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Showing papers on "Blood serum published in 2001"


Patent
04 Dec 2001
TL;DR: In this paper, the HMG CoA reductase inhibitors are defined as HMG coA inhibitors that are active in inhibiting cholesterol biosynthesis, modulating blood serum lipids such as lowering LDL cholesterol and/or increasing HDl cholesterol, and treating hyperlipidemia.
Abstract: Compounds of structure (1) are HMG CoA reductase inhibitors and thus are active in inhibiting cholesterol biosynthesis, modulating blood serum lipids such as lowering LDL cholesterol and/or increasing HDl cholesterol, and treating hyperlipidemia, hypercholesterolemia, hypertriglyceridemia and atherosclerosis and pharmaceutically acceptable salts thereof, wherein X is O or S; Z is (2) or (3); n is O or 1; R1 and R2 are the same or different and are independently selected from alkyl, arylalkyl, cycloalkyl, alkenyl, cycloalkenyl, aryl, heteroaryl or cycloheteroalkyl; and R3 to R9 are as defined herein.

220 citations


Journal ArticleDOI
TL;DR: An automated and on-line MIP SPME extraction method was developed for propranolol determination in biological fluids and showed improved selectivity in comparison to alternative in-tube stationary-phase materials, overcoming the limitations of existing S PME coating materials.
Abstract: A molecularly imprinted polymer (MIP) material was synthesized for use as an in-tube solid-phase microextraction (SPME) adsorbent. The inherent selectivity and chemical and physical robustness of the MIP material was demonstrated as an effective stationary-phase material for in-tube SPME. An automated and on-line MIP SPME extraction method was developed for propranolol determination in biological fluids. This simplified the sample preparation process and the chromatographic separation of several beta-blocker compounds. The method developed for propranolol showed improved selectivity in comparison to alternative in-tube stationary-phase materials, overcoming the limitations of existing SPME coating materials. Preconcentration of the sample by the MIP adsorbent increased the sensitivity, yielding a limit of detection of 0.32 microg/mL by UV detection. Excellent method reproducibility (RSD 500 injections) were observed over a fairly wide linear dynamic range (0.5-100 microg/mL) in serum samples. To our knowledge, this is the first report on the automated application of a MIP material for in-tube SPME. The method was inexpensive, simple to set up, and simplified the choice of SPME adsorbent for in-tube extraction. The approach can potentially be extended to other MIPs for the determination of a wide range of chemically significant analytes.

213 citations


Journal ArticleDOI
TL;DR: The paired analyses of adipose tissue and colostrum and mature milk contamination levels indicate a high degree of coherence, principally of DDT, in the body and lactation as a decontamination means.
Abstract: Organochlorine pesticides, due to their persistence, accumulate in food chains and cause elevated contamination in human beings. These residues bioconcentrate in lipid-rich tissues according to the equilibrium pattern of internal transport and lipid tissue content. The analyses of maternal adipose tissue, maternal blood serum, umbilical blood serum, colostrum, and mature milk indicate circulation of these compounds through all compartments of the maternal body, including their crossover of the placental barrier. The greatest residue levels found correspond to DDTs, with highest levels determined in colostrum (5.71 mg/kg of DDT total), followed by adipose tissue with 5.66 mg/kg and in mature milk with 4.70 mg/kg. Among DDTs, pp'DDE is the most predominant compound. The paired analyses of organochlorine pesticide residue levels between mother blood serum and umbilical blood serum demonstrate significant correlation and their transfer from mother to fetus through the placenta. The paired analyses of adipose tissue and colostrum and mature milk contamination levels indicate a high degree of coherence, principally of DDT, in the body and lactation as a decontamination means.

182 citations


Journal ArticleDOI
TL;DR: A multiple stable isotope and multiple tissue approach suggested that marine mammals occupied the highest trophic positions in the food webs of both communities and that they overlapped with one another to some extent trophically.
Abstract: The trophic relationships of both the benthic and pelagic communities in the Estuary and Gulf of St Lawrence regions were examined, with a special focus on the trophic position (TP) and relationship(s) among harbour, grey, hooded and harp seals and beluga whales. A multiple stable isotope and multiple tissue approach, used in conjunction with conventional dietary information, suggested that marine mammals occupied the highest trophic positions in the food webs of both communities and that they overlapped with one another to some extent trophically. Harbour seals Phoca vitulina and hooded seals Cystophora cristata occupied the highest TP, grey seals Halichoerus grypus, Gulf harp seals Phoca groenlandica, and male beluga whales Delphinapterus leucas were intermediate, and Estuary harp seals and female beluga whales were at the lowest TP. A general pattern of increasing enrichment of 13 C or 15 N with age was observed in marine mammals (as well as fishes), although yearlings showed a decreased enrichment compared to both younger and older age classes, Sex also influenced δ 15 N values. Males were more 15 N-enriched than females, with the difference between the sexes increasing with age, and being most pronounced in species that are sexually dimorphic with respect to body size. Geographical location also influenced isotope abundance. Estuary organisms were generally 13 C-enriched relative to Gulf animals. δ 13 C values were on average lower in short-term diet integrators (blood serum) than in longer-term diet integrators (red blood cells) of harbour seals captured in April to June in the Estuary, which suggests that they probably did not move outside the Lower Estuary during the winter. Grey seals captured in the Lower Estuary did, however, show evidence of having been in the Gulf region some weeks or months before capture.

181 citations


Journal ArticleDOI
TL;DR: In this paper, a two-step method for constructing cholesterol biosensors by entrapment of cholesterol oxidase (ChOx) within a composite poly(2-hydroxyethyl methacrylate) (p(HEMA))/polypyrrole (p pyrrole)) membrane has been developed.

178 citations


Journal ArticleDOI
TL;DR: It is indicated that a moderately intensive psychosocial manager program lasting for 1 year can be beneficial for the employees with regard to both lowered serum cortisol and improved authority over decisions.
Abstract: Background Possible health effects for employees of efforts to improve the psychosocial competence of managers have not been studied scientifically in the past. Objective To explore how efforts to improve management will change the work environment and health of the employees. Methods Managers of the experimental department in a large insurance corporation underwent 2-hour biweekly training sessions for 1 year—altogether, 60 hours. A control group of employees in other departments in the corporation not affected by the modification was followed with the same assessments. Morning blood samples for the assessment of serum cortisol were collected both at baseline and after 1 year in 155 participants in the experimental group and in 147 subjects in the control group. Liver enzymes and lipids were also assessed. In the questionnaire part of the 1-year follow-up study, there were 119 participants in the experimental group and 132 in the control group. Results When repeated-measures ANOVA was used, a significant interaction effect was found for the level of serum cortisol; serum cortisol levels were decreased in the intervention group and were unchanged in the control group (ANOVA two-way interaction, p = .02; after exclusion of the managers, p = .005). A significant interaction effect was also observed for decision authority, with increased decision authority in the intervention group and, conversely, a decreased level in the control group (p = .001; after exclusion of managers, p = .02). Conclusions The study indicates that a moderately intensive psychosocial manager program lasting for 1 year can be beneficial for the employees with regard to both lowered serum cortisol and improved authority over decisions.

158 citations


Journal ArticleDOI
TL;DR: The method developed for this purpose utilized ethyl acetate extraction of 100 microl samples and their derivatization with bis(trimethylsilyl)trifluoroacetamide (BSTFA) followed by gas-chromatographic analysis on a DB-5 column followed by mass selective detection employing two target ions and one qualifier ion for each compound.

150 citations


Journal ArticleDOI
TL;DR: Results suggest that dosimetry based on 86Y-DOTATOC and 111In-DTPA-octreotide yields similar organ doses, whereas there are relevant differences in estimated tumour doses.
Abstract: The somatostatin analogue (90)Y-DOTATOC (yttrium-90 DOTA- D-Phe(1)-Tyr(3)-octreotide) is used for treatment of patients with neuroendocrine tumours. Accurate pretherapeutic dosimetry would allow for individual planning of the optimal therapeutic strategy. In this study, the biodistribution and resulting dosimetric calculation for therapeutic exposure of critical organs and tumour masses based on the positron emission tomography (PET) tracer (86)Y-DOTATOC, which is chemically identical to the therapeutic agent, were compared with results based on the tracer commonly used for somatostatin receptor scintigraphy, (111)In-DTPA-octreotide (indium-111 DTPA- D-Phe(1)-octreotide, OctreoScan). Three patients with metastatic carcinoid tumours were investigated. Dynamic and static PET studies with 77-186 MBq (86)Y-DOTATOC were performed up to 48 h after injection. Serum and urinary activity were measured simultaneously. Within 1 week, but not sooner than 5 days, patients were re-investigated by conventional scintigraphy with (111)In-DTPA-octreotide (110-187 MBq) using an equivalent protocol. Based on the regional tissue uptake kinetics, residence times were calculated and doses for potential therapy with (90)Y-DOTATOC were estimated. Serum kinetics and urinary excretion of both tracers showed no relevant differences. Estimated liver doses were similar for both tracers. Dose estimation for organs with the highest level of radiation exposure, the kidneys and spleen, showed differences of 10.5%-20.1% depending on the tracer. The largest discrepancies in dose estimation, ranging from 23.1% to 85.9%, were found in tumour masses. Furthermore, there was a wide inter-subject variability in the organ kinetics. Residence times (tau(organs)) for (90)Y-DOTATOC therapy were: tau(liver) 1.59-2.79 h; tau(spleen) 0.07-1.68 h; and tau(kidneys) 0.55-2.46 h (based on (86)Y-DOTATOC). These data suggest that dosimetry based on (86)Y-DOTATOC and (111)In-DTPA-octreotide yields similar organ doses, whereas there are relevant differences in estimated tumour doses. Individual pretherapeutic dosimetry for (90)Y-DOTATOC therapy appears necessary considering the large differences in organ doses between individual patients. If possible, the dosimetry should be performed with the chemically identical tracer (86)Y-DOTATOC.

146 citations


Journal ArticleDOI
TL;DR: The levels of amino acids in serum from healthy donors and patients with ischemic stroke were determined using a simple, sensitive and reproducible isocratic high-performance liquid chromatography method.

141 citations


Journal ArticleDOI
TL;DR: Results from the analysis across selection lines showed a significant association of the BB genotype with higher weight gain during the first 20 d after weaning and a slight dominance effect of the marker on postweaning gain, while analysis within the low IGF-I line showed no significant association.
Abstract: The objective of this research was to evaluate a biallelic genetic marker identified in the first promoter region of the bovine IGF-I gene. The point mutation was identified as a T-to-C transition by sequencing the polymorphic fragments. A PCR-RFLP procedure was developed for determining the marker genotypes. Marker genotypes were determined for 760 Angus calves from divergent lines that were created by selection for high or low serum IGF-I concentration (allele A: 63.9%, B: 36.1%). Data were analyzed using the multiple-trait derivative-free restricted maximum likelihood computer programs with animal models. The full animal model included fixed effects of marker genotype, birth year, season of birth, sex, age of dam, and selection line; random effects of animal, maternal genetic, and maternal permanent environmental effects; and a covariate for age of calf. Traits analyzed included blood serum IGF-I concentrations on d 28, 42, and 56 of the postweaning test, mean IGF-I concentration, birth weight, weaning weight, on-test weight, off-test weight, off-test hip height, postweaning gain, and weight gain during the 20-d period immediately after weaning. Results from the analysis across selection lines showed a significant association of the BB genotype with higher weight gain during the first 20 d after weaning and a slight dominance effect of the marker on postweaning gain. Analysis within the low IGF-I line also showed a significant association of the BB genotype with higher weight gain during the first 20 d after weaning and with on-test weight, although analysis within the high IGF-I line did not show any significant association. The associated effects of the marker need to be verified in other cattle populations.

129 citations


Journal ArticleDOI
TL;DR: Soil samples from lassy County showed a lower contamination with organochlorines than samples from other Romanian regions, while DDTs concentrations in soil were significantly higher at rural sites, and only few samples exceeded the official Romanian norms for DDTs.

Journal ArticleDOI
TL;DR: A new strategy for overcoming glutathione-dependent 4-aminoquinoline resistance to Plasmodium falciparum is developed and work is in progress to extend and validate the strategy outlined here.
Abstract: Glutathione (GSH), which is known to guard Plasmodium falciparum from oxidative damage, may have an additional protective role by promoting heme catabolism An elevation of GSH content in parasites leads to increased resistance to chloroquine (CQ), while GSH depletion in resistant P falciparum strains is expected to restore the sensitivity to CQ High intracellular GSH levels depend inter alia on the efficient reduction of GSSG by glutathione reductase (GR) On the basis of this hypothesis, we have developed a new strategy for overcoming glutathione-dependent 4-aminoquinoline resistance To direct both a 4-aminoquinoline and a GR inhibitor to the parasite, double-drugs were designed and synthesized Quinoline-based alcohols (with known antimalarial activity) were combined with a GR inhibitor via a metabolically labile ester bond to give double-headed prodrugs The biochemically most active double-drug 7 of this series was then evaluated as a growth inhibitor against six Plasmodium falciparum strains that

Journal ArticleDOI
TL;DR: Significant increases in activities of AST, ALT, ALP, GGT, and LD were observed at 168 and 336 h, indicating possible liver toxicity due to chronic effects of the toxin.

Journal ArticleDOI
TL;DR: The study indicates the possibility of using rare earth elements as safe and inexpensive alternative performance enhancers for pig production.
Abstract: A feeding study was performed to investigate possible performance enhancing effects of rare earth elements (REE) in growing and fattening pigs, as well as their influence on the blood serum biochemical changes and the accumulation of REE in the organs of pigs treated with a REE diet for a longer time period. Fourteen crossbred piglets (Deutsche Landrasse x Pietrain) were allotted to two dietary treatments: a control group and the REE-treated group which was supplemented with 300 mg of an REE mixture per kg feed. The REE mixture contained mainly chlorides of lanthanum (La), cerium (Ce) and praseodymium (Pr). The whole feeding period consisted of a 2 months ad libitum feeding period M-I and a 1 month restricted feeding period M-II. It was found that in comparison with the control group, the REE group had a better daily body weight gain of 19% (p 0.05) in the period M-II. The REE had no significant (p > 0.05) influence on blood serum thyroxine (T(4)), aspartate-amino-transferase (AST), alanine-amino-transferase (ALT), alkaline-phosphatase (AP), total cholesterol, triglyceride, total protein, albumin, glucose, Ca, P, Na, K and Cl. However, serum triiodothyronine (T(3)) in the REE group was significantly (p < 0.01) lower than that in the control group. The accumulation rate of La and Ce in the muscle, liver and kidneys was very low after feeding the REE diet for 3 months. The study indicates the possibility of using rare earth elements as safe and inexpensive alternative performance enhancers for pig production.

Journal ArticleDOI
21 Jun 2001-Talanta
TL;DR: A mathematical model which relates the analytical signal to the analyte concentration was developed and the model served to obtain some of the thermodynamic constants of the system (the Michaelis constant and the turnover number) and the results were compared with those obtained by a commercial clinical analyzer.

Journal ArticleDOI
TL;DR: Comprehensive data derived from the Taiwanese population on the link between lipids and psychological symptoms are provided, for the first time, revealing a reverse correlation between depression and serum concentrations of HDL-C.
Abstract: This study examines the correlations between serum lipid levels and psychological distress. There were 4444 consecutive attendees of general health clinics who participated in the study. Psychological symptoms were measured by the Taiwanese version of the Symptoms Check List 90, revised (T-SCL-90-R). Levels of fasting serum lipids, including total cholesterol, total triglycerides and high-density lipoprotein cholesterol (HDL-C), were determined. Multiple linear regression analyses, with adjustment for confounders, revealed that the concentration of HDL-C had significant inverse associations with scores of depression, somatization and phobic anxiety. Women with an HDL-C level lower than 35 mg/dl scored significantly higher on depression, interpersonal sensitivity, phobia, anxiety, somatization and aggressive hostility, while subjects with a total cholesterol concentration lower than 160 mg/dl scored significantly higher on anxiety, aggressive hostility, phobia, and psychoticism. This study provides, for the first time, comprehensive data derived from the Taiwanese population on the link between lipids and psychological symptoms, revealing a reverse correlation between depression and serum concentrations of HDL-C.

Journal ArticleDOI
TL;DR: In this paper, the feasibility of developing procedures based on solid phase microextraction (SPME) for the determination of pesticides in human body fluids, including serum and urine samples, was explored.

Journal ArticleDOI
TL;DR: N levels affected N metabolism of steers more when they are fed gamagrass than when they were fed switchgrass, with a greater efficiency of N use at low N intakes.
Abstract: The effects of two forage species and N levels on urea kinetics and whole-body N metabolism were evaluated in eight Angus steers (initial BW 217+/-15 kg). In a replicated, 4 x 4 Latin square design, steers were fed gamagrass (Tripsacum dactyloides L.) or switchgrass (Panicum virgatum L.), each of which had 56.2 (LO) or 168.5 (HI) kg of N fertilization per hectare. Diets provided adequate energy for 0.5 kg ADG. Nitrogen balance and urea kinetics were measured from d 22 to 27 of each period. Urine samples collected during intravenous infusion of bis 15N urea were used to calculate production and recycling of urea N from relative abundance of urea isotopomers. Jugular blood serum was analyzed for serum urea N (SUN). Gamagrass differed from switchgrass (P < 0.05) in daily DMI (4,273 vs 4,185 g), N intake (72 vs 67 g), DM digestibility (61.0 vs 63.6%), fecal N (30.6 vs 28.3 g/d), urine urea N (10.5 vs 8.0 g/d), and percentage of urinary N present as urea N (53.5 vs 40.0%). After adjustment for differences in N intake, fecal N still tended to be greater (P < 0.09) for gamagrass than for switchgrass. The LO differed from the HI (P < 0.01) in daily N intake (63 vs 76 g), DM digestibility (61.3 vs 63.3%), urine N (13.6 vs 25.9 g/d), and N retained as a percentage of N digested (57.3 vs 43.5%). Compared to switchgrass, gamagrass had greater SUN, N digestibility, and N digested as N level increased (forage x N level interactions, P < 0.05). As N level increased, N retention increased from 19.5 to 23.5 g/d in gamagrass and decreased from 20.5 to 18.1 g/d in switchgrass (interaction, P < 0.07). The HI group was greater than the LO intake group (P < 0.03) in endogenous production of urea N (44.4 vs 34.0 g/d), gut entry rate of urea N (31.6 vs 28.2 g/d), and the amount of urea N that re-entered the ornithine cycle (9.4 vs 7.9 g/d). However, the percentage of urea N entering the gastrointestinal tract that was recycled was constant among treatments (29.1%), indicating that almost 70% of the urea N that entered the gastrointestinal tract was potentially available for anabolic purposes of the steers as a component of microbial products that were absorbed or excreted in the feces. In summary, N levels affected N metabolism of steers more when they were fed gamagrass than when they were fed switchgrass. Although the absolute amounts of N moving through the system changed with variations in intake, the proportions remained similar, with a greater efficiency of N use at low N intakes.

Journal ArticleDOI
TL;DR: This review summarizes general aspects of chromatographic analysis of tocopherols and carotenoids in human samples and deals with information on the outcome of human studies, in which such measurements were applied.

Journal ArticleDOI
TL;DR: Time-dependent analyses of urine showed that D-AAs are continuously excreted, and quantified enantiomers were quantified in urine samples of two volunteers fasting for 115 h, decreasing in fasting, although amounts of D-Ser and 77 micromol/L urine as well as other D-As were still detectable.
Abstract: Amino acid (AA) enantiomers were determined as N(O)-pentafluoropropionyl-(2)-propyl esters by chiral gas chromatography-mass spectrometry (GC-MS) in 24 h samples of the urine of three healthy volunteers and in their blood sera. In urine the largest amounts were determined for D-Ser (64-199 micromol/day) and D-Ala (24-138 micromol/day). In blood sera, D-Ala (2.3-4.2 micromol/L) and D-Ser (1.0-2.9 micromol/L) were most abundant. Varying amounts of the D-enantiomers of Thr, Pro, Asx, Glx, Phe, Tyr, Orn and Lys were also found, albeit not in all urines and sera. Further, enantiomers were quantified in urine samples of two volunteers fasting for 115 h. Quantities of renally excreted D-AAs decreased in fasting, although amounts of D-Ser (69 and 77 micromol/L urine) as well as other D-AAs were still detectable. Time-dependent analyses of urine showed that D-AAs are continuously excreted.

Journal ArticleDOI
TL;DR: Results are presented for cyclic voltammetry at a glassy carbon electrode in 50% methanol, 50% 0.1 M HClO4, a solution typically used in HPLC separations of natural antioxidants.
Abstract: An overview is provided of the use of cyclic voltammetry and electrochemical detectors for HPLC to characterize antioxidants that are active as reducing agents at inert electrodes. Results are presented for cyclic voltammetry at a glassy carbon electrode in 50% methanol, 50% 0.1 M HClO4, a solution typically used in HPLC separations of natural antioxidants. The relative reducing strength of each antioxidant is estimated by the formal potential, and information is also obtained regarding the reversibility of the oxidation of the antioxidants, and the extent to which the carbon electrode is contaminated by the products of oxidation. Cyclic voltammetry of complex mixtures such as blood serum and wine produces a measure of the total antioxidant status due to antioxidants with a low oxidation potential. The results of cyclic voltammetry studies are relevant to interpreting the performance of carbon electrodes in electrochemical detectors for HPLC.

Journal ArticleDOI
TL;DR: The presence of OTA and ZEA is shown in Romanian slaughtered pigs at levels comparable to those reported in other countries.
Abstract: Blood serum, kidney, liver and muscle sample per animal were collected from slaughtered pigs (n = 52). The samples were analysed for ochratoxin A (OTA) and B (OTB) by HPLC methods. Zearalenone (ZEA) in serum was analysed by enzyme immunoassay. A total of 98% serum samples were OTA positive in the range of 0.05-13.4 ng/ml and 85% contained under 5 ng OTA/ml. The incidences of OTA in kidney and liver were very similar (79%, 75%) with mean levels of 0.54 ng/g and 0.16 ng/g, respectively. The lowest incidence (17%) and the lowest mean level contamination (0.15 ng/g) were in muscle samples. The mean distribution in tissues followed the pattern serum > kidney > liver > muscle (100%: 26%: 8.5%: 2.57%). No kidney, liver or muscle sample was found OTA positive above the maximum admitted limit in Romania (5 ng/g). No sample was found to be positive for OTB. A very similar OTA contamination (mean = 4.19 ng/ml, coefficient of variation = 34.4%) was observed in the serum samples (n = 10) collected from the same farm. ...

Journal ArticleDOI
TL;DR: The objective was to determine the half-life of the most abundant carotenoids in blood serum from healthy adult women living under controlled conditions, and half-lives were unrelated to physical or demographic characteristics such as body mass, body fat, racial background or age in these relatively homogeneous groups.
Abstract: Dietary intakes of carotenoids are highly variable in human populations as are serum carotenoid concentrations. However, there are few controlled data relating carotenoid intake to concentration. Most of the data that are available are from measurements of the absorption and decay of large pharmacologic doses of carotenoids, and are therefore of unknown physiologic relevance. Our objective was to determine the half-life (t(1/2)) of the most abundant carotenoids in blood serum from healthy adult women living under controlled conditions. As part of two carotenoid isotopic studies, we measured serum concentrations of beta-carotene, alpha-carotene, lutein, zeaxanthin, beta-cryptoxanthin and lycopene in 19 healthy young adult women that were fed controlled low carotenoid diets for approximately 10 wk. All other nutrients (vitamins A, E and C) were provided at 100-150% of the 1989 U.S. recommended dietary allowance levels. Exercise and activities were controlled throughout the studies to simulate usual activity patterns. Carotenoid concentrations were measured by reversed-phase HPLC. Serum carotenoid concentration decreases during depletion followed first-order kinetics. The half-lives determined in decreasing order were as follows: lutein (76 d) > alpha-carotene (45 d) = beta-cryptoxanthin (39 d) = zeaxanthin (38 d) = beta-carotene (37 d) > lycopene (26 d). Half-lives were unrelated to physical or demographic characteristics such as body mass, body fat, racial background or age in these relatively homogeneous groups. Carotenoids decreased by similar first-order mechanisms, although the rates differed for individual carotenoids.

Journal ArticleDOI
TL;DR: Oral administration of clarithromycin at 7.5 mg/kg every 12 hours maintains concentrations in serum, PELF, and BAL cells that are higher than the minimum inhibitory concentration for Rhodococcus equiisolates for the entire 12-hour dosing interval.
Abstract: Objective—To determine pharmacokinetics of clarithromycin and concentrations in body fluids and bronchoalveolar (BAL) cells of foals. Animals—6 healthy 2-to 3-week-old foals. Procedures—In a crossover design, clarithromycin (7.5 mg/kg) was administered to each foal via IV and intragastric (IG) routes. After the initial IG administration, 5 additional doses were administered IG at 12-hour intervals. Concentrations of clarithromycin and its 14-hydroxy metabolite were measured in serum by use of high-performance liquid chromatography. A microbiologic assay was used to measure clarithromycin activity in serum, urine, peritoneal fluid, synovial fluid, CSF, pulmonary epithelial lining fluid (PELF), and BAL cells. Results—After IV administration, elimination half-life (5.4 hours) and mean ± SD body clearance (1.27 ± 0.25 L/h/kg) and apparent volume of distribution at steady state (10.4 ± 2.1 L/kg) were determined for clarithromycin. The metabolite was detected in all 6 foals by 1 hour after clarithromycin admini...

Journal ArticleDOI
TL;DR: It is proposed that other subsets of PAH mutations will have a high likelihood of being responsive to oral BH4 administration, and it is believed that some of these mutations result in expressed mutant enzymes that are Km variants (with a lower binding affinity for BH 4) of the standard PAH enzyme phenotype.
Abstract: Deficiencies in the human enzyme phenylalanine hydroxylase (PAH) due to mutations in the PAH gene (PAH) result in the inborn error of metabolism phenylketonuria (PKU) The clinical symptom of this disease is an elevated concentration of L-phenylalanine (L-Phe) in blood serum To prevent mental retardation due to the buildup of neurotoxic metabolites of L-Phe, patients with severe PKU must be treated with a low-L-Phe diet starting early in their life Owing to extensive newborn screening programmes and genotyping efforts, more than 400 different mutations have been identified in the PAH gene Recently, there have been several reports of PKU patients showing a normalization of their L-Phe concentrations upon oral administration of the natural cofactor to PAH, (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) In an attempt to correlate the clinical responsiveness to BH4 administration with PKU genotype, we propose specific structural consequences for this subset of PAH mutations Based on the location and proximity of this subset of mutations to the cofactor-binding site in the three-dimensional structure of PAH, a hypothesis for BH4 responsiveness in PKU patients is presented It is believed that some of these mutations result in expressed mutant enzymes that are Km variants (with a lower binding affinity for BH4) of the standard PAH enzyme phenotype Oral administration of excess BH4 thus makes it possible for these mutant enzymes to suppress their low binding affinity for BH4, enabling this subset of PAH mutations to perform the L-Phe hydroxylation reaction Most of the BH4-responsive PAH mutations map to the catalytic domain of PAH in either of two categories Residues are located in cofactor-binding regions or in regions that interact with the secondary structural elements involved in cofactor binding Based on the series of known mutations that have been found to be responsive to BH4, we propose that other subsets of PAH mutations will have a high likelihood of being responsive to oral BH4 administration

Journal ArticleDOI
01 Jan 2001-Analyst
TL;DR: A theophylline antiserum was covalently immobilized on the surface of a fused silica fiber, modified with 3-aminopropyltriethoxysilane (APTES) and glutaraldehyde, and used as a selective and sensitive extraction medium for the immunoaffinity solid phase microextraction (SPME) as mentioned in this paper.
Abstract: A theophylline antiserum was covalently immobilized on the surface of a fused silica fiber, modified with 3-aminopropyltriethoxysilane (APTES) and glutaraldehyde, and used as a selective and sensitive extraction medium for the immunoaffinity solid-phase microextraction (SPME) determination of theophylline in serum samples The specificity of the immunoaffinity SPME fiber was first investigated using a fixed concentration of [3H]theophylline together with various amounts of interference, possessing no cross-reactivity with the theophylline antibody No significant non-specific binding was observed The reproducibility of the fiber preparation and the immunoaffinity SPME analysis was also investigated, resulting in a relative standard deviation of 61% for five analyses of the same fiber The antigen–antibody binding isotherm was obtained by analyzing theophylline standards of various concentrations (01–5 ng mL−1) until saturation values were reached Initial binding of theophylline was linear with a r2 = 0968 The cross-reactivity of the theophylline immunoaffinity SPME fiber for the structural analog caffeine was investigated by adding various amounts of caffeine in the presence of theophylline at a saturation concentration and produced a low cross-reactivity value of 01% Finally, spiked serum samples (10 and 50 ng mL−1) were successfully analyzed with an excellent correlation with the standard binding isotherm, thus confirming the performance of the immunoaffinity SPME coating for improved bioanalysis

Journal ArticleDOI
TL;DR: Urea levels in the CNS, SC, and BS were highly correlated, which supports the assumption that urea is evenly distributed, and the CNS/SC urea ratio can therefore be used for monitoring the CNS probe's in vivo performance.
Abstract: Object. When evaluating the results of intracerebral microdialysis, the in vivo performance of the microdialysis probe must be considered, because this determines the fraction of the interstitial concentration obtained in the microdialysis samples. The in vivo performance is dependent on several factors, for example, the interstitial compartment's diffusion characteristics, which may vary during the course of the acute brain injury process. In the present study the authors investigated the method of controlling the in vivo performance by using urea, which is evenly distributed in all body fluid compartments, as an endogenous reference compound and by comparing the urea levels in three compartments: the brain (CNS), abdominal subcutaneous tissue (SC), and blood serum (BS). Methods. Sixty-nine patients with traumatic brain injury or cerebrovascular disease were included in the study. In 63 of these patients a CNS probe was used, an SC probe was used in 40, and both were used in 34. Urea was measured by enzy...

Journal ArticleDOI
TL;DR: In this paper, molecularly imprinted polymers (MIPs) for pinacolyl methylphosphonate, ethyl methylph phosphonate and methane phosphonic acid were prepared.

Journal ArticleDOI
TL;DR: The present method was successfully applied to the determination of glyphosate in urine and serum, and showed catalytic currents based on the oxidation of amines in their structures.

Journal ArticleDOI
TL;DR: The data indicate that eosinophil count and/or ECP and EPO levels can be used to estimate the short-term risk of deterioration and the need for corticosteroid treatment in cases of mild and moderate allergic asthma.
Abstract: Background: Markers of airway inflammation are needed for prediction of asthma deterioration and evaluation of disease severity. Few studies have focused on the dynamics of airway inflammation as reflected by the activity of the eosinophils and their proteins after withdrawal of inhaled corticosteroids. Objective: Our goal was to investigate the effect of withdrawal of inhaled budesonide on eosinophil count in blood and eosinophil proteins in serum and urine and to relate the levels of these markers to the risk of symptoms of asthma, increased bronchial hyperresponsiveness, and deterioration of lung function. Methods: Thirty-three children were randomly selected to continue or discontinue use of inhaled budesonide in a double-blind, placebo-controlled study. They were followed up for 4 months with regular analysis of blood, serum, and urine samples; lung function; and methacholine challenges. Eosinophil activity markers were analyzed. Age-matched healthy children provided reference data for all parameters measured. Results: The eosinophil number in blood and eosinophil protein levels in serum (serum eosinophil cationic protein [ECP] and serum eosinophil peroxidase [EPO]) increased significantly in the withdrawal group, and the difference between the groups was significant ( P = .02 for all). Twenty-nine percent of the children in the withdrawal group remained symptom free. This subgroup had eosinophil counts at baseline below 350/μL, a serum ECP level below 15 μg/L, and a serum EPO level below 25 μg/L, each of which was related to a low risk of exacerbation (relative risk=0.37, 0.48, and 0.37 respectively; P Conclusion: Our data indicate that eosinophil count and/or ECP and EPO levels can be used to estimate the short-term risk of deterioration and the need for corticosteroid treatment in cases of mild and moderate allergic asthma. (J Allergy Clin Immunol 2001;107:812-7.)