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Biomedical subjects

U Moser

Publications and source records attributed to U Moser.

At least 19 recordsLinked to original sources

A method for the estimation of femoral bone mineral density from variables of ultrasound transmission through the human femur.

Quantitative ultrasound (QUS) measurements at peripheral sites can be used to estimate osteoporotic fracture risk. However, measurements at these sites are less suitable to predict bone mineral density (BMD) or fracture risk at the central skeleton. We investigated whether direct QUS measurements at the femur would allow to estimate dual X-ray absorptiometry (DXA) BMD of the total proximal femur with errors comparable to established DXA accuracy errors. Two independent sets of femora were measured in Kiel (6 f, 4 m, age: 55-90) and Paris (19 f, 20 m age: 45-95) using different benchtop systems in the two laboratories. The femora were scanned in transverse transmission mode using focused US transducers of 500 kHz center frequency. The QUS values were averaged over a region similar to the total hip region of dual X-ray absorptiometry (DXA) measurements. BMD was measured using DXA. SOS and BMD correlated significantly (p<0.0001) in both data sets (R2=0.81-0.93). Correlations between BUA and BMD were also significant at p<0.001, but correlation coefficients were lower (R2=0.61-0.75). Residual errors for the estimation of BMD were 8%-10% for SOS as predictor, and 14%-16% for BUA as predictor. The residual error of 8 to 10% for the estimation of BMD from SOS is comparable to variabilities among different DXA femur subregions and accuracy errors of femoral DXA measurements caused by the impact of soft tissue. It is substantially smaller than the errors of 13% for the estimation of total femur BMD from spine BMD, 14% for the estimation of total femur BMD from calcaneus SOS or 16% for the estimation of ash weight from DXA. The results of the study show that SOS is able to predict total BMD with adequate accuracy. If femoral BMD could be obtained in vivo with comparable accuracy, femoral QUS would be suited for the assessment of bone status at one of the main osteoporotic fracture sites.

Absorptiometry, Photon↗

Optimal prediction of bone mineral density with ultrasonic measurements in excised human femur.

Bone mineral density (BMD) measured with dual energy X-ray absorptiometry (DXA) techniques is the current gold standard for osteoporotic fracture risk prediction. Quantitative ultrasound (QUS) techniques in transmission measurements are, however, increasingly recognized as an alternative approach. It is feasible to select different QUS methods, one type being optimized to assess microarchitectural properties of bone structure and another to assess BMD. Broadband ultrasonic attenuation (BUA) and ultrasonic velocity (UV) measured on the proximal human femur have been shown to be both significantly correlated with BMD. However, a great diversity of algorithms has been reported to measure the time-of-flight used to derive UV values. The purpose of this study was to determine which procedure results in the optimal BMD prediction at the proximal femur from ultrasound measurements. Thirty-eight excised human femurs were measured in transmission with a pair of focused 0.5-MHz central frequency transducers. Two-dimensional scans were performed and radiofrequency (RF) signals were recorded digitally at each scan position. BUA was estimated and eight different signal processing techniques were performed to estimate UV. For each signal-processing technique UV was compared to BMD. We show that the best prediction of BMD was obtained with signal-processing techniques taking into account only the first part of the transmitted signal (r2BMD-SOS = 0.86). Moreover, we show that a linear multiple regression using both BUA and speed of sound (SOS) and applied to site-matched regions of interest improved the accuracy of BMD predictions (r2BMD-SOS/BUA = 0.95). Our results demonstrate that selecting specific signal-processing methods for QUS variables allows optimal assessment of BMD. Correlation is sufficiently high that this specific QUS method can be considered as a good surrogate of BMD.

Absorptiometry, Photon↗

[Safety aspects of folic acid for the general population].

Periconceptional use of folic acid reduces the risk of neural tube defects considerably. In Switzerland, implementation of these findings could be improved through fortification of a staple food with folic acid. The present paper reviews possible hazards associated with high intake of folic acid in the general population. Among the potential safety issues are interaction between folic acid and zinc, interaction between folic acid and drugs (phenytoin, methotrexate etc.) and hypersensitivity to folic acid. Of main concern are adverse effects of folic acid in cobalamin deficiency. Solutions are discussed.

Adult↗

Folate and the risk of colorectal, breast and cervix cancer: the epidemiological evidence.

It is only recently that folate deficiency has been implicated in the development of cancer. The mechanisms by which folate might protect against cancer are not clear but may relate to its role in DNA methylation and DNA synthesis. All case-control, cohort and intervention trials reported in English, French, or German, on folate intake or blood levels in relation to the risk of colorectal, breast, and cervix cancer were reviewed. Twenty case-control, and 12 nested case-control or cohort studies were identified. The epidemiological studies consistently show an inverse association between intake and/or levels of folate and the frequency of colorectal carcinomas, and less clearly of adenomas. Long-term use of supplements of folate seems to be of greater benefit than dietary intake. The effect of folate seems to be modulated by alcohol, methionine, and MTHFR polymorphisms. Results from animal studies suggest that folate supplementation might decrease or increase cancer risk depending on dosage and timing. Recent studies also suggest an inverse association between folate intake and breast cancer among women who regularly consume alcohol. Conversely, epidemiological evidence remains uncertain for the role of folate in cervical cancer prevention; the results of two intervention trials on rates of cervical intraepithelial neoplasia regression or progression were negative. An effect of folate later in carcinogenesis is not supported by the few (nested) case-control studies on invasive cervical cancer. Some of the conflicting results may be due to the fact that dietary intake or blood levels of folate do not accurately reflect folate concentrations in the cells of cancer origin. Furthermore, only a few studies have taken into account the modulating effect of alcohol, methionine, and MTHFR polymorphisms in their analyses. The observed inverse associations between folate and risk of cancer, on the other hand, may be confounded by various factors, especially by other potentially protective constituents in fruits and vegetables. Ongoing intervention studies can strengthen evidence for causality by excluding such confounding, but the optimal dose, duration, and stage of carcinogenesis and the appropriate (genetically predisposed) study group for folate chemoprevention are not yet defined.

Breast Neoplasms↗

No significant effects of lutein, lycopene or beta-carotene supplementation on biological markers of oxidative stress and LDL oxidizability in healthy adult subjects.

OBJECTIVE: The objective of this study was to determine the effect of individual carotenoid supplementation on biochemical indices of oxidative status in apparently healthy adult males. METHODS: The study was a placebo controlled single blind study. Healthy male volunteers (n= 175) were assigned to four groups. They received daily supplements of beta-carotene (15 mg), lutein (15 mg), lycopene (15 mg) and placebo for three months. The effects of the supplementation on antioxidant status were monitored by plasma carotenoid, vitamin C and A levels, glutathione (GSH and GSSG) concentrations, protein SH groups. erythrocyte antioxidant enzyme activities (Cu-Zn SOD, Se-GSH-Px) and susceptibility of LDL to copper-induced oxidation. RESULTS: beta-carotene, lycopene and lutein supplementation led to significant plasma and LDL increases in each of these carotenoids, without modifications of other carotenoid levels in plasma or in LDL. The supplementation failed to enhance the resistance of LDL to oxidation or to modify the LDL polyunsaturated/ saturated fatty acid ratio. Vitamin C, GSH, protein SH groups and antioxidant metalloenzyme activities were also unchanged. CONCLUSION: We did not observe beneficial or adverse effects of lutein, lycopene or beta-carotene supplementation on biomarkers of oxidative stress. In apparently healthy subjects, carotenoid supplementation does not lead to significantly measurable improvement in antioxidant defenses.

Adult↗

Determination of polychlorinated dibenzo-p-dioxins and dibenzo-furans in solid residues from wood combustion by HRGC/HRMS.

PCDD/PCDF were determined in solid samples from wood combustion. The samples included grate ashes, bottom ashes, furnace ashes as well as fly and cyclone ashes. The solid waste samples were classified into bottom and fly ash from native wood and bottom and fly ash from waste wood. For each of the four classes concentration distribution patterns from individual congeners, the sums of PCDD/PCDF and the international toxicity equivalents (I-TEQ) values are given. The I-TEQ levels of fly ash from waste wood burning can be approximately up to two thousand times higher than the values from fly ashes of natural wood. The I-TEQ levels in bottom ashes from waste wood combustion systems are as low as the corresponding ashes from the combustion of native wood. Grate ash samples from waste wood combustion systems with low carbon burnout show high levels of PCDD/PCDF.

Benzofurans↗

Vitamin C concentrations in plasma as a function of intake: a meta-analysis.

The purpose of this study was to estimate the intake-plasma relationship for vitamin C by means of a meta-analysis. A MEDLINE search revealed 30 publications matching our inclusion criteria. We completed the set with 5 older papers and with one monograph. The proposed statistical model corrects for inconsistencies with regard to methodological differences between the various studies. Therefore, the contribution of a particular study to the estimation is independent of the number of data points. The estimations were performed for the complete data set as well as for different subgroups: "adult" aged 15-65 years, "elderly" aged 60-96 years, "nonsmokers" and "smokers". The 50th percentile of the plasma concentration for a daily vitamin C intake of 60 mg was 42.4 mumol/L. The corresponding values for the different subgroups were: "adult" 44.1 mumol/L, "elderly" 31.0 mumol/L, "nonsmokers" 42.4 mumol/L, and "smokers" 33.6 mumol/L. Thus, this meta-analysis confirms earlier results that the requirements of vitamin C is higher in "elderly" and "smokers" compared to "adult" and "nonsmokers" and it can be used for the estimation of the vitamin C intake in order to achieve a desired plasma level within a target population. In the general population the assumed optimal plasma concentration of 50 mumol/L, as proposed by a consensus conference, can be achieved by the intake of 100 mg per day, which is the new recommendation of the Austrian, German, and Swiss Nutrition Societies.

Adolescent↗

Muscarinic properties of compounds related to arecaidine propargyl ester.

A series of new analogues of the arecaidine propargyl ester (CAS 35516-99-5), APE, 1a) with alcohols consisting of 4 or 5 carbon atoms were investigated at muscarinic receptor subtypes. The muscarinic activity of the quaternary and tertiary salts of the APE-related compounds were assayed on the isolated guinea-pig ileum (M3 receptor subtype) and guinea-pig left atria (M2 receptor subtype) as well as on rabbit isolated vas deferens (M1 receptor subtype). The structural variations made in the APE molecule, replacing the triple bond in the ester side chain with structures such as double bond, an allene moiety, a single bond, a cyclopropyl group or two triple bonds should alter the selectivity and potency in favour of the M2 subtype. Enhanced, though modest, selectivity for M2 receptors was achieved with the 2-butynyl ester 2a. The other structural variations resulted in a loss of potency, but not necessarily of efficacy.

Animals↗

Flow-cytometric investigation of cellular metabolism during oxidative stress and the effect of tocopherol.

Many studies and scientific publications report on potentially beneficial effects of the lipophilic anti-oxidant vitamin E on cellular metabolic pathways. The present work presents data on the influence of tocopherol on different intracellular parameters of intact and living human skin fibroblasts by flow-cytometric measurements. The parameters analysed were the intracellular pH, representing cell metabolism and cell function, intracellular glutathione, representing one of the cell's own radical scavenger enzyme systems, membrane potential and cell viability. In order to cause large numbers of free radicals cells were UVB-irradiated prior to measurement. The results of the flow-cytometric measurements indicate that vitamin E has significant protecting effects on the measured biochemical parameters during oxidative stress. In the presence of the lipophilic radical scavenger a significant stabilizing effect on pH, intracellular glutathione levels and membrane potential could be observed. Furthermore, vitamin E administration was associated with increased cell viability after UVB irradiation.

Antioxidants↗

Attenuation of the near-infrared and red photoplethysmographic signal by different depth of tissues.

Photoplethysmography enables non-invasive investigation of the volume pulse in the microvasculature of patients. We previously have shown that time-discrete analysis enables identification of highly reproducible characteristics of the volume pulse in absolute values. The method would be of particular interest, if the perfusion of deeper tissue layers like the skeletal muscle can be assessed. The aim of the current study was to investigate the attenuation of the photoplethysmographic signal by different tissues and up to which depth of tissue a time-discrete analysis of the photoplethysmographic signal would be possible. For the recordings we used the time-discrete near-infra-red photoplethysmography (NIRP), a reflection photoplethysmograph measuring at wavelengths of 840 nm and 640 nm. In an in vitro circuit filled with bovine blood we generated a typical and exactly reproducible volume pulse. On a platform the NIRP sensor probe was placed above the artificial vessel and recordings of the volume pulse were obtained by varying the sensor-vessel-distance with increasing layers of water, blood-agar or bovine skeletal muscle tissue. - The amplitude of the NIR signal was attenuated to 50% by each layer of 2.01 mm of water, 1.42 mm of blood-agar and 1.05 mm of bovine skeletal muscle tissue. A time-discrete analysis could be performed up to a depth of 15 mm of water, 6 mm of blood-agar and 5 mm of bovine skeletal muscle tissue. - As the photoplethysmographic curve is strongly attenuated even by a few millimetres of water we suggest that the NIRP signal mirrors the perfusion of the superficial tissue layer and mainly originates from the subpapillary capacious plexus. - We conclude that with the equipment used in this study volume pulsations in deeper layers of tissue like skeletal musculature can not be assessed.

Agar↗

Effect of vitamin E and probucol on dietary cholesterol-induced atherosclerosis in rabbits.

The preventive effect of vitamin E and Probucol against atherosclerosis in rabbits were compared. Atherosclerosis was induced by a 2% cholesterol-containing vitamin E-poor diet (5-10 ppm). Six groups of five rabbits each were studied. Group I (control) was fed on a vitamin E-poor diet. The other groups had the following supplements: group II, 50 mg/kg vitamin E i.m.; group III, 2% cholesterol; group IV, 2% cholesterol plus 50 mg/kg vitamin E i.m., group V, 2% cholesterol plus 1% Probucol; group VI, 2% cholesterol + 1% Probucol plus 50 mg/kg vitamin E i.m. After 4 weeks, aortas were removed and analyzed by light and scanning electron microscopy for atherosclerotic lesions. Samples of the media were analyzed for protein kinase C activity. The aortas of cholesterol-fed rabbits showed typical atherosclerotic lesions, detected by microscopic examination, their media smooth muscle cells exhibited an increase in protein kinase C activity. Vitamin E fully prevented cholesterol-induced atherosclerotic lesions and the induction of protein kinase C activity. Probucol was not effective in preventing either cholesterol-induced atherosclerotic lesions or the induction of protein kinase C activity. These results show that the protective effect of vitamin E against hypercholesterolemic atherosclerosis is not produced by an other antioxidant such as Probucol, and therefore, may not be linked to the antioxidant properties of this vitamin. The effects observed at the level of smooth muscle cells ex vivo suggest an involvement of signal transduction events in the protective effect of vitamin E against atherosclerosis.

Animals↗

Quantitative colorimetric and gas chromatographic determination of arecaidine propargyl ester.

Arecaidine propargyl ester (APE) is a potent muscarinic agonist often used in pharmacological studies. To date, no sensitive quantitative analytical method for APE has been published. In this study, two methods for the quantitative determination of APE are compared: a colorimetric assay, based on the formation of the corresponding ferric(III)-hydroxamic acid complex, and a direct gas chromatographic method, using arecoline as the internal standard. The latter method was found to be more precise. The utility of the gas chromatographic assay was further demonstrated in a stability study of the drug in the biological fluid aqueous humor of rabbits.

Animals↗

Vitamin E supplementation in elderly lowers the oxidation rate of linoleic acid in LDL.

Oxidation of LDL-linoleic acid (LDL-LA), a major substrate for lipid peroxidation, may be counteracted by the antioxidant vitamin E. In a 3-month randomized double-blind placebo-controlled trial in 83 apparently healthy Dutch elderly, aged 67-85 years, the direct protective effect of 100 IU vitamin E on the rate of oxidized LDL-LA was studied. The oxidation of LDL-LA was measured by its disappearance after a 5-h in vitro Cu-oxidation of LDL isolated from 1 ml plasma. In the vitamin E group, the decrease in oxidized LDL LA of 10.4, (p < 0.05) was significantly different (p < 0.05) from the smaller 4.6% p< 0.01) decrease in the control group. Moreover, within the vitamin E group the decrease was even more marked over tertiles of alpha-tocopherol to LDL-LA ratio with a significant difference in decrease (p < 0.05) from the lowest compared to the highest tertile of, respectively, 18.4% [-24; -2%] (median and range) and 2.0% [-16: 34%]. In conclusion, supplementation with 100 IU vitamin E in elderly is beneficial in lowering the rate of oxidation of LDL LA. The protective effect of vitamin E might best be monitored by using the ratio of alpha-tocopherol to LDL-LA as this reflects the degree of alpha-tocopherol available to protect the amount of LDL-LA present.

Aged↗

Modelling of mortality data from a multi-centre study in Japan by means of Poisson regression with error in variables.

BACKGROUND: Death rates of particular categories in epidemiological studies are often based on a small number of occurrences which can be well described by a Poisson distribution. METHOD: We applied this model for the analysis of a multi-centre study in five Japanese counties where the death rates of stomach cancer (ICD-9 code 151) in four age groups are known. In our example some covariates of the cases (e.g. plasma lycopene levels) are unknown values and are estimated from a randomly chosen collective. Therefore these values are subject to a sampling error. The inclusion of errors in variables (e-i-v) into the statistical model can adequately describe such a situation. The model is estimated in a Bayesian framework by means of resampling techniques. RESULTS: Based on the posterior distribution of the parameters the relative risk of stomach cancer is 0.46 (95% confidence interval: 0.23-0.79) comparing the maximum of the population medians of lycopene with the minimum. The estimated overdispersion is close to zero indicating only minor interference with other possible explanatory variables. In addition, we show that inclusion of e-i-v can give more accurate estimates of the parameters even from small sample sizes. CONCLUSIONS: Appropriate statistical methods allow the accurate estimation of relative risks from small sample sizes and from low number of cases. Lycopene plasma levels are good predictors for stomach cancer.

Adult↗

Stabilization of rat heart mitochondria by alpha-tocopherol in rats.

alpha-Tocopherol (alpha-T) acts by different mechanisms: scavenging free oxygen radicals (FOR) and stabilizing membranes; both may contribute to the prevention of the pathogenesis of diseases like cardiovascular events. The present work shows that alpha-T breaks the vicious cycle generated by damaged mitochondria. The latter stimulate the immune system increasing FOR formation that leads to more damaged mitochondria. alpha-T inhibits lipid peroxidation induced by recombinant human tumor necrosis factor (rh-TNF). Polymorphonuclear neutrophils (PMN) are activated by TNF to produce FOR causing lipid peroxidation of cardiomyocyte membranes. Since TNF is used as a therapeutic agent against certain tumors, treating patients with alpha-T could protect them against systemic side effects of TNF.

Animals↗