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Biomedical subjects

A Schaefer

Publications and source records attributed to A Schaefer.

At least 19 recordsLinked to original sources
PubMed2006

Effect of ethanol on cardiac single sodium channel gating.

Alcohol in modest and higher doses has the potential to induce cardiac arrhythmias. The most famous alcohol-related arrhythmia is the "holiday heart syndrome". Furthermore, there is a clear association between excessive alcohol consumption and the risk of sudden cardiac death. However, the acute effects of ethanol on arrhythmia induction are not well understood. The effect of ethanol on single cardiac sodium channels has not been studied yet. To elucidate the effect of ethanol on human cardiac sodium channels we performed a patch clamp study in HEK-293 cells overexpressing the human cardiac sodium channel. We used HEK-293 cells overexpressing the human cardiac sodium channel (Na(1.5)). Single channel gating was investigated by the cell-attached patch clamp technique. Sodium channel currents were elicited by depolarizing pulses from -120 to -20mV for a duration of 150ms. Single channel availability, open probability and peak average current were assessed baseline and after addition of ethanol in increasing concentrations (0.50 per thousand (10.9mM), 1.00 per thousand (21.7mM), 2.00 per thousand (43.5mM) and 4.00 per thousand (87.0mM)). We found a concentration-dependent reduction of open probability which was statistically significant at 2.00 per thousand ethanol (66.5+/-14% of control). At higher concentrations (4.00 per thousand) also availability decreased to 66.5+/-11.0% of control. This resulted in a significant decrease of peak average current at 2.00 per thousand and at 4.00 per thousand ethanol (61.8+/-7.4 and 53.0+/-8.2% of control). For the first time the present study demonstrates acute inhibitory effects of ethanol on single cardiac sodium channel gating and provides one potential mechanism for the well known clinical observation that ethanol triggers supraventricular and ventricular arrhythmias.

Cell Line↗
PubMed2006

Explaining variability in the relationship between antiretroviral adherence and HIV mutation accumulation.

OBJECTIVES: Determining the relationship between antiretroviral adherence and resistance accumulation is important for the design and evaluation of adherence interventions. Our objective was to explain heterogeneity observed in this relationship. METHODS: We first conducted a systematic review to locate published reports describing the relationship between adherence and resistance. We then used a validated computer simulation to simulate the patient populations in these reports, exploring the impact of changes in individual patient characteristics (age, CD4, viral load, prior antiretroviral experience) on the shape of the adherence-resistance (A-R) curve. RESULTS: The search identified 493 titles, of which 3 contained relevant primary data and 2 had sufficient follow-up for inclusion (HOMER and REACH cohorts). When simulating HOMER, the A-R curve had a high peak with a greatly increased hazard ratio (HR) of accumulating mutations at partial compared to complete adherence (simulation, HR 2.9; HOMER, HR 2.7). When simulating REACH, the A-R curve had a shallow peak with a slightly increased hazard of accumulating mutations at partial adherence (simulation, HR 1.2; REACH, HR 1.4). This heterogeneity was primarily attributable to differences in antiretroviral experience between the cohorts. CONCLUSIONS: Our computer simulation was able to explain much of the heterogeneity in observed A-R curves.

Anti-Retroviral Agents↗
PubMed2006

Chronic L-arginine supplementation enhances endurance exercise tolerance in heart failure patients.

The purpose of the study was to determine the potential beneficial effect of six weeks oral L-arginine supplementation (LAS) on endurance exercise, an important determinant of daily-life activity in patients with chronic stable heart failure (CHF). After an initial incremental maximal exercise test, CHF patients performed an identical thirty-minute interval endurance exercise test before and after six weeks with (L-arginine group; ARG) or without LAS (control group; CTL). Hemodynamic, respiratory, and metabolic parameters were determined at rest, during exercise, and during recovery. Mean heart rate decreased throughout exercise and recovery after LAS (- 8.2 +/- 1.4 b x min(-1); p = 0.003 and - 6.7 +/- 1.6 b x min(-1); p < 0.001, respectively), systemic blood pressure and respiratory parameters remaining unchanged. Resting L-argininaemia increased from 102 +/- 11 to 181 +/- 37 micromol x l(-1) (p < 0.004) and exercise-induced peak increase in plasma lactate was blunted after LAS (4.13 +/- 0.75 vs. 3.13 +/- 0.39 mmol x l(-1); p = 0.02). No significant change was observed in the control group. In heart failure patients, six weeks oral LAS enhances endurance exercise tolerance, reducing both heart rate and circulating lactates. This suggests that chronic LAS might be useful as a therapeutic adjuvant in order to improve the patient's physical fitness.

Administration, Oral↗
PubMed2006

[Tick bites and borreliosis in children attending forest kindergarten: a challenge for prevention].

AIM: The aim of this study was to analyse the influence of preventive measures on the risk of being bitten by a tick and of suffering from borreliosis in children attending so-called 'forest kindergartens' (nurseries located in forested areas where children spend all-season full-time outdoors), compared to children attending regular kindergartens. In addition, we aimed to analyse sources of information and the risk of being bitten more than once. METHODS: 53 kindergartens (25 forest kindergartens, 28 regular kindergartens) in the state of Baden-Württemberg, Germany participated in this study and protective parental behaviour was recorded. In a prospective cohort study, the numbers of tick bites and cases of borreliosis were recorded monthly (March to October 2004) using a questionnaire. The influence of preventive measures was estimated using multivariate log-binomial regression. RESULTS: Altogether, 1707 children of 'forest kindergartens' (506 children) and regular kindergartens (1201 children) were included. Parental protective behaviour was significantly better in forest kindergartens compared to regular kindergartens. There were no substantial differences between effect estimates after stratification for parental protective behaviour. For children attending a 'forest kindergarten, the adjusted risk ratio of being tick bitten was 2.6 (3.3-3.0) which was only slightly different from the unadjusted risk, ratio. CONCLUSION: Although protective parental behaviour in 'forest kindergarten' children was significantly better compared to regular kindergarten, children in forest kindergartens are at a considerable risk of tick bites and borreliosis. Implementing effective preventive measures against borreliosis represents a public health challenge.

Borrelia↗
PubMed2005

Complete genome sequence of Vibrio fischeri: a symbiotic bacterium with pathogenic congeners.

Vibrio fischeri belongs to the Vibrionaceae, a large family of marine gamma-proteobacteria that includes several dozen species known to engage in a diversity of beneficial or pathogenic interactions with animal tissue. Among the small number of pathogenic Vibrio species that cause human diseases are Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus, the only members of the Vibrionaceae that have had their genome sequences reported. Nonpathogenic members of the genus Vibrio, including a number of beneficial symbionts, make up the majority of the Vibrionaceae, but none of these species has been similarly examined. Here we report the genome sequence of V. fischeri ES114, which enters into a mutualistic symbiosis in the light organ of the bobtail squid, Euprymna scolopes. Analysis of this sequence has revealed surprising parallels with V. cholerae and other pathogens.

Aliivibrio fischeri↗
PubMed2005

Ocular motility findings in chronic progressive external ophthalmoplegia.

AIMS: To characterise the ocular motility features of chronic progressive external opthalmoplegia by quantitative and semiquantitative means. To assess the prevalence of diplopia and the binocular adaptations to nonaligned visual axes. METHOD: We studied 25 patients with chronic progressive external ophthalmoplegia. In each case muscle biopsies were consistent with mitochondrial myopathy. All patients underwent cover test in the primary position, assessment of binocular status, and measurement of uniocular fields of fixation using the Goldmann perimeter. RESULTS: A total of 23 (92%) patients had an exo-deviation, with six (26%) of those having an associated vertical deviation: 12 patients were binocular. Of the 13 patients with a manifest deviation seven had diplopia and six had suppression. Of all paired extra-ocular muscles (EOM), 68% had symmetry of movement within 5 degrees of each other. CONCLUSION: Almost all patients had an exo-deviation. Diplopia was more common than expected. The majority of patients had symmetry of EOM limitation.

Adult↗
PubMed2004

Migration from can coatings: part 2. Identification and quantification of migrating cyclic oligoesters below 1000 Da.

Metal cans for food use can be coated with lacquers based on polyester resins. Recent research has focussed on the identification and quantification of migrants released by coatings that are potentially absorbable (below 1000 Da). The presented method describes a procedure that was optimized to hydrolyse the polyester migrants into their monomers, polyvalent acids and polyols. The polyols were identified by gas chromatography with flame ionization detection GC-FID and the acids by high-performance liquid chromatography (HPLC) coupled with an ultraviolet and an electrospray ionization-mass selective detector (HPLC-ESI-MSD/UVD), respectively. With the knowledge of the polyester monomers, it was possible--at least tentatively--to identify the main components in the migrate as cyclic oligoesters by HPLC-ESI-MSD/UVD. A cyclic oligomer, CYCLO [3IPA (isophthalic acid) 3EG (ethylene glycol)] was synthesized and characterized by infrared, nuclear magnetic resonance and mass spectrometry as well as by elementary analysis for further confirmation. To determine the amount of migrating cyclic oligoesters, the response of the migrating substances was compared using different detectors, UVD, MSD and evaporative light scattering detector (ELSD). The response of the ELSD was dependent on the molecular weight of the analytes that reduced the accuracy of this detection type. The wavelength with the same absorption coefficient for IPA and terephthalic acid (TPA) was obtained at 232 nm. The UV(232nm) response of an oligoester is proportional to the number of its IPA/TPA moieties, which was verified for several TPA/IPA esters. The amount of the migrating oligoesters was determined using an UV(232nm) calibration of a commercially available TPA ester and the number of IPA/TPA moieties molecules gained from the ESI-MSD spectra. According to this method, the amount of migrating oligoesters below 1000 Da in the 95% ethanol migrate varied from 0.1 to 0.6 mg dm(-2) (0.6-3.6 mg kg(-1) food) in the examined coatings. The determined amounts account for about 50% of the total migrate below 1000 Da.

Chromatography, Gas↗
PubMed2004

Migration from can coatings: Part 1. A size-exclusion chromatographic method for the simultaneous determination of overall migration and migrating substances below 1000 Da.

The Council of Europe Resolution on coatings suggests a limit of 10 mg dm-2 for the sum of substances migrating into food simulants from an internal can coating. The Scientific Committee on Food differentiates the migrants into the substances with a molecular weight below 1000 Da, potentially being of toxicological concern, and the less toxicologically relevant species above 1000 Da. Hitherto, the determination of overall migration was based on a gravimetric method. A new method is described for the simultaneous determination of both overall migration and the migration of substances below 1000 Da based on separation by size exclusion chromatography (SEC) followed by ultraviolet detection (UVD) and evaporative light scattering detection (ELSD). The method is suitable for all volatile extraction media and simulants recommended by the European Union. For statistical comparison of both methods, the slightly modified reference method was validated in-house and extended to an additional gravimetric measurement of the migrants below 1000 Da. For the determination of the overall migration, both methods provided similar reproducibility (validated gravimetry: standard deviation (SD) = 0.16 mg dm-2; SEC-ELSD/UVD: SD = 0.12 mg dm-2) but significantly better results were obtained by the SEC-ELSD/UVD method. For migrating substances below 1000 Da, the gravimetric determination provides a poor sensitivity (limit of detection = 0.35 mg dm-2) compared with the SEC-ELSD/UVD method (limit of detection = 0.04 mg dm-2). The new method offers a lower limit of detection and higher precision as well as being less time consuming and easier to use.

Chromatography↗
PubMed2004

Migration from can coatings: part 3. Synthesis, identification and quantification of migrating epoxy-based substances below 1000 Da.

Bisphenol A-derived glycidyl ethers as well as its reaction products with other lacquer components can migrate into the packed food from epoxy-based can coatings. A sensitive and selective method is presented using high-performance liquid chromatography coupled with ultraviolet light, fluorescence and electrospray ionization-mass selective detection for the identification and quantification of all migrants with a bisphenol A backbone and a molecular weight below 1000 Da, an estimated boundary for the absorption in the gastrointestinal tract. The identification of migrants was confirmed by microreactions of technical bisphenol A diglycidyl ether with solvents and phenols, which provided the fragmentation pattern of the mass selective detection and relative retentions of 42 different bisphenol A-related substances. It was shown by calibration of different isolated and synthesized bisphenol A derivatives that the fluorescence response relies on the amount of bisphenol A moiety in the respective molecule. Therefore, all migrating bisphenol A-related substances below 1000 Da were determined as bisphenol A diglycidyl ether equivalents using a calibration (fluorescence detection) of the commercially available bisphenol A diglycidyl ether monomer. The limit of quantification was set at 5 microg bisphenol A diglycidyl ether equivalents kg(-1) (or 0.8 microg dm(-2)). This method was validated for epoxy coatings (0.1 microg dm(-2) limit of detection and 24 microg bisphenol A-related substances below 1000 Da dm(-2) standard deviation, corresponding to 4.4% relative standard deviation). The quantification could be extended by combining the fluorescence response and structural information gained from the mass spectra, which provides more accurate results for each migrant. The calculation is based on the calibration of the bisphenol A chromophore content of the molecule. According to this method, the amount of migrating bisphenol A-related substances below 1000 Da in the acetonitrile extract (assuming a worst case) varied from about 0.4 to 0.7 mg dm(-2) in the examined coatings. The determined amounts comply with about 50% of the total migrate below 1000 Da.

Benzhydryl Compounds↗
PubMed2004

New multiple antigenic peptide-based enzyme immunoassay for detection of simian immunodeficiency virus infection in nonhuman primates and humans.

Infections with human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2, respectively) are zoonotic infections. In Africa, the potential exists for additional cross-species transmissions from at least 33 different species of simian immunodeficiency virus (SIV)-infected nonhuman primates (NHPs) through hunting and butchering of these animals for food. Here we describe a highly sensitive and specific enzyme immunoassay (EIA) with chemically modified, multiple antigenic peptides (MAPs) developed for the detection and discrimination of antibodies to SIV genetic lineages. The SIV EIA was developed by using a comprehensive array of MAPs covering two envelope gene regions from all of the SIV lineages for which env sequences were available. Assay sensitivity was evaluated by using 63 plasma or serum samples obtained from primates naturally or experimentally infected with SIVs from 10 genetic lineages. Assay specificity was determined by using 97 known SIV-negative plasma specimens from these same species. Also used in the evaluations were 369 human samples: 198 HIV seronegative, 170 HIV-1 and/or HIV-2 seropositive, and 1 from a human SIVsm infection. Overall assay sensitivity and specificity were 100% with both immunodominant region (IDR) and V3 region MAPs. Although SIV env sequences from talapoin monkeys were not available for specific MAP inclusion, 5 (100%) of 5 SIVtal-infected samples were detected through cross-reactivity with other SIV IDR MAPs used in the assay. The one human SIVsm infection was identified. In conclusion, our SIV MAP EIA proved to be highly sensitive and specific for detecting SIV infections in NHPs and humans. As shown with SIV-infected talapoin monkeys, this assay has the potential to detect previously unidentified SIV strains and should be suitable for sentinel surveillance for potential new cross-species transmissions of SIVs to humans.

Amino Acid Sequence↗
PubMed2003

Migration of lubricants from food packagings. Screening for lipid classes and quantitative estimation using normal-phase liquid chromatographic separation with evaporative light scattering detection.

A normal-phase high-performance liquid chromatography (NP-HPLC) method is introduced for the identification and quantitative estimation of 12 lipid classes (paraffin, wax esters, cholesterol esters, fatty acid methyl esters, triacyl glycerols, fatty alcohols, free fatty acids, cholesterol, 1,3-diacyl glycerols, 1,2-diacyl glycerols, monoacyl glycerols and fatty acid amide) used as lubricantsin food packaging materials. The HPLC separation is carried out on a LiChrospher Diol (100 A, 5 microm, 125 mm x 3 mm) column with gradient elution (isooctane/0.1% acetic acid in tert-butyl methyl ether) and evaporative light scattering detection (ELSD). The method has been calibrated with representatives of each class in working ranges of about 5-150 mg/l, depending on the lipid class. Intra-day variance for all representatives range from 1.9 to 5.1%, inter-day variances from 7.0 to 26.5% and the limits of detection from 0.79 to 3.65 mg/l (except for two classes). A simple sample preparation could be established for the determination of migrating lubricants obtained from packaging materials containing external or internal lubricants. Since the detector response depends on the chain length and the degree of saturation, the quantification of a lipid class with unknown composition is only semi-quantitative. The amount of migrating lubricants from an epoxy-based can coating could be estimated with 0.3 mg/dm2 and from a light weight container with 5.5 mg/dm2.

Chromatography, High Pressure Liquid↗
PubMed2003

Relative bioavailability and bioequivalence of a newly developed fixed combination sachet of acetylsalicylic acid and pseudoephedrine compared with a preliminary combination.

Acetylsalicylic acid (ASA) and pseudoephedrine (PSE) are often administered together for the treatment of symptoms of the common cold, i.e., nasal congestion, runny nose, sore throat and headache. Based on this fact we developed a fixed combination of 500 mg ASA and 30 mg PSE, the recommended doses for both drugs for treating symptoms of the common cold, as granulate to be dissolved in water for administration. The purpose of this open, randomized, three-factorial (three-treatment, three-period, six-sequence) Latin Square clinical study was to investigate the relative bioavailability of ASA and PSE as well as the establishment of bioequivalence after single administration of the fixed combination (final formulation for approval) of 500 mg ASA/30 mg PSE*HCl and the preliminary formulation of this combination. Pharmacokinetic characteristics AUC(norm) and C(max,norm) of ASA, its metabolite SA, and PSE, were determined as measure of rate and extent of absorption of the two formulations. The treatment ratios final/preliminary formulation and their corresponding 90% confidence intervals were calculated to establish bioequivalence. Additionally, descriptive statistics were calculated for the parameters t(max), t((1/2)), and mean residence time (MRT). In total, data from 18 healthy male volunteers were included in the pharmacokinetic evaluation. The primary target parameters were analyzed using an analysis of variance (ANOVA) after logarithmic transformation of the data. Confidence intervals of 90% were calculated for the geometric means of ratios using the mean square error term of the ANOVA. Bioequivalence criteria were fulfilled for AUC(norm) and C(max,norm). Geometric means of individual ratios of AUC(norm) and of C(max,norm) showed equal bioavailability of the new formulation compared with the preliminary. Furthermore, a relative bioavailability of approximately 100% of the preliminary formulation was shown for the newly developed formulation for all parameters. The parameters t(max), t((1/2)), and MRT showed comparable results for ASA, SA, and PSE, respectively, in both formulations. The supplementary evaluation for the non-normalized original parameters AUC and C(max) also revealed bioequivalence. For the newly developed formulation, the arithmetic means of the parameters AUC and C(max) for PSE were 1040.66 mg/h*l and 134.52 mg/l, for SA 142.28 mg/h*l and 30.34 mg/l, respectively. The median t(max) values were 0.67 h for PSE and 0.92 h for SA. Both treatments were safe and well tolerated.

Administration, Oral↗
PubMed2002

Comparison of anthracycline-induced death of human leukemia cells: programmed cell death versus necrosis.

We investigated the mode of cell death induced by the anthracyclines, aclarubicin, doxorubicin and daunorubicin in the human leukemia cell lines, HL60 and Jurkat. The cells were incubated with drug concentrations up to 500 nM for periods between 3 and 24 hours, followed by morphological and biochemical analyses. All three substances induced DNA fragmentation, evident as DNA laddering and appearance of cells with hypodiploid DNA content, externalization of phosphatidyl serine, activation of caspases and degradation of the apoptosis-specific endonuclease inhibitor DFF45. However, concentrations and times necessary for these effects to occur were different, aclarubicin being the quickest acting drug with a lag phase of 3 h, followed by daunorubicin with 6 h and doxorubicin with 24 h. More importantly, aclarubicin induced these effects while the cell membrane was intact, whereas doxorubicin and daunorubicin led to immediate loss of membrane integrity. Programmed cell death is characterised by preservation of membrane integrity in order to allow removal of apoptotic bodies, whereas cell rupture is an early event in necrosis. We therefore suggest that, in our experimental settings, doxorubicin- and daunorubicin-induced cell death occurs by necrosis, while aclarubicin induces programmed cell death.

Aclarubicin↗
PubMed2002

L-arginine reduces exercise-induced increase in plasma lactate and ammonia.

To investigate the effect of L-arginine supplementation (L-ARG) on physiological and metabolic changes during exercise, we determined in a double-blind study the cardiorespiratory (heart rate, oxygen consumption (VO(2)) and carbon dioxide production (VCO(2)) and the metabolic (lactate and ammonia) responses to maximal exercise after either an intravenous L-ARG hydrochloride salt or placebo load in 8 healthy subjects. Exercise-induced increases in heart rate, VO(2) and VCO(2) were not significantly different after L-ARG or placebo. By contrast, peak plasma ammonia and lactate were significantly decreased after L-ARG load (60.6 +/- 8.2 vs. 73.1 +/- 9.1 micro mol x l(-1), p < 0.01 and 7.1 +/- 0.7 vs. 8.2 +/- 1.1 mmol x l(-1), p < 0.01, for ammonia and lactate, respectively). Plasma L-citrulline increased significantly during exercise only after L-ARG load, despite a concomitant decrease in plasma L-ARG. Furthermore, a significant inverse relationship was observed between changes in lactate and L-citrulline concentrations after L-ARG load (r = -0.84, p = 0.009). These results demonstrate that intravenous L-ARG reduces significantly exercise-induced increase in plasma lactate and ammonia. Taken together, the specific L-citrulline increase and the inverse relationship observed between L-citrulline and plasma lactate after L-ARG might support that L-ARG supplementation enhances the L-arginine-nitric oxide (NO) pathway during exercise.

Adult↗