Dehydrogenation Of Lactate Research Articles

Effects of lactate on metabolism and differentiation of CD4+T cells

BackgroundLactate accumulation caused by abnormal tumor metabolism can induce the formation of an inhibitory immune microenvironment through a variety of pathways, which is characterized by regulatory T cells (Treg) infiltration and effector T cells (Teff) depletion. Studies have found that the key reason why Treg cells can survive in harsh environments lies in their flexible metabolic mode, which can use lactate in tumor microenvironment (TME) as an alternative energy substance to maintain their inhibitory activity. In addition, lactate could also promote the differentiation of CD4+T cells into Treg, but the mechanism was not completely clear. The purpose of this study was to investigate the possible mechanism by which lactate is utilized by CD4+T cells to influence Th17/Treg ratio. MethodsBasal cytokines (anti-CD3, anti-CD28, TGF-β) and 10 mM lactate was added into Naïve CD4+T cells basal medium for 3 days. After TCR stimulation, Naïve CD4+T converted to CD4+T. Flow cytometry was used to detect the proportion of Treg cells; ELISA was used to detect the activity of LDHA, LDHB and NADH and the amount of α -Ketoglutaric Acid (α-KG) and 2-Hydroxyglutaric Acid (2HG) after lactate entered the cells; Western Blot and RT-PCR were used to detect the protein and gene expression of Foxp3, RORγt, LDHA and LDHB. In the validation experiment, lactate uptake inhibitor AZD3965, LDHA inhibitor GSK2837808A and NADH conversion inhibitor Rotenone were added respectively to observe the differentiation ratio of Treg cells and confirm the key points of metabolism; the degradation of Treg cell transcription factor Foxp3 was interfered with ubiquitination inhibitors to observe whether it co-ubiquitinated with HIF-1α; the expression and activity of LDHA, LDHB and NADH in mitochondria and cytoplasm were detected to confirm cell localization. ResultsWhen basal cytokines (anti-CD3, anti-CD28, TGF-β) stimulated, lactate was added to the culture medium, and CD4+T cells absorbed a large amount of lactate not only through MCT1 (monocarboxylic acid transporter), but also increased the expression of lactate dehydrogenase and accelerated the intracellular metabolism of lactate. LDHB in cytoplasm mainly catalyzed the dehydrogenation of lactate to pyruvate, accompanied by the transformation reaction between NAD+ and NADH. The latter further entered the mitochondria and participates in the tricarboxylic acid cycle metabolism. In addition, lactate could significantly increase the level of LDHA in mitochondria and promote the transformation of α-KG to 2HG, accompanied by the transformation of NADH to NAD+. These metabolic changes eventually led to an increase in the intracellular 2HG/α-KG ratio. Abnormal 2HG increased the proportion of Treg by inhibiting ATP5B-mediated phosphorylation of mTOR and the synthesis of HIF-1α, causing it not be enough to ubiquitinate and degrade with Foxp3. ConclusionsLactate plays an important role in regulating the differentiation of Treg cells, inducing the expression and function of LDHA and promoting the transformation of α-KG to 2HG may be an important mechanism.

Catalytic direct dehydrogenation of ethyl lactate to produce ethyl pyruvate over a synergetic Cu0/Cu+ interface

The direct dehydrogenation of ethyl lactate (EL) to produce ethyl pyruvate (EP) over non-precious heterogeneous catalysts is highly desirable, but challenging. Herein, we report a highly efficient silica-supported copper catalyst prepared via a hydrolysis-precipitation method (Cu/SiO2-HP) for the dehydrogenation of ethyl lactate, which exhibited an 85.4 % EL conversion with 91.1 % selectivity toward EP at 320 °C. XAFS, in situ XPS, and CO-adsorption FT-IR spectra revealed that the Cu/SiO2-HP catalyst had abundant Cu0/Cu+ interfaces. In situ FT-IR spectra, kinetic studies, and theoretical calculations also demonstrated that the Cu0/Cu+ interfaces synergistically activate the O−H and C−H bonds in the adsorbed EL for direct dehydrogenation into EP. The H/D kinetic isotope effect for model reaction confirmed that C−H bond activation is the key step in the dehydrogenation reaction. This study offers a new approach toward the selective conversion of EL into EP, which is of great significance for biomass conversion.

Hepatoprotective effect of Trigonella foenum graecum against ethanol-induced cell death in human liver cells (HepG2 and Huh7).

The plant Trigonella foenum graecum, also known as fenugreek, has been shown to have anticancer, antidiabetic, anti-inflammatory, and antioxidant properties. In this study, the hepatoprotective effect of fenugreek seed extract (FSE) against ethanol-induced cell death was investigated in human liver cells (HepG2 and Huh7). The cytotoxic effect of FSE and ethanol on cells was evaluated by exposing the cells at different concentrations. Following that, the cells were pre-incubated with 5-25μg/ml FSE, followed by a cytotoxic concentration (0.5mM) of ethanol. MTT and neutral red uptake assays were performed in treated cells to assess the ability of FSE to protect cells from the cytotoxic effects of ethanol. When compared to controls, ethanol treatment significantly reduced the viability of HepG2 and Huh7 cells and altered the cell morphology, whereas treatment with FSE significantly increased cell viability and reversed ethanol-induced morphological changes. Furthermore, pretreatment with FSE dose-dependently reduced lactate dehydrogenate (LDH) leakage, lipid peroxidation (LPO) level, and catalase activities while increasing glutathione (GSH) level induced by ethanol. Pretreatment with FSE also reduced the generation of reactive oxygen species (ROS), caspase enzyme activities, and protein expression of caspase-3 and -9. In HepG2 cells, ethanol-induced apoptosis was observed, whereas FSE treatment reduced apoptosis by downregulating the expression of pro-apoptotic marker genes and upregulating the antiapoptotic gene. In conclusion, this study reports on the mechanistic details of the hepatoprotective potential of FSE. The results also suggest that fenugreek seeds may be useful in preventing liver diseases caused by toxicants such as ethanol.

Catalytic Amination of Polylactic Acid to Alanine.

In comparison to the traditional petroleum-based plastics, polylactic acid, the most popular biodegradable plastic, can be decomposed into carbon dioxide and water in the environment. However, the natural degradation of polylactic acid requires a substantial period of time and, more importantly, it is a carbon-emitting process. Therefore, it is highly desirable to develop a novel transformation process that can upcycle the plastic trash into value-added products, especially with high chemical selectivity. Here we demonstrate a one-pot catalytic method to convert polylactic acid into alanine by a simple ammonia solution treatment using a Ru/TiO2 catalyst. The process has a 77% yield of alanine at 140 °C, and an overall selectivity of 94% can be reached by recycling experiments. Importantly, no added hydrogen is used in this process. It has been verified that lactamide and ammonium lactate are the initial intermediates and that the dehydrogenation of ammonium lactate initiates the amination, while Ru nanoparticles are essential for the dehydrogenation/rehydrogenation and amination steps. The process demonstrated here could expand the application of polylactic acid waste and inspire new upcycling strategies for different plastic wastes.

Oxidative dehydrogenation of ethyl lactate to ethyl pyruvate over vanadium and iron antimonates catalysts

The oxidative dehydrogenation of ethyl lactate to ethyl pyruvate, corresponding to the first step of a new process in the industrial production of methionine, has been investigated. Iron and vanadium antimonates were developed as catalysts, and were optimized to reach 87 % conversion of ethyl lactate, with 88 % selectivity to ethyl pyruvate, at only 275 °C. The catalysts were characterized before and after catalytic testing, and in situ using various techniques, including X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and XANES spectroscopy. The results show that neither the Sb3+/Sb5+ nor the Fe2+/Fe3+ redox couple were involved in the dehydrogenation of ethyl lactate, or in the catalysts re-oxidation. The active and selective catalytic sites correspond to surface V5+ species. These species should not be considered as part of the bulk oxide, but as supra-surface species whose surface content is monitored with the bulk composition.

Effects of Pre-cooling and Per-cooling on Neural, Physiological, and Functional Responses in Active Young Girls

Background: Stressful environments, especially air temperature, have significant effects on human physiological responses to physical activity. Objectives: The current study aimed to determine the effects of pre-cooling and per-cooling on neural, physiological, and functional responses in active young girls. Methods: Twelve active girls (age 24.6 ± 1.4, weight 55.46 ± 8.18, height 165.1 ± 5.91) were tested in three separate sessions with intervals of three days between each session. All subjects performed the Balke test in three groups either without an ice vest (control and pre-cooling) or with an ice vest (per-cooling) in each session, randomly. Pre-cooling was applied with an ice vest for 30 min just before the test, while per-cooling was used with an ice vest from the beginning of the test to exhaustion. A Buerer FT-70 digital thermometer, polar-FT60 heart rate monitoring, Microlife blood pressure monitoring, and ELISA technique were used to measure core body temperature, heart rate, blood pressure, dopamine, cortisol, and lactate dehydrogenase, respectively. Two-way repeated-measures ANOVA was applied to analyze the data with a confidence interval of 95%. Results: The heart rate and core body temperature significantly decreased at the end of the test in the pre-cooling and per-cooling groups (P < 0.05). There was an improved performance with an increase in Tmax in the per-cooling group compared to the control group (P < 0.05) although this difference was not significant in the pre-cooling group compared to the control group (P > 0.05). Dopamine, cortisol, and lactate dehydrogenize increased in the groups in comparison with the pretest (P < 0.05) even though these differences were not significant in the comparison between the groups (P > 0.05). Conclusion: The findings suggest that pre-cooling and per-cooling could be used as a beneficial method to improve performance due to not only a decrease in core body temperature and heart rate but also an increase in the level of dopamine and cortisol. Moreover, per-cooling was more effective than pre-cooling to increase performance.

Screening of catalysts for the oxidative dehydrogenation of ethyl lactate to ethyl pyruvate, and optimization of the best catalysts

This study reports on a new industrial gas-phase process to produce ethyl pyruvate, using the oxidative dehydrogenation of ethyl lactate. In an initial approach, twenty catalysts were screened under reaction conditions required for industrial applications. When evaluated in terms of their maximum selectivity to ethyl pyruvate and their productivity, the best catalyst was found to be a phosphomolybdic polyoxometalate, with iron counter-cations: FePMo12O40. To improve this catalyst, a study was carried out by including cesium counter-cations. The new catalysts exhibited higher yields because of higher Mo active surface site density related to higher specific surface area and although their intrinsic activity was lower. Their ethyl pyruvate selectivity increased with iron content but never overpass that of FePMo12O40. These results are explained in terms of changes in structure and iron counteraction coordination leading or not to electron exchange between iron and molybdenum and influencing the acidity of the catalyst's surface.

Vanadium-based highly active and selective catalysts for oxidative dehydrogenation of ethyl lactate to ethyl pyruvate

Pyruvates are important intermediates for various bioactive and pharmaceutical molecules. Synthesis of pyruvates is challenging due to low selectivity, as the pyruvates are prone to polymerisation. In the present work, oxidative dehydrogenation of ethyl lactate to ethyl pyruvate was carried out under very mild conditions using vanadium-based homogeneous and heterogeneous catalysts in the presence of aqueous t-butyl hydroperoxide as an oxidant. Homogenous vanadium-based catalyst, VO(acac)2 in acetonitrile solvent, gave excellent conversion (upto 83%) with 100% selectivity to ethyl pyruvate at room temperature. However, the heterogeneous catalyst, V2O5 exhibited very high activity for oxidative dehydrogenation of ethyl lactate only at higher temperature (80 °C). At higher temperature, significant TBHP decomposition was observed if all TBHP was added in one lot. In case of ethyl lactate dehydrogenation using V2O5 catalyst at 80 °C with two equivalents TBHP, 60% ethyl lactate conversion with 100% TBHP conversions were observed after 5 h when all TBHP was added initially in the reaction mixture. However, the ethyl lactate conversion at 80 °C, after 5 h increased to 72% when the same amount of TBHP was added batch wise over a period of 4 h, indicating improved conversion of TBHP to ethyl pyruvate. The heterogeneous catalyst, V2O5 exhibited up to 98% conversion with 100% ethyl pyruvate selectivity at 80 °C after 10 h with 3 equivalent TBHP added batch wise. The homogeneous catalyst could not be reused while V2O5 could be successfully recycled five times without catalytic performances loss. Oxidation proceeds by radical mechanism, as proved by experiment with radical scavenger.

Modulation of the unfolded protein response pathway as an antiviral approach in airway epithelial cells

IntroductionRhinovirus (RV) infection is a major cause of cystic fibrosis (CF) lung morbidity with limited therapeutic options. Various diseases involving chronic inflammatory response and infection are associated with endoplasmic reticulum (ER) stress and subsequent activation of the unfolded protein response (UPR), an adaptive response to maintain cellular homeostasis. Recent evidence suggests impaired ER stress response in CF airway epithelial cells, this might be a reason for recurrent viral infection in CF. Therefore, assuming that ER stress inducing drugs have antiviral properties, we evaluated the activation of the UPR by selected ER stress inducers as an approach to control virus replication in the CF bronchial epithelium. MethodsWe assessed the levels of UPR markers, namely the glucose-regulated protein 78 (Grp78) and the C/EBP homologous protein (CHOP), in primary CF and control bronchial epithelial cells and in a CF and control bronchial epithelial cell line before and after infection with RV. The cells were also pretreated with ER stress-inducing drugs and RV replication and shedding was measured by quantitative RT-PCR and by a TCID50 assay, respectively. Cell death was assessed by a lactate dehydrogenate (LDH) activity test in supernatants. ResultsWe observed a significantly impaired induction of Grp78 and CHOP in CF compare to control cells following RV infection. The ER stress response could be significantly induced in CF cells by pharmacological ER stress inducers Brefeldin A, Tunicamycin, and Thapsigargin. The chemical induction of the UPR pathway prior to RV infection of CF and control cells reduced viral replication and shedding by up to two orders of magnitude and protected cells from RV-induced cell death. ConclusionRV infection causes an impaired activation of the UPR in CF cells. Rescue of the ER stress response by chemical ER stress inducers reduced significantly RV replication in CF cells. Thus, pharmacological modulation of the UPR might represent a strategy to control respiratory virus replication in the CF bronchial epithelium.

Aerobic Oxidative Dehydrogenation of Ethyl Lactate Over Reduced MoVNbOx Catalysts

The present study investigated the effect of low-valent transition metal ions and oxygen vacancies on the catalytic selective oxidation properties over reduced MoVNbOx catalysts. The MoVNbOx-catalyzed synthesis of ethyl pyruvate (EP) from ethyl lactate (EL) using molecular oxygen (O2) as the hydrogen acceptor under mild aerobic and normal pressure conditions is described. It was found that the nitrogen (N2) calcined catalysts with low-valent metal ions (V4+ and Mo4+) increased the oxidative dehydrogenation (ODH) reaction rate and the EL conversion reached 90.6% (~ 21.1 mmol [EP] mmol [V4+]−1 h−1). The ODH catalytic activity of the N2–MoVNbOx catalyst was four times higher than that of the pristine MoVNbOx catalyst. Low-valent V4+ ions introduced plenty of oxygen vacancies to the surface structure and increased the oxygen mobility, which facilitated the ODH reaction. Together, the results of the temperature programmed reduction of hydrogen (H2-TPR), X-ray photoelectron spectroscopy (XPS) and ODH reaction experiments revealed that the presence of low-valent V4+/Mo4+ ions not only lowers the reduction temperature of oxide catalysts, but also facilitates the capture of O2 on the site of oxygen vacancies. The presence of active sites of low-valent V4+ ions and oxygen vacancies was proposed as the reaction mechanism responsible for the high activity. These results have implications for our understanding of the effects of oxidation processes on reduced multi-component oxides.

Oxidative dehydrogenation of ethyl lactate over nanocarbon catalysts: Effect of oxygen functionalities and defects

Pyruvic acid and pyruvate derivatives are important chemical intermediates which are normally produced using metal-based catalytic materials that could cause serious environmental problems. In the present work, renewable nanocarbon catalysts are applied in this system, and a solvent free and highly selective oxidative dehydrogenation of ethyl lactate (EL) process is achieved to produce ethyl pyruvate (EP) under mild reaction conditions. Chemical titration results provide direct evidence that ketonic carbonyl groups on nanocarbon are active sites for this reaction. Raman, XPS and model catalyst experimental results have shown that there is a dynamic transformation between defects and oxygen functionalities during the catalytic reactions. The reaction pathway is revealed via kinetic analysis, which may shed light on the rational design of carbon catalysts and their potential catalytic applications in the field of fine chemical productions.

Protective effect of thymoquinone, the main component of Nigella Sativa, against diazinon cardio-toxicity in rats

Several studies have shown that oxidative stress and cell damage can occur at very early stages of diazinon (DZN) exposure. The present study was designed to determine the beneficial effect of thymoquinone (Thy), the main component of Nigella sativa (black seed or black cumin), against DZN cardio-toxicity in rats. In the present experimental study, 48 male Wistar rats were randomly divided into six groups: control (corn oil gavages), DZN gavages (20 mg/kg/day), Thy gavages (10 mg/kg/day) and Thy + DVN gavages (2.5, 5 and 10 mg/kg/day). Treatments were continued for 28 days, then the animals were anesthetized by ether and superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), lactate dehydrogenize (LDH) and glutathione peroxide (GPX) activity was evaluated. In addition, glutathione (GSH) and malondialdehyde (MDA) the heart tissue and creatinephosphokinase-MB (CPK-MB) and troponin (TPI) levels and cholinesterase activity in the blood were evaluated. DZN-induced oxidative damage and elevated the levels of the cardiac markers CK-MB, TPI, MDA and LDH and decreased SOD, CAT and cholinesterase activity and GSH level compared with the control group. Treatment with Thy reduced DZN cardio-toxicity and cholinesterase activity. The success of Thy supplementation against DZN toxicity can be attributed to the antioxidant effects of its constituents. Administration of Thy as a natural antioxidant decreased DZN cardio-toxicity and improved cholinesterase activity in rats through the mechanism of free radical scavenging.

Understanding the oxidative dehydrogenation of ethyl lactate to ethyl pyruvate over vanadia/titania

We studied the vapour-phase oxidative dehydrogenation of ethyl lactate to ethyl pyruvate over V2O5/TiO2 catalysts in a fixed-bed reactor.

Serum C-Reactive Protein in Children with Liver Disease and Ascites.

BackgroundThe diagnosis of peritonitis as a complication of cirrhosis is an important clinical problem.ObjectivesThe aim of this study was to evaluate serum C-reactive protein levels as a diagnostic factor for spontaneous bacterial peritonitis (SBP) in child patients with liver disease.MethodsIn this study, 150 children diagnosed with liver disease and ascites upon admission to Nemazee Teaching Hospital (Shiraz, Iran) were examined. Patients were divided into spontaneous bacterial peritonitis and sterile ascetic fluid groups according to the PMN count ≥ 250/mm3 in the ascetic fluids. Routine laboratory tests were conducted and quantitative C-reactive protein (CRP) levels were measured for all of the patients. Accuracy, sensitivity, and specificity of CRP was evaluated for diagnosis of SBP.ResultsOf 150 cirrhotic patients, 109 patients presented without SBP (52.29% male, mean age: 5.02 ± 4.49 years) and 41 patients presented with SBP (51.21% male, mean age: 4.71 years). Cell counts, protein levels, albumin levels, and lactate dehydrogenize (LDH) levels of the ascetic fluid and serum samples in the SBP group were higher than the rates for those without SBP (P < 0.05(. The mean ± SD of CRP in the SBP group (36.89 ± 23.43) increased significantly compared to the rate among those without SBP (21.59 ± 15.43, P = 0.001). The percentages for sensitivity and specificity of CRP, the diagnosis of SBP based on the PMN count ≥ 250/mm3, and cultured ascites were 69.23%, 90.25%, 88.43%, and 84.32%, respectively. The areas under the curve of CRP for SBP based on the PMN count ≥ 250/mm3 and cultured ascites was 0.94 (CI 95%: 0.90 to 0.96) and 0.85 (CI 95%: 0.84 to 0.92), respectively (P < 0.001).ConclusionsOur study showed that CRP is a marker with high sensitivity and specificity for the diagnosis of SBP in cirrhotic children.

Serum C-Reactive Protein in Children with Liver Disease and Ascites

Background: The diagnosis of peritonitis as a complication of cirrhosis is an important clinical problem. Objectives: The aim of this study was to evaluate serum C-reactive protein levels as a diagnostic factor for spontaneous bacterial peritonitis (SBP) in child patients with liver disease. Methods: In this study, 150 children diagnosed with liver disease and ascites upon admission to Nemazee Teaching Hospital (Shiraz, Iran) were examined. Patients were divided into spontaneous bacterial peritonitis and sterile ascetic fluid groups according to the PMN count ≥ 250/mm3 in the ascetic fluids. Routine laboratory tests were conducted and quantitative C-reactive protein (CRP) levels were measured for all of the patients. Accuracy, sensitivity, and specificity of CRP was evaluated for diagnosis of SBP. Results: Of 150 cirrhotic patients, 109 patients presented without SBP (52.29% male, mean age: 5.02 ± 4.49 years) and 41 patients presented with SBP (51.21% male, mean age: 4.71 years). Cell counts, protein levels, albumin levels, and lactate dehydrogenize (LDH) levels of the ascetic fluid and serum samples in the SBP group were higher than the rates for those without SBP (P < 0.05(. The mean ± SD of CRP in the SBP group (36.89 ± 23.43) increased significantly compared to the rate among those without SBP (21.59 ± 15.43, P = 0.001). The percentages for sensitivity and specificity of CRP, the diagnosis of SBP based on the PMN count ≥ 250/mm3, and cultured ascites were 69.23%, 90.25%, 88.43%, and 84.32%, respectively. The areas under the curve of CRP for SBP based on the PMN count ≥ 250/mm3 and cultured ascites was 0.94 (CI 95%: 0.90 to 0.96) and 0.85 (CI 95%: 0.84 to 0.92), respectively (P < 0.001). Conclusions: Our study showed that CRP is a marker with high sensitivity and specificity for the diagnosis of SBP in cirrhotic children.

Kinetics study for the oxidative dehydrogenation of ethyl lactate to ethyl pyruvate over MoVNbOx based catalysts

Mo0.61V0.31Nb0.08Ox and Mo0.61V0.31Nb0.08Ox/TiO2 catalysts were prepared for the oxidative dehydrogenation of ethyl lactate to ethyl pyruvate in a continuous fixed-bed reactor under atmospheric pressure. The transport effects and catalytic stability over Mo0.61V0.31Nb0.08Ox/TiO2 catalyst were investigated to ensure that the experimental results were not significantly influenced by interphase transportation and catalytic deactivation. Mo0.61V0.31Nb0.08Ox/TiO2 catalyst exhibited extremely higher conversion rate of ethyl lactate but relatively lower apparent activation energy in comparison with Mo0.61V0.31Nb0.08Ox, indicating its superior catalytic activity beneficial from the good dispersion of active Mo0.61V0.31Nb0.08Ox component on TiO2 support. It was experimentally verified that the conversion rate of ethyl lactate was simply first-order dependence on the partial pressure of O2 over Mo0.61V0.31Nb0.08Ox/TiO2. The analysis of elementary reaction steps and the derivation of reaction rate equation were performed based on typical Mars–van Krevelen (MvK) redox mechanism under the assumption that surface oxygen vacancies were the most abundant species. The obtained reaction rate equation was a first-order function towards O2 partial pressure, which was good consistent with the experimental kinetics results.

Clinical Characteristics and Outcome of 104 Patients with Gastric Diffuse B-Cell Non-Hodgkin Lymphoma (DLBCL) a Multicenter Study

Background: Gastric lymphoma is the most common extra nodal B cell Non Hodgkin Lymphoma and DLBCL accounts for 70% of cases in the stomach. The clinical course is heterogeneous and clinical symptoms, laboratorial abnormalities and Helicobacter pylori and hepatitis B and C infections, in addition to classical IPI factors, have been related to prognosis. Different clinical behaviors may reflect distinct pathogenic mechanisms. In order to improve outcomes, a better characterization of prognostic factors is required.Aim: We aimed to identify factors with a potential prognosis impact in a consecutive series of gastric DLBCL patients diagnosed and treated in three referee Centers in Brazil, Portugual and Italy, by analyzing demographic and clinical characteristics, response to treatment and outcome (overall survival). The clinical picture of European and Brazilian populations was also compared.Patients and Methods: Between January 2010 and May 2015, 104 DLBCL were enrolled in this study. In order to establishing correlations between the clinical features and response to treatment the following parameters were analyzed: clinical symptoms, serum albumin, serum lactate dehydrogenize (LDH),b 2microglobulin, tumor bulky stage of disease, age-adjusted international prognostic index (aaIPI), and response to treatment. Statistical analysis using SPSS software included descriptive analyses, Kaplan-Meyer estimates for overall survival and Cox regression;p values <0.05 were considered significant. The final analyses were adjusted to Brazilian and European patients due to different clinical data at diagnosis.Results: 104 patients, median age 69 (28-88) years, were enrolled in this study, with a female: male ratio of 1.2:1. Their ECOG performance status was 0 in 48.5%; 1 and 2 in 42.6% and ≥3 in 8.9% cases, whereas aaIPI risk distribution was 12 (12.6%) high risk, 20 (21.1.%) high-intermediate risk and 63 (66.3%) low/low-intermediate high in 57/80 patients (71.2%). The test for identification of Helicobacter Pillory (HP) was performed in 45 patients and was positive in 13 (28.9%); also Hepatitis B serology, available in 97 cases, 46.4% positive. The most common symptoms included abdominal pain (63/74) and weight loss (57/73), dysphalgia (37/72) and nausea, vomiting (37/72). Bulky wasfound in 24%, plus anemia (33/76) and bleeding (22/72). Endoscopic examination was realized in 95%, however, only 10% was submitted to surgery. Brazilian patients were younger and more frequently symptomatic at diagnosis, although aaIPI was similar among the two populations. Almost all patients received chemotherapy (96% RCHOP-like).The median follow-up time was 14 (1-77) months, with 1- and 5-year survival rates of 79 and 76%, respectively. 5-year survival rates were significantly influenced by anemia (p= 0.007), LDH at the diagnosis (p< 0.0001), B symptoms (p<0.0001), clinical stage (p= 0.003), aaIPI 2 and 3 (p<0.0001), nausea (p=0.04) and bulky disease (p=0.02). Other variables, including gender (p= 0.17), presence of dysphagia (p= 0.08), weigh loss (p= 0.11), pain (p= 0.14) and bleeding (p= 0.06) and elevated β2microglobulin at diagnosis (p= 0.09) didn't influence the outcome.Furthermore, multivariate analysis applying Cox Regression and adjusted by Brazilian and European patients confirmed that overall survival was only influenced by aaIPI 2 and 3 (HR 9.16, CI95%: 2.16-16.8; p< 0.0001) and female gender (HR 2.71, CI95%: 1.03-7.13; p= 0.004).In conclusionIn this series of European and Brazilian gastric DLBCL patients were confirmed the impact of aaIPI on survival and identified female gender as poor prognosis factor. Differences in clinical presentation among countries may relate to heterogeneous disease biology and deserve further investigations. DisclosuresLuminari:Roche: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees.

Protective effect of carbachol postconditioning on hypoxia/reoxygenation-induced injury in human gastric epithelial cells.

We investigated the protective effects of carbachol postconditioning (CAR-P) on acute gastric mucosal injury induced by hypoxia/reoxygenation (H/R) and its possible mechanisms. Cell viability was detected by methyl thiazolyl tetrazolium (MTT). The apoptotic cells were examined by Hoechst 33258 staining. Flow cytometric analysis, lactate dehydrogenate (LDH) release assay, immunocytochemistry, and western blotting were used to investigate the effects of CAR-P on acute gastric mucosal injury induced by H/R. The model of H/R was established by hypoxia induction(94% N2+1% O2+5% CO2 for 2 h) and reoxygenation (normoxic condition for 4 h, 8 h and 16 h). Our study observed the protective effect of carbachol postconditioning on H/R-induced injury in human gastric epithelial cell lines (hGES-1) cells, which is achieved by direct activation of vanilloid receptor subtype 1 (VR1) and production of calcitonin gene-related peptide (CGRP), and in the inhibition of cell apoptosis. In the study, we demonstrate that CAR-P has protective effects on the H/R-induced injury in hGES-1 cells, and these effects are associated with cholinergic muscarinic receptors (CMR), VR1, and extracellular signal-regulated kinase (ERK) signaling pathway. Our findings might provide a new and improved understanding of CAR-P function and an effective treatment strategy for acute gastric mucosal injury induced by H/R.

Clinical Characteristics and Outcome of 41 Patients with Upper GI Diffuse B-Cell Non-Hodgkin Lymphoma. Results of Brazilian-Italy Lymphoma Registry

Background: Gastrointestinal lymphoma represents only 1-4% of the malignant tumors in the gastrointestinal tract and is the most common extranodal site among all types of Non- Hodgkin Lymphomas (NHL). Only 3% of gastric neoplasms are primary lymphomas.Aim: Identification of factors with a potential prognostic impact among all cases with aggressive gastric diffuse large B-cell lymphoma - the clinical characteristics, the response to therapy and overall survival in the Brazilian-Italy Lymphoma registry.Patients and Methods: Between January 1st 2010 and May 1st 2014, 267 patients with DLBCL were recorded of which 41 (15%) had gastric involvement. The following parameters were evaluated to establish correlations with the response to treatment and survival data: clinical symptoms, serum albumin, serum lactate dehydrogenize (LDH), b2 microglobulin, presence of local regional adenopathies, bulky tumor, stage of disease, international prognostic index (IPIa), type of treatment – surgery plus chemotherapy.Results: A total of 41 patients, with a median age of 69 (28-86) years, were enrolled in this study, with a female: male ratio of 1.7:1. Their ECOG performance status was distributed in 44% grade 0; 34% grade 1; 14.6% grade 2 and 7.4% grade 3, whereas IPIa classification was 5 (12.2%) patients with high risk; 14 (34.2%) high-intermediate risk and 22 (53.6%) low- intermediate risk.Stage III-IV was presented in 66% of cases. LDH values were elevated in 17 patients (41.5%), b2 microglobulin value were elevated in 31 patients (75.6%). The test for identification of Helicobacter Pillory (HP) was available in 33 patients and was positive in 9 patients (27%). The most common symptoms included abdominal pain and weight loss (both 86%), dysphagia (80%) and nausea, vomiting (74%). Bulky were found in 27%, plus anemia (44%) and bleeding (25%). Endoscopic examination was realized in 94%, however, only 8% was submitted to surgery. 39 patients received chemotherapy (84% R-CHOP), one Brazilian case died early and one Italian case was lost follow up. Overall 17.5% (7/40) received radiotherapy. The median follow-up time was 14 (1-71) months, with 1-, 2- and 5-year survival rates of 73, 63 and 58%, respectively. It was found the 5-year overall survival (OS) rate differed significantly according to Anemia (p= 0.02) and LDH at the diagnosis (p< 0.0001). Among Brazilian and Italian patients the difference clinical characteristics were B symptoms (p=0.02); weight loss (p= 0.003); nausea/vomiting (p= 0.002); pain and dysphagia (p< 0.0001); showing a wider severity in Brazilian group. Although it did not mean a worst outcome. There was no statistically significant differences in terms of OS according to gender (p=0.19); B symptoms (p= 0.12); bleeding at the diagnosis (p= 0.08) and clinical stage (p= 0.14). Furthermore, the only confirmed factor that influenced OS applying Cox Regression was the LDH (HR 8.74, 95% CI: 2.32-32.8; p= 0.001).In conclusion, the median follow-up time of DLBCL group with gastric involvement does not differ in relation to overall DLBCL patients; nevertheless, it was found negative factors for these patients: anemia and increased LDH at the diagnosis. Furthermore, in the Brazilian patients the HP researching is necessary due the high frequency in this population. DisclosuresNo relevant conflicts of interest to declare.

Plasma biochemistry values in wild female hawksbill turtles (Eretmochelys imbricata), during nesting and foraging seasons in Qeshm Island, Persian Gulf

Normal reference ranges of biochemical parameters are considered important for assessing and monitoring the health status of sea turtles. For this study, plasma biochemistry determinations were analyzed in normal adult nesting and foraging hawksbill turtles (Eretmochelys imbricata). Blood samples were collected in March–April during (nesting season) and December–November (foraging season). Differences in plasma biochemistry values, except for creatinine and lipase, were statistically different (P < 0.05) between the two periods. Glucose, cholesterol, triglycerides, ALP (alkaline phosphates), AST (aspartate aminotransferase), bilirubin, total protein, LDH (lactate dehydrogenize), CK (creatine kinase), and amylase were significantly higher in nesting season than foraging season (P < 0.05). Whereas, urea, ALT (alanine aminotransferase), and albumin in the nesting season were significantly lower than during the foraging season (P < 0.05). It was concluded that the nesting E. imbricata showed significant variation in their biochemical profile due to reproductive output. This study has produced working reference intervals useful for hawksbill turtles for future conservation and rehabilitation projects in the Persian Gulf and may be of assistance in similar programs worldwide.