Background:This study evaluates the efficacy of gabexate mesylate thermosensitive in-situ gel(GMTI) in the treatment of beagle grade Ⅲ pancreatic trauma(PT) with the assistance of contrast-enhanced ultrasound(CEUS) a...Background:This study evaluates the efficacy of gabexate mesylate thermosensitive in-situ gel(GMTI) in the treatment of beagle grade Ⅲ pancreatic trauma(PT) with the assistance of contrast-enhanced ultrasound(CEUS) and investigates its mechanism of action.Methods:A grade Ⅲ PT model consisting of 15 beagle dogs with severed main pancreatic ducts was created and treated with cephalic vein injection of gabexate mesylate(GM)(1.54mL/10kg,TID) and peripancreatic injection of GMTI(4.63 mL/10 kg,QD) guided by CEUS within 24h post-surgery.Ascites and serum levels of amylase(AMY),lipase(LPS),C-reactive protein(CRP),interleukin(IL)-6,tumor necrosis factor(TNF)-α,and urinary trypsinogen activating peptide(TAP) were detected by ELISA.Histopathological changes in the canine pancreas were observed by Hematoxylin and Eosin staining.Results:CEUS accurately displayed pancreatic lesions and guided catheterisation.Compared to the control group,the ascites was significantly reduced after treatment(p<0.01).AMY and LPS ascites significantly decreased on post-operative 1st and 2nd day(p<0.01).The levels of AMY,LPS,CRP,IL-6,and TNF-α in serum were decreased(p<0.05 or p <0.01).Urinary TAP was decreased 1 and 2 days after treatment(p<0.05or p<0.01,respectively).In the control group,pancreatic tissue necrosis was evident in the wound area.Normal glandular cell structures and fibrous tissue hyperplasia were observed in the wound area after GMTI treatment.The GMTI group performed better than the GM group in improving pancreatic histology and reducing AMY levels in the early post-operative period.Conclusion:Guided by CEUS,daily peripancreatic injections of GMTI in Beagles effectively inhibit pancreatic enzyme activity and aid in the adjuvant treatment of pancreatic trauma.展开更多
AIM： To evaluate the efficacy of continuous regional arterial infusion therapy （CRAI） with gabexate mesilate and antibiotics for severe acute pancreatitis （SAP）. METHODS： We conducted a prospective study on pati...AIM： To evaluate the efficacy of continuous regional arterial infusion therapy （CRAI） with gabexate mesilate and antibiotics for severe acute pancreatitis （SAP）. METHODS： We conducted a prospective study on patients who developed SAP with or without CRAI. Out of 18 patients fulfilled clinical diagnostic criteria for SAP in Japan, 9 patients underwent CRAI, while 9 patients underwent conventional systemic protease inhibitor and antibiotics therapy （non-CRAI）. CRAI was initiated within 72 h of the onset of pancreatitis. Gabexate mesilate （2400 mg/d） was continuously administered for 3 to 5 d. The clinical outcome including serum inflammation-related parameters were examined. RESULTS- The duration of abdominal pain in the CRAI group was 1.9 =1：0.26 d, whereas that in the non-CRAI group was 4.3 ±0.50. The duration of SIRS in the CRAI group was 2.2 ± 0.22 d, whereas that in the non- CRAI group was 3.2 ± 0.28. Abdominal pain and SIRS disappeared significantly in a short period of time after the initiation of CRAI using gabexate mesilate. The average length of hospitalization significantly differed between the CRAI and non-CRAI groups, 53.3 ± 7.9 d and 87.4± 13.9 d, respectively. During the first two weeks, levels of serum CRP and the IL6/IL10 ratio in the CRAI group tended to have a rapid decrease compared to those in the non-CRAI group. CONCLUSION： The present results suggest that CRAI using gabexate mesilate was effective against SAP.展开更多
Objective:To study the effects of octreotide combined with gabexate on related cytokines in patients with severe acute pancreatitis (SAP).Methods:A total of 92 patients with SAP from January 2014 to December 2017 in o...Objective:To study the effects of octreotide combined with gabexate on related cytokines in patients with severe acute pancreatitis (SAP).Methods:A total of 92 patients with SAP from January 2014 to December 2017 in our hospital were enrolled in this study. According to random number table method, the patients were divided into the control group and the treatment group, each groups has 46 patients. The control group were treated with octreotide, the treatment group were treated with octreotide combined with gabexate. To compare the serum B7-H3, PCT, sICAM-1, NF-κB, sTREM-1, BAFF, SAA, NGAL, ghrelin, hs-CRP, MDA and SOD of the two groups before and after treatment.Results: The serum B7-H3, PCT, sICAM-1, NF-κB, sTREM-1, BAFF, SAA, NGAL, ghrelin, hs-CRP, MDA and SOD of the two groups before treatment have no no significantly differences. The serum B7-H3, PCT, sICAM-1, NF-κB, sTREM-1, BAFF, SAA, NGAL, ghrelin, hs-CRP, MDA of the two groups after treatment were significantly lower than before treatment, the serum SOD of the two groups after treatment were significantly better than before treatment, and that of the treatment group were significantly better than the control group after treatment.Conclusion: Octreotide combined with gabexate for patients with SAP can reduce the serum B7-H3, PCT, sICAM-1, NF-κB, sTREM-1, BAFF, SAA, NGAL, ghrelin, hs-CRP, MDA levels, improve serum SOD levels, and it was worthy clinical application.展开更多
The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (...The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may be useful as prophylaxis against Post Endoscopic retrograde cholangiopancreatography Pancreatitis (PEP). The protease inhibitor Gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL) is a nitrogen oxide (NO) donor, which relaxes the sphincter of Oddi. Studies show conflicting results when applied prior to ERCP and a large multicenter randomized study is warranted. Steroids administered as prophylaxis against PEP has been validated without effect in several randomized trials. The non-steroidal anti-inflammatory drugs (NSAID) indomethacin and diclofenac have in randomized studies showed potential as prophylaxis against PEP. Interleukin 10 (IL-10) is a cytokine with anti-inflammatory properties but two trials testing IL-10 as prophylaxis to PEP have returned conflicting results. Antibodies against tumor necrosis factor-alpha (TNF-α) have a potential as rescue therapy but no clinical trials are currently being conducted. The antibiotics beta- lactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis. Evidence based pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted.展开更多
Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). The only way to prevent this complication is to avoid an ERCP all together. Because of the risks involved, a...Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). The only way to prevent this complication is to avoid an ERCP all together. Because of the risks involved, a careful consideration should be given to the indication for ERCP and the potential risk/benefit ratio of the test. Once a decision to perform an ERCP is made, the procedure should be carried out with meticulous care by an experienced endoscopist, and with a minimum of pancreatic duct opacification. Several pharmacologic agents have been tested, but to date the most important method of reducing post ERCP pancreatitis is the placement of pancreatic stent. Pancreatic stents should be placed in all patients at high risk of this complication such as those undergoing pancreatic sphincterotomy, pancreatic duct manipulation and intervention, and patients with suspected sphincter of Oddi dysfunction. Pancreatic stents should be also considered in patients requiring precut sphincterotomy to gain biliary access.展开更多
文摘Background:This study evaluates the efficacy of gabexate mesylate thermosensitive in-situ gel(GMTI) in the treatment of beagle grade Ⅲ pancreatic trauma(PT) with the assistance of contrast-enhanced ultrasound(CEUS) and investigates its mechanism of action.Methods:A grade Ⅲ PT model consisting of 15 beagle dogs with severed main pancreatic ducts was created and treated with cephalic vein injection of gabexate mesylate(GM)(1.54mL/10kg,TID) and peripancreatic injection of GMTI(4.63 mL/10 kg,QD) guided by CEUS within 24h post-surgery.Ascites and serum levels of amylase(AMY),lipase(LPS),C-reactive protein(CRP),interleukin(IL)-6,tumor necrosis factor(TNF)-α,and urinary trypsinogen activating peptide(TAP) were detected by ELISA.Histopathological changes in the canine pancreas were observed by Hematoxylin and Eosin staining.Results:CEUS accurately displayed pancreatic lesions and guided catheterisation.Compared to the control group,the ascites was significantly reduced after treatment(p<0.01).AMY and LPS ascites significantly decreased on post-operative 1st and 2nd day(p<0.01).The levels of AMY,LPS,CRP,IL-6,and TNF-α in serum were decreased(p<0.05 or p <0.01).Urinary TAP was decreased 1 and 2 days after treatment(p<0.05or p<0.01,respectively).In the control group,pancreatic tissue necrosis was evident in the wound area.Normal glandular cell structures and fibrous tissue hyperplasia were observed in the wound area after GMTI treatment.The GMTI group performed better than the GM group in improving pancreatic histology and reducing AMY levels in the early post-operative period.Conclusion:Guided by CEUS,daily peripancreatic injections of GMTI in Beagles effectively inhibit pancreatic enzyme activity and aid in the adjuvant treatment of pancreatic trauma.
基金Supported by Grant from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, No. 20590808The Research Committee of Intractable Diseases of the Pancreas, provided by the Ministry of Health, Labour, and Welfare Japan, No. 50253448
文摘AIM： To evaluate the efficacy of continuous regional arterial infusion therapy （CRAI） with gabexate mesilate and antibiotics for severe acute pancreatitis （SAP）. METHODS： We conducted a prospective study on patients who developed SAP with or without CRAI. Out of 18 patients fulfilled clinical diagnostic criteria for SAP in Japan, 9 patients underwent CRAI, while 9 patients underwent conventional systemic protease inhibitor and antibiotics therapy （non-CRAI）. CRAI was initiated within 72 h of the onset of pancreatitis. Gabexate mesilate （2400 mg/d） was continuously administered for 3 to 5 d. The clinical outcome including serum inflammation-related parameters were examined. RESULTS- The duration of abdominal pain in the CRAI group was 1.9 =1：0.26 d, whereas that in the non-CRAI group was 4.3 ±0.50. The duration of SIRS in the CRAI group was 2.2 ± 0.22 d, whereas that in the non- CRAI group was 3.2 ± 0.28. Abdominal pain and SIRS disappeared significantly in a short period of time after the initiation of CRAI using gabexate mesilate. The average length of hospitalization significantly differed between the CRAI and non-CRAI groups, 53.3 ± 7.9 d and 87.4± 13.9 d, respectively. During the first two weeks, levels of serum CRP and the IL6/IL10 ratio in the CRAI group tended to have a rapid decrease compared to those in the non-CRAI group. CONCLUSION： The present results suggest that CRAI using gabexate mesilate was effective against SAP.
文摘Objective:To study the effects of octreotide combined with gabexate on related cytokines in patients with severe acute pancreatitis (SAP).Methods:A total of 92 patients with SAP from January 2014 to December 2017 in our hospital were enrolled in this study. According to random number table method, the patients were divided into the control group and the treatment group, each groups has 46 patients. The control group were treated with octreotide, the treatment group were treated with octreotide combined with gabexate. To compare the serum B7-H3, PCT, sICAM-1, NF-κB, sTREM-1, BAFF, SAA, NGAL, ghrelin, hs-CRP, MDA and SOD of the two groups before and after treatment.Results: The serum B7-H3, PCT, sICAM-1, NF-κB, sTREM-1, BAFF, SAA, NGAL, ghrelin, hs-CRP, MDA and SOD of the two groups before treatment have no no significantly differences. The serum B7-H3, PCT, sICAM-1, NF-κB, sTREM-1, BAFF, SAA, NGAL, ghrelin, hs-CRP, MDA of the two groups after treatment were significantly lower than before treatment, the serum SOD of the two groups after treatment were significantly better than before treatment, and that of the treatment group were significantly better than the control group after treatment.Conclusion: Octreotide combined with gabexate for patients with SAP can reduce the serum B7-H3, PCT, sICAM-1, NF-κB, sTREM-1, BAFF, SAA, NGAL, ghrelin, hs-CRP, MDA levels, improve serum SOD levels, and it was worthy clinical application.
文摘The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may be useful as prophylaxis against Post Endoscopic retrograde cholangiopancreatography Pancreatitis (PEP). The protease inhibitor Gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL) is a nitrogen oxide (NO) donor, which relaxes the sphincter of Oddi. Studies show conflicting results when applied prior to ERCP and a large multicenter randomized study is warranted. Steroids administered as prophylaxis against PEP has been validated without effect in several randomized trials. The non-steroidal anti-inflammatory drugs (NSAID) indomethacin and diclofenac have in randomized studies showed potential as prophylaxis against PEP. Interleukin 10 (IL-10) is a cytokine with anti-inflammatory properties but two trials testing IL-10 as prophylaxis to PEP have returned conflicting results. Antibodies against tumor necrosis factor-alpha (TNF-α) have a potential as rescue therapy but no clinical trials are currently being conducted. The antibiotics beta- lactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis. Evidence based pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted.
文摘Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). The only way to prevent this complication is to avoid an ERCP all together. Because of the risks involved, a careful consideration should be given to the indication for ERCP and the potential risk/benefit ratio of the test. Once a decision to perform an ERCP is made, the procedure should be carried out with meticulous care by an experienced endoscopist, and with a minimum of pancreatic duct opacification. Several pharmacologic agents have been tested, but to date the most important method of reducing post ERCP pancreatitis is the placement of pancreatic stent. Pancreatic stents should be placed in all patients at high risk of this complication such as those undergoing pancreatic sphincterotomy, pancreatic duct manipulation and intervention, and patients with suspected sphincter of Oddi dysfunction. Pancreatic stents should be also considered in patients requiring precut sphincterotomy to gain biliary access.
