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Biomedical subjects

G Engelhardt

Publications and source records attributed to G Engelhardt.

At least 55 records · Page 3Linked to original sources
PubMed1987

Extensive glomerular immaturity associated with renal tubular acidosis, nephrogenic diabetes insipidus and nephrocalcinosis.

Neonatal renal failure and glomerular immaturity have been described in 1983. The present paper describes 3 cases with the same histological features. However, follow-up of the patients during 14, 18 and 4 years, respectively, showed the following: The histologic immaturity may be followed by maturation. Thus, late maturation may be a term more suitable to designate this constellation. Renal failure may not necessarily ensue, at least not during early infancy. In the 3 cases presented in this report, the histological finding is associated with renal tubular acidosis, renal diabetes insipidus and nephrocalcinosis. The association of transient glomerular immaturity (or late glomerular maturation) and renal tubular acidosis may enhance the development of nephrocalcinosis.

Acidosis, Renal Tubular↗
PubMed1987

In vivo screening of glutathione related detoxification products in the early state of drug development.

Glutathione (GSH) adducts and consecutive degradation products thereof are indications of reactive intermediates during drug metabolism. As demonstrated with the analgesic SX-PP 16 (4-amino-3,5-dibromacetanilide), however, interactions of a drug with GSH can be detected by labelling the GSH-stores with labelled cysteine, and consecutive administration of the unlabelled drug even at therapeutic doses. The GSH-adducts are sensitively and specifically traced by HPLC, applying column-switching and a combination of diode-array- and radioactivity detection. This approach seems to be much more sensitive than a classical GSH-depletion study. The structure of the main metabolite of SX-PP 16 (46% of urinary excretion) was elucidated as 3-bromo-4-amino-5-mercapturyl-acetanilid.

Acetanilides↗
PubMed1987

Effect of corticosteroids on the toxic pulmonary oedema induced by nitrogen dioxide inhalation in the rat.

Various corticoid derivatives administered by inhalation or intraperitoneally were investigated for a preventive effect on the pulmonary oedema of the rat induced by the 30-min inhalation of 100-105 ppm NO2. After inhalational administration in the form of an aqueous aerosol, dexamethasone-21-isonicotinate showed a considerably greater efficacy than beclomethasone-17,21-dipropionate or dexamethasone-21-dihydrogen phosphate. With prophylactic intraperitoneal administration dexamethasone (free alcohol), dexamethasone-21-dihydrogen phosphate and 6 alpha-methylprednisolone-21-dihydrogen succinate had to be given in much higher doses than dexamethasone-21-isonicotinate to achieve the same effects on the toxic pulmonary oedema.

Adrenal Cortex Hormones↗
PubMed1986

Acetyl-coenzyme A: arylamine N-acetyltransferases in microorganisms: screening and isolation of an enzyme from Bacillus cereus.

The raw extracts of a series of microorganisms were screened for the presence of acetyl-coenzyme A: arylamine N-acetyltransferase (AAAT) using a radioactive assay with 3H-acetyl-coenzyme A and aniline as substrates. Enzyme activities were primarily detected in the soluble fractions of Bacillus and Nocardia species, and in some further soil organisms. Only strains of Bacillus cereus were able to acetylate 4-nitroaniline and 3,5-dimethyl-4-nitroaniline. The fermentation conditions for the production of the enzyme were optimized. The AAAT from one strain of Bacillus cereus was purified 24-fold and characterized.

Acetyl Coenzyme A↗
PubMed1985

Pharmacological properties of an extremely selective beta 1-adrenoceptor antagonist, 2-[4-[3-(tert-Butylamino)-2-hydroxypropoxy] phenyl]-3-methyl-6-methoxy-4(3H)-quinazolinone [+/-)HX-CH 44 BS).

2-[4-[3-(tert-Butylamino)-2-hydroxypropoxy] phenyl]-3-methyl-6-methoxy-4(3H)-quinazolinone (+/-)HX-CH 44 BS) is a new beta 1-selective adrenoceptor antagonist. Affinity for beta 1-adrenoceptors was determined in isolated guinea-pig papillary muscle (pA2 = 7.4), in isoprenaline-stimulated guinea-pig cardiac adenylate cyclase (pA2 = 7.3) and in receptor binding experiments with rat heart membranes (pKi = 8.0). Due to a direct relaxing action of (+/-)HX-CH 44 in smooth muscles its beta 2-affinity could only be estimated from receptor binding experiments (pKi = 5.0). (+/-)HX-CH 44 BS shows an extremely high beta 1/beta 2-affinity ratio of about 800 and therefore appears to be much more selective than atenolol or metoprolol (beta 1/beta 2 = 10-50). In contrast to propranolol or atenolol, (+/-)HX-CH 44 hardly antagonized bronchodilation induced by i.v. isoproterenol in anaesthetized guinea-pigs in vivo. Furthermore, cardiac actions of the beta 1-selective agonist norepinephrine in cats in vivo were competitively antagonized by (+/-)HX-CH 44 whereas inotropic and chronotropic effects of the non-selective beta-agonist epinephrine were not. This phenomenon may be explained by the mixed population of beta 1-and beta 2-adrenoceptors in cat heart and by the high beta 1-selectivity of (+/-)HX-CH 44.

Acetylcholine↗
PubMed1984

Structure-activity relationships in further series of amino-halogen substituted phenyl-aminoethanols.

Series of 1-(4-amino-phenyl)-2-aminoethanol derivatives having different substituents in the phenyl nucleus were compared with 1-(4-amino-3,5-dichloro-phenyl)-2-tert.-butylamino-ethanol (clenbuterol) with regard to their action on the adrenergic beta-receptors of guinea pigs, cats and rats. The exchange of the two chlorine atoms of clenbuterol led to substances with a potent beta 2-mimetic activity, surpassing that of clenbuterol, in the bronchial muscles and/or to a beta 1-blocking action in the heart with a relatively low beta 1-intrinsic activity. The strongest action was found with the chloro-cyano, fluoro-cyano and mono-cyano substituted compounds. The chloro-fluoro, bromo-fluoro, mono-fluoro and chloro-trifluoromethyl substituted compounds showed a good oral absorption, comparable to that of clenbuterol. Because of a particularly low beta 1-intrinsic activity in the heart with a long-lasting beta 2-mimetic action on the bronchial muscles also after oral administration, the 1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butylamino-ethanol hydrochloride (mabuterol) must come of all the structures investigated particularly into consideration as broncholytic agent for therapeutic use.

Adrenergic beta-Agonists↗
PubMed1984

[Animal experimental studies on the question of the interaction of paracetamol and acetylsalicylic acid].

The mutual effects of acetylsalicylic acid and paracetamol used in combination were studied in rats and mice. The antiexudative effects of acetylsalicylic acid in the edema tests on the hind paw of the rat, the antipyretic activity against yeast-fever of the rat and the analgesic effect on the inflamed hind paw of the rat was potentiated by paracetamol given simultaneously. The biosynthesis of prostaglandins in vitro by an enzyme preparation from bovine seminal vesicles was inhibited by acetylsalicylic acid and paracetamol in additive synergistic mode. The hepatotoxicity of paracetamol in mice measured by an increase of GOT in serum is antagonized by acetylsalicylic acid in dose-dependent manner. The suppression of the hepatotoxicity of paracetamol by acetylsalicylic acid in mice is not the consequence of interaction during absorption. The 3H-content of the liver following an oral dose of 3H-paracetamol is not influenced by acetylsalicylic acid given in combination with paracetamol. The mechanism of interactions between acetylsalicylic acid and paracetamol is discussed.

Acetaminophen↗
PubMed1983

Criteria for the standardization of Salmonella mutagenicity tests: results of a collaborative study. II. Studies to investigate the effect of bacterial liquid culture preparation conditions on Salmonella mutagenicity test results.

The influence of various parameters and growth conditions in the "overnight culture" of Salmonella typhimurium strains on mutagenicity test results was investigated. A number of factors were first suspected to be of some importance for the quantitative outcome of the mutagenicity test. None of them, however, was found to influence the results to such a marked extent as to be a major source of variability. Only the brand of nutrient broth used for the propagation of the bacteria proved finally to have a certain effect on the number of (spontaneous and induced) revertant colonies, although no precise and quantitative statements can be made with regard to a possible standardization of this experimental segment in the Salmonella mutagenicity test. The occurrence of such unpredictable but noticeable influences is, however, evidence for the importance of an intralaboratory optimization and standardization of all parts of the test procedure.

Animals↗
PubMed1978

[Admissable and limited extrapolation of pharmacological and toxicological results on man demonstrated on selected examples (author's transl)].

The results of comparative studies with respect to pharmacological, toxicological, pharmacokinetic and clinico-pharmacological effects of the non-steroid anti-inflammatory drugs 4-[4-(2'-fluorobiphenylyl)]-4-hydroxycrotonic acid and 3-(2'-fluoro-4-biphenylyl)-butyric acid as well as the intrinsic activities of their metabolites in vitro are discussed. The variation in gastrointestinal side effects caused by the two compounds in different species can conveniently be explained in terms of different pharmacokinetic pathways. This leads to a species dependent formation of pharmaco-dynamically active metabolites.

Animals↗
PubMed1978

[Effect of non-steroidal anti-inflammatory drugs on plasma protein binding of corticosterones (author's transl)].

A series of non-steroid antiinflammatory drugs (NSAD) as well as substances with different spectra of pharmacological action were investigated with regard to the influence on binding of corticosterone to plasma protein in rats after repeated oral administration. At pharmacologically active doses, NSAD cause a time and dose dependent increase in rat plasma of the corticosterone fraction which can be ultra-filtrated. The effect on corticosterone binding to plasma protein largely parallels the antiinflammatory efficacy of the NSAD. This does not occur by a mere displacement of corticosterone from the plasma protein binding, but is apparently the consequence of a qualitative and/or quantitative change of the binding proteins. Organic acids, cytostatic or other drugs which strongly bind to plasma protein do not show any corresponding influence on the corticosterone binding to plasma protein under comparable conditions. The increase of the fraction of corticosterone which can be ultra-filtrated effected by the NSAD accelerates the excretion of corticosterone into the bile of rats. The phenomenon of decrease in binding of corticosteroids to plasma protein is discussed with respect to its importance for the mode of action of the NSAD.

Administration, Oral↗
PubMed1977

Bacterial metabolism of substituted phenols. Oxidation of 4-(methylmercapto)-and 4-(methylsulfinyl)-phenol by Nocardia spec. DSM 43251.

4-(Methylmercapto)-phenol (MMP) and 4-(methylsulfinyl)-phenol (MSP) are oxidized by the soil isolate Nocardia spec. DSM 43251, which is closely related to Nocardia calcarea. The rate of degradation depends on the capability of a substrate to support growth and is strongly enhanced in the presence of a second carbon source under the conditions of cooxidation. MMP and MSP are cometabolized by hydroxylation of the benzene ring with the formation of the substituted catechol following by ring cleavage between carbon atoms 2 and 3 ("meta" fission) to give 2-hydroxy-5-methylmercapto-or-2-hydroxy-5-methylsulfinylmuconic semialdehyde. Oxidation of MMP to MSP represents a bypath of MMP-oxidation. The intermediates were identified on the basis of their physical properties. The enzymes responsible for the metabolism of MMP and MSP are induced by growth with MMP or MSP, but not with glucose. MMP-and MSP-induced cells catalyze the oxidation of a variety of substituted phenols. This indicates a rather low substrate specificity of the enzymes induced by MMP and MSP.

Acetates↗
PubMed1976

[Profile of pharmacological actions of NAB 365 (clenbuterol), a novel broncholytic agent with selective activity on adrenergic beta2-receptors (author's transl)].

Effects of 4-amino-alpha-[(tert.-butylamino)methyl]-3,5-dichlorobenzyl alcohol hydrochloride (clenbuterol, NAB 365) on the adrenergic beta-receptors were investigated and compared with those of isoproterenol and salbutamol. The beta2-mimetic activity of clenbuterol on the smooth muscle of bronchi, uterus and vessels after i.v. injection corresponds to that of salbutamol in all laboratory animals. When given subcutaneously or as an aerosol clenbuterol is even somewhat more effective than isoproterenol. Clenbuterol differs from the known beta-mimetic drugs in its much longer duration of action. Therefore the integral of activity of single doses of clenbuterol, which are equally effective in the period of their maximal action, is remarkably greater than that of the other beta-mimetic substances. Clenbuterol differs from known beta-mimetic drugs used as bronchodilators in its efficacy after oral administration and in its mode of action on the heart. In the isolated auricle of the rabbit it has proved to be a weak partial agonist. In conscious rabbits, anesthetised guinea-pigs, dogs and cats the maximum of tachycardia obtainable by clenbuterol is lower than that of salbutamol. The higher degree of tachycardia in conscious dogs provoked by clenbuterol is a result of a reflex reaction to the vasodilation analogous to that of salbutamol. In higher doses clenbuterol shows beta1-blocking properties. Like other beta-blocking agents it owns qualities of a local-anesthetic and prolongs refractory period of the heart of guinea-pigs. In contrast to other beta-mimetic substances, clenbuterol causes only slight mobilization of heart muscle glycogen by doses higher than those which have broncholytic effects. The lipolytic and lactacidemia inducing activity of clenbuterol in rabbits corresponds to that of isoproterenol. The blood sugar is only slightly increased by clenbuterol as well as by other beta-mimetic agents. Degree and duration of action of clenbuterol and the other sympathomimetic amines on skeletal muscle of the cat shows parallelism with that of the broncholytic effect. In the rat clenbuterol inhibits the gastric secretion more than does isoproterenol. In contrast to other broncholytic substances, a very small dosage of clenbuterol is sufficient to protect rats against the liberation of histamine and serotonin caused by the anaphylactic reaction.

Adrenergic beta-Agonists↗
PubMed1976

[Hydrolysis of methoxysubstituted phenylureas, acylanilides and phenylcarbamates by a microbial aryl acylamidase (author's transl)].

The phenylurea herbicide linuron is hydrolyzed by Bacillus sphaericus ATCC 12123 quantitatively forming 3,4-dichloroaniline, CO2, and N,O-dimethylhydroxylamine. The inducible enzyme responsible for this hydrolysis was purified to homogeneity as judged by polyacrylamide gel electrophoresis. Its molecular weight was 75 000 +/- 10%. Studies on its substrate specificity showed that either whole cells as the linuron-induced enzyme hydrolyze a large number of herbicidal and fungicidal acylanilides, the methoxysubstituted phenylureas and the phenylcarbamate propham at the carbonyl-aniline bond. This would classify the enzyme as an aryl acylamidase (E.C. 3.5.1). Hydrolysis of phenylamides by whole cells and by the enzyme is inhibited by different methylcarbamate and organophosphorus insecticides. Inhibition of hydrolysis of linuron by the aryl acylamidase by methylcarbamates is a competitive one.

Amidohydrolases↗
PubMed1975

Inhibition of phenylamide hydrolysis by Bacillus sphaericus with methylcarbamate and organophosphorus insecticides.

The degradation of the phenylamide herbicides monolinuron, linuron, and solan by cultures of Bacillus sphaericus ATCC 12123 was inhibited by the methylcarbamate insecticides metmercapturon, aldicarb, propoxur, and carbaryl and by the organophosphorus insecticides fenthion and parathion. The extent of inhibition was largest with metmercapturon and smallest with parathion inhibition of hydrolysis of the two phenylurea herbicides was greater than of the acylanilide compound. Tests with crude enzyme preparations of aryl acylamidase derived from B. sphaericus showed that the inhibition of the hydrolysis of linuron with methylcarbamates is a competitive one. The insecticides tested did induce the enzyme, nor could they serve as its substrate.

Amidohydrolases↗
PubMed1975

[On the pharmacology of 9,10-dihydro-10-(1-methyl-4-piperidylidene)-9-anthrol (WA 335), a histamine and serotonin antagonist (author's transl)].

The substance 9,10-dihydro-10-(1-methyl-4-piperidylidene)-9-anthrol (WA 335) was examined for its antagonistic effects against histamine and serotonin, for its atropine-like properties as well as for a series of other qualities in comparison with cyproheptadine and pimethixene. The anti-histamine and anti-serotonin activities of compound WA 335 on the smooth muscle and the capillary do not only exceed that of cyproheptadine but also that of pimethixene. WA 335 shows an extremely strong binding to histamine and serotonin receptors. In the dose range in which it causes already an antamine effect, its oral absorption is very good. The anti-anaphylactic effect is much stronger than that of cyproheptadine. Like pimethixene and cyproheptadine, WA 335 has no distinct antagonistic qualities against bradykinin. The anticholinergic effects of WA 335 are dependent on the test object. In examinations on the bronchus of the guinea pig and the pupil of the mouse, the atropine-like efficiency corresponds to that of cyproheptadine; it is stronger on the stimulated vagus of the cat and less efficient than cyproheptadine on the stomach of the rat. WA 335 has distinct central atropine-like properties. It possesses a strong surface anesthetic activity. The effects of WA 335 on circulation are dependent on species. In contrast to pimethixene, compound WA 335 like cyproheptadine potentiates the effects of norepinephrine in cats. The reduction of the carotid sinus reflex in the cat is more distinct after WA 335 than after pimethixene and corresponds to that produced by cyproheptadine. Higher doses of WA 335 than are necessary to demonstrate antaminic effects are needed to provoke central nervous effects. WA 335 shows no analgesic potency in mice. The influence on body temperature in the rat is similar to that of cyproheptadine. WA 335 is equally efficient as pimethixene with regard to the inhibition of spontaneous motility and prolongation of barbiturate sleep in mice, and shows the same anti-emetic activity as does chlorpromazine in dogs. In contrast to chlorpromazine the behaviour of dogs and cats is distinctly altered already by doses of WA 335 which cause a slight sedation.

Analgesics↗