accelerated colonic healing followed by a rise in plasma NO x content and CBF,suppression of MPO and downregulation of COX-2,iNOS,IL-1β and TNF-α mRNAs.Treatment with GTN,the NO donor,significantly inhibited the ASA-induced colonic lesions and increased CBF,while carboxy-PTIO or capsaicin-denervation counteracted the NO-ASAinduced improvement of colonic healing and the accompanying increase in the CBF.These effects were restored by co-treatment with calcitonin gene related peptide (CGRP) and NO-ASA in capsaicin-denervated animals.CONCLUSION:NO-releasing ASA,in contrast to ASA,COX-1 inhibitors,and SC-560,accelerated the healing of colitis via a mechanism involving NO mediated improvement of microcirculation and activation of sensory nerves releasing CGRP.展开更多
Objective To investigate the anti-inflammation effect and possible mechanism of Salvianic acid A(SAA)in mouse peritoneal macrophages.Methods Peritoneal macrophages were obtained from BALB/c mice.LPS induced nitric oxi...Objective To investigate the anti-inflammation effect and possible mechanism of Salvianic acid A(SAA)in mouse peritoneal macrophages.Methods Peritoneal macrophages were obtained from BALB/c mice.LPS induced nitric oxide(NO),tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in supernatant,protein expression of inducible nitric oxide synthase(iNOS),matrix metalloproteinase-9(MMP-9)and activation of nuclear factor-kappa B(NF-κB)in the extract were measured.Results SAA strongly inhibited the excessive production of NO,TNF-α and IL-6 in LPS-induced peritoneal macrophages in a concentration-dependent manner and blocked the expression of iNOS and MMP-9.Treatment with LPS alone increased the translocation of NF-κB(p65)from cytosol to the nucleus,but the SAA inhibited the translocation of NF-κB(p65).Conclusions The results showed that SAA had strong anti-inflammatory effects in LPS-stimulated peritoneal macrophages.The important mechanism is due to its inhibition of NF-κB activation.展开更多
BACKGROUND Coronary artery disease(CAD)is a major cause of death worldwide,and India contributes to about one-fifth of total CAD deaths.The development of CAD has been linked to the accumulation of Nε-carboxymethyl-l...BACKGROUND Coronary artery disease(CAD)is a major cause of death worldwide,and India contributes to about one-fifth of total CAD deaths.The development of CAD has been linked to the accumulation of Nε-carboxymethyl-lysine(CML)in heart muscle,which correlates with fibrosis.AIM To assess the impact of CML and inflammatory markers on the biochemical and cardiovascular characteristics of CAD patients with and without diabetes.METHODS We enrolled 200 consecutive CAD patients who were undergoing coronary angiography and categorized them into two groups based on their serum glycosylated hemoglobin(HbA1c)levels(group I:HbA1c≥6.5;group II:HbA1c<6.5).We analyzed the levels of lipoproteins,plasma HbA1c levels,CML,interleukin-6(IL-6),tumor necrosis factor alpha(TNF-α),and nitric oxide.RESULTS Group I (81 males and 19 females) patients had a mean age of 54.2 ± 10.2 years, with a mean diabetes duration of4.9 ± 2.2 years. Group II (89 males and 11 females) patients had a mean age of 53.2 ± 10.3 years. Group I had moresevere CAD, with a higher percentage of patients with single vessel disease and greater stenosis severity in the leftanterior descending coronary artery compared to group II. Group I also exhibited a larger left atrium diameter.Group I patients exhibited significantly higher levels of CML, TNF-α, and IL-6 and lower levels of nitric oxide ascompared with group II patients. Additionally, CML showed a significant positive correlation with IL-6 (r = 0.596,P = 0.001) and TNF-α (r = 0.337, P = 0.001) and a negative correlation with nitric oxide (r=-4.16, P = 0.001). Oddsratio analysis revealed that patients with CML in the third quartile (264.43-364.31 ng/mL) were significantlyassociated with diabetic CAD at unadjusted and adjusted levels with covariates.展开更多
基金Supported by KB and Associates Representing Certification International(United Kingdom)Limited
文摘Acute pancreatitis is an inflammatory disorder of the pancreas that may cause life-threatening complications.Etiologies of pancreatitis vary,with gallstones accounting for the majority of all cases,followed by alcohol.Other causes of pancreatitis include trauma,ischemia,mechanical obstruction,infections,autoimmune,hereditary,and drugs.The main events occurring in the pancreatic acinar cell that initiate and propagate acute pancreatitis include inhibition of secretion,intracellular activation of proteases,and generation of inflammatory mediators.Small cytokines known as chemokines are released from damaged pancreatic cells and attract inflammatory cells,whose systemic action ultimately determined the severity of the disease.Indeed,severe forms of pancreatitis may result in systemic inflammatory response syndrome and multiorgan dysfunction syndrome,characterized by a progressive physiologic failure of several interdependent organ systems.Stress occurs when homeostasis is threatened,and stressors can include physical or mental forces,or combinations of both.Depending on the timing and duration,stress can result in beneficial or harmful consequences.While it is well established that a previous acute-short-term stress decreases the severity of experimentally-induced pancreatitis,the worsening effects of chronic stress on the exocrine pancreas have received relatively little attention.This review will focus on the influence of both prior acute-short-term and chronic stress in acute pancreatitis.
基金Project supported by the National Natural Science Foundation of China,No.39770861.and JANSSEN Science Research Foundation.
文摘AIM To study the effects of aminoguanidine(AG) and two L-arginine analogues Nω-nitro-L-arginine methyl ester (L-NAME) and Nω-nitro-L-arginine (L-NNA) on nitric oxide (NO) productioninduced by cytokines (TNF-α, IL-11β, and IFN-γ)and bacterial lipopolysaccharide (LPS) mixture(CM) in the cultured rat hepatocytes, andexamine their mechanisms action.METHODS Rat hepatocytes were incubatedwith AG, L-NAME, L-NNA, Actinomycin D (ActD)and dexamethasene in a medium containing CM(LPS plus TNF-α, IL-1β, and IFN-γ) for 24 h. NOproduction in the cultured supernatant wasmeasured with the Griese reaction. IntracellularcGMP level was detected with radioimmunoasey.RESULTS NO production was markedlyblocked by AG and L-NAME in a dose-dependentmanner under inflammatory stimuli conditiontriggered by CM in vitro. The rate of themaximum inhibitory effects of L-NAME (38.9%)was less potent than that obtained with AG(53.7%, P<0.05). There was no significantdifference between the inhibitory effects of AGand two L-arginine analogues on intracellularcGMP accumulation in rat cultured hepatocytes.Non-specific NOS expression inhibitordexamethasone ( DEX ) and iNOS mRNAtranscriptional inhibitor ActD also significantlyinhibited CM-induced NO production. AG(0.1mmol.L-1) and ActD (0.2ng@Lt) wereequipotent in decreasing NO production inducedby inflammatory stimuli in vitro, and botheffects were more potent than that induced bynon-selectivity NOS activity inhibitor L-NAME(0. 1 mmol@ L- 1) under similar stimuli conditions(P＜O.O1).CONCLUSION AG is a potent selectiveinhibitor of inducible isoform of NOS, and themechanism of action may be not onlycompetitive inhibition in the substrate level, butalso the gene expression level in rathepatocytes .
基金Supported by The financial grant K/PBW/000067 of the Polish Ministry of Science and Higher Education
文摘AIM:To determine the effect of non-selective cyclooxygenase (COX) inhibitors,selective COX-2 inhibitors and nitric oxide (NO)-releasing aspirin in the healing of ulcerative colitis.METHODS:Rats with 2,4,6 trinitrobenzenesulfonic acid (TNBS)-induced colitis received intragastric (ig) treatment with vehicle,aspirin (ASA) (a nonselective COX inhibitor),celecoxib (a selective COX-2 inhibitor) or NO-releasing ASA for a period of ten days.The area of colonic lesions,colonic blood flow (CBF),myeloperoxidase (MPO) activity and expression of proinflammatory markers COX-2,inducible form of nitric oxide synthase (iNOS),IL-1β and tumor necrosis factor (TNF)-α were assessed.The effects of glyceryl trinitrate (GTN),a NO donor,and 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide,onopotassium salt (carboxy-PTIO),a NO scavenger,administered without and with ASA or NO-ASA,and the involvement of capsaicin-sensitive afferent nerves in the mechanism of healing the experimental colitis was also determined.RESULTS:Rats with colitis developed macroscopic and microscopic colonic lesions accompanied by a significant decrease in the CBF,a significant rise in colonic weight,MPO activity and plasma IL-1β and TNF-α levels.These effects were aggravated by ASA and 5-(4-chlorophenyl)-1-(4-methoxyphenyl)3-(trifluoromethyl)-1H-pyrazole (SC-560),but not celecoxib and counteracted by concurrent treatment with a synthetic prostaglandin E 2 (PGE 2) analog.Treatment with NO-ASA dose-dependently accelerated colonic healing followed by a rise in plasma NO x content and CBF,suppression of MPO and downregulation of COX-2,iNOS,IL-1β and TNF-α mRNAs.Treatment with GTN,the NO donor,significantly inhibited the ASA-induced colonic lesions and increased CBF,while carboxy-PTIO or capsaicin-denervation counteracted the NO-ASAinduced improvement of colonic healing and the accompanying increase in the CBF.These effects were restored by co-treatment with calcitonin gene related peptide (CGRP) and NO-ASA in capsaicin-denervated animals.CONCLUSION:NO-releasing ASA,in contrast to ASA,COX-1 inhibitors,and SC-560,accelerated the healing of colitis via a mechanism involving NO mediated improvement of microcirculation and activation of sensory nerves releasing CGRP.
文摘Objective To investigate the anti-inflammation effect and possible mechanism of Salvianic acid A(SAA)in mouse peritoneal macrophages.Methods Peritoneal macrophages were obtained from BALB/c mice.LPS induced nitric oxide(NO),tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in supernatant,protein expression of inducible nitric oxide synthase(iNOS),matrix metalloproteinase-9(MMP-9)and activation of nuclear factor-kappa B(NF-κB)in the extract were measured.Results SAA strongly inhibited the excessive production of NO,TNF-α and IL-6 in LPS-induced peritoneal macrophages in a concentration-dependent manner and blocked the expression of iNOS and MMP-9.Treatment with LPS alone increased the translocation of NF-κB(p65)from cytosol to the nucleus,but the SAA inhibited the translocation of NF-κB(p65).Conclusions The results showed that SAA had strong anti-inflammatory effects in LPS-stimulated peritoneal macrophages.The important mechanism is due to its inhibition of NF-κB activation.
文摘BACKGROUND Coronary artery disease(CAD)is a major cause of death worldwide,and India contributes to about one-fifth of total CAD deaths.The development of CAD has been linked to the accumulation of Nε-carboxymethyl-lysine(CML)in heart muscle,which correlates with fibrosis.AIM To assess the impact of CML and inflammatory markers on the biochemical and cardiovascular characteristics of CAD patients with and without diabetes.METHODS We enrolled 200 consecutive CAD patients who were undergoing coronary angiography and categorized them into two groups based on their serum glycosylated hemoglobin(HbA1c)levels(group I:HbA1c≥6.5;group II:HbA1c<6.5).We analyzed the levels of lipoproteins,plasma HbA1c levels,CML,interleukin-6(IL-6),tumor necrosis factor alpha(TNF-α),and nitric oxide.RESULTS Group I (81 males and 19 females) patients had a mean age of 54.2 ± 10.2 years, with a mean diabetes duration of4.9 ± 2.2 years. Group II (89 males and 11 females) patients had a mean age of 53.2 ± 10.3 years. Group I had moresevere CAD, with a higher percentage of patients with single vessel disease and greater stenosis severity in the leftanterior descending coronary artery compared to group II. Group I also exhibited a larger left atrium diameter.Group I patients exhibited significantly higher levels of CML, TNF-α, and IL-6 and lower levels of nitric oxide ascompared with group II patients. Additionally, CML showed a significant positive correlation with IL-6 (r = 0.596,P = 0.001) and TNF-α (r = 0.337, P = 0.001) and a negative correlation with nitric oxide (r=-4.16, P = 0.001). Oddsratio analysis revealed that patients with CML in the third quartile (264.43-364.31 ng/mL) were significantlyassociated with diabetic CAD at unadjusted and adjusted levels with covariates.
