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Extracellular Volume (extracellular + volume)
Selected AbstractsMRI tumor characterization using Gd-GlyMe-DOTA-perfluorooctyl-mannose-conjugate (Gadofluorine MÔ), a protein-avid contrast agentCONTRAST MEDIA & MOLECULAR IMAGING, Issue 3 2006Hans-Jürgen Raatschen Abstract The rationale and objectives were to define the MRI tumor-characterizing potential of a new protein-avid contrast agent, Gd-GlyMe-DOTA-perfluorooctyl-mannose-conjugate (Gadofluorine MÔ; Schering AG, Berlin, Germany) in a chemically induced tumor model of varying malignancy. Because of the tendency for this agent to form large micelles in water and to bind strongly to hydrophobic sites on proteins, it was hypothesized that patterns of dynamic tumor enhancement could be used to differentiate benign from malignant lesions, to grade the severity of malignancies and to define areas of tumor necrosis. Gadofluorine M, 0.05,mmol,Gd,kg,1, was administered intravenously to 28 anesthetized rats that had developed over 10 months mammary tumors of varying degrees of malignancy as a consequence of intraperitoneal administration of N -ethyl- N -nitrosourea (ENU), 45,250,mg,kg,1. These tumors ranged histologically from benign fibroadenomas to highly undifferentiated adenocarcinomas. Dynamic enhancement data were analyzed kinetically using a two-compartment tumor model to generate estimates of fractional plasma volume (fPV), apparent fractional extracellular volume (fEV*) and an endothelial transfer coefficient (KPS) for this contrast agent. Tumors were examined microscopically for tumor type, degree of malignancy (Scarff,Bloom,Richardson score) and location of necrosis. Eighteen tumor-bearing rats were successfully imaged. MRI data showed an immediate strong and gradually increasing tumor enhancement. KPS and fEV*, but not fPV obtained from tumors correlated significantly (p,<,0.05) with the SBR tumor grade, r,=,0.65 and 0.56, respectively. Estimates for KPS and fEV* but not fPV were significantly lower in a group consisting of benign and low-grade malignant tumors compared with the group of less-differentiated high-grade tumors (1.61,±,0.64 vs 3.37,±,1.49, p,<,0.01; 0.45,±,0.17 vs 0.78,±,0.24, p,<,0.01; and 0.076,±,0.048 vs 0.121,±,0.088, p,=,0.24, respectively). It is concluded that the protein-avid MRI contrast agent Gadofluorine M enhances tumors of varying malignancy depending on the tumor grade, higher contrast agent accumulation for more malignant lesions. The results show potential utility for differentiating benign and low-grade malignant lesions from high-grade cancers. Copyright © 2006 John Wiley & Sons, Ltd. [source] Volume natriuresis vs. pressure natriuresisACTA PHYSIOLOGICA, Issue 4 2004P. Bie Abstract Body fluid regulation depends on regulation of renal excretion. This includes a fast vasopressin-mediated water-retaining mechanism, and slower, complex sodium-retaining systems dominated by the renin,angiotensin aldosterone cascade. The sensory mechanisms of sodium control are not identified; effectors may include renal arterial pressure, renal reflexes, extrarenal hormones and other regulatory factors. Since the pioneering work of Guyton more than three decades ago, pressure natriuresis has been in focus. Dissociations between sodium excretion and blood pressure are explained as conditions where regulatory performance exceeds the precision of the measurements. It is inherent to the concept, however, that sudden transition from low to high sodium intake elicits an arterial pressure increase, which is reversed by the pressure natriuresis mechanism. However, such transitions elicit parallel changes in extracellular fluid volume thereby activating volume receptors. Recently we studied the orchestration of sodium homeostasis by chronic and acute sodium loading in normal humans and trained dogs. Small increases in arterial blood pressure are easily generated by acute sodium loading, and dogs appear more sensitive than humans. However, with suitable loading procedures it is possible , also acutely , to augment renal sodium excretion by at least one order of magnitude without any change in arterial pressure whatsoever. Although pressure natriuresis is a powerful mechanism capable of overriding any other controller, it seems possible that it is not operative under normal conditions. Consequently, it is suggested that physiological control of sodium excretion is neurohumoral based on extracellular volume with neural control of renin system activity as an essential component. [source] A fresh look at dry weightHEMODIALYSIS INTERNATIONAL, Issue 4 2008Jochen RAIMANN Abstract The concept of dry weight (DW) is central to dialysis therapy. The most commonly used definition of DW is the weight below which patients become hypotensive on dialysis. However, this definition is dependent on patient symptoms. A more rigorous definition of DW is the body weight at a physiological extracellular volume (ECV) state. Overhydration is an excess in ECV above that found in healthy subjects. In healthy subjects, within extremes of salt intake, ECV may vary between 280 and 340 mL/kg lean body mass. Sodium accumulation is one of the many consequences of renal failure; it results in increased water intake and an increase in ECV, and an accompanying rise in blood pressure with its clinical sequelae, most prominently cardiovascular and cerebrovascular diseases. Recently characterized endogenous digitalis-like factors which are released in response to ECV expansion have extended this traditional picture. Efforts to reduce a positive sodium balance include dietary counseling and avoidance of iatrogenic intradialytic sodium loading, such as dialysate sodium exceeding serum levels, sodium profiling, and intravenous saline. Excess ECV is predominantly located in the interstitial compartment and must be removed during dialysis therapy by ultrafiltration. During this process, interstitial fluid redistributes to the intravascular space via uptake in the capillary bed. In addition to that mechanism, we propose that increased lymphatic flow into the venous system contributes to plasma refilling. Both clinical and technical means are used to assess the presence of DW. Continuous segmental calf bioimpedance is a promising new technology for intradialytic DW diagnosis. [source] Catecholamine exocytosis is diminished in R6/2 Huntington's disease model miceJOURNAL OF NEUROCHEMISTRY, Issue 5 2007Michael A. Johnson Abstract In this work, the mechanisms responsible for dopamine (DA) release impairments observed previously in Huntington's disease model R6/2 mice were evaluated. Voltammetrically measured DA release evoked in striatal brain slices from 12-week old R6/2 mice by a single electrical stimulus pulse was only 19% of wild-type (WT) control mice. Iontophoresis experiments suggest that the concentration of released DA is not diluted by a larger striatal extracellular volume arising from brain atrophy, but, rather, that striatal dopaminergic terminals have a decreased capacity for DA release. This decreased capacity was not due to an altered requirement for extracellular Ca2+, and, as in WT mice, the release in R6/2 mice required functioning vesicular transporters. Catecholamine secretion from individual vesicles was measured during exocytosis from adrenal chromaffin cells harvested from R6/2 and WT mice. While the number of exocytotic events was unchanged, the amounts released per vesicle were significantly diminished in R6/2 mice, indicating that vesicular catecholamines are present in decreased amounts. Treatment of chromaffin cells with 3-nitropropionic acid decreased the vesicular release amount from WT cells by 50%, mimicking the release observed from untreated R6/2 cells. Thus, catecholamine release from tissues isolated from R6/2 mice is diminished because of impaired vesicle loading. [source] | |||||||||||||