Kegg Pathway: Carbohydrate Metabolism

Physiol Plant. 2008 Jul 8;
Pagter M, Jensen CR, Petersen KK, Liu F, Arora R

Cold injury is frequently seen in the commercially important shrub Hydrangea macrophylla but not in Hydrangea paniculata. Cold acclimation and de-acclimation and associated physiological adaptations were investigated from late September 2006 to early May 2007 in stems of field-grown H. macrophylla ssp. macrophylla (Thunb.) Ser. cv. Blaumeise and H. paniculata Sieb. cv. Kyushu. Acclimation and de-acclimation appeared approximately synchronized in the two species, but they differed significantly in levels of mid-winter cold hardiness, rates of acclimation and de-acclimation and physiological traits conferring tolerance to freezing conditions. Accumulation patterns of sucrose and raffinose in stems paralleled fluctuations in cold hardiness in both species, but H. macrophylla additionally accumulated glucose and fructose during winter, indicating species-specific differences in Carbohydrate Metabolism. Protein profiles differed between H. macrophylla and H. paniculata, but distinct seasonal patterns associated with winter acclimation were observed in both species. In H. paniculata concurrent increases in xylem sap ABA concentrations ([ABA](xylem)) and freezing tolerance suggests an involvement of ABA in cold acclimation. In contrast, ABA from the root system was seemingly not involved in cold acclimation in H. macrophylla, suggesting that species-specific differences in cold hardiness may be related to differences in [ABA](xylem). In both species a significant increase in stem freezing tolerance appeared long after growth ceased, suggesting that cold acclimation is more regulated by temperature than by photoperiod.

Int J Gynaecol Obstet. 2008 Jul 15;
Ozdemir S, Görkemli H, Gezginç K, Ozdemir M, Kiyici A

Objectives: To investigate the effects of treatment with medroxyprogesterone acetate (MPA), 10 days per month for 6 months, on lipid and Carbohydrate Metabolism in women with polycystic ovary syndrome (PCOS). Methods: Sixty-three women with PCOS were randomized to receive MPA or ethinyl estradiol plus drospirenone. Results: There were no changes in lipid or Carbohydrate Metabolism in the MPA group, but serum levels of luteinizing hormone (P<0.001) and total testosterone (P<0.003) significantly decreased, as did the free androgen index (P<0.02) and acne (P<0.03) and seborrhea (P<0.04) scores. In the ethinyl estradiol plus drospirenone group lipid and hormone values significantly increased whereas acne, seborrhea, hair loss, and Ferriman-Gallwey scores decreased. There was no statistically significant change in the total cholesterol to high-density cholesterol ratio in either group. Conclusion: Treatment of PCOS patients with MPA provided good menstrual cycle control, beneficial changes in hormonal values associated with hyperandrogenism, and no significant changes in lipid or Carbohydrate Metabolism.

Eur J Pharmacol. 2008 Mar 18;
Chandramohan G, Ignacimuthu S, Pugalendi KV

Casearia esculenta root (Roxb.) is widely used in traditional system of medicine to treat diabetes in India. An active compound 3-hydroxymethyl xylitol (3-HMX) has been isolated and its optimum dose has been determined in a short duration study and patented. In the present study, the long-term effect of 3-HMX in type 2 diabetic rats has been investigated. An optimum dose of 3-HMX (40 mg/kg body weight) was orally administered for 45 days to streptozotocin-diabetic rats for the assessment of glucose, insulin, hemoglobin (Hb), glycated hemoglobin (HbA(1c)), hepatic glycogen, and activities of Carbohydrate metabolizing enzymes, such as glucokinase, glucose 6-phosphatase, fructose 1,6-bisphosphatase and glucose-6-phosphate dehydrogenase and hepatic marker enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gammaglutamyl transferase (GGT) in normal and streptozotocin-diabetic rats. 3-HMX at 40 mg dose produced similar effects on all biochemical parameters studied as that of glibenclamide, a standard drug. Histological study of pancreas also confirmed the biochemical findings. These results indicate that 3-hydroxymethyl xylitol, the compound from C. esculenta, possesses antihyperglycemic effect on long-term treatment also.

Prog Cardiovasc Dis. 2008 Jul-Aug; 51(1): 74-88
Kassiotis C, Rajabi M, Taegtmeyer H

Myocardial energy substrate Metabolism entails a complex system of enzyme catalyzed reactions, in which the heart efficiently converts chemical to mechanical energy. The system is highly regulated and responsive to changes in workload as well as in substrate and hormone supply to the heart. Akin to the terms "contractile reserve" and "coronary flow reserve" we propose the term "metabolic reserve" to reflect the heart's capacity to respond to increases in workload. The heart's metabolic response to inotropic stimulation involves the ability to increase oxidative Metabolism over a wide range, by activating the oxidation of glycogen and Carbohydrate substrates. Here we review the known biochemical mechanisms responsible for those changes. Specifically, we explore the notion that disturbances in the metabolic reserve result in contractile dysfunction of the stressed heart.

Pol Merkur Lekarski. 2008 May; 24(143): 468-71
Lapiński TW, Dabrowska MM

Liver failure is decadent stage of its severe damage, in which, processes of detoxication, Carbohydrate and lipid Metabolism, nitrogen balance and synthesis of high-energy compounds are significantly diminished or even totally blocked. Moreover, these incorrect metabolic pathways as well as oxygen deficiency in hepatocytes are implicated in the pathogenesis of endocrine system diseases. The different endocrinal dysfunctions make worse patient's prognosis.

Pol Merkur Lekarski. 2008 May; 24(143): 396-8
Mrowicka M, Garncarek P, Bortnik K, Gałecka E, Miller E, Smigielski J

Hip osteoarthritis leads, among others, to abnormally decreased physical activity (hypokinesia). Adverse effect of physical inactivity can cause inhibition of anabolic processes in favour of enhancement of protein, Carbohydrate, and lipid catabolitic reactions, as well as inadequate Metabolism of polyunsaturated fatty acids. These alterations can induce an increased lipid peroxide synthesis, overproduction of reactive oxygen species (ROS) and acceleration of lipid peroxidation processes. The aim of the study was to determine superoxide dismutase activity (CuZn-SOD) in red blood cells of patients suffering from hip osteoarthritis prior to and following total alloplasty as compared to healthy subjects, and also to evaluate effect of hypokinesia on oxidative stress. MATERIAL AND METHODS; CuZn-SOD activity in red blood cells was determined according to the Misra and Fridovich method in 36 patients with hip osteoarthritis hospitalized at the Traumatic-Orthopaedic Department of the Ministry of Internal Affairs and Administration Hospital in Lódź. RESULTS: In patients with decreased physical activity in ten days after alloplasty, enzyme activity increased (+24.9%), one month since the operation it decreased, but it higher as compared to result activity of CuZn-SOD prior to surgery (+16.8%). CONCLUSIONS: The results activity of superoxide dysmutase leads to ROS generation and their overgeneration in hip osteoarthritis and in first time of treatment.

Funct Integr Genomics. 2008 Jul 17;
Mathiason K, He D, Grimplet J, Venkateswari J, Galbraith DW, Or E, Fennell A

Endodormant grapevine buds require a period of chilling before they break and begin to grow. Custom Vitis bud cDNA microarrays (9,216 features) were used to examine gene expression patterns in overwintering Vitis riparia buds during 2,000 h of 4 degrees C chilling. Three-node cuttings collected concurrently with buds were monitored to determine dormancy status. Chilling requirement was fulfilled after 1,500 h of chilling; however, 2,000 h of chilling significantly increased the rate of bud break. Microarray analysis identified 1,469 significantly differentially expressed (p value < 0.05) array features when 1,000, 1,500, and 2,000 h of chilling were compared to 500 h of chilling. Functional classification revealed that the majority of genes were involved in Metabolism, cell defense/stress response, and genetic information processing. The number of significantly differentially expressed genes increased with chilling hour accumulation. The expression of a group of 130 genes constantly decreased during the chilling period. Up-regulated genes were not detected until the later stages of chilling accumulation. Hierarchical clustering of non-redundant expressed sequence tags revealed inhibition of genes involved in Carbohydrate and energy Metabolism and activation of genes involved in signaling and cell growth. Clusters with expression patterns associated with increased chilling and bud break were identified, indicating several candidate genes that may serve as indicators of bud chilling requirement fulfillment.

ISME J. 2008 Jul 17;
Sharif DI, Gallon J, Smith CJ, Dudley E

Quorum sensing involving acyl homoserine lactones (AHLs) is a density-dependent form of intercellular communication that occurs in many different members of the group Proteobacteria. However, to date, there have been few investigations of its occurrence in cyanobacteria. Here, using both a bioreporter Agrobacterium tumefaciens NTL4 (PZLR4) and mass spectrometry, we provide evidence of N-octanoyl homoserine lactone (C8-AHL) production in axenic cultures of the cyanobacterium Gloeothece PCC6909 and its sheathless mutant PCC6909/1. Accumulation of C8-AHL in the culture medium of laboratory cultures of Gloeothece followed a pattern characteristic of the phenomenon of autoinduction, a common feature of functional AHL-based quorum-sensing systems. Analysis by two-dimensional gel electrophoresis showed that, in response to treatment with C8-AHL, early growth-stage cells of PCC6909/1 showed changes in expression of 43 proteins compared with untreated cells. Among the 15 proteins that showed more than a twofold change in expression were RuBisCo, glutamate synthase, chorismate synthase, a member of the LysR family of transcriptional regulators (all upregulated), and enolase and aldolase, both of which were downregulated. The significance of such changes in response to C8-AHL is discussed in relation to Carbohydrate and amino-acid Metabolism and involvement of Gloeothece in biofilms.The ISME Journal advance online publication, 17 July 2008; doi:10.1038/ismej.2008.68.

Biotechnol Bioeng. 1996 Feb 5; 49(3): 247-58
Torres NV, Voit EO, González-Alcón C

The metabolic pathway and the properties of many of the enzymes involved in the citric acid biosynthesis in the mold Aspergillus niger are well known. This fact, together with the availability of new theoretical frameworks aimed at quantitative analyses of control and dynamics in metabolic systems, has allowed us to construct a mathematical model of the Carbohydrate Metabolism in Aspergillus niger under conditions of citric acid accumulation. The model makes use of the S-system representation of biochemical systems, which renders it possible to use linear programming to optimize the process. It was found that maintaining the metabolite pools within narrow physiological limits (20% around the basal steady-state level) and allowing the enzyme concentrations to vary within a range of 0.1 to 50 times their basal values it is possible to triple the glycolytic flux while maintaining 100% yield of substrate transformation. To achieve these improvements it is necessary to modulate seven or more enzymes simultaneously. Although this seems difficult to implement at present, the results are useful because they indicate what the theoretical limits are and because they suggest several alternative strategies. (c) 1996 John Wiley & Sons, Inc.

J Natl Cancer Inst. 1970 Nov; 45(5): 869-77
Morgan JF, Eng CP

Primary monolayer cultures were prepared from mouse ascites tumor cells of the Ehrlich-Lettré line and cultivated in chemically defined media containing various Carbohydrates as the sole energy source. An absolute glucose requirement for culture survival was found, which could be satisfied by either the alpha or beta forms. The cultures died within 2-3 days when D-mannose, D-fructose, or D-galactose was substituted for D-glucose. Of over 50 other Carbohydrates and related compounds tested, none could replace glucose. Cells of the Ehrlich and Ehrlich-Lettré lines suspended in balanced salt solutions containing various Carbohydrates removed D-glucose, D-mannose, D-fructose, D-glucosamine, and 2-deoxy-D-glucose from the suspending fluid. In the presence of D-glucose, culture survival was inhibited by D-mannose, D-fructose, L-glucose, and D-galactose. D-Glucosamine and 2-deoxy-D-glucose strongly inhibited culture survival with the 50% inhibition points at 375 mg/liter and 62.5 mg/liter, respectively. The inhibition by D-glucosamine could be reversed by alpha- and beta-glucose, but not by D-mannose or D-fructose. The inhibition by 2-deoxy-D-glucose could be reversed completely by alpha- and beta-glucose, to a slight degree by D-mannose, and not at all by D-fructose.

Int J Toxicol. 2007; 26 Suppl 2: 79-112

Glycyrrhetinic Acid and its salts and esters and Glycyrrhizic Acid and its salts and esters are cosmetic ingredients that function as flavoring agents or skin-conditioning agents - miscellaneous or both. These chemicals may be isolated from licorice plants. Glycyrrhetinc Acid is described as at least 98% pure, with 0.6% 24-OH-Glycyrrhetinic Acid, not more than 20 mu g/g of heavy metals and not more than 2 mu g/g of arsenic. Ammonium Glycyrrhizate has been found to be at least 98% pure and Dipotassium Glycyrrhizate has been found to be at least 95% pure. Glycyrrhetinic Acid is used in cosmetics at concentrations of up to 2%; Stearyl Glycyrrhetinate, up to 1%; Glycyrrhizic Acid, up to 0.1%; Ammonium Glycyrrhizate, up to 5%; Dipotassium Glycyrrhizate, up to 1%; and Potassium Glycyrretinate, up to 1%. Although Glycyrrhizic Acid is poorly absorbed by the intestinal tract, it may be hydrolyzed to Glycyrrhetinic Acid by a beta -glucuronidase produced by intestinal bacteria. Glycyrrhetinic Acid and Glycyrrhizic Acid bind to rat and human albumin, but do not absorb well into tissues. Glycyrrhetinic Acid and Glycyrrhizic Acid and metabolites are mostly excreted in the bile, with very little excreted in urine. Dipotassium Glycyrrhizate was undetectable in the receptor chamber when tested for transepidermal permeation through pig skin. Glycyrrhizic Acid increased the dermal penetration of diclofenac sodium in rat skin. Dipotassium Glycyrrhizate increased the intestinal absorption of calcitonin in rats. In humans, Glycyrrhetinic Acid potentiated the effects of hydrocortisone in the skin. Moderate chronic or high acute exposure to Glycyrrhizic Acid, Ammonium Glycyrrhizate, and their metabolites have been demonstrated to cause transient systemic alterations, including increased potassium excretion, sodium and water retention, body weight gain, alkalosis, suppression of the renin-angiotensis-aldosterone system, hypertension, and muscular paralysis; possibly through inhibition of 11beta -hydroxysteroid dehydrogenase-2 (11beta -OHSD2) in the kidney. Glycyrrhetinic Acid and its derivatives block gap junction intracellular communication in a dose-dependent manner in animal and human cells, including epithelial cells, fibroblasts, osteoblasts, hepatocytes, and astrocytes; at high concentrations, it is cytotoxic. Glycyrrhetinic Acid and Glycyrrhizic Acid protect liver tissue from carbon tetrachloride. Glycyrrhizic Acid has been used to treat chronic hepatitis, inhibiting the penetration of the hepatitis A virus into hepatocytes. Glycyrrhetinic Acid and Glycyrrhizic Acid have anti-inflammatory effects in rats and mice. The acute intraperitoneal LD(50) for Glycyrrhetinic Acid in mice was 308 mg/kg and the oral LD(50) was > 610 mg/kg. The oral LD(50) in rats was reported to be 610 mg/kg. Higher LD(50) values were generally reported for salts. Little short-term, subchronic, or chronic toxicity was seen in rats given ammonium, dipotassium, or disodium salts of Glycyrrhizic Acid. Glycyrrhetinic Acid was not irritating to shaved rabbit skin, but was considered slightly irritating in an in vitro test. Glycyrrhetinic Acid inhibited the mutagenic activity of benzo[a]pyrene and inhibited tumor initiation and promotion by other agents in mice. Glycyrrhizic Acid inhibited tumor initiation by another agent, but did not prevent tumor promotion in mice. Glycyrrhizic Acid delayed mortality in mice injected with Erlich ascites tumor cells, but did not reduce the mortality rate. Ammonium Glycyrrhizate was not genotoxic in in vivo and in vitro cytogenetics assays, the dominant lethal assay, an Ames assay, and heritable translocation tests, except for possible increase in dominant lethal mutations in rats given 2000 mg/kg day(-1) in their diet. Disodium Glycyrrhizate was not carcinogenic in mice in a drinking water study at exposure levels up to 12.2 mg/kg day(-1) for 96 weeks. Glycyrrhizate salts produced no reproductive or developmental toxicity in rats, mice, golden hamsters, or Dutch-belted rabbits, except for a dose-dependent increase (at 238.8 and 679.9 mg/kg day(-1)) in sternebral variants in a study using rats. Sedation, hypnosis, hypothermia, and respiratory depression were seen in mice given 1250 mg/kg Glycyrrhetinic Acid intraperitoneally. Rats fed a powdered diet containing up to 4% Ammonium Glycyrrhizate had no treatment related effects in motor function tests, but active avoidance was facilitated at 4%, unaffected at 3%, and depressed at 2%. In a study of 39 healthy volunteers, a no effect level of 2 mg/kg/day was determined for Glycyrrhizic Acid given orally for 8 weeks. Clinical tests in seven normal individuals given oral Ammonium Glycyrrhizate at 6 g/day for 3 days revealed reduced renal and thermal sweat excretion of Na+ and K+, but Carbohydrate and protein Metabolism were not affected. Glycyrrhetinic Acid at concentrations up to 6% was not a skin irritant or a sensitizer in clinical tests. Neither Glycyrrhizic Acid, Ammonium Glycyrrhizate, nor Dipotassium Glycyrrhizate at 5% were phototoxic agents or photosensitizers. Birth weight and maternal blood pressure were unrelated to the level of consumption of Glycyrrhizic Acid in 1049 Finnish women with infants, but babies whose mother consumed > 500 mg/wk were more likely to be born before 38 weeks. The Cosmetic Ingredient Review (CIR) Expert Panel noted that the ingredients in this safety assessment are not plant extracts, powders, or juices, but rather are specific chemical species that may be isolated from the licorice plant. Because these chemicals may be isolated from plant sources, however, steps should be taken to assure that pesticide and toxic metal residues are below acceptable levels. The Panel advised the industry that total polychlorobiphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and that toxic metal levels must not contain more than 3 mg/kg of arsenic (as As), not more than 0.002% heavy metals, and not more than 1 mg/kg of lead (as Pb). Although the Panel noted that Glycyrrhizic Acid is cytotoxic at high doses and ingestion can have physiological effects, there is little acute, short-term, subchronic, or chronic toxicity and it is expected that these ingredients would be poorly absorbed through the skin. These ingredients are not considered to be irritants, sensitizers, phototoxic agents, or photosensitizers at the current maximum concentration of use. Accordingly, the CIR Expert Panel concluded that these ingredients are safe in the current practices of use and concentration. The Panel recognizes that certain ingredients in this group are reportedly used in a given product category, but the concentration of use is not available. For other ingredients in this group, information regarding use concentration for specific product categories is provided, but the number of such products is not known. In still other cases, an ingredient is not in current use, but may be used in the future. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used and at what concentration indicate a pattern of use. Within this overall pattern of use, the Expert Panel considers all ingredients in this group to be safe.

Int J Obes (Lond). 2008 Jul 15;
Herling AW, Kilp S, Juretschke HP, Neumann-Haefelin C, Gerl M, Kramer W

Objective:The severity of obesity is often more determined by the distribution of fat depots rather than by body weight itself. Therefore, the effect of rimonabant on fat distribution pattern was investigated in female candy-fed Wistar rats.Design:Female Wistar rats were fed a high fat, high Carbohydrate (candy-) diet for 12 weeks. During the last 6 weeks rats were treated with rimonabant. Food intake and body weight development were investigated, as well as effects on total body fat, especially visceral fat and ectopic lipid accumulation in skeletal muscle and liver, determined by in vivo magnetic resonance imaging/magnetic resonance spectroscopy.Results:Candy-diet increased body weight, which was predominantly due to the increased total fat mass with predominance of visceral fat accumulation. Treatment with rimonabant fully reversed the weight gain and fat deposition in the visceral cavity and skeletal muscle, in contrast to pair feeding. In spite of an only transient reduction of food intake, body weight reduction, as well as normalized body fat, reduced visceral fat and intramyocellular lipids were maintained over the treatment period.Conclusions:We conclude that additional factors other than reduced caloric intake must be responsible for the improvements in these lipid parameters. The complete cluster of results is consistent with increased lipid oxidation caused by rimonabant.International Journal of Obesity advance online publication, 15 July 2008; doi:10.1038/ijo.2008.105.

Neurotherapeutics. 2008 Jul; 5(3): 470-80
Henderson ST

An early feature of Alzheimer's disease (AD) is region-specific declines in brain glucose Metabolism. Unlike other tissues in the body, the brain does not efficiently metabolize fats; hence the adult human brain relies almost exclusively on glucose as an energy substrate. Therefore, inhibition of glucose Metabolism can have profound effects on brain function. The hypoMetabolism seen in AD has recently attracted attention as a possible target for intervention in the disease process. One promising approach is to supplement the normal glucose supply of the brain with ketone bodies (KB), which include acetoacetate, beta-hydroxybutyrate, and acetone. KB are normally produced from fat stores when glucose supplies are limited, such as during prolonged fasting. KB have been induced both by direct infusion and by the administration of a high-fat, low-Carbohydrate, low-protein, ketogenic diets. Both approaches have demonstrated efficacy in animal models of neurodegenerative disorders and in human clinical trials, including AD trials. Much of the benefit of KB can be attributed to their ability to increase mitochondrial efficiency and supplement the brain's normal reliance on glucose. Research into the therapeutic potential of KB and ketosis represents a promising new area of AD research.

Mol Reprod Dev. 2008 Jul 10;
Harris SE, Leese HJ, Gosden RG, Picton HM

Growing oocytes in vitro from the most immature stages until they are developmentally competent is a major goal of reproductive technology, requiring fundamental knowledge of metabolic processes. Carbohydrate Metabolism and oxygen consumption have been analysed in a series of experiments designed to investigate important energy substrates for mouse oocytes and to reveal any qualitative or quantitative changes between the primordial and ovulatory follicle stages. Primordial follicles were incubated in groups in modified-KSOM medium, whereas growing or ovulated oocytes were studied singly and, in both cases, the depletion or accumulation of metabolites in spent medium were analysed using ultramicrofluorometric assays. The rates of glucose (0.014 +/- 0.006 pmol/hr) and pyruvate (0.028 +/- 0.009 pmol/hr) consumption and l-lactate (0.058 +/- 0.023 pmol/hr) production by primordial follicles suggested that energy production was supported by a combination of metabolic pathways, including glycolysis. Pyruvate and oxygen consumption per oocyte increased two- and ninefold, respectively, between the primary and pre-ovulatory stages (0.82 +/- 0.1 and 1.67 +/- 0.1 pmol pyruvate/hr, respectively and 1.4 +/- 0.3 and 7 +/- 0.6 pmol oxygen/hr) after which oxygen (12.7 +/- 1.1 pmol/hr) utilisation nearly doubled. Oxygen consumption by fully grown oocytes was in excess of oxidation requirements for pyruvate. When pyruvate and oxygen consumption rates were normalised for oocyte cellular volume, which increased over 130-fold during growth, oocyte Metabolism was higher in primary follicles than at any subsequent stage, indicating that energy needs are greater during a developmental transition. To conclude, pyruvate and oxygen were consumed throughout oocyte development at increasing rates. When oocyte cellular volume was accounted for, oocytes from primary follicles displayed greatest metabolic rates. Mol. Reprod. Dev. (c) 2008 Wiley-Liss, Inc.

J Appl Physiol. 2008 Jul 10;
Judelson DA, Maresh CM, Yamamoto LM, Farrell MJ, Armstrong LE, Kraemer WJ, Volek JS, Spiering BA, Casa DJ, Anderson JM

Hypohydration (decreased total body water) exacerbates the catabolic hormonal response to endurance exercise with unclear effects on anabolic hormones. Limited research exists that evaluates the effect of hypohydration on endocrine responses to resistance exercise; this work merits attention as the acute post-exercise hormonal environment potently modulates resistance training adaptations. The purpose of this study was to examine the effect of hydration state on the endocrine and metabolic responses to resistance exercise. Seven healthy resistance-trained males (age = 23 +/- 4 y, body mass = 87.8 +/- 6.8 kg, body fat = 11.5 +/- 5.2%) completed three identical resistance exercise bouts in different hydration states: euhydrated (EU), hypohydrated by ~2.5% body mass (HY25), and hypohydrated by ~5.0% body mass (HY50). Investigators manipulated hydration status via controlled water deprivation and exercise-heat stress. Cortisol, epinephrine, norepinephrine, testosterone, growth hormone, IGF-1, insulin, glucose, lactate, glycerol, and free fatty acids were measured during euhydrated rest, immediately preceding resistance exercise, immediately post-exercise, and during 60 minutes of recovery. Body mass decreased 0.2 +/- 0.4%, 2.4 +/- 0.4%, and 4.8 +/- 0.4% during EU, HY25, and HY50, respectively, supported by humoral and urinary changes that clearly indicated subjects achieved three distinct hydration states. Hypohydration significantly 1) increased circulating concentrations of cortisol and norepinephrine, 2) attenuated the testosterone response to exercise, and 3) altered Carbohydrate and lipid Metabolism. These results suggest that hypohydration can modify the hormonal and metabolic response to resistance exercise, influencing the post-exercise circulatory milieu. Key words: dehydration, hormone, muscle, strength, water.

J Proteomics. 2008 Jul 21; 71(2): 133-47
de la Luz-Hernández KR, Rojas-Del Calvo L, Rabasa-Legón Y, Lage-Castellanos A, Castillo-Vitlloch A, Díaz J, Gaskell S

Proteomics and metabolomics technologies are potentially useful tool for the study of the very complex process of cell adaptation to protein-free medium. In this work, we used the iTRAQ technology to analyze different protein levels in adapted and non-adapted NS0 myeloma cell line. Several proteins with differential expression profile were characterized and quantified. Carbohydrate Metabolism, protein synthesis and membrane transport were the principal pathways that change after the adaptation. Changes in lactate production rate with respect to glucose consumption rate were observed according to the changes observed by proteomic.

Alcohol Clin Exp Res. 2008 Jun 20;
Nixon PF

Introduction: The earliest observed effect in the pathogenesis of experimental Wernicke's encephalopathy and of ethanol intoxication in rats is impairment of the blood cerebrospinal fluid (CSF) barrier at the choroid plexus (CP). For an explanation, these observations direct attention to the role of the CP in maintaining glutamate homeostasis in the CSF. Methods: Characteristics of the CP epithelium (CPE) are reviewed, focusing on its role in removal of glutamate from the CSF and its potential for impairment by ethanol oxidation or by thiamin-deficient glucose oxidation. Results: The export of glutamate from CSF to blood at the CP is energy dependent, saturable, and stereospecific. However, the incapacity of the CP to convert glutamate to other metabolites makes it vulnerable to glutamate accumulation should alpha-ketoglutarate dehydrogenase activity be decreased. Elsewhere ethanol Metabolism and thiamin-deficiency independently decrease the activity of this mitochondrial enzyme. We argue that they have the same effect within the mitochondria-rich CPE, thereby decreasing energy production necessary for export of glutamate from CSF to blood; diverting its energy Metabolism to further glutamate production; and impairing its blood CSF barrier function. This impairment appears to be mediated by glutamate and is attenuated by MK801 but whether it involves one of the CPE glutamate receptors is yet uncertain. This impairment exposes the CSF and hence the paraventricular brain extracellular fluid to neuroactive substances from the blood, including further glutamate, explaining the paraventricular location of neuropathology in Wernicke's encephalopathy. Other organs normally protected from blood by a barrier are affected also by ethanol abuse and by thiamin deficiency, namely the eye, peripheral nerves, and the testis. Much less is known regarding the function of these barriers. Conclusions: Impairment of the CP by ethanol intoxication and by thiamin-deficient Carbohydrate Metabolism has a common, rational explanation that can guide future research.

Mol Vis. 2008; 14: 1209-21
Clement C, Popp MP, Bloom DC, Schultz G, Liu L, Neumann DM, Bhattacharjee PS, Hill JM

PURPOSE: To analyze the rabbit host global gene expression patterns in uninfected and herpes simplex virus type 1 (HSV-1) latent trigeminal ganglia (TG) for identification of host response-initiated transcriptional changes during the maintenance of viral latency. METHODS: The corneas of eight-week-old New Zealand White rabbits were scarified and inoculated with HSV-1 strain McKrae, 5x10(5) plaque forming units/eye. Corneal infection was verified by slit-lamp examination. Prior to sacrifice at 30 days post infection, ocular swabs confirmed no infectious virus was present. TG were aseptically removed from rabbits and placed in RNA stabilization solution. Host RNA was isolated from two groups of TG, uninfected and HSV-1 latent infected, and used to create labeled cRNA. Labeled cRNA was hybridized to two new and novel custom oligonucleotide rabbit arrays, containing a total of 3,123 probes for rabbit genes. RESULTS: The rabbit TG expressed approximately 80% of genes out of a total of 3,123. A one-way ANOVA performed on the log2 transformed signal ratios showed 611 genes were significantly altered (p< or =0.05) in HSV-1 latent TG. These genes, if annotated, were separated by biologic process categories. Five broad categories were most heavily represented: protein processing, Carbohydrate processing, cell adhesion, apoptosis, and host defense and immune response. Sixty of the significantly altered genes were found to be altered by more than 2 fold, and five were altered by more than 4 fold. The genes altered by more than 4 fold were all upregulated and related to host defense and immune response. Viral latency had a large effect on protein processing. Of the differentially expressed genes with an assigned biologic process, 90/349 (25.7%) were associated with protein processing. The next most populated categories were Carbohydrate Metabolism 39/349 (11.1%) and host defense and immune response 17/349 (4.9%). CONCLUSIONS: The results of this microarray study demonstrate that host gene expression is altered in the HSV-1 latent rabbit TG. The shift in molecular processes at a pathway level reveals the presence of potential therapeutic significance inherent in the maintenance of HSV-1 latency. This is the first large-scale rabbit gene expression study, using microarray analysis, that documents the involvement of host immunity in maintaining HSV-1 latency.

Clin Nutr. 2008 Jul 7;
Parente LB, Aguila MB, Mandarim-de-Lacerda CA

BACKGROUND & AIMS: Pre- and postnatal environmental changes can reset the developmental path during intrauterine development leading to obesity and cardiovascular and metabolic disorders later in life. The effects of high-fat diets on body mass, fat mass, the plasma level of glucose, insulin and leptin, as well as the insulin/glucose ratio and cardiovascular parameters in adult rat offspring were studied. METHODS: Pregnant Wistar rats in a standard chow group (SC) or high-fat chow group (HFC), at weaning their SC and HFC offspring were randomly divided into two postnatal groups: fed on SC or HFC. With euthanasia at 6-month-old, three-way ANOVA there were three-factor interactions among gender, perinatal diet and postweaning diet to body mass (BM), BP, left ventricle (LV) thickness, Carbohydrate Metabolism, plasma corticosterone concentrations and leptin/fat mass/adipocyte size pattern. RESULTS: HFC/SC and SC/HFC offspring of both genders had high BM and BP, which were increased in HFC/HFC offspring. There was hyperinsulinism, hyperleptinemia, as well as high insulin/glucose ratio and high plasma corticosterone concentrations mainly in HFC/HFC offspring with adipocytes and LV hypertrophy. CONCLUSIONS: Postweaning HFC was deleterious to the health of adult offspring from dams fed HFC during pregnancy and then during the first half of lactation period. HFC administrated in both periods shows supplementary effects, elevating BP with consequent LV hypertrophy, altering Carbohydrate Metabolism, plasma corticosterone concentrations and disturbing leptin/fat mass/adipocyte size pattern.

J Biol Chem. 2008 Jul 8;
Oosterveer MH, van Dijk TH, Grefhorst A, Bloks VW, Havinga R, Kuipers F, Reijngoud DJ

Besides its well-established role in control of cellular cholesterol homeostasis, the Liver X Receptor (LXR) has been implicated in the regulation of hepatic gluconeogenesis. We investigated the role of the major hepatic LXR isoform in hepatic glucose Metabolism during the feeding-to-fasting transition in vivo. In addition, we explored hepatic glucose sensing by LXR during Carbohydrate refeeding. Lxra-/- mice and their wild-type littermates were subjected to a fasting-refeeding protocol and hepatic Carbohydrate fluxes as well as whole-body insulin sensitivity were determined in vivo by stable isotope procedures. Lxra-/- mice showed an impaired response to fasting in terms of hepatic glycogen depletion and triglyceride accumulation. Hepatic glucose-6-phosphate turnover was reduced in 9h-fasted Lxra-/- mice as compared to controls. Although hepatic gluconeogenic gene expression was increased in 9h-fasted Lxra-/- mice compared to wild-type controls, the actual gluconeogenic flux was not affected by Lxra deficiency. Hepatic and peripheral insulin sensitivity were similar in Lxra-/- and wild-type mice. Compared to wildtype controls, the induction of hepatic lipogenic gene expression was blunted in Carbohydrate-refed Lxra-/- mice, which was associated with lower plasma triglyceride concentrations. Yet, expression of 'classic' LXR target genes Abca1, Abcg5 and Abcg8 was not affected by Lxra deficiency in Carbohydrate-refed mice. In summary, these studies identify LXRa as a physiologically relevant mediator of the hepatic response to fasting. However, the data do not support a role for LXR in hepatic glucose sensing.