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Biomedical subjects

H Liebich

Publications and source records attributed to H Liebich.

16 recordsLinked to original sources

Heparin-induced release of protein-bound solutes during hemodialysis is an in vitro artifact.

BACKGROUND: Several studies have pointed to a release of drugs or protein-bound solutes from their binding sites during heparinization. The effect is attributed to the metabolism of triglycerides to free fatty acids (FFAs), which compete with drugs for protein binding sites. This study evaluated the impact of intradialytic heparin on the free concentration of the uremic toxin p-cresol and on FFAS: METHODS: Blood samples from hemodialysis (HD) patients, before and during HD, were collected with selected anticoagulation strategies. We assessed the effects of standing time, temperature, pH, and the addition of a lipase inhibitor, tetrahydrolipstatin (THL) to blood samples on the free p-cresol concentration. p-Cresol was analyzed by HPLC with fluorescence detection. We measured FFAs by gas chromatography, and the free fractions of added valproic acid and phenytoin were evaluated by fluorescence polarization immunoassay. RESULTS: In blood samples (n = 22) not submitted to a specific treatment, free p-cresol increased from 9.9 +/- 5.1 to 31.9 +/- 22.3 micromol/L after 30 min of heparin HD (P < 0.001) and correlated significantly with FFAs (r = 0.80; P = 0.002; n = 12). There was no increase in free p-cresol during heparin-free HD (n = 6) and trisodium citrate HD (n = 9). In addition, p-cresol in ultrafiltrates (n = 3) did not correspond to the free p-cresol in heparinized blood, suggesting that the increase in free p-cresol was artifactual. The release of p-cresol in the test tube was enhanced by standing time (n = 6), sample temperature (n = 6), and alkaline pH (n = 6). Inhibition of lipase activity with THL prevented the increase of FFAs (n = 6) and the release of free p-cresol during HD (n = 22). These results were corroborated by the study of the free fraction of valproic acid (n = 6) and phenytoin (n = 6). CONCLUSIONS: The free concentrations of protein-bound solutes in plasma of heparinized patients are influenced by external factors that alter the lipase activity in the test tube. The free fraction does not increase during HD when lipase activity is neutralized at the time of blood sampling, so that previously reported increases are probably artifacts.

Aged↗

Two approaches for determining the urinary excretion patterns of nucleosides--HPLC and CE.

Cancer patients excrete in their urine increased amounts of modified purines and pyrimidines. These modified mucleosides are primary constituents of RNA and are synthesized at the macromolecular level. When RNA is catabolized, most of these modified nucleosides cannot be reutilized; consequently, they are excreted. Due to their increased urinary excretion in conjunction with altered RNA turnover in carcinogenesis, they have been proposed as tumour markers. We developed both reversed-phase high performance liquid chromatographic and capillary electrophoretic approaches to determine normal and modified nucleosides in urine. Data obtained with CE are in good accordance with those from HPLC. The reference excretion levels of urinary nucleosides from healthy volunteers were established, and elevated ones of modified nucleosides from 34 patients with different kinds of cancer were observed. The developed methods are suitable for the analysis of large series of samples for clinical studies.

Biomarkers, Tumor↗

High prevalence of bone disorders after gastrectomy.

BACKGROUND: Studies indicate that gastrectomy might alter calcium and bone metabolism, resulting in bone disorders. No data are currently available on the prevalence of bone disorders after gastrectomy. METHODS: Sixty gastrectomy patients were investigated for serum parameters of calcium and bone metabolism 5 to 20 years postoperatively and compared to an age- and sex-matched healthy control population. Forty patients agreed to a radiological investigation of the spine by anterior-posterior and lateral radiographs of the thoracic and lumbar spine and by computed tomography (CT) osteodensitometry. RESULTS: Serum calcium and 25-(OH)-vitamin D were decreased in gastrectomized patients, while parathyroid hormone and 1,25-(OH)2-vitamin D were increased. Serum parameters of calcium metabolism were altered in as many as 68% of patients. We found 31 vertebral fractures in 13 patients, 30 grade 2 vertebral deformities in 18 patients, and osteopenia in 15 patients, corresponding to a prevalence of 33%, 45%, and 37% in gastrectomized patients, respectively. The overall rate of gastrectomy patients having vertebral fractures and/or osteopenia was 55%. The risk of having a vertebral deformity was increased by more than sixfold after gastrectomy. Our study is the first report evaluating vertebral deformities in gastrectomized patients, and the largest series of gastrectomized patients investigated by CT osteodensitometry. CONCLUSION: We found a high prevalence of bone disorders in gastrectomized patients, possibly resulting from disorders in calcium metabolism. Postgastrectomy bone disease might derive from a calcium deficit, which increases calcium release from bone and impairs calcification of newly build bone matrix.

Absorptiometry, Photon↗

Hydroxyalkenal formation induced by advanced glycosylation of low density lipoprotein.

Advanced glycosylation end products (AGEs) have been identified to be present on both the apolipoprotein and lipid components of low density lipoprotein (LDL) and to act to prevent its recognition and uptake by high affinity, tissue LDL receptors. Lipid-linked AGEs form readily in vitro by the covalent addition of glucose to the amine-containing head groups of phospholipids. This process is accompanied by oxidation of the unsaturated fatty acid side chains and occurs in the absence of exogenously added transition metals or free radical generating systems, suggesting that AGE formation may contribute significantly to lipid oxidation in vivo. To assess more precisely the chemical basis of AGE-induced oxidative modification, we performed gas chromatography-mass spectrometry analysis of the lipid products which form over time during LDL-advanced glycosylation in vitro. Negative ion chemical ionization mass spectroscopy of two major compounds that were identified were consistent with the structures of the fatty acid oxidation products 4-hydroxyhexenal and 4-hydroxynonenal. These data support the concept that AGE formation in close proximity to unsaturated fatty acyl groups leads to lipid oxidation and provide additional evidence that advanced glycosylation is an important pathogenic modification of the LDL particle in vivo.

Aldehydes↗

Capillary electrophoresis of human serum proteins and apolipoproteins.

Capillary electrophoresis (CE) analysis of human serum proteins and apolipoproteins is described and compared with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and cellulose acetate membrane electrophoresis. Under optimized CE conditions apolipoproteins I could be determined directly in the serum and quantitated with a linear correlation between peak area and concentration up to a concentration of 100 mg/dL.

Apolipoprotein A-I↗

Selected ion monitoring gas chromatography/mass spectrometry using uniformly labelled (13C)glucose for determination of glucose turnover in man.

An optimized method is described for the mass fragmentographic determination of uniformly labelled (13C)glucose in human plasma using a butylboronic acid acetate derivative, and capillary gas chromatography. The advantages of the method are the ease and speed of the derivatization procedure, the small sample size, high precision (interassay coefficient of variation 5.7%), and applicability of a relatively low-cost mass spectrometer. This method allows glucose tracer experiments to be performed in man using the bolus injection technique, necessitating analysis of many samples. The results on glucose turnover obtained in a clinical experiment were in full agreement with previously published data.

Adult↗

Mechanisms of postural ataxia after intake of alcohol.

The effect of an acute intoxication with alcohol on the stability of stance was examined in 12 healthy subjects. They drank 11 of wine within 1 h. The resulting blood alcohol concentrations ranged between 0.9 and 1.67 mg/ml. Static posturography at the end of drinking and 1 h later revealed a significant increase in body sway which was mainly due to an increase in anteroposterior sway only present with closed eyes. A comparison of the results of posturography after acute intoxication with the data of patients with permanent lesions confined to the different functional subunits of the cerebellum shows that the acute effect of alcohol largely resembles that of a chronic lesion of the cerebellar anterior lobe (the spinocerebellum).

Adult↗

Advantages in the analysis of UDP-sugars by capillary electrophoresis-comparison of the conventional HPLC method with two new capillary electrophoretic micro-procedures.

Two different capillary electrophoretic separation modes for the analysis of UDP-sugars have been tested. In comparison to the traditionally used HPLC method the micellar electrokinetic capillary chromatography (MECC) as well as the capillary zone electrophoresis (CZE) results in an improvement of the separation profile and the speed of the analysis.

Chromatography, High Pressure Liquid↗

Moderate carbon monoxide exposure during sleep: neuro- and psychophysiological effects in young and elderly people.

In order to assess age-related effects of carbon monoxide (CO) on brain wave-activity and sleep, auditory evoked potentials (AEP) were measured during sleep in 10 healthy young volunteers (20-25 years) and in a group (N = 10) of healthy elderly Ss (55-72 years) under control- and exposure-conditions in counterbalanced order. Sleep-stages were classified according to the Rechtschaffen and Kales scoring-system. In addition to electrophysiological measures memory-performance and subjective feeling (mood-scale) was assessed before and after sleep. Eight hours of CO-exposure (100 ppm) gave rise to about 8% COHb. In the group of young Ss there was a significant (p less than 0.05) increase of deep sleep (stages 3,4), and a decrease of stage REM-sleep during CO-exposure, whereas in elderly Ss similar but non-significant sleep-changes occurred. Some CO-related AEP-changes within different sleep-stages, namely shorter latencies in elderly Ss and higher amplitudes in young Ss, approached significance. Within the group of young Ss there was a tendency to more depressed mood after CO-exposure, as well as to CO-related impairment of memory consolidation; no such effects were observed in elderly Ss. The general hypothesis of more pronounced CO-susceptibility of elderly people was, therefore, not supported in this study.

Adult↗