Acute Pancreatitis Group Research Articles

The role of IL17-A in the second hit of acute pancreatitis

Background: Acute pancreatitis is characterised by distinct clinical phases. An initial systemic inflammation response syndrome (SIRS) and occasional subsequent ‘second hit’ usually initiated by systemic sepsis. The pro-inflammatory T-helper 17 pathway has been shown to be an initiator of early SIRS in AP, however to date interleukin-17A has not been evaluated as a marker of the septic second hit in SAP. Methods: Seventeen patients (aged 28-65) with mild (n=10), moderate (n=1) and severe (n=6) acute pancreatitis were enrolled. Peripheral blood samples were drawn on days 7, 9, 11 and 13 of illness for routine clinical markers as well as cytokine analysis. Flow cytometry was performed using a Th1/Th2/Th17 Cytokine Bead Array (BD Biosciences). Statistical analysis was performed using a Mann-Whitney U tests, with a p=value of <0.05 considered significant. Results: The mean concentration of IL-17A on days 7, 9, 11 and 13 in mild and severe acute pancreatitis patients were 2.45, 2.11, 2.12, 6.91 and 3.63, 3.48, 5.76, 3.56 pg/ml respectively, with no statistical significance between the two groups. Statistically significant differences exist between the mild and severe acute pancreatitis groups regarding the mean WCC (7.38 & 23.49), CRP (73.6 & 245.3) and PCT (0.37 & 20.7). Conclusion: The IL-17A concentration in the study population did not statistically identify the second hit of acute pancreatitis. Further studies to confirm this are underway.

The role of IL17-A in the second hit of acute pancreatitis

Background: Acute pancreatitis is characterised by distinct clinical phases. An initial systemic inflammation response syndrome (SIRS) and occasional subsequent ‘second hit’ usually initiated by systemic sepsis. The pro-inflammatory T-helper 17 pathway has been shown to be an initiator of early SIRS in AP, however to date interleukin-17A has not been evaluated as a marker of the septic second hit in SAP. Methods: Seventeen patients (aged 28-65) with mild (n=10), moderate (n=1) and severe (n=6) acute pancreatitis were enrolled. Peripheral blood samples were drawn on days 7, 9, 11 and 13 of illness for routine clinical markers as well as cytokine analysis. Flow cytometry was performed using a Th1/Th2/Th17 Cytokine Bead Array (BD Biosciences). Statistical analysis was performed using a Mann-Whitney U tests, with a p=value of <0.05 considered significant. Results: The mean concentration of IL-17A on days 7, 9, 11 and 13 in mild and severe acute pancreatitis patients were 2.45, 2.11, 2.12, 6.91 and 3.63, 3.48, 5.76, 3.56 pg/ml respectively, with no statistical significance between the two groups. Statistically significant differences exist between the mild and severe acute pancreatitis groups regarding the mean WCC (7.38 & 23.49), CRP (73.6 & 245.3) and PCT (0.37 & 20.7). Conclusion: The IL-17A concentration in the study population did not statistically identify the second hit of acute pancreatitis. Further studies to confirm this are underway.

Levels of TNF-α and IL-8 in patients with acute and chronic pancreatitis

The aim of the study was to research levels of TNF-α and IL-8 in patients with acute and chronic pancreatitis. The study included 86 patients with a confirmed diagnosis of acute edematous pancreatitis (group 1) and 36 patients with a confirmed diagnosis of chronic pancreatitis (group 2). Control group consisted of 70 conditionally healthy people, in whom laboratory and instrumental indices were determined similar to those in patients with acute and chronic pancreatitis. According to the aim and objectives of the study, we analyzed the levels of amylase, lipase, TNF-α and IL-8. The data was processed using the SPSS 20.0 statistical software package for Windows. Determined that the level of amylase in group 1 was significantly (p&lt;0.01) different from the same indicator in group 2 and in the control group. A similar trend was observed in the study of lipase levels in all groups. At the same time, there was no significant difference between the indicators of group 2 and the control group (p&gt;0.05). Regarding the levels of TNF-α, its highest rates were observed in group 1. In a statistical analysis, it turned out that the level of TNF-α was significantly higher (p&lt;0.05) in group 1 than in group 2 and the control group. The levels of IL-8 both in group 1 and group 2 were significantly higher (p&lt;0.01) than in the control group. At the same time, the value of this indicator also differed significantly in the statistical comparison of groups 1 and 2. Thus, in acute pancreatitis, the levels of TNF-α were significantly higher (p&lt;0.05) than in chronic pancreatitis, but its concentration did not correlate with other studied parameters. IL-8 levels progressively increase with an increase in the degree of activity of the inflammatory process, both in acute and in chronic pancreatitis, and correlates with an increase in such indicators as amylase and lipase in the acute form of the disease.

MIP-1α induces inflammatory responses by upregulating chemokine receptor 1/chemokine receptor 5 and activating c-Jun N-terminal kinase and mitogen-activated protein kinase signaling pathways in acute pancreatitis.

We aimed to investigate the association of macrophage inflammatory protein (MIP)-1α (CCL3) expression with the severity of acute pancreatitis (AP). The patients with AP were selected and divided into mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP) groups according to the severity of AP. The pancreatic acinar cell line Ar42 j was treated with cerulein to induce in vitro cell AP model. The expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and the activation of the c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) signaling pathway in stimulated or transfected Ar42 j cells were detected. We detected that the upregulation of MIP-1α was associated with the severity of AP. Patients with SAP showed the highest MIP-1α contents, followed by MSAP, and, lastly, MAP. In cerulein-stimulated Ar42 j cells, the upregulation of MIP-1α, CCR5, TNF-α, and IL-6 was time dependent. In addition, in human recombinant MIP-1α treated Ar42 j cells, the upregulation of TNF-α and IL-6 was MIP-1α-dose-dependent. In contrast, we detected the inhibition of TNF-α and IL-6 in MIP-1α small interfering RNA (siRNA)-treated cells. Also, the activation of the JNK/p38 MAPK signaling pathway was induced and inhibited by human recombinant MIP-1α and MIP-1α siRNA, respectively. These results suggested that MIP-1α might be used as a biomarker for the prognosis of AP severity. The MIP-1α-induced inflammatory responses in AP were mediated by TNF-α and IL-6, which were associated with the activation of the JNK/p38 MAPK signaling pathway.

Free Thyroxine Determination in the Emergency Department Is a Predictor of Acute Pancreatitis Evolution.

The aim of this study was to determine the prevalence and type of thyroid hormone levels alterations in patients with acute pancreatitis (AP) and analyze if variations are useful AP progression predictors. Three groups of patients were analyzed: AP patients (n = 90), abdominal pain patients (n = 30), and healthy control subjects (n = 40). Usual blood parameters for AP diagnosis and prognosis, thyroid-stimulating hormone (or thyrotropin), FT4 (free thyroxine), FT3 (free triiodothyronine), and TT3 (total triiodothyronine) levels were analyzed. Thyroid hormone level alterations were detected only within the AP group (41% of total cases), being the reduction in T3 levels the most frequently detected deviation (15.6% of FT3 and 8.3% of TT3 cases). Alterations were not influenced by age or sex. Free thyroxine average values were also significantly higher in the AP group, compared with the healthy control group (P = 0.0005), resulting as independent predictors of both severity and mortality. Mortality in this group was 50%, with deceased patients showing FT4 levels above the reference limit. Our results show that FT4 level determination during the initial clinical evaluation of patients admitted to the emergency service with AP can be included as a severity indicator to help determine the differential care of these cases.

Relationship between the neutrophil-to-lymphocyte ratio in acute pancreatitis and the severity and systemic complications of the disease.

In 80% of the patients, Acute pancreatitis (AP) occurs as a self-limiting disease that does not require any specific treatment; however, in 20% of the cases it occurs in its clinically severe form that may lead to local or systemic complications. The aim of this prospective study was to examine the relationship between the neutrophil to lymphocyte ratio (NLR) and the systemic complications and severity of AP. This prospective study included 100 patients with AP. Age, sex, NLR, Ranson scores and the revised Atlanta classification of the patients were recorded. The patients were divided into two groups according to the Ranson scores as mild and severe AP. According to the Revised Atlanta classification, the patients were divided into two groups as mild and moderate+severe AP. According to the Ranson score, NLR at the time of admission and at the 48th hour in the severe group was found to be statistically higher than the mild AP group (p<0.01). The receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off value of NLR at the emergency department in order for it to be used for distinguishing AP patients with and without systemic complications. The area under the ROC curve was 0.81. Sensitivity and specificity were 87.50% and 69.05%, respectively, when the NLR cut-off value was >7.13. Neutrophil to lymphocyte ratio is associated with severe AP. We also regard NLR as a valuable parameter for predicting the development of systemic complications in patients with AP.

Dynamic thiol/disulphide homeostasis in acute pancreatitis

The dynamic thiol/disulfide homeostasis plays pivotal roles in many physiological mechanisms in an organism. We aimed to investigate whether dynamic thiol/disulfide homeostasis changes among patients with acute pancreatitis. This prospective trial contained 45 patients with acute pancreatitis and 45 sex-and age-matched healthy volunteers as control group. Thiol/disulfide homeostasis parameters were measured by a novel and automated assay, and detected results were compared between the two groups. Disulfide/total thiol percent ratio and disulfide/native thiol percent ratios were significantly higher in acute pancreatitis group; besides the native thiol, total thiol levels and native thiol/total thiol percent ratios were significantly lower (for all p < 0.001). The thiol/disulfide homeostasis is impaired in acute pancreatitis with a shift toward the oxidative status, and this deficiency might be a pathogenic factor in acute pancreatitis. The correction of this thiol/disulfide imbalance may be a new target in the management of acute pancreatitis.

The identification and roles of microRNA targeting protein kinase D1 in rat with acute pancreatitis

Objective To predict and verify the upstream regulatory microRNA (miRNA) of protein kinase D1 (PKD1), and to investigate its role in cerulein induced acute pancreatitis (AP) in rats. Methods Potential upstream regulatory miRNA of PKD1 was predicted by using bioinformatics software.Dual luciferase reporter gene system and Western blot were applied to verify the regulation of PKD1 by the selected miRNA.Experimental AP was induced by 6 intraperitoneal injection of cerulein (20 μg/kg) at hourly intervals after administration of the CY5-labeled notarget control (AP group, n=20) or selected miRNA (treatment group, n=20), respectively by intraperitoneal injection into rats.Other rats were divided randomly into a normal control group (n=10) without any treatment.Besides 10 rats in either AP or treatment group were sacrificed 6 hours after the first injection of cerulein, and the rats were all sacrificed 24 hours after the first injection.The blood samples and pancreatic tissues of each rat were collected to test serum amylase and lipase activities, or to make hematoxylin-eosin stain for AP pathological scores as well as PKD1 immunohistochemical staining, respectively. Results TargetScan 7.1 software analysis showed that miR-128-3p was the potential upstream regulatory miRNA of PKD1, which was verified by dual luciferase reporter gene system and Western blot detection.Compared to the normal control group, serum amylase and lipase activities after 6 h exposure to cerulein increased in both AP group and the treatment group[13 313.00(9 424.00-15 995.00) U/L, 13 552.00(10 399.50-18 408.25) U/L vs.1 430.50(1 214.25-1 543.25) U/L; 547.00 (515.00-627.00) U/L, 857.50(522.00-1 222.25) U/L vs.34.00(32.50-34.75) U/L], and the differences were significant(χ2=8.715, P<0.05; χ2=9.115, P<0.05), which indicated that the rat models of AP were successfully established.The immunohistochemical scores of PKD1 after 24 h exposure to cerulein decreased in the treatment group[0.50(0-2.75) scores], compared with the normal control group [4.00(4.00-8.00) scores]and the AP group [4.00(3.75-8.00) scores], and difference was significant(χ2=18.302, P<0.05). Accordingly, the total pathological scores of HE staining decreased significantly in the treatment group, as compared to the AP group (3.80±0.85 vs.6.90±1.15, t=4.481, P<0.01). The results showed that the inflammatory cell infiltration and tissue necrosis were significantly improved after miR-128-3p treatment. Conclusions miR-128-3p is the upstream regulatory microRNA of PKD1 which protects pancreata from necrotic injury and inflammatory cell infiltration in PKD1-mediated acute pancreatitis. Key words: Acute pancreatitis; miR-128-3p; Protein kinase D1; Necrosis

The regulation mechanism of silencing the DUSP1 gene on the release of proinflammatory cytokines in mice with acute pancreatitis

Objective To investigate the regulation mechanism of silencing the DUSP1 gene on the release of proinflammatory cytokines in mice with acute pancreatitis(AP). Methods Two DUSP1-siRNA and one scramble siRNA sequences were designed, and the sequence with higher silence efficiency was selected.Mice models with AP were established, and KM mice were divided into 6 groups: control group, AP group, AP+ PD98059 group, AP+ scramble group, AP+ siRNA group and AP+ PD98059+ siRNA group.Expressions of proinflammatory cytokines tumor necrosis factor-α(TNF-α), interleukin(IL)-1β and IL-6 in serum were detected by using enzyme linked immunosorbent assay(ELISA) after 12 h, 24 h, 48 h of modeling.Serum amylase levels were detected.The mRNA expression levels of DUSP1, TNF-α, IL-1β and IL-6 in pancreatic tissues were detected by using quantitative real time polymerase chain reaction (qPCR). The protein expression levels of DUSP1, extracellular regulated protein kinases(ERK), c-Jun N-terminal kinase(JNK), p38, p-ERK, p-JNK and p-p38 in pancreatic tissues were detected by using Western blot. Results Compared with the control group, the other 5 groups displayed the increased expressions of TNF-α, IL-1β, IL-6 and amylase in serum, and expressions of DUSP1, TNF-α, IL-1β, IL-6, p-ERK, p-JNK, p-p38 in tissues, and there was a statistical significance (all P<0.05). Compared with the AP group, the AP+ PD98059+ siRNA group showed the decreased DUSP1 expression in tissues, and there was a statistical significance (all P<0.05); the AP+ PD98059 group had decreased expressions of TNF-α, IL-1β, IL-6 and amylase in serum, and expressions of TNF-α, IL-1β, IL-6, p-ERK, p-JNK, p-p38 in tissues, and there were statistical significances (all P<0.05); while the opposite results were observed in the AP+ siRNA group with DUSP1 expression decreased. Conclusions The results support that silencing the DUSP1 gene promotes the release of proinflammatory cytokines through activating the mitogen-activated protein kinase signaling pathway in mice with AP. Key words: Mitogen-activated protein kinase signaling pathway; Acute pancreatitis; Proinflammatory cytokines; Lentiviral vectors; DUSP1 gene

Relationship between somatostatin and interleukin-6: A cross-sectional study in patients with acute pancreatitis

ObjectivesThe aim of the analysis is to determine dynamic changes in somatostatin (SS) and interleukin-6 (IL-6) concentrations during in acute pancreatitis (AP). MethodsThe influence of tobacco smoking on IL-6 and SS levels in the serum of non-smoking (n = 10) and smoking (n = 27) patients with diagnosed AP and control group: non-smoking (n = 44), smoking (n = 42) and passive smoking (n = 29) healthy persons was proved. The concentration of IL-6 and SS was determined by means of ELISA. Differences between the groups analyzed were tested using the U Mann Whitney test. The Spearman rank correlation analysis was used to evaluate the correlations. ResultsThe concentrations of IL-6 and SS were significantly higher in smoking patients with AP and healthy persons when compared with non-smoking population on every day (1 day: p = 0.0002, p = 0.015; 3 day: p = 0.005, p = 0.001 and 7 day: p = 0.025, p = 0.038). Dynamic changes in concentrations of IL-6 and SS in the serum of patients with AP were demonstrated in the ensuing days of the disease. In case of non-smoking and smoking patients, significant positive correlations between IL-6 and SS was observed. ConclusionsThese findings suggest that some of the antiinflammatory effects of SS against acute pancreatitis may be mediated by reducing the local proinflammatory cytokine secretion in the pancreas.

Activity of TNF-α in patients with acute and chronic pancreatitis

The aim of the study was to study the activity of TNF-α in patients with acute and chronic pancreatitis. The study included 86 patients with a confirmed diagnosis of acute edematous pancreatitis (group 1) and 36 patients with a confirmed diagnosis of chronic pancreatitis (group 2). A separate control group consisted of 70 conditionally healthy people, in whom laboratory and instrumental indices were determined similar to those in patients with acute and chronic pancreatitis. According to the aim and objectives of the study, we analyzed the levels of amylase, lipase and TNF-α. The level of amylase in group 1 was 1664.1±185.2 U/L and was significantly (p&lt;0.01) different from the same indicator in group 2 (81.2±40.2 U/L) and in the control group (75.2±23.2 U/L). A similar trend was observed in the study of lipase levels in all groups. Thus, the level of lipase in group 1 was 1058.5±120.7 U/L and was significantly (p&lt;0.01) different from the same indicator in group 2 (37.6±22.1 U/L) and in the control group (42.7±13.8 U/L). At the same time, there was no significant difference between the indicators of group 2 and the control group (p&gt;0.05). Regarding the levels of TNF- α, its highest rates were observed in group 1 - 65.2±7.8 pg/mL. In group 2, the level of this marker was 52.5±6.2 pg/mL, and in the control group - 48.9±5.6 pg/mL. In a statistical analysis, it turned out that the level of TNF-α was significantly higher (p&lt;0.05) in group 1 than in group 2 and the control group. Although we noted an increase in the numerical index of the level of TNF-α in group 2, however, there was no significant difference between this indicator in group 2 and the control group (p&gt;0.05). So, in acute pancreatitis, the levels of TNF-α were significantly higher (p&lt;0.05) than in chronic pancreatitis, but its concentration did not correlate with other studied parameters.

The effects of different GSK-3β inhibitors and dose-response relationship in severe acute pancreatitis associated kidney injury in rats

Objective To observe the dose-response relationship of the GSK-3β inhibitor TDZD-8 in severe acute pancreatitis (SAP) associated kidney injury in rats. In order to identify the most effective class of GSK-3β inhibitor and its effective and reasonable safe dose in SAP associated kidney injury model in rats by comparing three kinds of frequently-used GSK-3β inhibitor TDZD-8, lithium chloride (LiCL), SB216763 in this model. Methods Totally 96 SPF male Wistar rats were randomly(random number) divided into 8 groups (n=12): sham operation group (SO group), severe acute pancreatitis group (SAP group), TDZD-8 pretreatment groups (TD group, marked TD1, TD2, TD3 and TD4 group, respectively) at different dosage (0.25, 0.5, 1.0 and 2.0 mg/kg), LiCL pretreatment groups (L group, 40 mg/kg), and SB216763 pretreatment group (SB group, 1 mg/kg). SAP model was induced by retrograde infusion of 5% sodium taurocholate into the biliopancreatic duct. Rats in each group were sacrificed at 12 h after operation. Then the mortality, quantity of ascites, serum AMY, Cr, BUN and ALT were recorded, and the pathological changes of pancreatic tissues and kidney tissues were observed. Results Compared with the SO group, the levels of ascites, serum AMY, Cr, BUN, ALT and pancreatic and renal pathologic score in the SAP group were all significantly increased (P 0.05), but the levels of AMY, Cr, BUN, ALT, pancreatic and renal pathologic score were significantly reduced in the TD3 group than those in the L and SB groups (P 0.05), while p-GSK-3β ser9 protein expression in the SAP group was lower than that in the SO group (P<0.05), and p-GSK-3β ser9 protein expression in the TD3, L and SB groups were stronger than that in the SAP group. Among them, p-GSK-3β ser9 protein expression was highest in the TD3 group, followed by the L group, finally the SB group, and the differences were statistically significant (P<0.05). Conclusions Among the three different GSK-3β inhibitors, TDZD-8 is the most effective GSK-3β inhibitor for SAP associated with kidney injury in rats. The GSK-3β inhibitor TDZD-8 1 mg/kg administered intravenously is safe, effective and optimal dosage for attenuating the severity of severe acute pancreatitis associated with kidney injury. Key words: Severe acute pancreatitis; Kidney injury; Glycogen synthase kinase-3β inhibitor; TDZD-8; Dose-response relationship

Acute pancreatitis and recurrent acute pancreatitis: an exploration of clinical and etiologic factors and outcomes

ObjectiveTo describe the epidemiology and clinical features of acute pancreatitis and recurrent acute pancreatitis in children. MethodsObservational and retrospective study with an analytical component. Patients were classified into two groups: Acute pancreatitis and recurrent pancreatitis. The relationship with each parameter obtained was analyzed using the chi-squared test, Student's t-test, or the Mann–Whitney U test. ResultsThere were 130 patients with acute pancreatitis; recurrent pancreatitis was diagnosed in 23.8% of the cases. The most frequent causes were anatomical (29.6%), pharmacological (19.2%), and biliary (14.6%), although in 29.2% etiology was not identified. Fasting lasted 3.5±3.8 days and parenteral nutrition was indicated in 26.9% of the cases for 10.8±11.3 days. A statistical association with anatomical (p=0.02) and pharmacological causes (p=0.01) was found in the recurrent pancreatitis group; no other differences between acute pancreatitis and recurrent pancreatitis groups were observed. The mortality rate was 3.1%, it was not attributable to acute pancreatitis in any cases. ConclusionAcute pancreatitis is associated with a high frequency of acute recurrent pancreatitis. Severity and complications did not show statistically significant differences in this investigation. Anatomical etiologies were the most relevant cause in this cohort. Fasting time and parenteral nutrition use were relevant. Genetics testing is required in this population.

Changes of angiopoietin-2 levels in serum of rats with acute pancreatitis

Objective To investigate dynamic changes of angiopoietin-2 (Ang-2) in acute pancreatitis (AP) and its significance. Methods Forty healthy SD rats were randomly divided into 5 groups: control group, acute pancreatitis model group (AP 6 h group, AP 12 h group, AP 24 h group and AP 48 h group). AP group were killed at 6, 12, 24 and 48 h after modeling. The control group was killed after the second injection of 24 hours. The levels of serum Ang-2, tumor necrosis factor-α (TNF-α), interleukin (IL-6) were detected by enzyme-linked immunosorbentassay (ELISA). The expression of phosphatidylinositol-3-hydroxy kinase (PI3K) and protein kinase B (PKB, Akt) mRNA expression levels were detected by Real-time polymerase chain reaction. Results The serum level of Ang-2 in the AP group was significantly higher than that in the control group(P=0.032). The expression of PI3K/Akt mRNA in pancreatic tissue of AP group was significantly higher than that in the control group (P=0.028), and the levels of TNF-α and IL-6 were significantly increased (P=0.026, 0.011). The level of Ang-2 in 6-24 h was positively correlated with Ang-2 mRNA in pancreas (r=0.392, P=0.034). The expression of PI3K and Akt was positively correlated with Ang-2 mRNA level (r=0.432, 0.451, P=0.029) and the levels of serum TNF-α and IL-6 were positively correlated with Ang-2 mRNA levels in pancreas (r=0.412, 0.389, P=0.035). Conclusion Serum Ang-2 level of AP groupis significantly higher than that of the control group. Ang-2 can activate PI3K/Akt signaling pathway and may be one of the reasons of high TNF-α and IL-6 levels in AP. SerumAng-2 level detectionmay provide the basis for early assessment of the severity of acute pancreatitis. Key words: Acute pancreatitis; Angiopoietin-2; Phosphatidylinositol-3-hydroxy kinase/protein kinase B; Serological examination

Resolvin D1 Resolve Inflammation in Experimental Acute Pancreatitis by Restoring Autophagic Flux.

Acute pancreatitis (AP) is a common acute gastrointestinal disorders. Increasing evidence indicated that autophagy is involved in the development of AP. Resolvin D1 is an endogenous pro-resolving lipid mediator, which can protect mice from cerulein-induced acute pancreatitis and facilitate autophagy in macrophage, but its mechanism remians unclear. To investigate the effect of resolvin D1 on autophagy in mouse models of cerulein-induced AP. C57BL/6 mice were randomly divided into control group, AP group and resolvin D1 group. The models of cerulein-induced AP were constructed by intraperitoneally cerulein. Resolvin D1 group was established by intraperitoneally resolvin D1 based on AP models, simultaneously, control group received normal saline. The severity of AP, the level of inflammatory cytokines, the number of autophagic vacuoles, and the expression of autophagy-related markers were evaluated among three groups. The AP models were established successfully. Compared to control group, the number of autophagic vacuoles and expressions of autophagy-related markers including Beclin-1, p62 and LC3-II were increased in AP models, In contrast, the degree of inflammation and levels of inflammatory cytokines in AP models were reduced after resolvin D1 treatment. Moreover, resolvin D1 attenuated the number of autophagic vacuoles and expressions of autophagy-related markers. Autophagic flux is impaired in cerulein-induced AP. Resolvin D1 ameliorate the severity of mice with cerulein-induced acute pancreatitis, possible attributing to its reducing impaired autophagy and restoring autophagic flux.

Single Nucleotide Polymorphisms in the Vitamin D Receptor Gene (VDR) May Have an Impact on Acute Pancreatitis (AP) Development: A Prospective Study in Populations of AP Patients and Alcohol-Abuse Controls.

Vitamin D imbalance is suggested to be associated with the development of pancreatitis. Single nucleotide polymorphisms (SNPs), Apa-1, Bsm-1, Fok-1, and Taq-1, in the vitamin D receptor gene (VDR) are known in various diseases, but not yet in pancreatitis. The aim of this study was to explore possible associations of the four SNPs in the VDR receptor gene in a population of acute pancreatitis patients and alcohol-abuse controls, and to investigate the association with acute pancreatitis (AP) susceptibility. The study population (n = 239) included acute pancreatitis patients (n = 129) and an alcohol-abuse control group (n = 110). All patients met the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria for alcohol dependence. DNA was extracted from peripheral leukocytes and analyzed for VDR polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis. To date, we have found allele T in Taq-1 (OR = 2.61; 95% CI: 1.68–4.03; p < 0.0001) to be almost three times more frequent in the AP group compared to the alcohol-abuse control patients. Polymorphism Taq-1 occurring in the vitamin D receptor may have an impact on the development of acute pancreatitis due to the lack of the protective role of vitamin D.

Хірургічне лікування гострого біліарного панкреатиту

Introduction. Despite the widespread of associated damage of the biliary system and the pancreas, a lot of issues of treatment tactics remain unresolved. There is no doubt that an adequate treatment of this pathology should combine the surgical and conservative components which will be determined by the peculiarities of the course of pathological processes in the bile ducts and in the pancreas.Materials and methods. A clinical examination and treatment of 126 patients with acute biliary pancreatitis have been performed. Men were 32 (25.4%), women – 94 (74.6%). There was isolated cholecystolithiasis in 65 patients with acute biliary pancreatitis (group 1). 35 patients were diagnosed small concrements in different parts of the common bile duct, which did not cause obstruction of the common bile duct (group 2). 26 patients were diagnosed obturating concretions of the common bile duct, including – impacted into a large duodenal papilla (third group).Results and their discussion. Clinical symptomatology, biochemical blood count, elevation of α-amylase, lipase, pancreatic α-amylase, and positive ACTIM Pancreatitis test allowed us to establish a preliminary diagnosis of acute pancreatitis. Ultrasound examination evaluated changes in the pancreas, but did not always fully describe the state of extrahepatic bile ducts. Magnetic resonance imaging (MRI) was used to fully characterize the pathology of the common bile duct, which made it possible to clearly identify the genesis of acute biliary pancreatitis. At the first stage of treatment, all diagnostic-therapeutic measures were performed during 24 hours. The absence of pathological inclusions in the common bile duct was determined in 80.0% of patients of group 1 using ultrasound examination. MRI was performed for 20.0% of patients. 25.7% of patients of group 2 needed MRI, and 74.3% – transpacillary endoscopic radiography. The ultrasound examination was effective only in 7.7% of patients of group 3. Other patients in this group to verify the cause of acute biliary pancreatitis required the use of other methods of radiotherapy. During 24 hours, laparoscopic cholecystectomy (LCE) was performed in 49 patients (75.4%) of group 1. Patients of groups 2 and 3 were performed endoscopic diagnostics and revision of extrahepatic biliary ducts, followed by LCE during 24 hours. 12 (9.5%) patients had complications related to the unfavorable course of the inflammatory process in the pancreas and peripanecratic tissue. The formation of false pancreatic cysts was diagnosed in 2 patients of group 1, in 3 patients – group 2 and in 2 patients – group 3. Taking into account their favourable course and the absence of laboratory and clinical data for their infection, these patients were recommended to follow dynamic observation in the outpatient settings. Abscesses of retroperitoneal space developed in 5 patients (group 2 – in 3 patients and group 3 – in 2 patients).Conclusion. Diagnostic tactics in acute biliary pancreatitis should include: determination of the activity of lipase, α- amylase, pancreatic α-amylase, ACTIM Pancreatitis test and MRI. Active surgical tactics involving LCE should be used in patients with acute biliary pancreatitis in cholecystolithiasis, and also endoscopic transpasillary decompression of the common bile duct in choledocholithiasis, within 24 hours of patient’s stay in the surgical department.

Effects of resolvin D1 on the autophagy in acute pancreatitis in mice

Objective To investigate the effects of resolvin D1 on autophagy in the prevention of acute pancreatitis (AP) in mice. Methods Thirty C57BL/6 mice were divided into control group, AP group and resolvin D1 group. AP model was established by intraperitoneal injection of cerulein at 50 μg·kg-1·h-1. Resolvin D1 was intraperitoneally given at 50 μg/kg one hour before and four hours after modeling. The mice of control group were intraperitoneally injected the same volume of 0.9% sodium chloride solution. The serum levels of amylase and lipase were measured by colorimetric method. The pathological injury of the lung and pancreatitis were observed under optical microscope. Autophagic vacuoles in acinar cells of pancreas of mice were evaluated by transmission electron microscope. And the expressions of autophagy related markers Beclin-1, p62 and LC3-Ⅱ at the mRNA and protein levels in pancreas of mice were detected by real time quantitative polymerase chain reaction (RT-qPCR) and Western blotting method. One-way analysis of variance and SNK-q were performed for statistical analysis. Results There were statistically significant differences in serum amylase and lipase levels between control group, AP group and resolvin D1 group (F=62.99 and 149.69, both P<0.01). The serum amylase and lipase levels of mice in resolvin D1 group were lower than those of AP group ((525.08±41.12) U/L vs. (752.62±42.03) U/L, (758.24±134.77) U/L vs. (1 201.06±112.53) U/L), and the differences were both statistically significant (both SNK-q test and P<0.01). In addition, there were statistically significant differences in the ratio of the pancreas and lung wet mass to body mass between control group, AP group and resolvin D1 group (F=11.36 and 18.51, both P<0.05). Pathological injury scores of pancreas and lung of resolvin D1 group were both lower than those of AP group (3.3±0.6 vs. 5.6±0.6, 5.4±0.5 vs. 8.8±0.4), and the differences were statistically significant (both SNK-q test and P<0.05). The results of transmission electron microscopy observation revealed that the number of autophagic vacuole of resolvin D1 group was less than that of AP group, and the size was smaller. Moreover, there were statistically significant differences in Beclin-1, p62 and LC3-Ⅱ mRNA between control group, AP group and resolvin D1 group (F=270.95, 151.83 and 124.77, all P<0.05). The relative expression mRNA levels of Beclin-1, p62 and LC3-Ⅱ of resolvin D1 group were 1.59±0.12, 2.75±0.27 and 1.34±0.14, respectively, which were lower than those of AP group (2.68±0.13, 3.32±0.30 and 3.37±0.26, respectively), and the differences were statistically significant (all SNK-q test and P<0.05). There were statistically significant differences in the expressions of Beclin-1, p62 and LC3-Ⅱat the protein level between control group, AP group and resolvin D1 group (F=116.63, 384.40 and 192.45, all P<0.05). The expressions of Beclin-1, p62 and LC3-Ⅱ at protein level of resolvin D1 group were 0.98±0.03, 0.57±0.04 and 0.31±0.03, respectively, which were lower than those of AP group (1.34±0.07, 1.02±0.03 and 0.48±0.04, respectively), and the differences were statistically significant (all SNK-q test and P<0.05). Conclusion Resolvin D1 ameliorates the severity of AP by attenuating the impaired autophagy and restoring autophagic flux in AP mice. Key words: Autophagy; Acute pancreatitis; Resolvin D1; Mice

Predictive value of serum cyclophilin A concentrations after acute pancreatitis

BackgroundCyclophilin A is identified as a biomarker for inflammation. We elucidated prognostic significance of serum cyclophilin A (CypA) concentrations in acute pancreatitis (AP). MethodsIn this prospective and observational study, serum CypA concentrations were quantified in 210 AP patients and 100 healthy controls. We recorded local complication, in-hospital mortality and organ failure. Disease severity was assessed using the traditional predictors, namely Acute Physiology and Chronic Health Care Evaluation II score, Ranson score, multiple organ dysfunction score and sequential organ failure assessment score. ResultsSerum CypA concentrations were significantly lower in controls than in AP group. CypA concentrations after AP were highly correlated with the traditional predictors and other inflammatory mediators, including blood erythrocyte sedimentation rate, procalcitonin levels, white blood cell count and C-reactive protein levels. Serum CypA emerged as an independent predictor for in-hospital local complication, organ failure and mortality. Under receiver operating characteristic curve, serum CypA possessed similar prognostic ability, as compared to the traditional predictors. Its predictive ability was almost similar to that of procalcitonin levels and significantly exceeded those of the other inflammatory mediators. Also, it significantly improved prognostic performance of the traditional predictors. ConclusionsIncreased serum CypA concentrations have close relation to the severity, inflammation and prognosis, substantializing CypA as a potential prognostic biomarker of AP.

Acute Pancreatitis After Laparoscopic Transcystic Common Bile Duct Exploration: An Analysis of Predisposing Factors in 447 Patients.

In laparoscopic transcystic common bile duct exploration (LTCBDE), the risk of acute pancreatitis (AP) is well recognized. The present study assesses the incidence, risk factors, and clinical impact of AP in patients with choledocholithiasis treated with LTCBDE. A retrospective database was completed including patients who underwent LTCBDE between 2007 and 2017. Univariate and multivariate analyses were performed by logistic regression. After exclusion criteria, 447 patients were identified. There were 70 patients (15.7%) who showed post-procedure hyperamylasemia, including 20 patients (4.5%) who developed post-LTCBDE AP. Of these, 19 were edematous and one was a necrotizing pancreatitis. Patients with post-LTCBDE AP were statistically more likely to have leukocytosis (p < 0.004) and jaundice (p = 0.019) before surgery and longer operative times (OT, p < 0.001); they were less likely to have incidental intraoperative diagnosis (p = 0.031) or to have biliary colic as the reason for surgery (p = 0.031). In the final multivariate model, leukocytosis (p = 0.013) and OT (p < 0.001) remained significant predictors for AP. Mean postoperative hospital stay (HS) was significantly longer in AP group (p < 0.001). The risk of AP is moderate and should be considered in patients with preoperative leukocytosis and jaundice and exposed to longer OT. AP has a strong impact on postoperative HS.