Previously, we have purified Jerdonitin from Trimeresurusjerdonii venom. Compared with other P-Ⅱ class snake venom metalloproteinases (SVMPs), Jerdonitin has a primary structure comprising metalloproteinase and dis...Previously, we have purified Jerdonitin from Trimeresurusjerdonii venom. Compared with other P-Ⅱ class snake venom metalloproteinases (SVMPs), Jerdonitin has a primary structure comprising metalloproteinase and disintegrin domains. However, no hemorrhagic and fibrinogenolytic activities were detected for Jerdonitin. We thought that organic buffer of high performance liquid charamatography (HPLC) might affect its enzymatic activity. In this study, we purified Jerdonitin by another procedure excluding the HPLC. It was homogenous as judged by SDS-PAGE and had an apparent molecular weight of 36 kDa under non-reducing conditions and 38 kDa under reducing conditions, respectively. Like other typical metalloproteinases, Jerdonitin preferentially degraded alpha-chain of human fibrinogen and this fibrinogenolytic activity was completely inhibited by EDTA, but not by PMSF. It was interesting that Jerdonitin did not induce hemorrhage after intradermal injection in mice.展开更多
AIM: To investigate the role of Kupffer cells (KCs) in acute hemorrhagic necrotizing pancreatitis-associated lung injury (AHNP-U). METHODS: Forty-two rats were allocated to four groups [sham operation, AHNP mode...AIM: To investigate the role of Kupffer cells (KCs) in acute hemorrhagic necrotizing pancreatitis-associated lung injury (AHNP-U). METHODS: Forty-two rats were allocated to four groups [sham operation, AHNP model, gadolinium chloride (GdCl3) pretreatment, GdCl3 control]. In GdCl3 pretreatment group, GdCl3 was administered by caudal vein injection 24 h before the AHNP model induction. Blood from the iliac artery, alveolar macrophages and tissues from the pancreas and lung, were collected in six animals per group 3 and 6 h after acute pancreatitis induction. TNF-α, IL-1 of Lserum, myeloperoxidase (MPO) of lung tissue, NF-κB activation of alveolar macrophages were detected. Serum AST and ALT in sham operation group and GdCl3 control group were tested. In addition, histopathological changes of the pancreas and lung were observed under light microscope. RESULTS: MPO of lung tissue and TNF-α, IL-1 levels of serum were all reduced significantly in GdCl3 pretreatment group compared to those in AHNP group (P〈0.01). NF-KB activation of alveolar macrophages was also attenuated significantly in GdCl3 pretreatment group compared to that in AHNP group (P〈0.01). The pathological injury of the lung was ameliorated obviously in GdCl3 pretreatment group compared to that in AHNP group. Nevertheless, the serum amylase level did not reduce and injury of the pancreas was not prevented in GdCl3 pretreatment group. CONCLUSION: Pulmonary injury induced by AHNP is mediated by KC activation and AHNP-LI can be significantly ameliorated by pretreatment with GdCh and KCs play a vital role in AHNP-LI.展开更多
AIM: To investigate the functional, morphological changes of the gut barrier during the restitution process after hemorrhagic shock, and the regional differences of the large intestine and small intestine in response...AIM: To investigate the functional, morphological changes of the gut barrier during the restitution process after hemorrhagic shock, and the regional differences of the large intestine and small intestine in response to ischemia/ reperfusion injury. METHODS: Forty-seven Sprague-Dawley rats with body weight of 250-300 g were divided into two groups: control group (sham shock n = 5) and experimental group (n = 42). Experimental group was further divided into six groups (n = 7 each) according to different time points after the hemorrhagic shock, including 0^th group, 1^st group, 3^rd group, 6th h group, 12^th group and 24^th group. All the rats were gavaged with 2 mL of suspension of lactulose (L) (100 mg/2 mL) and mannitol (M) (50 mg/each) at the beginning and then an experimental rat model of hemorrhagic shock was set up. The specimens from jejunum, ileum and colon tissues and the blood samples from the portal vein were taken at 0, 1, 3, 6, 12 and 24 h after shock resuscitation, respectively. The morphological changes of the intestinal mucosa, including the histology of intestinal mucosa, the thickness of mucosa, the height of villi, the index of mucosal damage and the numbers of goblet cells, were determined by light microscope and/or electron microscope. The concentrations of the bacterial endotoxin lipopolysaccharides (LPS) from the portal vein blood, which reflected the gut barrier function, were examined by using Limulus test. At the same time point, to evaluate intestinal permeability, all urine was collected and the concentrations of the metabolically inactive markers such as L and M in urine were measured by using GC-9A gas chromatographic instrument.RESULTS: After the hemorrhagic shock, the mucosal epithelial injury was obvious in small intestine even at the 0th h, and it became more serious at the 1^stand the 3^rd h. The tissue restitution was also found after 3 h, though the injury was still serious. Most of the injured mucosal restitution was established after 6 h and completed in 24 h. Two distinct models of cell deathapoptosis and necrosis-were involved in the destruction of rat intestinal epithelial cells. The number of goblet cells on intestinal mucosa was reduced significantly from 0 to 24 h (the number from 243±13 to 157±9 for ileum, 310±19 to 248±18 for colon; r= -0.910 and -0.437 respectively, all P〈0.001), which was the same with the large intestine, but the grade of injury was lighter with the values of mucosal damage index in 3 h for jejunum, ileum, and colon being 2.8, 2.6, 1.2, respectively. The mucosal thickness and the height of villi in jejunum and ileum diminished in 1 h (the average height decreased from 309±24 to 204±23 pm and 271±31 to 231±28 pm, r = -0.758 and -0.659, all P〈0.001, the thickness from 547±23 to 418±28μm and 483±45 to 364±35μm, r= -0.898 and -0.829, all P〈0.001), but there was no statistical difference in the colon (F= 0.296, P = 0.934). Compared with control group, the urine L/M ratio and the blood LPS concentration in the experimental groups raised significantly, reaching the peak in 3-6 h (L/M: control vs 3 h vs6 h was 0.029±0.09 vs 0.063±0.012 vs 0.078±0.021, r = -0.786, P〈0.001; LPS: control vs3 h vs6 h was 0.09±0.021 vs 0.063±0.012 vs0.25±0.023, r=- -0.623, P〈0.001), and it kept increasing in 24 h. CONCLUSION: The gut barrier of the rats was seriously damaged at the early phase of ischemic reperfusion injury after hemorrhagic shock, which included the injury and atrophy in intestinal mucosa and the increasing of intestinal permeability. Simultaneously, the intestinal mucosa also showed its great repairing potentiality, such as the improvement of the intestinal permeability and the recovery of the morphology at different phases after ischemic reperfusion injury. The restitution of gut barrier function was obviously slower than that of the morphology and there was no direct correlation between them. Compared with the small intestine, the large intestine had stronger potentiality against injury. The reduction of the amount of intestinal goblet cells by injury did not influence the ability of intestinal mucosal restitution at a certain extent and it appeared to be intimately involved in the restitution of the epithelium.展开更多
Objective: To investigate the early effects of hypertonic and isotonic saline solutions on apoptosis of intestinal mucosa in rats with hemorrhagic shock. Methods: A model of rat with severe hemorrhagic shock was estab...Objective: To investigate the early effects of hypertonic and isotonic saline solutions on apoptosis of intestinal mucosa in rats with hemorrhagic shock. Methods: A model of rat with severe hemorrhagic shock was established in 21 Sprague-Dawley (SD) rats. The rats were randomly divided into the sham group, normal saline resuscitation (NS) group, and hypertonic saline resuscitation (HTS) group, with 7 in each group. We detected and compared the apoptosis in small intestinal mucosa of rats after hemorrhagic shock and resuscitation by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), FITC (fluo- rescein-iso-thiocyanate)-Annexin V/PI (propidium iodide) double staining method, and flow cytometry. Results: In the early stage of hemorrhagic shock and resuscitation, marked apoptosis of small intestinal mucosa in the rats of both NS and HTS groups was observed. The numbers of apoptotic cells in these two groups were significantly greater than that in the sham group (P<0.01). In the HTS group, the apoptic cells significantly decreased, compared with the NS group (P<0.01). Conclusion: In this rat model of severe hemorrhagic shock, the HTS resuscitation of small volume is more effective than the NS resuscitation in reducing apoptosis of intestinal mucosa in rats, which may improve the prognosis of trauma.展开更多
AIM: To investigate the role of nitric oxide (NO) in Tolllike receptor 2 (TLR2)/4mRNA expression in livers of acute hemorrhagic necrotizing pancreatitis (AHNP) rats. METHODS: One hundred and ten SD male rats w...AIM: To investigate the role of nitric oxide (NO) in Tolllike receptor 2 (TLR2)/4mRNA expression in livers of acute hemorrhagic necrotizing pancreatitis (AHNP) rats. METHODS: One hundred and ten SD male rats were randomly divided into sham-operated group (n = 10), AHNP group (n = 30), chloroquine (CQ)-treated group (n = 30) and L-Arg-treated group (n = 40). TLR2/4mRNA expression in the liver of AHNP rats was measured by RT-PCR. RESULTS: Expression of TLR2/4mRNA could be detected in the liver of AHNP rats in sham-operated group (0.155E-5±0.230E-6 and 0.115E-2±0.545E-4), but was markedly increased at 3 h in AHNP group (0.197E-2±0.114E-3 and 0.175±0.349E-2) peaking at 12 h (0.294E-2 ± 0.998E-4 and 2.673 ± 2.795E-2, P〈 0.01). Hepatic injuries were aggravated, TNF-α concentration in the liver was increased and NO concentration was decreased (P〈 0.05 or P〈 0.01). When TLR2/4mRNA expression was inhibited by CQ (3 h: 1.037E-4±3.299E-6 and 0.026±3.462E-3; 6 h: 1.884E-4±4.679E-6 and 0.108±6.115E-3; 12 h: 2.443E-4±7.714E-6 and 0.348±6.807E-3; P 〈 0.01), hepatic injuries were relieved, NO concentration in the liver was increased and TNF-α concentration was decreased (P〈0.05 or P〈0.01). When rats with AHNP were treated with L-Arg, TLR2/4mRNA expression in the liver could be effectively inhibited (50 mg-T: 0.232E-2±0.532E-4 and 0.230±6.883E-3; 100 mg-T: 0.210E-2± 1.691E-4 and 0.187±0.849E-2; 200 mg-T: 0.163E-2±0.404E-4 and 0.107±0.195E-2; 400 mg-T: 0.100E-2±0.317E-4 and 0.084±0.552E-2; P〈0.01) and hepatic injuries were relieved. At the same time, NO concentration in the liver was markedly increased and TNF-α concentration was decreased (P〈0.05 or P〈O.OI), CONCLUSION: The expression of TLR2/4mRNA is increased and hepatic injuries are aggravated in the liver of AHNP rats. TLR2/4mRNA gene expression in the liver of AHNP rats can be markedly inhibited by NO, leading to the relief of hepatic injuries.展开更多
Anemia of diverse etiology is a common complication of chronic liver diseases. The causes of anemia include acute or chronic gastrointestinal hemorrhage, and hypersplenism secondary to portal hypertension. Severe hepa...Anemia of diverse etiology is a common complication of chronic liver diseases. The causes of anemia include acute or chronic gastrointestinal hemorrhage, and hypersplenism secondary to portal hypertension. Severe hepatocellular disease predisposes to hemorrhage because of impaired blood coagulation caused by deficiency of blood coagulation factors synthesized by hepatocytes, and/or thrombocytopenia. Aplastic anemia, which is characterized by pancytopenia and hypocellular bone marrow, may follow the development of hepatitis. Its presentation includes progressive anemia and hemorrhagic manifestations. Hematological complications of combination therapy for chronic viral hepatitis include clinically signif icant anemia, secondary to treatment with ribavirin and/or interferon. Ribavirininduced hemolysis can be reversed by reducing the dose of the drug or discontinuing it altogether. Interferons may contribute to anemia by inducing bone marrow suppression. Alcohol ingestion is implicated in the pathogenesis of chronic liver disease and may contribute to associated anemia. In patients with chronic liver disease, anemia may be exacerbated by defi ciency of folic acid and/or vitamin B12 that can occur secondary to inadequate dietary intake or malabsorption.展开更多
Acute upper gastrointestinal bleeding(UGIB) is a gastroenterological emergency with a mortality of 6%-13%.The vast majority of these bleeds are due to peptic ulcers.Nonsteroidal anti-inflammatory drugs and Helicobacte...Acute upper gastrointestinal bleeding(UGIB) is a gastroenterological emergency with a mortality of 6%-13%.The vast majority of these bleeds are due to peptic ulcers.Nonsteroidal anti-inflammatory drugs and Helicobacter pylori are the main risk factors for peptic ulcer disease.Endoscopy has become the mainstay for diagnosis and treatment of acute UGIB,and is recommended within 24 h of presentation.Proton pump inhibitor(PPI) administration before endoscopy can downstage the bleeding lesion and reduce the need for endoscopic therapy,but has no effect on rebleeding,mortality and need for surgery.Endoscopic therapy should be undertaken for ulcers with high-risk stigmata,to reduce the risk of rebleeding.This can be done with a variety of modalities.High-dose PPI administration after endoscopy can prevent rebleeding and reduce the need for further intervention and mortality,particularly in patients with high-risk stigmata.展开更多
AIM:To evaluate and compare the clinical outcomes of prophylactic submucosal saline-epinephrine injection and saline injection alone for large colon polyps by conventional polypectomy. METHODS:A prospective study was ...AIM:To evaluate and compare the clinical outcomes of prophylactic submucosal saline-epinephrine injection and saline injection alone for large colon polyps by conventional polypectomy. METHODS:A prospective study was conducted from July 2003 to July 2004 at 11 tertiary endoscopic centers. Large colon polyps (> 10 mm in diameter) wererandomized to undergo endoscopic polypectomy with submucosal saline-epinephrine injection (epinephrine group) or normal saline injection (saline group). Endoscopic polypectomy was performed by the conventional snare method,and early (< 12 h) and late bleeding complications (12 h-30 d) were observed. RESULTS:A total of 561 polyps in 486 patients were resected by endoscopic polypectomy. Overall,bleeding complications occurred in 7.6% (37/486) of the patients,including 4.9% (12/244) in the epinephrine group,and 10.3% (25/242) in the saline group. Early and late postpolypectomy bleeding (PPB) occurred in 6.6% (32/486) and 1% (5/486) of the patients,respectively,including 4.5% (11/244),0.4% (1/244) in the epinephrine group,and 8.7% (21/242),1.7% (4/242) in the saline group. No significant differences in the rates of overall,early and late PPB were observed between the 2 groups. Multivariate stepwise logistic regression analysis revealed that large size (> 2 cm) and neoplastic polyps were independently and significantly associated with the presence of PPB. CONCLUSION:The prophylactic submucosal injection of diluted epinephrine does not appear to provide an additional advantage over the saline injection alone for the prevention of PPB.展开更多
AIM: To study the protective effect of Astragalus rnernbranaceus on intestinal mucosa reperfusion injury and its mechanism after hemorrhagic shock in rats. METHODS: A total of 32 SD rats were randomly divided into f...AIM: To study the protective effect of Astragalus rnernbranaceus on intestinal mucosa reperfusion injury and its mechanism after hemorrhagic shock in rats. METHODS: A total of 32 SD rats were randomly divided into four groups (n = 8, each group): normal group, model group, low dosage group (treated with 10 g/kg Astragalus membranaceus) and high dosage group (treated with 20 g/kg Astragalus membranaceus). The model of hemorrhagic shock for 60 min and reperfusion for 90 min was established. Therapeutic solution (3 mL) was administrated before reperfusion. At the end of the study, the observed intestinal pathology was analyzed. The blood concentrations of lactic acid (LD), nitric oxide (NO), endothelin-1 (ET-1), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) in intestinal mucosa were determined. RESULTS: The intestinal mucosa pathology showed severe damage in model group and low dosage group, slight damage in high dosage group and no obvious damage in normal group. The Chiu's score in low dose group and high dose group was significantly lower than that in model group. The content of MDA in model group was higher than that in low and high dose groups, while that in high dose group was almost the same as in normal group. The activity of SOD and GSH-PX was the lowest in model group and significantly higher in high dose group than in normal and low dose groups. The concentrations of LD and ET-1 in model group were the highest. The concentrations of NO in model group and low dose group were significantly lower than those in high dose group and normal group. CONCLUSION: High dose Astraga/us membranaeus has much better protective effect on hemorrhagic shockreperfusion injury of intestinal mucosa than low dose Astragalus membranaceus. The mechanism may be that Astragalus membranaceus can improve antioxidative effect and regulate NO/ET level during hemorrhagic reperfusion.展开更多
Background The CRUSADE, ACTION and ACUITY-HORIZONS scores are commonly used for predicting in-hospital major bleeding events in patients with acute coronary syndrome (ACS), but the homogeneous nature of these models...Background The CRUSADE, ACTION and ACUITY-HORIZONS scores are commonly used for predicting in-hospital major bleeding events in patients with acute coronary syndrome (ACS), but the homogeneous nature of these models' population limits simple ex- trapolation to other local population. We aimed to compare the performance of the three risk models in Chinese patients. Methods We evaluated the performance of the three predicting scores for predicting in-hospital major bleeding events defined by thrombolysis in myocar- dial infarction (TIMI) serious (major and minor) episodes, in a cohort of Chinese ACS patients with either non-ST-elevation ACS (NSTE-ACS) or ST-elevation myocardial infarction (STEMI). Calibration and discrimination of the three risk models were evaluated by the Hosmer-Lemeshow test and C-statistic, respectively. We compared the predictive accuracy of the risk scores by the Delong non-parametric test. Results TIMI serious bleeding rate was 1.1% overall (1.9% and 0.86% for STEMI and NSTE-ACS, respectively). The CRUSADE, ACTION and ACUTIY-HOR/ZONS scores showed an adequate discriminatory capacity for major bleeding: in overall patients, the C-statistic was 0.80, 0.77, and 0.70, respectively; in NSTE-ACS patients, the C-statistic was 0.73, 0.72, and 0.64, respectively; in STEMI patients, the C-statistic was 0.91, 0.92, and 0.75, respectively. The C-statistic for the ACUITY-HORIZONS model was significantly lower than those of the CRUSADE and ACTION scores for the prediction of TIM/serious bleeding in overall patients (compared with CRUSADE, z = 3.83, P = 0.02; compared with ACTION, z = 3.51, P = 0.03); in NSTE-ACS patients (compared with CRUSADE, z = 2.37, P = 0.01; compared with ACTION, z = 2.11, P = 0.04), and in STEMI patients (compared with CRUSADE, z = 2.6.77, P = 0.02; compared with AC- TION, z = 7.91, P = 0.002). No differences were observed when the CRUSADE and ACTION models were compared to each other, regard- less of overall patients (z = 0.68, P = 0.31) and both of ACS types (NSTE-ACS, z = 0.52, P = 0.60), and STEMI patients (z = 0.36, P = 0.74). However, the three risk scores all overestimated the absolute major bleeding risk in each risk stratification in our study. For example, the predicted rate of CRUSADE score at high risk stratification was 11.9% vs. an actual rate of 5.3%. Conclusions The CRUSADE and AC- TION scores had a greater calibration and discrimination for in-hospital major bleeding compared with the ACUITY-HORIZONS score in Chinese patients with ACS undergoing PCI. However, they all overestimated the bleeding risk rate for Chinese populations. Calibration of these risk scores would be useful for the generalization in Chinese populations.展开更多
AIM: To evaluate the diagnostic angiography and therapy for acute massive hemorrhage in gastrointestinal tract. METHODS: Twenty-five cases of acute hemorrhage in gastrointestinal tract admitted between April 2002 an...AIM: To evaluate the diagnostic angiography and therapy for acute massive hemorrhage in gastrointestinal tract. METHODS: Twenty-five cases of acute hemorrhage in gastrointestinal tract admitted between April 2002 and September 2004 were reviewed and analyzed by angiography and embolotherapyo RESULTS: Fifteen patients were men and ten patients were women. The Seldinger technique and method of coaxial duct were used to get access to the bleeding region. PVA particles, gelfoam, and coils were used for embolism. All bleeding sites could be confirmed and were successfully embolized. Hemostasis was achieved in all the patients without bleeding again. The cure rate was 100%. CONCLUSION: Interventional therapy can not only ascertain the bleeding site, but also stop the bleeding .The method is simple and the effect is certain.展开更多
Crohn's disease and ulcerative colitis can be grouped as the inflammatory bowel diseases (IBD). These conditions have become increasingly common in recent years, including in children and young people. Although muc...Crohn's disease and ulcerative colitis can be grouped as the inflammatory bowel diseases (IBD). These conditions have become increasingly common in recent years, including in children and young people. Although much is known about aspects of the pathogenesis of these diseases, the precise aetiology is not yet understood, and there remains no cure. Recent data has illustrated the importance of a number of genes-several of these are important in the onset of IBD in early life, including in infancy. Pain, diarrhoea and weight loss are typical symptoms of paediatric Crohn's disease whereas bloody diarrhoea is more typical of colitis in children. However, atypical symptoms may occur in both conditions: these include isolated impairment of linear growth or presentation with extra-intestinal manifestations such as erythma nodosum. Growth and nutrition are commonly compromised at diagnosis in both Crohn's disease and colitis. Consideration of possible IBD and completion of appropriate investigations are essential to ensure prompt diagnosis, the- reby avoiding the consequences of diagnostic delay. Patterns of disease including location and progression of IBD in childhood differ substantially from adult- onset disease. Various treatment options are available for children and adolescents with IBD. Exclusive enteral nutrition plays a central role in the induction of remission of active Crohn's disease. Medical and surgical therapies need to considered within the context of a growing and developing child. The overall management of these chronic conditions in children should include multi-disciplinary expertise, with focus upon maintaining control of gut inflammation, optimising nutrition, growth and quality of life, whilst preventing disease or treatment-related complications.展开更多
Inducible heat shock protein 70 kD (HSP-70i) has been shown to protect cells, tissues, and organs from harmful assaults in in vivo and in vitro experimental models. Hemorrhagic shock followed by resuscitation is the p...Inducible heat shock protein 70 kD (HSP-70i) has been shown to protect cells, tissues, and organs from harmful assaults in in vivo and in vitro experimental models. Hemorrhagic shock followed by resuscitation is the principal cause of death among trauma patients and soldiers in the battlefield. Although the underlying mechanisms are still not fully understood, it has been shown that nitric oxide (NO) overproduction and inducible nitric oxide synthase (iNOS) overexpression play important roles in producing injury caused by hemorrhagic shock including increases in polymorphonuclear neutrophils (PMN) infiltration to injured tissues and leukotriene B4 (LTB4) generation. Moreover, transcription factors responsible for iNOS expression are also altered by hemorrhage and resuscitation. It has been evident that either up-regulation of HSP-70i or down-regulation of iNOS can limit tissue injury caused by ischemia/reperfusion or hemorrhage/resuscitation. In our laboratory, geldanamycin, a member of ansamycin family, has been shown to induce HSP-70i overexpression and then subsequently to inhibit iNOS expression, to reduce cellular caspase-3 activity, and to preserve cellular ATP levels. HSP-70i is found to couple to iNOS and its transcription factor. Therefore, the complex formation between HSP-70i and iNOS may be a novel mechanism for protection from hemorrhage/resuscitation-in-duced injury.展开更多
AIM: To investigate acute nonvariceal bleeding in the upper gastrointestinal (GI) tract and evaluate the effects of endoscopic hemoclipping. METHODS: Sixty-eight cases of acute nonvariceal bleeding in the upper GI...AIM: To investigate acute nonvariceal bleeding in the upper gastrointestinal (GI) tract and evaluate the effects of endoscopic hemoclipping. METHODS: Sixty-eight cases of acute nonvariceal bleeding in the upper GI tract were given endoscopic treatment with hemoclip application. Clinical data, endoscopic findings, and the effects of the therapy were evaluated. RESULTS: The 68 cases (male:female = 42:26, age from 9 to 70 years, average 54.4) presented with hernatemesis in 26 cases (38.2%), melena in nine cases (13.3%), and both in 33 cases (48.5%). The causes of the bleeding included gastric ulcer (29 cases), duodenal ulcer (11 cases), Dieulafoy's lesion (11 cases), Mallory-Weiss syndrome (six cases), post-operative (three cases), post-polypectomy bleeding (five cases), and post-sphincterotomy bleeding (three cases); 42 cases had active bleeding. The mean number of hemoclips applied was four. Permanent hemostasis was obtained by hemoclip application in 59 cases; 6 cases required emergent surgery (three cases had peptic ulcers, one had Dieulafoy's lesion, and two were caused by sphincterotomy); three patients died (two had Dieulafoy's lesion and one was caused by sphincterotomy); and one had recurrent bleeding with Dieulafoy's lesion 10 mo later, but in a different location. CONCLUSION: Endoscopic hemoclip application was an effective and safe method for acute nonvariceal bleeding in the upper GI tract with satisfactory outcomes.展开更多
文摘Previously, we have purified Jerdonitin from Trimeresurusjerdonii venom. Compared with other P-Ⅱ class snake venom metalloproteinases (SVMPs), Jerdonitin has a primary structure comprising metalloproteinase and disintegrin domains. However, no hemorrhagic and fibrinogenolytic activities were detected for Jerdonitin. We thought that organic buffer of high performance liquid charamatography (HPLC) might affect its enzymatic activity. In this study, we purified Jerdonitin by another procedure excluding the HPLC. It was homogenous as judged by SDS-PAGE and had an apparent molecular weight of 36 kDa under non-reducing conditions and 38 kDa under reducing conditions, respectively. Like other typical metalloproteinases, Jerdonitin preferentially degraded alpha-chain of human fibrinogen and this fibrinogenolytic activity was completely inhibited by EDTA, but not by PMSF. It was interesting that Jerdonitin did not induce hemorrhage after intradermal injection in mice.
基金Supported by the Natural Scientific Foundation of Tianjin,No.013612511
文摘AIM: To investigate the role of Kupffer cells (KCs) in acute hemorrhagic necrotizing pancreatitis-associated lung injury (AHNP-U). METHODS: Forty-two rats were allocated to four groups [sham operation, AHNP model, gadolinium chloride (GdCl3) pretreatment, GdCl3 control]. In GdCl3 pretreatment group, GdCl3 was administered by caudal vein injection 24 h before the AHNP model induction. Blood from the iliac artery, alveolar macrophages and tissues from the pancreas and lung, were collected in six animals per group 3 and 6 h after acute pancreatitis induction. TNF-α, IL-1 of Lserum, myeloperoxidase (MPO) of lung tissue, NF-κB activation of alveolar macrophages were detected. Serum AST and ALT in sham operation group and GdCl3 control group were tested. In addition, histopathological changes of the pancreas and lung were observed under light microscope. RESULTS: MPO of lung tissue and TNF-α, IL-1 levels of serum were all reduced significantly in GdCl3 pretreatment group compared to those in AHNP group (P〈0.01). NF-KB activation of alveolar macrophages was also attenuated significantly in GdCl3 pretreatment group compared to that in AHNP group (P〈0.01). The pathological injury of the lung was ameliorated obviously in GdCl3 pretreatment group compared to that in AHNP group. Nevertheless, the serum amylase level did not reduce and injury of the pancreas was not prevented in GdCl3 pretreatment group. CONCLUSION: Pulmonary injury induced by AHNP is mediated by KC activation and AHNP-LI can be significantly ameliorated by pretreatment with GdCh and KCs play a vital role in AHNP-LI.
基金Supported by the Grants from the Health Research Foundation (A2003189) and the Science Research Project (2004B30601001) of Guangdong Province, China
文摘AIM: To investigate the functional, morphological changes of the gut barrier during the restitution process after hemorrhagic shock, and the regional differences of the large intestine and small intestine in response to ischemia/ reperfusion injury. METHODS: Forty-seven Sprague-Dawley rats with body weight of 250-300 g were divided into two groups: control group (sham shock n = 5) and experimental group (n = 42). Experimental group was further divided into six groups (n = 7 each) according to different time points after the hemorrhagic shock, including 0^th group, 1^st group, 3^rd group, 6th h group, 12^th group and 24^th group. All the rats were gavaged with 2 mL of suspension of lactulose (L) (100 mg/2 mL) and mannitol (M) (50 mg/each) at the beginning and then an experimental rat model of hemorrhagic shock was set up. The specimens from jejunum, ileum and colon tissues and the blood samples from the portal vein were taken at 0, 1, 3, 6, 12 and 24 h after shock resuscitation, respectively. The morphological changes of the intestinal mucosa, including the histology of intestinal mucosa, the thickness of mucosa, the height of villi, the index of mucosal damage and the numbers of goblet cells, were determined by light microscope and/or electron microscope. The concentrations of the bacterial endotoxin lipopolysaccharides (LPS) from the portal vein blood, which reflected the gut barrier function, were examined by using Limulus test. At the same time point, to evaluate intestinal permeability, all urine was collected and the concentrations of the metabolically inactive markers such as L and M in urine were measured by using GC-9A gas chromatographic instrument.RESULTS: After the hemorrhagic shock, the mucosal epithelial injury was obvious in small intestine even at the 0th h, and it became more serious at the 1^stand the 3^rd h. The tissue restitution was also found after 3 h, though the injury was still serious. Most of the injured mucosal restitution was established after 6 h and completed in 24 h. Two distinct models of cell deathapoptosis and necrosis-were involved in the destruction of rat intestinal epithelial cells. The number of goblet cells on intestinal mucosa was reduced significantly from 0 to 24 h (the number from 243±13 to 157±9 for ileum, 310±19 to 248±18 for colon; r= -0.910 and -0.437 respectively, all P〈0.001), which was the same with the large intestine, but the grade of injury was lighter with the values of mucosal damage index in 3 h for jejunum, ileum, and colon being 2.8, 2.6, 1.2, respectively. The mucosal thickness and the height of villi in jejunum and ileum diminished in 1 h (the average height decreased from 309±24 to 204±23 pm and 271±31 to 231±28 pm, r = -0.758 and -0.659, all P〈0.001, the thickness from 547±23 to 418±28μm and 483±45 to 364±35μm, r= -0.898 and -0.829, all P〈0.001), but there was no statistical difference in the colon (F= 0.296, P = 0.934). Compared with control group, the urine L/M ratio and the blood LPS concentration in the experimental groups raised significantly, reaching the peak in 3-6 h (L/M: control vs 3 h vs6 h was 0.029±0.09 vs 0.063±0.012 vs 0.078±0.021, r = -0.786, P〈0.001; LPS: control vs3 h vs6 h was 0.09±0.021 vs 0.063±0.012 vs0.25±0.023, r=- -0.623, P〈0.001), and it kept increasing in 24 h. CONCLUSION: The gut barrier of the rats was seriously damaged at the early phase of ischemic reperfusion injury after hemorrhagic shock, which included the injury and atrophy in intestinal mucosa and the increasing of intestinal permeability. Simultaneously, the intestinal mucosa also showed its great repairing potentiality, such as the improvement of the intestinal permeability and the recovery of the morphology at different phases after ischemic reperfusion injury. The restitution of gut barrier function was obviously slower than that of the morphology and there was no direct correlation between them. Compared with the small intestine, the large intestine had stronger potentiality against injury. The reduction of the amount of intestinal goblet cells by injury did not influence the ability of intestinal mucosal restitution at a certain extent and it appeared to be intimately involved in the restitution of the epithelium.
基金Project (No. 20061420) supported by the Education and Research Foundation of Zhejiang Province, China
文摘Objective: To investigate the early effects of hypertonic and isotonic saline solutions on apoptosis of intestinal mucosa in rats with hemorrhagic shock. Methods: A model of rat with severe hemorrhagic shock was established in 21 Sprague-Dawley (SD) rats. The rats were randomly divided into the sham group, normal saline resuscitation (NS) group, and hypertonic saline resuscitation (HTS) group, with 7 in each group. We detected and compared the apoptosis in small intestinal mucosa of rats after hemorrhagic shock and resuscitation by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), FITC (fluo- rescein-iso-thiocyanate)-Annexin V/PI (propidium iodide) double staining method, and flow cytometry. Results: In the early stage of hemorrhagic shock and resuscitation, marked apoptosis of small intestinal mucosa in the rats of both NS and HTS groups was observed. The numbers of apoptotic cells in these two groups were significantly greater than that in the sham group (P<0.01). In the HTS group, the apoptic cells significantly decreased, compared with the NS group (P<0.01). Conclusion: In this rat model of severe hemorrhagic shock, the HTS resuscitation of small volume is more effective than the NS resuscitation in reducing apoptosis of intestinal mucosa in rats, which may improve the prognosis of trauma.
基金Supported by the National Natural Science Foundation of China,No.30200272
文摘AIM: To investigate the role of nitric oxide (NO) in Tolllike receptor 2 (TLR2)/4mRNA expression in livers of acute hemorrhagic necrotizing pancreatitis (AHNP) rats. METHODS: One hundred and ten SD male rats were randomly divided into sham-operated group (n = 10), AHNP group (n = 30), chloroquine (CQ)-treated group (n = 30) and L-Arg-treated group (n = 40). TLR2/4mRNA expression in the liver of AHNP rats was measured by RT-PCR. RESULTS: Expression of TLR2/4mRNA could be detected in the liver of AHNP rats in sham-operated group (0.155E-5±0.230E-6 and 0.115E-2±0.545E-4), but was markedly increased at 3 h in AHNP group (0.197E-2±0.114E-3 and 0.175±0.349E-2) peaking at 12 h (0.294E-2 ± 0.998E-4 and 2.673 ± 2.795E-2, P〈 0.01). Hepatic injuries were aggravated, TNF-α concentration in the liver was increased and NO concentration was decreased (P〈 0.05 or P〈 0.01). When TLR2/4mRNA expression was inhibited by CQ (3 h: 1.037E-4±3.299E-6 and 0.026±3.462E-3; 6 h: 1.884E-4±4.679E-6 and 0.108±6.115E-3; 12 h: 2.443E-4±7.714E-6 and 0.348±6.807E-3; P 〈 0.01), hepatic injuries were relieved, NO concentration in the liver was increased and TNF-α concentration was decreased (P〈0.05 or P〈0.01). When rats with AHNP were treated with L-Arg, TLR2/4mRNA expression in the liver could be effectively inhibited (50 mg-T: 0.232E-2±0.532E-4 and 0.230±6.883E-3; 100 mg-T: 0.210E-2± 1.691E-4 and 0.187±0.849E-2; 200 mg-T: 0.163E-2±0.404E-4 and 0.107±0.195E-2; 400 mg-T: 0.100E-2±0.317E-4 and 0.084±0.552E-2; P〈0.01) and hepatic injuries were relieved. At the same time, NO concentration in the liver was markedly increased and TNF-α concentration was decreased (P〈0.05 or P〈O.OI), CONCLUSION: The expression of TLR2/4mRNA is increased and hepatic injuries are aggravated in the liver of AHNP rats. TLR2/4mRNA gene expression in the liver of AHNP rats can be markedly inhibited by NO, leading to the relief of hepatic injuries.
基金Supported by CIBEREHD is funded by the Instituto de Salud Carlos III, Madrid, Spain
文摘Anemia of diverse etiology is a common complication of chronic liver diseases. The causes of anemia include acute or chronic gastrointestinal hemorrhage, and hypersplenism secondary to portal hypertension. Severe hepatocellular disease predisposes to hemorrhage because of impaired blood coagulation caused by deficiency of blood coagulation factors synthesized by hepatocytes, and/or thrombocytopenia. Aplastic anemia, which is characterized by pancytopenia and hypocellular bone marrow, may follow the development of hepatitis. Its presentation includes progressive anemia and hemorrhagic manifestations. Hematological complications of combination therapy for chronic viral hepatitis include clinically signif icant anemia, secondary to treatment with ribavirin and/or interferon. Ribavirininduced hemolysis can be reversed by reducing the dose of the drug or discontinuing it altogether. Interferons may contribute to anemia by inducing bone marrow suppression. Alcohol ingestion is implicated in the pathogenesis of chronic liver disease and may contribute to associated anemia. In patients with chronic liver disease, anemia may be exacerbated by defi ciency of folic acid and/or vitamin B12 that can occur secondary to inadequate dietary intake or malabsorption.
文摘Acute upper gastrointestinal bleeding(UGIB) is a gastroenterological emergency with a mortality of 6%-13%.The vast majority of these bleeds are due to peptic ulcers.Nonsteroidal anti-inflammatory drugs and Helicobacter pylori are the main risk factors for peptic ulcer disease.Endoscopy has become the mainstay for diagnosis and treatment of acute UGIB,and is recommended within 24 h of presentation.Proton pump inhibitor(PPI) administration before endoscopy can downstage the bleeding lesion and reduce the need for endoscopic therapy,but has no effect on rebleeding,mortality and need for surgery.Endoscopic therapy should be undertaken for ulcers with high-risk stigmata,to reduce the risk of rebleeding.This can be done with a variety of modalities.High-dose PPI administration after endoscopy can prevent rebleeding and reduce the need for further intervention and mortality,particularly in patients with high-risk stigmata.
基金a grant from the Korean Association for the Study of Intestinal Diseases
文摘AIM:To evaluate and compare the clinical outcomes of prophylactic submucosal saline-epinephrine injection and saline injection alone for large colon polyps by conventional polypectomy. METHODS:A prospective study was conducted from July 2003 to July 2004 at 11 tertiary endoscopic centers. Large colon polyps (> 10 mm in diameter) wererandomized to undergo endoscopic polypectomy with submucosal saline-epinephrine injection (epinephrine group) or normal saline injection (saline group). Endoscopic polypectomy was performed by the conventional snare method,and early (< 12 h) and late bleeding complications (12 h-30 d) were observed. RESULTS:A total of 561 polyps in 486 patients were resected by endoscopic polypectomy. Overall,bleeding complications occurred in 7.6% (37/486) of the patients,including 4.9% (12/244) in the epinephrine group,and 10.3% (25/242) in the saline group. Early and late postpolypectomy bleeding (PPB) occurred in 6.6% (32/486) and 1% (5/486) of the patients,respectively,including 4.5% (11/244),0.4% (1/244) in the epinephrine group,and 8.7% (21/242),1.7% (4/242) in the saline group. No significant differences in the rates of overall,early and late PPB were observed between the 2 groups. Multivariate stepwise logistic regression analysis revealed that large size (> 2 cm) and neoplastic polyps were independently and significantly associated with the presence of PPB. CONCLUSION:The prophylactic submucosal injection of diluted epinephrine does not appear to provide an additional advantage over the saline injection alone for the prevention of PPB.
基金Supported by the Chinese Traditional Medicine Foundation of Guangdong Province, China, No. 102061
文摘AIM: To study the protective effect of Astragalus rnernbranaceus on intestinal mucosa reperfusion injury and its mechanism after hemorrhagic shock in rats. METHODS: A total of 32 SD rats were randomly divided into four groups (n = 8, each group): normal group, model group, low dosage group (treated with 10 g/kg Astragalus membranaceus) and high dosage group (treated with 20 g/kg Astragalus membranaceus). The model of hemorrhagic shock for 60 min and reperfusion for 90 min was established. Therapeutic solution (3 mL) was administrated before reperfusion. At the end of the study, the observed intestinal pathology was analyzed. The blood concentrations of lactic acid (LD), nitric oxide (NO), endothelin-1 (ET-1), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) in intestinal mucosa were determined. RESULTS: The intestinal mucosa pathology showed severe damage in model group and low dosage group, slight damage in high dosage group and no obvious damage in normal group. The Chiu's score in low dose group and high dose group was significantly lower than that in model group. The content of MDA in model group was higher than that in low and high dose groups, while that in high dose group was almost the same as in normal group. The activity of SOD and GSH-PX was the lowest in model group and significantly higher in high dose group than in normal and low dose groups. The concentrations of LD and ET-1 in model group were the highest. The concentrations of NO in model group and low dose group were significantly lower than those in high dose group and normal group. CONCLUSION: High dose Astraga/us membranaeus has much better protective effect on hemorrhagic shockreperfusion injury of intestinal mucosa than low dose Astragalus membranaceus. The mechanism may be that Astragalus membranaceus can improve antioxidative effect and regulate NO/ET level during hemorrhagic reperfusion.
文摘Background The CRUSADE, ACTION and ACUITY-HORIZONS scores are commonly used for predicting in-hospital major bleeding events in patients with acute coronary syndrome (ACS), but the homogeneous nature of these models' population limits simple ex- trapolation to other local population. We aimed to compare the performance of the three risk models in Chinese patients. Methods We evaluated the performance of the three predicting scores for predicting in-hospital major bleeding events defined by thrombolysis in myocar- dial infarction (TIMI) serious (major and minor) episodes, in a cohort of Chinese ACS patients with either non-ST-elevation ACS (NSTE-ACS) or ST-elevation myocardial infarction (STEMI). Calibration and discrimination of the three risk models were evaluated by the Hosmer-Lemeshow test and C-statistic, respectively. We compared the predictive accuracy of the risk scores by the Delong non-parametric test. Results TIMI serious bleeding rate was 1.1% overall (1.9% and 0.86% for STEMI and NSTE-ACS, respectively). The CRUSADE, ACTION and ACUTIY-HOR/ZONS scores showed an adequate discriminatory capacity for major bleeding: in overall patients, the C-statistic was 0.80, 0.77, and 0.70, respectively; in NSTE-ACS patients, the C-statistic was 0.73, 0.72, and 0.64, respectively; in STEMI patients, the C-statistic was 0.91, 0.92, and 0.75, respectively. The C-statistic for the ACUITY-HORIZONS model was significantly lower than those of the CRUSADE and ACTION scores for the prediction of TIM/serious bleeding in overall patients (compared with CRUSADE, z = 3.83, P = 0.02; compared with ACTION, z = 3.51, P = 0.03); in NSTE-ACS patients (compared with CRUSADE, z = 2.37, P = 0.01; compared with ACTION, z = 2.11, P = 0.04), and in STEMI patients (compared with CRUSADE, z = 2.6.77, P = 0.02; compared with AC- TION, z = 7.91, P = 0.002). No differences were observed when the CRUSADE and ACTION models were compared to each other, regard- less of overall patients (z = 0.68, P = 0.31) and both of ACS types (NSTE-ACS, z = 0.52, P = 0.60), and STEMI patients (z = 0.36, P = 0.74). However, the three risk scores all overestimated the absolute major bleeding risk in each risk stratification in our study. For example, the predicted rate of CRUSADE score at high risk stratification was 11.9% vs. an actual rate of 5.3%. Conclusions The CRUSADE and AC- TION scores had a greater calibration and discrimination for in-hospital major bleeding compared with the ACUITY-HORIZONS score in Chinese patients with ACS undergoing PCI. However, they all overestimated the bleeding risk rate for Chinese populations. Calibration of these risk scores would be useful for the generalization in Chinese populations.
文摘AIM: To evaluate the diagnostic angiography and therapy for acute massive hemorrhage in gastrointestinal tract. METHODS: Twenty-five cases of acute hemorrhage in gastrointestinal tract admitted between April 2002 and September 2004 were reviewed and analyzed by angiography and embolotherapyo RESULTS: Fifteen patients were men and ten patients were women. The Seldinger technique and method of coaxial duct were used to get access to the bleeding region. PVA particles, gelfoam, and coils were used for embolism. All bleeding sites could be confirmed and were successfully embolized. Hemostasis was achieved in all the patients without bleeding again. The cure rate was 100%. CONCLUSION: Interventional therapy can not only ascertain the bleeding site, but also stop the bleeding .The method is simple and the effect is certain.
文摘Crohn's disease and ulcerative colitis can be grouped as the inflammatory bowel diseases (IBD). These conditions have become increasingly common in recent years, including in children and young people. Although much is known about aspects of the pathogenesis of these diseases, the precise aetiology is not yet understood, and there remains no cure. Recent data has illustrated the importance of a number of genes-several of these are important in the onset of IBD in early life, including in infancy. Pain, diarrhoea and weight loss are typical symptoms of paediatric Crohn's disease whereas bloody diarrhoea is more typical of colitis in children. However, atypical symptoms may occur in both conditions: these include isolated impairment of linear growth or presentation with extra-intestinal manifestations such as erythma nodosum. Growth and nutrition are commonly compromised at diagnosis in both Crohn's disease and colitis. Consideration of possible IBD and completion of appropriate investigations are essential to ensure prompt diagnosis, the- reby avoiding the consequences of diagnostic delay. Patterns of disease including location and progression of IBD in childhood differ substantially from adult- onset disease. Various treatment options are available for children and adolescents with IBD. Exclusive enteral nutrition plays a central role in the induction of remission of active Crohn's disease. Medical and surgical therapies need to considered within the context of a growing and developing child. The overall management of these chronic conditions in children should include multi-disciplinary expertise, with focus upon maintaining control of gut inflammation, optimising nutrition, growth and quality of life, whilst preventing disease or treatment-related complications.
文摘Inducible heat shock protein 70 kD (HSP-70i) has been shown to protect cells, tissues, and organs from harmful assaults in in vivo and in vitro experimental models. Hemorrhagic shock followed by resuscitation is the principal cause of death among trauma patients and soldiers in the battlefield. Although the underlying mechanisms are still not fully understood, it has been shown that nitric oxide (NO) overproduction and inducible nitric oxide synthase (iNOS) overexpression play important roles in producing injury caused by hemorrhagic shock including increases in polymorphonuclear neutrophils (PMN) infiltration to injured tissues and leukotriene B4 (LTB4) generation. Moreover, transcription factors responsible for iNOS expression are also altered by hemorrhage and resuscitation. It has been evident that either up-regulation of HSP-70i or down-regulation of iNOS can limit tissue injury caused by ischemia/reperfusion or hemorrhage/resuscitation. In our laboratory, geldanamycin, a member of ansamycin family, has been shown to induce HSP-70i overexpression and then subsequently to inhibit iNOS expression, to reduce cellular caspase-3 activity, and to preserve cellular ATP levels. HSP-70i is found to couple to iNOS and its transcription factor. Therefore, the complex formation between HSP-70i and iNOS may be a novel mechanism for protection from hemorrhage/resuscitation-in-duced injury.
文摘AIM: To investigate acute nonvariceal bleeding in the upper gastrointestinal (GI) tract and evaluate the effects of endoscopic hemoclipping. METHODS: Sixty-eight cases of acute nonvariceal bleeding in the upper GI tract were given endoscopic treatment with hemoclip application. Clinical data, endoscopic findings, and the effects of the therapy were evaluated. RESULTS: The 68 cases (male:female = 42:26, age from 9 to 70 years, average 54.4) presented with hernatemesis in 26 cases (38.2%), melena in nine cases (13.3%), and both in 33 cases (48.5%). The causes of the bleeding included gastric ulcer (29 cases), duodenal ulcer (11 cases), Dieulafoy's lesion (11 cases), Mallory-Weiss syndrome (six cases), post-operative (three cases), post-polypectomy bleeding (five cases), and post-sphincterotomy bleeding (three cases); 42 cases had active bleeding. The mean number of hemoclips applied was four. Permanent hemostasis was obtained by hemoclip application in 59 cases; 6 cases required emergent surgery (three cases had peptic ulcers, one had Dieulafoy's lesion, and two were caused by sphincterotomy); three patients died (two had Dieulafoy's lesion and one was caused by sphincterotomy); and one had recurrent bleeding with Dieulafoy's lesion 10 mo later, but in a different location. CONCLUSION: Endoscopic hemoclip application was an effective and safe method for acute nonvariceal bleeding in the upper GI tract with satisfactory outcomes.