Effects Of Acute Pancreatitis Research Articles

The molecular mechanism of PLD2-mediated regulation of apoptosis and cell edema in pancreatic cells via the Nrf2/NF-κB pathway

This study aimed to elucidate the molecular mechanisms by which PLD2 controls apoptosis and edema in pancreatic cells via the Nrf2/NF-κB pathway. AR42J rat pancreatic cells were treated with 10 nM mitomycin to create an in vitro pancreatitis model (model group), with a control group receiving phosphate-buffered saline. Cells were transfected with a PLD2 overexpression plasmid using Lipofectamine 3000, forming the PLD2 overexpression group. PLD2 protein expression was assessed by Western blotting, and TNF-α, IL-6, and IL-10 levels were measured by RT-qPCR. Nrf2/NF-κB protein expressions were also analyzed. Apoptosis and necrosis were evaluated using Annexin V-FITC/PI staining and the LDH release test. Cell edema was assessed by cell volume, ion content, and membrane damage. Western blotting was used to analyze pan-apoptosis-related proteins. PLD2 expression was lower in the model group compared to controls (P < 0.05) but higher in the PLD2 overexpression group (P < 0.05). TNF-α, IL-6, and IL-10 levels were elevated in the model group (P < 0.05) and reduced in the PLD2 overexpression group (P < 0.05). Nrf2 expression decreased in the model group but increased with PLD2 overexpression (P < 0.05). NF-κB expression increased in the model group but decreased with PLD2 overexpression (P < 0.05). Apoptosis and necrosis rates were higher in the model group (P < 0.05) but lower in the PLD2 overexpression group (P < 0.05). Cell volume, Na + content, and LDH release increased in the model group (P < 0.05) but decreased with PLD2 overexpression (P < 0.05). RIPK1 expression decreased in the model group (P < 0.05) but increased with PLD2 overexpression (P < 0.05). CASP8, FADD, and ZBP1 levels were higher in the model group (P < 0.05) and reduced with PLD2 overexpression (P < 0.05). PLD2 exerts a protective effect in acute pancreatitis by activating Nrf2 and inhibiting NF-κB, reducing apoptosis, cell swelling, and membrane damage. This highlights potential therapeutic targets for pancreatic inflammation.

Acute Pancreatitis and the Risk of Dementia in Diabetes: A Nationwide Cohort Study Using Korean Healthcare Claims Database.

Diabetes is a major risk factor for the development of dementia, which has been proven to be associated with systemic inflammation. Acute pancreatitis, also a local and systemic inflammatory disease, is the most common gastrointestinal disease requiring acute hospitalization. The effect of acute pancreatitis on dementia was investigated in type 2 diabetic patients. Data was collected from the Korean National Health Insurance Service. The study sample included type 2 diabetes patients who received general health examination from 2009 to 2012. Cox proportional hazard regression analysis was used to evaluate the association between acute pancreatitis and dementia with adjustment of confounders. Stratified subgroup analysis by age, sex, smoking, alcohol consumption, hypertension, dyslipidemia, and body mass index was conducted. Among the 2,328,671 participants in total, 4,463 patients had a history of acute pancreatitis before the health examination. During a median follow-up of 8.1 (IQR, 6.7-9.0) years, 194,023 participants (8.3%) developed all-cause dementia. Previous history of acute pancreatitis was a significant risk factor for dementia after adjustment of confounding variables (HR 1.39 [95% CI 1.26-1.53]). In the subgroup analysis, patient characteristics such as age under 65 years, male, current smoker, and alcohol consumption were significant risk factors for dementia in patients with a history of acute pancreatitis. The history of acute pancreatitis was associated with the development of dementia in patients with diabetes. Because the risk of dementia increases with alcohol consumption and smoking in diabetic patients with history of acute pancreatitis, abstinence from alcohol and smoking should be recommended.

Diallyl Disulfide Attenuates STAT3 and NF-κB Pathway Through PPAR-γ Activation in Cerulein-Induced Acute Pancreatitis and Associated Lung Injury in Mice.

We have previously shown that diallyl disulfide (DADS) protects mice against cerulein-induced acute pancreatitis (AP) and associated lung injury. However, the molecular mechanisms underlying its effect and the components involved have not been studied. We hypothesized that DADS may reduce TNF-α, CSE expression, H2S production, STAT3, and NF-κB activation and induce SOCS3 expression through peroxisome proliferator-activated receptor γ (PPAR-γ) pathway in cerulein-induced mice. Male Swiss mice were treated with hourly intraperitoneal injections of cerulein (50µg/kg) for 6h. Diallyl disulfide (200μg/kg) was administered in the presence or absence of PPAR-γ antagonist GW9662 (0.3mg/kg) (i.p) 1h after the induction of AP. Our findings revealed thatDADS blocked TNF-α, CSE expression, H2S production, and STAT3, and NF-κB activation was reversed by GW9662. Furthermore, GW9662 abrogated DADS-induced SOCS3 expression. The results show for the first that DADS-induced anti-inflammatory effect in acute pancreatitis is regulated through PPAR-γ.

S3211 Outcomes of Patients Admitted With Concurrent Pancreatitis and Rhabdomyolysis: An NIS Database Study

Introduction: There have been numerous studies on acute pancreatitis; however, the effect of acute pancreatitis and rhabdomyolysis have yet to be studied. Here, we aim to assess rhabdomyolysis in patients hospitalized with acute pancreatitis. Methods: Data between 2008 and 2016 from the Nationwide Inpatient Sample database was extracted. Inclusion criteria for both groups included patients over the age of 17 with a primary diagnosis of acute pancreatitis using International Classification of Diseases, 9th and 10th revision codes. Exclusion criteria included all ICD-9 and ICD-10 codes for chronic pancreatitis and malignant pancreatico-biliary disorders and indeterminate rhabdomyolysis status. The study group consisted of patients with a primary diagnosis of acute pancreatitis and a concurrent diagnosis of rhabdomyolysis. Other co-morbidities were then compared between the two groups. Univariate and multivariate analyses were used to generate odds ratios. Results: There were a total of 1,946,591 patients in the control group, and 5,421 patients in the study group. In univariate analysis, there was a statistically significant increase in severe sepsis, respiratory failure, septic shock, calculus and HIV, but not pseudocyst in the study group. In multivariate analysis with rhabdomyolysis as the dependent variable, the odds ratio was highest for respiratory failure (OR=7.749, p < 0.001), followed by HIV (OR = 2.070, p < 0.001), septic shock (OR = 1.586, p < 0.001) and severe sepsis (OR = 1.532, p < 0.001). Calculus had an odds ratio of 0.470 (p < 0.001), suggesting a negative association with rhabdomyolysis. A multivariate analysis with patient morbidity as a dependent variable showed that patients with respiratory failure and septic shock are most likely to die in the hospital, with respiratory failure having an odds ratio of 8.292 (p < 0.001) and septic shock having an odds ratio of 3.729 (P = 0.01431). Conclusion: Rhabdomyolysis appears to confer elevated risk to patients with acute pancreatitis. Patients that are admitted with acute pancreatitis along with rhabdomyolysis also have a high rate of other conditions such as respiratory failure, HIV, septic shock and severe sepsis. Of these, respiratory failure and septic shock are the most dangerous, as they are tied to the highest mortality among patients that have both acute pancreatitis and rhabdomyolysis. We suspect the additional mortality may be due to respiratory muscle weakness and the release of intracellular substances from damaged muscle cells.

Perinatal outcomes in pregnancies complicated by acute pancreatitis.

Acute pancreatitis is a rare condition that can be associated with significant complications. The objective of this study is to evaluate the maternal and newborn outcomes associated with acute pancreatitis in pregnancy. A retrospective cohort study using the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample from the United States was performed. All pregnant patients with acute pancreatitis were identified using International Classification of Disease-9 coding from 1999 to 2015. The effect of acute pancreatitis on maternal and neonatal outcomes in pregnancy was evaluated using multivariate logistic regression, while adjusting for baseline maternal characteristics. From 1999 to 2015, there were a total of 13,815,919 women who gave birth. There were a total of 14,258 admissions of women diagnosed with acute pancreatitis, including 1,756 who delivered during their admission and 12,502 women who were admitted in the antepartum period and did not deliver during the same admission. Acute pancreatitis was associated with increased risk of prematurity, OR 3.78 (95% CI 3.38-4.22), preeclampsia, 3.81(3.33-4.36), postpartum hemorrhage, 1.90(1.55-2.33), maternal death, 9.15(6.05-13.85), and fetal demise, 2.60(1.86-3.62) among women diagnosed with acute pancreatitis. Among women with acute pancreatitis, delivery was associated with increased risk of requiring transfusions, 6.06(4.87-7.54), developing venous thromboembolisms, 2.77(1.83-4.18), acute respiratory failure, 3.66(2.73-4.91), and disseminated intravascular coagulation, 8.12(4.12-16.03). Acute pancreatitis in pregnancy is associated with severe complications, such as maternal and fetal death. Understanding the risk factors that may lead to these complications can help prevent or minimize them through close fetal and maternal monitoring.

Administration of warfarin accelerates the recovery in ischemia/reperfusion-induced acute pancreatitis.

Acute pancreatitis is associated with activation of coagulation and there is a close relationship between coagulation and the severity of this disease. Administration of anticoagulants such as heparin or acenocoumarol has shown to reduce the severity of acute pancreatitis and accelerate the recovery. The aim of the current study was to determine the impact of warfarin administration on the course of ischemia/reperfusion-induced acute pancreatitis. Acute pancreatitis was induced in rats by pancreatic ischemia followed by reperfusion. Vehicle (1 ml/dose) or warfarin (45, 90 or 180 μg/kg/dose in 1 ml of vehicle) were administered intragastrically once a day. The first dose of warfarin was given 24 h after the start of pancreatic reperfusion. The severity of acute pancreatitis was assessed 2, 5, 9 and 14 days after the beginning of pancreatic reperfusion. Treatment with warfarin reduces pancreatic damage and accelerates recovery in histological examination and this effect is accompanied by a faster reduction in serum activity of pancreatic digestive enzymes, lipase and amylase. In addition, warfarin led to an earlier decrease in serum concentration of pro-inflammatory interleukin-1β and plasma level of D-dimer. These effects were associated with an improvement of pancreatic blood flow. We conclude that warfarin exhibits a therapeutic effect in acute pancreatitis evoked by pancreatic ischemia followed by reperfusion.

Screening of Sera from Patients with Pancreatitis by an Apoptosis Assay of Skin-derived Cells.

An excessive inflammatory response is typical in acute pancreatitis and a significant cause of early mortality in severe acute pancreatitis. This is believed to be caused by inflammatory molecules or upregulated cytokine levels in the serum of patients. The aim of this study was to identify the serum-mediated apoptosis-inducing effects in acute pancreatitis patients. A skin tissue-derived cell line, BJ, was treated for 24 hours with the sera of 22 healthy volunteers (control) and 71 acute pancreatitis patients (22 with gallstone pancreatitis, 16 with alcoholic pancreatitis, and 11 with pancreatitis with other causes) collected at the time of hospital admission (active) and discharge (resolved). Apoptosis was analyzed by flow cytometry. The average percentage of living cells, early apoptotic cells, and late apoptotic cells ranged from 78.8% to 85.0%, 5.5% to 7.3%, and 7.7% to 13.1%, respectively. The number of live cells increased significantly using the serum from the resolved state of gallstone-induced pancreatitis. In addition, the number of early apoptotic cells increased significantly using the serum from the resolved state of pancreatitis with other causes. The number of late apoptotic cells decreased significantly with the serum from the resolved state compared to the active state of gallstone- and alcohol-induced pancreatitis. Serum samples from patients with pancreatitis induced a change in the apoptosis profiles of skin-derived cells. These results indicate changes in the serum components in patients with acute pancreatitis.

Pay attention to the effect of acute pancreatitis induced by microstones

In recent years, small biliary calculi attracted more attention in the cause of induced acute pancreatitis.However, routine clinical imaging studies is often difficult to find microstones in gallbladder, and the incidence rate of acute pancreatitis induced by microlithiasis of the gallbladder was obviously higher than other stones, and the state of illness is more serious.Therefore, it must be attached great attention.The research progress of acute biliary pancreatitis caused by small stones was reviewed in the study.It aimed to explore the influence of acute pancreatitis induced by minute biliary calculi and for clinical to prevent the occurrence of acute gallstone pancreatitis, thus to provide basis for prevention of acute pancreatitis and the effective treatment of the disease. Key words: Cholelithiasis; Pancreatitis

Weekend Effect in Acute Pancreatitis-Related Hospital Admissions in the United States: An Analysis of the Nationwide Inpatient Sample.

This study aimed to assess the difference in overall outcomes between weekend admissions for acute pancreatitis (AP) and weekday admissions. Between 2005 and 2012, data were extracted from the Nationwide Inpatient Sample on adult patients with AP. Exclusion criteria were applied for chronic pancreatitis and other pancreatic and biliary malignancies. In-hospital mortality, length of stay, hospitalization costs, comorbidities, complications, and intervention rates were compared between the weekend and weekday admissions. During the study period, there were a total of 432,303 weekday admissions and 147,435 weekend admissions for AP in the United States hospitals. Weekend AP admissions were more likely to develop alcohol withdrawal (5.9% vs 5.7%, P = 0.001) and ileus (4.1% vs 3.1%, P = 0.04). They were also more likely to develop acute respiratory distress syndrome (4.7% vs 4.4%, P < 0.001) and required more endotracheal intubation (3.9% vs 3.6%, P < 0.001). There was no significant in-hospital mortality difference between the weekend and weekday admissions on both univariate and multivariate analysis. Weekend AP admissions develop more severe complications requiring intensive care. Despite this, there was no weekend effect for in-hospital mortality for AP-related admissions.

Effect of acute pancreatitis on the risk of developing osteoporosis: A nationwide cohort study.

PurposeChronic exocrine pancreatic insufficiency can lead to osteoporosis. However, the incidence and risk of osteoporosis after acute inflammation of pancreas remained known. Thus, we conducted a population-based cohort study to clarify the association between acute pancreatitis (AP) and osteoporosis.MethodsPatients newly diagnosed with AP with index date between 2000 and 2011 were identified from the National Health Insurance Research Database. Osteoporosis were defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes. We applied age-, sex-, and comorbidities-adjusted variable Cox proportional hazard models for assessing the association between AP and osteoporosis. Moreover, these models were used to adjust for the influences of patient characteristics and comorbidities.ResultsIn this study, 4,016 patients were included in the AP cohort (males, 67.9%; mean age, 51.8 years) and 4,016 matched controls in the non-AP cohort. After a mean follow-up period of 4.97 and 5.21 years in the AP and non-AP cohorts, respectively, the incidence of osteoporosis was 8.22 per 1000 person-years in the AP cohort. The AP cohort had a higher risk [adjusted hazard ratio (aHR) = 1.27, 95% confidence interval (CI) = 1.02–1.58] of osteoporosis than did the non-AP cohort. The risk of osteoporosis was highest in the female patients of the AP cohort (aHR = 2.26, 95% CI = 1.85–2.76) and patients aged 50–64 years (aHR = 4.14, 95% CI = 3.13–5.47).ConclusionAP patients are at a risk of osteoporosis, especially female gender and age 50–64 years. Those with > 3 episodes of AP had highest significant risk of developing osteoporosis.

Effect of microemulsion formulation on biodistribution of 99mTc-Aprotinin in acute pancreatitis models induced rats

Background: Aprotinin is a monomeric globular polypeptide, which derived from bovine lung tissue and theoretically attractive molecule in ameliorating the effects of acute pancreatitis. Acute pancreatitis is an inflammatory condition of the pancreas that is painful and at times deadly. Over the following two decades Aprotinin therapeutic potential on pancreatitis is proven experimentally, its clinical therapeutic success is limited due to low targeting to pancreas.Objective: The aim of this study was to evaluate the biodistribution of Technetium-99m (99mTc)-Aprotinin solution (99mTc-Aprotinin-S) and 99mTc-Aprotinin loaded microemulsion, which was prepared for the aim of treatment for acute pancreatitis.Method: Aprotinin was radiolabeled with 99mTc. Radiochemical purity was determined with radioactive thin layer chromatography studies. 99mTc-Aprotinin-S and 99mTc-Aprotinin loaded microemulsion (99mTc-Aprotinin-M) was administered to acute edematous, severe necrotizing pancreatitis and air pouch model induced rats. Tissue distribution of Aprotinin was investigated with gamma scintigraphy and biodistribution studies.Results: Aprotinin was radiolabeled by 99mTc with high radiochemical purity (95.430 ± 0.946%). The complex was found to be stable at room temperature up to 6 h. Animal studies have shown that similar to that of other small proteins Aprotinin is accumulated primarily in the kidney. The scintigraphy and biodistribution studies showed that, while i.v. administration of 99mTc-Aprotinin-S distributed mostly in kidneys and bladder, 99mTc-Aprotinin-M, with droplet size of 64.550 ± 3.217 nm, has high uptake in liver, spleen and pancreas.Conclusion: This might be concluding that microemulsions may be suggested as promising formulations for selectively targeting Aprotinin to pancreas inflammation.

Mechanisms of interleukin-22's beneficial effects in acute pancreatitis.

Acute pancreatitis (AP) is a disorder characterized by parenchymal injury of the pancreas controlled by immune cell-mediated inflammation. AP remains a significant challenge in the clinic due to a lack of specific and effective treatment. Knowledge of the complex mechanisms that regulate the inflammatory response in AP is needed for the development of new approaches to treatment, since immune cell-derived inflammatory cytokines have been recognized to play critical roles in the pathogenesis of the disease. Recent studies have shown that interleukin (IL)-22, a cytokine secreted by leukocytes, when applied in the severe animal models of AP, protects against the inflammation-mediated acinar injury. In contrast, in a mild AP model, endogenous IL-22 has been found to be a predominantly anti-inflammatory mediator that inhibits inflammatory cell infiltration via the induction of Reg3 proteins in acinar cells, but does not protect against acinar injury in the early stage of AP. However, constitutively over-expressed IL-22 can prevent the initial acinar injury caused by excessive autophagy through the induction of the anti-autophagic proteins Bcl-2 and Bcl-XL. Thus IL-22 plays different roles in AP depending on the severity of the AP model. This review focuses on these recently reported findings for the purpose of better understanding IL-22's regulatory roles in AP which could help to develop a novel therapeutic strategy.

Effect of acute pancreatitis on the pharmacokinetics of Chinese herbal micron Liuhe Pill ointment in rats.

To explore the effect of acute pancreatitis (AP) on the pharmacokinetics of herbal ointment micron Liuhe Pill, MLHP) components in anesthetized rats. Rats were randomly divided into a AP model group (n=6) and a normal group as a control (n=6). The rat model of AP was induced by intraperitoneal injection of L-arginine in rats (15 mg/kg, twice, interval 1 h). Chinese herbal ointment MLHP was used externally on the belly after the 2nd injection for 48 h in both groups. Emodin, rhein, aloe emodin, physcion, chrysophanol from MLHP were detected and quantified in rat serum and pancreas (at 48 h) by high performance liquid chromatography-tandem mass spectrometry. Among the five components, only emodin, aloe emodin and physcion from MLHP were detected in all rat serum and most of the rats' pancreas. Rhein and chrysophanol were not detected in both serum and pancreas. T1/2α of emodin and physcion in MLHP were obviously shorter in the AP model group than those in the normal group (P<0.05), while there was no difference for T1/2α of aloe emodin. The peak concentration and area under curve of all three components were much higher in the AP group than those in the normal group with MLHP in external application for 48 h (P<0.05). Furthermore, the mean residence time (MRT) and maximum plasma concentration (Tmax) of emodin and aloe emodin were obviously longer in the AP model group than those in the normal control group (P<0.05). There was no significant difference for Ka of all components between the two groups. Emodin could be detected in all rats' pancreas at 48 h in both groups, while its mean pancreatic concentration was higher in the AP model group than in the normal group (0.61±0.54 ng/mL, 0.42±0.37 ng/mL, respectively,P<0.05). Aloe emodin could be detected in all rats' pancreas at 48 h in both groups and their mean pancreatic concentration were similar (0.31±0.24 ng/mL, 0.33±0.17 ng/mL, respectively,P>0.05). Physcion could be detected in pancreas of most rats in the AP model while only two rats in the normal group. AP could significantly affect the pharmacokinetics of absorbed components of Chinese herbal MLHP ointment in rats.

Expression and Purification of Serine Protease Inhibitor, OH-TCI, in &lt;i&gt;Escherichia coli&lt;/i&gt; as a Thioredoxin Fusion Protein

The OH-TCI was the first report of Kunitz/BPTI serine proteinase inhibitor from snake venom with strong inhibitory activity against trypsin and chymotrypsin. Thus it is theoretically attractive in ameliorating the effects of acute pancreatitis and reducing allogeneic blood product transfusion during cardiac surgery. To accomplish preclinical evaluation with OH-TCI, large-scale production of OH-TCI is produced in Escherichia coli. The optimized OH-TCI codons were cloned into pET32a (+). OH-TCI expressed as Trx tag is solubility as fusion bodies. The amount of the purified Trx-OH-TCI from 1 liter culture was roughly 200 mg. The inhibitor constants (Ki) of Trx-OH-TCI, similar to the native OH-TCI, were 2.67×10-7 and 3.60×10-7 M M for trypsin and chymotrypsin, respectively.

The SDF-1/CXCR4 axis regulates migration of transplanted bone marrow mesenchymal stem cells towards the pancreas in rats with acute pancreatitis

Stromal cell-derived factor-1 (SDF-1) and its receptor, CXC chemokine receptor-4 (CXCR4), are important regulators in the migration of bone marrow mesenchymal stem cells (BMSCs). However, the mechanisms underlying this effect in acute pancreatitis (AP) have not been investigated. In this study, BMSCs were identified by specific cell surface markers and differentiation potentials, and labeled with chloromethylbenzamido-1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (CM-Dil) for in vivo cell tracking. AP was induced by retrograde infusion of sodium taurocholate into the common bile duct in rats. The expression of SDF-1 in the injured pancreas was determined by immunohistochemistry and western blot analysis. BMSCs were incubated with or without anti-CXCR4 antibody and the contribution of SDF-1 to the migration of BMSCs was investigated. Our results demonstrated that the expression of SDF-1 was significantly increased in the injured pancreas, and that these levels peaked on days 5–7 and began to decrease on day 10. SDF-1 induced a dose-dependent migration of BMSCs in an in vitro transwell migration assay, which was almost completely blocked by AMD3100 (CXCR4-specific antagonist) or anti-CXCR4 antibody. In addition, by encouraging the migration of CM-Dil-labeled BMSCs, the SDF-1/CXCR4 axis facilitated the repair of the injured pancreas. This effect was inhibited by the anti-CXCR4 antibody. Taken together, these results indicate that the interaction of locally produced SDF-1 with CXCR4 on BMSCs, has an important regulatory role in the migration of BMSCs towards the injured pancreas in AP.

Is there a relationship between beginning time and efficiency of octreotide in the treatment of experimental acute pancreatitis?

PurposeThe efficacy of octreotide in the treatment of acute pancreatitis is controversial. Octreotide treatment for acute pancreatitis often shows poor correlation between results obtained in experimental studies and results of clinical trials. In a clinical setting, there is always a delay between the onset of the disease and initiation of the octreotide treatment. The aim of this study is to investigate the relationship between the beginning of treatment and alteration in effectiveness of octreotide.MethodsAcute pancreatitis was induced by pancreatic duct ligation in 50 rats. The rats were randomly divided into five groups. Octreotide was not used in group 1 (control group). Only single dose (4 µg/kg) octreotide was administered subcutaneously to rats in group 2, having induced pancreatitis. Octreotide treatment was begun at different times (8th, 24th, 48th hour) in three other groups and continued treatment at a dosage of 4 µg/kg t.i.d. The animals were sacrificed at the end of the 72nd hour and blood and tissue samples were collected.ResultsLeukocyte count and plasma amylase values were less in groups 2 and 3. Hemorrhagic focuses were encountered less at pancreas tissues in group 3. Pancreatic necrosis and alveolar capillary basal membrane damage were lower in groups 3 and 4. No difference was found in fasting blood glucose, calcium and hematocrit.ConclusionOctreotide had benefical effects in acute pancreatitis when octreotide treatment was begun in the first 24 hours.

Effects of Systemic Administration of a Local Anesthetic on Pain in Acute Pancreatitis

Intravenous local anesthetics may ameliorate pain and clinical course in patients with major abdominal surgery. To investigate their effects in acute pancreatitis. Forty-six consecutive patients with acute pancreatitis randomly received intravenous procaine (2 g/24 h) or placebo for 72 hours in a double-blind fashion. Pain severity (visual analog scale, 0-100), on-demand pain medication (metamizole and/or buprenorphine), and the clinical course were monitored every 24 hours. Data of 44 patients were subjected to intention-to-treat analysis. Although there were no differences between groups before treatment, procaine treatment was associated with a stronger decrease in pain compared with placebo (median visual analog scale decrement, -62 vs -39, P = 0.025). Moreover, there was a greater proportion of patients with adequate (≥ 67%) pain reduction (75% vs 43%, P = 0.018), less use of additional analgesics (P = 0.042), and overall analgesic superiority (P = 0.015). Compared with placebo, the proportion of patients hospitalized after 2 weeks was reduced by 80% after procaine treatment (P = 0.012). These findings support the hypothesis that systemic administration of local anesthetics might improve pain and accelerate clinical recovery in acute pancreatitis.

T1814 Autophagy Mediated By Transgenic Pancreas Expression of VMP1 Prevents the Severe Effects of Acute Pancreatitis in Mice

T1814 Autophagy Mediated By Transgenic Pancreas Expression of VMP1 Prevents the Severe Effects of Acute Pancreatitis in Mice

Dual, time-dependent deleterious and protective effect of anandamide on the course of cerulein-induced acute pancreatitis. Role of sensory nerves

Some recent studies indicate that cannabis may induce acute pancreatitis in humans and administration of anandamide increases the severity of acute pancreatitis; whereas another study exhibits some therapeutic effects in acute pancreatitis. Aim of the present study was to discover what is the reason for these opposite confusing results and to determine the role of sensory nerves in this effect. Acute pancreatitis was induced in rats by cerulein. Anandamide, an endogenous cannabinoid, was administered i.p. (1.5 μmol/kg) before or 2 h after cerulein administration. Stimulation of sensory nerves was performed by capsaicin (0.5 mg/kg s.c.). In rats treated with combination of anandamide plus capsaicin, capsaicin was given 10 min after each dose of anandamide. After the last injection of cerulein or 4 h later, the study was terminated. In our study we observed that stimulation of sensory nerves by capsaicin, before administration of cerulein, reduced the severity of acute pancreatitis. Anandamide, administered alone before cerulein, increased pancreatic damage in acute pancreatitis. Anandamide administered in combination with capsaicin, before cerulein, abolished the capsaicin-induced protective effect on the pancreas. Opposite effects were observed when capsaicin and anandamide were administered after injection of cerulein. Capsaicin increased the severity of acute pancreatitis, whereas anandamide reduced pancreatic damage and reversed the deleterious effect of capsaicin. We conclude that the effect of anandamide on the severity of acute pancreatitis depends on the phase of this disease. Administration of anandamide, before induction of pancreatitis, aggravates pancreatic damage; whereas anandamide administered after induction of pancreatitis, reduces the severity of acute pancreatitis. Sensory nerves are involved in the mechanism of this biphasic effect of anandamide.

膵と耳下腺の連関性に関する実験的研究 第1報 急性膵炎の耳下腺に及ぼす影響について (ラツト使用実験)

膵と耳下腺の連関性に関する実験的研究 第1報 急性膵炎の耳下腺に及ぼす影響について (ラツト使用実験)