Comparative study on the enzymatic degradation of phenolic esters: The HPLC-UV quantification of tyrosol and gallic acid liberated from tyrosol acyl esters and alkyl gallates by hydrolytic enzymes.

HPLC-UV analysis was used to evaluate the enzymatic degradation characteristics of tyrosol acyl esters (TYr-Es) and alkyl gallates (A-GAs). Among various hydrolytic enzymes, TYr-Es can be hydrolyzed by pancrelipase, while A-GAs cannot be hydrolyzed by pancrelipase. Interestingly, carboxylesterase-1b (CES-1b), carboxylesterase-1c (CES-1c) and carboxylesterase-2 (CES-2) are able to hydrolyze TYr-Es and A-GAs, and thus to liberate tyrosol (TYr) and gallic acid (GA). By contrast, the degrees of hydrolysis (DHs) of TYr-Es and A-GAs by CES-1b and CES-1c were significantly higher than those by CES-2. Meanwhile, the DHs of TYr-Es were much higher than those of A-GAs. Especially, the DHs firstly increased and then decreased with the increasing alkyl chain length. Besides, DHs positively correlated with the unsaturation degree at the same chain length. Through regulating carbon length, unsaturation degree and the ester bond structure, controlled-release of phenolic compounds and fatty acids (or fatty alcohols) from phenolic esters will be easily achieved.

Anti-Incretin Gut Features Induced by Feed Supplementation with Alpha-Amylase: Studies on EPI Pigs.

The acini-islet-acinar (AIA) axis concept justifies the anatomical placement of the Langerhans islets within the exocrine pancreatic parenchyma and explains the existence of the pancreas as a single organ. Amylase has been suggested to play a key role as an anti-incretin factor. Oral glucose tolerance tests (OGTT) were performed on 18 piglets in both a healthy (prior to pancreatic duct ligation (PDL) surgery, study Day 10) and an exocrine pancreatic insufficient (EPI) state (30 days after PDL, study Day 48)). Amylase (4000 units/feeding) or Creon® (100,000 units/feeding) was administered to pigs with the morning and evening meals, according to study design randomization, for 37 days following the first OGTT. Blood glucose levels, as well as plasma levels of insulin, GLP-1, and GIP, were measured, and the HOMA-IR index was calculated. EPI status did not affect the area under the curve (AUC) of insulin release, fasting insulin levels, or the HOMA-IR index, while amylase supplementation led to a significant (p < 0.05) decrease in the above-mentioned parameters. At the same time, EPI led to a significant (p < 0.05) increase in GLP-1 levels, and neither amylase nor Creon® supplementation had any effects on this EPI-related increase. Fasting plasma levels of GIP were not affected by EPI; however, the GIP response in EPI and Amylase-treated EPI animals was significantly lower (p < 0.05) when compared to that of the intact, healthy pigs. Orally administered amylase induces gut anti-incretin action, normalizing glucose homeostasis and reducing HOMA-IR as a long-term outcome, thus lowering the risk of diabetes type II development. Amylase has long-lasting anti-incretin effects, and one could consider the existence of a long-lasting gut memory for amylase, which decreases hyperinsulinemia and hyperglycemia for up to 16 h after the last exposure of the gut to amylase.

Exocrine Pancreatic Insufficiency Induced by Immune Checkpoint Inhibitors.

BACKGROUND: Scant data describe exocrine pancreatic insufficiency (EPI) secondary to immune checkpoint inhibitor (ICI) use. The goal of this study is to describe the incidence, risk factors, and clinical characteristics of patients with ICI-related EPI. PATIENTS AND METHODS: A single center, retrospective case-control study was performed of all ICI-treated patients at Memorial Sloan Kettering Cancer Center between January 2011 and July 2020. ICI-related EPI patients had steatorrhea with or without abdominal discomfort or weight loss, started pancrelipase after initiation of ICI, and demonstrated symptomatic improvement with pancrelipase. Controls were matched 2:1 by age, race, sex, cancer type, and year of ICI start. RESULTS: Of 12 905 ICI-treated patients, 23 patients developed ICI-related EPI and were matched to 46 controls. The incidence rate of EPI was 1.18 cases per 1000 person-years and the median onset of EPI was 390 days after the first dose of ICI. All 23 (100%) EPI cases had steatorrhea that improved with pancrelipase, 12 (52.2%) had weight loss, and 9 (39.1%) had abdominal discomfort; none had changes of chronic pancreatitis on imaging. Nine (39%) EPI patients had episodes of clinical acute pancreatitis preceding the onset of EPI, compared to 1 (2%) control (OR 18.0 (2.5-789.0), P < .001). Finally, the EPI group exhibited higher proportions of new or worsening hyperglycemia after ICI exposure compared with the control group (9 (39.1%) vs. 3 (6.5%), P < .01). CONCLUSION: ICI-related EPI is a rare but clinically significant event that should be considered in patients with late onset diarrhea after ICI treatment and often is associated with development of hyperglycemia and diabetes.

Noninvasive evaluation of donor and native pancreases following simultaneous pancreas-kidney transplantation using positron emission tomography/computed tomography.

It is crucial to develop practical and noninvasive methods to assess the functional beta-cell mass in a donor pancreas, in which monitoring and precise evaluation is challenging. A patient with type 1 diabetes underwent noninvasive imaging following simultaneous kidney-pancreas transplantation with positron emission tomography/computed tomography (PET/CT) using an exendin-based probe, [18 F]FB(ePEG12)12-exendin-4. Following transplantation, PET imaging with [18 F]FB(ePEG12)12-exendin-4 revealed simultaneous and distinct accumulations in the donor and native pancreases. The pancreases were outlined at a reasonable distance from the surrounding organs using [18 F]FB(ePEG12)12-exendin-4 whole-body maximum intensity projection and axial PET images. At 1 and 2 h after [18 F]FB(ePEG12)12-exendin-4 administration, the mean standardized uptake values were 2.96 and 3.08, respectively, in the donor pancreas and 1.97 and 2.25, respectively, in the native pancreas. [18 F]FB(ePEG12)12-exendin-4 positron emission tomography imaging allowed repeatable and quantitative assessment of beta-cell mass following simultaneous kidney-pancreas transplantation.

Validation of an omega-3 substrate challenge absorption test as an indicator of global fat lipolysis.

INTRODUCTION: The coefficient of fat absorption (CFA) quantifies fat that remains in stool after digestion and is not a direct measure of lipolysis. CFA has been used to assess treatment of pancreatic insufficiency but does not correlate with pancreatic enzyme replacement therapy dose. We explored use of an omega-3 substrate absorption challenge test as a sensitive test of lipolysis and absorption. METHODS: We studied a novel microbially-derived lipase (SNSP003) employing an established surgical model commonly used to study the uptake of macronutrients, the exocrine pancreatic insufficient pig. Pigs were fed a high-fat diet and given a standardized omega-3 substrate challenge to test the effect of lipolysis on its absorption. Blood was drawn at 0, 1, 2, 4, 6, 8, 12, and 24 hours following the substrate challenge and was analyzed for omega-3 and total fat levels (c14:c24). SNSP003 was also compard to porcine pancrelipase. RESULTS: The absorption of omega-3 fats was significantly increased following administration of 40, 80 and 120 mg SNSP003 lipase by 51% (p = 0.02), 89%, (p = 0.001) and 64% (p = 0.01), respectively, compared to that observed when no lipase was administered to the pigs, with Tmax at 4 hours. The two highest SNSP003 doses were compared to porcine pancrelipase and no significant differences were observed. Both doses increased plasma total fatty acids (141% for the 80 mg dose (p = 0.001) and 133% for the 120 mg dose (p = 0.006), compared to no lipase) and no significant differences were observed between the SNSP003 lipase doses and porcine pancrelipase. CONCLUSION: The omega-3 substrate absorption challenge test differentiates among different doses of a novel microbially-derived lipase and correlates with global fat lipolysis and absorption in exocrine pancreatic insufficient pigs. No significant differences were observed between the two highest novel lipase doses and porcine pancrelipase. Studies in humans should be designed to support the evidence presented here that suggests the omega-3 substrate absorption challenge test has advantages over the coefficient of fat absorption test to study lipase activity.

The effects of hydroxytyrosol on Prdx6 and insulin expression in diabetic rat pancreases.

Diabetes mellitus is a widespread endocrine disease worldwide, accompanying chronic hyperglycemia. In this study, we investigated the effect of hydroxytyrosol, which exerts an antioxidant effect, on the expressions of insulin and peroxiredoxin-6 (Prdx6), which protect cells against oxidative injury in diabetic rat pancreas. This experimental study had four groups with ten animals in each group: control (nondiabetic) group, hydroxytyrosol group [10 mg/kg/day intraperitoneal injection (ip) hydroxytyrosol for 30 days], streptozotocin group (single ip injection of 55 mg/kg streptozotocin), and streptozotocin + hydroxytyrosol group (single ip injection of streptozotocin and ip injection of 10 mg/kg/day hydroxytyrosol for 30 days). During the experiment, blood glucose levels were measured at regular intervals. Insulin expression was determined by immunohistochemistry and Prdx6 expression was determined by immunohistochemistry and western blot. Immunohistochemistry and western blot results were analyzed by one-way ANOVA with applied Holm-Sidak multiple comparison test, and blood glucose results were analyzed by two-way repeated measures ANOVA with applied Tukey's multiple comparison test. Blood glucose levels on days 21 and 28 were significantly lower in the streptozotocin + hydroxytyrosol group compared with the streptozotocin group (day 21, p = 0.049 and day 28, p = 0.003). Expression of both insulin and Prdx6 were lower in the streptozotocin and the streptozotocin + hydroxytyrosol groups compared with the control and hydroxytyrosol groups (p < 0.001). Insulin and Prdx6 expression in the streptozotocin + hydroxytyrosol group were higher compared with the streptozotocin group (p < 0.001). The immunohistochemical findings of Prdx6 and western blot were the same. In conclusion, hydroxytyrosol, which is an antioxidant compound, increased Prdx6 and insulin expression in diabetic rats. Insulin increased by hydroxytyrosol may have been effective in reducing blood glucose levels. Furthermore, hydroxytyrosol may exert its effect on insulin by increasing Prdx6 expression. Thus, hydroxytyrosol may decrease or prevent several hyperglycemia-dependent complications by increasing the expression of these proteins.

Efficacy of a Viokace Pancreatic Enzyme Protocol for Clearing Occluded Enteral Feeding Tubes: A Quality Assurance Evaluation.

Background: A previous retrospective study documented restored patency to 48.2% of occluded enteral feeding tubes using alkalinized Creon pancreatic enzyme capsules. In light of the low efficacy rate, the institutional enteral feeding tube clearance protocol was subsequently revised to incorporate a newly marketed non-enteric-coated Viokace pancreatic enzyme tablet, despite the lack of published data for this indication. Objective: This study aims to evaluate the effectiveness of a Viokace-based alkalinized pancreatic enzyme protocol to clear occluded enteral feeding tubes in a university health system. Methods: This retrospective, cohort quality assurance study included adult and pediatric patients receiving a Viokace-based pancreatic enzyme protocol for enteral feeding tube occlusions in a university health system during a 12-month period. The primary outcome was effectiveness in enteral tube clearance as documented in the electronic medical record. Efficacy of the new protocol was also compared with a Creon-based alkalinized solution using historical data. Results: The Viokace protocol successfully cleared 176 of the 277 (63.5%) occluded enteral feeding tubes occurring in 205 patients included in the analysis. The revised protocol was significantly more effective at clearing occluded enteral feeding tubes (P = 0.0056) than a protocol using Creon pancreatic enzyme capsules. Conclusion: According to this retrospective evaluation, an alkalinized Viokace pancreatic enzyme protocol was effective in clearing 63.5% of occluded enteral feeding tubes. This significantly higher success rate than previously documented with a Creon-based protocol supports the change in pancreatic enzyme formulations in the institutional protocol.

In vitro evaluation of the gastrointestinal delivery of acid-sensitive pancrelipase in a next generation enteric capsule using an exocrine pancreatic insufficiency disease model.

The dissolution characteristics of five capsules (Next Generation Enteric [NGE], Vcaps® Enteric [VCE], VCE DUOCAP® [VCE/VCE] system, Hard Gelatin Capsule [HGC] as negative control, and Creon® 10,000 U as market reference) were evaluated using an in vitro simulation of the stomach and upper intestinal tract with an acidic duodenal incubation (pH 4.5 for the first 10 min, pH 6 for the remaining 17 min) to simulate exocrine pancreatic insufficiency. Caffeine was a marker of capsule dissolution, and tributyrin to butyrate conversion measured pancrelipase activity. All capsules were filled with pancrelipase; the NGE, VCE, VCE/VCE, and HGC capsules also contained 50 mg caffeine. Caffeine was released first from the HGC capsule, followed by the VCE, NGE, and VCE/VCE capsules. Pancrelipase activity followed this trend and demonstrated a similar activity level over time for the NGE, VCE/VCE, and Creon® capsules. The HGC formulation confirmed gastric degradation of unprotected pancrelipase. NGE capsules provided similar protection to the simple fill formulation as observed for the complex formulation of the Creon® capsule in a setting with increased pepsin activity and may hasten the time needed to go from formula development to first-in-human studies for pH sensitive drugs or those requiring small intestine targeting.

MIRAGE Syndrome Enteropathy Responding to Pancrelipase Despite Normal Pancreatic Fecal Elastase: A Case Report.

BACKGROUND Major findings of myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy (MIRAGE) syndrome is a rare genetic condition caused by a gain-of-function mutation in the SAMD9 gene. It acts as a growth repressor expressed in the endothelial cells. Pathogenic variants in the SAMD9 gene lead to profound growth-restricting activity intrinsic to the protein, which further reduces cellular proliferation and instigates this growth-limiting condition. Gastrointestinal features include chronic diarrhea, severe diaper rash, and colonic dilatation. Until now, there has been no description of exocrine pancreatic insufficiency as a possible cause of enteropathy in MIRAGE syndrome. CASE REPORT We report a case of MIRAGE syndrome affecting multiple systems in an infant who had severe enteropathy which responded well to porcine-derived pancreatic enzyme supplements despite normal pancreatic fecal elastase level. The infant is being followed up by multidisciplinary teams in our outpatient department. CONCLUSIONS Porcine-derived pancreatic enzyme is beneficial in enteropathy due to MIRAGE syndrome and is worth considering.

Aggressive Intervention of Pancrelipase After Pancreatectomy Prevents Deterioration of Postoperative Nutritional Status.

OBJECTIVES: This study aimed to investigate the effect of early administration of delayed-release high-titer pancrelipase. METHODS: The medical records of 120 patients who had undergone pancreatectomy with computed tomography (CT) before and 6 months after surgery were retrospectively reviewed. Delayed-release high-titer pancrelipase were administered daily starting on postoperative day 3, which was defined as the EP group. The postoperative nutritional status and CT attenuation values of the liver were compared between the EP and control groups. RESULTS: Thirty-three patients (28%) were categorized into the EP group. With regard to the postoperative nutritional status 6 months after surgery, the body mass index, total lymphocyte count, and Onodera's prognostic nutritional index were higher, and controlling nutritional status score was lower in the EP group than that in the control group. The CT attenuation values of the liver were not significantly different. After propensity score matching analysis, body mass index (20.7 vs 19.2, P = 0.049) and Onodera's prognostic nutritional index (47.9 vs 44.2, P = 0.045) were significantly higher, and controlling nutritional status score was significantly lower in the EP group than that in the control group (1 vs 3, P = 0.046). CONCLUSIONS: The early administration of pancrelipase after pancreatectomy improved nutritional status after pancreatectomy.

Impact of Pancreatic Enzymes on Enteral Fat and Nitrogen Absorption in Short Bowel Syndrome.

OBJECTIVES: Patients with short bowel syndrome (SBS) can have a high morbidity rate. To minimize morbidity, enteral autonomy is the primary goal in clinical management of patients with SBS. This is often difficult to achieve because of significant malabsorption. To date, there are limited therapies that improve absorption in patients with SBS. The impact of pancreatic enzyme replacement treatment on enteral absorption has not been studied in this population and was the primary aim of this study. SUBJECTS/METHODS: This was an interventional study in 11 subjects (6 pediatric subjects ages 4.0-17.9 years, 5 adult subjects 18-75 years) that compared enteral absorption in each subject before and after pancreatic enzyme medication (Creon). Coefficient of fat absorption (CFA) and coefficient of nitrogen absorption (CNA) were used as markers of enteral absorption of fat and protein, respectively. RESULTS: There was no statistically significant mean change in CFA and CNA before and after pancreatic enzyme medication therapy. Six subjects demonstrated an increase in CFA and 8 subjects demonstrated an increase in CNA after the use of pancreatic enzyme medication therapy. CONCLUSIONS: There was no statistically significant improvement in enteral fat and protein absorption in the cohort as a whole, though several subjects demonstrated an improvement. These results suggest that some patients with SBS may benefit from treatment with pancreatic enzymes. Further studies are needed to better evaluate the effect of pancreatic enzyme therapy on enteral absorption in subjects with SBS and to characterize factors that may predict a positive response.

The effect of HTLV1 infection on inflammatory and oxidative parameters in the liver, kidney, and pancreases of BALB/c mice.

Viral infections are linked to the progression of inflammatory reactions and oxidative stress that play pivotal roles in systemic diseases. To confirm this phenomenon, in the present study, TNF-α level and oxidative stress markers were examined in the liver, kidney, and pancreas of HTLV1-infected male BALB/c mice. To this end, twenty BALB/c mice were divided into HTLV1-infected mice that were inoculated with 1-million HTLV1-infected cells (MT-2), and the control groups. Two months after inoculation, the peripheral blood, mesenteric lymph nodes, liver, kidney, and pancreas were collected after deep anesthetization of mice (ketamine, 30 mg/kg). The extracted DNA of mesenteric lymph nodes was obtained to quantify proviral load (PVL) using quantitative real-time polymerase chain reaction (qRT-PCR). The levels of lipid peroxidation, total thiol (SH), nitric oxide (NO), TNF-α, catalase (CAT), and superoxide dismutase (SOD) activities were examined in the liver, kidney, and pancreases. Furthermore, histopathological changes in the liver and kidney were evaluated. In liver tissue, the levels of MDA, TNF-α, and blood cell infiltration were significantly increased, and the levels of CAT and SOD were significantly decreased. In the kidney, a reduction in SOD, CAT, and total SH and an increase in MDA and NO were observed. In the pancreas, CAT activity, total SH, and SOD were decreased, and the levels of MDA and NO were enhanced. In terms of TNF-α production, it has been shown that the level of this inflammatory cytokine was increased in the liver, kidney, and pancreas. The HTLV1 may have a role in inducing inflammatory reactions and oxidative stress pathways in the tissues.

Feasibility and Reproducibility of Multifrequency Magnetic Resonance Elastography in Healthy and Diseased Pancreases.

BACKGROUND: The feasibility and reproducibility of multifrequency MR elastography (MRE) for diagnosing pancreatic ductal adenocarcinoma (PDAC) have not been reported. PURPOSE: To determine the feasibility and reproducibility of multifrequency MRE for assessing pancreatic stiffness in healthy and diseased pancreases. STUDY TYPE: Prospective. SUBJECTS: A total of 40 healthy volunteers and 10 patients with PDAC were prospectively recruited between March 2018 and October 2021. FIELD STRENGTH/SEQUENCE: A 3.0-T pancreatic MRE at frequencies in the order of 30, 40, 60, 80, and 100 Hz. ASSESSMENT: Body mass index (BMI) and wave distance of the healthy pancreas and PDAC were measured. Image quality was assessed using the image quality score (IQS: 1-4, ≥3 were considered diagnostic quality). Three readers independently performed the pancreatic stiffness and IQS assessments to evaluate reproducibility. STATISTICAL TESTS: Logistic regression analyses were performed to determine variables that influenced IQS. Statistical significance was set at P <0.05. Levels of inter- and intrarater agreement were assessed using intraclass correlation coefficients (ICC) and Cohen's kappa coefficient (κ). Good reproducibility was set at ICC and κ ≥ 0.8. RESULTS: In logistic regression analysis, a diagnostic IQS in healthy volunteers was independently associated with a lower BMI (odds ratio [OR] = 0.89 kg/m-2 ), shorter wave distance (OR = 0.70 cm-1 ), and lower frequency (30 and 40 Hz: OR = 170.01 and 96.02). In PDAC, frequency was the only independent factor for diagnostic IQS (30-60 Hz: OR = 46.18, 46.18, and 17.20, respectively) with 100 Hz as a reference. In healthy volunteers, good reproducibility was observed at 30 and 40 Hz. In PDAC, good reproducibility was observed at 30-60 Hz. DATA CONCLUSION: MRE at 30 and 40 Hz provides diagnostic wave images and reliable measurements of pancreatic stiffness in healthy volunteers. MRE at 30-60 Hz is acceptable for PDACs (IQS ≥ 3, ICC and κ ≥ 0.80). EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

A Retrospective Real-World Evidence Evaluation of the Characteristics of Exocrine Pancreatic Insufficiency in Patients With Chronic Pancreatitis and Type 2 Diabetes Treated With Pancrelipase in the United States.

OBJECTIVES: This retrospective real-world data analysis assessed clinical/health care professional characteristics of gastrointestinal symptom profiles in pancrelipase-treated patients with exocrine pancreatic insufficiency symptoms and chronic pancreatitis (CP) or type 2 diabetes (T2D). METHODS: Data were from the Decision Resources Group Real-World Evidence Data Repository US database. Patients 18 years and older receiving pancrelipase (Zenpep) between index dates August 2015 and June 2020 were included. Gastrointestinal symptoms were assessed 6, 12, and 18 months post-index versus baseline. RESULTS: A total of 10,656 pancrelipase-treated patients with CP (n = 3215) or T2D (n = 7441) were identified. Significant/sustained reductions in gastrointestinal symptoms were observed in both cohorts after pancrelipase treatment (P < 0.001) versus baseline. Significantly fewer patients with CP compliant with treatment for more than 270 days (n = 1553) reported abdominal pain (P < 0.001) and nausea/vomiting (P < 0.05) versus those compliant for less than 90 days (n = 1115). Significantly fewer patients with T2D compliant with treatment for more than 270 days (n = 2964) reported abdominal pain (P < 0.001) and diarrhea/steatorrhea (P < 0.05) versus those compliant for less than 90 days (n = 2959). CONCLUSIONS: Pancrelipase reduced exocrine pancreatic insufficiency symptoms in patients with CP or T2D, with greater treatment compliance associated with improved gastrointestinal symptom profiles.

Centranthus ruber (L.) DC. and Tropaeolum majus L.: Phytochemical Profile, In Vitro Anti-Denaturation Effects and Lipase Inhibitory Activity of Two Ornamental Plants Traditionally Used as Herbal Remedies.

Ornamental plants often gain relevance not only for their decorative use, but also as a source of phytochemicals with interesting healing properties. Herein, spontaneous Centranthus ruber (L.) DC. and Tropaeolum majus L., mainly used as ornamental species but also traditionally consumed and used in popular medicine, were investigated. The aerial parts were extracted with methanol trough maceration, and resultant crude extracts were partitioned using solvents with increasing polarity. As previous studies mostly dealt with the phenolic content of these species, the phytochemical investigation mainly focused on nonpolar constituents, detected with GC-MS. The total phenolic and flavonoid content was also verified, and HPTLC analyses were performed. In order to explore the potential antiarthritic and anti-obesity properties, extracts and their fractions were evaluated for their anti-denaturation effects, with the use of the BSA assay, and for their ability to inhibit pancreatic lipase. The antioxidant properties and the inhibitory activity on the NO production were verified, as well. Almost all the extracts and fractions demonstrated good inhibitory effects on NO production. The n-hexane and dichloromethane fractions from T. majus, as well as the n-hexane fraction from C. ruber, were effective in protecting the protein from heat-induced denaturation (IC50 = 154.0 ± 1.9, 270.8 ± 2.3 and 450.1 ± 15.5 µg/mL, respectively). The dichloromethane fractions from both raw extracts were also effective in inhibiting pancreatic lipase, with IC50 values equal to 2.23 ± 0.02 mg/mL (for C. ruber sample), and 2.05 ± 0.02 mg/mL (T. majus). Obtained results support the traditional use of these species for their beneficial health properties and suggest that investigated plant species could be potential sources of novel antiarthritic and anti-obesity agents.

Polysaccharides from mulberry (Morus alba L.) leaf prevents obesity by inhibiting pancreatic lipase in high-fat diet induced mice.

Pancreatic lipase (PL) is a key enzyme related to the prevention and treatment of obesity. The aim of the study was to evaluate the inhibitory effects of mulberry leaf polysaccharides (MLP) on PL and possible interaction mechanism, inhibition on lipid accumulation in vitro and in vivo. The results revealed that MLP had obvious inhibitory effects on PL (P < 0.05). The interaction of MLP-PL complexes was in a spontaneous way driven by enthalpy, and hydrogen bonds were the main factors in the binding. MLP could significantly inhibit the development of lipid accumulation in HepG2 cells (P < 0.05). Furthermore, consumption of high-fat diet containing MLP showed protective effects on liver and adipose tissue damages in mice, and inhibited the lipid absorption in digestive tract. MLP also significantly reduced the increased expression level of pancreatic digestive enzymes (P < 0.05). The study indicated that the anti-obesity effect of MLP might be caused by inhibition of lipid absorption via reducing PL activity.

Development of ex situ normothermic reperfusion as an innovative method to assess pancreases after preservation.

Static cold storage (SCS) is the standard method for pancreas preservation prior to transplantation; however, it does not permit organ assessment. Normothermic reperfusion (NR) is utilized clinically for other organs to assess viability. Our aim was to develop NR using normothermic machine perfusion technique to simulate reperfusion at the time of transplantation, enabling evaluation of oxygenated hypothermic machine perfusion (HMPO2) as a newer strategy to optimize pancreas preservation. 13 porcine pancreases procured after circulatory death were divided into 3 groups: 4 pancreases preserved using SCS, and 2 groups preserved by HMPO2 (n = 4 and n = 5, differing by type of preservation solution). Duration of perfusion or cold storage was 6 hours before the 1-hour assessment using NR. Outcome measures were perfusion characteristics, biochemistry and change in tissue water mass as oedema assessment. During NR, the HMPO2 groups demonstrated better perfusion characteristics, normal macroscopic appearances, decreased water mass and one HMPO2 group demonstrated a response to glucose stimulation. Conversely, the SCS group showed an increased water mass and developed early macroscopic appearances of oedema, interstitial haemorrhage and minimal portal outflow. This study suggests that ex situ assessment of pancreases by NR is promising, and that HMPO2 may be better than SCS.