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Mmol Kg (mmol + kg)
Selected Abstracts3D MR angiography of intratumoral vasculature using a novel macromolecular MR contrast agentMAGNETIC RESONANCE IN MEDICINE, Issue 3 2001Hisataka Kobayashi Abstract Noninvasive methods to visualize blood flow in the intratumoral vasculature have not previously been studied. In the present study, the use of a novel intravascular MR contrast agent with a generation-6 polyamidoamine dendrimer core (G6-(1B4M-Gd)192; MW: 175kD) was investigated, and the vasculature in experimental tumors was visualized using 3D MR angiography (MRA). Xenografted tumors in nude mice of two different histologies,KT005 (human osteogenic sarcoma) and LS180 (human colon carcinoma),were used to obtain 3D MRA using G6-(1B4M-Gd)192 and Gd-DTPA. The contrast MR sectional images were correlated with the corresponding histological sections. The intratumoral vasculature in the KT005 tumor was clearly visualized by 3D MRA, which became more evident with the growth of the tumor xenograft. In contrast, the intratumoral vasculature in the LS180 tumor was sparser and much less developed than that in KT005 tumors. Blood vessels with a diameter as small as 100 ,m based on histology were visualized using 0.033 mmol Gd/kg of G6-(1B4M-Gd)192. In conclusion, intratumoral vasculature with a 100-,m diameter was visualized better using 3D MRA with G6-(1B4M-Gd)192 than with Gd-DTPA. Magn Reson Med 46:579,585, 2001. © 2001 Wiley-Liss, Inc. [source] Increased fat oxidation and regulation of metabolic genes with ultraendurance exerciseACTA PHYSIOLOGICA, Issue 1 2007J. W. Helge Abstract Aim:, Regular endurance exercise stimulates muscle metabolic capacity, but effects of very prolonged endurance exercise are largely unknown. This study examined muscle substrate availability and utilization during prolonged endurance exercise, and associated metabolic genes. Methods:, Data were obtained from 11 competitors of a 4- to 5-day, almost continuous ultraendurance race (seven males, four females; age: 36 ± 11 years; cycling o2peak: males 57.4 ± 5.9, females 48.1 ± 4.0 mL kg,1 min,1). Before and after the race muscle biopsies were obtained from vastus lateralis, respiratory gases were sampled during cycling at 25 and 50% peak aerobic power output, venous samples were obtained, and fat mass was estimated by bioimpedance under standardized conditions. Results:, After the race fat mass was decreased by 1.6 ± 0.4 kg (11%; P < 0.01). Respiratory exchange ratio at the 25 and 50% workloads decreased (P < 0.01) from 0.83 ± 0.06 and 0.93 ± 0.03 before, to 0.71 ± 0.01 and 0.85 ± 0.02, respectively, after the race. Plasma fatty acids were 3.5 times higher (from 298 ± 74 to 1407 ± 118 ,mol L,1; P < 0.01). Muscle glycogen content fell 50% (from 554 ± 28 to 270 ± 25 nmol kg,1 d.w.; n = 7, P < 0.01), whereas the decline in muscle triacylglycerol (from 32 ± 5 to 22 ± 3 mmol kg,1 d.w.; P = 0.14) was not statistically significant. After the race, muscle mRNA content of lipoprotein lipase and glycogen synthase increased (P < 0.05) 3.9- and 1.7-fold, respectively, while forkhead homolog in rhabdomyosarcoma, pyruvate dehydrogenase kinase 4 and vascular endothelial growth factor mRNA tended (P < 0.10) to be higher, whereas muscle peroxisome proliferator-activated receptor , co-activator-1, mRNA tended to be lower (P = 0.06). Conclusion:, Very prolonged exercise markedly increases plasma fatty acid availability and fat utilization during exercise. Exercise-induced regulation of genes encoding proteins involved in fatty acid recruitment and oxidation may contribute to these changes. [source] Human soleus muscle protein synthesis following resistance exerciseACTA PHYSIOLOGICA, Issue 2 2004T. A. Trappe Abstract Aim:, It is generally believed the calf muscles in humans are relatively unresponsive to resistance training when compared with other muscles of the body. The purpose of this investigation was to determine the muscle protein synthesis response of the soleus muscle following a standard high intensity bout of resistance exercise. Methods:, Eight recreationally active males (27 ± 4 years) completed three unilateral calf muscle exercises: standing calf press/heel raise, bent-knee calf press/heel raise, and seated calf press/heel raise. Each exercise consisted of four sets of 15 repetitions (,15 repetition maximum, RM, or ,70% 1RM). Fractional rate of muscle protein synthesis (FSR) was determined with a primed constant infusion of [2H5]phenylalanine coupled with muscle biopsies immediately and 3 h following the exercise in both the exercise and non-exercise (resting control) leg. Results:, FSR was elevated (P < 0.05) in the exercise (0.069 ± 0.010) vs. the control (0.051 ± 0.012) leg. Muscle glycogen concentration was lower (P < 0.05) in the exercise compared with the control leg (Decrease from control; immediate post-exercise: 54 ± 5; 3 h post-exercise: 36 ±4 mmol kg,1 wet wt.). This relatively high amount of glycogen use is comparable with previous studies of resistance exercise of the thigh (i.e. vastus lateralis; ,41,49 mmol kg,1 wet wt.). However, the exercise-induced increase in FSR that has been consistently reported for the vastus lateralis (,0.045,0.060% h,1) is on average ,200% higher than reported here for the soleus (0.019 ± 0.003% h,1). Conclusions:, These results suggest the relatively poor response of soleus muscle protein synthesis to an acute bout of resistance exercise may be the basis for the relative inability of the calf muscles to respond to resistance training programs. [source] Fate of fatty acids at rest and during exercise: regulatory mechanismsACTA PHYSIOLOGICA, Issue 4 2003M. D. Jensen Abstract Fatty acids are a major fuel source for humans both at rest and during exercise. Plasma free fatty acids (FFA), although present only in micromolar concentrations, are the major circulating lipid fuel. FFA availability can increase two- to four-fold with moderate intensity exercise. Other potential sources of fatty acids include circulating very low-density lipoprotein (VLDL) triglycerides (TGs) (,1/5 the fuel availability of FFA) and intramyocellular TGs (,2 mmol kg,1 muscle). At rest ,40% of systemic FFA uptake occurs in the splanchnic bed and uptake in legs is ,15,20%. During leg exercise the uptake of FFA in leg tissue increases to 30,60% of systemic uptake and splanchnic uptake decreases to 15%. The fate of VLDL TG fatty acids has not been adequately studied. Intramyocellular TG hydrolysis increases during exercise, but the factors that regulate this response are not clear. The fact that contraction of isolated muscles can stimulate the hydrolysis and oxidation of intramyocellular TGs (in the absence of hormonal or neural input) suggests an intracellular regulation of this process. Additional regulation from changes in catecholamines and insulin may also occur. During moderate intensity exercise circulating FFA and intramyocellular TG provide roughly equal portions of fatty acids for oxidation. In addition to endurance training, dietary factors have been shown to modulate the fatty acid oxidation response to exercise. Much remains to be learned about fatty acid trafficking during exercise. What role do VLDL TG play? How is the oxidation of intramyocellular TGs regulated? Techniques to address these questions in humans are only now becoming available. [source] Glutathione deficiency intensifies ischaemia-reperfusion induced cardiac dysfunction and oxidative stressACTA PHYSIOLOGICA, Issue 1 2001S. Leichtweis The efficacy of glutathione (GSH) in protecting ischaemia-reperfusion (I-R) induced cardiac dysfunction and myocardial oxidative stress was studied in open-chest, stunned rat heart model. Female Sprague,Dawley rats were randomly divided into three experimental groups: (1) GSH-depletion, by injection of buthionine sulphoxamine (BSO, 4 mmol kg,1, i.p.) 24 h prior to I-R, (2) BSO injection (4 mmol kg,1, i.p.) in conjunction with acivicin (AT125, 0.05 mmol kg,1, i.v.) infusion 1 h prior to I-R, and (3) control (C), receiving saline treatment. Each group was further divided into I-R, with surgical occlusion of the main left coronary artery (LCA) for 30 min followed by 20 min reperfusion, and sham. Myocardial GSH content and GSH : glutathione disulphide (GSSG) ratio were decreased by ,50% (P < 0.01) in both BSO and BSO + AT125 vs. C. Ischaemia-reperfusion suppressed GSH in both left and right ventricles of C (P < 0.01) and left ventricles of BSO and BSO + AT125 (P < 0.05). Contractility (+dP/dt and ,dP/dt) in C heart decreased 55% (P < 0.01) after I and recovered 90% after I-R, whereas ±dP/dt in BSO decreased 57% (P < 0.01) with ischaemia and recovered 76 and 84% (P < 0.05), respectively, after I-R. For BSO + AT125, ±dP/dt were 64 and 76% (P < 0.01) lower after ischaemia, and recovered only 67 and 61% (P < 0.01) after I-R. Left ventricular systolic pressure in C, BSO and BSO + AT125 reached 95 (P > 0.05) 87 and 82% (P < 0.05) of their respective sham values after I-R. Rate-pressure double product was 11% (P > 0.05) and 25% (P < 0.05) lower in BSO and BSO + AT125, compared with Saline, respectively. BSO and BSO + AT125 rats demonstrated significantly lower liver GSH and heart Mn superoxide dismutase activity than C rats after I-R. These data indicate that GSH depletion by inhibition of its synthesis and transport can exacerbate cardiac dysfunction inflicted by in vivo I-R. Part of the aetiology may involve impaired myocardial antioxidant defenses and whole-body GSH homeostasis. [source] Sex differences in ionoregulatory responses to dietary oil exposure in polar codJOURNAL OF FISH BIOLOGY, Issue 2000J. S. Christiansen Serum osmolalities and chloride concentrations were examined in polar cod. When exposed to oil male and female fish responded differently. Ingestion of food contaminated with oil led to a significant decrease in osmolality (from 503 to 492 mOsm kg,1) in males. There was no significant effect of oil ingestion on serum osmolality in females, but chloride concentrations were increased (from 196 to 203 mmol kg,1). Gender related responses should, therefore, be considered when assessing the possible effects of environmental pollutants on fish physiology. [source] A new gadolinium-based contrast agent for magnetic resonance imaging of brain tumors: Kinetic study on a C6 rat glioma modelJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 2 2001Emmanuel Fonchy Abstract T1 -weighted magnetic resonance imaging (MRI) was used to evaluate the potential interest of a new Gd-based contrast agent, termed P760, to characterize brain tumor heterogeneity and vascularization and to delineate regions containing permeable vessels. The C6 rat glioma model was used as a model of high-grade glioblastoma. The signal enhancement was measured as a function of time in the vascular compartment and in different regions of interest (ROIs) within the tumor after the injection of 0.02 mmol kg,1 of P760. The results were compared to those obtained after the injection of 0.1 mmol kg,1 of Gd-DOTA. We showed that P760, in spite of a Gd concentration five times smaller, produces an enhancement in the blood pool similar to that produced by Gd-DOTA. It was shown that P760 makes possible an excellent delineation of regions containing vessels with a damaged blood-brain barrier (BBB). Images acquired 5,10 minutes after P760 injection showed the location of permeable vessels more accurately than Gd-DOTA-enhanced images. The enhancement produced in the tumor by P760 was, however, less than that produced by Gd-DOTA. The extravasation and/or diffusion rate of P760 in the interstitial medium were found to be strongly reduced, compared to those found with Gd-DOTA. This study suggests that the new contrast agent has promising capabilities in clinical imaging of brain tumors. J. Magn. Reson. Imaging 2001;14:97,105. © 2001 Wiley-Liss, Inc. [source] Evaluation of the anti-vascular effects of combretastatin in rodent tumours by dynamic contrast enhanced MRINMR IN BIOMEDICINE, Issue 2 2002Ross J. Maxwell The anti-vascular effects of the tubulin binding agent, disodium combretastatin A-4 3- O -phosphate (CA-4-P), have been investigated in the rat P22 carcinosarcoma by measurements of radiolabelled iodoantipyrine uptake and dynamic contrast-enhanced MRI. The iodoantipyrine estimates of absolute tumour blood flow showed a reduction from 0.35 to 0.04,ml g,1 min,1 6,h after 10,mg kg,1 CA-4-P and to <0.01,ml g,1 min,1 after 100,mg kg,1. Tumour blood flow recovered to control values 24,h after 10,mg kg,1 CA-4-P, but there was no recovery by 24,h after the higher dose. Dynamic contrast-enhanced MR images were obtained at 4.7 T, following injection of 0.1,mmol kg,1 Gd-DTPA and analysed assuming a model arterial input function. A parameter, Ktrans, which is related to blood flow rate and permeability of the tumour vasculature to Gd-DTPA, was calculated from the uptake data. Ktrans showed a reduction from 0.34 to 0.11 min,1 6,h after 10,mg kg,1 CA-4-P and to 0.07 min,1 after 100,mg kg,1. Although the magnitude of changes in Ktrans was smaller than that in tumour blood flow, the time course and dose-dependency patterns were very similar. The apparent extravascular extracellular volume fraction, ,e, showed a four-fold reduction 6,h after 100,mg kg,1 CA-4-P, possibly associated with vascular shutdown within large regions of the tumour. These results suggest that Ktrans values for Gd-DTPA uptake into tumours could be a useful non-invasive indicator of blood flow changes induced by anti-vascular agents such as combretastatin. Copyright © 2002 John Wiley & Sons, Ltd. [source] Extracellular complexation of Cd in the Hartig net and cytosolic Zn sequestration in the fungal mantle of Picea abies , Hebeloma crustuliniforme ectomycorrhizasPLANT CELL & ENVIRONMENT, Issue 11 2000B. Frey ABSTRACT Compartmentation of heavy metals on or within mycorrhizal fungi may serve as a protective function for the roots of forest trees growing in soils containing elevated concentrations of metals such as Cd and Zn. In this paper we present the first quantitative measurements by X-ray microanalysis of heavy metals in high-pressure frozen and cryosectioned ectomycorrhizal fungal hyphae. We used this technique to analyse the main sites of Cd and Zn in fungal cells of mantle and Hartig net hyphae and in cortical root cells of symbiotic Picea abies , Hebeloma crustuliniforme associations to gain new insights into the mechanisms of detoxification of these two metals in Norway spruce seedlings. The mycorrhizal seedlings were exposed in growth pouches to either 1 mM Cd or 2 mM Zn for 5 weeks. The microanalytical data revealed that two distinct Cd- and Zn-binding mechanisms are involved in cellular compartmentation of Cd and Zn in the mycobiont. Whereas extracellular complexation of Cd occurred predominantly in the Hartig net hyphae, both extracellular complexation and cytosolic sequestration of Zn occurred in the fungal tissue. The vacuoles were presumed not to be a significant pool for Cd and Zn storage. Cadmium was almost exclusively localized in the cell walls of the Hartig net (up to 161 mmol kg,1 DW) compared with significantly lower concentrations in the cell walls of mantle hyphae (22 mmol kg,1 DW) and in the cell walls of cortical cells (15 mmol kg,1 DW). This suggests that the apoplast of the Hartig net is a primary accumulation site for Cd. Zinc accumulated mainly in the cell walls of the mantle hyphae (111 mmol kg,1 DW), the Hartig net hyphae (130 mmol kg,1 DW) and the cortical cells (152 mmol kg,1 DW). In addition, Zn occurred in high concentrations in the cytoplasm of the fungal mantle hyphae (up to 164 mmol kg,1 DW) suggesting that both the cell walls and the cytoplasm of fungal tissue are the main accumulation sites for Zn in P. abies resulting in decreased Zn transfer from the fungus to the root. [source] Distribution of Zn in functionally different leaf epidermal cells of the hyperaccumulator Thlaspi caerulescensPLANT CELL & ENVIRONMENT, Issue 7 2000B. Frey ABSTRACT The aim of this study was to show the potential of Thlaspi caerulescens in the cleaning-up of a moderately Zn -contaminated soil and to elucidate tolerance mechanisms at the cellular and subcellular level for the detoxification of the accumulated metal within the leaf. Measured Zn concentrations in shoots were high and reached a maximum value of 83 mmol kg,1 dry mass, whereas total concentrations of Zn in the roots were lower (up to 13 mmol kg,1). In order to visualize and quantify Zn at the subcellular level in roots and leaves, ultrathin cryosections were analysed using energy-dispersive X-ray micro-analysis. Elemental maps of ultrathin cryosections showed that T. caerulescens mainly accumulated Zn in the vacuoles of epidermal leaf cells and Zn was almost absent from the vacuoles of the cells from the stomatal complex, thereby protecting the guard and subsidiary cells from high Zn concentrations. Observed patterns of Zn distribution between the functionally different epidermal cells were the same in both the upper and lower epidermis, and were independent of the total Zn content of the plant. Zinc stored in vacuoles was evenly distributed and no Zn-containing crystals or deposits were observed. From the elemental maps there was no indication that P, S or Cl was associated with the high Zn concentrations in the vacuoles. In addition, Zn also accumulated in high concentrations in both the cell walls of epidermal cells and in the mesophyll cells, indicating that apoplastic compartmentation is another important mechanism involved in zinc tolerance in the leaves of T. caerulescens. [source] | |||||||||||||