Effect of vaccines against pancreas disease in farmed Atlantic salmon.

Pancreas disease (PD) caused by salmonid alphavirus (SAV) continues to negatively impact salmon farming. To assess the effect on growth and mortality of three vaccines against PD, two controlled field designs were employed: one controlled field study with individual marked fish (PIT tag) assessing three PD vaccines and three controls groups, and a second controlled field study with group marked fish (Maxilla) comparing two PD vaccines against controls. In addition, a descriptive study using whole cages compared fish immunized with two different PD vaccines against controls. The target populations experienced a natural PD outbreak where both SAV 2 and SAV 3 were identified. Only one of the PD vaccines provided statistically significant improvements in harvest weight of 0.43 kg (CI: 0.29-0.57) and 0.51 kg (CI: 0.36-0.65) compared with the control in the PIT tag and the Maxilla study, respectively. In the latter, a significant reduction in mortality of 1.31 (CI:0.8-1.8) per cent points was registered for the same vaccine compared with controls. These results aligned with the growth and PD-specific mortality registered in the descriptive Cage study. The data in this study show a difference in the efficacy of PD vaccines in farmed Atlantic salmon.

New insight on the role of liraglutide in alleviating dexamethasone-induced pancreatic cytotoxicity via improving redox status, autophagy flux, and PI3K/Akt/Nrf2 signaling.

Chronic glucocorticoids therapy is commonly complicated by steroid diabetes, although the underlying mechanisms are still elusive. Liraglutide, a glucagon-like peptide-1, was initially found to induce glycemic control and recently it was found to have many pleotropic effects; however, its role in pancreas remains unknown. The present study aims to estimate the protective role of liraglutide on dexamethasone-induced pancreatic cytotoxicity and hyperglycemia, highlighting the possible underlying biochemical, molecular, and cellular mechanisms. Twenty-eight male Wistar rats were involved in this study and were randomly divided into four groups. Group III and IV were treated with 1 mg/kg dexamethasone daily for 10 days. Group II and IV were treated with liraglutide in a dose of 0.8 mg/kg per day for 2 weeks. Pancreatic caspase-9, nuclear factor erythroid 2-related factor 2 (Nrf2), phospho-protein kinase-B (pAkt), and sequestrome 1 (p62) levels were assessed by immunoassay. Moreover, phosphoinositide 3-kinase (PI3K) expression by real-time PCR, microtubule-associated protein light chain 3 (LC3B) expression by immunohistochemistry, glycemic status, ß-cell function by homoeostasis model assessment (HOMA) ß index, and pancreatic redox status were assessed. Liraglutide improved blood glucose level, ß-cell function, pancreatic caspase-9 level, redox status, and autophagy. Additionally, it increased pancreatic PI3K, pAkt, and Nrf2 levels. Moreover, preservation of pancreatic histological and the ultrastructural morphological features of ß- and α-cells were observed. In conclusion, liraglutide protected against dexamethasone-induced pancreatic injury and hyperglycemia and decelerated the progression towards steroid diabetes via activating PI3K/Akt/Nrf2 signaling and autophagy flux pathways.

Genetically modified attenuated salmonid alphavirus: A potential strategy for immunization of Atlantic salmon.

Pancreas disease (PD) is a serious challenge in European salmonid aquaculture caused by salmonid alphavirus (SAV). In this study, we report the effect of immunization of Atlantic salmon with three attenuated infectious SAV3 strains with targeted mutations in a glycosylation site of the envelope E2 protein and/or in a nuclear localization signal in the capsid protein. In a pilot experiment, it was shown that the mutated viral strains replicated in fish, transmitted to naïve cohabitants and that the transmission had not altered the sequences. In the main experiment, the fish were immunized with the strains and challenged with SAV3 eight weeks after immunization. Immunization resulted in infection both in injected fish and 2 weeks later in the cohabitant fish, followed by a persistent but declining load of the mutated virus variants in the hearts. The immunized fish developed clinical signs and pathology consistent with PD prior to challenge. However, fish injected with the virus mutated in both E2 and capsid showed little clinical signs and had higher average weight gain than the groups immunized with the single mutated variants. The SAV strain used for challenge was not detected in the immunized fish indicating that these fish were protected against superinfection with SAV during the 12 weeks of the experiment.

Effect of a novel DNA vaccine against pancreas disease caused by salmonid alphavirus subtype 3 in Atlantic salmon (Salmo salar).

Pancreas disease (PD) caused by salmonid alphavirus subtype 3 (SAV3) is a serious disease with large economic impact on farmed Norwegian Atlantic salmon production despite years of use of oil-adjuvanted vaccines against PD (OAVs). In this study, two commercially available PD vaccines, a DNA vaccine (DNAV) and an OAV, were compared in an experimental setting. At approximately 1040° days (dd) at 12 °C post immunization, the fish were challenged with SAV3 by cohabitation 9 days after transfer to sea water. Sampling was done prior to challenge and at 19, 54, and 83 days post-challenge (dpc). When compared to the OAV and control (Saline) groups, the DNAV group had significantly higher SAV3 neutralizing antibody titers after the immunization period, significantly lower SAV3 viremia levels at 19 dpc, significantly reduced transmission of SAV3 to naïve fish in the latter part of the viremic phase, significantly higher weight gain post-challenge, and significantly reduced prevalence and/or severity of SAV-induced morphologic changes in target organs. The DNAV group had also significantly higher post-challenge survival compared to the Saline group, but not to the OAV group. The data suggest that use of DNAV may reduce the economic impact of PD by protecting against destruction of the pancreas tissue and subsequent growth impairment which is the most common and costly clinical outcome of this disease.

Cucumis sativus and Cucurbita maxima extract attenuate diabetes-induced hepatic and pancreatic injury in a rat model.

Diabetes is usually associated with oxidative stress that causes hepatic and pancreatic tissue injury. This work was carried out to evaluate the effect of Cucumis sativus and Cucurbita maxima methanol extracts on the streptozotocin-induced diabetic hepatic and pancreatic injury in rats. Diabetes was induced in seven equal groups of rats by a single intraperitoneal injection of streptozotocin (40 mg/kg), in addition to the non-diabetic control group. Two diabetic groups were treated with Cucumis sativus methanol extract and two were treated with Cucurbita maxima, each at 200 and 400 mg/kg for 21 days after streptozotocin-induced diabetes. Another diabetic group was treated with both Cucumis sativus and Cucurbita maxima at 200 mg/kg of each. Another group was treated with metformin (200 mg/kg orally). The plant extracts normalized serum liver enzymes activities, oxidative stress markers, and restored serum proteins and lipid profile. They also significantly reduced blood sugar to values comparable to non-diabetic rats. The hypoglycemic effect is also confirmed by the improvement of the immunohistochemical expression of insulin in ß-cells of islets of Langerhans. Hepatic and pancreatic protection was also confirmed by the improvement of the histopathological picture as compared to STZ-diabetic rats. The GC-MS analysis revealed the presence of 35 and 34 compounds in the methanol extract of cucumber and pumpkin, respectively. Finally, the methanol extract of cucumber and pumpkin could be beneficial acting synergistically in the protection of the liver and pancreas against diabetes-induced tissue damage.

Effects of Pristine C60 Fullerenes on Liver and Pancreas in α-Naphthylisothiocyanate-Induced Cholangitis.

BACKGROUND: A significant role in pathogenesis of cholangitis is attributed to excessive reactive oxygen species production and oxidative stress. Therefore, antioxidants could be promising therapeutics. AIMS: The effects of powerful free radical scavenger C60 fullerene on hepatic and pancreatic manifestations of acute and chronic cholangitis in rats were aimed to be discovered. METHODS: Acute (AC, 3 days) and chronic (CC, 28 days) cholangitis models were simulated by single (AC) and 4 weekly (CC) α-naphthylisothiocyanate per os administrations. Pristine C60 fullerene aqueous colloid solution (C60FAS, 0.15 mg/ml, size of aggregates 1.2-100 nm) was administered either per os or intraperitoneally at a dose of 0.5 mg/kg C60 fullerene daily (AC) and every other day (CC). Prednisolone was used as a reference. Liver and pancreas autopsies were analyzed, and blood serum biochemical markers were measured. Pan-cytokeratin expression in HepG2 cells was assessed after 48-h incubation with C60FAS. RESULTS: On AC, C60FAS normalized elevated bilirubin, alkaline phosphatase, and triglycerides, diminished fibrotic alterations in liver, and improved pancreas state when applied by both ways. Additionally, C60FAS per os significantly reduced the signs of inflammation in liver and pancreas. On CC, C60FAS also mitigated liver fibrosis and inflammation, improved pancreas state, and normalized alkaline phosphatase and triglycerides. The remedy effect of C60FAS was more expressed compared to that of prednisolone on both models. Furthermore, C60FAS inhibited pan-cytokeratin expression in HepG2 cells in a dose-dependent manner. CONCLUSION: Pristine C60 fullerene inhibits liver inflammation and fibrogenesis and partially improved liver and pancreas state under acute and chronic cholangitis.

Fruit and vegetable consumption and health outcomes: an umbrella review of observational studies.

The aim of this study was to provide a comprehensive evaluation of current evidence on fruit and vegetable consumption and health outcomes. A systematic search for quantitative syntheses was performed. Several criteria, including study design, dose-response relationship, heterogeneity and agreement of results over time, and identification of potential confounding factors, were used to assess the level of evidence. The strongest (probable) evidence was found for cardiovascular disease protection; possible evidence for decreased risk of colon cancer, depression and pancreatic diseases was found for fruit intake; and colon and rectal cancer, hip fracture, stroke, depression and pancreatic diseases was found for vegetable intake. Suggestive and rather limited associations with other outcomes have been found. Evidence of potential confounding by sex and geographical localisation has been reported. Despite findings are consistent enough for hypothesising causation (at least for cardiovascular-related outcomes), further studies are needed to clarify the role of potential confounding factors.

Early local drug therapy for pancreatic contusion and laceration.

OBJECTIVES: To study the therapeutic effect of early local drug therapy on pancreatic contusion and laceration. METHODS: Twenty pigs were divided into 4 groups: model(PL), 1 ml of saline; medical protein glue (EC), 1 ml of medical protein glue; ulinastatin (UL), 50000U of ulinastatin; combined treatment (UE), 1 ml of medical protein glue and 50000U of ulinastatin. 30 min after model establishment, different groups received different local drug treatments. The pancreatic function, peritoneal effusion and pancreatic pathology were observed. RESULTS: The UE group got the best therapeutic effect. The changes of pancreatic function and the peritoneal effusion were compared with PL group as follows. 0-6h: amylase (p < 0.01), lipase (p > 0.05), effusion (p < 0.01); 6-12h: amylase (p > 0.05), lipase (p < 0.01), effusion (p < 0.01); 12-24h: amylase (p < 0.01), lipase (p < 0.01), effusion (p < 0.01). CONCLUSIONS: Early local drug therapy in pancreatic contusion and laceration could effectively control the development of the disease and improve the prognosis.

Prolonged retention of prophylactic pancreatic stents is not associated with increased complications.

OBJECTIVES: The risk of post-ERCP pancreatitis (PEP) can be reduced effectively by the placement of a self dislodging pancreatic stent. The present study analyzed whether a prolonged interval until stent passage evaluation and removal of retained stents is associated with an increased risk for clinically relevant complications. METHODS: In the retrospective study 182 patients receiving a pancreatic stent for PEP prophylaxis were included and clinical data and complications until documented spontaneous stent dislodgement or removal were analyzed. RESULTS: The main indication for ERCP was choledocholithiasis (40.1%) followed by malignant stenosis (30.8%). Stent passage evaluation was performed in 34.1% at day 1-4, 23.6% at day 5-10, 17.6% at day 11-28 and 24.7% at day >28. PEP occurred in 13.1% of patients with no case of severe PEP. No association between PEP and day of stent passage evaluation (p = 0.719), retention of the pancreatic stent at time of evaluation (0.867) or prolonged stent retention >10 days (0.234) was observed. Only the duration of the procedure was associated with risk for PEP (p = 0.037). Besides PEP only one clinically relevant complication was observed in the cohort (0.5%) which was a late possibly stent related pancreatitis at day 9 after the procedure that resolved completely. CONCLUSIONS: A prolonged interval for stent passage evaluation and stent retention is not associated with an increase of clinically relevant complications. A later evaluation and extraction of retained stents might be acceptable in selected cases where an additional endoscopic procedure can be saved due to a planned follow-up endoscopy.

Oligonol, a low-molecular-weight polyphenol derived from lychee peel, attenuates diabetes-induced pancreatic damage by inhibiting inflammatory responses via oxidative stress-dependent mitogen-activated protein kinase/nuclear factor-kappa B signaling.

This study investigated the effects of oligonol, a low-molecular-polyphenol derived from lychee peel, against diabetes-induced pancreatic damage via oxidative stress-induced inflammation. Oligonol was orally administered at 10 or 20 mg/kg body weight/day for 10 days to streptozotocin-induced diabetic rats, and the rats were compared with nondiabetic and diabetic control rats. The diabetic rats showed loss of body weight and increased pancreatic weight, and the oral administration of oligonol attenuated these parameters. Moreover, the administration of oligonol caused a significant decrease in the serum glucose level and a significant increase in the serum and pancreatic insulin and C-peptide levels in the diabetic rats. Oligonol also significantly reduced the enhanced levels of reactive oxygen species and 2-thiobarbituric acid reactive substance, which are oxidative stress biomarkers, in the serum and pancreas. Oligonol treatment reduced the overexpression of phospho-p38, phospho-ERK1/2, phospho-inhibitor of nuclear factor-kappa B (NF-κB), NF-κBp65, and NF-κBp65-induced inflammatory protein such as cyclooxygenase-2, inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-6. Furthermore, oligonol treatment led to significantly attenuated histological damage in the pancreas. On the basis of these results, we conclude that a plausible mechanism of oligonol's antidiabetic action may be its antioxidative stress-related anti-inflammatory action.

Pancreatic function and histoarchitecture in Wistar rats following chronic exposure to Bushfire®: the mitigating role of zinc.

Objectives To assess the toxicopathologic effects of chronic exposure to the glyphosate-based herbicide Bushfire® on the pancreas of Wistar rats and the protective role of zinc. Methods We exposed the rats to daily doses of 14.4 to 750 mg/kg body weight of the glyphosate-based herbicide Bushfire® and to 50 or 100 mg/kg zinc, and measured blood glucose levels and serum insulin levels. Tissue samples were evaluated for histopathological alterations. Results Levels of both blood glucose and serum insulin increased in glyphosate-exposed rats, and moderate to severe degenerative changes were observed in both glandular pancreatic acinar cells and islets of Langerhans in all rats exposed to glyphosate. These effects were prevented by pretreatment with zinc. Conclusion Chronic exposure to glyphosate can alter pancreatic function and histoarchitecture, but zinc supplementation can mitigate these toxicopathologic effects.

Molecular tracing confirms that infection with infectious pancreatic necrosis virus follows the smolt from hatchery to grow-out farm.

Infectious pancreatic necrosis (IPN) is an important restraint to production of salmonids in aquaculture globally. In order to implement efficacious mitigation strategies for control of this disease, it is important to understand infection routes under current production systems. IPN virus has been shown to be transmitted vertically in Rainbow trout, from broodstock to fingerlings in hatcheries, and there is circumstantial evidence suggesting that vertical transmission can also occur in Atlantic salmon, in addition to horizontal transmission between grow-out fish in farms. In this study, we show that the smolt carries infection with IPN from hatchery to the marine farm. We do this by comparing sequences from fish groups taken both in hatcheries and on corresponding marine grow-out farms. We use statistical analysis to prove that sequences obtained from the same fish group in both hatchery and marine farm are more similar than sequences obtained from random fish groups on hatcheries and marine farms.

Pancreatic duct obstruction after pancreaticojejunostomy: implications for early prediction and prevention of long-term pancreatic complications.

BACKGROUND: Pancreatic duct obstructions are common in patients with pancreaticoduodenectomy. However, it is often neglected in follow up. This study was to review the outcomes of pancreatic duct obstruction and explore the prevention of pancreatic duct obstruction. METHODS: A retrospective analysis of 78 patients undergoing pancreaticojejunostomy without reccurence of disease within 24 months between 2004 and 2014. Pancreatic duct obstruction and long-term pancreatic complications were analysed. RESULTS: Twenty-five patients developed pancreatic duct obstruction following pancreaticojejunostomy, 13 of whom were found to have long-term pancreatic complications. The presence of pancreatic duct obstruction and early pancreatic obstruction were associated with long-term pancreatic complications, respectively (p = 0.002, p = 0.002). There are 10 patients with pancreatic duct stent more than 24 months, the postoperative median pancreatic parenchymal thickness in these 10 patients (17.1 mm, range 8.0 to 24.7 mm) was not significantly change than the median in them preoperative (16.4 mm, range 7.2 to 24.7 mm; p = 0.747). All of them have no long-term pancreatic complications, though the difference was not significantly (p = 0.068). CONCLUSIONS: Early pancreatic duct obstruction is associated with postoperative pancreatic long-term complications. Sustained internal pancreatic stent may improve pancreatic duct obstruction.

Antifibrogenic effects of vitamin D derivatives on mouse pancreatic stellate cells.

AIM: To study the molecular effects of three different D-vitamins, vitamin D2, vitamin D3 and calcipotriol, in pancreatic stellate cells (PSCs). METHODS: Quiescent PSCs were isolated from mouse pancreas and activated in vitro by seeding on plastic surfaces. The cells were exposed to D-vitamins as primary cultures (early-activated PSCs) and upon re-culturing (fully-activated cells). Exhibition of vitamin A-containing lipid droplets was visualized by oil-red staining. Expression of α-smooth muscle actin (α-SMA), a marker of PSC activation, was monitored by immunofluorescence and immunoblot analysis. The rate of DNA synthesis was quantified by 5-bromo-2'-deoxyuridine (BrdU) incorporation assays. Real-time PCR was employed to monitor gene expression, and protein levels of interleukin-6 (IL-6) were measured by ELISA. Uptake of proline was determined using 18F-proline. RESULTS: Sustained culture of originally quiescent PSCs induced cell proliferation, loss of lipid droplets and exhibition of stress fibers, indicating cell activation. When added to PSCs in primary culture, all three D-vitamins diminished expression of α-SMA (to 32%-39% of the level of control cells; P < 0.05) and increased the storage of lipids (scores from 1.97-2.15 on a scale from 0-3; controls: 1.49; P < 0.05). No such effects were observed when Dvitamins were added to fully-activated cells, while incorporation of BrdU remained unaffected under both experimental conditions. Treatment of re-cultured PSCs with Dvitamins was associated with lower expression of IL-6 (-42% to -49%; P < 0.05; also confirmed at the protein level) and increased expression of the vitamin D receptor gene (209%-321% vs controls; P < 0.05). There was no effect of Dvitamins on the expression of transforming growth factor-ß1 and collagen type 1 (chain α1). The lowest uptake of proline, a main component of collagen, was observed in calcipotriol-treated PSCs. CONCLUSION: The three D-vitamins inhibit, with similar efficiencies, activation of PSCs in vitro, but cannot reverse the phenotype once the cells are fully activated.

Ethanolic extract of fenugreek seeds moderates dimethoate-induced pancreatic damage in male rats.

Dimethoate is a widely used organophosphate insecticide known to be toxic to the pancreas. The aim of this study is to detect the possible protective effects of the fenugreek seed ethanolic extract on the biochemical, histological, and ultra-structural abnormalities induced by dimethoate chronic exposure in the pancreas of adult male rats. The study was conducted on 50 adult male albino rats that were divided equally into 5 groups: (group I) negative control, (group II) vehicle control group, (group III) fenugreek-treated group that was given 400 mg/kg ethanolic fenugreek seed extract once daily, (group IV) dimethoate group received 20 mg/kg/day dimethoate, and (group V) dimethoate- + fenugreek-treated group received a combination of dimethoate and fenugreek in the same previous doses. Dimethoate treatment caused a significant increase in serum glucose, amylase, and lipase levels and a significant decrease in serum insulin. A significant increase in lipid peroxidation and pro-fibrotic cytokine (TGF-ß1) together with a significant reduction of the antioxidant {reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD)} activities and the anti-inflammatory (IL-4) in pancreatic tissues was also recorded. There was a histological and ultra-structural evidence of pancreatic acinar and islet cell injury. The recorded abnormalities were reversed in dimethoate+fenugreek treated group indicating that fenugreek ethanolic extract can serve as an antidote for dimethoate-induced pancreatic insult.

The potential role of gut microbiota in pancreatic disease: A systematic review.

BACKGROUND: Several studies have suggested a link between microbiota imbalance and some gastrointestinal, inflammatory and neoplastic diseases. However, the role in pancreatic diseases remain unclear. To evaluate the available evidence for pancreatic diseases, we undertook a systematic review. METHODS: OVID Medline (1946-2017), EMBASE (1980-2017) and the Cochrane Central Register of Controlled Trials (CENTRAL Issue 3, 2017) were searched for studies on microbiota in pancreatic disease. We also searched the reference lists of retrieved papers, and conference proceedings. We excluded animal studies, reviews, and case reports. RESULTS: A total of 2833 articles were retrieved. After screening and applying the exclusion criteria, 10 studies were included. Three studies showed lower levels of Bifidobacterium or Lactobacillus and higher levels of Enterobacteriaceae in chronic pancreatitis. Two of these studies were uncontrolled, and the third (controlled) study which compared patients with endocrine and exocrine insufficiency, reported that Bacteroidetes levels were lower in those patients without diabetes, while Bifidobacteria levels were higher in those without exocrine insufficiency. Only one study investigated acute pancreatitis, showing higher levels of Enterococcus and lower levels of Bifidobacterium versus healthy participants. There was an overall association between pancreatic cancer and lower levels of Neisseria elongate, Streptococcus mitis and higher levels of Porphyromonas gingivalis and Granulicatella adiacens. CONCLUSIONS: Current evidence suggests a possible link between microbiota imbalance and pancreatic cancer. Regarding acute and chronic pancreatitis, data are scarce, dysbiosis appears to be present in both conditions. However, further investigation is required to confirm these findings and to explore therapeutic possibilities.

Gastropancreatic ligament: Description, incidence, and involvement during laparoscopic sleeve gastrectomy.

During laparoscopic sleeve gastrectomy (LSG), adhesions between the stomach and the pancreas are sometimes found, forming a "gastropancreatic ligament" (GPL). However, the GPL has only been described once in the literature, in 1985. The objective of this study was to determine the incidence of the GPL during LSG, describe this structure and assess its effect on the surgical technique. All patients undergoing primary LSG in our institution (n = 240) and patients referred for gastric fistula (GF) after primary LSG (n = 18) between January 2015 and December 2015 were included. The primary endpoint was the incidence of a GPL during primary LSG. The secondary endpoints were the postoperative complication rate, the postoperative GF rate, and the presence of this ligament during reoperation for GF. Among the 240 patients, a GPL was visible in 49 cases (20.4%) and was described as thin in 34 of these (69.4%). Twelve postoperative complications (5%) were observed, including seven major (2.9%). The GF rate was 2% (n = 5), not requiring reoperation. The gastric stenosis rate was 0.4% (n = 1). The GPL had been previously sectioned in one of the five patients (20%) with postoperative GF. During the study period, 18 patients were referred for GF and 14 were reoperated. A non-sectioned GPL, not described in the operating report, was observed in four patients (28.5%). A GPL was identified in 20.4% of cases. Identification of a GPL could be important in the context of LSG, as section of the ligament allows tension-free stapling to be performed and can therefore possibly reduce the risk of postoperative complications, particularly GF. Clin. Anat. 30:336-341, 2017. © 2017 Wiley Periodicals, Inc.

A multicenter randomized controlled trial comparing pancreatic leaks after TissueLink versus SEAMGUARD after distal pancreatectomy (PLATS) NCT01051856.

BACKGROUND: Pancreatic leak is common after distal pancreatectomy. This trial sought to compare TissueLink closure of the pancreatic stump to that of SEAMGUARD. METHODS: A multicenter, prospective, trial of patients undergoing distal pancreatectomy randomized to either TissueLink or SEAMGUARD. RESULTS: Enrollment was closed early due to poor accrual. Overall, 67 patients were enrolled, 35 TissueLink and 32 SEAMGUARD. The two groups differed in American Society of Anesthesiologist class and diagnosis at baseline and were relatively balanced otherwise. Overall, 37 of 67 patients (55%) experienced a leak of any grade, 15 (46.9%) in the SEAMGUARD arm and 22 (62.9%) in the TissueLink arm (P = 0.19). The clinically significant leak rate was 17.9%; 22.9% for TissueLink and 12.5% for SEAMGUARD (P = 0.35). There were no statistically significant differences in major or any pancreatic fistula-related morbidity between the two groups. CONCLUSIONS: This is the first multicentered randomized trial evaluating leak rate after distal pancreatectomy between two common transection methods. Although a difference in leak rates was observed, it was not statistically significant and therefore does not provide evidence of the superiority of one technique over the other. Choice should remain based on surgeon comfort, experience, and pancreas characteristics.

Possible involvement of iNOS and TNF-α in nutritional intervention against nicotine-induced pancreatic islet cell damage.

Nicotine is the more abundant and most significant components of cigarette smoke. Epidemiological evidence strongly suggests an association between cigarette smoking and pancreatic injury. Although effects of smoking on endocrine pancreas are still controversial Here, we examined the impact and underlying mechanisms of action of folic acid and vitamin B12 on nicotine induced damage in pancreatic islets of rats. Male Wistar rats were treated with nicotine (3mg/kg body weight/day, intraperitonealy) with or without folic acid (36µg/kg body weight/day, orally) and vitamin B12 (0.63µg/kg body weight/day, orally) for 21days. Supplementation with folic acid and vitamin B12 suppressed the nicotine induced changes in HbA1c, insulin, TNF-α, IL-6, generation of reactive oxygen species, and attenuated the changes in markers of oxidative stress. Moreover, folic acid and vitamin B12 also counteracted the increased expression of protein and mRNA contents of TNF-α and iNOS produced by nicotine. Further, folic acid and vitamin B12 in combination limits the nicotine induced changes in cell cycle and excessive apoptosis of the pancreatic ß-cells and also successfully blunted the nicotine induced alteration in loss of mitochondrial membrane potential. In conclusion, data demonstrate that folic acid and vitamin B12 may be possible nutritional intervention against cellular oxidative stress, which is a critical step in nicotine-mediated islet injury, and improves islet cell functional status by scavenging free radicals and by inhibiting the generation of pro-inflammatory mediators.