Safety and tolerability of a novel oral nutritional supplement in healthy volunteers.

BACKGROUND AND OBJECTIVE: Foods for Special Medical Purposes (FSMPs) are formulated to support the nutritional needs of subjects with impaired capacity to ingest, digest or absorb ordinary food or nutrients. Polglumyt® is a proprietary highly purified, high quality glycogen obtained from mussels. Here we report the results of a single-center, single dose, open label, single arm study carried out to investigate acceptance (i.e. gastrointestinal tolerance and palatability), metabolic profile and safety of a low osmolarity, high-density energy Polglumyt®-based drink (the investigational product, IP) as a novel FSMP. METHODS: Twelve healthy subjects received a single oral administration of the IP under fasting conditions. The study endpoints were: changes in gastrointestinal system tolerability at 3 h, 6 h and 24 h after IP intake; IP palatability evaluation; metabolic evaluation through the kinetic profile of circulating glucose, insulin and C-peptide from 0 h to 6 h after IP intake and changes from baseline in circulating triglycerides at 3 h and 6 h after IP intake. RESULTS: The IP showed a good gastrointestinal tolerability and an acceptable palatability. The IP did not affect the physiological glycemic profile and the triglycerides levels 6 h after the intake. The IP was well tolerated by study subjects, with no or minor adverse events. CONCLUSIONS: The study results encourage additional clinical investigations on the IP as a novel FSMP in patients with impaired digestion or gastrointestinal absorption, unable to assume an ordinary diet, e.g. patients undergoing invasive gastrointestinal surgery, elderly or oncological patients, even with certain metabolic disorders.

Phytoglycogen Nanoparticle Delivery System for Inorganic Selenium Reduces Cytotoxicity without Impairing Selenium Bioavailability.

PURPOSE: Selenium is an essential trace element that supports animal health through the antioxidant defense system by protecting cells from oxidative-related damage. Using inorganic selenium species, such as sodium selenite (Na Sel), as a food supplement is cost-effective; however, its limitation as a nutritional supplement is its cytotoxicity. One strategy to mitigate this problem is by delivering inorganic selenium using a nanoparticle delivery system (SeNP). METHODS: Rainbow trout intestinal epithelial cells, bovine turbinate cells and bovine intestinal myofibroblasts were treated with soluble Na Sel or SeNPs. Two SeNP formulations were tested; SeNP-Ionic where inorganic selenium was ionically bound to cationic phytoglycogen (PhG) NPs, and SeNP-Covalent, where inorganic selenium was covalently bound to PhG NPs. Selenium-induced cytotoxicity along with selenium bioavailability were measured. RESULTS: SeNPs (SeNP-Ionic or SeNP-Covalent) substantially reduced cytotoxicity in all cell types examined compared to similar doses of soluble inorganic selenium. The SeNP formulations did not affect selenium bioavailability, as selenium-induced glutathione peroxidase (GPx) activity and GPx1 transcript levels were similarly elevated whether cells were treated with soluble Na Sel or SeNPs. This was the case for all three cell types tested. CONCLUSION: Nanoparticle-assisted inorganic selenium delivery, which demonstrated equal bioavailability without causing deleterious cytotoxic side effects, has potential applications for safely supplementing animal diets with inorganic selenium at what are usually toxic doses.

Effects of dietary protein and lipid levels on the growth performance, feed utilization, and liver histology of largemouth bass (Micropterus salmoides).

The reported requirements of largemouth bass (LMB, which is native to North America) for dietary protein and lipids varied substantially among previous studies, and this fish fed current formulated diets exhibit poor growth performance and pale liver syndrome. Because amino acids and lipids are known to affect hepatic metabolism and function in mammals, it is imperative to understand the impacts of these dietary macronutrients on the growth and liver morphology of LMB. In this study, we designed six isocaloric diets to determine the effects of different dietary crude protein (CP; 40%, 45%, and 50%; dry matter basis) and lipid levels (7.5% and 10%; dry matter basis) on fat and glycogen deposits, as well as hepatosis in LMB. There were four tanks (12 fish per tank, an average initial weight of 18.4 g/fish) per dietary treatment group and the trial lasted for 8 weeks. Fish were fed to apparent satiation three times daily. Results indicated that LMB fed the 45% or 50% CP diet grew faster (P < 0.05), had less (P < 0.05) glycogen in the liver and smaller (P < 0.05) hepatocyte sizes than fish fed the 40% CP diet, but there was no difference in weight gain or feed efficiency between the 45% and 50% CP diets. The hepatic lipid content did not differ between LMB fed the 40% and 45% CP diets, and the values for these two groups were 29% lower (P < 0.05) than those for LMB fed the 50% CP diet. Compared with the 40% CP group, LMB fed the 45% or 50% CP diet had 8-12% lower content of total minerals, phosphorus, and calcium in the body. Increasing the dietary lipid level from 7.5 to 10% enhanced the weight gains (+ 15%) and feed efficiency (+ 22%), as well as the retention of dietary protein (+ 18%), energy (+ 25%), and phosphorus (+ 7.6%) in the body. No fatty liver occurred in any group of LMB (with hepatic lipid concentrations being < 2%, wet weight basis). Based on these growth, metabolic and histologic data, we recommend dietary CP and lipids levels to be 45% and 10%, respectively, for juvenile LMB.

Glycogen as an advantageous polymer carrier in cancer theranostics: Straightforward in vivo evidence.

As a natural polysaccharide polymer, glycogen possesses suitable properties for use as a nanoparticle carrier in cancer theranostics. Not only it is inherently biocompatible, it can also be easily chemically modified with various moieties. Synthetic glycogen conjugates can passively accumulate in tumours due to enhanced permeability of tumour vessels and limited lymphatic drainage (the EPR effect). For this study, we developed and examined a glycogen-based carrier containing a gadolinium chelate and near-infrared fluorescent dye. Our aim was to monitor biodistribution and accumulation in tumour-bearing rats using magnetic resonance and fluorescence imaging. Our data clearly show that these conjugates possess suitable imaging and tumour-targeting properties, and are safe under both in vitro and in vivo conditions. Additional modification of glycogen polymers with poly(2-alkyl-2-oxazolines) led to a reduction in the elimination rate and lower uptake in internal organs (lower whole-body background: 45% and 27% lower MRI signals of oxazoline-based conjugates in the liver and kidneys, respectively compared to the unmodified version). Our results highlight the potential of multimodal glycogen-based nanopolymers as a carrier for drug delivery systems in tumour diagnosis and treatment.

Fuel Use during Exercise at Altitude in Women with Glucose-Fructose Ingestion.

PURPOSE: This study compared the coingestion of glucose and fructose on exogenous and endogenous substrate oxidation during prolonged exercise at terrestrial high altitude (HA) versus sea level, in women. METHOD: Five women completed two bouts of cycling at the same relative workload (55% Wmax) for 120 min on acute exposure to HA (3375 m) and at sea level (~113 m). In each trial, participants ingested 1.2 g·min of glucose (enriched with C glucose) and 0.6 g·min of fructose (enriched with C fructose) before and every 15 min during exercise. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate fat oxidation, total and exogenous carbohydrate oxidation, plasma glucose oxidation, and endogenous glucose oxidation derived from liver and muscle glycogen. RESULTS: The rates and absolute contribution of exogenous carbohydrate oxidation was significantly lower at HA compared with sea level (effect size [ES] > 0.99, P < 0.024), with the relative exogenous carbohydrate contribution approaching significance (32.6% ± 6.1% vs 36.0% ± 6.1%, ES = 0.56, P = 0.059) during the second hour of exercise. In comparison, no significant differences were observed between HA and sea level for the relative and absolute contributions of liver glucose (3.2% ± 1.2% vs 3.1% ± 0.8%, ES = 0.09, P = 0.635 and 5.1 ± 1.8 vs 5.4 ± 1.7 g, ES = 0.19, P = 0.217), and muscle glycogen (14.4% ± 12.2% vs 15.8% ± 9.3%, ES = 0.11, P = 0.934 and 23.1 ± 19.0 vs 28.7 ± 17.8 g, ES = 0.30, P = 0.367). Furthermore, there was no significant difference in total fat oxidation between HA and sea level (66.3 ± 21.4 vs 59.6 ± 7.7 g, ES = 0.32, P = 0.557). CONCLUSIONS: In women, acute exposure to HA reduces the reliance on exogenous carbohydrate oxidation during cycling at the same relative exercise intensity.

Biological characterization of a novel hybrid copolymer carrier system based on glycogen.

The effective drug delivery systems for cancer treatment are currently on high demand. In this paper, biological behavior of the novel hybrid copolymers based on polysaccharide glycogen were characterized. The copolymers were modified by fluorescent dyes for flow cytometry, confocal microscopy, and in vivo fluorescence imaging. Moreover, the effect of oxazoline grafts on degradation rate was examined. Intracellular localization, cytotoxicity, and internalization route of the modified copolymers were examined on HepG2 cell line. Biodistribution of copolymers was addressed by in vivo fluorescence imaging in C57BL/6 mice. Our results indicate biocompatibility, biodegradability, and non-toxicity of the glycogen-based hybrid copolymers. Copolymers were endocyted into the cytoplasm, most probably via caveolae-mediated endocytosis. Higher content of oxazoline in polymers slowed down cellular uptake. No strong colocalization of the glycogen-based probe with lysosomes was observed; thus, it seems that the modified externally administered glycogen is degraded in the same way as an endogenous glycogen. In vivo experiment showed relatively fast biodistribution and biodegradation. In conclusion, this novel nanoprobe offers unique chemical and biological attributes for its use as a novel drug delivery system that might serve as an efficient carrier for cancer therapeutics with multimodal imaging properties.

Preactivated thiolated glycogen as mucoadhesive polymer for drug delivery.

The purpose of this study was to synthesize and characterize a novel thiolated glycogen, so-named S-preactivated thiolated glycogen, as a mucosal drug delivery systems and the assessment of its mucoadhesive properties. In this regard, glycogen-cysteine and glycogen-cysteine-2-mercaptonicotinic acid conjugates were synthesized. Glycogen was activated by an oxidative ring opening with sodium periodate resulting in reactive aldehyde groups to which cysteine was bound via reductive amination. The obtained thiolated polymer displayed 2203.09±200µmol thiol groups per gram polymer. In a second step, the thiol moieties of thiolated glycogen were protected by disulfide bond formation with the thiolated aromatic residue 2-mercaptonicotinic acid (2MNA). In vitro screening of mucoadhesive properties was performed on porcine intestinal mucosa using different methods. In particular, in terms of rheology investigations of mucus/polymer mixtures, the S-preactivated thiolated glycogen showed a 4.7-fold increase in dynamic viscosity over a time period of 5h, in comparison to mucus/Simulated Intestinal Fluid control. The S-preactivated polymer remained attached on freshly excised porcine mucosa for 45h. Analogous results were obtained with tensile studies demonstrating a 2.7-fold increase in maximum detachment force and 3.1- fold increase in total work of adhesion for the S-preactivated polymer compared to unmodified glycogen. Moreover, water-uptake studies showed an over 4h continuing weight gain for the S-preactivated polymer, whereas disintegration took place for the unmodified polymer within the first hour. Furthermore, even in the highest tested concentration of 2mg/ml the new conjugates did not show any cytotoxicity on Caco-2 cell monolayer using an MTT assay. According to these results, S-preactivated glycogen represents a promising type of mucoadhesive polymers useful for the development of various mucosal drug delivery systems.

Manipulation of Muscle Creatine and Glycogen Changes Dual X-ray Absorptiometry Estimates of Body Composition.

Standardizing a dual x-ray absorptiometry (DXA) protocol is thought to provide a reliable measurement of body composition. PURPOSE: We investigated the effects of manipulating muscle glycogen and creatine content independently and additively on DXA estimates of lean mass. METHOD: Eighteen well-trained male cyclists undertook a parallel group application of creatine loading (n = 9) (20 g·d for 5 d loading; 3 g·d maintenance) or placebo (n = 9) with crossover application of glycogen loading (12 v 6 g·kg BM per day for 48 h) as part of a larger study involving a glycogen-depleting exercise protocol. Body composition, total body water, muscle glycogen and creatine content were assessed via DXA, bioelectrical impedance spectroscopy and standard biopsy techniques. Changes in the mean were assessed using the following effect-size scale: >0.2 small, >0.6, moderate, >1.2 large and compared with the threshold for the smallest worthwhile effect of the treatment. RESULTS: Glycogen loading, both with and without creatine loading, resulted in substantial increases in estimates of lean body mass (mean ± SD; 3.0% ± 0.7% and 2.0% ± 0.9%) and leg lean mass (3.1% ± 1.8% and 2.6% ± 1.0%) respectively. A substantial decrease in leg lean mass was observed after the glycogen depleting condition (-1.4% ± 1.6%). Total body water showed substantial increases after glycogen loading (2.3% ± 2.3%), creatine loading (1.4% ± 1.9%) and the combined treatment (2.3% ± 1.1%). CONCLUSIONS: Changes in muscle metabolites and water content alter DXA estimates of lean mass during periods in which minimal change in muscle protein mass is likely. This information needs to be considered in interpreting the results of DXA-derived estimates of body composition in athletes.

Enzymatically synthesized glycogen inhibits colitis through decreasing oxidative stress.

Inflammatory bowel diseases are a group of chronic inflammation conditions of the gastrointestinal tract. Disruption of the mucosal immune response causes accumulation of oxidative stress, resulting in the induction of inflammatory bowel disease. In this study, we investigated the effect of enzymatically synthesized glycogen (ESG), which is produced from starch, on dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in C57BL/6 mice. Oral administration of ESG suppressed DSS- and TNBS-induced shortening of large intestine in female mice and significant decreased DSS-induced oxidative stress and TNBS-induced pro-inflammatory cytokine expression in the large intestine. ESG increase in the expression levels of heme oxygenase-1 (HO-1) and NF-E2-related factor-2 (Nrf2), a transcription factor for HO-1 expressed in the large intestine. Furthermore, ESG-induced HO-1 and Nrf2 were expressed mainly in intestinal macrophages. ESG is considered to be metabolized to resistant glycogen (RG) during digestion with α-amylase in vivo. In mouse macrophage RAW264.7 cells, RG, but not ESG decreased 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced reactive oxygen species (ROS). Knockdown of Nrf2 inhibited RG-induced HO-1 expression and negated the decrease in AAPH-induced ROS brought about by RG. RG up-regulated the protein stability of Nrf2 to decrease the formation of Nrf2-Keap1 complexes. RG-induced phosphorylation of Nrf2 at Ser40 was suppressed by ERK1/2 and JNK inhibitors. Our data indicate that ESG, digested with α-amylase to RG, suppresses DSS- and TNBS-induced colitis by increasing the expression of HO-1 in the large intestine of mice. Furthermore, we demonstrate that RG induces HO-1 expression by promoting phosphorylation of Nrf2 at Ser40 through activation of the ERK1/2 and JNK cascade in macrophages.

Effects of Enzymatically Synthesized Glycogen and Exercise on Abdominal Fat Accumulation in High-Fat Diet-Fed Mice.

The combination of diet and exercise is the first choice for the treatment of obesity and metabolic syndrome. We previously reported that enzymatically synthesized glycogen (ESG) suppresses abdominal fat accumulation in obese rats. However, the effect of the combination of ESG and exercise on abdominal fat accumulation has not yet been investigated. Our goal in this study was therefore to evaluate the effects of dietary ESG and its combination with exercise on abdominal fat accumulation in high-fat diet (HFD)-fed mice. Male ICR mice were assigned to four groups: HFD, HFD containing 20% ESG, HFD with exercise, HFD containing 20% ESG with exercise. Treadmill exercise was performed for 3 wk (25 m/min, 30 min/d, 3 d/wk) after 5-d adaption to running at that speed. Both ESG and exercise significantly reduced the weights of abdominal adipose tissues. In addition, the combination of ESG and exercise significantly suppressed abdominal fat accumulation, suggesting that ESG and exercise showed an additive effect. Exercise significantly increased the mRNA levels of lipid metabolism-related genes such as lipoprotein lipase, peroxisome proliferator-activated receptor delta; factor-delta (PPARδ), carnitin palmitoyltransferase b, adipose triglyceride lipase (ATGL), and uncoupling protein-3 in the gastrocnemius muscle. On the other hand, dietary ESG significantly decreased the mRNA levels of PPARδ and ATGL in the gastrocnemius muscle. These results suggest that the combined treatment of ESG and exercise effectively suppresses abdominal fat accumulation in HFD-fed mice by different mechanisms.

The impact of sleeping with reduced glycogen stores on immunity and sleep in triathletes.

PURPOSE: We investigated the effects of a 3-week dietary periodization on immunity and sleep in triathletes. METHODS: 21 triathletes were divided into two groups with different nutritional guidelines during a 3-week endurance training program including nine twice a day sessions with lowered (SL group) or maintained (CON group) glycogen availability during the overnight recovery period. In addition to performance tests, sleep was monitored every night. Systemic and mucosal immune parameters as well as the incidence of URTI were monitored every week of the training/nutrition protocol. Two-ways ANOVA and effect sizes were used to examine differences in dependent variables between groups at each time point. RESULTS: The SL group significantly improved 10 km running performance (-1 min 13 s, P < 0.01, d = 0.38), whereas no improvement was recorded in the CON group (-2 s, NS). No significant changes in white blood cells counts, plasma cortisol and IL-6 were recorded over the protocol in both groups. The vitamin D status decreased in similar proportions between groups, whereas salivary IgA decreased in the SL group only (P < 0.05, d = 0.23). The incidence of URTI was not altered in both groups. All participants in both groups went to bed earlier during the training program (SL -20 min, CON -27 min, P < 0.05, d = 0.28). In the SL group, only sleep efficiency slightly decreased by 1.1 % (P < 0.05, d = 0.25) and the fragmentation index tended to increase at the end of the protocol (P = 0.06). CONCLUSION: Sleeping and training the next morning regularly with reduced glycogen availability has minimal effects on selected markers of immunity, the incidence of URTI and sleeping patterns in trained athletes.

Efectos de bebidas carbohidratadas y proteicas sobre la recuperación del esfuerzo / Effects of carbohydrate-protein beverages on recovery from exercise

Este artículo aporta una revisión del efecto de la coingesta de la proteína de suero de leche y proteína caseína administradas en bebidas carbohidratadas, sobre la recuperación y los parámetros del daño muscular en ejercicios de larga duración. La búsqueda se ha realizado en abril de 2013 en las bases de datos del ISI Web of Knowledge, SCOPUS, Sport Discuss, PubMed, Medline, Sportdiscus, y en las bases de datos CINDOC en las redes CTI-CSIC, RESH, DICE y DIALNET cruzando los descriptores "Exercise", "Resistance training" y "Recovery" con los términos "Ergogenic beverage", "Casein Protein" y "Whey Protein". La estrategia nutricional más respaldada es la ingesta de un preparado líquido carbohidratado en donde se combinan proteínas de diferentes fuentes sobre pruebas de esfuerzos prolongados similares a la competición tanto en deportes individuales como en colectivos, con resultados discrepantes (AU)

This manuscript shows a review about the effects of the whey and casein protein on recovery and parameters of muscle damage in long-term exercise. The search was conducted in April 2013 in the databases of ISI Web of Knowledge, SCOPUS, PubMed, Medline, SportDiscus, and databases on Spanish networks CINDOC CTI-CSIC, RESH, DICE, and DIALNET crossing the descriptors "Exercise", "Resistance training" and "Recovery" with the terms "Ergogenic Beverage", "Casein Protein" and "Whey Protein". The most used nutritional strategies are based in a carbohydrate beverage which combines different protein sources on prolonged exercise tests similar to sports competition, in both individual and collective sports, with discrepant results (AU)

An efficient nonviral gene-delivery vector based on hyperbranched cationic glycogen derivatives.

BACKGROUND: The purpose of this study was to synthesize and evaluate hyperbranched cationic glycogen derivatives as an efficient nonviral gene-delivery vector. METHODS: A series of hyperbranched cationic glycogen derivatives conjugated with 3-(dimethylamino)-1-propylamine (DMAPA-Glyp) and 1-(2-aminoethyl) piperazine (AEPZ-Glyp) residues were synthesized and characterized by Fourier-transform infrared and hydrogen-1 nuclear magnetic resonance spectroscopy. Their buffer capacity was assessed by acid-base titration in aqueous NaCl solution. Plasmid deoxyribonucleic acid (pDNA) condensation ability and protection against DNase I degradation of the glycogen derivatives were assessed using agarose gel electrophoresis. The zeta potentials and particle sizes of the glycogen derivative/pDNA complexes were measured, and the images of the complexes were observed using atomic force microscopy. Blood compatibility and cytotoxicity were evaluated by hemolysis assay and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, respectively. pDNA transfection efficiency mediated by the cationic glycogen derivatives was evaluated by flow cytometry and fluorescence microscopy in the 293T (human embryonic kidney) and the CNE2 (human nasopharyngeal carcinoma) cell lines. In vivo delivery of pDNA in model animals (Sprague Dawley rats) was evaluated to identify the safety and transfection efficiency. RESULTS: The hyperbranched cationic glycogen derivatives conjugated with DMAPA and AEPZ residues were synthesized. They exhibited better blood compatibility and lower cytotoxicity when compared to branched polyethyleneimine (bPEI). They were able to bind and condense pDNA to form the complexes of 100-250 nm in size. The transfection efficiency of the DMAPA-Glyp/pDNA complexes was higher than those of the AEPZ-Glyp/pDNA complexes in both the 293T and CNE2 cells, and almost equal to those of bPEI. Furthermore, pDNA could be more safely delivered to the blood vessels in brain tissue of Sprague Dawley rats by the DMAPA-Glyp derivatives, and then expressed as green fluorescence protein, compared with the control group. CONCLUSION: The hyperbranched cationic glycogen derivatives, especially the DMAPA-Glyp derivatives, showed high gene-transfection efficiency, good blood compatibility, and low cyto toxicity when transfected in vitro and in vivo, which are novel potential nonviral gene vectors.

Embryo gene expression in response to maternal supplementation with glycogenic precursors in the rabbit.

Disturbing maternal metabolism during the first pregnancy and postpartum period is associated with sub fertility in rabbit does. Nutritional strategies can be used during those periods and its effects to improve reproductive management may affect periconceptional events and early embryo development. Our goal was to elucidate if treatment with a glycogenic precursor such as propylene glycol (PG) could affect the maternal metabolic profile, follicular and oocyte quality and gene expression patterns in early embryos. Rabbit does were supplemented with 2.5% (v/v) PG from either mid-pregnancy and for 25 days of lactation (PG-GL group); only during lactation (PG-L group); or were not treated (control group). Ovarian parameters and embryos were studied at the end of treatment. At parturition serum non-esterified fatty acid concentrations increased whilst insulin decreased in all groups. Maternal feed intake was reduced in PG-supplemented does but glycaemia was maintained during the experimental period. When PG was suppressed, blood insulin immediately increased in PG-groups, but no differences in follicular population, follicular atresia, and nuclear and cytoplasmic oocyte maturation were observed compared with non-treated animals. Although embryo development was similar among groups, mRNA of SLC2A4, INSR, IGF1R, PLAC8, COX2 and IGF2R were up regulated in the blastocysts of PG-GL does. Transcripts of SOD1 were lower in PG-L embryos; but NOS3 and TP53 were similar among groups. PG did not affect the maternal metabolic profile during the postpartum period, nor the ovarian response or number of embryos developed. Nonetheless, PG supplied from mid-pregnancy modified mRNA transcripts involved in some important developmental and metabolic events in the blastocysts of those females. More experiments are needed to elucidate the physiological consequence of these results.

Enzymatically synthesized glycogen reduces lipid accumulation in diet-induced obese rats.

Based on a recent study indicating that enzymatically synthesized glycogen (ESG) possesses a dietary, fiber-like action, we hypothesized that ESG can reduce the risk of obesity. In this study, the antiobesity effects of ESG were investigated in a model of diet-induced obesity. Male Sprague-Dawley rats were divided into 4 groups and fed a normal or high-fat diet, with or without 20% ESG, for 4 weeks. Body weight, food intake, lipid deposition in the white adipose tissues and liver, fecal lipid excretion, and plasma lipid profiles were measured. At week 3, the body fat mass was measured using an x-ray computed tomography system, which showed that ESG significantly suppressed the high-fat diet-induced lipid accumulation. Similar results were observed in the weight of the adipose tissue after the experiment. Moreover, ESG significantly suppressed the lipid accumulation in the liver but increased fecal lipid excretion. The plasma concentrations of triacylglycerol and nonesterified fatty acid were lowered after a high-fat diet, whereas the total bile acid concentration was increased by ESG. However, the hepatic messenger RNA (mRNA) levels of enzymes related to lipid metabolism were not affected by ESG. Conversely, the mRNA levels of long-chain acyl-CoA dehydrogenase and medium-chain acyl-CoA dehydrogenase were up-regulated by ESG in the muscle. These results suggest that the combined effects of increased fecal lipid excretion, increased mRNA levels of enzymes that oxidize fatty acids in the muscle, and increased total bile acid concentration in the plasma mediate the inhibitory effect of ESG on lipid accumulation.

Metabolic fate of orally administered enzymatically synthesized glycogen in rats.

We developed a new process for enzymatically synthesized glycogen (ESG), which is equivalent in physicochemical properties to natural-source glycogen (NSG) except its resistant property to degradation by α-amylase in vitro. In this study the metabolic fates of orally administered ESG in rats were investigated by a single oral administration test and a 2 week ingestion test. The glycemic index of ESG was 79. After the 2 week ingestion of ESG, the cecal content and production of short chain fatty acids were significantly increased, the pH value of cecal content was lowered, and the counts of Bifidobacterium and Lactobacillus in feces were significantly increased. Additionally, plasma levels of triacylglycerol and total cholesterol were significantly reduced by ESG. In contrast, NSG did not affect these parameters at all. The results collectively suggest that around 20% of orally administered ESG was transferred to the cecum in the form of polymer and assimilated into short chain fatty acids by microbiota and the polymer affected lipid metabolism.

Hepatocellular glycogen in alleviation of liver ischemia-reperfusion injury during partial hepatectomy.

BACKGROUND: Temporary occlusion of liver blood supply for complex liver operation is common in liver surgery. However, hepatic vascular occlusion will undoubtedly impair liver function. This study was designed to elucidate the effect of hepatocellular glycogen in alleviation of liver ischemia-reperfusion injury during hepatic vascular occlusion for partial hepatectomy. METHODS: Fifty-seven patients were randomly divided into an experimental group (n = 29) and a control group (n = 28). In the experimental group, patients were given high-concentration glucose intravenously during 24 h before the operation. The hepatic lesion was resected after portal triad clamping in the two groups. Noncancer liver tissue was biopsied to measure hepatic tissue ATP content and change of malondialdehyde (MDA) and superoxide dismutase (SOD). Liver function of all patients was assessed by using an automatic biochemical analysis apparatus before the operation and the first and fifth days after operation. RESULTS: The mean hepatic vascular occlusion time in the experimental group was 19.21 +/- 4.54 min and in the control group it was 21.04 +/- 5.11 min. Hepatic tissue ATP content of the experimental group was significantly higher than that of the control group at the end of hepatic vascular occlusion (2.15 +/- 0.39 mumol/g wet tissue vs. 1.33 +/- 0.44, p < 0.01) and at the point of 1-h reperfusion (2.19 +/- 0.29 mumol/g wet tissue vs. 1.57 +/- 0.35, p < 0.01). There was significant difference in SOD activity between the two groups at the end of hepatic vascular occlusion (130.69 +/- 30.49 NU/mg pr vs. 97.83 +/- 26.23, p < 0.01) and at the point of 1-h reperfusion (139.55 +/- 39.88 NU/mg pr vs. 114.74 +/- 25.93, p < 0.01). Significant difference was shown in MDA content between the two groups at the end of hepatic vascular occlusion (3.02 +/- 0.30 nmol/mg pr vs. 3.99 +/- 0.49, p < 0.01) and at the point of 1-h reperfusion (3.81 +/- 0.69 nmol/mg pr vs. 5.75 +/- 1.17, p < 0.01). In addition, the liver function of the experimental group was significantly better than that of the control group the first and fifth days after the operation (p < 0.01). CONCLUSIONS: Abundant intracellular glycogen may reduce liver ischemia-reperfusion injury caused by hepatic vascular occlusion. It is beneficial to give a large amount of glucose before a complex liver operation during which temporary occlusion of hepatic blood flow is necessary.

Effect of acute exercise on glucose tolerance following post-exercise feeding.

It is well documented that a single bout of endurance exercise (EE) can improve insulin sensitivity, whereas relatively little is known about the acute effects of resistance exercise (RE) in humans. The objective of this study is to investigate the insulin and glucose responses to an oral glucose tolerance test (OGTT) following a high intensity bout of either EE or RE followed by post-exercise carbohydrate-protein hydrolysate ingestion. Eighteen participants were divided into two groups: a group in which nine participants completed 1 h of EE (cycle ergometry at 75% W (max)) and a RE group in which nine participants completed a RE circuit (3 sets of 10 repetitions). Participants ingested 1.5 l of a carbohydrate (200 g)-protein hydrolysate (50 g) beverage within 1 h of exercise completion. An OGTT was performed 6 h post-exercise. On the control day the endurance and resistance groups performed the above protocol without the prior exercise (CEE or CRE). The control and exercise days were counterbalanced. RE reduced plasma glucose AUC (822 +/- 68 vs. 694 +/- 23 mmol l(-1).120 min; CRE vs. RE, respectively; P < 0.05) but EE did not lead to a change (784 +/- 40 vs. 835 +/- 59 mmol l(-1).120 min; CEE vs. EE, respectively). Plasma insulin AUC remained unchanged compared to the control in both the RE and EE groups. The results suggest that the benefit of RE on glucose tolerance following CHO intake remains for 6 h even when a carbohydrate-protein hydrolysate beverage was ingested within 1 h after exercise, while the well documented benefit of EE was not observed.

Neutrophilic cell-free exudate induces antinociception mediate by the protein S100A9.

Calcium-binding protein S100A9 (MRP-14) induces antinociceptive effect in an experimental model of painful sensibility and participates of antinociception observed during neutrophilic peritonitis induced by glycogen or carrageenan in mice. In this study, the direct antinociceptive role of the protein S100A9 in neutrophilic cell-free exudates obtained of mice injected with glycogen was investigated. Mice were intraperitoneally injected with a glycogen solution, and after 4, 8, 24, and 48 hours, either the pattern of cell migration of the peritoneal exudate or the nociceptive response of animals was evaluated. The glycogen-induced neutrophilic peritonitis evoked antinociception 4 and 8 hours after inoculation of the irritant. Peritoneal cell-free exudates, collected in different times after the irritant injection, were transferred to naive animals which were submitted to the nociceptive test. The transference of exudates also induced antinociceptive effect, and neutralization of S100A9 activity by anti-S100A9 monoclonal antibody totally reverted this response. This effect was not observed when experiments were made 24 or 48 hours after glycogen injection. These results clearly indicate that S100A9 is secreted during glycogen-induced neutrophilic peritonitis, and that this protein is responsible by antinociception observed in the initial phase of inflammatory reaction. Thus, these data reinforce the hypothesis that the calcium-binding protein S100A9 participates of the endogenous control of inflammatory pain.

The role of cyclooxygenase inhibition in the effect of alpha-melanocyte-stimulating hormone on reactive oxygen species production by rat peritoneal neutrophils.

The effect of alpha-MSH on reactive oxygen species (ROS) production by rat peritoneal neutrophils and the effect of cyclooxygenase (COX) inhibition were investigated using the chemiluminescence (CL) technique. Cells were obtained by peritoneal lavage 4h after administration of oyster glycogen to rats and were stimulated with lipopolysaccharide (LPS) from Salmonella enderitidis and phorbol 12-myristate 13-acetate (PMA). The increasing concentrations of alpha-MSH (10(-12)-10(-6) M) were added to stimulated cells alone or along with the COX inhibitors indomethacin, ketorolac or nimesulide (10(-8)-10(-5) M). Luminol and lucigenin CL levels were significantly increased in cells stimulated with LPS and PMA compared to unstimulated ones. alpha-MSH significantly reduced lucigenin CL values and this effect was completely reversed in the presence of indomethacin (10(-8) and 10(-7) M). In conclusion, alpha-MSH inhibits the production of superoxide radicals by activated rat peritoneal neutrophils and COX contributes to this effect.