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Metabolic Responses (metabolic + response)
Selected AbstractsMetabolic response to two hydrocooling temperatures in sweet cherries cv Lapins and cv SunburstJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 12 2006Rafael Alique Abstract Physiological and metabolic characterisation and analysis of response to two hydrocooling temperatures in cv Sunburst (early season) and cv Lapins (mid-season) cherries during post-harvest life has been studied. Samples were hydrocooled with water at 1 °C to reach 6 °C inside the fruit (HC-6C) and 2 °C (HC-2C) inside the fruit. After harvesting, Sunburst samples presented higher respiration rates and lower malic acid and sorbitol contents than Lapins. Glucose and fructose contents were similar in the two varieties. Sunburst control exhibited a higher respiration rate than Lapins and a higher rate of conversion from sorbitol to fructose. The change of glucose and malic acid consumption over 4 days at 20 °C was similar for the two varieties. Hydrocooling reduced respiration and the consumption of respiratory substrates. The residual effect of hydrocooling was especially significant in cherries of both varieties that had been pre-cooled to 2 °C. Hydrocooling delayed loss of skin and pulp firmness, and reduced loss of titratable acid and soluble solid contents over 4 days at 20 °C in both varieties. Hydrocooling to 2 °C checked loss of quality with respect to controls for both varieties after 4 days at 20 °C. Lapins showed better conservation properties than Sunburst under all the experimental storage conditions. Hydrocooling reduced total losses in both varieties, especially in cherries pre-cooled to 2 °C. Hydrocooling also had several residual effects: reduction of the respiration rate and consumption of respiratory substrates, and slowing of loss of quality, particularly for Lapins. Copyright © 2006 Society of Chemical Industry [source] Metabolic responses of novel cellulolytic and saccharolytic agricultural soil Bacteria to oxygenENVIRONMENTAL MICROBIOLOGY, Issue 4 2010Stefanie Schellenberger Summary Cellulose is the most abundant biopolymer in terrestrial ecosystems and is degraded by microbial communities in soils. However, relatively little is known about the diversity and function of soil prokaryotes that might participate in the overall degradation of this biopolymer. The active cellulolytic and saccharolytic Bacteria in an agricultural soil were evaluated by 16S rRNA 13C-based stable isotope probing. Cellulose, cellobiose and glucose were mineralized under oxic conditions in soil slurries to carbon dioxide. Under anoxic conditions, these substrates were converted primarily to acetate, butyrate, carbon dioxide, hydrogen and traces of propionate and iso-butyrate; the production of these fermentation end-products was concomitant with the apparent reduction of iron(III). [13C]-cellulose was mainly degraded under oxic conditions by novel family-level taxa of the Bacteroidetes and Chloroflexi, and a known family-level taxon of Planctomycetes, whereas degradation under anoxic conditions was facilitated by the Kineosporiaceae (Actinobacteria) and cluster III Clostridiaceae and novel clusters within Bacteroidetes. Active aerobic sub-communities in oxic [13C]-cellobiose and [13C]-glucose treatments were dominated by Intrasporangiaceae and Micrococcaceae (Actinobacteria) whereas active cluster I Clostridiaceae (Firmicutes) were prevalent in anoxic treatments. A very large number (i.e. 28) of the detected taxa did not closely affiliate with known families, and active Archaea were not detected in any of the treatments. These collective findings suggest that: (i) a large uncultured diversity of soil Bacteria was involved in the utilization of cellulose and products of its hydrolysis, (ii) the active saccharolytic community differed phylogenetically from the active cellulolytic community, (iii) oxygen availability impacted differentially on the activity of taxa and (iv) different redox guilds (e.g. fermenters and iron reducers) compete or interact during cellulose degradation in aerated soils. [source] Uptake and diverse effects of polycyclic aromatic hydrocarbons on the metabolic activity of Elliptio complanata measured by calorespirometryENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2001Marcos A. Cheney Abstract Polycyclic aromatic hydrocarbons (PAHs) are important contaminants of world water resources, with effects on aquatic life. Metabolic responses to short-term acute toxicities of naphthalene, anthracene, and chrysene were investigated in the freshwater bivalve mollusk Elliptio complanata using differential scanning calorespirometry coupled with uptake and scanning electron microscopy. Comparing the uptakes of naphthalene, anthracene, and chrysene with that of inulin, which is known to occupy only extracellular space, showed that all compounds studied were taken up. The PAHs studied had diverse effects on the metabolic activity of E. complanata. Naphthalene and, to a lesser degree, chrysene caused stimulation of heat rates, possibly due to uncoupling of oxidative metabolism. Differential scanning calorespirometry coupled with studies of rates of oxygen consumption by the gill tissue exposed to the PAHs showed similar diverse patterns of respiratory rate stimulation and inhibition. Analysis of results of scanning electron microscopy suggested that irreversible damage to the gill tissue occurred in the presence of anthracene but not in the presence on naphthalene or chrysene. The batch calorespirometric method coupled with uptake and spectroscopy proved to be a useful technique to assess the toxicity of PAHs on the control of energy flux in gills of a freshwater bivalve mollusk. [source] Metabolic responses to oral tryptophan supplementation before exercise in horsesJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3-6 2005I. Vervuert Summary This study was conducted to evaluate the effects of oral tryptophan (Trp) supplementation on exercise capacity and metabolic responses in horses. Three horses had to perform an exercise test: a 15-min warm-up followed by a 60-min walk (1.7 m/s, W1), a 10-min trot (3.1 m/s, T1), a second 60-min walk (1.7 m/s, W2), a second 10-min trot (3.1 m/s, T2) and a final 30-min walk (1.7 m/s, W3) until the horses were unwilling to continue. The horses exercised on a treadmill at a 6% incline and with a constant draught load of 40 kg (0.44 kN). Two hours before exercise horses were given 50 g Trp (9.8,10.7 g Trp/100 kg BW) by nasogastric tube. A control exercise test was conducted without Trp. During the control test, one horse was able to finish the final 30-min walk (W3), whereas two horses finished W3 after Trp administration. Higher plasma Trp levels after Trp administration did not change significantly during exercise (Trp: start exercise, 524 ± 41 ,mol/l; end exercise 547 ± 20 ,mol/l; control: start exercise, 70 ± 10 ,mol/l; end exercise, 58 ± 21 ,mol/l). After Trp supplementation, blood lactate concentrations were significantly lower after the first and second trotting periods. Free fatty acids in plasma increased during exercise without any treatment-related differences. Although experimental plasma Trp levels were seven times higher than the control levels, Trp supplementation had no effect on exercise performance and metabolic responses to draught load exercise. [source] Metabolic responses in ischemic myocardium after inhalation of carbon monoxideACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2009K. AHLSTRÖM Background: To clarify the mechanisms of carbon monoxide (CO) tissue-protective effects, we studied energy metabolism in an animal model of acute coronary occlusion and pre-treatment with CO. Methods: In anesthetized pigs, a coronary snare and microdialysis probes were placed. CO (carboxyhemoglobin 5%) was inhaled for 200 min in test animals, followed by 40 min of coronary occlusion. Microdialysate was analyzed for lactate and glucose, and myocardial tissue samples were analyzed for adenosine tri-phosphate, adenosine di-phosphate, and adenosine mono-phosphate. Results: Lactate during coronary occlusion was approximately half as high in CO pre-treated animals and glucose levels decreased to a much lesser degree during ischemia. Energy charge was no different between groups. Conclusions: CO in the low-doses tested in this model results in a more favorable energy metabolic condition in that glycolysis is decreased in spite of maintained energy charge. Further work is warranted to clarify the possible mechanistic role of energy metabolism for CO protection. [source] Effects of cevoglitazar, a dual PPAR,/, agonist, on ectopic fat deposition in fatty Zucker ratsDIABETES OBESITY & METABOLISM, Issue 6 2009D. Laurent Aim:, By acting as both insulin sensitizers and lipid-lowering agents, dual-acting peroxisome proliferator-activated receptors ,/, (PPAR,/,) agonists may be used to improve glucose tolerance in type 2 diabetic patients without inducing adiposity and body weight gain. Here, in an animal model of obesity and insulin resistance, the metabolic response to cevoglitazar, a dual PPAR,/,, was characterized using a combination of in vivo and ex vivo magnetic resonance methodologies and compared to treatment effects of fenofibrate, a PPAR, agonist, and pioglitazone, a PPAR, agonist. Methods:, Four groups of fatty Zucker rats: (i) Vehicle; (ii) fenofibrate 150 mg/kg; (iii) pioglitazone 30 mg/kg; and (iv) cevoglitazar 5 mg/kg were investigated before and after treatment. Animals were fed a fat-enriched (54% kcal fat) diet for 6 weeks, 2 weeks high of fat,exposure alone followed by a 4-week dosing period. Results and conclusions:, Cevoglitazar was as effective as pioglitazone at improving glucose tolerance. However, unlike pioglitazone, both fenofibrate and cevoglitazar reduced BW gain and adiposity, independent of food intake. All three treatment regimens normalized intramyocellular lipids. Metabolic profiling showed that in the muscle cevoglitazar improves the lipid profile via both PPAR,- and PPAR,-mediated mechanisms. Pioglitazone reduced hepatic lipid accumulation, while cevoglitazar and fenofibrate reduced hepatic lipid concentration below baseline levels (p < 0.05). Metabolic profiling showed that in the liver, cevoglitazar functions largely through PPAR, agonism resulting in increased ,-oxidation. Cevoglitazar only induced small changes to the lipid composition of visceral fat. In subcutaneous fat, however, cevoglitazar induced changes similar to those observed with fenofibrate suggesting export of fatty acids from this depot. [source] Long-term modulation of glucose utilization by IL-1, and TNF-, in astrocytes: Na+ pump activity as a potential target via distinct signaling mechanismsGLIA, Issue 1 2002Céline Véga Abstract Interleukin-1, (IL-1,) and tumor necrosis factor-, (TNF-,) markedly stimulate glucose utilization in primary cultures of mouse cortical astrocytes. The mechanism that gives rise to this effect, which takes place several hours after application of cytokine, has remained unclear. Experiments were conducted to identify the major signaling cascades involved in the metabolic action of cytokine. First, the selective IL-1 receptor antagonist (IL-1ra) prevents the effect of IL-1, on glucose utilization in a concentration-dependent manner, whereas it has no effect on the action of TNF-,. Then, using inhibitors of three classical signaling cascades known to be activated by cytokines, it appears that the PI3 kinase is essential for the effect of both IL-1, and TNF-,, whereas the action of IL-1, also requires activation of the MAP kinase pathway. Participation of a phospholipase C-dependent pathway does not appear critical for both IL-1, and TNF-,. Inhibition of NO synthase by L-NAME did not prevent the metabolic response to both IL-1, and TNF-,, indicating that nitric oxide is probably not involved. In contrast, the Na+/K+ ATPase inhibitor ouabain prevents the IL-1,- and TNF-,-stimulated 2-deoxyglucose (2DG) uptake. When treatment of astrocytes with a cytokine was followed 24 h later by an acute application of glutamate, a synergistic enhancement in glucose utilization was observed. This effect was greatly reduced by ouabain. These data suggest that Na+ pump activity is a common target for both the long-term metabolic action of cytokines promoted by the activation of distinct signaling pathways and the enhanced metabolic response to glutamate. GLIA 39:10,18, 2002. © 2002 Wiley-Liss, Inc. [source] Clinical impact of, and prognostic stratification by, F-18 FDG PET/CT in head and neck mucosal squamous cell carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 11 2007Caroline A. Connell FRANZCR Abstract Background The aim of this study was to determine prospectively the incremental value of positron emission tomography/computed tomography (PET/CT) over conventional assessment (clinical examination and CT/MRI imaging). Methods All patients undergoing 18F-fluorodeoxyglucose (FDG)-PET/CT for primary head and neck mucosal squamous cell carcinoma between January 2002 and December 2003 (inclusive) were included in this study provided they had undergone contemporaneous conventional assessment of the head and neck region and had 12 months minimum follow-up. Results Seventy-six patients underwent 100 PET/CT scans. The majority of patients (74%) were treated with definitive (chemo)radiotherapy. Median follow-up time was 28 months. PET/CT led to a TNM classification alteration in 34% (12/35), a change in radiotherapy planning technique and/or dose in 29% (10/35), and altered treatment response assessment in 43% (13/30). A complete metabolic response was predictive of overall survival (p = .037). Conclusion Our results support incorporation of PET/CT into the management paradigm of head and neck mucosal squamous cell carcinoma. © 2007 Wiley Periodicals, Inc. Head Neck 2007 [source] Amino acid ingestion and glucose metabolism,A reviewIUBMB LIFE, Issue 9 2010Mary C. Gannon Abstract Interest in the effect of proteins or amino acids on glucose metabolism dates back at least a century, largely because it was demonstrated that the amino acids from ingested protein could be converted into glucose. Indeed, these observations influenced the dietary information provided to people with diabetes. Subsequently it was shown that ingested protein did not raise the blood glucose concentration. It also was shown that proteins could stimulate a rise in insulin and glucagon but the response to various proteins was different. In addition, it was shown that individual amino acids also could stimulate a rise in insulin and in glucagon concentrations. When individual amino acids are ingested by normal subjects, there is an ordering of the insulin and glucagon responses. However, the order is not the same for insulin and glucagon. In addition, the metabolic response cannot be predicted based on the functional groups of the amino acids. Thus, empirical prediction of the metabolic response to ingested single amino acids is not possible. © 2010 IUBMB IUBMB Life, 62(9): 660,668, 2010 [source] Mitochondria and Ca2+ signalingJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2000Emil C. Toescu Abstract Mitochondria play a central role in cell homeostasis. Amongst others, one of the important functions of mitochondria is to integrate its metabolic response with one of the major signaling pathways - the Ca2+ signaling. Mitochondria are capable to sense the levels of cytosolic Ca2+ and generate mitochondrial Ca2+ responses. Specific mechanisms for both Ca2+ uptake and Ca2+ release exist in the mitochondrial membranes. In turn, the mitochondrial Ca2+ signals are able to produce changes in the mitochondrial function and metabolism, which provide the required level of functional integration. This essay reviews briefly the current available information regarding the mitochondrial Ca2+ transport systems and some of the functional consequences of mitochondrial Ca2+ uptake [source] Effect of feeding level and feeding frequency on specific dynamic action in Silurus meridionalisJOURNAL OF FISH BIOLOGY, Issue 1 2005S. J. Fu The effect of feeding level (FL; 0·5 to 4% dry diet mass per wet fish body mass) and feeding frequency (once every 4 days to twice per day) on postprandial metabolic response was investigated in southern catfish Silurus meridionalis at 27·5° C. The results showed that there was no significant difference in the specific dynamic action (SDA) coefficient among the groups of different feeding levels (P > 0·05). The duration increased from 26·0 to 40·0 h and the peak metabolic rate increased from 207·8 to 378·8 mg O2 kg,1 h,1 when the feeding level was increased from 0·5 to 4%. The relationship between the peak metabolic rate (RP, mg O2 kg,1 h,1) and FL could be described as: RP = 175·4 + 47·3 FL(r2 = 0·943, n = 40, P < 0·001). The relationship between the SDA duration (D, h) and FL could be described as D=30·97FL0·248 (r2=0·729, n=40, P < 0·001). [source] Efficacy of dietary treatments for epilepsyJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 2 2010E. G. Neal Abstract The ketogenic diet (KD) is a high fat, restricted carbohydrate regime that has been used as a treatment for seizures since the 1920s, when it was designed to induce a similar metabolic response to fasting. A modification of this early classical version of the KD was introduced in the 1970s using medium chain triglycerides as an alternative fat source. More recently, two alternative, less-restrictive dietary treatments have been developed: the modified Atkins diet and the low glycaemic index diet. There are many case reports and observational studies reporting successful use of the KD, and a growing number of studies reporting similar success with the modified Atkins protocol. A recent randomised controlled trial has shown a significant benefit of the KD compared to no change in treatment. The use of these dietary therapies in the UK is supported by literature evidence, although often is limited by a lack of resources; increasing awareness and knowledge is fundamental to ensure availability for those individuals with intractable epilepsy who may benefit from them. [source] 18F-fluoro-2-deoxy-D-glucose positron emission tomography and positron emission tomography/computed tomography imaging of malignant pleural mesothelioma§JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 2 2009RM Subramaniam Summary Malignant pleural mesothelioma (MPM) is the most common primary pleural tumor and its incidence is rising. Its diagnosis, staging and response assessment are challenging for imaging. Integrated positron emission tomography (PET)/CT increases the accuracy of overall staging in patients with mesothelioma and improves the selection of patients for curative surgical resection. It is particularly useful in identifying occult distant metastases. It may be used to predict prognosis and to assess the metabolic response to therapy. [source] Chloramphenicol decreases brain glucose utilization and modifies the sleep,wake cycle architecture in ratsJOURNAL OF NEUROCHEMISTRY, Issue 6 2005Marcelle Moulin-Sallanon Abstract We studied the effects of chloramphenicol on brain glucose utilization and sleep,wake cycles in rat. After slightly anaesthetized animals were injected with [18F]fluoro-2-deoxy- d -glucose, we acquired time,concentration curves from three radiosensitive , microprobes inserted into the right and left frontal cortices and the cerebellum, and applied a three-compartment model to calculate the cerebral metabolic rates for glucose. The sleep,wake cycle architecture was analysed in anaesthetic-free rats by recording electroencephalographic and electromyographic signals. Although chloramphenicol is a well-established inhibitor of oxidative phosphorylation, no compensatory increase in glucose utilization was detected in frontal cortex. Instead, chloramphenicol induced a significant 23% decrease in the regional cerebral metabolic rate for glucose. Such a metabolic response indicates a potential mismatch between energy supply and neuronal activity induced by chloramphenicol administration. Regarding sleep,wake states, chloramphenicol treatment was followed by a 64% increase in waking, a 20% decrease in slow-wave sleep, and a marked 59% loss in paradoxical sleep. Spectral analysis of the electroencephalogram indicates that chloramphenicol induces long-lasting modifications of delta-band power during slow-wave sleep. [source] Fast food delivery: the response of nursing astrocytes to an exciting call from neuronsJOURNAL OF NEUROCHEMISTRY, Issue 2003L. Pellerin It was suggested long time ago that astrocytes might play a prominent role in the distribution of energy substrates to neurons but convincing evidence was lacking. More recently, the excitatory neurotransmitter glutamate was shown to enhance aerobic glycolysis in cultured cortical astrocytes by a mechanism involving glial glutamate transporters. Using specific knockout mice for these transporters, it was demonstrated that a classical metabolic response to neuronal activation in the whisker-to-barrel system, 2-deoxyglucose accumulation, was disrupted in the somatosensory cortex of these animals at postnatal day 10. From these data, it was concluded that a net transfer of some energy substrate, preferentially lactate, must be taking place in order to fulfill increasing neuronal energy needs during periods of enhanced activity. In support of this concept, the presence of specific transporters for lactate, known as monocarboxylate transporters, was recently described both on astrocytes and neurons in vitro as well as in vivo. [source] Temporal expression of growth factors and matrix molecules in healing tendon lesionsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2005Linda A. Dahlgren Abstract Overuse tendon injuries are common among elite and recreational athletes. Tendon healing may be enhanced at the cellular level through the use of exogenous growth factors; however, little is known about the endogenous expression of growth factors in healing tendon. This study describes the temporal expression of insulin-like growth factor-I (IGF-I), transforming growth factor-,1 (TGF-,1), and collagen types I and III in healing tendon lesions. Collagenase-induced lesions were created in the tensile region of the flexor digitorum superficialis tendon of both forelimbs of 14 horses. Tendons were harvested from euthanatized horses 1, 2, 4, 8 or 24 weeks following injury. Gene expression was evaluated using Northern blot analysis (collagen types I and III), real time PCR (IGF-I and TGF-,1), and in situ hybridization. Protein content was assayed by dye-binding assay (collagen types I and III), radioimmunoassay (IGF-I), ELISA (TGF-,1), and immunohistochemistry. Samples were also processed for differential collagen typing. DNA and glycosaminoglycan content, and routine H&E staining. Microscopically, lesions progressed from an amorphous, acellular lesion soon after injury to scar tissue filled with collagen fibers and mature fibroblasts organized along lines of tension. Early lesions were characterized by immediate increases in expression of growth factors and collagen. Message levels for TGF-,1 peaked early in the wound healing process (1 week), while IGF-I peaked later (4 weeks), as the regenerative phase of healing was progressing. In the first 2 weeks after lesion induction, tissue levels of IGF-I protein actually decreased approximately 40% compared to normal tendon. By 4 weeks, these levels had exceeded those of normal tendon and remained elevated through 8 weeks. Message expression for collagen types I and III increased by 1 week following injury and remained elevated throughout the course of the study. Collagen type I represented the major type of collagen in healing tendon at all time points of the study. Based on these results, IGF-I, administered exogenously during the first 2 weeks following injury, may provide a therapeutic advantage by bolstering low endogenous tissue levels and enhancing the metabolic response of individual tendon fibroblasts. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Neoadjuvant therapy of locally advanced gastric cancerJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2010James J. Mezhir MD Abstract Treatment of gastric cancer has evolved with the advent of randomized trials demonstrating chemotherapeutic agents with efficacy in advanced disease. Level I evidence supports delivering chemotherapy in the neoadjuvant setting; the data shows improvement in progression-free and overall survival. A clinical response to therapy is associated with improved R0 resection rates, pathologic response, and outcome in patients with locally advanced disease. Early assessment of metabolic response to therapy can potentially be utilized to tailor treatment. J. Surg. Oncol. 2010; 101:305,314. © 2010 Wiley-Liss, Inc. [source] Nutrigenomics,new approaches for human nutrition researchJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 8 2006Helen M Roche Abstract Food intake and nutrient exposure are key environmental factors involved in the pathogenesis and progression of the common polygenic, diet-related diseases. An individual's phenotype represents a complex interaction between the human genome and environmental factors during an individual's lifetime. This review explores the concept that there is a dynamic, two-way interaction between nutrition and the human genome which determines gene expression, the metabolic response and an individual's health status. It addresses the relevance of new high-throughput genomic, transcriptomic, proteomic and metabolomic technologies within human nutrition research. Common, polygenic, diet-related diseases (CVD, obesity, T2DM, etc.) reflect multiple genetic variants interacting with numerous environmental factors, each combination making a relatively small contribution to overall cellular homeostasis, whole body metabolism and health. This review highlights the value of a nutrigenomics-based systems biology approach to understanding human nutrition and identifying new biomarkers of nutrition and health. The challenge will be to develop and apply robust nutritional genomics research initiatives that are sensitive enough to take account of both human genetic heterogeneity and diverse nutrient exposure. If nutrigenomic approaches enhance our understanding of human nutrition at the molecular level, then it may be possible to apply a more targeted and effective personalized nutrition approach to attenuate the effect of risk factors associated with diet-related diseases. Indeed it could be proposed that a personalized nutrition approach may assist in improving the effectiveness of dietary guidelines/recommendations in general. Copyright © 2006 Society of Chemical Industry [source] The role of the yeast plasma membrane SPS nutrient sensor in the metabolic response to extracellular amino acidsMOLECULAR MICROBIOLOGY, Issue 1 2001Hanna Forsberg In response to discrete environmental cues, Saccharomyces cerevisiae cells adjust patterns of gene expression and protein activity to optimize metabolism. Nutrient-sensing systems situated in the plasma membrane (PM) of yeast have only recently been discovered. Ssy1p is one of three identified components of the Ssy1p,Ptr3p,Ssy5 (SPS) sensor of extracellular amino acids. SPS sensor-initiated signals are known to modulate the expression of a number of amino acid and peptide transporter genes (i.e. AGP1, BAP2, BAP3, DIP5, GAP1, GNP1, TAT1, TAT2 and PTR2) and arginase (CAR1). To obtain a better understanding of how cells adjust metabolism in response to extracellular amino acids in the environment and to assess the consequences of loss of amino acid sensor function, we investigated the effects of leucine addition to wild-type and ssy1 null mutant cells using genome-wide transcription profile analysis. Our results indicate that the previously identified genes represent only a subset of the full spectrum of Ssy1p-dependent genes. The expression of several genes encoding enzymes in amino acid biosynthetic pathways, including the branched-chain, lysine and arginine, and the sulphur amino acid biosynthetic pathways, are modulated by Ssy1p. Additionally, the proper transcription of several nitrogen-regulated genes, including NIL1 and DAL80, encoding well-studied GATA transcription factors, is dependent upon Ssy1p. Finally, several genes were identified that require Ssy1p for wild-type expression independently of amino acid addition. These findings demonstrate that yeast cells require the SPS amino acid sensor component, Ssy1p, to adjust diverse cellular metabolic processes properly. [source] Regulation of lactate production at the onset of ischaemia is independent of mitochondrial NADH/NAD+: insights from in silico studiesTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Lufang Zhou Ischaemia decreases mitochondrial NADH oxidation, activates glycolysis, increases the NADH/NAD+ ratio, and causes lactate production. The mechanisms that regulate anaerobic glycolysis and the NADH/NAD+ ratio during ischaemia are unclear. Although continuous measurements of metabolic fluxes and NADH/NAD+ in cytosol and mitochondria are not possible in vivo with current experimental techniques, computational models can be used to predict these variables by simulations with in silico experiments. Such predictions were obtained using a mathematical model of cellular metabolism in perfused myocardium. This model, which distinguishes cytosolic and mitochondrial domains, incorporates key metabolic species and processes associated with energy transfer. Simulation of metabolic responses to mild, moderate and severe ischaemia in large animals showed that mitochondrial NADH/NAD+ was rapidly reset to higher values in proportion to the reduced O2 delivery and myocardial oxygen consumption . Cytosolic NADH/NAD+, however, showed a biphasic response, with a sharp initial increase that was due to activation of glycogen breakdown and glycolysis, and corresponded with lactate production. Whereas the rate of glycolysis and the malate,aspartate shuttle had a significant effect on the cytosolic NADH/NAD+, their effects on the mitochondrial NADH/NAD+ were minimal. In summary, model simulations of the metabolic response to ischaemia showed that mitochondrial NADH/NAD+ is primarily determined by O2 consumption, while cytosolic NADH/NAD+ is largely a function of glycolytic flux during the initial phase, and is determined by mitochondrial NADH/NAD+ and the malate,aspartate shuttle during the steady state. [source] Time-series integrated "omic" analyses to elucidate short-term stress-induced responses in plant liquid cultures,BIOTECHNOLOGY & BIOENGINEERING, Issue 1 2009Bhaskar Dutta Abstract The research that aims at furthering our understanding of plant primary metabolism has intensified during the last decade. The presented study validated a systems biology methodological framework for the analysis of stress-induced molecular interaction networks in the context of plant primary metabolism, as these are expressed during the first hours of the stress treatment. The framework involves the application of time-series integrated full-genome transcriptomic and polar metabolomic analyses on plant liquid cultures. The latter were selected as the model system for this type of analysis, because they provide a well-controlled growth environment, ensuring that the observed plant response is due only to the applied perturbation. An enhanced gas chromatography,mass spectrometry (GC,MS) metabolomic data correction strategy and a new algorithm for the significance analysis of time-series "omic" data are used to extract information about the plant's transcriptional and metabolic response to the applied stress from the acquired datasets; in this article, it is the first time that these are applied for the analysis of a large biological dataset from a complex eukaryotic system. The case-study involved Arabidopsis thaliana liquid cultures subjected for 30 h to elevated (1%) CO2 stress. The advantages and validity of the methodological framework are discussed in the context of the known A. thaliana or plant, in general, physiology under the particular stress. Of note, the ability of the methodology to capture dynamic aspects of the observed molecular response allowed for 9 and 24 h of treatment to be indicated as corresponding to shifts in both the transcriptional and metabolic activity; analysis of the pathways through which these activity changes are manifested provides insight to regulatory processes. Biotechnol. Bioeng. 2009;102: 264,279. © 2008 Wiley Periodicals, Inc. [source] Early 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography may identify a subset of patients with estrogen receptor-positive breast cancer who will not respond optimally to preoperative chemotherapyCANCER, Issue 4 2010Andrea A. Martoni MD Abstract BACKGROUND: A pathologic complete response (pCR) and minimal residual disease (pMRD) after preoperative chemotherapy (PCT) for early stage or locally advanced breast cancer (BC) correlates with a good prognosis. METHODS: Patients who received from 6 to 8 cycles of PCT for BC were monitored by 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET), and the maximal standardized uptake value (SUVmax) was calculated at baseline, after 2 cycles, after 4 cycles, and at the end of PCT. SUVmax percentage changes (,-SUV) were compared with the pathologic response rate. Patients who had a pCR or pMRD in the tumor and an absence of cancer cells in ipsilateral axillary lymph nodes were defined as having obtained an optimal pathologic response (pR), whereas all the other conditions were classified as a pathologic nonresponse (pNR). RESULTS: Of 34 patients, 7 (21%) achieved a pR (3 patients had a pCR, and 4 patients had pMRD). After the second cycle, the ,-SUV threshold with optimal negative predictive value to predict a pR was 50%. Twenty-six patients (76%) had a ,-SUV >50%, including all 7 patients who had a pR and 19 patients who had a pNR. Conversely, all 8 patients who had a ,-SUV ,50% had a pNR. All 8 of those patients had estrogen recepetor-positive tumors. CONCLUSIONS: Early evaluation of metabolic response by 18F-FDG-PET during PCT was able to identify 30% of patients, all with estrogen receptor-positive tumors, who would not obtain pR after completion of chemotherapy program. Cancer 2010. © 2010 American Cancer Society. [source] AMPK activators , potential therapeutics for metabolic and other diseasesACTA PHYSIOLOGICA, Issue 1 2009G. Zhou Abstract AMP-activated protein kinase (AMPK)-mediated cellular metabolic responses to tissue-specific and whole-body stimuli play a vital role in the control of energy homeostasis. As a cellular energy-sensing mechanism, AMPK activation stimulates glucose uptake and fat oxidation, while it suppresses lipogenesis and gluconeogenesis. The cumulative effects of AMPK activation lead to beneficial metabolic states in liver, muscle and other peripheral tissues that are critical in the pathogenesis of obesity, type 2 diabetes and related metabolic disorders. Activators of AMPK that target selected tissues hold potential as novel therapeutics for diseases in which altered energy metabolism contributes to aetiology. [source] Effect of raisin consumption on oxidative stress and inflammation in obesityDIABETES OBESITY & METABOLISM, Issue 11 2008J. W. Rankin Aim:, Oxidative stress can initiate increased inflammation that elevates risk for cardiovascular disease. The objective of this study was to determine the effects of daily consumption of raisins on markers of oxidative stress, inflammation and endothelial activation in response to an acute high-fat meal in overweight individuals. Methods:, Seventeen overweight men and women consumed 90 g raisins or isocaloric placebo (264 kcal/day) for 14 days in a randomized, crossover design while following a low-flavonoid diet. The oxidative [urinary 8-iso-prostaglandin-F2, (8-epi PGF2,) and serum oxygen radical absorbance capacity (ORAC)], inflammatory (serum C-reactive protein and interleukin-6), endothelial (serum soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1, sVCAM-1) and metabolic [free fatty acids (FFAs), triacylglycerol, glucose and insulin] response to four high-fat (53%) meals was tested pre- and postintervention. Results:, Urinary 8-epi PGF2, decreased (,22%) and fasting ORAC increased (+3%) after both interventions combined. Fasting protein-free ORAC was modestly (+3.5%) higher during the raisin than the placebo intervention. Neither the meals nor the raisins consistently induced fasted markers of inflammation or endothelial dysfunction. Gender influenced postprandial metabolic responses in that males responded with higher serum FFAs, sVCAM-1 and glucose compared with females. Conclusions:, Serum antioxidant capacity was modestly increased by daily raisin consumption, but this did not alter fasted or postprandial inflammatory response in these relatively healthy but overweight individuals. Providing all food in regular pattern reduced measures of oxidative stress. [source] Evidence for a vicious cycle of exercise and hypoglycemia in type 1 diabetes mellitusDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2004A. C. Ertl Abstract Exercise is a cornerstone of diabetes management as it aids in glycemic control, weight management, reducing blood pressure, and improving the quality of life of patients. Unfortunately, owing to the complexity and difficulties of regulating exogenous insulin in a physiologic manner during exercise, physical activity often results in hypoglycemia in patients with type 1 diabetes mellitus (type 1 DM). When glucose levels fall below threshold glycemic levels, neuroendocrine, autonomic nervous system (ANS), and metabolic glucose counterregulatory mechanisms are activated. These hypoglycemic counterregulatory mechanisms in type 1 DM can be blunted irreversibly by disease duration or by acute episodes of prior stress. These reduced (or absent) counterregulatory responses result in a threefold increase in severe hypoglycemia when intensive glycemic control is implemented in type 1 DM 1. Much recent work has been focused on determining the in vivo mechanisms responsible for causing the increased incidence of severe hypoglycemia in type 1 DM. Studies from several laboratories have demonstrated the role played by episodes of antecedent hypoglycemia in producing blunted glucose counterregulatory responses during subsequent exposures of hypoglycemia. Until recently, the mechanisms responsible for exercise related hypoglycemia in type 1 DM have been attributed to relative or absolute increases of insulin levels or incomplete glycogen repletion after physical activity. Owing to the qualitative similarity of neuroendocrine, ANS, and metabolic responses to hypoglycemia and exercise, we have hypothesized that neuroendocrine and ANS counterregulatory dysfunction may also play an important role in the pathogenesis of exercise-related hypoglycemia in type 1 DM. Vicious cycles can be created in type 1 DM, where an episode of hypoglycemia or exercise can feed forward to downregulate neuroendocrine and ANS responses to a subsequent episode of either stress, thereby creating further hypoglycemia (Figure 1). This article will review the recent work that has studied the contribution of counterregulatory dysfunction to exercise-induced hypoglycemia in type 1 DM. Copyright © 2004 John Wiley & Sons, Ltd. 1. Reciprocal vicious cycles may be created in type 1 diabetes mellitus (type 1 DM), whereby an episode of hypoglycemia or exercise can feed forward to downregulate neuroendocrine and autonomic nervous system responses to a subsequent episode of either stress, thereby creating further hypoglycemia [source] Exercise training in late middle-aged male Fischer 344 × Brown Norway F1-hybrid rats improves skeletal muscle aerobic functionEXPERIMENTAL PHYSIOLOGY, Issue 7 2008Andrew C. Betik The Fischer 344 × Brown Norway F1-hybrid (F344BN) rat has become an increasingly popular and useful strain for studying age-related declines in skeletal muscle function because this strain lives long enough to experience significant declines in muscle mass. Since exercise is often considered a mechanism to combat age-related declines in muscle function, determining the utility of this strain of rat for studying the effects of exercise on the ageing process is necessary. The purpose of this study was to evaluate the plasticity of skeletal muscle aerobic function in late middle-aged male rats following 7 weeks of treadmill exercise training. Training consisted of 60 min per day, 5 days per week with velocity gradually increasing over the training period according to the capabilities of individual rats. The final 3 weeks involved 2 min high-intensity intervals to increase the training stimulus. We used in situ skeletal muscle aerobic metabolic responses and in vitro assessment of muscle mitochondrial oxidative capacity to describe the adaptations of aerobic function from the training. Training increased running endurance from 11.3 ± 0.6 to 15.5 ± 0.8 min, an improvement of ,60%. Similarly, distal hindlimb muscles from trained rats exhibited a higher maximal oxygen consumption in situ (23.2 ± 1.3 versus 19.7 ± 0.8 ,mol min,1 for trained versus sedentary rats, respectively) and greater citrate synthase and complex IV enzyme activities in gastrocnemius (29 and 19%, respectively) and plantaris muscles (24 and 28%, respectively) compared with age-matched sedentary control animals. Our results demonstrate that skeletal muscles from late middle-aged rats adapt to treadmill exercise by improving skeletal muscle aerobic function and mitochondrial enzyme activities. This rat strain seems suitable for further investigations using exercise as an intervention to combat ageing-related declines of skeletal muscle aerobic function. [source] Is ,nocturnal hypothermia' a valid physiological concept in small birds?: a study on Bronze Mannikins Spermestes cucullatusIBIS, Issue 4 2003Barry G. Lovegrove The thermoregulatory capacity and metabolic responses to light,dark cycles under various mild food-deprivation treatments were measured in Bronze Mannikins Spermestes cucullatus (10,11 g). We measured the response of minimum oxygen consumption to ambient temperature in order to determine the basal metabolic rate (BMR), thermal conductance and limits of thermoneutrality of the Mannikins. In addition, we measured oxygen consumption in response to light,dark cycles and three mild food-deprivation treatments. Bronze Mannikins have a low BMR (1.67 mlO2/g/h) that is c. 50,60% of that predicted from phylogenetically independent allometric curves for all birds. A low BMR resulted in amplitudes of metabolism between the active and rest phases that were double those predicted allometrically from body mass. The reduced nocturnal metabolic rate did not represent torpor. Typically, Mannikins would need to reduce their metabolic rate during the rest phase to c. 17% of BMR to attain the average torpor metabolic rate of other birds. The data are, however, consistent with those of other group-living Afrotropical birds that benefit energetically from group huddling in environments in which moderate seasonality is accompanied by unpredictable climates , and thus unpredictable energy inputs in time and space. When food-deprived and placed under moderate cold stress (20 °C), Mannikins decreased their rest-phase metabolic rates to the same magnitude as several small Holarctic birds. We suggest that, in the context of the progress made to quantify and define proximate heterothermic responses in endotherms, such as torpor and hibernation, the term nocturnal hypothermia often applied to moderate nocturnal reductions in metabolic rate is vague, misleading and inappropriate. [source] Metabolic responses to oral tryptophan supplementation before exercise in horsesJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3-6 2005I. Vervuert Summary This study was conducted to evaluate the effects of oral tryptophan (Trp) supplementation on exercise capacity and metabolic responses in horses. Three horses had to perform an exercise test: a 15-min warm-up followed by a 60-min walk (1.7 m/s, W1), a 10-min trot (3.1 m/s, T1), a second 60-min walk (1.7 m/s, W2), a second 10-min trot (3.1 m/s, T2) and a final 30-min walk (1.7 m/s, W3) until the horses were unwilling to continue. The horses exercised on a treadmill at a 6% incline and with a constant draught load of 40 kg (0.44 kN). Two hours before exercise horses were given 50 g Trp (9.8,10.7 g Trp/100 kg BW) by nasogastric tube. A control exercise test was conducted without Trp. During the control test, one horse was able to finish the final 30-min walk (W3), whereas two horses finished W3 after Trp administration. Higher plasma Trp levels after Trp administration did not change significantly during exercise (Trp: start exercise, 524 ± 41 ,mol/l; end exercise 547 ± 20 ,mol/l; control: start exercise, 70 ± 10 ,mol/l; end exercise, 58 ± 21 ,mol/l). After Trp supplementation, blood lactate concentrations were significantly lower after the first and second trotting periods. Free fatty acids in plasma increased during exercise without any treatment-related differences. Although experimental plasma Trp levels were seven times higher than the control levels, Trp supplementation had no effect on exercise performance and metabolic responses to draught load exercise. [source] Fasting modulates metabolic responses to cortisol, GH and IGF-I in Arctic charr hepatocytesJOURNAL OF FISH BIOLOGY, Issue 6 2005Ø. Aas-Hansen Hepatocytes in primary culture from fed and 2 month fasted Arctic charr Salvelinus alpinus were exposed to physiological doses of either cortisol, salmon growth hormone (GH), salmon insulin-like growth factor-I (IGF-I) or a combination of salmon GH and salmon IGF-I. Fasting significantly lowered medium glucose levels compared to the fed fish, but had no significant effects on hepatocyte glycogen content or on the activities of enzymes involved in the intermediary metabolism. Cortisol treatment had no effect on hepatocyte glycogen content or on the enzyme activities investigated, but resulted in a significant increase in medium glucose concentration in hepatocytes isolated from fasted, but not fed fish. GH and IGF-I treatments, both singly and in combination, significantly increased the glycogen content of hepatocytes isolated from fed fish, with less pronounced effects on hepatocytes isolated from fasted fish. The combination of GH and IGF-I significantly increased lactate dehydrogenase activity regardless of the feeding state and significantly reduced the phosphenolpyruvate carboxykinase activity and medium glucose concentration in hepatocytes isolated from fed fish. Further, GH and IGF-I significantly increased the activities of alanine aminotransferase and aspartate aminotransferase in hepatocytes isolated from fasted fish, but not fed fish. There were no effects of GH, IGF-I, or their combination, on glucose 6-phosphate dehydrogenase or 3-hydroxyacyl-CoA dehydrogenase activities. The results demonstrated that nutritional status of the animal modulates hepatocyte responsiveness to metabolic hormones, and suggested a role for GH and IGF-I in hepatic glycogen conservation. [source] Abnormalities of whole body protein turnover, muscle metabolism and levels of metabolic hormones in patients with chronic heart failureJOURNAL OF INTERNAL MEDICINE, Issue 1 2006H. NØRRELUND Abstract. Objective., It is well known that chronic heart failure (CHF) is associated with insulin resistance and cachexia, but little is known about the underlying substrate metabolism. The present study was undertaken to identify disturbances of basal glucose, lipid and protein metabolism. Design., We studied eight nondiabetic patients with CHF (ejection fraction 30 ± 4%) and eight healthy controls. Protein metabolism (whole body and regional muscle fluxes) and total glucose turnover were isotopically assayed. Substrate oxidation were obtained by indirect calorimetry. The metabolic response to exercise was studied by bicycle ergometry exercise. Results., Our data confirm that CHF patients have a decreased lean body mass. CHF patients are characterised by (i) decreased glucose oxidation [glucose oxidation (mg kg,1 min,1): 1.25 ± 0.09 (patients) vs. 1.55 ± 0.09 (controls), P < 0.01] and muscle glucose uptake [a , v diffglucose (,mol L,1): ,10 ± 25 (patients) vs. 70 ± 22 (controls), P < 0.01], (ii) elevated levels of free fatty acids (FFA) [FFA (mmol L,1): 0.72 ± 0.05 (patients) vs. 0.48 ± 0.03 (controls), P < 0.01] and 3-hydroxybutyrate and signs of elevated fat oxidation and muscle fat utilization [a , v diffFFA (mmol L,1): 0.12 ± 0.02 (patients) vs. 0.05 ± 0.01 (controls), P < 0.05] and (iii) elevated protein turnover and protein breakdown [phenylalanine flux (,mol kg,1 h,1): 36.4 ± 1.5 (patients) vs. 29.6 ± 1.3 (controls), P < 0.01]. Patients had high circulating levels of noradrenaline, glucagon, and adiponectin, and low levels of ghrelin. We failed to observe any differences in metabolic responses between controls and patients during short-term exercise. Conclusions., In the basal fasting state patients with CHF are characterized by several metabolic abnormalities which may contribute to CHF pathophysiology and may provide a basis for targeted intervention. [source] | |||||||||||||||||||||||||||||||