In vivo detection of brain Krebs cycle intermediate by hyperpolarized magnetic resonance.

The Krebs (or tricarboxylic acid (TCA)) cycle has a central role in the regulation of brain energy regulation and metabolism, yet brain TCA cycle intermediates have never been directly detected in vivo. This study reports the first direct in vivo observation of a TCA cycle intermediate in intact brain, namely, 2-oxoglutarate, a key biomolecule connecting metabolism to neuronal activity. Our observation reveals important information about in vivo biochemical processes hitherto considered undetectable. In particular, it provides direct evidence that transport across the inner mitochondria membrane is rate limiting in the brain. The hyperpolarized magnetic resonance protocol designed for this study opens the way to direct and real-time studies of TCA cycle kinetics.

Energy consumption of European and African shrews

Is the extremely high oxygen consumption of shrews due to an unusually high basal metabolism? In an attempt to answer this long-standing question, we have measured the oxygen consumption of 13 species of shrews of different origin: from Europe - Sorex araneus, S. Minutus, Neomys fodiens, Crocidura russula, and Suncus etruscus; from Africa - Crocidura bottegi, C. bicolor, C. jouvenetae; C. poensis, C. theresae, C. Wimmeri, C. flavescens, and C. giffardi, The measurements, taken over a period of 20-30 minutes, were made in small, closed-system chambers at 25°C. The metabolic rat our shrews of the subfamily Soricinae lies between the eman and minimum values of the Soricini (M=126.2 W0.52 cal/h and M=82.6 W0.53 cal/h, respectively), as recorded in the literature. Zhe average for the African Crocidurinae is much lower (M= 43.6 W0.67). The metabolic rate of the European Croccidura russula agrees with that of the African species. Thus, the Crocidurinae are characterized by a relatively low metabolic rate; the Soricinae, and in particular the tribe of the Soricini, by an extremely high metabolic rate. The tribes Neomyini and Blarinini occupy an intermediate position. These differences are also to be found at the level of the basal metabolism. This main difference between the two sub-families can most likely be explained by evolution in geographical isolation under differential climatic conditions: the Crocidurinae having evolved in tropical Africa and the Soricinae in temperate Eurasia

Transepidermal water loss and resting energy expenditure in preterm infants.

Skin water loss of preterm infants, nursed naked in incubators under thermoneutral conditions, was assessed by a method based on the measurement of water vapor pressure gradient close to the skin surface. The corresponding skin evaporative heat loss was calculated using an energy equivalent of 0.58 kcal/g water vaporised. During the first 5 weeks of life, 128 sets of measurements were made on 56 infants whose gestational age ranged from 28 to 37 weeks. In the first week of life, infants of less than 30 weeks of gestation had substantially higher transepidermal water loss (TEWL) and skin evaporative heat loss (skin EHL) (41.5 +/- 11.5 g/kg X day TEWL; 24.1 +/- 6.5 kcal/kg X day skin EHL) than infants of 34 weeks and greater (11.1 +/- 4.1 g/kg X day; 6.4 +/- 2.4 kcal/kg X day). Infants of 30-33 weeks of gestation had intermediate values (22.4 +/- 7.6 g/kg X day; 13 +/- 4.4 kcal/kg X day). From the third week of life on, TEWL was similar for all preterm infants, i.e. 14.2 +/- 2.6 to 12.7 +/- 1.9 g/kg X day and corresponds to skin EHL of 8.2 +/- 1.5 to 7.4 +/- 1.1 kcal/kg X day. There was a significant inverse relationship between gestational age and TEWL and also between postnatal age and TEWL. In an additional group of 7 preterm infants (30-34 weeks of gestation, mean postnatal age of 21 +/- 9 days) transepidermal water loss and energy expenditure were measured simultaneously. The skin evaporative heat loss (8.8 +/- 2.5 kcal/kg X day) accounted for 17 +/- 5% of energy expenditure (53.3 +/- 4.1 kcal/kg X day). This study emphasizes that in infants of less than 30 weeks of gestation, the transepidermal water loss is of great importance and makes a major contribution to water and heat balances.

The kinetic parameters and energy cost of the Hsp70 chaperone as a polypeptide unfoldase.

Hsp70-Hsp40-NEF and possibly Hsp100 are the only known molecular chaperones that can use the energy of ATP to convert stably pre-aggregated polypeptides into natively refolded proteins. However, the kinetic parameters and ATP costs have remained elusive because refolding reactions have only been successful with a molar excess of chaperones over their polypeptide substrates. Here we describe a stable, misfolded luciferase species that can be efficiently renatured by substoichiometric amounts of bacterial Hsp70-Hsp40-NEF. The reactivation rates increased with substrate concentration and followed saturation kinetics, thus allowing the determination of apparent V(max)' and K(m)' values for a chaperone-mediated renaturation reaction for the first time. Under the in vitro conditions used, one Hsp70 molecule consumed five ATPs to effectively unfold a single misfolded protein into an intermediate that, upon chaperone dissociation, spontaneously refolded to the native state, a process with an ATP cost a thousand times lower than expected for protein degradation and resynthesis.

New measurements of energy expenditure and physical activity in chronic kidney disease.

The accurate estimation of total daily energy expenditure (TEE) in chronic kidney patients is essential to allow the provision of nutritional requirements; however, it remains a challenge to collect actual physical activity and resting energy expenditure in maintenance dialysis patients. The direct measurement of TEE by direct calorimetry or doubly labeled water cannot be used easily so that, in clinical practice, TEE is usually estimated from resting energy expenditure and physical activity. Prediction equations may also be used to estimate resting energy expenditure; however, their use has been poorly documented in dialysis patients. Recently, a new system called SenseWear Armband (BodyMedia, Pittsburgh, PA) was developed to assess TEE, but so far no data have been published in chronic kidney disease patients. The aim of this review is to describe new measurements of energy expenditure and physical activity in chronic kidney disease patients.

Creation of an Age-Adjusted, Dual-Energy X-ray Absorptiometry-Derived Trabecular Bone Score Curve for the Lumbar Spine in Non-Hispanic US White Women.

The trabecular bone score (TBS, Med-Imaps, Pessac, France) is an index of bone microarchitecture texture extracted from anteroposterior dual-energy X-ray absorptiometry images of the spine. Previous studies have documented the ability of TBS of the spine to differentiate between women with and without fractures among age- and areal bone mineral density (aBMD)-matched controls, as well as to predict future fractures. In this cross-sectional analysis of data collected from 3 geographically dispersed facilities in the United States, we investigated age-related changes in the microarchitecture of lumbar vertebrae as assessed by TBS in a cohort of non-Hispanic US white American women. All subjects were 30 yr of age and older and had an L1-L4aBMDZ-score within ±2 SD of the population mean. Individuals were excluded if they had fractures, were on any osteoporosis treatment, or had any illness that would be expected to impact bone metabolism. All data were extracted from Prodigy dual-energy X-ray absorptiometry devices (GE-Lunar, Madison, WI). Cross-calibrations between the 3 participating centers were performed for TBS and aBMD. aBMD and TBS were evaluated for spine L1-L4 but also for all other possible vertebral combinations. To validate the cohort, a comparison between the aBMD normative data of our cohort and US non-Hispanic white Lunar data provided by the manufacturer was performed. A database of 619 non-Hispanic US white women, ages 30-90 yr, was created. aBMD normative data obtained from this cohort were not statistically different from the non-Hispanic US white Lunar normative data provided by the manufacturer (p = 0.30). This outcome thereby indirectly validates our cohort. TBS values at L1-L4 were weakly inversely correlated with body mass index (r = -0.17) and weight (r = -0.16) and not correlated with height. TBS values for all lumbar vertebral combinations decreased significantly with age. There was a linear decrease of 16.0% (-2.47 T-score) in TBS at L1-L4 between 45 and 90 yr of age (vs. -2.34 for aBMD). Microarchitectural loss rate increased after age 65 by 50% (-0.004 to -0.006). Similar results were obtained for other combinations of lumbar vertebra. TBS, an index of bone microarchitectural texture, decreases with advancing age in non-Hispanic US white women. Little change in TBS is observed between ages 30 and 45. Thereafter, a progressive decrease is observed with advancing age. The changes we observed in these American women are similar to that previously reported for a French population of white women (r(2) > 0.99). This reference database will facilitate the use of TBS to assess bone microarchitectural deterioration in clinical practice.

Enteral versus parenteral nutrition: comparison of energy metabolism in healthy subjects.

Continuous respiratory exchange measurements were performed on 10 healthy young women for 1 h before, 3 h during, and 3 h after either parenteral (iv) or intragastric (ig) administration of a nutrient mixture (52% glucose, 18% amino acid, and 30% lipid energy) infused at twice the postabsorptive resting energy expenditure (REE). REE rose from 0.98 +/- 0.02 (iv) and 0.99 +/- 0.02 kcal/min (ig) postabsorptively to 1.13 +/- 0.03 (iv) and 1.13 +/- 0.02 kcal/min (ig), resulting in nutrient-induced thermogenesis of 10 +/- 0.6 and 9.3 +/- 0.9%, respectively, when related to the metabolizable energy. The respiratory quotient rose from preinfusion values of 0.81 +/- 0.02 (iv) and 0.80 +/- 0.01 (ig) to 0.86 +/- 0.01 (iv) and 0.85 +/- 0.01 (ig). After nutrient administration the respiratory quotient fell significantly to below the preinfusion values. Plasma glucose and insulin concentrations rose during nutrient administration but were higher during the intravenous route. It is concluded that, although the response time to intragastric administration was delayed, the thermic effects and overall substrate oxidations were comparable during intravenous or intragastric administration, albeit, at lower plasma glucose and insulin concentrations via the intragastric route.

Macronutrients and energy balance in obesity.

Energy balance is the difference between metabolizable energy intake and total energy expenditure. Energy intake is difficult to measure accurately; changes in body weight, for example, are not a good measure of the adequacy of energy intake, because fluctuations in body weight are common even if the overall trend is toward weight loss. It is now customary to assess energy requirements indirectly from total energy expenditure. Total energy expenditure consists of basal metabolism, postprandial thermogenesis, and physical activity. Energy expenditure is related to both body weight and body composition. A reduction in total energy expenditure accompanies weight loss, because basal metabolic rate decreases with the loss of lean tissue mass. Similarly, with weight gain, there is an increase in basal metabolic rate, because lean tissue mass grows to support the increase in fat tissue mass. Excess energy intake over energy expenditure causes weight gain and an accompanying increase in total energy expenditure. Following a period of adaptation, total energy expenditure will match energy intake and body weight will stabilize at a higher level. This same relationship holds for weight loss. Respiratory quotient (measured in steady state) is an indication of the proportion of energy expenditure derived from fat and carbohydrate oxidation. Over long periods of time, fat balance is equivalent to energy balance, as an excess of fat intake over fat oxidation causes fat storage.

Social isolation causers mortality by disrupting energy homeostrasis in ants

Social deprivation can have negative effects on the lives of social animals, including humans, yet little is known about the mechanisms by which social withdrawal affects animal health. Here we show that in the carpenter ant Camponotus fellah, socially isolated workers have a greatly reduced life span relative to ants kept in groups of ten individuals. By using a new tracking system, we found that social isolation resulted in important behavioral changes and greatly increased locomotor activity. The higher activity of single ants and their increased propensity to leave the nest to move along the walls suggested that the increased mortality of isolated ants might stem from an imbalance of energy income and expenditure. This view was supported by the finding that while isolated ants ingested the same amount of food as grouped ants, they retained food in the crop, hence preventing its use as an energy source. Moreover, the difference in life span between single and grouped individuals vanished when ants were not fed. This study thus underlines the role of social interactions as key regulators of energy balance, which ultimately affects aging and health in a highly social organism.

Reduced quality of life associated adverse events in intermediate hepatocellular carcinoma patients treated with PRECISION TACE with drug eluting beads: Results from the PRECISION V randomized trial : B-241

Purpose: To evaluate the extent of quality of life (QoL) associated adverse events (AEs) following PRECISION TACE with DC Bead compared with conventional transarterial chemoembolisation (cTACE). Methods and Materials: 201 intermediate HCC patients were treated with DC Bead (PRECISION TACE) or conventional TACE (cTACE) with doxorubicin in the PRECISION V clinical study. 93 patients were treated with DC Bead and 108 Patients with cTACE every 2 months and followed up for 6 months. AEs were classified according to the South West Oncology Group criteria. QoL associated AEs were defined as alopecia, constipation, nausea, vomiting, pyrexia, chills, asthenia, fatigue, and headache. Results: The biggest difference in QoL associated AEs was for alopecia: 2 patients (2.2%) for DC-Bead versus 21 patients (19.4%) for cTACE. For other clinical symptoms, constipation (n=10; 10.8% vs. n=13; 12%), vomiting (n=10; 10.8% vs. n=14; 13.0%), pyrexia (n=16; 17.2% vs. n=26; 24.1%), chills (n=1; 1.1% vs. n=5; 4.6%), and headache (n=2; 2.2% vs. n=8; 7.4%) showed lower incidence in the DC Bead group versus cTACE. Nausea, n= 15; 13.9% (n=15; 16.1%) and fatigue, n=6; 5.6% (n=13; 14.0%) were lower for cTACE. Total dose of doxorubicin was on average 35% higher in the DC Bead group. Conclusion: Although patients in the DC Bead group received a higher doxorubicin dose, less QoL associated AEs were reported for this group. Alopecia, the most obvious outward sign of toxicity, was only reported in a tenth of DC Bead patients. Thus, PRECISION TACE with DC Bead improves quality of life associated adverse events.