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Biomedical subjects

R Preuss

Publications and source records attributed to R Preuss.

At least 19 recordsLinked to original sources

Di(2-ethylhexyl)phthalate (DEHP): human metabolism and internal exposure-- an update and latest results.

Di(2-ethylhexyl)phthalate (DEHP) is a reproductive and developmental toxicant in animals and a suspected endocrine modulator in humans. There is widespread exposure to DEHP in the general population. Patients can be additionally exposed through DEHP-containing medical devices. Toxicokinetic and metabolic knowledge on DEHP in humans is vital not only for the toxicological evaluation of DEHP but also for exposure assessments based on human biomonitoring data. Secondary oxidized DEHP metabolites like mono-(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl)phthalate (5oxo-MEHP), mono-(2-ethyl-5-carboxypentyl)phthalate (5cx-MEPP) and mono-[2-(carboxymethyl)hexyl]phthalate (2cx-MMHP) are most valuable biomarkers of DEHP exposure. They represent the major share of DEHP metabolites excreted in urine (about 70% for these four oxidized metabolites vs. about 6% for MEHP); they are immune to external contamination and possibly the ultimate developmental toxicants. Long half-times of elimination make 5cx-MEPP and 2cx-MMHP excellent parameters to measure the time-weighted body burden to DEHP. 5OH-MEHP and 5oxo-MEHP more reflect the short-term exposure. We calculated the daily DEHP intake for the general population (n = 85) and for children (n = 254). Children were significantly higher exposed to DEHP than adults. Exposures at the 95th percentile (21 and 25 microg/kg/day, respectively) scooped out limit values like the Reference Dose (RfD, 20 microg/kg/day) and the Tolerable Daily Intake (TDI, 20-48 microg/kg/day) to a considerable degree. Up to 20-fold oversteppings for some children give cause for concern. We also detected significant DEHP exposures for voluntary platelet donors (n = 12, 38 microg/kg/apheresis, dual-needle technique). Premature neonates (n = 45) were exposed to DEHP up to 100 times above the limit values depending on the intensity of medical care (median: 42 microg/kg/day; 95th percentile: 1,780 microg/kg/day).

Biomarkers↗

Genotoxic risk assessment in white blood cells of occupationally exposed workers before and after alteration of the polycyclic aromatic hydrocarbon (PAH) profile in the production material: comparison with PAH air and urinary metabolite levels.

OBJECTIVE: Workers in various industries can be exposed to polycyclic aromatic hydrocarbons (PAHs). The relationship between biomarkers of genotoxic risk, PAH compounds in air (ambient monitoring) and PAH metabolites in urine (internal exposure) were studied in 17 workers exposed to PAHs in a fireproof-material producing plant before and 3 months after the PAH profile was altered in the binding pitch. METHODS: Two biomarkers of exposure, specific DNA adducts of (+/-)-r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) and non-specific DNA adduct of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) were determined in white blood cells (WBCs). In addition, DNA strand breaks were analysed in lymphocytes by single-cell gel electrophoresis in a genotoxic risk assessment. Sixteen PAH compounds in air were determined by personal air sampling, and hydroxylated metabolites of phenanthrene, pyrene and naphthalene were determined in urine. RESULTS: After substitution of the binding pitch the concentrations of benzo[a]pyrene in air decreased (P<0.01). No changes could be observed for pyrene, while levels of phenanthrene (P=0.0013) and naphthalene (P=0.0346) in air increased. Consequently, median DNA adduct rates of anti-BPDE decreased after alteration of the production material (from 0.9 to <0.5 adducts/10(8) nucleotides). No changes in the excretion of 1-hydroxypyrene in urine could be determined, whereas increased levels of 1-, 2+9-, 3- and 4-hydroxyphenanthrene (P<0.0001) and 1-naphthol and 2-naphthol (P=0.0072) were found in urine. In addition, a statistically significant increase in DNA strand break frequencies (P<0.01) and elevated 8-oxodGuo adduct levels (P=0.7819, not statistically significant) were found in the WBCs of exposed workers 3 months after the PAH profile in the binding pitch had been altered. CONCLUSION: The results presented here show that the increased concentration of naphthalene and/or phenanthrene in the air at the work place could induce the formation of DNA strand breaks and alkali-labile sites in WBCs of exposed workers.

Adult↗

A simple method to estimate force plate inertial components in a moving surface.

Support surface perturbations are a common paradigm for the study of balance and postural control. Forces and moments acquired from force plates mounted on, or within, the moving surface will contain components resulting from the inertia of the force plate itself. These force plate inertial components must be removed in order to accurately estimate forces resulting from contact with the force plate. This is particularly important when these contact forces are to be used in further calculations, such as an inverse dynamics analysis of joint kinetics. An estimate of the FPIC can be derived using the kinematics of the moving surface and the inertial properties of the force plate. This technique allowed for a reduction of up to 85% of the peak and integrated FPIC acquired from AMTI (OR6-7) force plates during translations of 0.1m, and surface rotations of 10 degrees, using a ramp stimulus of 150 ms duration.

Biomechanical Phenomena↗

Decomposition of multicomponent mass spectra using Bayesian probability theory.

We present a method for the decomposition of the mass spectra of mixed gases using Bayesian probability theory. The method works without any calibration measurement and therefore applies also to the analysis of spectra containing unstable species. For the example of mixtures of three different hydrocarbon gases the algorithm provides concentrations and cracking coefficients of each mixture component and also their confidence intervals. The amount of information needed to obtain reliable results and its relation to the accuracy of our analysis are discussed.

Journal Article↗

Design and synthesis of inhibitors of adenosine and AMP deaminases.

Nucleosides and nucleotides which are able to undergo covalent hydration in the aglycone ring system are potential inhibitors of the enzymes adenosine deaminase (ADA) and AMP deaminase, respectively. Calculations of the enthalpy of covalent hydration and of enzyme binding energy have been used to design new inhibitors of ADA. The ribosyl triazolotriazine 16, which was synthesized as a result of these calculations, exists predominantly as the covalent hydrate 18 in water and is a potent inhibitor of mammalian ADA (IC(50) 50 nM).

AMP Deaminase↗

Analysis of multicomponent mass spectra applying Bayesian probability theory.

In this paper we develop a method for the decomposition of mass spectra of gas mixtures, together with the relevant calibration measurements. The method is based on Bayesian probability theory. Given a set of spectra, the algorithm returns the relative concentrations and the associated margin of confidence for each component of the mixture. In addition to the concentrations, such a data set enables the derivation of improved values of the cracking coefficients of all contributing species, even for those components for which the set does not contain a calibration measurement. This latter feature also allows one to analyze mixtures that contain radicals in addition to stable molecules. As an example, we analyze and discuss the mass spectra obtained from the pyrolysis of azomethane, which contain the radical CH3 apart from nitrogen and C1- and C2-hydrocarbons.

Azo Compounds↗

Probing RNA-protein interactions using pyrene-labeled oligodeoxynucleotides: Qbeta replicase efficiently binds small RNAs by recognizing pyrimidine residues.

Binding of small RNAs by the RNA-dependent RNA polymerase of coliphage Qbeta was studied utilizing a fluorometric assay. A DNA oligonucleotide probe of sequence 5'-d(TTTTTCC) was 5'-end-labeled with pyrene. In this construct, the proximal thymine residues efficiently quench the fluorophore emission in solution. Upon stoichiometric binding of one probe per polymerase molecule, the pyrene steady-state fluorescence increases by two orders of magnitude, the fluorescence anisotropy increases, and a long fluorescence lifetime component of 140 ns appears. With addition of replicable RNA, steady-state fluorescence decreases in a concentration dependent manner and the long lifetime component is lost. This observation most likely reflects displacement of the pyrene-labeled probe from the proposed nucleic acid binding site II of Qbeta replicase. The effect was utilized to access binding affinities of different RNAs to this site in a reverse titration assay format. In 10 mM sodium phosphate (pH 7.0), 100 mM NaCl, at 16 degrees C, equilibrium dissociation constants for different template midi- and minivariant RNAs were calculated to be in the nanomolar range. In general, the minus and plus strands, concomitantly synthesized by Qbeta replicase during replication, exhibited discriminative affinities, while their hybrid bound less efficiently than either of the single strands. Different non-replicable tRNAs also bound to the polymerase with comparable dissociation constants. By titration with DNA homo-oligonucleotides it was shown that the probed site on Qbeta replicase does not require a 2' hydroxyl group for binding nucleic acids, but recognizes pyrimidine residues. Its interaction with thymine is lost in an A.T base-pair, while that with cytosine is retained after Watson-Crick base-pairing. These findings can explain the affinities of RNA-Qbeta replicase interactions reported here and in earlier investigations. The sensitivity of the described fluorometric assay allows detection of RNA amplification by Qbeta replicase in real-time.

Base Sequence↗

Secondary hyperparathyroidism and depression in chronic renal failure.

UNLABELLED: This study was aimed at examining the relation between secondary hyperparathyroidism (sHPT) and depressive syndromes in chronic renal failure (CRF). SAMPLE AND METHODS: 59 chronic CRF patients and 16 depressive patients without CRF were included. Parathyroid hormone (PTH), calcium and phosphate as well as psychopathology were measured. RESULTS: Depressive CRF patients with cognitive disorders show higher levels of PTH than less or not depressive subjects. With respect to the literature, our results give reason to assume that sHPT may play a pathogenetic role in those depressive syndromes which are additionally characterized by cognitive disorders.

Adult↗

[alpha 2-macroglobulin in urine. Significance for differential diagnosis of rejection and infections after kidney transplantation].

The value of measuring the urinary concentration of alpha 2-macroglobulin in addition to that of C-reactive protein (CRP) was assessed in a prospective study of 78 consecutive patients (29 women, 49 men; mean age 48.7 [19-75] years) after renal transplantation. alpha 2-Macroglobulin was never demonstrated in urine when the course was normal (n = 38), cytomegalovirus infection had occurred (n = 26) or acute cyclosporin nephrotoxicity (n = 5) or glomerular disease in the transplant (n = 10). CRP was present in only a few such cases. Interstitial rejections (n = 26) always led to urinary alpha 2-macroglobulin and CRP excretion without haematuria, while in vascular rejection (n = 3) the haemoglobin test was also positive. Urinary infection (n = 20) and urosepticaemia (n = 6) always brought about the urinary excretion of alpha 2-macroglobulin and CRP, as well as a usually highly positive haemoglobin test. alpha 2-Macroglobulin was absent but CRP always present in extrarenal bacterial infections (n = 30). Postrenal blood admixture was always characterized by a positive haemoglobin test and alpha 2-macroglobulin in urine, while in most cases (83%) CRP was absent. --These results indicate that the constellation "alpha 2-macroglobulin negative/CRP positive" is a pathognomonic for extrarenal bacterial infection (sensitivity 100%, specificity 98.9%). The presence of alpha 2-macroglobulin alone makes postrenal blood admixture probable. If both proteins are present in the urine, rejection and urogenital bacterial infection must be excluded by further tests.

Adult↗

[C-reactive protein in the urine. The differential diagnosis of renal functional disorders following kidney transplantation].

A prospective study was undertaken in 73 patients (24 women, 49 men; mean age 47.9 [21-64] years) after renal transplantation to discover whether the presence of C-reactive protein in urine (CRPu) and its serum concentration (CRPs) are of value in the differential diagnosis of abnormal function in the transplanted kidney. CRPu concentration was measured with a highly sensitive immunoluminometric assay (minimal threshold value 6 micrograms/l). CRPu was demonstrated in 36 histologically proven rejection episodes and 21 bacterial infections proven by culture. In contrast, no CRPu was demonstrated when the course was normal and in individual cases of cyclosporin renal toxicity, as well as in 27 of 34 cases of cytomegalovirus infection. In addition, the CRPs to CRPu ratio was a sensitive means of distinguishing between rejection (CRPs/CRPu less than 1) and bacterial infection (CRPs/CRPu greater than 1). Determining CRPu concentration thus proved to be useful in the initial monitoring of renal transplantation before starting any specific urinary protein diagnosis, as well as (together with CRPs) in the diagnosis of severe posttransplantation complications.

Adult↗