Free Total Rhubarb Anthraquinones Protect Intestinal Injury via Regulation of the Intestinal Immune Response in a Rat Model of Severe Acute Pancreatitis.
Xiong Yuxia,Chen Li,Fan Ling,Wang Lulu,Zhou Yejiang,Qin Dalian,Sun Qin,Wu Jianming,Cao Shousong
Frontiers in pharmacology
Intestinal mucosal immune barrier dysfunction plays a key role in the pathogenesis of severe acute pancreatitis (SAP). Rhubarb is a commonly used traditional Chinese medicine as a laxative in China. It markedly protects pancreatic acinar cells from trypsin-induced injury in rats. Free total rhubarb anthraquinones (FTRAs) isolated and extracted from rhubarb display the beneficial effects of antibacteria, anti-inflammation, antivirus, and anticancer. The principal aim of the present study was to investigate the effects of FTRAs on the protection of intestinal injury and modification of the intestinal barrier function through regulation of intestinal immune function in rats with SAP. We established a rat model of SAP by injecting 3.5% sodium taurocholate (STC, 350 mg/kg) into the biliopancreatic duct via retrograde injection and treated the rats with FTRAs (36 or 72 mg/kg) or normal saline (control) immediately and 12 h after STC injection. Then, we evaluated the protective effect of FTRAs on intestinal injury by pathological analysis and determined the levels of endotoxin (ET), interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), nitric oxide (NO), myeloperoxidase (MPO), capillary permeability, nucleotide-binding oligomerization domain-like receptors 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD domain (ASC), casepase-1, secretary immunoglobulin A (SIgA), regulatory T cells (Tregs), and the ratio of Th1/Th2 in the blood and/or small intestinal tissues or mesenteric lymph node (MLN) cells. Moreover, the chemical profile of FTRAs was analyzed by HPLC-UV chromatogram. The results showed that FTRAs significantly protected intestinal damage and decreased the levels of ET, IL-1β, TNF-α, and NO in the blood and TNF-α, IL-1β, and protein extravasation in the intestinal tissues in SAP rats. Furthermore, FTRAs significantly decreased the expressions of NLRP3, ASC, and caspase-1, the number of Tregs and the ratio of Th1/Th2, while significantly increased the expression of SIgA in the intestinal tissues and/or MLN cells in SAP rats. Our results indicate that FTRAs could protect intestinal injury and improve intestinal mucosal barrier function through regulating immune function of SAP rats. Therefore, FTRAs may have the potential to be developed as the novel agent for the treatment of SAP clinically.
[Clinical observation on treatment of severe acute pancreatitis by combined administration of Qingyi Decoction and Glauber's salt].
Wu Rui-qiao,Chen Yue,Liu Liang-pei
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine
OBJECTIVE:To investigate the value of Qingyi Decoction (QYD) and Glauber's salt (GS) for treatment of severe acute pancreatitis (SAP). METHODS:Sixty-five patients with SAP were randomly assigned to two groups, the treated group (33 patients) and the control group (32 patients). They received the same therapy except that to the patients in the treated group, QYD was given through naso-gastric tube and GS was applied externally. RESULTS:Compared with those in the control group, the alleviating time of clinical symptoms, such as abdominal pain and distention, time of hospitalization and time of blood amylase recovery in the treated group were shorter, with lesser complications and lower rate of transferring to operation (all with P < 0.05), showing a better efficacy in all aspects, but the mortality in the two groups was not different (P > 0.05). CONCLUSION:Combined use of QYD and GS has significant therapeutic effect for treatment of SAP.
[Effect of qingyi decoction in treating severe acute pancreatitis and its impacts on blood level of tumor necrosis factor-alpha, interleukin-6 and inteleukin-8].
Yang Dong-ying,Duan Shao-bin,Aili Julai-ti
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine
OBJECTIVE:To observe the effect of Qingyi Decoction (QYD) in treating severe acute pancreatitis (SAP) and its impacts on blood levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 and 8 (IL-6 and IL-8). METHODS:One hundred and ten patients of SAP were equally randomized into the treated group and the control group, they were treated with the same therapeutic program excepting that QYD was given only to the treated group. The post-treatment incidence of severe complication, mortality and operation transferring rate, as well as the changes of APACHE II scores and blood levels of TNF-alpha, IL-6 and IL-8 in patients of both groups were observed. RESULTS:The incidences of the two severe complications, acute respiratory distress syndrome and intestinal paralysis, in the treated group was 3.6% and 5.4% respectively, while in the control group, 12.7% and 18.2%, showing statistical significance between groups (P < 0.05). The APACHE II score in the treated group decreased significantly on the 7th day, which was better than that in the control group (8.14 +/- 2.30 scores vs 3.35 +/- 2.20 scores, P < 0. 05). In addition, the efficacy in the treated group was also superior to that in the control group in terms of reducing mortality, operation transferring rate, and blood levels of TNF-alpha, IL-6 and IL-8 on the 7th and 9th day (P < 0. 05). CONCLUSION:QYD could markedly improve the prognosis of SAP patients by way of lowering the blood levels of TNF-alpha, IL-6 and IL-8.
[Effect of Qingyi Chengqi Decoction on severe acute pancreatitis patients: a clinical study].
Zhang Xiao-Ming,Ma Ping-An,Sun Jian-Wei,Duan Chun-Ning,Hou Xian-Hai,Zhang You-Cheng
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine
OBJECTIVE:To observe the change of intra-abdominal pressure (IAP) in severe acute pancreatitis (SAP) patients, and to study the effect of Qingyi Chengqi Decoction (QCD) on it. METHODS:Eighty-six SAP patients from Department of General Surgery and Department of Digestive Diseases, Qingyang People's Hospital, Gansu Province, who were in line with diagnosis standard of SAP, were assigned to the treatment group (44 cases) and the control group (42 cases) from March 2012 to May 2013. All patients received routine Western medicine. Those in the treatment group took QCD additionally. Main clinical symptoms and APACHE II were observed. The serum levels of amylase (AMY), C-reactive protein (CRP), and IAP were examined. The incidence of secondary infection rate (SIR), drainage rate (percutaneous catheter drainage and operation), mortality, and mean days in ward were also recorded. RESULTS:Main clinical symptoms were significantly improved in the treatment group. APACHE II score, serum levels of AMY, CRP, and IAP obviously decreased in the treatment group. The incidence of SIR, drainage rate, and the mortality were also significantly lower in the treatment group than in the control group. The mean days in ward were also markedly shortened (P < 0.01). CONCLUSION:QCD could relieve inflammatory response, lower IAP, SIR, and mortality, increase the curative rate and improve the prognosis of SAP.
Synergetic effect of yihuo qingyi decoction (see text) and recombinant staphylokinase in treatment of severe acute pancreatitis of rats.
Chen Yong-Feng,Sha Jian-Ping,Wu Zhong-Min
Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan
OBJECTIVE:To investigate the effect of recombinant staphylokinase (r-Sak) and the Chinese medicine Yihuo Qingyi Decoction ((see test) Herbal decoction for severe acute pancreatitis) in the treatment of the severe acute pancreatitis (SAP) in rats, and to observe the synergistic effect of the two. METHODS:One hundred and sixty-two adult male SD rats with the body mass of 250-280 g were randomly divided into the following 5 groups: sham operation group (n = 18), control group (n = 36), Yihuo Qingyi Decoction treatment group (n = 36), r-Sak treatment group (n = 36), and Yihuo Qingyi Decoction plus r-Sak treatment group (n = 36). The SAP ratmodel was prepared by retrograde injection of 5% sodium taurocholate into the cholangiopancreatic duct. Two days before modeling, Yihuo Qingyi Decoction was intragastrically administrated, and r-Sak was intraperitoneally injected. The survival rate within 18 h after modeling was determined. The pancreatic blood flow, the weight of ascites, and the serum amylase and lipase were investigated at 6 h, 12 h, and 18kh after modeling, and the pancreatic tissue was examined under light microscopy to see its pathological change. RESULTS:The 18 h survival count of group A, B, C, D and E rats was 9, 2, 6, 7 and 8 respectively. After r-Sak and Yihuo Qingyi Decoction intervention, the serum amylase and lipase and the weight of ascites were significantly decreased, especially in group E.18 h after modeling, the level of the serum amylase and lipase and the weight of ascites in group E was 1 100 +/- 118 U x L(-1), 1 000 +/- 150 U x L(-1) and 13.40 +/- 1.80 g respectively, obviously lower than that of group B (P < 0.05). After SAP was induced, the pancreatic blood flow showed a tendency to decrease, but the decrease extent in the treatment groups was smaller than that in the control group. 18h after modeling, the pancreatic blood flow in group B and group E was 30.16 +/- 8.96 mL x 100 g(-1) x min(-1), and 129.10 +/- 42.58 mL x 100 g(-1) x min respectively, there was significant difference (P < 0.05). The pathological change of the pancreatic tissue was alleviated in the treatment groups. CONCLUSION:Both r-Sak and Yihuo Qingyi Decoction play a beneficial role in the treatment of rat SAP and there is a synergistic effect between the two.
Qingyi decoction attenuates severe acute pancreatitis in rats via inhibition of inflammation and protection of the intestinal barrier.
Su Song,Liang Tiancheng,Zhou Xiang,He Kai,Li Bo,Xia Xianming
The Journal of international medical research
OBJECTIVE:Qingyi decoction (QYD) has beneficial effects in severe acute pancreatitis (SAP). We assessed the therapeutic effect and mechanisms of QYD in SAP. METHODS:A rat model of SAP was induced by pancreatic ductal injection of sodium taurocholate. QYD was administered intragastrically immediately postoperatively and once every 12 hours. Serum amylase, endotoxin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and D-lactate levels were measured at 12, 24, and 48 hours. Histological changes in the pancreas and ileum were analyzed. Expression of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-κB p65), Toll-like receptor 4 (TLR4), and zonula occludens-1 (ZO-1) in the small intestinal mucosa was also assessed. RESULTS:Pancreatic tissue showed extracellular space expansion, inflammatory infiltration, vessels with necrotic walls, and hemorrhage. Ileal tissue showed hemorrhage, inflammatory infiltration, and ileal mucosa destruction. These histological features were dramatically improved by QYD. Increased serum levels of amylase, endotoxin, TNF-α, IL-6, and D-lactic acid were significantly decreased by QYD administration. Increased expression of NF-κB p65 and TLR4 and decreased expression of ZO-1 in the ileal mucosa were also restored to normal levels by QYD treatment. CONCLUSION:QYD alleviates SAP by reducing intestinal barrier dysfunction, inhibiting intestinal bacteria and endotoxin translocation, and preventing NF-κB activation.
Emodin ameliorates ulcerative colitis by the flagellin-TLR5 dependent pathway in mice.
Luo Shuang,Deng Xiangliang,Liu Qi,Pan Zengfeng,Zhao Zhongxiang,Zhou Lian,Luo Xia
Emodin is an anthraquinone compound derived from Rheum officinale Baill. Several reports showed that emodin had efficacy on acute pancreatitis, keratitis, myocarditis, and rheumatoid arthritis. However, the potency of emodin on ulcerative colitis(UC) remains unclear. In this study, we investigated the effect of emodin on dextran sodium sulfate (DSS)-induced ulcerative colitis in mice. Our results showed that emodin significantly alleviated the symptoms of DSS-induced UC in mice, involving prevented the loss of body weight and colon shortening, decreased the disease activity index (DAI), intestinal damages and the count of white blood cells (WBC) in peripheral blood. In addition, emodin treatment decreased the level of anti-flagellin antibody in serum and significantly down-regulated the expression of TLR5 and NF-κB p65 in colon of the UC mice. Further study in vitro showed that emodin down-regulated the expression of TLR5 and MyD88, up-regulated the expression of IκB, inhibited the nuclear translocation of NF-κB p65 and decreased the release of IL-8 in flagellin-stimulated HT-29 cells. These results, for the first time, demonstrated that emodin had the therapeutic potential to ameliorate UC symptoms possibly via regulating the flagellin-TLR5 signaling pathway. Emodin may be a potential candidate ingredient for ulcerative colitis.
[Role of a virus in hemorrhagic pancreatitis and the therapeutic effect of rhubarb].
Zhong xi yi jie he za zhi = Chinese journal of modern developments in traditional medicine
The living measles vaccine was injected into both of the main pancreatic duct and the ear vein of the rabbits in the model group. The serum amylase was significantly higher than that of the control saline group (P less than 0.001 after 24h; P less than 0.05 after 48h). The aggregation function of platelets were increased after 24h(P less than 0.01, P less than 0.01) and 48h (P less than 0.01, P less than 0.05) as compared with both two control groups. The blood stasis and hemorrhage of pancreases were observed in the model group. In the treatment group with Rhubarb the increase of serum amylase was much less marked than the control (P less than 0.001 after 24h, P less than 0.05 after 48h). The platelet aggregation reactivity was inhibited (P less than 0.01 after 24h, P less than 0.05 after 48h). The blood stasis and hemorrhage of pancreases were less evident. The results suggested that: (1) the virus may be one of pathogenetic factor of the hemorrhagic pancreatitis; (2) the rhubarb was effective in the treatment of hemorrhagic pancreatitis under our experimental conditions.
Up-regulation of Toll-like receptor 4 was suppressed by emodin and baicalin in the setting of acute pancreatitis.
Li Zongfang,Xia Xianming,Zhang Shu,Zhang Aijun,Bo Wangjun,Zhou Rui
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Acute pancreatitis (AP) activates the systemic inflammatory response and is potentially lethal. Recent studies demonstrated that pancreatic enzymes could induce cytokine expression via Toll-like receptor 4 (TLR4) signal pathway, indicating a possible role of TLR4 in local pancreatic injury and systemic inflammatory response. Emodin, an anthraquinone derivative from Radix et Rhizoma Rhei, and baicalin, a flavone from Scutellaria baicalensis Georgi, both have been reported to possess anti-inflammatory activities. In present study, we investigated the combined effect of emodin and baicalin on pancreatic damage and pancreatitis associated lung injury, as well as tissue TLR4 expression in the setting of AP. The results showed that combination of emodin and baicalin significantly reduced serum amylase, tumor necrosis factor-alpha and interleukin-6, attenuated pancreatic and pulmonary damage, also suppressed TLR4 expression in pancreas and lung. It could be speculated that amelioration of pancreatic and pulmonary damage by emodin and baicalin might contribute, in part at least, to the suppression of TLR4 expression. The present study provides beneficial evidence as to simultaneous treatment for AP, and also suggests an important role of TLR4 in pathophysiology of AP.
Rhubarb attenuates the severity of acute necrotizing pancreatitis by inhibiting MAPKs in rats.
Feng Zhen,Fei Jin,Wenjian Xiong,Jiachen Jing,Beina Ji,Zhonghua Cheng,Xiangyi Yang,Shaoying Wang
AIM:To investigate the effect of rhubarb on MAPK activation in sodium taurocholate-induced pancreatitis in rats. METHODS:All rats were randomly divided into three groups: control, acute pancreatitis (AP) and rhubarb treatment groups. The MAPK activation was detected by western blotting. The levels of TNFα and IL6 in serum were estimated by ELISA. The pathological changes of the pancreas were examined microscopically. RESULTS:It was found that hemorrhage, exudates and infiltration of inflammatory cells in the pancreas were significantly less in the rhubarb group than in the AP group. In the AP group, the activation of MAPKs in pancreatic tissues was enhanced significantly at every time point compared with the control group and the levels of TNFα and IL6 were also increased. Rhubarb treatment markedly inhibited activation of MAPKs concomitantly with inhibition of TNFα and IL6 expression. CONCLUSION:We suggest that rhubarb probably attenuates AP by inhibiting activation of MAPKs and expression of inflammatory mediators.
[Experimental studies of therapeutic effect of Rheum officinale on acute pancreatitis].
Yang Chang-yong,Shen Li,Xie Zhen-guo,Jiang Xing,Liang Nan,Chen Zhong-hua
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials
OBJECTIVE:To investigate the therapeutic effect of Rheum offĩcinale on acute pancreatitis. METHODS:Buffered sodium taurocholate (3% m/V) was injected into the pancreatico-biliary duct to induce acute pancreatitis. Death rate,coefficient of pancreas, serum amylyse (AMY), hemocuprein (SOD), TNF-alpha and IL-1beta level were examined at 6, 12 and 24 hours after operations. Pathology analysis were also obtained. RESULTS:Compared with corresponding pancreatitis groups,death rate, coefficient of pancreas, serum TNF-alpha and IL-1beta level of drug groups decreased remarkably (P < 0.05), while serum SOD level significantly increased (P < 0.01). Serum AMY level of drug groups increased at 6 h (P < 0.01), decreased at 12 h (P < 0.01) and had no statistics disparity at 24 h (P > 0.05) compared with respective pancreatitis group. Although score points of all drug groups were lower than corresponding pancreatitis groups, the growth tendency of both were similar. CONCLUSION:Rheum officinale Baill has the effect of prevention to pancreas pathological changes in the animal pattern, but not able to reverse the tendency.
Emodin has a protective effect in cases of severe acute pancreatitis via inhibition of nuclear factor‑κB activation resulting in antioxidation.
Yao Wei-Yan,Zhou Yu-Fen,Qian Ai-Hua,Zhang Yong-Ping,Qiao Min-Min,Zhai Zu-Kang,Yuan Yao-Zong,Yang Song-Lin
Molecular medicine reports
Severe acute pancreatitis (SAP) accounts for up to 20% of acute pancreatitis (AP) cases. The absence of effective treatment options has resulted in a high rate of morbidity and mortality. Emodin is a major component of the Chinese herb rhubarb, which has been widely used in the treatment of numerous diseases, including inflammation and cancer. There are a limited number of studies however, that have investigated the effectiveness of emodin in the treatment of SAP. The present study used a rat model of SAP, to investigate the effect and molecular mechanisms of emodin treatment. Administration of emodin was identified to significantly attenuate SAP, as determined by serum amylase analysis and histological assessment of edema, vacuolization, inflammation and necrosis (P<0.01). Furthermore, treatment with emodin markedly inhibited nuclear factor (NF)‑κB DNA‑binding activity (P<0.01) and the serum expression levels of tumor necrosis factor‑α, interleukin (IL)‑6 and IL‑1β (P<0.05). This attenuation was associated with decreased malondialdehyde and increased superoxide dismutase levels in the pancreatic tissues and serum (P<0.05). This study indicated that administration of exogenous emodin had therapeutic effects on the severity of SAP. The mechanism may be due to inhibition of NF‑κB activation resulting in an antioxidation response, which can subsequently suppress the expression of cytokines.
Emodin attenuated severe acute pancreatitis via the P2X ligand‑gated ion channel 7/NOD‑like receptor protein 3 signaling pathway.
Zhang Qingkai,Tao Xufeng,Xia Shilin,Qu Jialin,Song Huiyi,Liu Jianjun,Li Hailong,Shang Dong
Acute pancreatitis (AP) is an aseptic inflammation characterized with an annual incidence rate, and ~20% patients progressing to severe AP (SAP) with a high mortality rate. Although Qingyi decoction has been frequently used for SAP treatment over the past 3 decades in clinic, the actual mechanism of its protective effects remains unknown. As the major active ingredient of Qingyi decoction, emodin was selected in the present study to investigate the effect of emodin against severe acute pancreatitis (SAP) in rats through NOD‑like receptor protein 3 (NLRP3) inflammasomes. The rats were randomly divided into a sham operation group, an SAP model group induced by a standard retrograde infusion of 5.0% sodium taurocholate into the biliopancreatic duct, and low‑dose (30 mg/kg) and high‑dose (60 mg/kg) emodin‑treated groups. At 12 h after the event, the plasma amylase, lipase, interleukin (IL)‑1β, IL‑18 and myeloperoxidase (MPO) activities were examined. Furthermore, the pathological scores of pancreases were evaluated by hematoxylin and eosin staining. The expression levels of P2X ligand‑gated ion channel 7 (P2X7), NLRP3, apoptosis‑associated speck‑like protein containing a C‑terminal caspase recruitment domain and caspase‑1 were also analyzed by western blot analysis. The data demonstrated that, compared with the SAP group, emodin could significantly relieve the pancreatic histopathology and acinar cellular structure injury, and notably downregulate the plasma amylase and lipase levels, as well as the MPO activities in pancreatic tissues, in a dose‑dependent manner. Furthermore, emodin inhibited the P2X7/NLRP3 signaling pathway followed by the decrease of pro‑inflammatory factors, and the latter is beneficial for the recovery of SAP. Collectively, the data indicated that emodin may be an efficient candidate natural product for SAP treatment.
Efficacy of rhubarb combined with early enteral nutrition for the treatment of severe acute pancreatitis: a randomized controlled trial.
Wan Bing,Fu Haiyan,Yin Jiangtao,Xu Fang
Scandinavian journal of gastroenterology
OBJECTIVE:To investigate the effect of rhubarb combined with early enteral nutrition (EEN) on the gastrointestinal function, disease severity and systemic inflammation in patients with severe acute pancreatitis (SAP). METHODS:A total of 126 patients with SAP were randomly assigned into three groups: parenteral nutrition group, treated with standard solution first and EN 14 days later; EEN group, treated with EN suspension; or EEN combined with rhubarb group, treated with rhubarb and then EN 2 h later. The gastrointestinal function, APACHE II scores, the levels of plasma IL-6, IL-11, C-reactive proteins (CRP) and the liver and kidney functional measures were longitudinally analyzed. RESULTS:Patients in the EEN/rhubarb group had the shortest period of abdominal pain and the fastest recovery from abnormal bowel movement and high fever as well as significantly shorter periods of intensive-care unit and hospital stays. The combination of EEN and rhubarb significantly reduced the values of APACHE II scores. Combination therapies significantly reduced abnormally higher white blood cell (WBC) counts and levels of plasma CRP and IL-6, but increased the levels of plasma IL-11. Finally, combination therapies improved the SAP-related damages of liver and kidney function by reducing abnormally higher levels of plasma alanine aminotransferase, aspartate aminotransferase, and creatinine (Cr). CONCLUSION:Combination of EEN and rhubarb significantly improved the gastrointestinal function, inhibited systemic inflammation and disease severity and mitigated the disease-related damages of liver and kidney function in SAP patients.
Expression and clinical significance of rhubarb on serum amylase and TNF-alpha of rat model of acute pancreatitis.
Zhang W F,Li Z T,Fang J J,Wang G B,Yu Y,Liu Z Q,Wu Y N,Zheng S S,Cai L
Journal of biological regulators and homeostatic agents
The aim of this study was to evaluate the therapeutic effect of rhubarb extract on acute pancreatitis. Ninety-six healthy Sprague Dawley rats, weighing 301±5.12 g were randomly divided into 4 groups: sham surgery (group A), acute pancreatitis model (group B), acute pancreatitis with normal saline (group C), and acute pancreatitis model with rhubarb (group D). The levels of serum amylase (AMY) and TNF-α were measured at 1st, 6th, 12th and 24th hour after modeling, and the pancreatic tissue were used to observe the pathologic changes. Compared to the sham group, the serum AMY and serum tumor necrosis factor (TNF-α) levels were significantly increased in the other groups (p <0.05). Compared to the model group and the saline group, the serum AMY, serum TNF-α level and pathological changes of rats in the rhubarb group were significantly lower (p <0.05). The serum AMY and TNF-α levels increased in acute pancreatitis. The rhubarb reduced the serum AMY and TNF-α level in rats with acute pancreatitis and reduced the pathological changes of pancreas and other tissues.
Add-on effect of crude rhubarb to somatostatin for acute pancreatitis: A meta-analysis of randomized controlled trials.
Zhou Yejiang,Wang Lulu,Huang Xinwu,Li Hua,Xiong Yuxia
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:Rhubarb is one of the common herbs used in traditional Chinese complex prescriptions for the treatment of various inflammatory diseases. We sought to determine the add-on effect of crude rhubarb to somatostatin in patients with acute pancreatitis by conducting a meta-analysis. MATERIALS AND METHODS:We searched the Pubmed, EMBASE, Cochrane Library, CNKI, Wanfang, VIP databases up to November 2015. Randomized controlled trials (RCTs) comparing crude rhubarb plus somatostatin to somatostatin alone for acute pancreatitis were included. Risk ratio (RR) or weighted mean difference (WMD) with their 95% confidence interval (CI) was calculated between with and without crude rhubarb therapy. RESULTS:A total of 19 RCTs involving 1161 patients were identified. Compared with somatostatin alone, crude rhubarb plus somatostatin significantly reduced the total complications (RR 0.55; 95% CI 0.41-0.73) and APACHE Ⅱ scores (WMD -1.16; 95% CI -1.91 to -0.41) as well as shortened the duration of elevated serum amylase (WMD -2.01 days; 95% CI -2.57 to -1.44), duration of abdominal pain (WMD -1.33 days; 95% CI -1.61 to -1.05), the first defecation time (WMD -2.27 days; 95% CI -3.06 to -1.47), and duration of hospital stay (WMD -6.70 days; 95% CI -8.81 to -4.60). However, there were no significant differences in total mortality rates (RR 0.61; 95% CI 0.34 to 1.12) between two groups. CONCLUSIONS:Crude rhubarb as adjuvant therapy to somatostatin appears to have additional benefits in patients with acute pancreatitis. However, interpretation of these results should be cautioned due to the methodological flaws.
A minimally invasive multiple percutaneous drainage technique for acute necrotizing pancreatitis.
Terayama Takero,Hifumi Toru,Kiriu Nobuaki,Kato Hiroshi,Koido Yuichi,Ichinose Yoshiaki,Morimoto Kohei,Yasuhiro Kuroda
World journal of emergency medicine
BACKGROUND:In approximately 20% of patients, necrotizing pancreatitis is complicated with severe acute pancreatitis, with high morbidity and mortality rates. Minimally invasive step-up approach is both safe and effective, but sometimes requires multiple access sites. METHODS:A 62-year-old woman was admitted with diabetic ketoacidosis, and initial computed tomography (CT) revealed no evidence of acute pancreatitis. She was clinically improved with insulin therapy, fluid administration, and electrolyte replacement. However, on the 14(th) day of admission, she developed a high-grade fever, and CT demonstrated evidence of acute necrotizing pancreatitis with a large collection of peripancreatic fluid. Percutaneous transgastric drainage was performed and a 14 French gauge (Fr) pigtail catheter was placed 1 week later, which drained copious pus. Because of persistent high-grade fever and poor clinical improvement, multiple 8 and 10 Fr pigtail catheters were placed via the initial drainage route, allowing the safe and effective drainage of the extensive necrotic tissue that was occupying the bilateral anterior pararenal space. RESULTS:After drainage, the patient recovered well and the last catheter was removed on day 123 of admission. CONCLUSIONS:Multiple percutaneous drainage requires both careful judgment and specialist skills. The perforation of the colon and small bowel as well as the injury of the kidney and major vessels can occur. The current technique appears to be safe and minimally invasive compared with other drainage methods in patients with extended, infected necrotic pancreatic pseudocysts.
Poorly controlled type 2 diabetes complicated by an episode of severe hypertriglyceridaemia-induced pancreatitis.
Denecker Nathalie,Decochez Katelijn
BMJ case reports
A 23-year-old woman with a history of type 2 diabetes and non-compliance presented to the emergency department with abdominal epigastric pain and nausea. Laboratory examination revealed a mild ketoacidosis while an abdominal CT scan performed the following day demonstrated a severe acute pancreatitis of the body and tail (Balthazar grade E) despite normal amylase serum levels on admission. The presence of a lactescent serum was the clue to an extremely high triglyceride level (>10 000 mg/dl) causing the pancreatitis. The hypertriglyceridaemia itself was attributed mainly to the diabetic ketoacidosis. There was no family history of hypertriglyceridaemia. The triad consisting of diabetic ketoacidosis, hypertriglyceridaemia and acute pancreatitis is an unusual presentation of poorly controlled diabetes which can occur in type 1 as well as type 2 diabetic adults and children. Treatment with intravenous insulin and hydration successfully resolved the ketoacidosis and hypertriglyceridaemia and reversed the episode of acute pancreatitis.
What a type of diabetes is having your patient? Challenges in diagnosing diabetes in children and adolescent - case report.
Niechciał Elżbieta,Bogdańska-Kaczmarek Barbara,Skowrońska Bogda
Pediatric endocrinology, diabetes, and metabolism
Diabetes mellitus (DM) is due to either defects in not producing enough insulin by the pancreatic -cells, or defects in insulin action on peripheral tissues. Type 1 diabetes (T1D) is the most common type in childhood, resulted from the autoimmunity directed at the pancre-atic -cells. T1D classically presents in lean children with an acute onset of polyuria, polydipsia, weight loss. We describe the case of a 14-year-old girl with acute onset of DM complicated with diabetic ketoacidosis, appendicitis and pancreatitis which was suspected of having T1D. However, regardless a suggestive patient's phenotype at the disease onset tentative diagnosis of T1D was not confirmed. The case report shows that the overlap of the clinical phenotypes of diabetes displays the diversity of diabetes in young population. Then, diagnostic process must be carefully planned to exclude other diabetes forms and accurately ascertain childhood diabetes type.
Acute Pancreatitis Induced by Diabetic Ketoacidosis with Major Hypertriglyceridemia: Report of Four Cases.
Bouchaala Karama,Bahloul Mabrouk,Bradii Sabrine,Kallel Hela,Chtara Kamilia,Bouaziz Mounir
Case reports in critical care
Acute pancreatitis (AP) is a real clinical challenge. Acute pancreatitis remains a common cause of emergency department consultations and a major cause for hospitalization. Gallstones and drinking a lot of alcohol are the most frequent causes of AP. Moreover, AP can be induced by diabetic ketoacidosis (DKA) complicated by hypertriglyceridemia. We report 4 cases of DKA with hypertriglyceridemia complicated by AP in previously undiagnosed diabetes patients. All of our patients presented to the emergency ward with abdominal pain. Their physical exam showed epigastric tenderness. An abdominal CT scan was performed for each patient, showing an AP grade E. Laboratory samples showed high serum glucose levels. They had metabolic acidosis with elevated anion gap. They had high lipasemia and amylasemia. Their lipid panel was disturbed with a high level of cholesterol (from 12.8 mmol/l to 33 mmol/l) and triglyceridemia (from 53 to 133 mmol/l). Our patients were admitted into our ICU where they received fluid resuscitation and intravenous insulin, and their triglycerides rates decreased gradually. Two patients recovered to a good health state, and the two others developed septic shock, requiring the use of large-spectrum antibiotics, and acute kidney injury (AKI) with refractory metabolic acidosis, requiring hemodialysis. Despite the intensive treatment, they developed an unrecoverable multiorgan failure. Through our case series, we aim to highlight the importance of making an early diagnosis, which can be difficult in some situations due to overlapping signs; however, it is crucial for a good recovery. A good understanding of the pathway of hypoinsulinemic states causing hypertriglyceridemia then AP is important because it is the key to best management.
Severe hypertriglyceridemia in diabetic ketoacidosis accompanied by acute pancreatitis: case report.
Hahn Suk Jae,Park Jung-hyun,Lee Jong Ho,Lee Jun Kyu,Kim Kyoung-Ah
Journal of Korean medical science
We report a case of diabetic ketoacidosis (DKA) and hypertriglyceridemia (severely elevated to 15,240 mg/dL) complicated by acute pancreatitis, which was treated successfully with insulin therapy and conservative management. A 20-yr-old woman with a history of type 1 diabetes came to the emergency department 7 months after discontinuing insulin therapy. DKA, severe hypertriglyceridemia and acute pancreatitis were diagnosed, with DKA suspected of contributing to the development of the other conditions. In Korea, two cases of DKA-induced hypertriglyceridemia and 13 cases of hypertriglyceridemia-induced acute pancreatitis have been previously reported separately.
Acute Pancreatitis Complicated with Diabetic Ketoacidosis in a Young Adult without Hypertriglyceridemia: A Case Report.
Kim Jung Hyun,Oh Myung Jin
The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi
Systemic complications related to acute pancreatitis include acute respiratory distress syndrome, multiple organ dysfunction syndrome, disseminated intravascular coagulation, hypocalcemia, hyperglycemia, and insulin dependent diabetes or diabetic ketoacidosis. In practice, the development of diabetic ketoacidosis induced by acute pancreatitis is rare and generally associated with hypertriglyceridemia. However, herein we report a case of a 34-year-old female without hypertriglyceridemia, who was diagnosed with acute pancreatitis complicated with diabetic ketoacidosis. The patient was admitted with complaints of febrile sensation, back pain, and abdominal pain around the epigastric area. Levels of serum amylase and lipase were elevated to 663 U/L and 3,232 U/L. Contrast-enhanced abdominal CT showed pancreatic swelling, peri-pancreatic fat infiltration and fluid collection. The patient was initially diagnosed with simple acute pancreatitis. Though the symptoms were rapidly relieved after initiation of treatment, severe hyperglycemia (575 mg/dL), severe metabolic acidosis (pH 6.9), and ketonuria developed at four days after hospitalization. However, serum triglyceride levels remained within the normal range (134 mg/dL). Finally, the patient was diagnosed with acute pancreatitis complicated with diabetic ketoacidosis unrelated to hypertriglyceridemia. She recovered through insulin and fluid therapy, and receives insulin therapy at the outpatient clinic.
Diabetic Ketoacidosis and the Domino Effect.
Shaikh Bilal H,Sohaib Muneebah,Alshantti Raeda,Barrera Francisco,Faridi Farah S,Murvelashvili Natia
The American journal of case reports
BACKGROUND Severe hypertriglyceridemia is a well-known cause of acute pancreatitis. Mild elevations of triglyceride levels are common in patients presenting with diabetic ketoacidosis (DKA). Rarely, DKA can be accompanied by an elevation of serum triglyceride level severe enough to lead to AP. CASE REPORT We report one such case of a young diabetic male who presented with DKA that was complicated by hypertriglyceridemia-induced acute pancreatitis (HTGAP). We were able to treat the condition with a slightly prolonged infusion of intravenous (IV) regular insulin in an efficient and cost-effective manner with a good outcome. CONCLUSIONS From our experience, DKA-associated HTGAP can be rapidly, efficiently, and cost-effectively treated with IV regular insulin and close biochemical monitoring. A high index of suspicion for acute pancreatitis is necessary in patients with DKA, especially with co-existing hypertriglyceridemia; and all efforts should be made to diagnose it in a timely manner to prevent subsequent complications.
Proinflammatory cytokines, markers of cardiovascular risks, oxidative stress, and lipid peroxidation in patients with hyperglycemic crises.
Stentz Frankie B,Umpierrez Guillermo E,Cuervo Ruben,Kitabchi Abbas E
Acute and chronic hyperglycemia are proinflammatory states, but the status of proinflammatory cytokines and markers of oxidative stress and cardiovascular risks is not known in hyperglycemic crises of diabetic ketoacidosis (DKA) and nonketotic hyperglycemia (NKH). We studied 20 lean and 28 obese patients with DKA, 10 patients with NKH, and 12 lean and 12 obese nondiabetic control subjects. We measured 1) proinflammatory cytokines (tumor necrosis factor-alpha, interleukin [IL]-6, IL1-beta, and IL-8), 2) markers of cardiovascular risk (C-reactive protein [CRP], homocysteine, and plasminogen activator inhibitor-1 [PAI-1]), 3) products of reactive oxygen species (ROS; thiobarbituric acid [TBA]-reacting material, and dichlorofluorescein [DCF]), and 4) cortisol, growth hormone (GH), and free fatty acids (FFAs) on admission (before insulin therapy) and after insulin therapy and resolution of hyperglycemia and/or ketoacidosis. Results were compared with lean and obese control subjects. Circulating levels of cytokines, TBA, DCF, PAI-1, FFAs, cortisol, and GH on admission were significantly increased two- to fourfold in patients with hyperglycemic crises compared with control subjects, and they returned to normal levels after insulin treatment and resolution of hyperglycemic crises. Changes in CRP and homocysteine in response to insulin therapy did not reach control levels after resolution of hyperglycemia. We conclude that DKA and NKH are associated with elevation of proinflammatory cytokines, ROS, and cardiovascular risk factors in the absence of obvious infection or cardiovascular pathology. Return of these values to normal levels with insulin therapy demonstrates a robust anti-inflammatory effect of insulin.
Differential effects of fasting and dehydration in the pathogenesis of diabetic ketoacidosis.
Burge M R,Garcia N,Qualls C R,Schade D S
Metabolism: clinical and experimental
Glycemia varies widely in patients with diabetic ketoacidosis (DKA), with plasma glucose concentrations between 10 to 50 mmol/L commonly encountered. The mechanism of this glycemic variability is uncertain. Our study examined the differential effects of fasting and dehydration on hyperglycemia induced by withdrawal of insulin in type 1 diabetes. To evaluate the respective roles of dehydration and fasting in the pathogenesis of DKA, 25 subjects with type 1 diabetes were studied during 5 hours of insulin withdrawal before (control) and after either 32 hours of fasting (n = 10) or dehydration of 4.1% +/- 2.0% of baseline body weight (n = 15). Samples were obtained every 30 minutes during insulin withdrawal for substrate and counterregulatory hormone levels and rates of glucose production and disposal. Fasting resulted in reduced plasma glucose concentrations compared with the control study, while dehydration resulted in increased plasma glucose concentrations compared with the control study (P < .001). Glucose production and disposal were decreased during the fasting study and increased during the dehydration study compared with the control study. Glucagon concentrations and rates of development of ketosis and metabolic acidosis were increased during both fasting and dehydration compared with control. These data suggest that fasting and dehydration have differential effects on glycemia during insulin deficiency, with dehydration favoring the development of hyperglycemia and fasting resulting in reduced glucose concentrations. This finding is probably attributable to the differing effect of these conditions on endogenous glucose production, as well as to differences in substrate availability and counterregulatory hormone concentrations. The severity of pre-existing fasting and dehydration likely explains much of the variability in plasma glucose concentrations observed in DKA.
Diabetic ketoacidosis and its treatment increase plasma 3-deoxyglucosone.
Hoffman William H,Kappler Frank,Passmore Gregory G,Mehta Renuka
OBJECTIVES:Highly reactive dicarbonyl compounds are known to be increased by hyperglycemia, ketone bodies and lipid peroxidation. This study was carried out to investigate the effect of diabetic ketoacidosis (DKA) and its treatment on the plasma concentration of 3 deoxyglucosone (3-DG) one of the dicarbonyl compounds. DESIGN AND METHODS:3-DG was measured in 7 children before, during and following correction of severe DKA. 3-DG was elevated before treatment (610 nmol/L +or/- 70) in comparison to baseline (120 h) (200 nmol/L+/or- 17) (p < 0.05). At 6 to 24 h into treatment 3-DG was further elevated (1080 nmol/L +or/- 80) in comparison to both pretreatment (p < 0.05) and baseline (p < 0.05). CONCLUSION:3-DG is significantly elevated before the treatment of DKA and increases further during the treatment of DKA. The time course of the increase of 3-DG coincides with the time of progression of subclinical brain edema, which occurs in DKA.
Polyunsaturated fatty acids in plasma lipids of diabetic children during and after diabetic ketoacidosis.
Decsi Tamás,Szabó Eva,Kozári Adrienn,Erhardt Eva,Marosvölgyi Tamás,Soltész Gyula
Acta paediatrica (Oslo, Norway : 1992)
BACKGROUND AND AIM:Previously we reported significantly higher plasma values of the essential fatty acids but significantly lower values of their longer-chain metabolites in diabetic children than in healthy controls. Here, we report data on the acute effect of diabetic ketoacidosis (DKA) on the fatty acid composition of plasma lipids. METHODS:Diabetic children (n=9; age: 16.1 [3.3] y; duration of diabetes: 5.0 [5.3.] y; daily insulin dose: 0.87 [0.66] unit/kg body weight/d; glycated haemoglobin: 13.4 [2.8] %; median [IQR]) were investigated at admission for DKA (during DKA) and at the end of the treatment of DKA (after DKA). Fatty acid composition of plasma lipid classes was determined by high-resolution capillary gas-liquid chromatography. RESULTS:Blood glucose (27.0 [8.5] vs 6.5 [1.6] mmol/l), pH (7.28 [0.35] vs 7.36 [0.06]) and base excess (-8.9 [15.1] vs -2.2 [6.3] mmol/l) were grossly abnormal during but not after DKA. Values of linoleic acid were significantly lower after than during DKA (non-esterifed fatty acids (NEFA): 15.55 [1.47] vs 12.27 [5.74] % wt/wt; triacylglycerols (TG): 20.84 [9.23] vs 17.40 [5.78]; p<0.05). In contrast, values of gamma-linolenic acid (NEFA: 0.87 [0.54] vs 2.34 [1.85]; p<0.05) and arachidonic acid (TG: 1.37 [0.71] vs 1.74 [0.57]; p<0.05) were significantly lower during than after DKA. The product/substrate ratios for delta-6 desaturation were significantly lower during than after DKA. CONCLUSION:Successful treatment of diabetic ketoacidosis is associated with a significant increase of long-chain polyunsaturated fatty acid values in blood plasma in diabetic children. This observation suggests that disturbances of essential fatty acid metabolism in diabetic children are related not only to diet but to hypoinsulinaemia as well.
Murine remote ischemic preconditioning suppresses diabetic ketoacidosis by enhancing glycolysis and entry into tricarboxylic acid cycle in the liver.
Kurabayashi Atsushi,Iwashita Waka,Tanaka Chiharu,Naganuma Seiji,Furihata Mutsuo,Inoue Keiji,Kakinuma Yoshihiko
AIMS:Hindlimb ischemia-reperfusion (IR) was previously demonstrated by our group to decrease blood sugar levels by suppressing hepatic gluconeogenesis and enhancing glucose uptake using activation of the parasympathetic nervous system. While IR attenuated hyperglycemia in diabetic mice, it was unclear whether IR regulated energy metabolism in the liver. We investigated the mechanisms by which IR regulates energy metabolism in the liver from type1 diabetic mice. MAIN METHODS:Streptozotocin-induced diabetic male C57BL/6J mice were used to determine the effect of IR on the factors involved in energy metabolism in the liver (i.e., activation levels of AMP-activated protein kinase, aconitase and pyruvate dehydrogenase; adenosine triphosphate and fumarate concentrations; sirtuin (Sirt) 1 expression). These various signaling pathways and key enzyme activities were examined using western blot analysis and a biochemical technique including a colorimetric assay. KEY FINDINGS:Under feeding conditions (free access to normal murine chow and water), blood glucose levels and serum ketone body levels were significantly suppressed by IR, whereas phospho-AMP-activated protein kinase and its activity, pyruvate dehydrogenase, aconitase activity, and Sirt 1expression were upregulated. In contrast, peroxisome proliferator-activated receptor γ coactivator-1, which accelerated fatty acid use, was suppressed by IR. SIGNIFICANCE:These results indicated that in the IR-treated diabetic liver, energy production was promoted through acceleration of the tricarboxylic acid cycle linked with increased glucose preference rather than fatty acid under feeding conditions. Therefore, IR may be beneficial against diabetic hyperglycemia, but also ketoacidosis.
Raltegravir-associated Diabetic Ketoacidosis in a Patient with HIV Infection: A Case Report.
Horikawa Mari,Toyoda Masao,Saito Nobumichi,Kimura Moritsugu,Kobayashi Takako,Takagi Atsushi,Fukagawa Masafumi
The Tokai journal of experimental and clinical medicine
Antiretroviral drugs, especially protease inhibitors (PI), are known to induce disorders of lipid and glucose metabolism. However, there are only a few reports of these side effects in patients treated with integrase strand transfer inhibitors (INSTI). We encountered the case of a 46-year-old man who had been treated for type 2 diabetes with diet and exercise. He contracted immunodeficiency virus (HIV) infection two years earlier and received highly active antiretroviral therapy (HAART). Three months before the current admission, HAART was switched from a non-nucleic acid reverse transcriptase inhibitor (NNRTI) to an INSTI (raltegravir: 800 mg/day). He developed diabetic ketoacidosis and was admitted for treatment. The state of health prior to admission was not well documented but he showed no clinical signs of acute infection. Accordingly, diabetic ketoacidosis was considered to be associated with INSTI. Diabetic ketoacidosis was treated appropriately and blood glucose level was controlled with medications before discharge from the hospital. Although the present case does not provide direct evidence for raltegravir-induced diabetic ketoacidosis, we caution physicians about the potential of such side effect associated with the use of INSTI.