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Biomedical subjects

W Klemm

Publications and source records attributed to W Klemm.

At least 19 recordsLinked to original sources

A simple method of target preparation for the bulk analysis of powder samples by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS).

A simple and rapid procedure using a glue technique has been developed for the preparation of stable targets from powder samples for bulk analysis by LA-ICP-MS. The procedure was evaluated for the analysis of trace elements in SiC, of rare-earth elements in different types of silicate (rocks, sediments, and soils), and of Au and platinum-group elements in geological silicates. The test analysis was conducted using an IR laser in combination with a quadrupole mass spectrometer. The recommended preparation procedure offers the possibility of different types of calibration, for example application of certified reference samples in combination with prepared spiked samples on a base of a natural or synthetic matrix, or addition calibration. The resulting calibration functions are linear over a range of several decades. The trueness of the results was evaluated by use of certified reference samples. Analytical concentration ranges, detection limits, and the relative standard deviations are reported.

Journal Article↗

[Biotransformation and pharmacokinetics of AWD 26-06, 8-chloro-5,10-dihydro-5-[bis(2-hydroxyethyl)aminoacetyl]-11H-dibenzo[d, c][1,4]diazepin-11-one hydrochloride in the rat].

After p.o. administration to rats AWD 26-06 (1) is rapidly but incompletely absorbed. The relatively short distribution (t1/2 alpha = 37 min) is followed by a middle-long elimination (t1/2 beta = 14 h). The volumen of distribution do not suggest an uncommon accumulation in deep compartments. About 70% of 1 were excreted unchanged with the feces. In urine and feces 18 metabolites were identified. The structure of 10 products could be elucidated. All metabolites have changed side-chains. Furthermore, the tricyclic molecule without side-chain and a N-methyl derivative were identified. The metabolites with so far unknown structure contain the unsubstituted tricyclic moiety too.

Animals↗

[Biotransformation and pharmacokinetics of AWD 26-06, 8-chloro- 5,10-dihydro-5-[bis(2-hydroxyethyl)aminoacetyl]-11H-dibenzo[b,c] [1,4]diazepin-11-one hydrochloride, in the rat].

Following p.o. and i.v. application of the 14C-labelled AWD 26-06 (6 mg/kg b.w.) with anticholinergic activity, blood levels (-24 h) and excretion (urine, feces-72 h; bile-7 h) were studied in Wistar rats. Intestinal absorption amounted to 30% of the dose administered in water solution. Elimination half-lives in blood were 0.6 h and (after Cmax 3-4 h p.a.) 8 h. Excretion was mainly by feces (unchanged drug and biliary excreted metabolites) and to less extent by urine.

Animals↗

Relation between renal and hepatic excretion of drugs: XIII. Pharmacokinetics of new antiarrhythmic drug Bonnecor in rats with normal and impaired excretory functions.

The clearance of 14C-Bonnecor, a weak organic cation, was measured in anaesthetized rats during 6 h after administration. The drug and its labelled metabolites are excreted both via kidney and liver. The renal excretion dominates especially following high doses. After bile duct ligation the renal excretion of Bonnecor increases significantly whereas in nephrectomized rats the biliary excretion of this substance is distinctly reduced. Plasma protein binding ratios amount to 60-70%. Renal removal of Bonnecor and the formed metabolites is in part a result of glomerular filtration. Increased urinary excretion of 14C-Bonnecor-activity under conditions of forced diuresis indicates the involvement of tubular reabsorption in renal handling of the drug and its metabolites. These in vivo results could be confirmed in experiments on renal cortical slices indicating a distinct tubular transport of the drug and its metabolites. In the kidney the aerobic accumulation of Bonnecor is very effective. Surprisingly, under anaerobic incubation conditions, uptake of Bonnecor into renal tissue remains relatively high indicating a distinct binding of Bonnecor within the tubular cells. In the liver the accumulation of Bonnecor is lower compared to the kidney. Furthermore, enterohepatic circulation of Bonnecor and its metabolites was checked. In animals with intact biliary tract, renal removal of 14C-Bonnecor-activity from the organism is significantly higher than in rats with bile duct cannulation. Reinfusion of bile increased renal excretion of 14C-Bonnecor-activity additionally. Both results indicate an effective intestinal reabsorption and enterohepatic circulation of this drug.

Animals↗

[Pharmacokinetics and metabolism of 3-carbethoxyamino-5-dimethylamino-acetyl-iminodibenzyl hydrochloride (Bonnecor, AWD 19-166, GS 015) in the rat].

Excretion, blood level, distribution, and metabolite samples were studied on the rat after application of GS 015 marked by 14C. The compound is quickly and completely absorbed and metabolized from an aqueous solution. The marked substances form a broad blood level maximum, at the occasion of which a main metabolite distinguishes itself apart from the initial compound at first provable yet. The elimination half-life from the blood is 6 h. An intense influx of radioactive substance into the tissues takes place. The excretion of the marked metabolites occurs mainly renally making appear a second main metabolite. Striking sex differences are partly observed in the parameters tested.

Animals↗

[Pharmacokinetics and pharmacodynamics of 3-carbethoxyamino-5-dimethylamino-acetyl-iminodibenzyl hydrochloride (Bonnecor, AWD 19-166, GS 015) in the cat].

The antiarrhythmic action of GS 015 was studied proportionally to its plasma concentrations ascertained in parallel, using the model of the electrofibrillation of the cat's heart. Blood levels of about 1.3 micrograms/ml after i.v. injection of 2 mg/kg caused a marked short-term increase of the fibrillation threshold which then remained at the increased level for a longer period yet, observing GS 015 concentrations between 0.8 and 0.5 micrograms/ml. Individual differences existed in the height of the blood level as well as in its proportion to the effect.

Animals↗

[Pharmacokinetics and pharmacodynamics of 3-carbethoxyamino-5-dimethylamino-acetyl-iminodibenzyl hydrochloride (Bonnecor, AWD 19-166, GS 015) in the dog].

The antiarrhythmic action of GS 015 was studied in proportion to its plasma concentrations ascertained in parallel, making use of the model of the two-step coronary ligature in the conscious dog. Blood levels of 1.0 microgram/ml (2 mg/kg i.v.) or of 0.8 microgram/ml (5 mg/kg orally) brought about a complete suppression of ectopic arrhythmias. The limit concentration for this effect is about 0.5 microgram/ml.

Animals↗

Augmentation of in vitro pituitary biotransformation of testosterone due to orchidectomy and its relation to serum gonadotropins in the rat.

The biotransformation of testosterone to its metabolites by the anterior pituitary gland and the relation between the products formed and the circulating levels of LH and FSH were examined in male rats at various stages of sexual maturation. The animals were either intact controls or castrated 4 and 7 days prior to the investigation. Castration greatly increased testosterone biotransformation to its 5alpha-reduced products, but did not affect the formation of androstendione. It was concluded that castration and the eventual rise of LH-RH stimulated the 5alpha-reductase activity but not the 17beta-ol-dehydrogenase system. This is reflected in the significant relationship between the circulating gonadotropins and 5alpha-metabolites of testosterone but not androstendione.

Androstenedione↗

[Phenyketonuria associated with Rubinstein-Taybi syndrome, spondylic dysplasia, left vascular shrinking of adrenal gland (author's transl)].

Report of a 10 year old girl, who demonstrated the following diseases independent from each other: Phenylketonuria, Rubinstein-Taybi syndrome, dysplasias of the skeleton, especially dysplasia of the vertebra and finally, left-sided shrinkes adrenal gland, which caused presumably an increased production of androgens with a premature pubarche.

Abnormalities, Multiple↗

Plasma levels of 5alpha-androstane-3alpha,17beta-diol in boys during adolescent growth.

A radioimmunoassay using as antibody against testosterone-3-carboxymethyloxime-BSA is described for the measurement of androstanediol (5alpha-androstane-3alpha,17beta-diol) in human plasma. Sephadex LH 20-column chromatography was used to separate other steroids croos-reaching with the antibody from androstanediol. The sensitivity of the assay was 7 pg and the recovery of labelled androstanediol was 65.1%. The intra-assay coefficient of variation was 9.9%. The existence of 5alpha-androstane-3alpha,17beta-diol in the androstanediol fraction could be demonstrated by gas chromatography and mass spectrometry (GC-MS). Plasma concentration of this substance was measured in 53 normally developing pre-pubertal and pubertal boys and in 13 adult men. The mean concentrations significantly rose from puberty stage 1 to 2, and stage 2 to 3. Although there was no significant difference between the plasma concentrations at stages 3 and 4, an increment from stage 4 and 5 was highly significant. Levels in adult males were significantly higher than those in the stage 5 of normal puberty.

Adolescent↗

[Acute adrenal hemorrhage in newborn infants: the importance of early diagnosis (author's transl)].

Two case reports demonstrate the importance of an early diagnosis for the therapy of adrenal hemorrhage. In the first case with unilateral hemorrhage, the hemorrhage as such was of importance. In the second case with bilateral hemorrhage, the course was dominated by acute adrenal insufficiency with circulatory collapse and major salt loss. The diagnosis was supported by the typical changes in electrolyte levels as well as by radiography, and endocrinological results. With early therapy (in the first instance by surgery, and in the latter by substitution of corticosteroids), both children safely passed the critical period. In the second child ACTH administration did not, in the first phase of the disease, result in a significant rise of plasma cortisol. However, two months later there was a normal rise of the cortisol level following ACTH administration. From this observation we conclude that a favourable regeneration of the adrenal glands has resulted.

Addison Disease↗

[Speech behavior of schizophrenics. Assay of an experimental point of departure (author's transl)].

Schizophrenic subjects and a control group of healthy subjects were tested with the following three language tasks: (1) to complete interruptions in a text, (2) to compose sentences from a sample of words written on cards and (3) to associate word cards to certain concepts. Besides the correct words, so-called irrelevant words were given as distracting stimuli. The inferior performance of the acute paranoid hallucinating subjects is interpreted in the sense of disturbance of cognitive selective functions. It is assumed that the central nervous inhibition of irrelevant stimuli fails to work successfully in certain groups of schizophrenics.

Female↗