Ligustrazine alleviates gastric mucosal injury in a rat model of acute necrotizing pancreatitis

BACKGROUND: Acute necrotizing pancreatitis (ANP) leads to a systemic inflammatory response characterized by widespread leukocyte activation and, as a consequence, distant organ injury. The aim of this study was to explore the relationship between gastric microcirculatory impairment and inflammatory mediators released in rats and to evaluate the therapeutic effect of ligustrazine extracted from Rhizoma ligusticum wallichii on gastric mucosa injury in a rat model of ANP. METHODS: Ninety-six Sprague-Dawley rats were randomly divided into three groups: normal control (group C); ANP without treatment (group P); and ANP treated with ligustrazine (group T). The ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane (4 ml/kg). Group C was given isovolumetric injection of 9 g/L physiological saline by the same route. Group T was injected with ligustrazine (10 ml/kg) via the portal vein. The radioactive biomicrosphere technique was used to measure the blood flow 2 and 12 hours after the induction of ANP. Samples of the pancreas and stomach were taken to assess pathological changes by a validated histology score; meanwhile, the levels of serum interleukin-1β (IL-1β) were determined. Gastric tissues were also used to measure the level of myeloperoxidase (MPO), which is expressed intracellularly in the azurophilic granules of neutrophils. RESULTS: Blood flow in group P was significantly lower than that in group C (P<0.01). Pathological changes were significantly aggravated in group P. The gastric MPO activity in group P was significantly higher than that in group C (P<0.01). The level of serum IL-1β in group P increased more significantly than that in group C (P<0.01). Blood flow of the stomach in group T was significantlyhigher than that in group P after 2 hours (P<0.01). The pathological changes were significantly alleviated in group T. The MPO activity of group T was significantly lower than that of group P (P<0.01). Although serum IL-1β level of group T, was higher than of group C (P<0.01), it was lower than that of group P (P<0.01). There was a negative correlation between gastric blood flow and MPO activity (r=-0.983, P<0.01), and between gastric blood flow and pathological score (r=-0.917, P<0.05). CONCLUSIONS: Decreased gastric blood flow and increased inflammatory mediators can be seen early in ANP, and both are important factors for gastric and mucosal injury. Ligustrazine can ameliorate microcirculatory disorder and alleviate the damage to the pancreas and stomach.     

Are glucocorticoids really useful for the treatment of acute pancreatitis?

Journal of Gastroenterology -     

Human β-defensin-3 induction in H pylori-infected gastric mucosal tissues

INTRODUCTION Defensins are antimicrobial peptide components of the innate immune system. Three subfamilies, α-defensins, β-defensins, and θ-defensins, distinguished according to structural features at the gene and protein levels, have been identified i…     

Are the causes similar for benign and severe forms of acute pancreatitis?

The frequency of severe acute pancreatitis not due to alcohol or biliary causes is not well known. AIMS: To evaluate the distribution of causes responsible for benign and severe cases of acute pancreatitis in an effort to identify causes to search for in patients with severe acute pancreatitis. PATIENT: All patients hospitalized for acute pancreatitis between January 1994 and May 2001 with a good quality CT scan. METHODS: All patients had a complete, standardized evaluation to look for all possible causes of acute pancreatitis. The following severity criteria were retrospectively reviewed: maximal C-reactive protein level, Ranson's score, Balthazar's score, percentage of patients hospitalized in intensive care unit or a high-dependency unit, hospitalization duration, and local or general complications. RESULTS: One hundred thirty-nine patients were included. The cause of acute pancreatitis were: alcohol (34%), biliary (27%), obstructive (16%), miscellaneous (10%), unknown (9%), post endoscopic retrograde cholangio-pancreatography (4%). The studied severity factors did not differ with respect to the cause of acute pancreatitis with the exception of Balthazar's score. Non-alcoholic non-biliary causes were found in 19 (27%) of the 71 patients with severe necrotic acute pancreatitis (Balthazar > or =D) and 35 (51%) of the 68 patients with acute pancreatitis with Balthazar score or =D). For the other severity scores, the distribution of causes was similar. After exclusion of biliary and alcoholic causes, a careful search for other etiologies should be carried out in both benign and severe cases of acute pancreatitis.     

A critical role of gastric mucosal ascorbic acid in the progression of acute gastric mucosal lesions induced by compound 48／80 in rats

AIM: To study the role of gastric mucosal ascorbic acid (AA) in the progression of acute gastric mucosal lesions induced by compound 48/80 (C48/80), a mast cell degranulator, in rats. METHODS: C48/80 (0.75 mg/kg) was intraperitoneally injected to fasted Wistar rats. Oral administration of AA (10, 50 or 100 mg/kg) was performed 0.5 h after C48/80 treatment. Determinations for gastric mucosal lesion severity and blood flow, and assays for gastric mucosal total AA, reduced AA, oxidized AA, vitamin E, thiobarbituric acid reactive substances (TBARS), adherent mucus, nitrite/ nitrate (NOx), non-protein SH (NPSH), and myeloperoxidase (MPO), and serum total AA, reduced AA, oxidized AA, and NOx were conducted 0.5 and 3 h after C48/80 treatment. RESULTS: Gastric mucosal lesions occurred 0.5 h after C48/80 treatment and progressed at 3 h. Gastric mucosal blood flow decreased 0.5 h after C48/80 treatment but the decrease was recovered at 3 h. Gastric mucosal total AA, reduced AA, vitamin E, and adherent mucus concentrations decreased 3 h after C48/80 treatment. Gastric mucosal oxidized AA concentration remained unchanged after C48/80 treatment. Gastric mucosal NPSH concentration decreased 0.5 h after C48/80 treatment, but the decrease was recovered at 3 h. Gastric mucosal TBARS concentration and MPO activity increased 0.5 h after C48/80 treatment and further increased at 3 h. Serum total AA and reduced AA concentrations increased 0.5 h after C48/80 treatment and further increased at 3 h, while serum oxidized AA concentration increased at 0.5 h. Serum and gastric mucosal NOx concentrations increased 3 h after C48/80 treatment. AA administration to C48/80-treated rats at 0.5 h after the treatment prevented the gastric mucosal lesion progression and the changes in gastric mucosal total AA, reduced AA, vitamin E, adherent mucus, NOx, and TBARS concentrations and MPO activity and serum NOx concentration found at 3 h after the treatment dose-dependently. The AA administration to C48/80-treated rats caused further increases in serum total AA and reduced AA concentrations at 3 h after the treatment dose-dependently. CONCLUSION: Gastric mucosal AA plays a critical role in the progression of C48/80-induced acute gastric mucosal lesions in rats.     

AgNOR and rasp21 expression in gastric mucosal lesions with Hellicobacter pylori infection

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Are visual feedback delays responsible for aging-related increases in force variability?

The current investigation examined if age-related differences in the control of isometric force production are related to an increase in visual motor processing time. Young and old adults produced isometric force production to a visually displayed target while visual feedback delay was manipulated over a broad range (50 to 3200 ms). The force output of the oldest age group was more variable across the range of delays, but only demonstrated enhanced time dependent structure at short delays. It is concluded that age differences in visual motor processing time contribute to decrements in both the feedback and feedforward control of force output.     

Severity scoring for acute pancreatitis: Where do we stand in 1999?

The last few years have seen a rapid evolution in the care of acute pancreatitis. Interventions such as endoscopic sphincterotomy with stone extraction and administration of platelet activating factor are effective but must be applied early. Ranson criteria and modified Glasgow score are widely used, but these systems often cannot separate mild versus severe pancreatitits within 24 hours of hospital admission. The Acute Physiology and Chronic Health Evaluation (APACHE II) is a good predictive system for severity of disease at admission. New single agent biologic markers hold some promise. The CT severity index is better than APACHE II for predicting local complications but not as good for predicting mortality and systemic morbidity. Modern care of acute pancreatitis requires the development of a rapid response team model, with early assessment by APACHE II, biologic markers, and, if indicated, the CT Severity Index.     

Effect of captopril on serum TNF-α level in acute lung injury rats induced by HCL

Objective:To observe the effect of captopril on the tumor necrosis factor-α(TNF- α) level and arterial blood gases in acute lung injury(All) induced by HCL in rats,and to analyze its protective mechanism.Methods:Fifty Wistar rats were selected and randomly divided into three groups,with 20 rats in Group Ⅰ and Ⅱ,respectively and 10 animals in Group Ⅲ.ALI model was constructed by intratracheal injection of diluted hydrochloric acid(pH=1.25.1.2 mL/kg).Group Ⅰrats received not any treatment after construction of AM model.Group Ⅱ rats were treated with captopril(5 mg/kg,i.p.) 5 min after induction of ALI.Group Ⅲ served as normal control without any treatment.Ninety minutes after construction of ALI model,all the rats were sacrificed.Blood was withdrawn for detection of TNF- α level and arterial blood gases index.And lung tissue slices of the three groups were prepared for observation of pathologic histology changes.Results:TNF- α level in serum of Group Ⅰ and Ⅱ rats was significantly higher than that in Group Ⅲ(P0.05),while TNF- α level in serum of Group Ⅱ was significantly lower in Group Ⅰ(P0.05).PaCO_2 level was significantly higher(P0.05),while PaO_2 was significantly lower(P0.05) in Group Ⅰ and Ⅱ rats than those in Group Ⅲ.PaCO_2 was significantly lower(P0.05) and PaO_2 was significantly higher(P0.05) in Group Ⅱ than those in Group Ⅰ.Histological observation showed diffuse congestion and severe edema of luug tissue,obvious thickening and structure damage of alveolar walls and a large amount of neutrophil infiltration in Group Ⅰ rats.Group Ⅱ rats showed mild edema of lung tissue;only a small portion of alveolar walls showed thickening and only a few of neutrophil infiltration could be observed.The degree of injury was remarkably slighter than that of Group Ⅰ rats.Group Ⅲ rats showed clear lung tissue structure and normal morphology:alveolar walls were uniform and the margin was smooth and few neutrophil could be observed.Conclusions:Captopril can significantly reduce serum TNF- α level,elevate PaO_2 and reduce PaCO_2 in rats with ALI.It has a protective effect on ALI rats.     

Lower folate levels in gastric cancer:Is it a cause or a result?

Folate deficiency and its association with cancer have been studied in the literature, but its clinical impact is still unknown. Folate deficiency and its result on gastric cancer is a mysterious part of oncology, with ongoing studies hopefully clarifying its impact on gastric cancer management. Lee et al studied folate deficiency and its impact on staging and clinical results. Here we try to contribute to the field by expressing our own thoughts about the paper.     

Is there a role for serum endothelin in predicting the severity of acute pancreatitis?

BACKGROUND: Acute pancreatitis remains a common presentation to acute surgical units and carries significant morbidity and mortality. The progression of the disease to necrotizing pancreatitis and multi-organ dysfunction syndrome (MODS) is associated with a very poor clinical outcome, and persistendy high mortality. Increases in serum endothelin (ET) have been seen in animal models of acute pancreatitis and this study aims to investigate whether there is a change in serum ET-1 in patients with acute pancreatitis and whether any such change is linked to disease severity. METHODS: All patients admitted with acute pancreatitis were prospectively recruited from die emergency admissions at the Norfolk and Norwich University Hospital. Serum ET levels were determined on admission, at 24 hours and 5 days post admission. Healthy adult controls were recruited from dermatology outpatients. RESULTS: A total of 21 patients joined the trial after giving informed consent. There were 3 men and 18 women with a median age of 65 years (range 26-87 years). Serum ET levels were significantly higher in acute pancreatitis patients than in normal controls (P <0. 05). An association was seen between persistendy raised serum ET levels and progression to MODS. CONCLUSIONS: The study does demonstrate a correlation between the circulating levels of ET and acute pancreatitis in humans, although it does not elicit its involvement in the pathogenesis of the disease. The observation that a persistendy high level of circulating ET-1 is associated with progression to MODS may indicate a role for ET in the monitoring of acute pancreatitis patients for recovery or progression to MODS.     

Are regulatory molecules for T cells involved in the development of autoimmune pancreatitis?

Impaired regulatory functions such as CTLA4 on T cells and naive regulatory T cells may be involved in the development of AIP.