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OBJECTIVE@#This study demonstrated that dexamethasone (DEX) protects the endothelial glycocalyx from damage induced by the inflammatory stimulus tumor necrosis factor-α (TNF-α) during severe acute pancreatitis (SAP), and improves the renal microcirculation.@*METHODS@#Ninety mice were evenly divided into 3 groups (Sham, SAP, and SAP+DEX). The SAP mice model was established by ligature of pancreatic duct and intraperitoneal injection of cerulein. Renal perfusion and function, and morphological changes of the glycocalyx were evaluated by laser Doppler velocimetry, electron microscopy, and histopathology (hematoxylin and eosin (H&E) staining), respectively. Serum levels of syndecan-1 and TNF-α were assessed by enzyme-linked immunosorbent assay (ELISA). The protective effects of dexamethasone on the glycocalyx and renal microcirculation were evaluated.@*RESULTS@#Significantly high levels of serum TNF-α were detected 3 h after the onset of SAP. These levels might induce degradation of the glycocalyx and kidney hypoperfusion, resulting in kidney microcirculation dysfunction. The application of dexamethasone reduced the degradation of the glycocalyx and improved perfusion of kidney.@*CONCLUSIONS@#Dexamethasone protects the endothelial glycocalyx from inflammatory degradation possibly initiated by TNF-α during SAP. This is might be a significant discovery that helps to prevent tissue edema and hypoperfusion in the future.
Subject(s)
Animals , Male , Mice , Acute Disease , Dexamethasone/pharmacology , Disease Models, Animal , Edema/metabolism , Endothelium, Vascular/metabolism , Enzyme-Linked Immunosorbent Assay , Glycocalyx/drug effects , Kidney/drug effects , Mice, Inbred C57BL , Microcirculation , Pancreatitis/drug therapy , Perfusion , Protective Agents/pharmacology , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Objective: This study demonstrated that dexamethasone (DEX) protects the endothelial glycocalyx from damage induced by the inflammatory stimulus tumor necrosis factor-α (TNF-α) during severe acute pancreatitis (SAP), and improves the renal microcirculation. Methods: Ninety mice were evenly divided into 3 groups (Sham, SAP, and SAP+DEX). The SAP mice model was established by ligature of pancreatic duct and intraperitoneal injection of cerulein. Renal perfusion and function, and morphological changes of the glycocalyx were evaluated by laser Doppler velocimetry, electron microscopy, and histopathology (hematoxylin and eosin (H&E) staining), respectively. Serum levels of syndecan-1 and TNF-α were assessed by enzyme-linked immunosorbent assay (ELISA). The protective effects of dexamethasone on the glycocalyx and renal microcirculation were evaluated. Results: Significantly high levels of serum TNF-α were detected 3 h after the onset of SAP. These levels might induce degradation of the glycocalyx and kidney hypoperfusion, resulting in kidney microcirculation dysfunction. The application of dexamethasone reduced the degradation of the glycocalyx and improved perfusion of kidney. Conclusions: Dexamethasone protects the endothelial glycocalyx from inflammatory degradation possibly initiated by TNF-α during SAP. This is might be a significant discovery that helps to prevent tissue edema and hypoperfusion in the future.
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Objective To study the impact of early abdominal paracentesis drainage (APD) on the clinical course in patients with severe acute pancreatitis and massive peritoneal effusion.Methods From January 2012 to January 2017,107 patients with severe acute pancreatitis treated at the Chengdu Military General Hospital were retrospective studied.According to whether the patients underwent abdominal paracentesis drainage within a week of hospital admission,they were divided into the APD group (n=66) and the Non-APD group (n=41).The APD group was further subgrouped into the 0-2 d (within 48 h),3-5 d and 6 -7 d subgroups.The mortality rates,progression rates,length of stay,cost of stay,organ failure rates and inflammatory state of each subgroup of the APD were statistically analyzed and compared.Results 22 patients in the Non-APD group progressed in four weeks to require percutaneous catheter drainage (PCD).The rate of progression was 53.7％,and the mortality rate was 22％.In the APD group,21 patients underwent PCD treatment within 4 weeks.The rate of progression was 31.8％ and the mortality rate was 9.1％.In the APD group,the progression rate for the patients in the 0-2 d subgroup was 6.9％,and the in-hospital mortality rate was O.When compared with the other subgroups,the 0 to 2 d subgroup of patients had significantly lower progression and in-hospital mortality rates,lower hospitalization duration and hospitalization costs.These patients at 1 week after hospitalization also had significantly better inflammatory indexes,less incidence of organ failure and better disease severity scores (P＜0.05).Conclusions The results confirmed the effectiveness of APD in treating patients with severe acute pancreatitis with significant peritoneal effusion.Puncture treatment within 48 hours significantly improved prognosis of patients.The best time window of APD treatment for patients with severe acute pancreatitis with massive abdominal fluid is within 48 hours of hospitalization.
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Objective To investigate the efficacy and safety of continuous regional arterial infusion (CRAI) in patients with severe acute pancreatitis (SAP).Methods One hundred SAP patients (including 41 gallstone,26 alcoholism,13 hypertriglyceridemia,11 after heavy meals,and 9 unknown) who were admitted into our hospital from January 2013 to October 2017 were assigned to the CRAI group (n =58) and the control group (n =42).The levels of laboratory measurements,hospitalization time and costs,complications and outcomes were compared between the two groups.Results On the sixth and tenth day of treatment,the levels of white blood cell,hemodiastase,urine amylase,blood glucose,blood calcium and APACHE-Ⅱ score improved in both the 2 groups.The degrees of improvement in the CRAI group were better than that in the control group.The abdominal pain relief time [(3.3± 1.2)d vs.(5.9±2.3)d],hemodiastase recovery time [(7.9±1.8)d vs.(13.3±2.5)d],and hospitalization stay [(21.3±3.6)d vs.(32.4±4.3)d] were shorter in the CRAI group.The costs were similar in the two groups.Retroperitoneal infection,pancreatic pseudocyst,and pancreatic drainage were less in the CRAI group.The improved and cure rates were 94.8％ and 70.7％ in the CRAI group,which were higher than those in the control group (71.4％ and 47.6％,respectively).Moreover,the ineffective treatment and mortality rates were 5.2％ and 1.7％ in the CRAI group,which were lower than those in the control group (28.6％ and 14.3％,respectively).Conclusions CRAI was an efficacious and safe treatment for patients with SAP.It can be used as an alternative to other effective treatments.
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Multidrug-resistant (MDR) bacterial infection is a common complication of severe acute pancreatitis (SAP).This study aimed to explore the association between human leukocyte antigen-antigen D-related (HLA-DR) expression and multidrug-resistant infection in patients with SAP.A total of 24 SAP patients who were admitted to Nanjing Drum Tower Hospital between May 2015 and December 2016 were enrolled in the study.The percentages of CD4+,CD8+,natural killer (NK),and HLA-DR (CD14+) cells and the CD4+/CD8+ cell ratio on days 1,7,14,and 28 after admission were determined by flow cytometry.Eighteen patients presented with the symptoms of infection.Among them,55.6％ patients (10/18) developed MDR infection.The most common causative MDR organisms were Enterobacter cloacae and Acinetobacter baumannii.The CD4+/CD8+ cell ratio and the percentage of NK cells were similar between patients with non-MDR and patients with MDR infections.In patients without infection,the HLA-DR percentage was maintained at a high level throughout the 28 days.Compared to the patients without any infection,the HLA-DR percentage in patients with non-MDR infection was reduced on day 1 but increased and reached similar levels on day 28.In patients with MDR infection,the HLA-DR percentage remained below normal levels at all-time points.It was concluded that persistent down-regulation of HLA-DR expression is associated with MDR bacterial infection in patients with SAP.
ABSTRACT
Multidrug-resistant (MDR) bacterial infection is a common complication of severe acute pancreatitis (SAP).This study aimed to explore the association between human leukocyte antigen-antigen D-related (HLA-DR) expression and multidrug-resistant infection in patients with SAP.A total of 24 SAP patients who were admitted to Nanjing Drum Tower Hospital between May 2015 and December 2016 were enrolled in the study.The percentages of CD4+,CD8+,natural killer (NK),and HLA-DR (CD14+) cells and the CD4+/CD8+ cell ratio on days 1,7,14,and 28 after admission were determined by flow cytometry.Eighteen patients presented with the symptoms of infection.Among them,55.6％ patients (10/18) developed MDR infection.The most common causative MDR organisms were Enterobacter cloacae and Acinetobacter baumannii.The CD4+/CD8+ cell ratio and the percentage of NK cells were similar between patients with non-MDR and patients with MDR infections.In patients without infection,the HLA-DR percentage was maintained at a high level throughout the 28 days.Compared to the patients without any infection,the HLA-DR percentage in patients with non-MDR infection was reduced on day 1 but increased and reached similar levels on day 28.In patients with MDR infection,the HLA-DR percentage remained below normal levels at all-time points.It was concluded that persistent down-regulation of HLA-DR expression is associated with MDR bacterial infection in patients with SAP.
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Objective To study the effect of early mechanical ventilation in treatment of patients with severe acute pancreatitis(SAP).Methods Fifty-two patients with SAP admitted in the First People's Hospital of Zhaoqing from January 2010 to January 2015 were randomly allocated into two groups (n =26),early mechanical ventilation group(observation group) and conventional mechanical ventilation group(control group).Patients in the observation group treated with early lung protective ventilation when PaO2 ＜ 13.3kPa.Patients in the control group treated without mechanical ventilation untill PaO2 ＜ 8kPa.The symptoms,the extent of inflammatory reaction,the severity of lung lesions and the mortality of two groups were compared through monitoring vital signs,abdominal circumference,APACHE Ⅱ score,bladder pressure,oxygenation index (PaO2/FiO2),C reactive protein (CRP),procalcitonin (PCT),hospital stay and mortality.Results No statistically significant differences in the APACHE Ⅱ score,bladder pressure,oxygenation index,CRP and PCT in two groups before treatment were observed(P ＞ 0.05).The APACHE Ⅱ score (12.8 ± 7.6) points,bladder pressure (14.9± 7.9) cmH2O,CRP (48.8 ± 30.1) rmg/L,PCT (1.25 ± 0.55) μg/L,mortality (3.84％) of the observation group after treatment were significantly lower than those of the control group (t =2.057,2.091,3.252,2.697,x2 =4.305,all P ＜ 0.05),while the oxygenation index in the observation group [(300.0 ± 34.9) mmHg] was significantly higher than that in the control group [(278.1 ± 32.8) mmHg],the difference of the two groups was statistically significant (t =3.322,P ＜ 0.05).Conclusion Early lung protective ventilation is safe and effective for treatment of the patients with SAP.
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Objective To explore the protective effect of resveratrol on rat brain injury resulting from severe acute pancreatitis (SAP). Methods Ninety-six male Sprague-Dawley rats were randomly divided into four groups:sham-operation (SO) group,severe acute pancreatitis (SAP) group,resveratrol-treated (RES) group and dexamethasone-treated (DEX) group,with eight rats in each group evaluated at 3,6 and 12 h. Levels of serum myelin basic protein (MBP),tight junction protein zonula occludens 1 (Zo-1),TNF-? and IL-6 were determined by ELISA. The ultrastructural changes of the brain and pancreatic tissues were examined using a transmission electron microscope. Results MBP,Zo-1,TNF-? and IL-6 levels in RES group were lower than those in SAP group at all time points (P0.05). Conclusion The degradation of Zo-1 is involved in the pathophysiology of brain injury in SAP; MBP can be used as a marker of brain injury in SAP rats. Resveratrol can inhibit brain injury associated with SAP.