Metabolic Demand (metabolic + demand)

Distribution by Scientific Domains
Distribution within Life Sciences

Selected Abstracts


Paul M O'Connor
SUMMARY 1The kidneys are second only to the heart in terms of O2 consumption; however, relative to other organs, the kidneys receive a very high blood flow and oxygen extraction in the healthy kidney is low. Despite low arterial,venous O2 extraction, the kidneys are particularly susceptible to hypoxic injury and much interest surrounds the role of renal hypoxia in the development and progression of both acute and chronic renal disease. 2Numerous regulatory mechanisms have been identified that act to maintain renal parenchymal oxygenation within homeostatic limits in the in vivo kidney. However, the processes by which many of these mechanisms act to modulate renal oxygenation and the factors that influence these processes remain poorly understood. 3A number of such mechanisms specific to the kidney are reviewed herein, including the relationship between renal blood flow and O2 consumption, pre- and post-glomerular arterial,venous O2 shunting, tubulovascular cross-talk, the differential control of regional kidney blood flow and the tubuloglomerular feedback mechanism. 4The roles of these mechanisms in the control of renal oxygenation, as well as how dysfunction of these mechanisms may lead to renal hypoxia, are discussed. [source]

Stroke volume decreases during mild dynamic and static exercise in supine humans

M. Elstad
Abstract Aim:, The contributions of cardiac output (CO) and total peripheral resistance to changes in arterial blood pressure are debated and differ between dynamic and static exercise. We studied the role stroke volume (SV) has in mild supine exercise. Methods:, We investigated 10 healthy, supine volunteers by continuous measurement of heart rate (HR), mean arterial blood pressure, SV (ultrasound Doppler) and femoral beat volume (ultrasound Doppler) during both dynamic mild leg exercise and static forearm exercise. This made it possible to study CO, femoral flow (FF) and both total and femoral peripheral resistance beat-by-beat. Results:, During a countdown period immediately prior to exercise, HR and mean arterial pressure increased, while SV decreased. During mild supine exercise, SV decreased by 5,8%, and most of this was explained by increased mean arterial pressure. Dynamic leg exercise doubled femoral beat volume, while static hand grip decreased femoral beat volume by 18%. FF is tightly regulated according to metabolic demand during both dynamic leg exercise and static forearm exercise. Conclusion:, Our three major findings are, firstly, that SV decreases during both dynamic and static mild supine exercise due to an increase in mean arterial pressure. Secondly, femoral beat volume decreases during static hand grip, but FF is unchanged due to the increase in HR. Finally, anticipatory responses to exercise are apparent prior to both dynamic and static exercise. SV changes contribute to CO changes and should be included in studies of central haemodynamics during exercise. [source]

Assessing the potential for fish predation to impact zebra mussels (Dreissena polymorpha): insight from bioenergetics models

M. A. Eggleton
Abstract,,, Rates of annual food consumption and biomass were modeled for several fish species across representative rivers and lakes in eastern North America. Results were combined to assess the relative potential of fish predation to impact zebra mussels (Dreissena polymorpha). Predicted annual food consumption by fishes in southern waters was over 100% greater than that in northern systems because of warmer annual water temperatures and presumed increases in metabolic demand. Although generally increasing with latitude, biomasses of several key zebra mussel fish predators did not change significantly across latitudes. Biomasses of some less abundant fish predators did increase significantly with latitude, but increases were not of the magnitude to offset predicted decreases in food consumption. Our results generally support the premise that fishes in rivers and lakes of the southern United States (U.S.) have inherently greater potential to impact zebra mussels by predation. Our simulations may provide a partial explanation of why zebra mussel invasions have not been as rapid and widespread in southern U.S. waters compared to the Great Lakes region. Resumen 1Modelamos la tasa de consumo anual de alimento y biomasa para varias especies de peces en una muestra representativa de ríos y lagos del este de Norte América. Combinamos los resultados para evaluar el potencial relativo que estas especies de peces pueden ejercer sobre la abundancia del mejillón asiático Dreissena polymorpha. Las predicciones sobre consumo para peces en lagos y ríos del sur fueron más del 100% comparadas con sistemas septentrionales. Esto se puede deber a las temperaturas anuales más altas y aumentos en la demanda metabólica de peces en ríos y lagos del sur de Norte América. 2La biomasa de varias especies claves de peces que consumen D. polymorpha no cambió apreciablemente con latitud. La biomasa de algunos peces que consumen D. polymorpha aumentó significativamente con latitud, pero este aumento no era de una magnitud suficiente para compensar la disminución en el consumo de alimento. 3Nuestros resultados apoyan generalmente la premisa de que los peces en ríos y lagos del sur de los Estados Unidos (EE.UU.) tienen un potencial inherente mayor para poder controlar D. polymorpha. Nuestras simulaciones proporcionan una explicación parcial de por qué las invasiones de D. polymorpha no han sido tan rápidas y ampliamente distribuidas en aguas sureñas comparado con la región de los Grandes Lagos. [source]

Effects of acute vagal nerve stimulation on the early passive electrical changes induced by myocardial ischaemia in dogs: heart rate-mediated attenuation

Carlos L. Del Rio
Parasympathetic activity during acute coronary artery occlusion (CAO) can protect against ischaemia-induced malignant arrhythmias; nonetheless, the mechanism mediating this protection remains unclear. During CAO, myocardial electrotonic uncoupling is associated with autonomically mediated immediate (i.e. type 1A) arrhythmias and can modulate pro-arrhythmic dispersion of repolarization. Therefore, the effects of acutely enhanced or decreased cardiac parasympathetic activity on early electrotonic coupling during CAO, as measured by myocardial electrical impedance (MEI), were investigated. Anaesthetized dogs were instrumented for MEI measurements, and left circumflex coronary arterial occlusions were performed in intact (CTRL) and vagotomized (VAG) animals. The CAO was followed by either vagotomy (CTRL) or vagal nerve stimulation (VNS, 10 Hz, 10 V) in the VAG dogs. Vagal nerve stimulation was studied in two additional sets of animals. In one set heart rate (HR) was maintained by pacing (220 beats min,1), while in the other set bilateral stellectomy preceded CAO. The MEI increased after CAO in all animals. A larger MEI increase was observed in vagotomized animals (+85 ± 9 ,, from 611 ± 24 ,, n= 16) when compared with intact control dogs (+43 ± 5 ,, from 620 ± 20 ,, n= 7). Acute vagotomy during ischaemia abruptly increased HR (from 155 ± 11 to 193 ± 15 beats min,1) and MEI (+12 ± 1.1 ,, from 663 ± 18 ,). In contrast, VNS during ischaemia (n= 11) abruptly reduced HR (from 206 ± 6 to 73 ± 9 beats min,1) and MEI (,16 ± 2 ,, from 700 ± 44 ,). These effects of VNS were eliminated by pacing but not by bilateral stellectomy. Vagal nerve stimulation during CAO also attenuated ECG-derived indices of ischaemia (e.g. ST segment, 0.22 ± 0.03 versus 0.15 ± 0.03 mV) and of rate-corrected repolarization dispersion [terminal portion of T wave (TPEc), 84.5 ± 4.2 versus 65.8 ± 5.9 ms; QTc, 340 ± 8 versus 254 ± 16 ms]. Vagal nerve stimulation during myocardial ischaemia exerts negative chronotropic effects, limiting early ischaemic electrotonic uncoupling and dispersion of repolarization, possibly via a decreased myocardial metabolic demand. [source]

Differences in Local Environment Determine the Site of Physiological Angiogenesis in Rat Skeletal Muscle

I. Badr
The specificity in location of angiogenesis to either glycolytic or oxidative fibre types, or muscle regions, was examined in the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles of rat. Angiogenesis was induced by mechanical means either with (chronic muscle stimulation) or without (muscle stretch by overload) changes in blood flow, treatments which invoked only minor changes in fibre type and fibre size. Proliferation estimated by PCNA labelling of cells co-localised with capillaries was very rare in control muscles, where it occurred mainly in the glycolytic regions, but was increased in both models of angiogenesis. However, when labelled capillaries were scored according to the type of surrounding fibres, only muscle stimulation significantly accentuated proliferation of capillaries surrounded by glycolytic fibres. We conclude that while mechanical stimuli are important for proliferation in glycolytic regions in both models, capillary growth occurs specifically around glycolytic fibres in that region when the angiogenic stimulus includes increased blood flow and/or increased metabolic demand. [source]

The influence of reproductive state on cardiac parameters and hypoxia tolerance in the Grass Shrimp, Palaemonetes pugio

Summary 1In many crustaceans, female reproduction represents a time of increased metabolic demand. Palaemonetes pugio are typically hypoxia tolerant; but the energetic demands of reproduction may compromise their ability to tolerate hypoxic conditions. Given the correlation between cardiac output and metabolic demand, we used cardiac output (CO) to measure differences in metabolic demand in the life-history stages of P. pugeo. 2We hypothesized that (1) the cost of egg production would result in an increased CO for gravid females compared with non-gravid females; (2) those females that were both ovigerous and gravid would have an additional metabolic demand due to brooding behaviour (pleopod fanning) and hence an even greater CO; and (3) hypoxia tolerance would decrease with increasing reproductive demand. To test these hypotheses, we compared cardiac output across three reproductive states and at decreasing water oxygen tensions. 3Ovigerous females had significantly greater pleopod fanning frequency than non-ovigerous females at all oxygen tensions. Additionally, ovigerous/gravid females had significantly higher cardiac output at all oxygen tensions than gravid only or non-gravid females. 4Changes in cardiac output indicate that females became more sensitive to environmental oxygen tension with increasing reproductive demand. Non-gravid females were able to maintain cardiac output down to 15 mm Hg O2, whereas gravid and ovigerous/gravid females maintained cardiac output down to 50 mm Hg and 75 mm Hg O2, respectively. 5These differences in CO suggest that metabolic demands of females change with reproductive state and, while gravid and ovigerous/gravid females appear more sensitive to low oxygen tensions, they are able to physiologically tolerate low environmental oxygen conditions. [source]

Disturbed hepatic carbohydrate management during high metabolic demand in medium-chain acyl,CoA dehydrogenase (MCAD),deficient mice,

HEPATOLOGY, Issue 6 2008
Hilde Herrema
Medium-chain acyl,coenzyme A (CoA) dehydrogenase (MCAD) catalyzes crucial steps in mitochondrial fatty acid oxidation, a process that is of key relevance for maintenance of energy homeostasis, especially during high metabolic demand. To gain insight into the metabolic consequences of MCAD deficiency under these conditions, we compared hepatic carbohydrate metabolism in vivo in wild-type and MCAD,/, mice during fasting and during a lipopolysaccharide (LPS)-induced acute phase response (APR). MCAD,/, mice did not become more hypoglycemic on fasting or during the APR than wild-type mice did. Nevertheless, microarray analyses revealed increased hepatic peroxisome proliferator-activated receptor gamma coactivator-1, (Pgc-1,) and decreased peroxisome proliferator-activated receptor alpha (Ppar ,) and pyruvate dehydrogenase kinase 4 (Pdk4) expression in MCAD,/, mice in both conditions, suggesting altered control of hepatic glucose metabolism. Quantitative flux measurements revealed that the de novo synthesis of glucose-6-phosphate (G6P) was not affected on fasting in MCAD,/, mice. During the APR, however, this flux was significantly decreased (,20%) in MCAD,/, mice compared with wild-type mice. Remarkably, newly formed G6P was preferentially directed toward glycogen in MCAD,/, mice under both conditions. Together with diminished de novo synthesis of G6P, this led to a decreased hepatic glucose output during the APR in MCAD,/, mice; de novo synthesis of G6P and hepatic glucose output were maintained in wild-type mice under both conditions. APR-associated hypoglycemia, which was observed in wild-type mice as well as MCAD,/, mice, was mainly due to enhanced peripheral glucose uptake. Conclusion: Our data demonstrate that MCAD deficiency in mice leads to specific changes in hepatic carbohydrate management on exposure to metabolic stress. This deficiency, however, does not lead to reduced de novo synthesis of G6P during fasting alone, which may be due to the existence of compensatory mechanisms or limited rate control of MCAD in murine mitochondrial fatty acid oxidation. (HEPATOLOGY 2008.) [source]

Modulation of angiogenesis is effective in a model of rheumatoid arthritis

A. O. Afuwape
A feature of rheumatoid arthritis (RA) is prominent hyperplasia of the synovium, which results in an increased distance between the invasive pannus and the existing synovial vasculature. Concomitantly the hyperplastic tissue imposes an augmented metabolic demand on the pre-existing vasculature. As a consequence the synovium in RA becomes hypoxic, resulting in an increased rate of formation of new blood vessels, to supply nutrients and oxygen. Targeting the vasculature in RA is a potential therapeutic approach in RA. VEGF, a key vascular permeability and angiogenic factor, is expressed in RA. In this study we utilised adenovirus expressing the secreted form of the extracellular domain of the Flt-1 VEGF receptor (sFlt-1) to inhibit VEGF in the collagen-induced arthritis (CIA) model, to determine whether blocking the effects of vegf might be an effective treatment for RA. AdvsFlt-1, administered intravenously on the first day of arthritis, significantly suppressed CIA. For example, on d 6 of arthritis the mean increase in paw thickness, which reflects oedema, for untreated and null adenovirus-treated animals was 0.23 ± 0.05 mm and 0.38 ± 0.08, respectively, compared to 0.07 ± 0.05 for AdvsFlt-1-treated mice (P < 0.001 vs. Adv0-treated and untreated mice by 2-way anova). Western blot analyses revealed the presence of a 100-kDa band, corresponding to human sFlt-1, in liver extracts from arthritic mice infected with AdvsFlt-1 at 24 h but not 72 h after infection. This band was absent in liver extracts from Adv0-infected mice and all synovial extracts. Measurement of protein levels by ELISA demonstrated the presence of sFlt-1 in liver, synovium and serum, although levels declined by 72 h post infection. These data suggest efficient but transient expression of sFlt-1. Sera from adenovirus infected mice were found to contain antiviral antibodies and additionally, sera from AdvsFlt-1-infected but not Adv0-infected mice recognised human recombinant sFlt-1. These observations demonstrate that adenoviral mediated delivery of human sFlt-1 leads to transient gene expression and suppression of CIA. This effect is reduced later in the course of disease due to the expression of antiadenovirus as well as antisFlt-1 antibodies. Future studies will assess the effect of combination treatment, using AdvsFlt-1 together with anti-TNF(antibody, to prolong the beneficial effects of VEGF blockade. These results suggest that blocking the pro-angiogenic and permeability action of VEGF may be beneficial for treatment of RA. [source]

Elevated endogenous GABA level correlates with decreased fMRI signals in the rat brain during acute inhibition of GABA transaminase

Zhengguang Chen
Abstract Vigabatrin and gabaculine, both highly specific inhibitors of GABA (,-aminobutyric acid) transaminase, cause significant elevation of endogenous GABA levels in brain. The time course of GABA concentration after acute GABA transaminase inhibition was measured quantitatively in the ,-chloralose-anesthetized rat brain using in vivo selective homonuclear polarization transfer spectroscopy. The blood oxygenation level-dependent (BOLD) effect in functional magnetic resonance imaging (fMRI) has been considered to be coupled tightly to neuronal activation via the metabolic demand of associated glutamate transport. Correlated with the rise in endogenous GABA level after vigabatrin or gabaculine treatment, the intensity of BOLD-weighted fMRI signals in rat somatosensory cortex during forepaw stimulation was found to be reduced significantly. These results are consistent with previous findings that inhibition of GABA transaminase leads to augmented GABA release and potentiation of GABAergic inhibition. © 2004 Wiley-Liss, Inc. [source]

Alternatives to the double vena cava method in partial liver transplantation

Yoji Kishi
Minimizing graft congestion in partial liver transplantation is important, especially when the graft weight is marginal for the recipient metabolic demand. We prefer the double vena cava technique for reconstructing middle hepatic vein tributaries with thick, short hepatic veins because the technique can reduce the warm ischemic time of the graft and make a wide anastomosis. This technique requires a cryopreserved superior or inferior vena cava. We devised an alternative double vena cava method using iliac or femoral vein grafts and applied it to two right liver transplantation patients. There was no postoperative hepatic venous outflow block in either patient. In conclusion, application of this technique, even in the absence of a suitable vena cava, can help to minimize graft congestion. (Liver Transpl 2005;11:101,103.) [source]

Obesity, Insulin Resistance, and Microvessel Density

Jefferson C. Frisbee
ABSTRACT The growing incidence and prevalence of the overweight/obese condition across developed economies worldwide has an enormous impact on increasing the risk for the development of impaired glycemic control or insulin resistance and ultimately peripheral vascular disease (PVD) in afflicted individuals. This places an enormous economic and social burden on these societies, in terms of additional health care costs and lost productivity and through a reduction in the quality of life of the individual owing, in part, to the progressive PVD. Characterized by an inability of the vascular systems to adequately perfuse tissues and organs relative to their metabolic demand, PVD is in part a function of a structural remodeling of the microvascular networks such that the density of microvessel and capillaries within tissues is reduced below that under normal conditions, with the potential for profound negative impacts on the processes of mass transport and exchange. The review discusses the severity of the obesity "epidemic" from the perspective of PVD and the effects of the development of the obese, insulin-resistant condition on tissue/organ microvessel density. Additional material is reviewed that addresses ameliorative treatments, primarily exercise training, on blunting microvessel loss in the obese, insulin-resistant individual, and on potential mechanistic contributors that warrant considerable future investigation. [source]

Foraging capacities and effects of competitive release on ontogenetic diet shift in bream, Abramis brama

OIKOS, Issue 2 2002
Anders Persson
Bream (Abramis brama) undergo ontogenetic diet shift from zooplankton to benthic macroinvertebrates, but the switching size may be highly variable. To unravel under what conditions bream are pelagic versus benthic foragers, we experimentally determined size-dependent foraging capacities on three prey types from the planktivory and benthivory niche; zooplankton, visible and buried macroinvertebrates. From these data we derived predictions of size-dependent diet preferences from estimates of prey value and competitive ability, and tested these predictions on diet data from the field. Planktivorous foraging capacity described a hump-shaped relationship with bream length that peaked for small bream of 67 mm total length. Benthivory capacity increased with increasing bream size, irrespective if benthic prey were visible on the sediment surface or buried in the sediment. From the experimental data and relationships of metabolic demand we calculated minimum resource requirement for maintenance (MRR) for each of the prey categories used in experiments. MRR increased with bream size for both zooplankton and visible chironomids, but decreased with bream size for buried chironomids, suggesting that intermediate sized bream (120,300 mm) may be competitively sandwiched between small and large bream that are more competitive planktivores and benthivores, respectively. Prey value estimates and competitive abilities qualitatively predicted diet shift in a bream population being released from competition. Competitive release did not change the diet of the largest size-class feeding on an optimal diet of benthic invertebrates both before and after competitive release. However, profound diet shifts towards benthic macroinvertebrates were recorded for intermediate size-classes that fed on a suboptimal diet prior to competitive release. Thus, laboratory estimates of size-dependent foraging capacity of bream in planktivorous and benthivorous feeding niches provided useful information on size-specific competitive ability, and successfully predicted diet preference in the field. [source]

Long-Term Insulin-Independence After Allogeneic Islet Transplantation for Type 1 Diabetes: Over the 10-Year Mark

T. Berney
Results of islet of Langerhans transplantation have markedly improved in recent years, but most patients still lose insulin independence in the long-term. We report herein the longest (over 11 years) case of insulin independence after allogeneic islet transplantation. The subject had a 27-year history of type 1 diabetes and received a single islet-after-kidney graft of 8800 islet equivalents (IEQ)/kg, pooled from 2 donors. Insulin was discontinued by 3 months posttransplant and the patient has remained off insulin ever since. Yearly follow-up studies have revealed normal metabolic control, including normal oral glucose tolerance test (OGTT). Reasons for success may involve choice of immunosuppression, low metabolic demand and low immune responsiveness as suggested by an excellent HLA matching and a high count of circulating regulatory T cells. This observation is so far an exceptional case, but clearly demonstrates the validity of the concept that long-term insulin independence after allogeneic islet transplantation is an achievable target. [source]

Degradation of xenobiotics in a partitioning bioreactor in which the partitioning phase is a polymer

Brian G. Amsden
Abstract Two-phase partitioning bioreactors (TPPBs) are characterized by a cell-containing aqueous phase and a second immiscible phase that contains toxic and/or hydrophobic substrates that partition to the cells at subinhibitory levels in response to the metabolic demand of the organisms. To date, the delivery phase in TPPBs has been a hydrophobic solvent that traditionally needed to possess a variety of important properties including biocompatibility, nonbioavailability, low volatility, and low cost, among others. In the present work we have shown that the organic solvent phase can be replaced by inexpensive polymer beads that function in a similar fashion as organic solvents, delivering a toxic substrate to cells based on equilibrium considerations. Specifically, 3.4 mm diameter beads of poly(ethylene-co-vinyl acetate) (EVA) were used to reduce the aqueous concentration of phenol in a bioreactor from toxic levels ( ,2,000 mg/L) to subinhibitory levels (,750 mg/L), after which Pseudomonas putida ATCC 11172 was added to the system and allowed to consume the total phenol loading. Thus, the beads absorbed the toxic substrate and released it to the cells on demand. The EVA beads, which could be reused, were able to absorb 14 mg phenol/g EVA. This work has opened the possibility of using widely mixed cultures in TPPB systems without concern for degradation of the delivery material and without concern of contamination. © 2003 Wiley Periodicals. Biotechnol Bioeng84: 399,305, 2003. [source]

Mid-term survival after abdominal aortic aneurysm surgery predicted by cardiopulmonary exercise testing

J. Carlisle
Background: Cardiopulmonary exercise (CPX) testing measures how efficiently subjects meet increased metabolic demand. This study aimed to determine whether preoperative CPX testing predicted postoperative survival following elective abdominal aortic aneurysm (AAA) repair. Methods: Some 130 patients had CPX testing before elective open AAA repair. Additional preoperative, operative and postoperative variables were recorded prospectively. Median follow-up was 35 months. The correlation of variables with survival was assessed by single and multiple regression analyses. Results: CPX testing identified 30 of 130 patients who had been unfit before surgery. Two years after surgery the Kaplan,Meier survival estimate was 55 per cent for the 30 unfit patients, compared with 97 per cent for the 100 fit patients. The absolute difference in survival between these two groups at 2 years was 42 (95 per cent confidence interval 18 to 65) per cent (P < 0·001). Conclusion: Preoperative CPX testing, combined with simple co-morbidity scoring, identified patients unlikely to survive in the mid-term, even after successful AAA repair. Copyright © 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source]

3254: Neurovascular coupling in the retrobulbar ciliary circulation

Purpose Perfusion of the retina is adapted to the metabolic demand by neurovascular coupling. Neurovascular coupling has shown to be present in the retinal vasculature, but not in vessels supplying the optic nerve. The present study investigated the presence of neurovascular coupling in the anterior part of the optic nerve in healthy and glaucoma subjects. Methods Retrobulbar blood flow velocities were determined by color Doppler imaging (CDI). A Siemens Elegra ultrasound system with a 7.5L40 transducer was used. Peak-systolic and end-diastolic velocities (PSV and EDV) in the central retinal artery (CRA) or the short posterior ciliary artery (SPCA) were the primary readout. CDI measurements were performed shortly before, during, immediately after, 60 s after, and 120 s after a 10-Hz flicker stimulation of the retina. Results Thirty-five glaucoma patients and 44 healthy control subjects were included in the study. In the SPCA of healthy controls, flicker stimulation led to a rise of PSV from 9.7±0.8 to 12.5±0.8 cm/s (P<0.001; N=24) and of EDV from 2.4±0.3 to 3.6±0.3 cm/s (P<0.001; N=24). This effect was not detectable in glaucoma patients. In the CRA, flicker light led to an increase of EDV from 2.1±0.2 to 3.0±0.3 cm/s (P=0.002; N=20) in healthy volunteers and from 1.3±0.2 to 2.0±0.2 cm/s in glaucoma patients (P=0.004; N=15). PSV was affected by flicker stimulation in neither the healthy volunteers nor glaucoma patients. Conclusion The data indicate the presence of neurovascular coupling in the vascular bed supplied by the paraoptic SPCA. The response pattern to the flicker stimulus differs between healthy and glaucoma subjects. [source]

VMAT2 quantitation by PET as a biomarker for ,-cell mass in health and disease

M. Freeby
The common pathology underlying both type 1 and type 2 diabetes (T1DM and T2DM) is insufficient ,-cell mass (BCM) to meet metabolic demands. An important impediment to the more rapid evaluation of interventions for both T1DM and T2DM lack of biomarkers of pancreatic BCM. A reliable means of monitoring the mass and/or function of ,-cells would enable evaluation of the progression of diabetes as well as the monitoring of pharmacologic and other interventions. Recently, we identified a biomarker of BCM that is quantifiable by positron emission tomography (PET). PET is an imaging technique which allows for non-invasive measurements of radioligand uptake and clearance, is sensitive in the pico- to nanomolar range and of which the results can be deconvoluted into measurements of receptor concentration. For BCM estimates, we have identified VMAT2 (vesicular monoamine transporter type 2) as a biomarker and [11C] DTBZ (dihydrotetrabenazine) as the transporter's ligand. VMAT2 is highly expressed in ,-cells of the human pancreas relative to other cells of the endocrine and exocrine pancreas. Thus measurements of [11C] DTBZ in the pancreas provide an indirect measurement of BCM. Here we summarize our ongoing efforts to validate the clinical utility of this non-invasive approach to real-time BCM measurements [source]

Population ecology and prey consumption by fathead minnows in prairie wetlands: importance of detritus and larval fish

B. R. Herwig
Abstract,,, The fathead minnow Pimephales promelas occurs in high densities in wetlands of the prairie pothole region (PPR) of North America, but food resources sustaining these populations are poorly known. We assessed population dynamics and prey consumption of fathead minnow populations in three PPR wetlands for 2 years. Fish density peaked at 107 fish per m2 for all age classes combined. Larval and juvenile fish dominated these populations in terms of abundance and accounted for 83% of total prey consumption. Detritus dominated fish diets, representing 53%, 40% and 79% of diet mass for larval, juvenile and adult fish respectively. Detritus consumption was positively related to minnow density and negatively related to invertebrate abundance, but only for adult fish. Seasonal production:biomass ratios were unrelated to proportions of detritus in the diet for all ages of fish, indicating that detritus is an important food resource capable of meeting metabolic demands and sustaining fish growth in high-density populations. Detritus consumption may also weaken links between abundance of invertebrate prey and minnows, promoting dense fish populations with strong, consistent influences on wetland ecosystems. [source]


EVOLUTION, Issue 6 2006
Stephen A. Arnott
Abstract There is strong evidence that genetic capacity for growth evolves toward an optimum rather than an absolute maximum. This implies that fast growth has a cost and that trade-offs occur between growth and other life-history traits, but the fundamental mechanisms are poorly understood. Previous work on the Atlantic silverside fish Menidia menidia has demonstrated a trade-off between growth and swimming performance. We hypothesize that the trade-off derives from the competing metabolic demands associated with growth and swimming activity. We tested this by measuring standard metabolic rate (MSTD), maximum sustainable metabolic rate (MACT) and metabolic scope of laboratory-reared silversides originating from two geographically distinct populations with well-documented differences in genetic capacity for growth. The fast-growth genotype had a significantly greater MSTD than the slow-growth genotype, but a similar MACT when swum to near exhaustion. The scope for activity of the fast-growth genotype was lower than that of the slow-growth genotype. Furthermore, the fast-growth genotype eats larger meals, thereby incurring a greater postprandial oxygen demand. We conclude that a metabolic trade-off occurs between growth and other metabolic demands and that this trade-off provides a general mechanism underlying the evolution of growth rate. [source]

The influence of reproductive state on cardiac parameters and hypoxia tolerance in the Grass Shrimp, Palaemonetes pugio

Summary 1In many crustaceans, female reproduction represents a time of increased metabolic demand. Palaemonetes pugio are typically hypoxia tolerant; but the energetic demands of reproduction may compromise their ability to tolerate hypoxic conditions. Given the correlation between cardiac output and metabolic demand, we used cardiac output (CO) to measure differences in metabolic demand in the life-history stages of P. pugeo. 2We hypothesized that (1) the cost of egg production would result in an increased CO for gravid females compared with non-gravid females; (2) those females that were both ovigerous and gravid would have an additional metabolic demand due to brooding behaviour (pleopod fanning) and hence an even greater CO; and (3) hypoxia tolerance would decrease with increasing reproductive demand. To test these hypotheses, we compared cardiac output across three reproductive states and at decreasing water oxygen tensions. 3Ovigerous females had significantly greater pleopod fanning frequency than non-ovigerous females at all oxygen tensions. Additionally, ovigerous/gravid females had significantly higher cardiac output at all oxygen tensions than gravid only or non-gravid females. 4Changes in cardiac output indicate that females became more sensitive to environmental oxygen tension with increasing reproductive demand. Non-gravid females were able to maintain cardiac output down to 15 mm Hg O2, whereas gravid and ovigerous/gravid females maintained cardiac output down to 50 mm Hg and 75 mm Hg O2, respectively. 5These differences in CO suggest that metabolic demands of females change with reproductive state and, while gravid and ovigerous/gravid females appear more sensitive to low oxygen tensions, they are able to physiologically tolerate low environmental oxygen conditions. [source]

Liver failure following partial hepatectomy

HPB, Issue 3 2006
Thomas S. Helling
Abstract While major liver resections have become increasingly safe due to better understanding of anatomy and refinement of operative techniques, liver failure following partial hepatectomy still occurs from time to time and remains incompletely understood. Observationally, certain high-risk circumstances exist, namely, massive resection with small liver remnants, preexisting liver disease, and advancing age, where liver failure is more likely to happen. Upon review of available clinical and experimental studies, an interplay of factors such as impaired regeneration, oxidative stress, preferential triggering of apoptotic pathways, decreased oxygen availability, heightened energy-dependent metabolic demands, and energy-consuming inflammatory stimuli work to produce failing hepatocellular functions. [source]

Metabolic phenotyping of mouse mutants in the German Mouse Clinic

Abstract The German Mouse Clinic was established as a phenotyping center to provide the scientific community with systematic standardized phenotyping of mouse models from various genetic backgrounds. We found metabolic phenotypes in nine out of 20 mutant lines screened in a primary screen. Based on these findings, the mutants were analyzed in secondary and tertiary screens. Mice of a sample mutant line, isolated from the ENU-screen at the National Research Center for Environment and Health in Munich, were found to have lower body weight, consume less food, but have higher ratios of metabolized energy per unit body weight compared with their wild-type littermates. Basal metabolic rate and heat production were simultaneously increased by 16,18%, whereas body fat content was reduced by 11,16%. The combination of various parameters of energy consumption, expenditure and energy storage illustrate the metabolic demands of the sample mutant mouse line and demonstrate the utility of the powerful phenotyping tool used at the German Mouse Clinic. [source]

Selective induction of mucin-3 by hypoxia in intestinal epithelia

Nancy A. Louis
Abstract Epithelial cells line mucosal surfaces (e.g., lung, intestine) and critically function as a semipermeable barrier to the outside world. Mucosal organs are highly vascular with extensive metabolic demands, and for this reason, are particularly susceptible to diminished blood flow and resultant tissue hypoxia. Here, we pursue the hypothesis that intestinal barrier function is regulated in a protective manner by hypoxia responsive genes. We demonstrate by PCR confirmation of microarray data and by avidin blotting of immunoprecipitated human Mucin 3 (MUC3), that surface MUC3 expression is induced in T84 intestinal epithelial cells following exposure to hypoxia. MUC3 RNA is minimally detectable while surface protein expression is absent under baseline normoxic conditions. There is a robust induction in both the mRNA (first evident by 8 h) and protein expression, first observed and maximally expressed following 24 h hypoxia. This is followed by a subsequent decline in protein expression, which remains well above baseline at 48 h of hypoxia. Further, we demonstrate that this induction of MUC3 protein is associated with a transient increase in the barrier restorative peptide, intestinal trefoil factor (ITF). ITF not only colocalizes with MUC3, by confocal microscopy, to the apical surface of T84 cells following exposure to hypoxia, but is also found, by co-immunoprecipitation, to be physically associated with MUC3, following 24 h of hypoxia. In exploration of the mechanism of hypoxic regulation of mucin 3 expression, we demonstrated by luciferase assay that the full-length promoter for mouse Mucin 3 (Muc3) is hypoxia-responsive with a 5.08,±,1.76-fold induction following 24 h of hypoxia. Furthermore, analysis of both the human (MUC3A) and mouse (Muc3) promoters revealed potential HIF-1 binding sites which were shown by chromatin immunoprecipitation to bind the pivotal hypoxia-regulating transcription factor HIF-1,. Taken together, these studies implicate the HIF-1, mediated hypoxic induced expression of mucin 3 and associated ITF in the maintenance of intestinal barrier function under hypoxic conditions. J. Cell. Biochem. 99: 1616,1627, 2006. © 2006 Wiley-Liss, Inc. [source]

Early versus late enteral nutritional support in adults with burn injury: a systematic review

J. Wasiak
Abstract Background Burn injury increases the body's metabolic demands, and therefore nutritional requirements. Provision of an adequate supply of nutrients is believed to lower the incidence of metabolic abnormalities, thus reducing septic morbidity, and improving survival rates. Enteral nutrition support is the best feeding method in a patient who is unable to achieve an adequate oral intake, but optimal timing of its introduction after burn injury (i.e. early versus late) needs to be established. The purpose of this review is to examine evidence for the effectiveness and safety of early versus late enteral nutrition support in adults with burn injury. Methods An examination of randomized and controlled clinical trials using various medical databases such as The Cochrane Library (Issue 3, 2006), MEDLINE (from 1950), CINHAL (from 1982) and EMBASE (from 1980). Results The trial evidence about the benefit of early enteral nutritional support on standardized clinical outcomes such as length of hospital stay and mortality remained inconclusive. Similarly, the question of whether early enteral feeding influenced or decreased metabolic rate, reduced septic and other complications remained uncertain. Conclusions Promising results suggest early enteral nutrition support may blunt the hypermetabolic response to thermal injury, but it is insufficient to provide clear guidelines for practice. Further research incorporating larger sample sizes and rigorous methodology that utilizes valid and reliable outcome measures is essential. [source]

Small-for-size liver syndrome after auxiliary and split liver transplantation: Donor selection

Nigel Heaton
Small-for-size liver grafts can be defined by a recognizable clinical syndrome that results from the transplantation of too small a functional mass of liver for a designated recipient. A graft to recipient body weight ratio less than 0.8, impaired venous inflow, and enhanced metabolic demands in patients with poor clinical conditions must be considered as main factors leading to the small-for-size syndrome (SFSS) when using living and cadaveric partial grafts such as split and auxiliary liver grafts. Increased risk of graft dysfunction is currently observed in fatty infiltration of more than 30%, abnormal liver test results (especially bilirubin and gamma glutaryl transferase), and other donor risk factors such as high inotrope administration and donor stay in the intensive care unit (>5 days). Older donors are especially vulnerable to prolonged cold ischemia and high inotrope levels, giving rise to early graft dysfunction and prolonged cholestasis. Increased metabolic need on a functionally small-for-size graft predisposes to surgical and septic complications and poorer survival. Splitting livers into right and left lobe grafts increases the potential risk of small-for-size grafts for both recipients. Several techniques of venous outflow reconstruction/implantation have been proposed to reduce the risk of obstruction postoperatively. Prevention and management of SFSS will improve in parallel with the increased experience, allowing us optimum usage of available organs and reducing overall morbidity and mortality. (Liver Transpl 2003;9:S26-S28.) [source]

Living on the edge: feeding of subtropical open ocean copepods

MARINE ECOLOGY, Issue 2 2006
Gustav-Adolf Paffenhöfer
Abstract The objective of this study was to provide quantitative information on environmental feeding rates of warm water oceanic epipelagic copepods. We determined clearance rates at 23 °C for various particle size ranges in shipboard studies in the western oligotrophic subtropical Atlantic Ocean for females of the calanoid species Clausocalanus furcatus and Mecynocera clausii. These in situ clearance rates were then applied to the various particle size ranges of environmental particle spectra of auto- and heterotrophs at different depths from three stations in the western Atlantic. After calculating the metabolic demands of each of these two copepod species and applying an assimilation efficiency of 90%, we determined that C. furcatus meets its metabolic demands in all six cases, and M. clausii in two of six cases. Clausocalanus furcatus would also meet its energy demands at 25 °C, where it is often found, while M. clausii at 20 °C, where it is regularly found, would cover its metabolic needs in four of six cases. It is hypothesized that these species, and most likely most of the other co-occurring copepod species, are limited in their abundance by food availability, or, better said, are ,living on the edge' in relation to food abundance. [source]

Hibernation as a far-reaching program for the modulation of RNA transcription

Manuela Malatesta
Abstract In eukaryotic cells, pre-mRNAs undergo several transformation steps to generate mature mRNAs ready to be exported to the cytoplasm. The molecular and structural apparatus for mRNA production is generally able to promptly respond to variations of metabolic demands. Hibernating mammals, which periodically enter a hypometabolic state, represent an interesting physiological model to investigate the adaptive morpho-functional modifications of the pre-mRNA transcriptional and processing machinery under extreme metabolic conditions. In this study, the subnuclear distribution of some transcriptional, splicing, and cleavage factors was investigated by ultrastructural immunocytochemistry in cell nuclei of the liver (a highly metabolizing organ involved in multiple regulatory functions) and the brown adipose tissue (responsible for nonshivering thermogenesis) from euthermic, hibernating, and arousing hazel dormice (Muscardinus avellanarius). Our observations demonstrate that, during hibernation, transcriptional activity significantly decreases and pre-mRNA processing factors undergo an intranuclear redistribution moving to domains usually devoid of such molecules; moreover, in hepatocytes, there is a preferential accumulation of pre-mRNAs at the splicing stage, whereas, in brown adipocytes, pre-mRNAs are mainly stored at the cleavage stage. Upon arousal, the pre-mRNAs at the cleavage stage are immediately utilized, while the maturation of pre-mRNAs at the splicing stage seems to be restored before transcription had taken place. Our data suggest a programmed intranuclear reorganization of the RNA maturation machinery aimed at efficiently and rapidly restoring the pre-mRNA processing, and, consequently, the specific cellular activities upon arousal. Once again natural hibernation appears as a highly programmed hypometabolic state rather than a simple fall of metabolic and physiological functions. Microsc. Res. Tech., 2008. © 2008 Wiley-Liss, Inc. [source]

Synchrony between growth and reproductive patterns in human females: Early investment in growth among Pumé foragers

Karen L. Kramer
Abstract Life history is an important framework for understanding many aspects of ontogeny and reproduction relative to fitness outcomes. Because growth is a key influence on the timing of reproductive maturity and age at first birth is a critical demographic variable predicting lifetime fertility, it raises questions about the synchrony of growth and reproductive strategies. Among the Pumé, a group of South American foragers, young women give birth to their first child on average at age 15.5. Previous research showed that this early age at first birth maximizes surviving fertility under conditions of high infant mortality. In this study we evaluate Pumé growth data to test the expectation that if early reproduction is advantageous, then girls should have a developmental trajectory that best prepares them for young childbearing. Analyses show that comparatively Pumé girls invest in skeletal growth early, enter puberty having achieved a greater proportion of adult body size and grow at low velocities during adolescence. For early reproducers growing up in a food-limited environment, a precocious investment in growth is advantageous because juveniles have no chance of pregnancy and it occurs before the onset of the competing metabolic demands of final reproductive maturation and childbearing. Documenting growth patterns under preindustrial energetic and demographic conditions expands the range of developmental variation not otherwise captured by normative growth standards and contributes to research on human phenotypic plasticity in diverse environments. Am J Phys Anthropol, 2010. © 2009 Wiley-Liss, Inc. [source]

Factors affecting fecal glucocorticoid levels in semi-free-ranging female mandrills (Mandrillus sphinx)

Joanna M Setchell
Abstract Subordinate female cercopithecine primates often experience decreased reproductive success in comparison with high-ranking females, with a later age at sexual maturity and first reproduction and/or longer interbirth intervals. One explanation that has traditionally been advanced to explain this is high levels of chronic social stress in subordinates, resulting from agonistic and aggressive interactions and leading to higher basal levels of glucocorticoids. We assessed the relationships among fecal cortisol levels and reproductive condition, dominance rank, degree of social support, and fertility in female mandrills (Mandrillus sphinx) living in a semi-free-ranging colony in Franceville, Gabon. Lower-ranking females in this colony have a reproductive disadvantage relative to higher-ranking females, and we were interested in determining whether this relationship between dominance rank and reproductive success is mediated through stress hormones. We analyzed 340 fecal samples from 19 females, collected over a 14-month period. We found that pregnant females experienced higher fecal cortisol levels than cycling or lactating females. This is similar to results for other primate species and is likely owing to increased metabolic demands and interactions between the hypothalamus,pituitary,adrenal axis, estrogen, and placental production of corticotrophin releasing hormones during pregnancy. There was no influence of dominance rank on fecal cortisol levels, suggesting that subordinate females do not suffer chronic stress. This may be because female mandrills have a stable social hierarchy, with low levels of aggression and high social support. However, we found no relationship between matriline size, as a measure of social support, and fecal cortisol levels. Subordinates may be able to avoid aggression from dominants in the large enclosure or may react only transiently to specific aggressive events, rather than continuously expecting them. Finally, we found no relationship between fecal cortisol levels and fertility. There was no difference in fecal cortisol levels between conceptive and nonconceptive cycles, and no significant relationship between fecal cortisol level and either the length of postpartum amenorrhea or the number of cycles before conception. This suggests that the influence of dominance rank on female reproductive success in this population is not mediated through chronic stress in subordinate females, and that alternative explanations of the relationship between social rank and reproduction should be sought. Am. J. Primatol. 70:1023,1032, 2008. © 2008 Wiley-Liss, Inc. [source]

The role of oestrogens in the adaptation of islets to insulin resistance

Angel Nadal
Pregnancy is characterized by peripheral insulin resistance, which is developed in parallel with a plasma increase of maternal hormones; these include prolactin, placental lactogens, progesterone and oestradiol among others. Maternal insulin resistance is counteracted by the adaptation of the islets of Langerhans to the higher insulin demand. If this adjustment is not produced, gestational diabetes may be developed. The adaptation process of islets is characterized by an increase of insulin biosynthesis, an enhanced glucose-stimulated insulin secretion (GSIS) and an increase of ,,cell mass. It is not completely understood why, in some individuals, ,,cell mass and function fail to adapt to the metabolic demands of pregnancy, yet a disruption of the ,,cell response to maternal hormones may play a key part. The role of the maternal hormone 17,-oestradiol (E2) in this adaptation process has been largely unknown. However, in recent years, it has been demonstrated that E2 acts directly on ,,cells to increase insulin biosynthesis and to enhance GSIS through different molecular mechanisms. E2 does not increase ,,cell proliferation but it is involved in ,,cell survival. Classical oestrogen receptors ER, and ER,, as well as the G protein-coupled oestrogen receptor (GPER) seem to be involved in these adaptation changes. In addition, as the main production of E2 in post-menopausal women comes from the adipose tissue, E2 may act as a messenger between adipocytes and islets in obesity. [source]