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Metabolic Function (metabolic + function)

Distribution by Scientific Domains

Medical Sciences	51%
Life Sciences	37%
Chemistry	10%

Selected Abstracts

Determinants of the nucleocytoplasmic shuttling of muscle glycogen synthase

FEBS JOURNAL, Issue 12 2005
Emili Cid
Muscle glycogen synthase (MGS) presents a nuclear speckled pattern in primary cultured human muscle and in 3T3-L1 cells deprived of glucose and with depleted glycogen reserves. Nuclear accumulation of the enzyme correlates inversely with cellular glycogen content. Although the glucose-induced export of MGS from the nucleus to the cytoplasm is blocked by leptomycin B, and therefore mediated by CRM1, no nuclear export signal was identified in the sequence of the protein. Deletion analysis shows that the region comprising amino acids 555,633 of human MGS, which encompasses an Arg-rich cluster involved in the allosteric activation of the enzyme by Glc6P, is crucial for its nuclear concentration and aggregation. Mutation of these Arg residues, which desensitizes the enzyme towards Glc6P, interferes with its nuclear accumulation. In contrast, the known phosphorylation sites of MGS that regulate its activity are not involved in the control of its subcellular distribution. Nuclear human MGS colocalizes with the promyelocytic leukaemia oncoprotein and p80-coilin, a marker of Cajal bodies. The subnuclear distribution of MGS is altered by incubation with transcription inhibitors. These observations suggest that, in addition to its metabolic function, MGS may participate in nuclear processes. [source]

Alcohol consumption and body weight

HEALTH ECONOMICS, Issue 7 2010
Michael T. French
Abstract The number of Americans who are overweight or obese has reached epidemic proportions. Elevated weight is associated with health problems and increased medical expenditures. This paper analyzes Waves 1 and 2 of the National Epidemiological Survey of Alcohol and Related Conditions to investigate the role of alcohol consumption in weight gain. Alcohol is not only an addictive substance but also a high-calorie beverage that can interfere with metabolic function and cognitive processes. Because men and women differ in the type and amount of alcohol they consume, in the biological effects they experience as a result of alcohol consumption, and in the consequences they face as a result of obesity, we expect our results to differ by gender. We use first-difference models of body mass index (BMI) and alcohol consumption (frequency and intensity) to control for time-invariant unobservable factors that may influence changes in both alcohol use and weight status. Increasing frequency and intensity of alcohol use is associated with statistically significant yet quantitatively small weight gain for men but not for women. Moreover, the first-difference results are much smaller in magnitude and sometimes different in sign compared with the benchmark pooled cross-sectional estimates. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Allostatic Load and Frailty in Older Adults

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 9 2009
Tara L. Gruenewald PhD
OBJECTIVES: To examine the association between allostatic load (AL), an index of multisystem physiological dysregulation, and frailty development over a 3-year follow-up in a sample of older adults. DESIGN: Longitudinal cohort study. SETTING: Community. PARTICIPANTS: High-functioning men and women aged 70 to 79 at study entry. MEASUREMENTS: Multisystem physiological dysregulation, or AL, was assessed according to 13 biomarkers of cardiovascular, endocrine, immune, and metabolic function. An AL score was computed as the total number of biomarkers for which participant values fell into high-risk biomarker quartiles. Frailty status (not frail, intermediate frail, frail) was determined according to the total number of five indicators of frailty: weight loss, exhaustion, weak grip, slow gait, and low physical activity. The association between level of AL at baseline and frailty status 3 years later was examined using ordinal logistic regression in 803 participants not frail at baseline. RESULTS: In a multivariable model adjusting for sociodemographic, health, and behavioral characteristics, each 1-unit increase in AL at baseline was associated with a 10% greater likelihood of frailty at the 3-year follow-up (cumulative adjusted odds ratio=1.10, 95% confidence interval=1.03,1.19). CONCLUSION: These findings support the hypothesis that dysregulation across multiple physiological systems is associated with greater risk of frailty. Greater levels of multisystem physiological dysregulation may serve as a warning sign of frailty development in later life. [source]

Ultrastructure of the gingiva in cardiac patients treated with or without calcium channel blockers

JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 8 2003
P. Bullon
Abstract Objectives: In the last few years, several studies have suggested that periodontal diseases are related to the development of atherosclerosis and its complications. Our objective was to study the ultrastructural morphology of the gingiva from cardiac patients, some of whom were treated and some not with calcium channel blockers compared to a control group. Material and Methods: Fifty-five patients were studied and grouped in the following way: (a) healthy group (HG) (n=12) healthy patients with at least two pockets between 3 and 5 mm; (b) cardiac group (CG) (n=12) patients with cardiac disease untreated with calcium channel blockers; (c) diltiazem group (DG) (n=13) cardiac patients treated with diltiazem; (d) nifedipine group (NG) (n=18) cardiac patients treated with nifedipine. Results: Ultrastructural studies in the CG showed inflammatory cells, collagen fibers disruption and a more extended morphologically compromised fibroblast mitochondria. Morphometric studies in CG showed mitochondria that were impaired in number but increased in volume, suggesting metabolic cell suffering. In DG and NG, morphometric data were similar to HG. The presence of myofibroblasts and collagen neosynthesis was detected in DG and NG. Conclusions: Our data showed differences in the ultrastructure of the gingival fibroblasts between the studied groups; the DG and NG showed features that could be interpreted as an attempt to restore the cellular metabolic function. Zusammenfassung Ziele: In den letzten Jahren haben einige Studien darauf hingewiesen, dass parodontale Erkrankungen zur Entwicklung von Arteriosklerose und deren Komplikationen in Beziehung stehen. Unser Ziel war das Studium der gingivalen ultrastrukturellen Morphologie von herzkranken Patienten, von denen einige mit Kalzium-Kanal-Blockern und andere ohne diese Medikamente behandelt wurden, und mit Kontrollen zu vergleichen. Material und Methoden: 55 Patienten wurden untersucht und in eine der folgenden Gruppen eingeteilt: a, gesunde Gruppe (HG) (n=12): gesunde Patienten mit mindestens 2 Taschen zwischen 3 und 5 mm, b, herzkranke Gruppe (CG) (n=12): Patienten mit Herzerkrankung und nicht mit Kalzium-Kanal-Blockern behandelt, c, Diltiazem Gruppe (DG) (n=13): Herzkranke Patienten, die mit Diltiazem behandelt wurden, d, Nifedipin Gruppe (NG) (n=18): Herzkranke Patienten, die mit Nifedipin behandelt wurden. Ergebnisse: Die Ultrastruktur bei CG zeigte Entzündungszellen, zerrissene Kollagenfasern und stärker ausgedehnte morphologisch gefährdete Fibroblastenmitochondrien. Morphometrische Studien bei CG zeigten Mitochondrien, die in der Anzahl beeinträchtigt waren, aber im Volumen zugenommen hatten, was auf einen gestörten Zellstoffwechsel deutet. Bei DG und NG waren die morphometrischen Daten ähnlich zu HG. Die Präsenz von Myofibroblasten und Kollagensynthese wurde in DG und NG entdeckt. Schlussfolgerung: Unsere Daten zeigten Differenzen in der Ultrastruktur der gingivalen Fibroblasten zwischen den untersuchten Gruppen. DG und NG zeigten Eigenschaften, die als Versuch zur Restauration der zellulären Stoffwechselfunktion gedeutet werden könnten. Résumé Objectifs: Lors des dernières années, plusieurs études ont suggéré que les maladies parodontales sont liées au développement de l'athérosclérose et de ses conséquences. Notre objectif est d'étudier la morphologie ultrastructurale de la gencive de patients cardiaques traités et non traités par des bloqueurs des flux de calcium comparée à un groupe contrôle. Matériel et méthodes: 55 patients furent étudiés et groupés de la façon suivante: (a) groupe sain (HG) (n=12), patients sains avec au moins 2 poches entre 3 et 5 mm (b) groupe cardiaque(CG) (n=12) patients ayant une maladie cardiaque non traitée par des bloqueurs des flux de calcium (c) groupe diltiazem (DG) (n=13) patients cardiaques traits par diltiazem; (d) groupe nifedipine (NG) (n=18 patients cardiaques traits par nifedipine). Résultats: Des études ultrastructurale du groupe CG montraient des cellules inflammatoires, des interruptions des fibres de collagènes, et un nombre plus important de mitochondries des fibroblastes morphologiquement compromises. Les études morphométriques du groupe CG montraient des mitochondries altérées en nombre mais au volume augmenté ce qui suggérait une souffrance métabolique cellulaire. Dans les groupes DG et NG, les données morphométriques étaient similaires à celles du groupe HG. La présence de myofibroblastes et d'une néo-synthèse de collagène étaient détectées dans les groupes DG et NG. Conclusions: Nos données montrent des différences de l'ultrastructure des fibroblastes gingivaux entre les groupes étudiés, les groupes DG et NG présentant des caractéristiques qui peuvent être interprétées comme une tentative de restauration de la fonction métabolique cellulaire. [source]

Reversal of suppressed metabolism in prolonged cold preserved cartilage

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2008
Tamara K. Pylawka
Abstract Chondrocytes in cold preserved cartilage are metabolically suppressed. The goal of this study was to address this metabolic suppression and seek ways to reverse it. Specifically, we examined the roles of rewarming protocols and nitric oxide (NO) in this metabolic suppression. Bovine and canine full-thickness articular cartilage explants were cultured under various temperature conditions, and NO production, proteoglycan (PG) synthesis, and cell viability were measured. Nitric oxide was shown to be negatively correlated with PG synthesis following abrupt rewarming of cold preserved osteochondral allografts. Gradual rewarming of the allograft tissue decreased NO production with higher PG synthesis. Inhibition of nitric oxide synthases (NOS) led to a decrease in NO production and a concomitant increase in PG synthesis. We were able to partially reverse metabolic suppression of cold preserved osteochondral allograft material with gradual rewarming and decrease NO production with NOS inhibition. Chondrocytes in cold preserved allograft material may be metabolically suppressed predisposing the graft to failure in vivo. Minimizing this loss of metabolic function by gradual graft rewarming and decreasing NO production by NOS inhibition at the time of graft implantation may have implications on graft survival in vivo. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:247,254, 2008 [source]

Hypothalamic Function in Response to 2-Deoxy- d -Glucose in Long-Term Abstinent Alcoholics

ALCOHOLISM, Issue 5 2001
John C. Umhau
Background: The body adapts to diverse stressful stimuli with a response characterized by activation of the hypothalamic-pituitary-adrenal (HPA) axis. Chronic alcohol consumption can cause changes in the function of this neuroendocrine system. Although many studies have examined this phenomenon in drinking and recently sober alcoholics, few studies have examined HPA axis function in long-term sober alcoholics. Methods: To characterize HPA axis function in long-term sober alcoholics, we used a challenge paradigm with 2-deoxy-d-glucose (2-DG). An infusion of 2-DG (a nonmetabolizable glucose analog) induces a well-characterized stress response. In a previous study, our laboratory found an exaggerated corticotropin and cortisol response in alcoholics abstinent 3 weeks; in this investigation we compared the effects of an infusion of 2-DG on 19 healthy volunteers and 20 community-living alcoholics who had been abstinent more than 6 months. Results: In contrast to the previous study, long-term sober alcoholics did not have an exaggerated corticotropin and cortisol response after 2-DG. Conclusions: Previously observed abnormalities in cortisol regulation in 3-week-sober alcoholics may be related to the acute effects of recent alcohol consumption and withdrawal. Future investigations into the metabolic function of alcoholics, particularly investigations involving the HPA system, should consider the possibility that normalization may not occur until long-term abstinence has been achieved. [source]

Investigating the importance of flow when utilizing hyaluronan scaffolds for tissue engineering

JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 2 2010
Gail C. Donegan
Abstract Esterified hyaluronan scaffolds offer significant advantages for tissue engineering. They are recognized by cellular receptors, interact with many other extracellular matrix proteins and their metabolism is mediated by intrinsic cellular pathways. In this study differences in the viability and structural integrity of vascular tissue models cultured on hyaluronan scaffolds under laminar flow conditions highlighted potential differences in the biodegradation kinetics, processes and end-products, depending on the culture environment. Critical factors are likely to include seeding densities and the duration and magnitude of applied biomechanical stress. Proteomic evaluation of the timing and amount of remodelling protein expression, the resulting biomechanical changes arising from this response and metabolic cell viability assay, together with examination of tissue morphology, were conducted in vascular tissue models cultured on esterified hyaluronan felt and PTFE mesh scaffolds. The vascular tissue models were derived using complete cell sheets derived from harvested and expanded umbilical cord vein cells. This seeding method utilizes high-density cell populations from the outset, while the cells are already supported by their own abundant extracellular matrix. Type I and type IV collagen expression in parallel with MMP-1 and MMP-2 expression were monitored in the tissue models over a 10 day culture period under laminar flow regimes using protein immobilization technologies. Uniaxial tensile testing and scanning electron microscopy were used to compare the resulting effects of hydrodynamic stimulation upon structural integrity, while viability assays were conducted to evaluate the effects of shear on metabolic function. The proteomic results showed that the hyaluronan felt-supported tissues expressed higher levels of all remodelling proteins than those cultured on PTFE mesh. Overall, a 21% greater expression of type I collagen, 24% higher levels of type IV collagen, 24% higher levels of MMP-1 and 34% more MMP-2 were observed during hydrodynamic stress. This was coupled with a loss of structural integrity in these models after the introduction of laminar flow, as compared to the increases in all mechanical properties observed in the PTFE mesh-supported tissues. However, under flow conditions, the hyaluronan-supported tissues showed some recovery of the viability originally lost during static culture conditions, in contrast to PTFE mesh-based models, where initial gains were followed by a decline in metabolic viability after applied shear stress. Proteomic, cell viability and mechanical testing data emphasized the need for extended in vitro evaluations to enable better understanding of multi-stage remodelling and reparative processes in tissues cultured on biodegradable scaffolds. This study also highlighted the possibility that in high-density tissue culture with a biodegradable component, dynamic conditions may be more conducive to optimal tissue development than the static environment because they facilitate the efficient removal of high concentrations of degradation end-products accumulating in the pericellular space. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Maintenance of integrity and function of isolated hepatocytes during extended suspension culture at 25°C

LIVER INTERNATIONAL, Issue 3 2003
Alan J. Wigg
Abstract: Isolated hepatocytes in suspension provide a number of advantages for use in bioartificial liver device, however, poor stability of this cell preparation at physiological temperatures is an apparent barrier preventing their use. We therefore investigated the integrity and differentiated function of isolated rat hepatocytes under conditions of mild hypothermia. Isolated hepatocytes were suspended in a bicarbonate buffered saline medium, supplemented with glucose and bovine serum albumin (BSA), and maintained for 48 h at 25 °C on a rotary shaker under an atmosphere of 95% O2 and 5% CO2. Under these conditions there was no significant decline in cell viability and good preservation of cellular morphology on transmission electron microscopy for at least 24 h. Isolated hepatocytes in suspension at 25 °C were also able to maintain normal Na + and K + ion gradients. The cellular energy status ([ATP], ATP/ADP ratio, cytoplasmic and mitochondrial redox potentials), metabolic function (urea synthesis and ammonia removal), albumin synthesis and phase I and phase II drug detoxification activity of these cells were also maintained for at least 24 h post isolation. These observations demonstrate the robust nature of mildly hypothermic isolated hepatocytes in suspension and encourage further studies re-examining the feasibility of using this cell preparation in bioartificial livers. [source]

Altered metabolic fluxes result from shifts in metabolite levels in sucrose phosphorylase-expressing potato tubers

PLANT CELL & ENVIRONMENT, Issue 10 2002
A. R. Fernie
Abstract As reported in a previous paper (Plant, Cell and Environment 24, 357,365, 2001), introduction of sucrose phosphorylase into the cytosol of potato results in increased respiration, an inhibition of starch accumulation and decreased tuber yield. Herein a more detailed investigation into the effect of sucrose phosphorylase expression on tuber metabolism, in order to understand why storage and growth are impaired is described. (1) Although the activity of the introduced sucrose phosphorylase was low and accounted for less than 10% of that of sucrose synthase its expression led to a decrease in the activities of enzymes of starch synthesis relative to enzymes of glycolysis and relative to total amylolytic activity. (2) Incubation of tuber discs in [14C]glucose revealed that the transformants display a two-fold increase of the unidirectional rate of sucrose breakdown. However this was largely compensated by a large stimulation of sucrose re-synthesis and therefore the net rate of sucrose breakdown was not greatly affected. Despite this fact major shifts in tuber metabolism, including depletion of sucrose to very low levels, higher rates of glycolysis, and larger pools of amino acids were observed in these lines. (3) Expression of sucrose phosphorylase led to a decrease of the cellular ATP/ADP ratio and energy charge in intact growing tubers. It was estimated that at least 30% of the ATP formed during respiration is consumed as a result of the large acceleration of the cycle of sucrose breakdown and re-synthesis in the transformants. Although the absolute rate of starch synthesis in short-term labelling experiments with discs rose, starch synthesis fell relative to other fluxes including respiration, and the overall starch content of the tubers was lower than in wild-type tubers. (4) External supply of amino acids to replace sucrose as an osmoticum led to a feed-back inhibition of glycolysis, but did not restore allocation to starch. (5) However, an external supply of the non-metabolizable sucrose analogue palatinose , but not sucrose itself , stimulated flux to starch in the transformants. (6) The results indicate that the impaired performance of sucrose phosphorylase-expressing tubers is attributable to decreased levels of sucrose and increased energy consumption during sucrose futile cycling, and imply that sucrose degradation via sucrose synthase is important to maintain a relatively large sucrose pool and to minimize the ATP consumption required for normal metabolic function in the wild type. [source]

Sources of variation in fecal cortisol levels in howler monkeys in belize

AMERICAN JOURNAL OF PRIMATOLOGY, Issue 7 2010
Alison M. Behie
Abstract High cortisol levels are known to cause low fecundity and increased mortality; thus, the prospect of using cortisol as a measure of population health is an exciting one. However, because so many factors can interact to influence cortisol release, it can be difficult to interpret what exactly is creating changes to cortisol levels. This study investigates variation in fecal cortisol levels in a population of black howlers (Alouatta pigra) from 350 fecal samples collected from 33 individuals in more than 4 years. A general linear mixed model revealed that cortisol varied significantly with fruit availability and contact with tourists. When fruit availability was low, cortisol increased, likely because when fruit availability is low monkeys eat less fruit, thus obtaining less sugar. This result may simply reflect cortisol's metabolic function of mobilizing glucose. It also indicates that these monkeys may be experiencing periods of food stress throughout the year, which was earlier thought to be minimal for a primarily folivorous species. Presence of tourists was the only other factor found to lead to high cortisol; with exposure to tourists increasing stress levels. These results highlight the importance of understanding how physiological factors can influence cortisol, making it easier to interpret results and determine the external social or ecological stressors that may increase cortisol. Am. J. Primatol. 72:600,606, 2010. © 2010 Wiley-Liss, Inc. [source]

Placental insulin-like growth factor II (IGF-II) and its relation to litter size in the common marmoset monkey (Callithrix jacchus)

AMERICAN JOURNAL OF PRIMATOLOGY, Issue 12 2009
Julienne N. Rutherford
Abstract The primate placenta produces a wide variety of hormones throughout gestation that regulate placental function and fetal growth. One such hormone is insulin-like growth factor-II (IGF-II), a peptide implicated in cell division, differentiation, and amino acid transport. IGF-II concentrations were measured in 23 common marmoset (Callithrix jacchus) term placentas from twin and triplet litters in order to determine whether previously described differences in fetoplacental phenotype such as placental and litter mass and placental surface area were related to differences in endocrine function. IGF-II was extracted from frozen tissue samples and measured using an enzyme-linked immunosorbent assay kit designed for human tissue, which was validated for marmoset placenta. IGF-II concentrations were not related to placental or litter mass, and twin and triplet placentas did not differ in total concentration. However, per individual fetus, triplets were associated with a significant 42% reduction in IGF-II concentration (P=0.03), and IGF-II concentration per gram of fetal mass was a third lower in triplet litters. The triplet placenta exhibits a global expansion of the surface area which was contrasted by a per unit area reduction in IGF-II concentration (r=,0.75, P=0.01), a pattern that explains why twin and triplet placentas overall did not differ in concentration. Per fetus, triplet pregnancies are associated with relatively less maternal mass, placental mass and microscopic surface area suggesting that the intrauterine growth of triplets is supported by systems that increase the efficiency of nutrient transfer. The finding that individual triplet fetuses are also associated with significantly lower IGF-II concentrations is consistent with the view that the marmoset fetoplacental unit exhibits a flexible pattern of placental allocation and metabolism. Plasticity in placental endocrine and metabolic function is likely to play an important role in the ability of the fetus to sense and accommodate the intrauterine environment and, by extension, the external ecology. Am. J. Primatol. 71:969,975, 2009. © 2009 Wiley-Liss, Inc. [source]

Short-term sprint interval training increases insulin sensitivity in healthy adults but does not affect the thermogenic response to ,-adrenergic stimulation

THE JOURNAL OF PHYSIOLOGY, Issue 15 2010
Jennifer C. Richards
Sprint interval training (SIT) and traditional endurance training elicit similar physiological adaptations. From the perspective of metabolic function, superior glucose regulation is a common characteristic of endurance-trained adults. Accordingly, we have investigated the hypothesis that short-term SIT will increase insulin sensitivity in sedentary/recreationally active humans. Thirty one healthy adults were randomly assigned to one of three conditions: (1) SIT (n= 12): six sessions of repeated (4,7) 30 s bouts of very high-intensity cycle ergometer exercise over 14 days; (2) sedentary control (n= 10); (3) single-bout SIT (n= 9): one session of 4 × 30 s cycle ergometer sprints. Insulin sensitivity was determined (hyperinsulinaemic euglycaemic clamp) prior to and 72 h following each intervention. Compared with baseline, and sedentary and single-bout controls, SIT increased insulin sensitivity (glucose infusion rate: 6.3 ± 0.6 vs. 8.0 ± 0.8 mg kg,1 min,1; mean ±s.e.m.; P= 0.04). In a separate study, we investigated the effect of SIT on the thermogenic response to beta-adrenergic receptor (,-AR) stimulation, an important determinant of energy balance. Compared with baseline, and sedentary and single-bout control groups, SIT did not affect resting energy expenditure (EE: ventilated hood technique; 6274 ± 226 vs. 6079 ± 297 kJ day,1; P= 0.51) or the thermogenic response to isoproterenol (6, 12 and 24 ng (kg fat-free mass),1 min,1: %,EE 11 ± 2, 14 ± 3, 23 ± 2 vs. 11 ± 1, 16 ± 2, 25 ± 3; P= 0.79). Combined data from both studies revealed no effect of SIT on fasted circulating concentrations of glucose, insulin, adiponectin, pigment epithelial-derived factor, non-esterified fatty acids or noradrenaline (all P > 0.05). Sixteen minutes of high-intensity exercise over 14 days augments insulin sensitivity but does not affect the thermogenic response to ,-AR stimulation. [source]

Metabolic and immunologic consequences of laparoscopy with helium or carbon dioxide insufflation: A randomized clinical study

ANZ JOURNAL OF SURGERY, Issue 8 2001
Susan J. Neuhaus
Background: Previous studies using animal models have demonstrated that carbon dioxide (CO2) pneumoperitoneum during laparoscopy is associated with adverse physiological, metabolic, immunological and oncological effects, and many of these problems can be avoided by the use of helium insufflation. The present study was performed in patients to compare the effect of helium and CO2 insufflation on intraperitoneal markers of immunological and metabolic function. Methods: Eighteen patients undergoing elective upper gastrointestinal laparoscopic surgery were randomized to have insufflation achieved by using either helium (n = 8) or CO2 (n = 10) gas. Intraperitoneal pH was monitored continuously during surgery, and peritoneal macrophage function was determined by harvesting peritoneal macrophages at 5 min and 30 min after commencing laparoscopy, and then assessing their ability to produce tumour necrosis factor-, (TNF-,), and their phagocytic function. Results: Carbon dioxide laparoscopy was associated with a lower intraperitoneal pH at the commencement of laparoscopy, although this difference disappeared as surgery progressed. The production of TNF-, was better preserved by CO2 laparoscopy, but the insufflation gas used did not affect macrophage phagocytosis. Patients undergoing helium laparoscopy required less postoperative analgesia. Conclusion: The choice of insufflation gas can affect intraperitoneal macrophage function in the clinical setting, and possibly acid,base balance. The present study suggested no immunological advantages for the clinical use of helium as an insufflation gas. The outcomes of the present study, however, are different to those obtained from previous laboratory studies and further research is needed to confirm this outcome. [source]

Prediction of metabolic function from limited data: Lumped hybrid cybernetic modeling (L-HCM)

BIOTECHNOLOGY & BIOENGINEERING, Issue 2 2010
Hyun-Seob Song
Abstract Motivated by the need for a quick quantitative assessment of metabolic function without extensive data, we present an adaptation of the cybernetic framework, denoted as the lumped hybrid cybernetic model (L-HCM), which combines the attributes of the classical lumped cybernetic model (LCM) and the recently developed HCM. The basic tenet of L-HCM and HCM is the same, that is, they both view the uptake flux as being split among diverse pathways in an optimal way as a result of cellular regulation such that some chosen metabolic objective is realized. The L-HCM, however, portrays this flux distribution to occur in a hierarchical way, that is, first among lumped pathways, and next among individual elementary modes (EM) in each lumped pathway. Both splits are described by the cybernetic control laws using operational and structural return-on-investments, respectively. That is, the distribution of uptake flux at the first split is dynamically regulated according to environmental conditions, while the subsequent split is based purely on the stoichiometry of EMs. The resulting model is conveniently represented in terms of lumped pathways which are fully identified with respect to yield coefficients of all products unlike classical LCMs based on instinctive lumping. These characteristics enable the model to account for the complete set of EMs for arbitrarily large metabolic networks despite containing only a small number of parameters which can be identified using minimal data. However, the inherent conflict of questing for quantification of larger networks with smaller number of parameters cannot be resolved without a mechanism for parameter tuning of an empirical nature. In this work, this is accomplished by manipulating the relative importance of EMs by tuning the cybernetic control of mode-averaged enzyme activity with an empirical parameter. In a case study involving aerobic batch growth of Saccharomyces cerevisiae, L-HCM is compared with LCM. The former provides a much more satisfactory prediction than the latter when parameters are identified from a few primary metabolites. On the other hand, the classical model is more accurate than L-HCM when sufficient datasets are involved in parameter identification. In applying the two models to a chemostat scenario, L-HCM shows a reasonable prediction on metabolic shift from respiration to fermentation due to the Crabtree effect, which LCM predicts unsatisfactorily. While L-HCM appears amenable to expeditious estimates of metabolic function with minimal data, the more detailed dynamic models [such as HCM or those of Young et al. (Young et al., Biotechnol Bioeng, 2008; 100: 542,559)] are best suited for accurate treatment of metabolism when the potential of modern omic technology is fully realized. However, in view of the monumental effort surrounding the development of detailed models from extensive omic measurements, the preliminary insight into the behavior of a genotype and metabolic engineering directives that can come from L-HCM is indeed valuable. Biotechnol. Bioeng. 2010;106: 271,284. © 2010 Wiley Periodicals, Inc. [source]

In vitro liver model using microfabricated scaffolds in a modular bioreactor

BIOTECHNOLOGY JOURNAL, Issue 2 2010
Bruna Vinci
Abstract Hepatocyte function on 3-D microfabricated polymer scaffolds realised with the pressure-activated microsyringe was tested under static and dynamic conditions. The dynamic cell culture was obtained using the multicompartment modular bioreactor system. Hepatocyte cell density, glucose consumption, and albumin secretion rate were measured daily over a week. Cells seeded on scaffolds showed an increase in cell density compared with monolayer controls. Moreover, in dynamic culture, cell metabolic function increased three times in comparison with static monolayer cultures. These results suggest that cell density and cell-cell interactions are mediated by the architecture of the substrate, while the endogenous biochemical functions are regulated by a sustainable supply of nutrients and interstitial-like flow. Thus, a combination of 3-D scaffolds and dynamic flow conditions are both important for the development of a hepatic tissue model for applications in drug testing and regenerative medicine. [source]

Obesity and polycystic ovary syndrome

CLINICAL ENDOCRINOLOGY, Issue 2 2006
T. M. Barber
Summary The aetiology of Polycystic Ovary Syndrome (PCOS) is complex and multifactorial. There is much evidence, however, to suggest that adipose tissue plays an important role in the development and maintenance of PCOS pathology. There is a close correlation between adiposity and symptom severity in women with PCOS, and even modest reductions in weight generally translate into significant improvements in menstrual regularity, fertility and hyperandrogenic features. This review article considers the various mechanisms that might underlie this link between excess adiposity and PCOS , including the effects of differential insulin sensitivity, abnormal steroid hormone metabolism and adipocytokine secretion. Greater attention to the therapeutic options available to reduce the impact of excess adiposity on ovarian and metabolic function is essential to the management of PCOS. [source]

Life before birth: effects of cortisol on future cardiovascular and metabolic function,

ACTA PAEDIATRICA, Issue 7 2003
PW Nathanielsz
The concept of fetal programming is an area that is now under rigorous investigation in many laboratories throughout the world. We need to engender a fascination in all segments of society, not just pregnant women, about life in the womb. Conclusion: Everyone needs to understand that improving the condition of the fetus will have personal, social and economic benefits. The time has come to realize that, in a sense, it is not just women who are pregnant but it is the family and the whole of society. [source]

Post-ingestive effects of nectar alkaloids depend on dominance status of bumblebees

ECOLOGICAL ENTOMOLOGY, Issue 4 2009
JESSAMYN S. MANSON
Abstract 1.,Secondary metabolites have acute or chronic post-ingestive effects on animals, ranging from death to growth inhibition to reduced nutrient assimilation. 2.,Although characterised as toxic, the nectar of Gelsemium sempervirens is not lethal to pollinators, even when the concentration of the nectar alkaloid gelsemine is very high. However, little is known about the sublethal costs of nectar alkaloids. 3.,Using a microcolony assay and paired worker bumblebees, the present study measured the effects of artificial nectar containing gelsemine on oocyte development. Oocytes are a sensitive indicator of protein utilisation and general metabolic processes. We also calculated carbohydrate concentrations in the haemolymph to examine energetic costs of gelsemine consumption. 4.,High concentrations of gelsemine significantly reduced mean oocyte width in subordinate bees, while dominant bees showed only a trend towards oocyte inhibition. Gelsemine consumption did not reduce carbohydrate concentrations in haemolymph. 5.,The cost of ingesting gelsemine may be due to direct toxicity of alkaloids or may be an expense associated with detoxifying gelsemine. Detoxification of alkaloids can require reallocation of resources away from essential metabolic functions like reproduction. The risks associated with nectar alkaloid consumption are tied to both the social and nutritional status of the bee. [source]

Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome

JOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 4 2009
Yoshitsugi Hokama
Abstract Examination of anticardiolipin antibodies (ACAs) in the sera of patients clinically diagnosed with chronic fatigue syndrome (CFS) using an enzyme-linked immunoassay procedure demonstrated the presence of immunoglobulin M isotypes in 95% of CFS serum samples tested. The presence of immunoglobulin G and immunoglobulin A isotypes were also detected in a subset of the samples. Future studies will focus on elucidating whether alterations to mitochondrial inner membranes and/or metabolic functions play a possible role in the expression of ACAs. J. Clin. Lab. Anal. 23:210,212, 2009. © 2009 Wiley-Liss, Inc. [source]

The Endocannabinoid System and Energy Metabolism

JOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2008
L. Bellocchio
Many different regulatory actions have been attributed to endocannabinoids, and their involvement in several pathophysiological conditions is under intense scrutiny. Cannabinoid receptors [cannabinoid receptor type 1 (CB1) and CB2] participate in the physiological modulation of many central and peripheral functions. The ability of the endocannabinoid system to control appetite, food intake and energy balance has recently received considerable attention, particularly in the light of the different modes of action underlying these functions. The endocannabinoid system modulates rewarding properties of food by acting at specific mesolimbic areas in the brain. In the hypothalamus, CB1 receptors and endocannabinoids are integrated components of the networks controlling appetite and food intake. Interestingly, the endocannabinoid system was recently shown to control several metabolic functions by acting on peripheral tissues such as adipocytes, hepatocytes, the gastrointestinal tract, the skeletal muscles and the endocrine pancreas. The relevance of the system is further strengthened by the notion that visceral obesity seems to be a condition in which an overactivation of the endocannabinoid system occurs, and therefore drugs interfering with this overactivation by blocking CB1 receptors are considered as potentially valuable candidates for the treatment of obesity and related cardiometabolic risk factors. [source]

Glycosomes: parasites and the divergence of peroxisomal purpose

MOLECULAR MICROBIOLOGY, Issue 3 2004
Marilyn Parsons
Summary Peroxisomes are membrane-bounded organelles that compartmentalize a variety of metabolic functions. Perhaps the most divergent peroxisomes known are the glycosomes of trypanosomes and their relatives. The glycolytic pathway of these organisms resides within the glycosome. The development of robust molecular genetic and proteomic approaches coupled with the completion of the genome sequence of the pathogens Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major provides an opportunity to determine the complement of proteins within the glycosome and the function of compartmentation. Studies now suggest that regulation of glycolysis is a strong driving force for maintenance of the glycosome. [source]

Cord blood lipid profile and associated factors: baseline data of a birth cohort study

PAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 6 2007
Roya Kelishadi
Summary The cord blood lipid profile may be associated with lifelong changes in the metabolic functions of the individual. The aim of the present study was for the first time in Iran to assess the cord blood lipid profile of neonates, as well as some of its environmental influencing factors. The subjects were 442 (218 boys and 224 girls) normal vaginal delivery newborns. Overall, 14.4% of neonates were preterm and the rest were full-term. In total, 9.2% (n = 35) of the full-term newborns were small-for-gestational-age (SGA), of which 16 had a ponderal index (PI) below the 10th percentile (SGA I) and 19 had a PI above the 10th percentile (SGA II), 5.5% (n = 21) were large-for-gestational-age (LGA), and the remainder were appropriate-for-gestational-age (AGA). Before becoming pregnant, 6.9% of mothers were underweight, 49.3% had normal body mass index (BMI), 39.4% were overweight and 4.4% were obese. Total and high-density lipoprotein cholesterol (HDL-C) in girls were significantly higher than in boys (80.3 ± 33.3 and 31.1 ± 9.9 vs. 73.3 ± 23.1 and 28.8 ± 8.7 mg/dL, respectively, P < 0.05). The mean apolipoprotein A (apoA) of neonates with underweight mothers was significantly lower, and the mean apoB level of those with overweight mothers was significantly higher than other neonates. The mean low-density lipoprotein cholesterol (LDL-C), HDL-C and apoA of the LGA newborns were significantly lower, and their apoB was significantly higher compared with AGA and SGA neonates. The SGA I neonates had significantly lower total cholesterol, LDL-C, HDL-C and apoA, as well as higher triglycerides, lipoprotein a and apoB than the SGA II group. The mean cord blood triglycerides of full-term neonates was significantly higher than preterm neonates (69.4 ± 11.9 vs. 61.4 ± 12.7 mg/dL, respectively, P = 0.04). A preconception maternal BMI of ,25 kg/m2 correlated significantly with the cord triglycerides (OR = 1.3, [95% CI 1.07, 1.5]) and with apoB (OR = 1.4, [95% CI 1.1, 1.5]). The BMI <18 of mothers before pregnancy correlated with low HDL-C (OR = 1.3, [95% CI 1.04, 1.7]). Birthweight correlated with high cord triglyceride level (SGA: OR = 1.4, [95% CI 1.1, 1.7]; LGA: OR = 1.6, [95% CI 1.3, 1.7] compared with AGA). These associations remained significant even after adjusting for the preconception BMI of mothers. Our findings reflect the possible interaction of environmental factors and fetal growth and the in utero lipid metabolism. Long-term longitudinal studies in different ethnicities would help to elucidate the relationship. [source]

Reproduction and lifespan: Trade-offs, overall energy budgets, intergenerational costs, and costs neglected by research,

AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 4 2009
Grazyna Jasienska
In human females allocation of resources to support reproduction may cause their insufficient supply to other metabolic functions, resulting in compromised physiology, increased risks of diseases and, consequently, reduced lifespan. While many studies on both historical and contemporary populations show that women with high fertility indeed have shorter lifespans. This relationship is far from universal: a lack of correlation between fertility and lifespan, or even an increased lifespan of women with high fertility have also been documented. Reduced lifespan in women with high fertility may be undetectable due to methodological weaknesses of research or it may be truly absent, and its absence may be explained from biological principles. I will discuss the following reasons for a lack of the negative relationship, described in some demographic studies, between the number of children and lifespan in women: (1) Number of children is only a proxy of the total costs of reproduction and the cost of breastfeeding is often higher than the pregnancy cost but is often not taken into account. (2) Costs of reproduction can be interpreted in a meaningful way only when they are analyzed in relation to the overall energy budget of the woman. (3) Trade-offs between risks of different diseases due to reproduction yield different mortality predictions depending on the socio-economic status of the studied populations. (4) Costs of reproduction are related not only to having children but also to having grandchildren. Such intergenerational costs should be included in analysis of trade-offs between costs of reproduction and longevity. Am. J. Hum. Biol., 2009. © 2009 Wiley-Liss, Inc. [source]

Multivariate analysis of protein profiles of metal hyperaccumulator Thlaspi caerulescens accessions

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 12 2006
Marjo H. Tuomainen
Abstract Thlaspi caerulescens is increasingly acknowledged as one of the best models for studying metal hyperaccumulation in plants. In order to study the mechanisms underlying metal hyperaccumulation, we used proteomic profiling to identify differences in protein intensities among three T.,caerulescens accessions with pronounced differences in tolerance, uptake and root to shoot translocation of Zn and Cd. Proteins were separated using two-dimensional electrophoresis and stained with SYPRO Orange. Intensity values and quality scores were obtained for each spot by using PDQuest software. Principal component analysis was used to test the separation of the protein profiles of the three plant accessions at various metal exposures, and to detect groups of proteins responsible for the differences. Spot sets representing individual proteins were analysed with the analysis of variance and non-parametric Kruskal-Wallis test. Clearest differences were seen among the Thlaspi accessions, while the effects of metal exposures were less pronounced. The 48,tentatively identified spots represent core metabolic functions (e.g. photosynthesis, nitrogen assimilation, carbohydrate metabolism) as well as putative signalling and regulatory functions. The possible roles of some of the proteins in heavy metal accumulation and tolerance are discussed. [source]

Protein expression profiling of glutathione S -transferase pi null mice as a strategy to identify potential markers of resistance to paracetamol-induced toxicity in the liver

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 2 2003
Neil R. Kitteringham
Abstract GST pi (GSTP) is a member of the glutathione S -transferase (EC 2.5.1.18; GST) family of enzymes that catalyse the conjugation of electrophilic species with reduced glutathione and thus play an important role in the detoxification of electrophilic metabolites. Deletion of GSTP in mice has previously been shown to lead to enhanced susceptibility to chemical-induced skin carcinoma, consistent with its known metabolic functions. A decreased susceptibility to paracetamol hepatotoxicity has also been observed, which has not been fully explained. One possibility is that deletion of the GSTP gene locus results in compensatory changes in other proteins involved in defence against chemical stress. We have therefore used complementary protein expression profiling techniques to perform a systematic comparison of the protein expression profiles of livers from GSTP null and wild-type mice. Analysis of liver proteins by two-dimensional electrophoresis confirmed the absence of GSTP in null mice whereas GSTP represented 3,5% of soluble protein in livers from wild-type animals. There was a high degree of quantitative and qualitative similarity in other liver proteins between GSTP null and wild-type mice. There was no evidence that the absence of GSTP in null animals resulted in enhanced expression of other GST isoforms in the null mice (GST alpha, 1.48%, GST mu, 1.68% of resolved proteins) compared with the wild-type animals (GST alpha, 1.50%, GST mu, 1.40%). In contrast, some members of the thiol specific antioxidant family of proteins, notably antioxidant protein 2 and thioredoxin peroxidases, were expressed at a higher level in the GSTP null mouse livers. These changes presumably reflect the recently described role of GSTP in cell signalling and may underlie the protection against paracetamol toxicity seen in these animals. [source]

Hepatocyte Function in a Radial-flow Bioreactor Using a Perfluorocarbon Oxygen Carrier

ARTIFICIAL ORGANS, Issue 11 2005
Martin J. Nieuwoudt
Abstract:, The aims of this study were, first, to indicate the metabolic activity of hepatocytes in a radial-flow polyurethane foam matrix bioreactor relative to monocultures, and second, to evaluate the effect on the hepatocytes of including a synthetic perfluorocarbon (PFC) oxygen carrier to the recirculating medium. The efficient O2 -carrying ability of PFCs may be beneficial to bioreactors employed in stressed cellular environments. Thus, they may also be useful in the treatment of an acute liver failure patient with a bioartificial liver support system (BALSS). Data on the function of three-dimensional (3-D) hepatocyte cultures exposed to emulsified PFCs are lacking. Results: the metabolic functions of the 3-D hepatocyte cultures were improved relative to monocultures. Three-dimensional cultures with and without PFC behaved similarly, and no adverse effects could be detected when PFC was included in the recirculating medium. The addition of PFC significantly improved lidocaine clearance possibly due to the presence of higher O2 tension in the medium. Imaging indicated that large aggregates formed and that seeding had followed flow through the matrix. Simulations indicated first, that the cell numbers used in this study had been insufficient to challenge the bioreactor O2 supply explaining the similarity in performance of the 3-D cultures, and second, that the benefit of adding PFC would be more pronounced at the cell densities likely to be used in a BALSS bioreactor. [source]

Improvement of Metabolic Performance of Cultured Hepatocytes by High Oxygen Tension in the Atmosphere

ARTIFICIAL ORGANS, Issue 1 2001
Kennichi Yanagi
Abstract: Maintaining metabolic functions of cultured hepatocytes at higher levels is an essential requirement for the development of a bioartificial liver. We investigated the effect of oxygen tension (10,40%) of the medium on immobilization efficiency and metabolic functions of cultured hepatocytes obtained from a rat for up to 4 days. Immobilization efficiencies of cultures in 10% oxygen showed a significantly lower value from those for the other conditions. The ammonium metabolic rate and the albumin secretion rate were significantly improved with an increase of dissolved oxygen tension for up to 2 days. These values remained similar in the later stage of the culture. The urea secretion rate showed similar values in all conditions. In conclusion, higher oxygen tension improved immobilization efficiency and metabolic functions of cultured rat hepatocytes in the earlier stage of culture for up to 2 days. [source]

Gene expression profiling differentiates autism case,controls and phenotypic variants of autism spectrum disorders: evidence for circadian rhythm dysfunction in severe autism

AUTISM RESEARCH, Issue 2 2009
Valerie W. Hu
Abstract Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by delayed/abnormal language development, deficits in social interaction, repetitive behaviors and restricted interests. The heterogeneity in clinical presentation of ASD, likely due to different etiologies, complicates genetic/biological analyses of these disorders. DNA microarray analyses were conducted on 116 lymphoblastoid cell lines (LCL) from individuals with idiopathic autism who are divided into three phenotypic subgroups according to severity scores from the commonly used Autism Diagnostic Interview-Revised questionnaire and age-matched, nonautistic controls. Statistical analyses of gene expression data from control LCL against that of LCL from ASD probands identify genes for which expression levels are either quantitatively or qualitatively associated with phenotypic severity. Comparison of the significant differentially expressed genes from each subgroup relative to the control group reveals differentially expressed genes unique to each subgroup as well as genes in common across subgroups. Among the findings unique to the most severely affected ASD group are 15 genes that regulate circadian rhythm, which has been shown to have multiple effects on neurological as well as metabolic functions commonly dysregulated in autism. Among the genes common to all three subgroups of ASD are 20 novel genes mostly in putative noncoding regions, which appear to associate with androgen sensitivity and which may underlie the strong 4:1 bias toward affected males. [source]