Wenkui Yu

Early gut mucosal dysfunction in patients with acute pancreatitis.

Objectives: A clinical study was made to test the hypothesis that gut mucosal damage happens and correlates with endotoxemia, systemic inflammation, severity of disease, septic complication, and outcome in acute pancreatitis (AP) patients. Methods: Patients were divided into 3 groups according to severity: grade 1 (n = 26, mild), grade 2 (n = 18, severe AP [SAP] without organ dysfunction), and grade 3 (n = 18, SAP with organ dysfunction). Twenty healthy volunteers were enrolled as control group. The intestinal lactulose and mannitol absorption ratio, d-xylose absorption, endotoxin, and tumor necrosis factor &agr; were detected in parallel to clinical data collection. Results: Lactulose and mannitol absorption ratio increased in patients with AP, and the increase was more pronounced in SAP (grade 1: 0.044 ± 0.017, grade 2: 0.39 ± 0.16, grade 3: 0.48 ± 0.22, control: 0.024 ± 0.009; P < 0.01 between control and AP, P < 0.01 between mild and severe group). d-Xylose absorption decreased in pancreatitis groups (P < 0.01) especially in severe groups (P < 0.01 between mild and SAP). We also observed a significant positive correlation of mucosal permeability with endotoxin (r = 0.902, P < 0.001) and tumor necrosis factor &agr; changes (r = 0.862, P < 0.001). The severity and septic complication in AP patients were different accompanied with severity of gut mucosal damage. Conclusions: Intestinal mucosal function is injured in early phase of AP especially in patients with organ dysfunction, which may be a stimulus for development of multiple organ dysfunction and correlate with bad outcome in AP patients.

Mononuclear Histocompatibility Leukocyte Antigen-DR Expression in the Early Phase of Acute Pancreatitis

Background: In acute pancreatitis (AP), several studies indicated that the balance between pro- and anti-inflammatory mediators is more important than the levels of proinflammatory response alone. This balance may be reflected by the expression of monocyte histocompatibility leukocyte antigen (HLA)-DR, with a low concentration indicating an excess of anti-inflammatory stimuli and relative immunodeficiency. We investigated the time course of HLA-DR expression in the early phase of AP and the relationship to markers of inflammation, severity of the disease, organ function, septic complications and outcome during AP. Methods: The expression of HLA-DR on peripheral monocytes was measured in 74 patients by flow cytometry and serum IL-6 was determined by using an immunochemiluminescence assay obtained 24 h, 48 h, 72 h, 7 days, 10 days and 14 days after admission in parallel with clinical data collection. 25 patients had mild disease (grade 1), 31 had severe disease but recovered without organ failure (grade 2) and 18 had severe disease and developed organ failure (grade 3). Results: In 49 patients with severe disease, 11 patients suffered from sepsis, and 3 of them died during the hospital stay. During the first 14 days of AP, the percentage of HLA-DR in AP was significantly below the normal range of healthy subjects, it dropped to the lowest level on day 3, but then gradually recovered from the prophase depression. The HLA-DR expression decreased in the order grade 3 < grade 2 < grade 1 (p < 0.001). We also observed a significant inverse correlation between the percentage of HLA-DR+ and AP severity as assessed by APACHE-II scores (r = 0.754, p < 0.001) and MODS score (r = 0.675, p < 0.001). The peak of systemic inflammatory reaction, documented by maximum serum concentration of CRP, coincided with the nadir of HLA-DR suppression. Moreover, IL-6 and CRP serum concentrations were inversely correlated with HLA-DR expression over the entire observation period. Persistent HLA-DR suppression and a second decrease in HLA-DR expression are associated with septic complications and poor outcome. Conclusion: Immune suppression develops early and rapidly in patients with AP, and the degree is parallel with the severity of the disease. Decreases in HLA-DR expression occurred simultaneously with signs of hyperinflammation in the early phase of AP, and persistent HLA-DR suppression and a second decrease in HLA-DR expression are associated with septic complications and poor outcome.

Berberine reduces rat intestinal tight junction injury induced by ischemia-reperfusion associated with the suppression of inducible nitric oxide synthesis.

Berberine (BBR) has been shown to attenuate the deleterious effects of ischemia/reperfusion (I/R) injury in the brain. We evaluated the effects of BBR on intestinal tight junction (TJ) changes during mesenteric I/R. I/R was induced in rats by the occlusion of the superior mesenteric artery and reperfusion. The rats were randomized into four groups: control, BBR, I/R, and I/R + BBR. Intestinal permeability was determined by the lactulose/mannitol test. The ileum and colon were harvested to assess mucosal injury and inducible nitric oxide synthase activity. The TJ ultrastructure was studied by transmission electron microscopy. The expressions and locations of the TJ proteins, occludin and ZO-1, in the epithelium were investigated by immunofluorescence microscopy. We also used Western blot analysis to detect the distribution of TJ proteins in lipid raft fractions. Our results suggest that I/R-induced intestinal TJ dysfunction can be improved by BBR, thereby demonstrating the therapeutic potential of BBR for intestinal I/R.

Percutaneous catheter drainage for infective pancreatic necrosis: is it always the first choice for all patients?

Objective To learn the clinical outcome of percutaneous catheter drainage (PCD) for patients with infective pancreatic necrosis and the possible influencing factors. Methods A retrospective review of medical records of patients with infective pancreatic necrosis who received PCD as the first choice for treatment in the recent 2 years. The patients were divided into 2 groups: (1) PCD success group and (2) PCD alteration group. Characteristics, complications, and PCD process were compared. Results In this study, 19 of 34 patients were cured by PCD alone (55.9%), whereas open necrosectomy were needed for 15 patients (44.1%). Between these 2 groups, most baseline and clinical characteristics did not show any statistical difference, including the number and size of catheter used and the bacterial culture result. The PCD alteration group had higher mean computed tomographic density (P = 0.012) and larger distribution range of infected pancreatic necrosis (4.53 ± 1.35 vs 5.93 ± 1.62; P = 0.009) than the PCD success group (P < 0.01). The logistic regression analysis revealed the same facts. Conclusion The mean computed tomographic density and distribution range of infective pancreatic necrosis could significantly influence the success rate of PCD; higher values of them indicate less appropriate for PCD; thus, it should be considered seriously before the treatment decision.

Effects of continuous high-volume hemofiltration on experimental severe acute pancreatitis in pigs.

Objective: To compare the effects of different doses of hemofiltration on severe acute pancreatitis (SAP) in pigs. Methods: The animal model of SAP was produced by intraductal injection of sodium taurocholate and trypsin. Animals in group 1 served as SAP control. Animals in group 2 received (20 mL/kg per hour) continuous low-volume hemofiltration (LVHF), and animals in group 3 received (100 mL/kg per hour) continuous high-volume hemofiltration (HVHF) immediately after the induction of SAP. After the instrumentation of the animals by arterial and Swan-Ganz catheters, hemodynamic indexes were monitored intermittently at different times. The rectal temperature and the concentration of amylase and cytokines in serum were measured at the same time. Results: The survival time of HVHF group was significantly prolonged (P < 0.01). The initial elevation of body temperature and the hypothermia in the late course of experiments were significantly ameliorated by HVHF (P < 0.01). Six hours after the induction of pancreatitis, the urine output of animals in HVHF group was obviously higher than that in control group (P < 0.05), which stayed behind 36 hours later (P < 0.05). The major hemodynamic finding was that pancreatitis-induced hypotension was significantly attenuated by HVHF (P < 0.01). The development of hyperdynamic circulatory failure was simultaneously attenuated, as reflected by a limited increase in CI, an attenuated decrease in systemic vascular resistance index. Plasma amylases in the HVHF group were significantly lower than those in control and LVHF groups (P < 0.01). The serum concentrations of cytokines such as tumor necrosis factor &agr; (TNF-&agr;), interleukin (IL) 6, and IL-10 all decreased significantly in treatment groups (P < 0.01), and those of HVHF group were less significant than the HVHF group (P < 0.01). Conclusions: The HVHF was associated with a better hemodynamic profile, a less hyperkinetic state, and more prolonged survival than that of LVHF, which may result from the HVHF that can remove the inflammatory cytokines more efficiently.

The effect of venovenous extra-corporeal membrane oxygenation (ECMO) therapy on immune inflammatory response of cerebral tissues in porcine model

BackgroundExtra-Corporeal Membrane Oxygenation (ECMO) therapy is associated with high risk of neurologic injury. But the mechanism of neurologic injury during and/or after ECMO therapy is still unclear. Recent animal experiments confirmed that ECMO treatment increases the immune inflammatory response. The aim of this study is to investigate the effect of VV- ECMO on immune inflammatory response of cerebral tissues and neurological impairment.Methods18 porcine were randomly divided into control, sham and ECMO group (n = 6/group). ECMO was run 24 h in the ECMO group, and serum collected at 0, 2, 6, 12 and 24 h during ECMO treatment for the analysis of cytokine (IL-1β, IL-6, IL-10, TNF-a) and cerebral injury specific biomarker S100B and NSE. After 24 h ECMO treatment, all animals were euthanized and cerebral tissues (hypothalamus, hippocampus and cortex) were collected for measure of mRNA and protein levels of cytokine (IL-1β, IL-6, IL-10, TNF-a).ResultsThe results during ECMO treatment showed that all the pro-inflammation cytokines were increased significantly after 2 h, and anti-inflammation IL-10 showed transient hoist in the first 2 h in serum. After 24 h ECMO therapy, the mRNA levels of pro-inflammation cytokines and anti-inflammation IL-10 were simultaneously up-regulated in cerebral tissues (hypothalamus, hippocampus and cortex). And protein concentrations also showed different increasing levels in cerebral tissues. However, during the ECMO treatment, S100B and NSE protein in serum did not change significantly.ConclusionThese findings suggest VV-ECMO treatment can not only lead to immune inflammatory response in blood, but can also produce immune and inflammatory response in cerebral tissues. However the extent of immune inflammation was not sufficient to cause significant neurological impairment in this study. But the correlation between cerebral inflammatory response and cerebral impairment need to further explore.

Peritoneal Air Exposure Elicits an Intestinal Inflammation Resulting in Postoperative Ileus

Background. The pathogenesis of postoperative ileus (POI) is complex. The present study was designed to investigate the effects of peritoneal air exposure on the POI intestinal inflammation and the underlying mechanism. Methods. Sprague-Dawley rats were randomized into five groups (6/group): the control group, the sham group, and three exposure groups with peritoneal air exposure for 1, 2, or 3 h. At 24 h after surgery, we analyzed the gastrointestinal transit, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10, the myeloperoxidase activity, and the levels of TNF-α, IL-1β, IL-6, and IL-10 in the ileum and colon. The oxidant and antioxidant levels in the ileum and colon were analyzed by measuring malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC). Results. Peritoneal air exposure caused an air-exposure-time-dependent decrease in the gastrointestinal transit. The length of peritoneal air exposure is correlated with the severity of both systemic and intestinal inflammations and the increases in the levels of MDA, SOD, GSH-Px, and T-AOC. Conclusions. The length of peritoneal air exposure is proportional to the degree of intestinal paralysis and the severity of intestinal inflammation, which is linked to the oxidative stress response.

Multidisciplinary Stepwise Management Strategy for Acute Superior Mesenteric Venous Thrombosis: An Intestinal Stroke Center Experience

BACKGROUD Acute superior mesenteric venous thrombosis (ASMVT) is an uncommon but catastrophic abdominal vascular emergency with high rate of intestinal failure and mortality. The retrospective pilot study was performed to assess the effect of a multidisciplinary stepwise management strategy on survival and mesenteric recanalization in an integrated intestinal stroke center (ISC). MATERIALS AND METHODS A modern management strategy performed by multidisciplinary specialists in ISC was evaluated among 43 ASMVT patients that were classified into central vs peripheral type, operative vs nonoperative, early vs late treated group from March 2009 to April 2013. Patients received specific medical therapy, endovascular treatment, damage-control surgery, selective second-look laparotomy, critical care management, and clinical nutrition support in a stepwise way. The demographics, etiology, imaging characteristics, treatment procedures, complications, clinical outcome, and 1-year follow-up data were analyzed and compared. Confounding factors of mortality were identified by univariate and ROC-curve analysis. A single-center experience of over 5years for this modern strategy was also reported. RESULTS The protocol of multidisciplinary stepwise management strategy was followed in all ASMVT patients successfully. The 30-day mortality and recanalization rate were 11.63% and 90.70%. Initial damage-control surgery was carried out in 46.51% patients, with selective second-look laparotomy in 23.26% patients. Endovascular thrombolysis was performed in 83.72% patients initially or postoperatively. Bowel resection was necessary in 18 patients with the length of 100.00 (47.50, 222.50) cm. The incidence of short-bowel syndrome was 13.95%. The rate and length of bowel resection, short-bowel syndrome rate were significantly lower in nonoperative and early-treated groups (P<0.05). During the follow-up survey, 1-year survival was 83.72%, with no additional death or re-thrombosis. CONCLUSION A multidisciplinary stepwise management strategy involving modern surgical and endovascular treatments that focus on early mesenteric recanalization and bowel viability salvage in a specialized ISC could significantly improve the clinical outcome of ASMVT patients.

Chemical sympathectomy attenuates inflammation, glycocalyx shedding and coagulation disorders in rats with acute traumatic coagulopathy.

Acute traumatic coagulopathy (ATC) may trigger sympathoadrenal activation associated with endothelial damage and coagulation disturbances. Overexcitation of sympathetic nerve in this state would disrupt sympathetic–vagal balance, leading to autonomic nervous system dysfunction. The aim of this study was to evaluate the autonomic function in ATC and its influence on inflammation, endothelial and coagulation activation. Male Sprague–Dawley rats were randomly assigned to sham, ATC control (ATCC) and ATC with sympathectomy by 6-hydroxydopamine (ATCS) group. Sham animals underwent the same procedure without trauma and bleeding. Following trauma and hemorrhage, rats underwent heart rate variability (HRV) test, which predicts autonomic dysfunction through the analysis of variation in individual R-R intervals. Then, rats were euthanized at baseline, and at 0, 1 and 2 h after shock and blood gas, conventional coagulation test and markers of inflammation, coagulation, fibrinolysis, endothelial damage and catecholamine were measured. HRV showed an attenuation of total power and high frequency, along with a rise of low frequency and low frequency : high frequency ratio in the ATC rats, which both were reversed by sympathectomy in the ATCS group. Additionally, sympathetic denervation significantly suppressed the increase of proinflammatory cytokines, tumor necrosis factor-&agr; and the fibrinolysis markers including tissue-type plasminogen activator and plasmin–antiplasmin complex. Serum catecholamine, soluble thrombomodulin and syndecan-1 were also effectively inhibited by sympathectomy. These data indicated that autonomic dysfunction in ATC involves both sympathetic activation and parasympathetic inhibition. Moreover, sympathectomy yielded anti-inflammatory, antifibrinolysis and endothelial protective effects in rats with ATC. The role of autonomic neuropathy in ATC should be explored further.

Berberine ameliorates intestinal mucosal barrier damage induced by peritoneal air exposure.

Berberine, an isoquinoline alkaloid derived from many medicinal plants, has been extensively used to treat various gastrointestinal diseases. In the present study, we investigated whether berberine could ameliorate intestinal mucosal barrier damage induced by peritoneal air exposure for 3 h. Peritoneal air-exposure rats received 100, 150, and 200 mg/kg berberine orally via gavage four times before and after surgery. Blood and terminal ileum samples were collected 24 h after surgery. The serum D-lactate levels were determined using an enzyme-linked immunosorbent assay (ELISA) kit. Intestinal permeability was determined by measuring the intestinal clearance of fluorescein isothiocyanate (FITC)-dextran (FD4). Intestinal inflammation was assessed by measuring myeloperoxidase activity. Intestinal histopathology was also assessed. The results revealed that berberine decreased the serum D-lactate level, intestinal FD4 clearance, and myeloperoxidase activity. Edema and inflammation were reduced by berberine in the intestinal mucosa and submucosa, and the Chius scores, indices of intestinal mucosal injury, also decreased in the berberine-treated group. In addition, berberine exerted these protective effects in a dose-dependent manner, with a significant difference from the control group at doses of 150 and 200 mg/kg. The results suggest that berberine could ameliorate intestinal mucosal barrier damage induced by peritoneal air exposure, which is linked to its anti-inflammatory activity. Berberine may be a promising treatment for intestinal mucosal barrier damage in open abdominal surgery.