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Low Plasma Concentrations (low + plasma_concentration)
Selected AbstractsFructose-mediated non-enzymatic glycation: sweet coupling or bad modificationDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2004Casper G. Schalkwijk Abstract The Maillard reaction is a process in which reducing sugars react spontaneously with amino groups in proteins to advanced glycation endproducts (AGEs). Although an elevated level of glucose had been thought to play a primary role in the Maillard reaction, on a molecular basis, glucose is among the least reactive sugars within biological systems. The formation of AGEs is now also known to result from the action of various metabolites other than glucose, which are primarily located intracellularly and participate in the non-enzymatic glycation reaction at a much faster rate, such as fructose, trioses and dicarbonyl compounds. In this review, we considered the glycation reaction with particular attention to the potential role of fructose and fructose metabolites. The two sources for fructose are an exogenous supply from the diet and the endogenous formation from glucose through the aldose reductase pathway. Despite its ,eightfold higher reactivity, the contribution of extracellular glycation by fructose is considerably less than that by glucose, because of the low plasma concentration of fructose (5 mmol/L glucose vs 35 µmol/L fructose). Intracellularly, fructose is elevated in a number of tissues of diabetic patients in which the polyol pathway is active. In the cells of these tissues, the concentrations of fructose and glucose are of the same magnitude. Although direct evidence is not yet available, it is likely that the high reactivity of fructose and its metabolites may substantially contribute to the formation of intracellular AGEs and may contribute to alterations of cellular proteins, dysfunction of cells and, subsequently, to vascular complications. Copyright © 2004 John Wiley & Sons, Ltd. [source] Pharmacokinetic characterization of 14C-vascular endothelial growth factor controlled release microspheres using a rat modelJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2002Tae-Kyoung Kim The objectives of this study were to characterize the pharmacokinetics of vascular endothelial growth factor (VEGF) in poly(lactic-co-glycolic) acid (PLGA) microspheres using a rat model, and to develop a pharmacokinetic model for this controlled release formulation. 14C-VEGF was encapsulated using a solid-in-oil-in-water emulsification method. The microspheres were administered subcutaneously to rats and the pharmacokinetic parameters were compared with those of protein solutions. Intravenous administration of protein solutions resulted in short half-lives and subcutaneous administration resulted in rapid clearance from the subcutaneous tissue, with high plasma concentrations as expressed by rapid absorption and elimination. The subcutaneous administration of the VEGF microspheres produced low plasma concentrations and high subcutaneous concentrations over a period of 7 weeks. The area under the curve (AUC), the time required to achieve the maximum concentration (tmax), the maximum concentration (Cmax) in blood samples and the elimination rate constant (kel) values at the subcutaneous tissue site were selected to compare the pharmacokinetic characterization of VEGF microspheres with that of protein solutions. The in-vivo release profiles of the proteins were slower than the in-vitro release profiles and they followed the same trend as the in-vitro and in-vivo PLGA degradation rates. The PLGA microsphere degradation was the determinant step for VEGF release from the microspheres and its absorption at the subcutaneous site. Microspheres appear to be an attractive system for the localized rate-controlled delivery of VEGF. 14C-Methylation via reductive alkylation of VEGF did not affect its mitogenic activity, however approximately 25% activity was lost following release from PLGA microspheres. This loss of activity may be due to degradation in an acidic environment as a result of PLGA degradation. [source] Quantification of clenbuterol in equine plasma, urine and tissue by liquid chromatography coupled on-line with quadrupole time-of-flight mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 17 2002Fuyu Guan Clenbuterol (CBL) is a potent ,2 -adrenoceptor agonist used for the management of respiratory disorders in the horse. The detection and quantification of CBL can pose a problem due to its potency, the relatively low dose administered to the horse, its slow clearance and low plasma concentrations. Thus, a sensitive method for the quantification and confirmation of CBL in racehorses is required to study its distribution and elimination. A sensitive and fast method was developed for quantification and confirmation of the presence of CBL in equine plasma, urine and tissue samples. The method involved liquid-liquid extraction (LLE), separation by liquid chromatography (LC) on a short cyano column, and pseudo multiple reaction monitoring (pseudo-MRM) by electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI-QTOF-MS/MS). At very low concentrations (picograms of CBL/mL), LLE produced better extraction efficiency and calibration curves than solid-phase extraction (SPE). The operating parameters for electrospray QTOF and yield of the product ion in MRM were optimized to enhance sensitivity for the detection and quantification of CBL. The quantification range of the method was 0.013,10,ng of CBL/mL plasma, 0.05,20,ng/0.1,mL of urine, and 0.025,10,ng/g tissue. The detection limit of the method was 13,pg/mL of plasma, 50,pg/0.1,mL of urine, and 25,pg/g of tissue. The method was successfully applied to the analysis of CBL in plasma, urine and various tissue samples, and in pharmacokinetic (PK) studies of CBL in the horse. CBL was quantified for 96,h in plasma and 288,h in urine post-administration of CLB (1.6,µg/kg, 2,×,daily,×,7 days). This method is useful for the detection and quantification of very low concentrations of CBL in urine, plasma and tissue samples. Copyright © 2002 John Wiley & Sons, Ltd. [source] Intestinal-FABP and Liver-FABP: Novel Markers for Severe Abdominal InjuryACADEMIC EMERGENCY MEDICINE, Issue 7 2010Borna Relja MSc ACADEMIC EMERGENCY MEDICINE 2010; 17:729,735 © 2010 by the Society for Academic Emergency Medicine Abstract Objectives:, Fatty acid,binding proteins (FABPs) have relatively high tissue concentrations and low plasma concentrations and are released into the circulation following organ injury. We explored the utility of intestinal-(I)-FABP and liver-(L)-FABP for the diagnosis of abdominal injury in patients with multiple trauma. Methods:, This prospective study included 102 trauma patients and 30 healthy volunteers. Plasma I-FABP and L-FABP levels were measured in the emergency department (ED) by enzyme-linked immunosorbent assay (ELISA). Forty-one patients suffered from serious or severe abdominal trauma (Abbreviated Injury Score [AIS] code "ai" for abdominal injury, AISai , 3) and nine were moderately abdominally injured (AISai < 3). Fifty-two had no abdominal injury. Results:, Median I-FABP and L-FABP levels in the AISai , 3 group (516 pg/mL and 135 ng/mL, respectively) were significantly higher compared to the AISai < 3 group (154 pg/mL and 13 ng/mL, respectively) or those without abdominal injury (207 pg/mL and 21 ng/mL, respectively) or normal controls (108 pg/mL and 13 ng/mL, respectively). The cutoff to distinguish the ai , 3 is 359 pg/mL for I-FABP and 54 ng/mL for L-FABP, with 93% specificity and 75% sensitivity for I-FABP and 93% and 82% for L-FABP, respectively. Conclusions:, High I-FABP and L-FABP levels correlate with relevant severity of abdominal tissue damage in patients with multiple trauma. I-FABP and L-FABP could be useful as markers for the early detection of significant abdominal injury in acute multiple trauma and identify patients who require rapid intervention. [source] | ||||||||||