Efficacy of Recombinant Human-Soluble Thrombomodulin for Severe Acute Pancreatitis in a Rat Experimental Model.

OBJECTIVES: Early death in severe acute pancreatitis (SAP) is caused by pancreatic necrosis and multiple-organ failure due to microcirculation disorder. The aim of this study was to prove that recombinant human-soluble thrombomodulin (rTM) has therapeutic effects on SAP by preventing pancreatic necrosis and organ failure. METHODS: Male Wister rats were used. Cerulein was administered intraperitoneally 4 times every 1 hour, and lipopolysaccharide was administered intraperitoneally 3 hours after. One hour after administration of lipopolysaccharide, rTM was injected intravenously. Rats were observed for 24 hours after starting the experiment, and the survival rate was evaluated. All surviving rats were killed, and the blood sample, liver, and pancreas were excised. Serum amylase, aspartate aminotransferase, alanine aminotransferase, and high mobility group box 1 were measured, and the liver and pancreas were examined histologically. For the evaluation of microcirculation, von Willebrand factor staining was performed. RESULTS: Serum amylase, aspartate aminotransferase, and alanine aminotransferase were significantly decreased. The survival rate was significantly improved to 100%. Moreover, serum high mobility group box 1 was decreased. Liver injury and pancreatic necrosis became less severe, and microcirculation was preserved histologically. CONCLUSIONS: Early administration of rTM prevents organ failure by maintenance of microcirculation and improves prognoses of SAP.

Pancreas lipiodol embolism induced acute necrotizing pancreatitis following transcatheter arterial chemoembolization for hepatocellular carcinoma: A case report and literature review.

RATIONALE: Transcatheter arterial chemoembolization (TACE) is recognized as one of the most commonly used modalities for non-surgical treatment for advanced hepatocellular carcinoma (HCC). Ectopic lipiodol embolism is an extremely rare complication of TACE. PATIENT CONCERNS: A 61-year-old man who had a 10-year history of cirrhosis caused by hepatitis B infection was diagnosed with ascites and HCC. Subsequently, the patient underwent TACE. However, he experienced persistent left upper abdominal pain, poor appetite, nausea, moderate fever and accompanied by elevation of serum and urine amylase on the 2nd and 3nd day after treatment. DIAGNOSES: The patient was diagnosed as having acute hemorrhagic necrotizing pancreatitis based on biochemical and inflammatory markers and CT findings. We deduced that the acute necrotizing pancreatitis was caused by a small branch of the left hepatic artery feeding the pancreas tail and embolizing the drug and lipiodol shunting to the tail of the pancreas. INTERVENTIONS: The patient was treated for 5 days according to the comprehensive treatment of acute necrotizing pancreatitis, by the inhibition of the secretion of pancreatic juice, relieving pain, and total parenteral nutrition and forbidding diet. The symptoms of the patient were observed to improve, and SAMS and urinary amylase (UAMS) level decreased to 143 IU/L and 254 IU/L, respectively and oral diet was permitted. OUTCOME: After a period of 2 weeks, the contrast abdominal CT showed slightly decreased fluid collection of the peri-pancreatic space. Moreover, it also showed flocculous and linear high-density shadow in the pancreatic tail, suggesting lipiodol deposition in the pancreatic tail. Subsequently, the symptoms were observed to abate, and the patient left the hospital. On the 21st day after TACE, the patient had a follow up in our outpatient department; the biochemical characteristics and inflammatory markers were observed to be normal CONCLUSION:: AP is still a rare complication after TACE. Etiology is still attributed to the occurrence of shunting and embolization drug reflux. Strategies strengthening the catheter tip that is placed as close to the distal branches of the hepatic artery for the possible careful injection of embolic materials is still the key to avoid post-TACE AP.

Amygdalin improves microcirculatory disturbance and attenuates pancreatic fibrosis by regulating the expression of endothelin-1 and calcitonin gene-related peptide in rats.

BACKGROUND: The pathogenesis of chronic pancreatitis (CP) is a complex process of interaction between tissue injury and repair, which involves microcirculatory disturbance. Amygdalin, an effective component extracted from Semen Persicae (a kind of Chinese herbal medicine), can decrease blood viscosity and improve microcirculation. In this study, we investigated the therapeutic effects of amygdalin on pancreatic fibrosis in rats with CP. METHODS: The rat CP model was induced by injecting dibutyltin dichloride (DBTC) into the right caudal vein. Amygdalin was administrated via the penile vein at a dose of 10 mg/(kg d) from the next day, after the induction of CP, once a day for the previous 3 days, and then once every 2 days, until the end of the experiment. Body weight was observed every 7 days. Pancreatic blood flow and histopathological changes were assessed at 28 days. The activation of pancreatic stellate cells (PSCs) was estimated by the expression of α-smooth muscle actin (α-SMA). At the same time, the expression of platelet-derived growth factor-BB (PDGF-BB), transforming growth factor ß-1 (TGFß-1), endothelin-1 (ET-1), and calcitonin gene-related peptide (CGRP) of pancreatic tissues were detected. RESULTS: Treatment of CP rats with amygdalin improved body weight and pancreatic blood flow, as well as alleviated pancreatic fibrosis and acinar destruction, accompanied by the down-regulation of the expressions of α-SMA, PDGF-BB, TGFß-1, and ET-1, and the up-regulation of the CGRP's expression. CONCLUSION: Amygdalin could reduce the production of pro-fibrotic cytokines, inhibit the activation of PSCs, and attenuate pancreatic fibrosis in a rat with CP. The mechanism probably includes improving microcirculatory disturbance by regulating the production of ET-1 and CGRP.

Chronically Increased Amino Acids Improve Insulin Secretion, Pancreatic Vascularity, and Islet Size in Growth-Restricted Fetal Sheep.

Placental insufficiency is associated with reduced supply of amino acids to the fetus and leads to intrauterine growth restriction (IUGR). IUGR fetuses are characterized by lower glucose-stimulated insulin secretion, smaller pancreatic islets with less ß-cells, and impaired pancreatic vascularity. To test whether supplemental amino acids infused into the IUGR fetus could improve these complications of IUGR we used acute (hours) and chronic (11 d) direct fetal amino acid infusions into a sheep model of placental insufficiency and IUGR near the end of gestation. IUGR fetuses had attenuated acute amino acid-stimulated insulin secretion compared with control fetuses. These results were confirmed in isolated IUGR pancreatic islets. After the chronic fetal amino acid infusion, fetal glucose-stimulated insulin secretion and islet size were restored to control values. These changes were associated with normalization of fetal pancreatic vascularity and higher fetal pancreatic vascular endothelial growth factor A protein concentrations. These results demonstrate that decreased fetal amino acid supply contributes to the pathogenesis of pancreatic islet defects in IUGR. Moreover, the results show that pancreatic islets in IUGR fetuses retain their ability to respond to increased amino acids near the end of gestation after chronic fetal growth restriction.

The Role of Neoadjuvant Chemoradiation Therapy in Patients With Borderline Resectable Pancreatic Cancer With Isolated Venous Vascular Involvement.

The rationale for neoadjuvant chemoradiation therapy (Neo-CRT) and the definition of borderline resectable pancreatic cancer (BRPC) are still controversial. In particular, surgical treatment of BRPC with isolated venous vascular involvement (IVVI) is debatable.From January 2000 to December 2013, 84 patients diagnosed with BRPC according to NCCN guidelines were identified, and 70 patients were found to have BRPC with IVVI. We divided all 70 patients into 3 groups: surgery first without Neo-CRT (Group 1); pancreatectomy following Neo-CRT (Group 2); and no operation following Neo-CRT (Group 3). Patient characteristics including oncologic outcomes were analyzed for each of the 3 patients groups.Thirty-seven patients were female and 33 were male, with a mean age of 61.7 ±â€Š9.74 years. Among the 70 BRPC patients with IVVI, 28 patients (40%) belonged to Group 1, 30 patients (42.9%) belonged to Group 2, and 12 patients (17.1%) belonged to Group 3. Pathological tumor size (P < 0.001), pT stage (P = 0.001), pTNM stage (P=0.002), combined vascular resection (P = 0.003), completeness of adjuvant therapy (P = 0.004) were found to be statistically significantly different between Groups 1 and 2. In addition, disease-free survival (P = 0.055) and disease-specific survival (DSS) (P=0.006) were improved in Group 2. Interestingly, when comparing DSS, there was no statistically significant difference between Groups 1 and 3 (P = 0.991).The clinical practice of pancreatectomy following Neo-CRT in BRPC with IVVI provided favorable oncologic outcomes. The effect of Neo-CRT in BRPC with IVVI may be multifactorial, providing proper patient selection, complete adjuvant chemotherapy, and potential therapeutic (downstaging) effect.

Obestatin Accelerates the Recovery in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

OBJECTIVE: Several previous studies have shown that obestatin exhibits protective and regenerative effects in some organs including the stomach, kidney, and the brain. In the pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis, and promotes survival of pancreatic beta cells and human islets. However, no studies investigated the effect of obestatin administration following the onset of experimental acute pancreatitis. AIM: The aim of this study was to evaluate the impact of obestatin therapy in the course of ischemia/reperfusion-induced pancreatitis. Moreover, we tested the influence of ischemia/reperfusion-induced acute pancreatitis and administration of obestatin on daily food intake and pancreatic exocrine secretion. METHODS: Acute pancreatitis was induced by pancreatic ischemia followed by reperfusion of the pancreas. Obestatin (8 nmol/kg/dose) was administered intraperitoneally twice a day, starting 24 hours after the beginning of reperfusion. The effect of obestatin in the course of necrotizing pancreatitis was assessed between 2 and 14 days, and included histological, functional, and biochemical analyses. Secretory studies were performed on the third day after sham-operation or induction of acute pancreatitis in conscious rats equipped with chronic pancreatic fistula. RESULTS: Treatment with obestatin ameliorated morphological signs of pancreatic damage including edema, vacuolization of acinar cells, hemorrhages, acinar necrosis, and leukocyte infiltration of the gland, and led to earlier pancreatic regeneration. Structural changes were accompanied by biochemical and functional improvements manifested by accelerated normalization of interleukin-1ß level and activity of myeloperoxidase and lipase, attenuation of the decrease in pancreatic DNA synthesis, and by an improvement of pancreatic blood flow. Induction of acute pancreatitis by pancreatic ischemia followed by reperfusion significantly decreased daily food intake and pancreatic exocrine secretion. Administration of obestatin at doses used was without significant effect with regard to daily food intake or pancreatic exocrine secretion in sham-operated rats, as well as in rats with acute pancreatitis. On the other hand, obestatin abolished a statistical significance of difference in food intake between animals with AP and control animals without pancreatic fistula and induction of AP. CONCLUSION: Treatment with the exogenous obestatin reduces severity of ischemia/reperfusion-induced acute pancreatitis and accelerates recovery in this disease. The involved mechanisms are likely to be multifactorial, and are mediated, at least in part, by anti-inflammatory properties of obestatin.

Blood lipids affect rat islet blood flow regulation through ß3-adrenoceptors.

Pancreatic islet blood perfusion varies according to the needs for insulin secretion. We examined the effects of blood lipids on pancreatic islet blood flow in anesthetized rats. Acute administration of Intralipid to anesthetized rats increased both triglycerides and free fatty acids, associated with a simultaneous increase in total pancreatic and islet blood flow. A preceding abdominal vagotomy markedly potentiated this and led acutely to a 10-fold increase in islet blood flow associated with a similar increase in serum insulin concentrations. The islet blood flow and serum insulin response could be largely prevented by pretreatment with propranolol and the selective ß3-adrenergic inhibitor SR-59230A. The nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester prevented the blood flow increase but was less effective in reducing serum insulin. Increased islet blood flow after Intralipid administration was also seen in islet and whole pancreas transplanted rats, i.e., models with different degrees of chronic islet denervation, but the effect was not as pronounced. In isolated vascularly perfused single islets Intralipid dilated islet arterioles, but this was not affected by SR-59230A. Both the sympathetic and parasympathetic nervous system are important for the coordination of islet blood flow and insulin release during hyperlipidemia, with a previously unknown role for ß3-adrenoceptors.

The effect of Chinese medicine Pu-Ren-Dan on pancreatic angiogenesis in high fat diet/streptozotocin-induced diabetic rats.

OBJECTIVES: The islet vascular system is critical for ß-cell function. This study investigated the antidiabetic effect of the Chinese Pu-Ren-Dan (PRD) recipe by regulating the pancreatic angiogenic factors in T2DM rats. MATERIALS METHODS: High fat diet/streptozotocin-induced obese type-2 diabetes mellitus rats were developed and treated with PRD for 4 weeks. Then glucolipid metabolism, insulin secretion, pancreatic blood flow, ultrastructure of islet ß-cell, histological changes of islet and protein expressions of pancreatic angiogenic factors were investigated. RESULTS: PRD-reduced T2DM rats' body weight and blood glucose level resisted the lipid metabolism disturbance, and ameliorated the insulin resistance and ß-cell function. In addition, the histological and morphological studies proved that PRD could maintain the normal distribution of endocrine cell in islet and normal ultrastructure of ß cell. An increased pancreatic blood flow was observed after the PRD treatment. In the investigation of pancreatic angiogenic factors, PRD inhibited the decreased expression of VEGF and Ang-1, and reversed the reduction of VEGFR2 and Tie2 phosphorylation in T2DM rats; the Ang-2 and TGFß expression were up-regulated by PRD while PKC was activated; endostatin and angiostatin were down-regulated by PRD. CONCLUSIONS: The results suggest that increasing VEGF expression, regulating VEGF/VEGFR2 signaling, stimulating Ang-1/Tie-2 signaling pathway, and inhibiting PKC-TGFß signaling and antiangiogenic factors might be the underlying mechanism of PRD's antidiabetic effect.

Pharmacokinetic evaluation of pancreatic arterial infusion chemotherapy with lipid emulsion as a drug carrier in an animal model.

The purpose of this study was to investigate the potential pharmacokinetic advantage of pancreatic arterial infusion chemotherapy with lipid emulsion as a drug carrier for pancreatic cancer in a dog model. The 20% Intralipid, as a solvent, was used in the experimental animals with 2 ml/kg (group A) and 1 ml/kg (group B). Normal sodium as a solvent was used as a control with 2 ml/kg (group C) and 1 ml/kg (group D), respectively. Cisplatin (4 mg/kg) was infused into the proximal segment of the splenic artery. The concentrations of cisplatin were measured in plasma of the portal vein and in the liver and pancreas of groups A and C. The area under the concentration-time curve (AUC), the maximum plasma concentration (C(max)), and the elimination half-life (t(1/2)) in plasma were calculated and compared statistically. Compared with group C, the AUC and C(max) of group A were significantly lower (P<0.01 and P<0.01, respectively), the t 1/2 was longer (P<0.05), and the tissue cisplatin concentration of the pancreas was higher (P<0.05). Compared with group D, the AUC and C(max) of group B were significantly lower (P<0.01 and P<0.01, respectively) and the t(1/2) was longer (P<0.01). Pancreatic arterial infusion chemotherapy with lipid emulsion as a drug carrier can increase the local concentration and prolong the retention time of a drug.

Pretreatment of cisplatin in recipients attenuates post-transplantation pancreatitis in murine model.

Pancreas transplantation is the definite treatment for type 1 diabetes that enables the achievement of long-term normoglycemia and insulin independence. However Post-Transplantation Pancreatitis (PTP) due to ischemia reperfusion (IR) injury and preservation is a major complication in pancreas transplantation. Owning the potential anti-inflammatory effect of Cisplatin (Cis) in liver IR injury, we have examined if Cis could attenuate PTP using a murine model. We found that Cis is able to prevent inflammatory response in PTP. Pretreatment of Cis in recipient mice reduce the impairments of the grafts and hyperamylasimea in the recipients. We documented that the protective mechanism of Cis in PTP involves improvement of microcirculation, reduction of the mononuclear cellular infiltration and apoptosis, suppression of inflammatory cytokine-cascade and inhibition of translocation of high-motility group box protein-1 (HMGB-1) from nucleus to cytoplasm. In short, our study demonstrated that pretreatment of Cis in recipients may reduce the onset of PTP in pancreas transplantation.

A new flow control technique using diluted epinephrine in the N-butyl-2-cyanoacrylate embolization of visceral artery pseudoaneurysms secondary to chronic pancreatitis.

Although n-butyl-2-cyanoacrylate (NBCA) has been used as an effective liquid embolization material, its indication for pseudoaneurysms has seemingly been limited because of the technical difficulties of using NBCA, such as reflux to the parent artery and causing significant infarction. Thus, considerable skill in using NBCA or a device to control blood flow during its polymerization is required to achieve embolization without severe complications. We report our new technique for controlling blood flow using diluted epinephrine in transcatheter arterial NBCA embolization of five pseudoaneurysms in four cases secondary to hemosuccus pancreaticus.

Imaging guided trials of the angiogenesis inhibitor sunitinib in mouse models predict efficacy in pancreatic neuroendocrine but not ductal carcinoma.

Preclinical trials in mice represent a critical step in the evaluation of experimental therapeutics. Genetically engineered mouse models (GEMMs) represent a promising platform for the evaluation of drugs, particularly those targeting the tumor microenvironment. We evaluated sunitinib, an angiogenesis inhibitor that targets VEGF and PDGF receptor signaling, in two GEMMs of pancreatic cancer. Sunitinib did not reduce tumor burden in pancreatic ductal adenocarcinoma (PDAC), whereas tumor burden was reduced in the pancreatic neuroendocrine tumor (PNET) model, the latter results confirming and extending previous studies. To explore the basis for the lack of pathologic response in PDAC, we used noninvasive microbubble contrast-enhanced ultrasound imaging, which revealed that sunitinib reduced blood flow both in PDAC and in PNET, concomitant with a reduction in vessel density; nevertheless, PDAC tumors continued to grow, whereas PNET were growth impaired. These results parallel the response in humans, where sunitinib recently garnered FDA and European approval in PNET, whereas two antiangiogenic drugs failed to demonstrate efficacy in PDAC clinical trials. The demonstration of on-target activity but with discordant benefit in the PDAC and PNET GEMMs illustrates the potential value of linked preclinical and clinical trials.

Synergetic effect of yihuo qingyi decoction (see text) and recombinant staphylokinase in treatment of severe acute pancreatitis of rats.

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.

Curcumin attenuates airway hyperreactivity induced by ischemia-reperfusion of the pancreas in rats.

OBJECTIVES: Ischemia-reperfusion (I/R) of the rat pancreas induces acute pancreatitis with a systemic inflammatory response. Activated inflammatory cells are sequestered in the lung, and the consequent respiratory burst may increase airway reactivity. In this study, we characterized the effect of the antioxidant curcumin on airway hyperreactivity induced by pancreatic I/R. METHODS: Ischemia of the pancreas was induced by clamping the gastroduodenal and the splenic artery for 2 hours followed by reperfusion for 6 hours. The pulmonary function data of Penh, a measurement of airway resistance, were used to show the airway responses to a methacholine challenge. The blood concentration of oxygen radicals, nitric oxide, and tumor necrosis factor-alpha (TNFalpha) were measured after pancreatic I/R. mRNA expressions of inducible nitric oxide synthase (iNOS) and TNFalpha in lung tissues were measured after pancreatic I/R. Pretreatment with curcumin (20 mg/kg) was administered by intraperitoneal injection 2 hours before pancreatic I/R. RESULTS: The protocol resulted in significant elevations of the blood concentrations of amylase, hydroxyl radical, nitric oxide, TNFalpha, and white cells among the I/R group. iNOS and TNFalpha mRNA expressions also significantly increased in lung tissues. Pulmonary function data showed that pancreatic I/R induced significant increases in responses to methacholine challenge: Penh increased significantly in the I/R group when compared with the sham group. Pretreatment with curcumin significantly attenuated the inflammatory, oxidative, and nitrosative responses and lung tissue iNOS and TNFalpha expressions. Curcumin also attenuated airway reactivity to methacholine challenge. CONCLUSIONS: I/R of the pancreas induced systemic inflammatory responses with respiratory burst, nitrosative stress, and hyperresponses in the airways. Curcumin, which has antioxidant and anti-inflammatory effects, significantly attenuated the inflammatory responses and airway hyperreactivity induced by pancreatic I/R.

[Types of microcirculation and laser therapy in chronic pancreatitis].

The aim of the study was to evaluate effect of low-intensity laser therapy (LILT) on systemic circulation in patients with chronic pancreatitis (CP) in the phase of exacerbation. 65 patients aged 36-77 years were divided into study (n = 20) and control (n = 45) groups. In addition, 30 healthy subjects were examined. Patients of the study group received drug therapy combined with intravenous blood or skin laser irradiation. Controls were treated with medicinal preparations alone. CP was diagnosed based on characteristic pain syndrome, compromised secretory function of the pancreas, results of laboratory and instrumental analysis. Microcirculation was studied by laser Doppler flowmetry with a LAKK-02 apparatus (Lazma, Russia). CP patients had heterogeneous microcirculation with a significantly increased frequency of its pathologic types (spastic, hyperemic, spastic-congestive). Major characteristics of microcirculation were significantly different from those in healthy subjects. Combination of drug therapy and LILT substantially improved microcirculation regardless of its hemodynamic type.

Enteral glutamine supplementation impairs intestinal blood flow in rats.

BACKGROUND: Clinical studies have shown that enteral immune-enhancing diets (IEDs) containing l-glutamine decrease septic complications and length of stay in some patient populations. Animal studies suggest IED benefits might include augmented gut blood flow. We hypothesized that enteral glutamine supplementation modulates gastrointestinal blood flow. METHODS: Blood flow was measured in male Sprague-Dawley rats via the colorimetric microsphere technique at baseline, 60, and 120 minutes. Four groups were studied: (1) control diet (CD) + enteral glutamine; (2) CD + enteral glycine; (3) CD + enteral saline; and (4) CD + intravenous glutamine. RESULTS: There were no differences in blood pressure or heart rate in any group. Group 1 blood flow was decreased at 120 minutes compared with controls (groups 2 and 3) in small intestine, colon, spleen, and pancreas, whereas the intravenous glutamine group (group 4) had no effect on blood flow. CONCLUSIONS: Enteral glutamine supplementation (as in IEDs) appears to impair gastrointestinal blood flow. Because glutamine provides energy directly to active enterocytes, enteral glutamine availability might diminish metabolic stimuli of absorptive hyperemia. This finding might partially explain the benefits observed with parenteral versus enteral glutamine supplementation in clinical studies (such as bone-marrow-transplant patients).

Hyperbaric oxygen improves capillary morphology in severe acute pancreatitis.

OBJECTIVES: This article aims to determine the effect of acute pancreatitis on microvascular morphology and the impact of treatment with hyperbaric oxygen (HBO). METHODS: Sixty-seven male Wistar rats were induced with acute pancreatitis by retrograde bile duct injection. Rats were randomized to 12-hourly HBO or control treatment. Two rats in each group were killed at baseline and 24, 48, and 72 hours postinduction, and a cast of the pancreatic microvasculature was examined using scanning electron microscopy. RESULTS: Normal pancreatic vasculature is a dense network with a consistent capillary diameter. In acute pancreatitis, mean capillary diameter is increased at 24 hours (P < 0.001) and further increased at 48 hours (P = 0.007). From 24 hours, diameter heterogeneity is increased (P < 0.001) and capillary density is reduced (P < 0.001). Hyperbaric oxygen has a significant effect on vascular morphology changes from 48 hours after induction. Capillary diameter and heterogeneity of diameter are decreased by HBO (both P < 0.001). Capillary density is increased by HBO at 48 and 72 hours (P < 0.001). CONCLUSIONS: In acute pancreatitis, structural capillary diameter and heterogeneity of diameter increase and capillary density decreases. These parameters are all improved by HBO treatment. Hyperbaric oxygen treatment normalizes the pancreatic microvasculature after acute pancreatitis and may be a potentially effective treatment of this disease.

Ligustrazine alleviates gastric mucosal injury in a rat model of acute necrotizing pancreatitis.

BACKGROUND: Acute necrotizing pancreatitis (ANP) leads to a systemic inflammatory response characterized by widespread leukocyte activation and, as a consequence, distant organ injury. The aim of this study was to explore the relationship between gastric microcirculatory impairment and inflammatory mediators released in rats and to evaluate the therapeutic effect of ligustrazine extracted from Rhizoma ligusticum wallichii on gastric mucosa injury in a rat model of ANP. METHODS: Ninety-six Sprague-Dawley rats were randomly divided into three groups: normal control (group C); ANP without treatment (group P); and ANP treated with ligustrazine (group T). The ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane (4 ml/kg). Group C was given isovolumetric injection of 9 g/L physiological saline by the same route. Group T was injected with ligustrazine (10 ml/kg) via the portal vein. The radioactive biomicrosphere technique was used to measure the blood flow 2 and 12 hours after the induction of ANP. Samples of the pancreas and stomach were taken to assess pathological changes by a validated histology score; meanwhile, the levels of serum interleukin-1beta (IL-1beta) were determined. Gastric tissues were also used to measure the level of myeloperoxidase (MPO), which is expressed intracellularly in the azurophilic granules of neutrophils. RESULTS: Blood flow in group P was significantly lower than that in group C (P<0.01). Pathological changes were significantly aggravated in group P. The gastric MPO activity in group P was significantly higher than that in group C (P<0.01). The level of serum IL-1beta in group P increased more significantly than that in group C (P<0.01). Blood flow of the stomach in group T was significantly higher than that in group P after 2 hours (P<0.01). The pathological changes were significantly alleviated in group T. The MPO activity of group T was significantly lower than that of group P (P<0.01). Although serum IL-1beta level of group T was higher than of group C (P<0.01), it was lower than that of group P (P<0.01). There was a negative correlation between gastric blood flow and MPO activity (r=-0.983, P<0.01), and between gastric blood flow and pathological score (r=-0.917, P<0.05). CONCLUSIONS: Decreased gastric blood flow and increased inflammatory mediators can be seen early in ANP, and both are important factors for gastric and mucosal injury. Ligustrazine can ameliorate microcirculatory disorder and alleviate the damage to the pancreas and stomach.

[Clinical early intervention of Tongxia Huayu Decoction on pancreatic microcirculatory disturbance in severe acute pancreatitis].

OBJECTIVE: To study the mechanisms of Tongxia Huayu Decoction (a Chinese herbal decoction for purgation and removing blood stasis) in prognostic improvement for severe acute pancreatitis by early intervention on pancreatic microcirculatory disturbance. METHODS: Fifty-three patients with severe acute pancreatitis were divided randomly into treatment group (n=28) and control group (n=25). Tongxia Huayu Decoction was given to the patients in treatment group in addition to the normal treatment in control group for one week. The clinical symptoms and signs, hemodiastase, urinary amylase, C-reactive protein (CRP) and endothelin (ET) of the patients in the two groups before and after treatment were observed and detected. RESULTS: The total response rate of the treatment group was 98.4%, while that of the control group was 80%, with significant difference between them (P<0.05). There was no significant difference of the contents of hemodiastase, urinary amylase, CRP and ET between the two groups before treatment, while they were significantly decreased after treatment (P<0.01) with more obvious change in treatment group (P<0.01). CONCLUSION: Tongxia Huayu Decoction brings satisfied therapeutic effect on severe acute pancreatitis. The mechanisms may associate with its reducing function on ET releasing so as to inhibit the pancreatic microcirculatory disturbance and acinar cell injury induced by ET.

Progress in research into the mechanism of Radix salviae miltiorrhizae in treatment of acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a common acute abdomen with high mortality, multiple complications and complicated causes. There is no effective therapy for AP. Radix salviae miltiorrhizae (Danshen), a traditional herbal medicine, has a low price and a wide range of clinical applications. It is effective to promote blood flow, eliminate stagnancy, and relieve pain. It is also found to be effective in treating AP. We reviewed the progress in research into the mechanism of Radix salviae miltiorrhizae in treatment of AP. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1988-2005) on Radix salviae miltiorrhizae (Danshen) and acute pancreatitis. RESULTS: The mechanisms of Danshen in the treatment of AP include improvement of microcirculatory disturbances; elimination of oxygen free radicals; modulation of the metabolism of lipid inflammatory mediator; and blocking of calcium inflow and prevention of calcium overload. CONCLUSION: Danshen can effectively reduce the mortality and complications of AP.