Potencial quimiopreventivo de lipídios estruturados obtidos da Tributirina e Tricaprilina na fase de promoção da hepatocarcinogênese experimental / Chemopreventive potential of structured lipids obtained from Tributyrin and Tricaprylin in the promotion phase of experimental hepatocarcinogenesis

A quimioprevenção do câncer refere-se ao uso de compostos naturais ou sintéticos para prevenir o desenvolvimento das neoplasias antes do estabelecimento da malignidade. O ácido butirico (AB) atua como um potente quimiopreventivo na hepatocarcinogênese, reduzindo o número e o tamanho de lesões pré neoplásicas persistentes (pLPN), induzindo a apoptose e modulando mecanismos epigenéticos. Já o ácido caprílico (AC), além da sua atuação como potencializador de absorção, vem sendo investigado na área da prevenção do câncer. Neste cenário, o objetivo do trabalho visa avaliar a atividade quimiopreventiva de lipídios estruturados (EST) obtidos por interesterificação enzimática da tributirina com a tricaprilina, na fase de promoção da hepatocarcinogênese experimental. Após o processo de interesterificação, o produto final apresentou novos triacilgliceróis com composição de duas moléculas de ácido butírico para uma de ácido caprilíco. Ratos machos isogênicos da linhagem Fischer 344 foram submetidos ao modelo do hepatócito resistente, sendo distribuídos em dois grupos e tratados diariamente por via intragástrica com lipídios estruturados (EST) ou com o seu controle isocalórico, a maltodextrina (MD), durante a fase de promoção. Como esperado, não houve diferença estatística (p>0,05) em relação ao peso inicial e final dos animais dos grupos MD e EST, o que indica ausência de toxicidade dos compostos administrados. Na análise macroscópica do fígado, foi observada uma redução de 33,3% no grupo EST em relação ao número médio de nódulos macroscópicos em comparação ao grupo MD, porém essa redução não atingiu diferença estatística (p>0,05). Para a avaliação das lesões pré neoplásicas (LPN) foi utilizada a marcação imunoistoquímica para glutationa-S-transferase (GST-P). O grupo EST apresentou uma redução no número de lesões em remodelação e total GSTP-P+, quando comparado com o grupo MD (p<0,05). Quando avaliada a % de corpúsculos apoptóticos e índice de proliferação celular, não houve diferença estatística entre os grupos (p>0,05). Animais tratados com lipídios estruturados apresentaram maiores (p<0,05) concentrações de AC e AB por grama de tecido hepático em relação ao tratamento com maltodextrina. Em relação aos danos no DNA, o grupo EST resultou em cometas de comprimentos menores (p<0,05), menores níveis de γ-H2AX (p<0,05) e maiores concentrações de p53 nuclear, quando comparados aos animais que receberam maltodextrina, sugerindo uma proteção contra danos no DNA no grupo tratado com EST. Os resultados mostraram que o tratamento com EST resultou em ações efetivas na fase de promoção da hepatocarcinogênese experimental

Cancer chemoprevention refers to the use of natural or synthetic compounds to prevent the development of neoplasms before the establishment of malignancy. Butyric acid (AB) acts as a potent chemopreventive in hepatocarcinogenesis, reducing the number and size of persistent preneoplastic lesions (pLPN), inducing apoptosis and modulating epigenetic mechanisms. Caprylic acid (CA), in addition to its role as an absorption enhancer, has been investigated in the area of cancer prevention. In this scenario, the objective of this work was to evaluate the chemopreventive activity of structured lipids (EST) obtained by enzymatic interesterification of tributyrin with tricaprylin, in the phase of promotion experimental hepatocarcinogenesis. After the interesterification process, the final product presented new triacylglycerols with a composition of two molecules of butyric acid to one of caprylic acid. Isogenic male Fischer 344 rats were submitted to the resistant hepatocyte model, divided into two groups and treated daily intragastrically with structured lipids (EST) or with its isocaloric control, maltodextrin (MD), during the promotion phase. As expected, there was no statistical difference (p>0.05) in relation to the initial and final weight of the animals in the MD and EST groups, which indicates the absence of toxicity of the administered compounds. In the macroscopic analysis of the liver, a reduction of 33.3% was observed in the EST group in relation to the mean number of macroscopic nodules compared to the MD group, but this reduction did not reach a statistical difference (p>0.05). For the evaluation of pre-neoplastic lesions (PNL) immunohistochemical staining for glutathione-Stransferase (GST-P) was used. The EST group showed a reduction in the number of remodeling lesions and total GSTP-P+, when compared to the MD group (p<0.05). Animals treated with structured lipids had higher (p<0.05) concentrations of AC and AB per gram of liver tissue compared to treatment with maltodextrin. Regarding DNA damage, the EST group resulted in comets of shorter lengths (p<0.05), lower levels of γ-H2AX (p<0.05) and high concentration of nuclear p53, when compared to animals that received maltodextrin, suggesting protection against DNA damage in the EST treated group. The results showed that EST treatment resulted in effective actions in the promotion phase of experimental hepatocarcinogenesis

Phytochemical Properties and In Vitro Biological Activities of Phenolic Compounds from Flower of Clitoria ternatea L.

Phenolic compounds from the flower of Clitoria ternatea L. (PCFCTL) were extracted using a high-speed shearing extraction technique and purified by AB-8 macroporous resins, and the phytochemical composition of the purified phenolic compounds from the flower of Clitoria ternatea L. (PPCFCTL) was then analyzed. Subsequently, its bioactivities including antioxidant properties, enzyme inhibitory activities, and antiproliferative activities against several tumor cell lines were evaluated. Results indicated that the contents of total phenolics, flavonoids, flavonols, flavanols, and phenolic acids in PPCFCTL were increased by 3.29, 4.11, 2.74, 2.43, and 2.96-fold, respectively, compared with those before being purified by AB-8 macroporous resins. The results showed PPCFCTL have significant antioxidant ability (measured by reducing power, RP, and ferric reducing antioxidant power method, FRAP) and good DPPH, ABTS+, and superoxide anion radical scavenging activities. They can also significantly inhibit lipase, α-amylase, and α-glucosidase. In addition, morphological changes of HeLa, HepG2, and NCI-H460 tumor cells demonstrated the superior antitumor performance of PPCFCTL. However, the acetylcholinesterase inhibitory activity was relatively weak. These findings suggest that PPCFCTL have important potential as natural antioxidant, antilipidemic, anti-glycemic and antineoplastic agents in health-promoting foods.

The Expression of PEDF and its Putative Receptors in Hepatocellular Carcinoma and Background Liver Tissue.

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) remains one of the biggest medical issues. Pigment epithelial-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors. PEDF interacts with its two receptors, adipose triglyceride lipase (ATGL) and laminin receptor (LR). MATERIALS AND METHODS: We conducted immunohistochemical staining for PEDF, LR and ATGL in 151 resected HCCs and their background liver tissues. RESULTS: High expression of LR in HCC was associated with high histological grade and portal vein invasion, while high expression of PEDF in HCC was associated with absence of portal vein invasion. High LR expression in background liver was statistically associated with low serum albumin levels and was an independent prognostic factor of worse outcomes. No cases with more than 5% fatty degeneration in the background liver tissue showed high PEDF expression. CONCLUSION: PEDF/LR/ATGL could be potential biomarkers in HCC and various chronic hepatic disorders.

Decoration of myocellular lipid droplets with perilipins as a marker for in vivo lipid droplet dynamics: A super-resolution microscopy study in trained athletes and insulin resistant individuals.

In many different cell types neutral lipids can be stored in lipid droplets (LDs). Nowadays, LDs are viewed as dynamic organelles, which store and release fatty acids depending on energy demand (LD dynamics). Proteins like perilipin 2 (PLIN2) and PLIN5 decorate the LD membrane and are determinants of LD lipolysis and fat oxidation, thus affecting LD dynamics. Trained athletes and type 2 diabetes (T2D) patients both have high levels of intramyocellular lipid (IMCL). While IMCL content scales negatively with insulin resistance, athletes are highly insulin sensitive in contrast to T2D patients, the so-called athlete's paradox. Differences in LD dynamics may be an underlying factor explaining the athlete's paradox. We aimed to quantify PLIN2 and PLIN5 content at individual LDs as a reflection of the ability to switch between fatty acid release and storage depending on energy demand. Thus, we developed a novel fluorescent super-resolution microscopy approach and found that PLIN2 protein abundance at the LD surface was higher in T2D patients than in athletes. Localization of adipocyte triglyceride lipase (ATGL) to the LD surface was lower in LDs abundantly decorated with PLIN2. While PLIN5 abundance at the LD surface was similar in athletes and T2D patients, we have observed previously that the number of PLIN5 decorated LDs was higher in athletes, indicating more LDs in close association with mitochondria. Thus, in athletes interaction of LDs with mitochondria was more pronounced and LDs have the protein machinery to be more dynamic, while in T2D patients the LD pool is more inert. This observation contributes to our understanding of the athlete's paradox.

[Analytical validation of 13 biochemistry parameters (CEA, CA 19-9, amylase, lipase, sodium, potassium, chloride, creatinine, glucose, protein, albumin, LDH, triglycerides) in body fluids]. / Validation de méthodes des dosages de 13 paramètres biochimiques (ACE, CA 19-9, amylase, lipase, sodium, potassium, chlorure, créatinine, glucose, protéines, albumine, LDH, triglycérides) dans un panel de liquides biologiques.

The measurement performance of 13 biochemistry parameters (CEA, CA 19-9, amylase, lipase, sodium, potassium, chloride, creatinine, glucose, protein, albumin, LDH, triglycerides) was tested in a panel of biological fluids other than blood and urine (peritoneal, pleural, pancreatic fluids ...). Our protocol, based on a risk analysis, allowed us to justify our choices and compare the performance obtained with those of the serum or plasma matrix already validated. Thus, the coefficients of variation obtained in body fluids are comparable. The assessment of accuracy (spiking and dilution tests) shows the absence of bias, which is consistent with the absence of matrix effect. The linearity studied by dilution tests shows that the upper limits of the measurement interval communicated by the supplier are applicable to body fluids. The absence of contamination and stability have been also confirmed. All analytes are stable for 3 days at room temperature, 7 days between 2 and 8̊C, and 6 months at -20̊C; except LDH and lipase. For most analytes, at least one interference (hemolysis, icterus, lipemia) was found. Finally, a bibliographical study, confronted with the experience of prescribers, led us to define optimal thresholds to help interpret patients' results. In conclusion, this work has allowed us to validate analytical methods for body fluids testing after relying on their comparability to the blood matrix. We have also been able to adapt our practices and finally be accredited according to the standard NF IN ISO 15189.

A new prognostic factor of breast cancer: High carboxyl ester lipase expression related to poor survival.

OBJECTIVE: The enzyme carboxyl ester lipase (CEL), known as bile salt-dependent lipase (BSDL) or bile salt-stimulated lipase (BSSL), is mainly expressed in pancreatic acinar cells and lactating mammary glands. To investigate the link between CEL expression of breast cancer (BC) tissues and the survival of BC patients by analyzing The Cancer Genome Atlas Breast Carcinoma (TCGA-BRCA) level 3 data. METHODS: The clinical information and RNA-sequencing (RNA-Seq) expression data were downloaded from TCGA. Patients were divided into a high CEL expression group and a low CEL expression group using the optimal cutoff value (5.611) identified from the ROC curve. Chi-square test and Fisher exact test were used to find the correlation between the expression of CEL and clinicopathologic features. To assess the diagnostic capability, the receiver operating characteristic (ROC) curve of CEL was drawn. The survival differences between high and low CEL expression groups were compared by Cox regression analysis. Log-rank test was applied to the calculation of p values and the comparison of the Kaplan-Meier curves. Furthermore, Gene Expression Omnibus (GEO) datasets were used for external data validation. RESULTS: Analysis of 1104 cases of tumor data showed that CEL was over-expressed in breast cancer. There were relationships between high CEL expression and clinicopathologic features. The high CEL expression group had a lower survival. By analyzing the area under the ROC curve (AUC) of CEL, it was found to have a limited diagnostic capability. CEL expression may be an independent prognostic factor for breast cancer survival through the multivariate analysis. The validation in GEO datasets also showed that CEL expression was higher in breast tumor tissues than in normal breast tissues. High CEL expression was associated with the poor overall survival of breast cancer. CONCLUSIONS: High CEL expression may be an independent prognostic factor for the poor survival of breast cancer.

2019 WSES guidelines for the management of severe acute pancreatitis.

Although most patients with acute pancreatitis have the mild form of the disease, about 20-30% develops a severe form, often associated with single or multiple organ dysfunction requiring intensive care. Identifying the severe form early is one of the major challenges in managing severe acute pancreatitis. Infection of the pancreatic and peripancreatic necrosis occurs in about 20-40% of patients with severe acute pancreatitis, and is associated with worsening organ dysfunctions. While most patients with sterile necrosis can be managed nonoperatively, patients with infected necrosis usually require an intervention that can be percutaneous, endoscopic, or open surgical. These guidelines present evidence-based international consensus statements on the management of severe acute pancreatitis from collaboration of a panel of experts meeting during the World Congress of Emergency Surgery in June 27-30, 2018 in Bertinoro, Italy. The main topics of these guidelines fall under the following topics: Diagnosis, Antibiotic treatment, Management in the Intensive Care Unit, Surgical and operative management, and Open abdomen.

Lipase Production by Aspergillus niger C by Submerged Fermentation

Abstract This study aimed to evaluate the effects of variables on the process of lipases production by Aspergillus niger C by submerged fermentation (SmF). The production assays were performed in shake flasks for 72 hours at 150 rpm and 32°C. First, a fractional factorial design 25-1 (FFD) was carried out to evaluate the effect of the following process variables: sucrose, ammonium sulphate, soybean oil, yeast extract concentration and pH. After the selection of the variables that significantly influenced the lipase production, a central composite rotational design 22 (CCRD) was used, aiming to find the most favorable operational conditions. The selected assay condition (15.0 g.L-1 sucrose, 4.0 g.L-1 ammonium sulphate, 4.0 g.L-1 soybean oil and 1.0 g.L-1 yeast extract at pH 5.0) was the one that presented a lipase activity of 27.46 U.mL-1. It was very close to that best assay (30.76 U.mL-1), but using half of the inducer concentration, consequently reducing process cost. The kinetics of lipase production showed that the highest specific activity was 57.17 U.mg-1. The pH and temperature effects on lipase activity produced in this study was investigated. The optimum activity was found in a more acidic pH (5.0-6.0) and 55°C.

Randomized clinical trial of the effect of a fibrin sealant patch on pancreatic fistula formation after pancreatoduodenectomy.

BACKGROUND: The potential for a fibrin sealant patch to reduce the risk of postoperative pancreatic fistula (POPF) remains uncertain. The aim of this study was to evaluate whether a fibrin sealant patch is able to reduce POPF in patients undergoing pancreatoduodenectomy with pancreatojejunostomy. METHODS: In this multicentre trial, patients undergoing pancreatoduodenectomy were randomized to receive either a fibrin patch (patch group) or no patch (control group), and stratified by gland texture, pancreatic duct size and neoadjuvant treatment. The primary endpoint was POPF. Secondary endpoints included complications, drain-related factors and duration of hospital stay. Risk factors for POPF were identified by logistic regression analysis. RESULTS: A total of 142 patients were enrolled. Forty-five of 71 patients (63 per cent) in the patch group and 40 of 71 (56 per cent) in the control group developed biochemical leakage or POPF (P = 0·392). Fistulas were classified as grade B or C in 16 (23 per cent) and ten (14 per cent) patients respectively (P = 0·277). There were no differences in postoperative complications (54 patients in patch group and 50 in control group; P = 0·839), drain amylase concentration (P = 0·494), time until drain removal (mean(s.d.) 11·6(1·0) versus 13·3(1·3) days; P = 0·613), fistula closure (17·6(2·2) versus 16·5(2·1) days; P = 0·740) and duration of hospital stay (22·1(2·2) versus 18·2(0·9) days; P = 0·810) between the two groups. Multivariable logistic regression analysis confirmed that obesity (odds ratio (OR) 5·28, 95 per cent c.i. 1·20 to 23·18; P = 0·027), soft gland texture (OR 9·86, 3·41 to 28·54; P < 0·001) and a small duct (OR 5·50, 1·84 to 16·44; P = 0·002) were significant risk factors for POPF. A patch did not reduce the incidence of POPF in patients at higher risk. CONCLUSION: The use of a fibrin sealant patch did not reduce the occurrence of POPF and complications after pancreatoduodenectomy with pancreatojejunostomy. Registration number: 2013-000639-29 (EudraCT register).

Study of virulence factor of Candida species in oral lesions and its association with potentially malignant and malignant lesions.

OBJECTIVE: The aim of this study was to explore the association between malignant and premalignant lesions and the virulence factor profile of Candida spp. recovered from different oral lesions. DESIGN: Candida spp. isolated from malignant lesions (squamous cell carcinoma, OC, n = 25), atypical lichen planus (AL, n = 11), chronic candidiasis (CC, n = 25), and asymptomatic carriers (WI, n = 15, control strains.) Isolates were identified in chromogenic medium, colony morphology and biochemical tests. The lipolytic and proteinase activity was determined on supplemented agar with olive oil and BSA, respectively. The biofilm formation with XTT reduction assay and cellular surface hydrophobicity (CSH) by water-hydrocarbon method were performed. RESULTS: All isolates recovered from oral lesions produced the four virulence factors studied with significantly higher levels than in WI isolates. Interestingly, lipolytic activity was absent in WI isolates. The proteolytic activity was similar in AL and OC isolates. OC isolates showed significantly higher CSH values than other clinical isolates. Non-albicans species showed higher biofilm formation than C.albicans (P = 0.03.) There were no significant differences in virulence factors among species. A strong positive correlation was found between proteinase and lipase activity (r = 0.90, P < 0.0001), and between hydrophobicity and biofilm (R = 0.81, P < 0.0001.) CONCLUSIONS: Our results indicate that OC Candida isolates exhibited a significant higher attributes of virulence than other lesions fungus isolates, providing evidence about the association between Candida pathogenicity and lesions severity.

A simple biomarker scoring matrix for early gastric cancer detection.

Gastric cancer (GC) is a major cause of death in many parts of the world. While 90% of early GC is curable by resection, only about 5% of patients diagnosed in the late stages survive beyond five years. This provides strong impetus to push for early GC detection through the use of non-invasive biomarkers, before metastatic complications arise. It is also of strong medical interest to identify patients of the diffuse subtype at the earliest time possible, since the disease variant progresses very rapidly and is associated with much higher mortality rate. In this study, we compared quantitatively the gastric fluid proteome of 70 GC patients to 17 individuals with benign gastritis in search of potential biomarkers that aid in GC diagnosis, prognosis and subtype stratification. We report that as much as half of the gastric fluid proteome is subject to regulation in diseased states, and propose a simple biomarker panel scoring matrix for early GC detection with diagnostic sensitivity of 95.7%. We also demonstrate as proof-of-concept that a digitised record generated with SWATH-MS based on 380 protein abundance signatures from the gastric fluid could segregate patients with diffuse-type GC.

Decreased LIPF expression is correlated with DGKA and predicts poor outcome of gastric cancer.

Gastric cancer (GC) is a common and deadly digestive tract tumor worldwide. Unfortunately, diagnosis of GC is usually confused and misleading because of atypical symptoms or incomplete complaints. Accordingly, exploring gene expression profile and identifying genes with analogical variance trend will bring new perspective into the diagnosis and treatment of GC. Herein, a RNA­Seq dataset from Caucasian GC and their matched non­cancerous samples [Gene Expression Omnibus (GEO): SRP049809] and datasets from four microarrays constituted with tumor and non­tumor tissues (GEO: GSE13911, GSE19826, GSE29272, GSE33335) were analyzed to explore the differentially expressed genes (DGEs). As a result, we identified a core set of 373 DGEs. Among these genes, we found that most downregulated genes were related to lipid­metabolic functions. Especially, the gastric lipase (LIPF) gene, which was connected with various lipid metabolism processes, was significantly decreased among all datasets. We then performed immunohistochemistry experiments using gastric tissue arrays to investigate the clinical effects, and the expression of a LIPF target gene, diacylglycerol kinase α (DGKA). Among the 90 samples of gastric adenocarcinoma, the LIPF and DGKA levels were both decreased in cancer tissues [LIPF, 59.1% (53/90); DGKA, 77.8% (70/90)] compared to normal tissues [LIPF, 94.4% (85/90); DGKA, 90% (81/90)]. The expression level of these two proteins in GC was associated with local invasion and disease stage. Cox regression identified high DGKA expression (HR, 0.49; 95% CI, 0.26­0.94; P=0.03) as a predictor of good prognosis and LNM status (HR, 4.63; 95% CI, 1.39­15.51; P=0.01) as a predictor of poor prognosis. Thus we speculated that LIPF­DGKA might serve as a potential possible biomarkers for diagnosis of GC, and their downregulation may bring new perspective into the investigation of GC prognosis.

Loss of adipose triglyceride lipase is associated with human cancer and induces mouse pulmonary neoplasia.

Metabolic reprogramming is a hallmark of cancer. Understanding cancer metabolism is instrumental to devise innovative therapeutic approaches. Anabolic metabolism, including the induction of lipogenic enzymes, is a key feature of proliferating cells. Here, we report a novel tumor suppressive function for adipose triglyceride lipase (ATGL), the rate limiting enzyme in the triglyceride hydrolysis cascade.In immunohistochemical analysis, non-small cell lung cancers, pancreatic adenocarcinoma as well as leiomyosarcoma showed significantly reduced levels of ATGL protein compared to corresponding normal tissues. The ATGL gene was frequently deleted in various forms of cancers. Low levels of ATGL mRNA correlated with significantly reduced survival in patients with ovarian, breast, gastric and non-small cell lung cancers. Remarkably, pulmonary neoplasia including invasive adenocarcinoma developed spontaneously in mice lacking ATGL pointing to an important role for this lipase in controlling tumor development.Loss of ATGL, as detected in several forms of human cancer, induces spontaneous development of pulmonary neoplasia in a mouse model. Our results, therefore, suggest a novel tumor suppressor function for ATGL and contribute to the understanding of cancer metabolism. We propose to evaluate loss of ATGL protein expression for the diagnosis of malignant tumors. Finally, modulation of the lipolytic pathway may represent a novel therapeutic approach in the treatment of human cancer.

Predictive Factors of Biliary Tract Cancer in Anomalous Union of the Pancreaticobiliary Duct.

The assessment of malignancies associated with anomalous union of the pancreaticobiliary duct (AUPBD) is essential for the design of appropriate treatment strategies. The aim of the present study is to measure the incidence of AUPBD-related pancreaticobiliary malignancy and to identify predictive factors. This retrospective cohort study included cases of 229 patients with AUPBD between January 1999 and December 2013. The impact of bile duct dilatation on the incidence of AUPBD-related pancreaticobiliary disease was measured, and predictive factors were evaluated.Among 229 patients with AUPBD, 152 had common bile duct dilatation (≥10 mm) (dilated group) and 77 did not (<10 mm) (nondilated group). Intrahepatic cholangiocarcinoma occurred more frequently in the nondilated group than in the dilated group (3.9% vs 0%; P < 0.05). By contrast, no significant difference in the incidence of extrahepatic cholangiocarcinoma was observed between the 2 groups (1.3% vs 3.9%; P = 0.271). By univariate analysis, age, type of AUPBD, and the level of pancreatic enzymes refluxed in the bile duct were associated with occurrence of biliary tract cancers. In multivariate analysis, age ≥45 years (odds ratio [OR] 1.042, 95% confidence interval [CI] 1.011-1.073, P < 0.05), P-C type (OR 3.327, 95% CI 1.031-10.740, P < 0.05), and a high level of biliary lipase (OR 4.132, 95% CI 1.420-12.021, P < 0.05) showed a significant association with AUPBD-related biliary tract cancer.Intrahepatic cholangiocarcinoma may occur more frequently in AUPBD patients without bile duct dilatation. Age ≥45 years, P-C type, and biliary lipase level ≥45,000 IU/L are significantly associated with AUPBD-related biliary tract cancer.

Preliminary report of the (13)C-mixed triglyceride breath test to assess timing of pancreatic enzyme replacement therapy in children with cystic fibrosis.

BACKGROUND: Despite guidelines suggesting pancreatic enzyme replacement therapy (PERT) should be taken before or during a meal, it is currently unknown whether this has benefits over administration after a meal in individuals with cystic fibrosis (CF). METHODS: 18 children with pancreatic insufficient CF were randomised to two (13)C-mixed triglyceride ((13)C-MTG) breath tests to assess lipase activity with PERT administered 10min before and 10min after a meal. Results were expressed as percentage cumulative dose recovered (PCDR) of (13)CO2 and were compared with established values in healthy subjects. Gastric half emptying time (T½) was also assessed by a (13)C-octanoate breath test. RESULTS: There was no difference in mean PCDR of (13)CO2 between taking PERT before versus after the meal (p=0.68). Eleven subjects had a greater PCDR when PERT was taken before and 7 when PERT was taken after the meal. 6/8 subjects (75%) with a lower than normal PCDR at one time point normalised PCDR when PERT timing was changed. When PERT was taken after the meal, PCDR was higher in normal vs. fast T½ (p=0.04). CONCLUSIONS: Changing PERT timing can result in normalised lipase activity. Gastric emptying rate may influence optimal timing of PERT. Clinical Trial Registration Number - This study was undertaken prior to the registration process being a commonly required practice.

Acute pancreatitis associated with pegylated interferon-alpha-2a therapy in chronic hepatitis C.

Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea.

Lipase member H frequently overexpressed in human esophageal adenocarcinomas.

Esophageal cancer is one of the most frequent causes of cancer-related deaths worldwide. This is due to its asymptomatic nature or mild nonspecific symptoms. Most patients are diagnosed after appearance of prominent symptoms, and tumors are frequently accompanied by severe infiltration. Therefore, molecular biomarkers for the prognosis of early-stage esophageal cancer are desired. In this study, we examined the prognostic potential of lipase H (LIPH), a recently reported biomarker for lung adenocarcinoma and squamous carcinoma. We found that LIPH mRNA is also frequently upregulated in esophageal adenocarcinoma. Immunohistochemical analysis confirmed LIPH protein expression in various esophageal tumor tissue sections. Interestingly, higher expression of LIPH in esophageal adenocarcinoma showed a positive correlation with longer survival of patients. Our data suggest that LIPH may have prognostic value for esophageal cancer.

Phenolic profiles of 20 Canadian lentil cultivars and their contribution to antioxidant activity and inhibitory effects on α-glucosidase and pancreatic lipase.

Phenolic extracts from 20 Canadian lentil cultivars (Lens culinaris) were evaluated for total phenolic contents and composition, antioxidant activities (DPPH, FRAP, ORAC), and inhibitory properties against α-glucosidase and pancreatic lipase. Twenty one phenolic compounds were identified in the present study, with the majority being flavonoids, including kaempeferol glycosides, catechin/epicatechin glucosides and procyanidins. These phenolic compounds not only contributed significantly to the antioxidant activities, but they were also good inhibitors of α-glucosidase and lipase, two enzymes, respectively, associated with glucose and lipid digestion in the human intestine, thus contributing significantly to the control of blood glucose levels and obesity. More interestingly, it was the flavonols, not the flavanols, which showed the inhibitory activities against α-glucosidase and pancreatic lipase. Our result provides supporting information for developing lentil cultivars and functional foods with improved health benefits and suggests a potential role of lentil consumption in managing weight and control of blood glucose.

Metabolite profile, antioxidant capacity, and inhibition of digestive enzymes in infusions of peppermint (Mentha piperita) grown under drought stress.

Peppermint (Mentha piperita) infusions represent an important source of antioxidants, which can be enhanced by inducing abiotic stress in plants. The aim of this study was to evaluate the effect of drought stress on peppermint cultivation as well as the metabolite profile, antioxidant capacity, and inhibition of digestive enzymes of resulting infusions. At 45 days after planting, irrigation was suppressed until 85 (control), 65, 35, 24, and 12% soil moisture (SM) was reached. The results showed that 35, 24, and 12% SM decreased fresh (20%) and dry (5%) weight. The 35 and 24% SM treatments significantly increased total phenolic and flavonoid contents as well as antioxidant capacity. Coumaric acid, quercetin, luteolin, and naringenin were detected only in some drought treatments; however, in these infusions, fewer amino acids and unsaturated fatty acids were identified. The 24 and 12% SM treatments slightly improved inhibition of pancreatic lipase and α-amylase activity. Therefore, induction of moderate water stress in peppermint is recommended to enhance its biological properties.

High drain amylase and lipase values predict post-operative pancreatitis for choledochal cyst.

BACKGROUND: Post-operative pancreatitis is a severe complication after cyst excision with hepaticoenterostomy (CEHE) for choledochal cysts. The aim of this study was to examine the dynamic post-operative changes in drain amylase and lipase values after CEHE for choledochal cysts, and then compare these values with the clinical outcomes in order to identify risk factors for post-operative pancreatitis after CEHE. PATIENTS AND METHODS: A total of 19 patients with choledochal cysts were retrospectively examined in the period between 2005 and 2012. The amylase and lipase values in the drainage and the serum, and the output of the effluent were measured post-operatively. The associations between their values and the clinical outcomes were evaluated. RESULTS: Six were found to have a pancreatic leak according to an international study group definition. In two of them, who developed post-operative pancreatitis, both amylase and lipase values in drainage were markedly elevated at 1 post-operative day (1 POD). The drain amylase value seemed to elevate rather specifically dependent on the occurrence of post-operative pancreatitis, whereas the drain lipase value tended to elevate regardless of the presence/absence of post-operative pancreatitis. CONCLUSION: It was indicated that amylase and lipase values in drainage at 1 POD could be effective predictors of post-operative pancreatitis after CEHE.