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[Scintigraphy of the bile ducts by means of the Tc-99m-acid N-(2,6 diethyl-acetanilide) iminodiacetic acid in pediatrics].

Results with diethyl-IDA in the diagnosis of dilatation and obstruction of the bile ducts are reported. By comparison with methyl-IDA, the more rapid blood clearance and slower renal excretion of diethyl-IDA do not lead to interference on the part of the right kidney and ureter during the first 30' of scintiscanning. The preparation was employed in 15 subjects with persistent neonatal icterus and clinically suspected diseases of the hepatic bile ducts. Personal experience is cited for the view that, thanks to its almost exclusively biliary excretion and high bile concentration, 99mTc-labelled diethyl-IDA gives better visualisation of the bile ducts than the methyl-IDA complex.

Acetanilides

Metabolism of 2-chloro-N-isopropylacetanilide (propachlor) in the rat.

Eleven urinary metabolites from [14C]propachlor were either identified or characterized by mass spectrometry. Those identified were 2-[S-(N-acetyl)cysteinyl]-N-isopropylacetanilide, 2-(methylsulfonyl)-acetanilide, 4'-hydroxy-2-(methylsulfonyl)-acetanilide, and 4'-hydroxyacetanilide. Those characterized were N-(1-hydroxyisopropyl)-2-(methylsulfonyl) acetanilide and its glucuronide, the glucuronides of 4'-hydroxy-N-isopropyl-2-(methylsulfonyl)acetanilide, N-(1-hydroxyisopropyl) aniline, 4'-hydroxy-2-(methylsulfonyl)acetanilide, and either N-(1-hydroxy-isopropyl) acetanilide or 2-hydroxy-N-isopropylacetanilide.

Acetanilides

Further studies of metyrapone effects upon anilide hydroxylation.

The enhancing effect of metyrapone upon the p-hydroxylation of acetanilide has been confirmed with the use of a new gas-chromatographic method for the determination of acetaminophen. This effect has been shown not to be due to inhibition of hydrolysis of acetaminophen or interference with its determination, or to preferential formation of other phenolic metabolites. This effect of metyrapone is remarkably substrate-specific: phenol formation from the homologues of acetanilide, formanilide and propionanilide, and that from the sulfonamide analog of acetanilide, methanesulfonanilide, is inhibited by metyrapone over the concentration range in which acetanilide hydroxylation is enhanced. The same substrate specificity was observed when the modifier was acetophenone. alpha,alpha'-Dipyridyl, however, enhances phenol formation from all three carbonacylanilides, but does not affect that from methanesulfonanilide.

2,2'-Dipyridyl

Isolation of an inducible amidase from Pseudomonas acidovorans AE1.

A bacterial strain, AEI, which hydrolysed acetanilide, was isolated from soil and identified as Pseudomonas acidovorans. Numerous amides, esters and enzyme inhibitors were tested as amidase inducers. Phenacetin was chosen as inducer for the large scale cultivation of these organisms because it was less toxic to the bacteria than acetanilide. The induction increased the enzymic activity 250-fold. In comparison, the type culture strain of P. acidovorans, ATTCCI5668, had no amidase activity which could be induced by phenacetin. Optimal growth conditions were established with respect to the concentration of carbon source and inducer so that about 10% of the extractable bacterial protein consisted of the amidase. The organisms were lysed with lysozyme in the presence of EDTA and the enzyme was isolated mainly by column chromatography procedures. A preparation form 60 g (wet wt) bacteria yielded about 100 mg highly purified amidase with a specific activity of 137 mugmol substrate hydrolysed/min/mg protien. In addition to acetanilide, the purified enzyme hydrolysed several other amides and esters. As standard substrate, p-nitroacetanilide was chosen.

Acetamides

Biotransformations with plant tissue cultures.

Suspension cultures of Catharanthus roseus, Apocynum cannabinum and Conium maculatum were examined for their capacity to transform aniline, anisole, acetanilide, benzoic acid and coumarin. None of the cultures transformed acetanilide but each produced acetanilide when fed aniline. All three cultures converted benzoic acid to its para-hydroxy derivative. Coumarin was selectively hydroxylated at the 7-position by Catharanthus and Conium and anisole was O-demethylated only by older Catharanthus tissue.

Acetanilides

Relationship between mutant amidases of Pseudomonas aeruginosa and hydroxyurea as an inhibitor.

Hydroxyurea inhibited growth of Pseudomonas aeruginosa strain AI 3 on media containing either acetanilide (N-phenyl acetamide) or acetamide as sole carbon sources. Mutants resistant to hydroxyurea inhibition of growth on acetanilide (OUCH strains) and acetamide (AmOUCH strains) displayed altered growth properties on various amide media compared with the parent strain AI3. AI3 amidase, which catalyses the initial step in the metabolism of acetanilide and acetamide, was inhibited by hydroxyurea in a time-dependent reaction that was slowly reversible at pH 7.2. Compared with AI3 amidase, amidases from the OUCH mutants were much less sensitive to inhibition by hydroxyurea and showed altered substrate specificities and pH/activity profiles; amidases from the AmOUCH mutants were more sensitive to hydroxyurea inhibition but showed increased activity towards acetamide. Association of resistance to hydroxyurea inhibition with a mutation in the amidase structural gene of strain OUCH 4 was confirmed by transduction.

Amidohydrolases

Assessment of the utility of gallbladder imaging with 99mTc-IDA.

Cholescintigraphy was performed in 113 patients of whom 38 had normal gallbladders, 37 had acute cholecystitis and 38 had chronic cholecystitis. The radiopharmaceuticals used in the study were either 99mTc-dimethyl acetanilide iminodiacetic acid or 99mTc-paraisopropyl acetanilide iminodiacetic acid, both of which performed equally well. All patients with non-visualized gallbladders had cholecystitis, but visualization did not exclude disease. The rapidity of obtaining the results (within one hour), the complete absence of untoward reactions to the radiopharmaceuticals, the much lower frequency of subtle or indeterminate results, the ability to render useful information in the presence of moderate jaundice and the lack of interference from overlying intestinal contents establishes these radionuclide agents as superior to both radiographic oral and intravenous cholangiography in the investigation of the acute abdomen.

Acetanilides