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Biomedical subjects

W Lindner

Publications and source records attributed to W Lindner.

At least 109 records · Page 6Linked to original sources

[Analysis of residues of the fungicide cymoxanil in grapes using multicolumn HPLC].

Residues of the contact fungicide Cymoxanil in grapes were determined by a multidimensional multicolumn high pressure liquid chromatography technique (MC-HPLC). The sample pretreatment is a simple water extraction. Further clean-up and trace enrichment of an aliquot of the aqueous acidic sample solution is performed on-line via an automatized microprocessor controlled MC-HPLC system. In the range of 0.05-2.0 mg/kg grapes good linearity is achieved. Recoveries of Cymoxanil added to untreated grapes range between 70% and 80% at 0.05 and 2.0 mg/kg values, respectively, with a reproductibility of s +/- 3% at 0.2 mg/kg (n = 5). The total time for analysis is approximately 30 min.

Acetamides↗

HPLC--residue analysis of the herbicide pyridate in cereals.

For many reasons residue analysis of plant protecting chemicals is becoming of increasing importance. The demand of modern trace analysis techniques is to detect significantly and sensitively values down to levels in the ppb range or even less. Aggravating circumstances are the complex multicomponent sample matrices out of whom the residue analysis has to be performed; theoretically thousands of compounds could be present and interferences with substances of interest are quite likely. One way to get around these difficulties is to employ multidimensional HPLC (MD-HPLC). A method using this invaluable analytical tool tracing Pyridate and its main metabolites in various plant extracts is presented. Based on a brief discussion about requirements of modern trace analysis HPLC in connection with column switching we designed an automatizable setup combining a weak anionexchanger (dimethylamine phase) with a reversed phase system handling relatively large aqueous sample volumes. Depending on specifically described sample pretreatment schemes detection limits down to 30 ppb are routinely obtained. At this level acceptable on-line UV-spectra can be obtained via inserting a spectrophotometric detector in a loop of a 6-port valve. The usefulness of the method described has been demonstrated by analysing several hundred samples.

Chromatography, High Pressure Liquid↗

[Studies on the clinical application of peritoneography (author's transl)].

Peritoneography is the radiological presentation of the peritoneal cavity or a part of it. In 20 patients a water-soluble contrast medium (Urovison for infusion 30%, 500 ml) was injected after addition of indifferent infusion solutions, or the contrast medium was mixed with the ascitic fluid remaining in the cavity after abdominal puncture of patients with ascites. In all 20 patients the diaphragm and the liver or its right lobe, in 16 patients (50%) the spleen, in 8 patients (40%) the right kidney and in 5 patients (25%) the fundus of the gall bladder could be defined. The filling of hernial sacs, outlining extraluminal tumors and the subphrenic space are considered to be the most important clinical indications for this simple and harmless method investigation.

Adult↗

Partition high-pressure liquid-chromatographic systems for the separation of digitalis glycosides of the cardenolide group.

Several multi-component liquid-systems have been investigated on silica gel SI-60 supports of particle size 10 mum. By using two solvent systems, it was possible to separate 14 digitalis glycosides, ranging from genins of relatively low polarity to the highly polar deacetyl-lanatosides. Solvents with good ultraviolet transparency at 220 nm (lambdamax. for the butenolide ring) were chosen in order to improve the sensitivity of detection. The technique should also permit the determination of by-products and degradation products of these drug substances. Detection limits are as low as 15 ng for a 5 mul injection, and separation times vary between 4 and 20 min. The reproducibility of the retention times and the baseline separations attainable make the systems suitable for quantitative work.

Cardanolides↗

Combined ultraviolet-fluorescence detection in high-pressure liquid chromatography of pharmaceuticals.

The use of combined UV-fluorescence detection for the evaluation of incompletely resolved compounds and trace components in the presence of large quantities of major components is described, analysis for thioridazine and some of its oxidation products by high-pressure liquid chromatography being chosen as a practical example. Mesoridazine and the ring oxide of thioridazine have been determined quantitatively with relative standard deviations (n = 6) of 2.0 and 3.6%, respectively, at concentrations below 0.1 mug per injection. Resolution of the two components is difficult and, in this instance, unnecessary. By a similar approach, it was possible to determine the highly fluoresecent sulforidazine at a concentration of 0.4% of the thioridazine with 6.2 mug of thioridazine injected. A relative standard deviation of 5% was attainable at this concentration. Fluorescence detection limits for mesoridazine and sulforidazine at a signal-to-noise ratio of 4:1 are between 5 and 10 ng per injection; this corresponds to about 0.1% of the active substance for the above example.

Chromatography, High Pressure Liquid↗

The liquid chromatographic properties of phenothiazines.

The high-pressure liquid chromatographic behaviour of different groups of phenothiazines (drug substances) has been investigated on 10-mu m silica gel particles. Variation of the ammonia concentration between 0.5 and 1.5% in an isopropanol-diisopropyl ether (15:85) mixture permits the adjustment of the solvent system to fit the different basicities of the various groups of interest. While the capacity factors (k') for pairs of compounds in two homologous oxidation series vary considerably owing to differences in basicity, there is reasonably good agreement between the relative retention (alphs) values. This fact can be utilized in order to identify phenothiazine homologues of series that have not previously been studied. Elutropic diagrams in connection with alpha values can be used to predict the chromatographic behaviour of new groups of phenothiazines.

Chromatography↗

[Hypoglycemia - aglycemia in virus hepatitis (author's transl)].

In a 64-year old woman with a histologically confirmed Au-SH antigen negative acute virus hepatitis with an otherwise normal course, an extreme hypoglycemia lasting four days developed in the florid stage, and was treated with intravenous glucose drips. In spite of the supply of 130 g/24 hrs glucose on the 2nd day of hypoglycemia, the fasting blood sugar level next morning was 0 mg% ("aglycemia"). The hypoglycemia ran a course without autonomic or psychoneurological symptoms. As the hepatitis regressed, the carbohydrate metabolic disorder regained its equilibrium. It is assumed that this was a hepatogenic hypoglycemia. This may have reduced the glycogen reserves in the liver, also partly as a result of minimal diet, disturbed the gluconeogenesis and glycolysis and slowed the breakdown of insulin.

Alanine Transaminase↗

Enantioselective bioanalysis of beta-blocking agents: focus on atenolol, betaxolol, carvedilol, metoprolol, pindolol, propranolol and sotalol.

The recent developments in enantioselective HPLC-separation techniques are impressive and are driven by industrial and academic interests; thus there is for instance a high demand for developing stereoselective assays for chiral drugs in biological fluids. The beta-blocking agents, which possess an amino-propanol- or -ethanol side chain with at least one chiral centre, represent one of the most intensively investigated groups of more than 40 drugs introduced world wide. Seven of the most popular beta-blockers were chosen as representatives: atenolol; betaxolol; carvedilol; metoprolol; pindolol; propranolol; and sotalol, these span the whole range of lipophilicity to hydrophilicity (polarity). Enantioselective HPLC bioassays for these beta-blockers published so far, including techniques based on chiral derivatizing agents (CDAs), chiral stationary phases (CSPs) and chiral mobile phase additives (CMPAs) have been reviewed and documented in the light of general aspects together with pharmacokinetic and pharmacodynamic considerations.

Adrenergic beta-Antagonists↗

Stereoselective electrophysiological effects of propafenone in Langendorff perfused guinea pig hearts.

The present study was focused on the stereoselective electrophysiological effects of (R)- and (S)-propafenone.HCl evaluated in isolated Langendorff perfused guinea pig hearts. Conduction intervals were measured using an ECG-recording method of high resolution. Refractory periods of the different parts of the myocardium were determined by stimulation with premature stimuli, as well as by stimulation with increasing pacing rate (rate-dependent/refractory periods). Drug concentrations of 0.1, 1 and 3 microM were tested. Both compounds induced a dose-dependent increase in AV-nodal, His-bundle, and intraventricular conduction time which reached significance (p less than 0.01) following 3 microM of either compound. Sinus rate was also dose-dependently and significantly reduced. (R)- and (S)-propafenone.HCl induced a marked prolongation of the rate-dependent refractory period of sino-atrial (by 140 +/- 22%, p less than 0.01 and by 141 +/- 14%, p less than 0.01, respectively) and AV-nodal (by 34 +/- 22%, p less than 0.01 and by 42 +/- 15%, p less than 0.01, respectively) conduction and of the atrial (by 182 +/- 21%, p less than 0.01 and by 195 +/- 15%, p less than 0.01, respectively) and ventricular (by 93 +/- 16%, p less than 0.01 and by 88 +/- 16%, p less than 0.01, respectively) myocardium. The effective refractory periods evaluated by stimulation with premature stimuli were also significantly prolonged under the influence of (R)- and (S)-propafenone.HCl, except the ventricular myocardial refractoriness by (R)-propafenone.HCl (increase to 114 +/- 23%, n.s.). Both compounds showed a strong rate-dependence of their effects and, thus, the refractory periods evaluated by stimulation with increasing pacing rate were significantly more prolonged than the refractory periods evaluated by stimulation with premature stimuli. The main difference between the effects of (R)- and (S)-propafenone.HCl on the cardiac electrical activity is the lack of effect of (R)-propafenone.HCl on the ventricular myocardial refractoriness evaluated by stimulation with premature stimuli.

Animals↗

The effects of the propranolol enantiomers on the intracardiac electrophysiological activities of Langendorff perfused hearts.

The optical isomers of the beta blocking agent propranolol exert beta receptor blocking as well as membrane stabilizing effects. The latter is thought to be responsible for the antiarrhythmic effect of the drug. In this study we quantified the electrophysiological effects of both isomers of propranolol on the conduction and pacemaker system of the heart. The experiments were performed on isolated hearts using a special ECG recording and stimulation technique. To abolish isoproterenol's beta adrenergic stimulatory effect on heart rate, 30-times higher concentrations of (+)propranolol were necessary than of (-)propranolol in order to be consistent. Both isomers caused a similar and marked slowing of conduction velocity through the bundle of His and ventricular myocardium. Also, heart rate, as well as atrio-ventricular conduction velocity were significantly slowed by a concentration of 10 microM of either drug, (-)propranolol being slightly more effective. Only in the presence of (-)propranolol did significant changes of atrio-ventricular and His-bundle conduction occur at a concentration of 1 microM. During programmed stimulation sinus node recovery time was more prolonged by (-)propranolol than during perfusion with (+)propranolol. The highest rate of pacing with 1:1 conduction of the sino-atrial conduction, the atrial and ventricular myocardium was significantly depressed to a comparable degree by either isomers of propranolol. These effects appear to be primarily responsible for the antiarrhythmic effects of both isomers. Because of the minor effects of (+)propranolol on sinus- and AV-node activity, as well as on beta adrenergic receptors, this isomer may have potential clinical importance in the treatment of arrhythmias.

Animals↗

Evaluation of six chiral stationary phases in LC for their selectivity towards drug enantiomers.

Six chiral stationary phases (CSP) were evaluated for their enantioselectivity towards a series of 45 drugs with different acidic, basic or neutral properties. These CSPs were: a polyacrylamide phase, Chiraspher; two polysaccharide-based phases, cellulose tris-3,5-dimethyl phenylcarbamate (Chiralcel OD) and the S-naphthylethylcarbamate derivative of beta-cyclodextrin (SN-beta-CD; Cyclobond I SN); and three protein-based CSPs--alpha 1-acid glycoprotein (Chiral-AGP), ovomucoid (OVM) and cellulase. A total of 28 different mobile phases were involved. Chiral-AGP, OVM and Chiralcel OD appeared to be the most promising CSPs for the enantio separation of the series of structurally different compounds evaluated. Cellulase and Chiralcel OD show particularly high enantioselectivity towards the group of beta-blocker drugs. The different protein-based CSPs were used in their usual reversed-phase mode. The other phases were used in combination with apolar mobile phases, except for SN-beta-CD, which was evaluated in both modes. Formal optimization strategies were not adopted, although the effect of organic modifier and eluent pH on enantioselectivity was briefly examined for the protein-based phases.

Adrenergic beta-Antagonists↗