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PubMed1979

Arprinocoid evaluation in broiler chicken pen trials in Europe.

The effect of arpinocid (9-[2-chloro-6-fluorophenyl)methyl]-9H-purin-6-amine) on artificial and natural coccidial infections in broiler chickens was evaluated in a series of pen trials conducted in England, France, and Germany. In trials with induced infections, mortality attributable to coccidiosis did not occur at 50, 60, and 70 ppm although it ranged from 3.2 to 9% in unmedicated groups. At 7 to 8 weeks of age, birds receiving arprinocoid in feed at levels of 40, 50, 60, and 70 ppm had improved body weights and feed conversion compared with unmedicated birds, the differences being significant (P is less than .05) in 4 out of 5 trials. Productivity of birds on arprinocid was equivalent or significantly superior (P is less than 0.5) to those on halofuginone (3 ppm), monensin (100 ppm), nicarbazin (125 ppm), and PANCOXIN (165 ppm). Based on the results of these pen trials, arprinocid at levels of 50 to 70 ppm in feed is a highly efficacious compound for the prophylaxis of coccidiosis, preventing mortality, and permitting good growth and feed conversion under conditions of both mild and severe infection pressure.

Adenine↗
PubMed1979

[Oxidative degradation of dibenzylsulfide].

Dibenzylsulfid (DBS) as a model of the organic sulfur compounds in crude oil was converted by a mixed culture (containing Pseudomonas aeruginosa) into several water soluble organic substances. Whereas these compounds are detectable with DC- and IR-spectroscopic techniques, benzylmercaptoacetic acid (BMA) was the only isolated product of DBS utilization. Efficiency of degradation, respectively, accumulation of BMA were dependent on aeration and pH-regulation.

Acetates↗
PubMed1978

Affinity chromatography of trypsin and related enzymes. V. Basic studies of quantitative affinity chromatography.

A detailed study of the quantitative affinity chromatography of trypsin [EC 3.4.21.4] is reported here. Frontal chromatography using an enzyme solution of very low concentration on an affinity adsorbent gave the dissociation constant of the enzyme-immobilized ligand complex (Kd). Kd values determined under various conditions enabled us to discuss in detail the interaction of trypsin and affinity adsorbents (mainly Gly-Gly-Arg Sepharose). The pH dependence of Kd was consistent with that of the interaction of trypsin and product-type compounds. The effects of changes in temperature, ionic strength, dielectric constant, etc., were also studied. The Ki values of soluble competitive inhibitors can be determined by analysis of their effects on the elution volume of the enzyme. The values obtained were in good agreement with those obtained by kinetic analysis. The present method proved to be useful as a general procedure to investigate the interaction of a protein and a specific ligand.

Arginine↗
PubMed1979

[Comparative investigations on the organotropic carcinogenic effect of different N-nitroso compounds with rat after single and chronic treatment (author's transl)].

After the gavage of 200 mg N-nitrosodiethylamine per kg body weight only kidney tumors developed while long-term administration of 10 ppm N-nitrosodiethylamine induced esophageal tumors and hepatocellular carcinomas in female rats (SIV 50). This change of the organ-specific carcinogenic effect is not observed in experiments with N-methyl-N-nitrosobenzylamines substituted with a methyl group at the phenyl moiety. Both chronic treatment and single doses induced tumors of the esophagus and the pharynx.

Animals↗
PubMed1975

A pharmacologic comparison of histamine receptors in isolated extracranial and intracranial arteries in vitro.

Isolated segments of cat extracranial and intracranial arteries were tested simultaneously for circular motor activity in an aerated Krebs-Ringer organ bath at constant temperature and pH. Histamine produced a strong contraction (about 850 dyn) in the extracranial arteries but a considerably weaker contraction, with a high half maximum response, in the intracranial arteries. The mode of inhibition of the latter response by antihistaminic compounds (chlorpheniramine and mepyramine) showed the response to be nonspecific; the contraction in the extracranial arteries was inhibited in a competitive manner, demonstrating the presence of histamine H1 receptors. The dilatory response was studied after the vessels had been given a tonic contraction with serotonin. Histamine produced similar dilatory effects (about 200 dyn) in both types of arteries and competitive inhibitions were obtained with burimamide, showing that the dilation was mediated through histamine H2 receptors. Dissociation constants were calculated for the receptor-antagonist complex.

Animals↗
PubMed1978

Benzyloxycarbonylarginine nitrophenyl ester salts: 1-hydroxybenzotriazole catalyzed acylations of amines.

Benzyloxycarbonylarginine p-nitrophenyl ester has been prepared by the p-nitrophenyltrifluoroacetate method. The p-nitrophenyl ester derivative was isolated as its crystalline picrate and nitrate salts. The ester salts couple with amino compounds in the presence of 1-hydroxybenzotriazole, but decompose without acylation of amines in the absence of the 1-hydroxybenzotriazole catalyst. Benzyloxycarbonylarginine p-nitrophenyl ester and other activated esters of N-a-sustituted arginine salts may be useful reagents for introduction of trypsin-labile protecting groups into peptide fragments for purpose of polypeptide semi-synthesis. At the same time, side reactions of such carboxyl-activated arginine derivatives may serve as models for side reactions in the couplings of peptide fragments with arginine residues in the carboxyl-terminal position. Peptide fragment couplings of this type may frequently be encountered in semisynthesis of polypeptides from tryptic fragments.

Acylation↗
PubMedDate not supplied

The metabolic disposition of [14C]pivhydrazine, [14C]mebanazine, and [14C]benzylhydrazine in the rat.

The hydrazine drugs, [14C]pivhydrazine and [14C]mebanazine and the related compound [14C]benzylhydrazine were readily absorbed from the rat gut and the radioactivity was excreted mainly in urine. The major urinary metabolite of pivhydrazine and benzylhydrazine was [14C]hippuric acid, whereas mebanazine was shown to be excreted largely unchanged. Biliary excretion (21 and 24%, respectively) of radioactive material was observed after administration of [14C]pivhydrazine and [14C]mebanazine to bile duct-cannulated rats but only small amounts (approximately 3%) were excreted in bile after [14C]benzylhydrazine administration. The major biliary metabolites of pivhydrazine and mebanazine are acid-labile conjugates, possibly N-glucuronides. In vitro studies with rat liver homogenate suggest that benzylhyrazine may be an intermediate in the metabolism of pivhydrazine. The distribution of radioactivity in the rat 7 days after the administration of [14C]pivhydrazine and [14C]pivhydrazine and [14C]mebanazine is described.

Animals↗
PubMed1975

Induction and suppression of hepatic and extrahepatic microsomal foreign-compound-metabolizing enzyme systems by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on a number of hepatic and extrahepatic foreign-compound-metabolizing enzyme systems in microsomes from rats, rabbits and guinea pigs were investigated. Following TCDD treatment, the N-demethylation of benzphetamine, aminopyrine and ethylmorphine was suppressed in hepatic microsomes from male but not from female rats. However, both cytochrome P-450 and benzpyrene hydroxylase were significantly stimulated in hepatic microsomes from both male and female rats at doses as small as 1 mug TCDD/kg body weight. The inductive effect on rat hepatic microsomal enzymes was considerably more persistent than the suppressive effect. Following a single oral dose of 25 mug TCDD/kg weight, benzpyrene hydroxylase of male rat liver microsomes remained significantly elevated for 73 days but the suppression of benzphetamine N-demethylase had gone after 35 days. The induction of benzpyrene hydroxylase in male rat liver microsomes by TCDD was independent of the age of the rat and the levels to which this enzyme was increased was similar in male rats of all ages. However, the suppression of benzphetamine N-demethylase in male rat liver microsomes was age related: the suppression was seen only in adult animals and in the very young (10 days old) the enzyme was actually induced by TCDD. Inductive effects appeared in both smooth and rough-surfaced hepatic microsomes from male rats but the suppression of N-demethylation occurred only in the smooth-surfaced microsomes (SER). In microsomes from extrahepatic tissues of the rat, induction of mixed-function oxidases (MFOs) by TCDD occurred only in the kidney. However, UDPglucuronyltransferase was induced in microsomes from lung, kidney, intestine and brain but not testes. The response in the rabbit and guinea pig to TCDD differed considerably from that in the rat. Benzpyrene hydroxylase was unaffected in hepatic microsomes from the guinea pig and actually suppressed in microsomes from rabbit liver. Benzphetamine N-demethylase was also suppressed in rabbit liver microsomes. Glucuronyl-transferase was unaffected by TCDD in microsomes from liver, lung or kidney of the rabbit and guinea pig. The only lung enzyme responsive to TCDD was biphenyl 4-hydroxylase of the rabbit and guinea pig. Suppression was not observed in any of the extraheptic tissues studied and may be confined to only certain hepatic systems.

Animals↗
PubMed1978

Gas phase carboxylate anions fron p-nitrobenzyl esters of fatty acids.

Gas phase carboxylate anions have been efficiently generated from the p-nitrobenzyl esters of nine fatty acids ranging in size from C6 to C22. The process involves the dissociative resonance capture of 2.9 e V electrons by the derivatives. The procedure is specific and gives the carboxylate anions as the base peak in all but two of the derivative. The technique gives extremely simple spectra, with little additional fragmentation and no rearrangement ions.

Benzyl Compounds↗
PubMed1979

Quantitative analysis of tiamenidine in human plasma by gas chromatography mass spectrometry of a dibenzyl derivative.

A gas chromatography mass spectrometry method has been developed and evaluated for the quantitative analysis of tiamenidine in plasma. Tiamenidine and internal standard are extracted from basified plasma, converted to dibenzyl derivatives by reaction with benzyl bromide and potassium t-butoxide in the presence of 18-crown-6 ether prior to analysis by selected ion monitoring. The method can be used over the range 0.2--10 ng ml-1 with a coefficient of variation of better than 20% at 1 ng ml-1.

Alkylation↗
PubMed1975

Cycloalkanones V: synthesis, distribution, and effects on triglyceride metabolism.

The 14-C-labeled 2,8-dibenzylcyclooctanone was synthesized to study its absorption, distribution, and excretion in rats. Maximum drug absorption from the GI tract occurred between 12 and 14 hr after administration. The major organs possessed maximum amounts of the drug in 1 hr, with the liver concentrating the most with 6.56% 14-C and the muscle mass reaching a maximum of 41% 14-C after 14 hr. The drug remained in the GI tract over the first 6 hr and was associated with the lipid and glycogen fractions. Eighty-seven percent was eliminated in the feces after 72 hr. 2,8-Dibenzylcyclooctanone caused a significant reduction in vitro of dihydroxyacetone phosphatase acyltransferase and sn-glycerol-3-phosphate acyltransferase, which is the proposed mechanism for the observed in vivo reduction of hepatic, intestinal, and serum triglycerides and total glycerolipids. In vivo administration of the drug resulted in a depression of liver acid phosphatidyl phosphatase, acid phosphatase and lipase, and adipose lipase. The drug increased the rates of excretion of exogenous cholesterol, palmitic acid, and progesterone.

Acid Phosphatase↗
PubMed1975

Drug-biomolecule interactions: topographical study of active site of erythrocyte carbonic anhydrase using spin-labeled sulfanilamide drugs.

The topography of the active sites of human erythrocyte carbonic anhydrases B and C and bovine erythrocyte carbonic anhydrase B was studied using a series of spin-labeled sulfanilamide analogs. Results show that the active site of human carbonic anhydrase C is a narrow cleft approximately 14 A in depth. This observation is in good agreement with previously published X-ray diffraction data. While the active sites of human carbonic anhydrase B and bovine carbonic anhydrase B have the same general shape as the active site of human carbonic anhydrase C, they are slightly deeper.

Benzyl Compounds↗