Blood Ratio (blood + ratio)

Distribution by Scientific Domains

Selected Abstracts

Validity of methyl mercury hair analysis: mercury monitoring in human scalp/nude mouse model

Grazyna Zareba
Abstract Objective. The grafting of human scalp hair was used as a new application of this method to explore methyl mercury incorporation into human hair and to validate this model for mercury monitoring in hair. Methods. Human scalp grafts were transplanted to athymic BALB/c nude mice. The animals were exposed to methyl mercury either as a single dose i.p. or continuously for 4 months, using ALZET osmotic pumps. The mercury concentration in hair was determined using x-ray fluorescence (XRF) spectrometry by segmental (2 mm) analysis of a single strand, and tissue concentrations were measured by cold vapor atomic absorption analysis. Results. Human scalp hair grown in nude mice showed long-term persistence of human features including the expression of histocompatibility antigens (KAB 3, W 6/32, SF 1-1.1.1) and normal hair morphometry. The disposition of methyl mercury in nude mice followed a one-compartment model with a whole body elimination half-life of 6.7 days (elimination constant, k = 0.1/day). Autoradiographic studies revealed that methyl mercury was rapidly incorporated into areas of the hair follicle undergoing active keratinization. Methyl mercury concentrations in human hair transplanted onto nude mice were two orders of magnitude higher than in blood and attained a mean hair: blood ratio of 217 : 1, similar to ratios reported only in human studies. Conclusions. This study demonstrated that human hair grown on nude mice can record the level of exposure to methyl mercury and can serve as a valuable research tool to study mercury incorporation into human hair. Copyright 2007 John Wiley & Sons, Ltd. [source]

Oral administration of a centrally acting ghrelin receptor agonist to conscious rats triggers defecation

A. D. Shafton
Abstract, Agonists of ghrelin receptors that cross the blood,brain barrier, but not ghrelin itself, administered peripherally (intravenous or subcutaneous), cause defecation by acting on centres in the lumbo-sacral spinal cord. It is not established whether orally administered ghrelin receptor agonists can have this action. We tested GSK894281 for its effectiveness at the ghrelin receptor and its ability to cross the blood,brain barrier. GSK894281 was effective at the human and rat ghrelin receptors at 1,10 nmol L,1, but was >1000-fold less potent at the motilin receptor. It achieved a similar blood concentration by oral or intravenous administration. Oral bioavailability was 74% and brain : blood ratio at steady state was 0.7 : 1. GSK894281 administered orally (1,100 mg kg,1) caused a prompt, dose-related production of faecal pellets; at 10 mg kg,1 faecal output was four times greater than after carrier. The output was the greatest in the first half hour and subsided over the next 90 min. At an oral dose of 10 mg kg,1, the compound was effective on eight successive days. Faecal output was, on average, increased threefold over control in the 2 h after administration on each of the 8 days. This dose also significantly increased food consumption. Rats showed no adverse behavioural effects to the drug on a single application, but at the end of a week of administration they avoided the gavaging pipette. Oral administration of ghrelin receptor agonists that enter the central nervous system could possibly be used to relieve acute cases of constipation or to clear the bowel for colonoscopy. [source]

Evaluation of Abdominal Fluid: Peripheral Blood Creatinine and Potassium Ratios for Diagnosis of Uroperitoneum in Dogs

Chad Schmiedt DVM, DACVS
Objective:To determine the clinical efficacy of abdominal fluid to peripheral blood ratios of creatinine and potassium concentrations to diagnose uroperitoneum in dogs. Design:Records of 13 dogs with confirmed uroabdomen were retrospectively analyzed. Prospective evaluation of 8 dogs with nonrenal ascites provided data for a control population. Setting:Veterinary Medical Teaching Hospital. Animals:Client owned dogs. Interventions:None Measurements and Main Results:Abdominal fluid potassium (mEq/L) and creatinine concentrations (mg/dl) were recorded. Peripheral blood potassium and creatinine concentrations were also recorded. Ratios were calculated based on these values. An abdominal fluid creatinine concentration to peripheral blood creatinine concentration ratio of > 2:1 was predictive of uroabdomen in dogs (specificity 100%, sensitivity 86%). An abdominal fluid potassium concentration to peripheral blood potassium concentration of > 1.4:1 is also predictive of uroabdomen in dogs (specificity 100%, sensitivity 100%). All dogs with uroabdomen had an abdominal fluid creatinine concentration that was at least 4 times normal peripheral blood levels. Conclusion:Abdominal fluid to peripheral blood potassium and creatinine ratios provide a means to diagnose uroperitoneum in dogs without elevated peripheral blood creatinine. [source]

Prediction of human pharmacokinetics , improving microsome-based predictions of hepatic metabolic clearance

Urban Fagerholm
Physiologically based methods generally perform poorly in predicting in-vivo hepatic CL (CLH) from intrinsic clearance (CLint) in microsomes in-vitro and unbound fraction in blood (fu,bl). Various strategies to improve the predictability have been developed, and inclusion of an empirical scaling factor (SF) seems to give the best results. This investigation was undertaken to evaluate this methodology and to find ways to improve it further. The work was based on a diverse data set taken from Ito and Houston (2005). Another objective was to evaluate whether rationalization of CLH predictions can be made by replacing blood/plasma-concentration ratio (Cbl/Cpl) measurements with SFs. There were apparently no or weak correlations between prediction errors and lipophilicity, permeability (compounds with low permeability missing in the data set) and main metabolizing CYP450s. The use of CLint class (high/low) and drug class (acid/base/neutral) SFs (the CD-SF method) gives improved and reasonable predictions: 1.3-fold median error (an accurate prediction has a 1-fold error), 76% within 2-fold-error, and a median absolute rank ordering error of 2 for CLH (n = 29). This approach is better than the method with a single SF. Mean (P < 0.05) and median errors, fraction within certain error ranges, higher percentage with most accurate predictions, and ranking were all better, and 76% of predictions were more accurate with this new method. Results are particularly good for bases, which generally have higher CLH and the potential to be incorrectly selected/rejected as candidate drugs. Reasonable predictions of fu,bl can be made from plasma fu (fu,pl) and empirical blood cell binding SFs (B-SFs; 1 for low fu,pl acids; 0.62 for other substances). Mean and median fu,bl prediction errors are negligible. The use of the CD-SF method with predicted fu,bl (the BCD-SF method) also gives improved and reasonable results (1.4-fold median error; 66% within 2-fold-error; median absolute rank ordering error = 1). This new empirical approach seems sufficiently good for use during the early screening; it gives reasonable estimates of CLH and good ranking, which allows replacement of Cbl/Cpl measurements by a simple equation. [source]

Synthesis and biodistribution in mice of a new 99mTc nitrido complex for brain imaging

Junbo Zhang
Abstract The bis(N -cyclopentyl dithiocarbamato) nitrido technetium-99m complex 99mTcN(CPEDTC)2 was synthesized by the reduction of 99mTcO into [99mTc,N]2+ with stannous chloride in the presence of succinic dihydrazide and propylenediamine tetraacetic acid, followed by the addition of sodium N -cyclopentyl dithiocarbamate monohydrate. The radiochemical purity (RCP) of the product was over 90% as measured by thin layer chromatography(TLC) and high performance liquid chromatography(HPLC). In vitro studies showed that the complex possessed good stability under physiological conditions. Its partition coefficient studies indicated it was a good lipophilic complex. The electrophoresis results showed the complex was neutral. The biodistribution results in mice indicated that 99mTcN(CPEDTC)2 was significantly retained into the brain. The brain uptake(ID%/g) was 3.58, 5.26, 3.73 and 2.72 and the brain/blood ratios were 0.79, 1.69, 1.59 and 1.58 at 5, 30, 60 and 90 min post-injection, respectively. These results suggested potential usefulness of the complex as a new brain perfusion imaging agent. Copyright 2004 John Wiley & Sons, Ltd. [source]