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PubMed2006

Exercise capacity and circulating endothelial progenitor cells in hemodialysis patients.

Mobilization of circulating endothelial progenitor cells (EPCs) is increased after acute exercise and training. This study aims to evaluate whether, in a low performance population, EPC levels may be related to exercise capacity in steady state conditions. Study population consisted of sixteen hemodialysis patients. The distance walked in the 6-minute walking test (6 MWD) and the maximal speed attained in an incremental treadmill test were used to assess the exercise capacity. Physical functioning was measured by the scale on the SF36 questionnaire. Quantification of peripheral blood CD34(+) cells and enumeration of EPCs, assessed as CD34(+) cells coexpressing AC 133 and vascular endothelial growth factor receptor-2, were performed. Hemoglobin concentration, white blood cells, high-sensitivity C-reactive protein, total cholesterol, and triglycerides were measured. Statistical analysis examined the relationship between blood progenitors cells versus performance parameters, laboratory parameters, age, body mass index, hemodialysis duration, and erythropoietin therapy. Univariate analysis revealed a significant association between percentage values of EPC and performance parameters only: 6 MWD (r=0.720; p=0.0017), maximal treadmill speed (r=0.721; p=0.0016), and physical functioning score (r=0.506; p=0.0453). A similar statistical association between EPC absolute values and performance parameters was found. No correlation between CD34 (+) and any parameter under study was observed. Multivariate analysis indicated 6 MWD as the most significant independent factor associated with EPC level. EPC percentage value was significantly lower (p=0.0087) in the worse (6 MWD < 300 m, n=8) than in the better performing group (6 MWD > 300 m, n=8). In a group of renal patients, mobilization of EPCs was related to the degree of exercise capacity, suggesting a possible connection with the cardiovascular risk in low performance populations limited by chronic diseases.

Aged↗

PubMed2002

Quantification and localization of expression of the retinoic acid receptor-beta and -gamma mRNA isoforms during neurulation in mouse embryos with or without spina bifida.

BACKGROUND: Previous studies observed that retinoic acid receptor-gamma (RARgamma) is expressed in the open caudal neuroepithelium but that RARbeta is expressed in the closed neural tube. Furthermore, retinoic acid (RA) induces RARbeta expression, a molecular event associated with neural tube closure, but treatment with RA at the appropriate gestation time causes failure of neural tube closure. Since there are four isoforms of RARbeta, perhaps the isoforms expressed in the closed neural tube and induced by RA are different. To investigate the hypothesis that the switch from RARgamma to RARbeta is mechanistically linked to neural tube closure, this study determined the concentrations and distributions of RARbeta and RARgamma isoforms in mouse embryos with RA-induced neural tube defects and in splotch (Sp) mutant embryos with spina bifida. METHODS: Absolute concentrations of RARbeta and RARgamma isoforms were determined throughout primary neurulation (gestational day 8.5-10.0) in treated or untreated C57BL/6J mouse whole embryos by ribonuclease protection analysis. Treatment consisted of an oral dose of 100 mg/kg of all-trans-RA on gestational day 8.5. Spatial distributions of RARbeta and RARgamma were examined in RA-treated and Sp mutant embryos by in situ hybridization. RESULTS: RARbeta2, gamma1, and gamma2 were expressed in untreated embryos and were induced 4.5-, 1.6-, and 4.0-fold, respectively, 4 hr after treatment with RA. In embryos with RA-induced spina bifida, RARbeta2 was expressed in the closed neural tube while RARgamma1 and RARgamma2 were expressed in the open caudal neuroepithelium. In splotch mice with spina bifida, the boundary between RARbeta and RARgamma did not correspond to the site of neural tube closure. CONCLUSIONS: In RA-treated embryos, the relationship between RARbeta expression in the closed and RARgamma in the open caudal neuroepithelium was not altered. However, in splotch embryos with spina bifida, the juncture between RARbeta and RARgamma expression remained in the same anatomical position in the neuroepithelium irrespective of the neural tube closure status and suggests that the switch from RARgamma to RARbeta expression in the closing caudal neuroepithelium may not be causally linked to neural tube closure in the splotch mutant.

Animals↗

PubMed1995

Quantification of the variation due to laboratory and physiologic sources in CD4 lymphocyte counts of clinically stable HIV-infected individuals.

We have conducted a study to quantify the amount of variation in the CD4 lymphocyte counts of HIV-infected individuals due to laboratory and physiological factors. Thirty HIV-infected male volunteers had blood drawn on six occasions: three times in each of 2 weeks, 4 weeks apart. Two tubes of blood were drawn at each visit, and duplicate measurements were obtained from one of the tubes of blood. Differences between duplicate measurements from a single tube of blood and between CD4 counts obtained from two tubes of blood drawn on the same day were attributed to laboratory factors. Differences between CD4 counts obtained on different days were attributed to a combination of laboratory factors and physiologic factors, which included the effects of exercise, tobacco, and the consumption of alcohol and caffeine. The mean absolute CD4 count at the first visit was 450 (range 86-1,081). The short-term coefficient of variation of CD4 count was 13.7 (95% CI: 12.9, 14.6). Physiologic and laboratory factors accounted for 85% and 15% of the variation in CD4 counts, respectively. Variation in the absolute white blood cell count, lymphocyte percentage, and CD4 percentage accounted fo 52%, 29%, and 19% of the physiologic variation in CD4 counts, respectively. Our results confirm a high degree of short-term variability of CD4 counts among HIV-infected individuals, which can be largely attributed to physiological factors. This variability can be minimized more effectively by repeating CD4 counts over time than by repeating measurements at a single visit.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2006

Isobaric tags for relative and absolute quantitation (iTRAQ) reproducibility: Implication of multiple injections.

We analyzed 10 isobaric tags for relative and absolute quantitation (iTRAQ) experiments using three different model organisms across the domains of life: Saccharomyces cerevisiae KAY446, Sulfolobussolfataricus P2, and Synechocystis sp. PCC6803. A double database search strategy was employed to minimize the rate of false positives to less than 3% for all organisms. The reliability of proteins with single-peptide identification was also assessed using the search strategy, coupled with multiple analyses of samples into LC-MS/MS. The outcomes of the three LC-MS/MS analyses provided higher proteome coverage with an average increment in total proteins identified of 6%, 33%, and 50% found in S. cerevisiae, S. solfataricus, and Synechocystis sp., respectively. The iTRAQ quantification values were found to be highly reproducible across the injections, with an average coefficient of variation (CV) of 0.09 (scattering from 0.14 to 0.04) calculated based on log mean average ratio for all three organisms. Hence, we recommend multiple analyses of iTRAQ samples for greater proteome coverage and precise quantification.

Amino Acid Sequence↗

PubMed1996

Ambulatory blood pressure monitoring: quantification of the early morning rise in blood pressure in normal case and in patients with symptoms of orthostatic dysregulation.

Though various parameters can be evaluated in ambulatory blood pressure monitoring, there is still a lack of reliable parameters for exact quantification of the early morning rise. Noninvasive ambulatory blood pressure monitoring (Space Labs 90207) was performed in 50 normotensive persons and in 52 patients with symptoms of orthostatic dysregulation. Twenty-two of the 52 patients showed normal and 19 showed sympathicotonic reactions in the orthostatic test by Thulesius. After smoothing the 24-h blood pressure profiles by Fourier analysis, the derivative was calculated from the profiles (differentiation) and the following parameters were determined: the beginning and the length of the early morning rise as well as time and point of the maximum rise. The maximum rise was compared to the difference between the nocturnal trough and the morning peak (absolute value) as well as to the percentage rise, where we found significant statistic correlations. Patients with sympathicotonic orthostatic dysregulation showed in comparison to the 50 normotensive persons a significantly lower (p < 0.05) maximum rise in blood pressure. Thus, Fourier analysis of 24-h blood pressure profiles allows determination of reliable parameters of the early morning rise in blood pressure and can be used for more precise differential diagnosis in patients with orthostatic dysregulation.

Adult↗

PubMed1987

Quantification of the mechanical properties of noncontracting canine myocardium under simultaneous biaxial loading.

Detailed understanding of cardiac mechanics depends upon accurate and complete characterization of the three-dimensional properties of both normal and diseased myocardial tissue. This, however, can only be obtained by performing multiaxial tests on cardiac tissue. In this study we subjected thin sheets of passive canine left ventricular myocardium to various combinations of simultaneous biaxial stretching. During each stretch the ratio of the orthogonal strains was kept constant and the corresponding stresses remained proportional. We fitted the biaxial stress-strain data both with exponential strain-energy functions with quadratic powers of strains as well as with an alternative function with nonintegral powers of strains. We used our recently developed nonparametric method to assess the reliability of the coefficients for each of these functions. The quadratic strain-energy functions resulted in wide intra- and interspecimen variability in the coefficients. Moreover, both their absolute and relative values demonstrated marked load history dependence such that interpretation of the direction of anisotropy was difficult. Fitting the data with the alternative nonintegral strain-energy function seemed to alleviate these problems. This alternative strain-energy function may provide more self-consistent results than the more commonly used quadratic strain-energy functions.

Animals↗

PubMed2002

Detection of single molecules: solution-phase single-molecule fluorescence correlation spectroscopy as an ultrasensitive, rapid and reliable system for immunological investigation.

More sensitive techniques in molecular and clinical immunology are essential for the development of reproducible profiles. We have developed a novel methodology named solution-phase single-molecule fluorescence correlation spectroscopy (SPSM-FCS) that fulfils these demands. It is based on the quantification of the probability density of single molecule events in solution is necessary. For example, the Brownian motion of the fluorophore rhodamine-green is detected. Counting about 100,000 photon counts per second and per molecule permits the identification of one single compound. In order to study the applicability of SPSM-FCS in immunology, we have detected and identified a larger nonfluorescent substance in a very complex mixture. The 'unknown' molecules studied were the autoantibodies in serum samples directed against the antigen alpha 3 chain of type IV collagen. In both systems, we were able to characterize the probability density of single fluorescent molecules by means of the averaged absolute molecule number without any calibration. The specific molecules exhibited a Poisson distribution in solution in terms of their 'critical' bulk concentration below about 1 nM. This proof of principle indicates how the SPSM-FCS methodology could be used in immunoassays.

Animals↗

PubMed1991

3 beta-Hydroxysteroid dehydrogenase activity in glandular and extraglandular human fetal tissues.

The expression of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) in steroidogenic tissues is an absolute requirement for mammalian reproduction, fetal growth, and life maintenance. We sought to identify extraglandular tissue sites in the human fetus where 3 beta HSD is expressed. To this effect, we conducted in vitro studies by use of homogenates prepared from second trimester fetal tissues. To facilitate the determination of 3 beta HSD activity, an abbreviated technique was developed that consisted in the use of [3 alpha-3H]dehydroepiandrosterone [( 3 alpha-3H]DHEA) as the substrate and NAD+ as the cofactor. With these reagents, the enzymatic reaction leads to the production of both nonradiolabeled androstenedione and NAD3H in equimolar amounts, and the radioactivity associated with NAD3H is used for quantification of 3 beta HSD activity. The kinetic isotope effect introduced by substitution of tritium for hydrogen at the C-3 alpha position of DHEA, determined with six different tissues, was 2.5 +/- 0.7 (mean +/- SD). The specific activities of the enzyme in peripheral tissues and ovary were relatively low, in the range of 0.03 nmol/mg protein.h for stomach (n = 2) to 0.18 +/- 0.14 nmol/mg protein.h for liver (mean +/- SD; n = 13), while in fetal testis and placenta the specific activities were relatively high, viz. 3.4 +/- 0.7 nmol/mg protein.h (mean +/- SD; n = 4) and 2.8 +/- 1.8 nmol/mg protein.h (mean +/- SD; n = 13), respectively. The findings of this study serve to demonstrate that 3 beta HSD is distributed widely among tissues of the human fetus. Although the enzymatic activity was easily demonstrated in peripheral tissues by the use of radiolabeled DHEA as the substrate, 3 beta HSD protein was not readily detected by Western analysis.

3-Hydroxysteroid Dehydrogenases↗

PubMed1998

Quantification of Atherosclerotic Burden in the Descending Aorta by Transesophageal Echocardiography: Inter- and Intraobserver Variability.

Atherosclerotic plaques had been imaged but not quantitated in the thoracic aorta using transesophageal echocardiography. The aim of this study was to describe a method for measuring the atherosclerotic plaque area in the descending aorta by transesophageal echocardiography (TEE) and to evaluate its reproducibility. TEE examinations were performed by two independent sonographers, in 21 patients with angiographically proven coronary artery disease. Two hundred fifty-six transverse segments (mean 12 +/- 3 patient) of the descending aorta were adequately recorded. In each segment the plaque and the lumen areas in the half of the aortic segment distant from the transesophageal probe were measured by one reader in the two studies (intersonographer reproducibility). Interreader reproducibility was also evaluated. The correlation coefficient between the first and second study (intersonographer reproducibility) was 0.81. The standard deviation of the difference between examinations equaled 0.137 cm(2) and the mean absolute difference between examinations was 0.003 cm(2) (95% CI: -0.015; 0.021; P = 0.75). The correlation coefficient between the two readers was 0.86, the standard deviation of the difference between readers was 0.175 cm(2) and the mean absolute difference was 0.006 cm(2) (95% CI: -0.029; 0.018; P = 0.63). A method for quantitative measurement of aortic atherosclerotic plaque area was evaluated and found to have high intersonographer and intereader reproducibilities. This method might be used in the future for noninvasive evaluation of regression or progression of aortic atherosclerosis.

Journal Article↗

PubMed1988

Rat heterotopic heart transplantation: quantification and analysis of cell mediated cytotoxicity.

Limiting dilution analysis was used to measure the frequency of PVG-reactive cytotoxic T lymphocytes (CTL) within the peripheral blood mononuclear cell population of Lewis rats before heterotopic transplantation of PVG rat derived cardiac tissue, and in both the blood and graft-infiltrating cell populations at daily time points afterwards. Before surgery, the frequency of PVG-reactive cells within the blood was between 1/31,700 and 1/50,300; however, this value increased rapidly on day 4 after transplantation to reach values of up to 1/1,100 by day 7. The frequency of these cells was first measurable in the graft-infiltrate on day 2 and also showed a rapid increase 4 days after surgery; peak values up to 1/4,800 were recorded on day 5. This time corresponded with that of functional cardiac rejection and maximum infiltration of the graft by mononuclear cells. The similar kinetic changes and absolute values recorded for the frequency of donor-reactive CTL within the blood and graft-derived cell populations was indicative of a rapid bi-directional passage of cells between these pools and provided no evidence for specific sequestration of CTL by the graft. Cells purified from the graft on post-operative day 5 mediated an immediate specific cytotoxicity towards PVG target cells (44% lysis during a 4 h assay at an effector:target ratio of 100:1) which was of a higher activity than would be predicted on the basis of an effector population containing only 1/4,800 PVG-reactive CTL. This finding implies that other mononuclear cell types than CTL present within the graft-infiltrating population were capable of mediating target cells lysis.

Animals↗

PubMed2005

Ability of the Hershberger assay protocol to detect thyroid function modulators.

In vivo screening methods for detection of thyroid function modulators are now under development in many research laboratories. We assessed the applicability of the Hershberger assay protocol to screen for thyroid function modulators. In experiment 1, castrated male BrlHan WIST@Jcl (GALAS) rats were administered a potent thyroid peroxidase inhibitor, 3-amino-1,2,4-triazole (AT), in doses of 0, 40, 200, and 1,000 mg/kg/day with gravimetric endpoint, and in experiment 2, castrated and intact male rats were administered in doses of 0, 40, and 200 mg/kg/day, with quantification of the extent of hypertrophy of the thyroid epithelium, to assess the effects of castration, by gavage to 8-week-old for 10 consecutive days. At necropsy of both experiments, the thyroid glands and hypophysis were collected and fixed with 10% neutral-buffered formalin. To avoid crushing during weighing because of their fragility, the thyroid glands and hypophysis were weighed approximately 24 h after fixation with 10% neutral-buffered formalin. All animals were sacrificed approximately 24 h after the final dose. In experiment 2, the thyroid glands of all animals were stained with hematoxylin and eosin for histological examination and morphometry of follicular epithelial height. In experiment 1, absolute and relative thyroid weights in all of the AT groups were statistically increased in a dose-dependent manner, regardless of the testosterone propionate (TP)-injection. In experiment 2, the results showed a significant increase in thyroid weight in the 200 mg/kg groups of both castrated and intact rats. Hypophyseal weight was unaltered by AT, but comparison of vehicle-treated groups showed that the hypophyseal weight of the castrated rats was greater than that of the intact rats. Enlarged thyroid glands were observed in the AT-treated rats at necropsy. Histological examination of the thyroid glands of all the AT-treated animals showed hypertrophy and hyperplasia of the follicular epithelial cells, and the height of follicular epithelium of the thyroid glands increased in a dose-dependent manner in both the castrated and intact rats. In experiment 1, assessment of the (anti-) androgenic action of AT in seminal vesicle weight revealed a significant increase in the 200 and 1,000 mg/kg + TP groups in a dose-dependent manner. These results suggest that the effect of AT can be detected by the Hershberger assay 10-day administration protocol and may be useful for screening for thyroid function modulators regardless of whether the animals have been castrated.

Amitrole↗

PubMed2005

Determination of boswellic acids in brain and plasma by high-performance liquid chromatography/tandem mass spectrometry.

Peritumoral edema, one of the major causes for neurological disorders in brain tumor patients, is mainly treated with steroids, which unfortunately have significant side effects and interfere with the efficacy of chemotherapy. Boswellic acids, the main active ingredients of Boswellia serrata, are antiinflammatory agents, inhibiting 5-lipoxygenase, the key enzyme of leukotriene biosynthesis and one of the pathophysiological mechanisms of peritumoral edema. Based on positive results in clinical trials and animal studies, B. serrata resin dry extract was designated an orphan drug by the European Commission for the treatment of peritumoral edema resulting from brain tumors. Thus boswellic acids may be alternative drugs to corticosteroids. However, the question of the availability of boswellic acids in brain has not been addressed until now. Accordingly, a highly sensitive LC/MS method has been developed for the simultaneous determination of KBA and AKBA, the most potent boswellic acids, in plasma and brain. This method involves matrix-assisted liquid-liquid extraction on Extrelut NT followed by separation on reversed-phase high-performance liquid chromatography and tandem mass spectrometry detection using atmospheric pressure chemical ionization. Excellent linearity was obtained for the entire calibration range from 5 to 1500 ng/mL KBA and AKBA in plasma and 5 to 1000 ng/mL KBA and AKBA in brain. Validation assays of the lower limit of quantification as well as for the intra- and interday precision and accuracy met the international acceptance criteria for bioanalytical method validation. Moreover, the interchangeability of calibration curves generated in pork and rat brain homogenates could be demonstrated. Using the developed analytical method, KBA and AKBA could be detected for the first time in brain up to a concentration of 99 and 95 ng/g of brain, respectively, 3 h after the single oral administration of 240 mg/kg of dry B. serrata resin extract to Wistar rats. The developed method represents an appropriate tool to further study the time-dependent distribution of KBA and AKBA in plasma and brain as well as the absolute brain concentration after multiple doses and contributes thus to the optimization of the dosage regimen and to a better understanding of the therapeutic effects of B. serrata.

Animals↗

PubMed1990

Improved quantification of in vivo 1H NMR spectra by optimization of signal acquisition and processing and by incorporation of prior knowledge into the spectral fitting.

Quantification of localized in vivo brain 1H spectra is in general very difficult due to excessive spectral overlap. In addition, intensity distortions may result from the effects of the NMR pulse sequence on the spins. This paper describes an approach to solving these problems. It comprises optimization of the pulse sequence; correction of the experimental lineshape; determination of intensity distortions, of relative line positions, and of linewidths using model solutions; and incorporation of the thus obtained prior knowledge into a nonlinear least-squares spectral fitting procedure. This approach resulted in greatly improved accuracy, precision, and reliability of the quantitation of our in vivo spectra of rat brain, and enabled us to estimate absolute metabolite concentrations.

Animals↗

PubMed2001

Estimation of autonomic response based on individually determined time axis.

The analysis of the time-dependence of autonomic response requires: 1. A reliable procedure for the quantification of autonomic activity under nonsteady conditions, such as an algorithm for time-frequency decomposition (ex. SDA. Wigner-Ville, or others). 2. The choice of an adequate time scale for focusing on the data: (a) the regular, universal time scale, independent of the unsteady physiological conditions, or (b) a time axis defined by specific events related to an applied perturbation, as the indicators of specific experimental or physiological conditions, so that each individual is considered according to his own intrinsic time scale. The alignment of the various subjects according to their intrinsic time scale, reflecting their individual response mechanisms, may help to disclose a common pattern of autonomic function. Using an absolute time scale to align and average results for different subjects may obscure the underlying mechanisms. Several examples of autonomic challenges are presented, in which the use of an individual time scale contributes to unveil a typical response pattern: tilt test in vasovagal syncope, the autonomic effect of active standing on hypertension, and the autonomic response to acute hypoxia.

Autonomic Nervous System↗

PubMed1995

Snake F(ab')2 antivenom from hyperimmunized horse: pharmacokinetics following intravenous and intramuscular administrations in rabbits.

PURPOSE: The pharmacokinetics of a currently available horse F(ab')2 antivenoms to Vipera aspis, V. ammodytes, and V. berus (Ipser Europe) and a new more purified and pasteurized preparation (SAV) was investigated in the rabbit. METHODS: An immunoradiometric assay using an affinity-purified goat IgG horse F(ab')2 specific and the same IgG labelled with iodine 125 as a tracer was developed. The limit of quantification in plasma was 0.032 microgram/ml. Specificity study showed that mouse F(ab')2 and Fab did not cross-react. RESULTS: Pharmacokinetic analysis showed that the plasma F(ab')2 concentration followed a biexponential decline after intravenous bolus administration with distribution and elimination half-lives of 2.66 +/- 0.18 hrs and 49.69 +/- 4.13 hrs, respectively. The total volume of distribution (Vdss or Vd beta) was between 209 and 265 ml.kg-1 and was similar to the volume of the extracellular fluid in the rabbit (300 ml.kg-1). Total body clearance ranged from 3.33 to 3.96 ml.h-1.kg-1. After intramuscular administration which was only investigated with SAV, Tmax was 48 hrs and the absolute bioavailability was 42%. CONCLUSIONS: No difference in pharmacokinetics was observed between the two antivenom preparations following the intravenous administration. In contrast, a reduced rate and extent of absorption was shown following intramuscular administration.

Animals↗

PubMed1992

Gas chromatographic analysis of nicotine and cotinine in hair.

Non-invasive validation of cigarette- or cigar-smoking behaviour is necessary for large population studies. Urine or saliva samples can be used for confirmation of recent nicotine intake by analysis of cotinine, the major metabolite of nicotine. However, this test is not suitable for validation of survey data, since the quantification of cotinine in saliva only reflects nicotine exposure during the preceding week. To validate information on tobacco use, we investigated hair samples for quantifying nicotine and cotinine by gas chromatography-mass spectrometry. Hair (about 50-100 mg) was incubated in 1 M sodium hydroxide at 100 degrees C for 10 min. After cooling, samples were extracted by diethyl ether, using ketamine as an internal standard. Drugs were separated on a 12-m BP-5 capillary column, and detected using selected-ion monitoring (m/z 84, 98 and 180 for nicotine, cotinine and ketamine, respectively). Hair from non-smokers and smokers contained nicotine and cotinine. Although it is difficult to determine an absolute cut-off concentration, more than 2 ng of nicotine per milligram of hair can be used to differentiate smokers from non-smokers. Some applications of this technique are developed to determine the status of passive smokers, the gestational exposure in babies and the pattern of an individual's nicotine use by cutting strands of hair into sections of one-month intervals.

Adolescent↗

PubMed2006

Simple liquid chromatography-tandem mass spectrometry method for determination of novel anti-methicillin-resistant Staphylococcus aureus fluoroquinolone WCK 771 in human serum.

A simple, rapid, specific, precise, accurate and sensitive method for determination of WCK 771 in human serum has been developed. The method uses high performance liquid chromatography with tandem mass spectrometric detection. Sample preparation involves protein precipitation method by addition of acetonitrile. Gatifloxacin was used as internal standard. The response was found to be linear from 0.312 to 40 microg/ml of serum with correlation coefficient greater than 0.99. Limit of detection and lower limit of quantification for WCK 771 was found to be 0.078 microg/ml and 0.312 microg/ml, respectively. The intra-day precision and accuracy from analysis of quality control (QC) samples at four concentrations was in the range of 2.36-2.58% and from 96.71 to 103.2%, respectively. The inter-day precision and accuracy from analysis of quality control samples at four concentrations was in the range of 3.14-6.82% and from 96.84 to 105.76%, respectively. WCK 771 was found to be stable for 24 h at auto-injector environment. WCK 771 was also found to be stable for 2h in serum at 25+/-3 degrees C and for 3 months at -20 degrees C. Mean absolute recovery at four different concentrations was 86.92% with standard deviation of 1.79. Throughput of the method is approximately one sample every 4 min. The method was also reproduced with monkey serum. The method was employed for estimation of drug serum levels during pre-clinical and clinical trials.

Animals↗

PubMed1996

Three-dimensional correction for spillover and recovery of myocardial PET images.

UNLABELLED: PET permits the quantification of myocardial blood flow, but is hampered by the limited spatial resolution of PET images. METHODS: We evaluated two methods for the correction of resolution effects in PET perfusion 13NH3-ammonia images. In one model, the spillover and recovery coefficients are estimated in the kinetic modeling analysis. The new, second model uses an explicit delineation of the left ventricular wall and a convolution model for the system point spread function to compute the regional values of the spillover and recovery coefficients. RESULTS: The new method is validated with phantom measurements. The two methods are evaluated on animal experiments using 13NH3-ammonia. Both two- and three- compartment models were used to compute absolute flow values. Excellent linear correlations with microsphere data were obtained. The slope of the regression line was lower for corrections based on kinetic modeling as compared to convolution-based correction. In animal experiments, recovery coefficients of 59% for the myocardial wall and 86% for the blood pool were obtained. Spillover from the blood pool into the myocardial was was 14%. CONCLUSION: The new correction method strongly suppresses spillover and recovery effects due to limited resolution.

Algorithms↗