ABSTRACT
Possible interferences with aflatoxin B1 metabolism, of some compounds naturally present in food (quercetin, beta-naphthoflavone), resulting from way of cooking method (2-aminodipyrido [1,2-a; 1',2'-d] imidazole (Glu-P-2), norharmane; NH) or used as food additives (butylated hydroxytoluene; BHT) have been studied in vivo by evaluating the production of adducts to glutathione and adducts to serum proteins in laboratory rats. Glu-P-2 and norharmane inhibit strongly the production of adducts to glutathione whereas quercetin and beta-naphthoflavone have only a low effect. BHT is completely ineffective. The adducts to proteins are inhibited by the five compounds, norharmane being the most efficient.
Subject(s)
Aflatoxin B1/pharmacokinetics , Butylated Hydroxytoluene/pharmacology , Carcinogens, Environmental/pharmacokinetics , Food Additives/pharmacology , Harmine/analogs & derivatives , Harmine/pharmacology , Imidazoles/pharmacology , Quercetin/pharmacology , beta-Naphthoflavone/pharmacology , Animals , Biotransformation/drug effects , Blood Proteins/drug effects , Carbolines , Food Handling , Glutathione/drug effects , Male , Rats , Rats, WistarABSTRACT
Some compounds naturally present in food (quercetin, beta-naphthoflavone), used as food additives (butylated hydroxytoluene, sodium sulfite) or resulting from the way they were cooked (2-aminodipyrido [1,2-a; 3', 2'-d] imidazole, norharmane) can interfere with AFB1 metabolism. These interferences have been studied in vitro by evaluating the production of adducts to glutathione and by the Ames test on Salmonella typhimurium. Whereas all compounds produced a drastic decrease of the mutagenic activity, the first three only (quercetin, beta-naphthoflavone, butylated hydroxytoluene) interfered with the production of the adducts to glutathione.
Subject(s)
Aflatoxin B1/metabolism , Butylated Hydroxytoluene/pharmacology , Carcinogens, Environmental/metabolism , Food Additives/pharmacology , Glutathione/drug effects , Harmine/analogs & derivatives , Harmine/pharmacology , Imidazoles/pharmacology , Quercetin/pharmacology , Salmonella typhimurium/drug effects , Sulfites/pharmacology , beta-Naphthoflavone/pharmacology , Animals , Carbolines , Food Handling , Food Preservatives/pharmacology , Glutathione/metabolism , Mutagenicity Tests , Salmonella typhimurium/geneticsABSTRACT
This work investigated the means for the efficient encapsulation of muramyl dipeptide (MDP) in poly(epsilon-caprolactone) (PCL) microparticles (MP) by a solvent evaporation method in order to optimize the effect of the adjuvant for oral immunization. Therefore, the influence of MDP concentration in the inner aqueous phase was evaluated on MP characteristics such as size, morphology, drug entrapment, entrapment efficiency and the eventual interactions of MDP with co-entrapped model antigen, bovine serum albumin (BSA). The process of manufacturing produced a high entrapment efficiency of MDP (63.58 +/- 0.40%) without altering its integrity, as shown by chromatogram peaks analysis of a and beta anomers. The crystallinity of the polymer was dramatically increased (+24.6%) either with or without MDP loading but the entrapment of BSA reduced this crystallinity suggesting BSA-PCL interaction. These MP were resistant to simulated gastric fluid and exhibited a continuous BSA release. Moreover, their average diameter (<10 microm) combined with their high hydrophobicity make of this delivery system an exciting alternative for enhanced oral immunization.
Subject(s)
Acetylmuramyl-Alanyl-Isoglutamine/chemistry , Adjuvants, Immunologic/chemistry , Polyesters/chemistry , Acetylmuramyl-Alanyl-Isoglutamine/administration & dosage , Adjuvants, Immunologic/administration & dosage , Administration, Oral , Calorimetry, Differential Scanning , Chemistry, Pharmaceutical/methods , Chromatography, High Pressure Liquid , Delayed-Action Preparations , Hot Temperature , Particle Size , Polyesters/administration & dosage , Serum Albumin, Bovine/administration & dosage , Serum Albumin, Bovine/chemistry , Solvents , Surface Properties , Volatilization , Water/chemistryABSTRACT
Radiation sterilisation is a promising method to sterilise pharmaceutical products. However, this process is accompanied by a modification of odour due to volatile compounds formation. The origin of malodorous compounds produced during solid cefotaxime radiosterilisation has been investigated and several mechanisms are proposed to explain their appearance. Moreover, some quantitative data are given. Analysis of the degradation products was performed using a GC-ITD system with an injection by the static headspace technique. It appeared that some of the radio-induced compounds (such as carbon oxide sulfide and carbon disulfide) came from the degradation of the drug itself, whereas the formation of others required the presence of residual solvents which are volatile impurities already present before irradiation. Acetaldehyde directly came from impurities but the appearance of esters and acetaldehyde O-methyloxime was due to the presence of both cefotaxime and residual solvents together. Thus, the residual solvents play a key role in the radiolysis compounds formation (six of eight require the presence of them) and consequently in the modification of odour as well.
Subject(s)
Cefotaxime/chemistry , Drug Contamination , Gamma Rays , Solvents/chemistry , Sterilization , Chromatography, Gas , Odorants , Oximes/chemistry , Radiation , VolatilizationABSTRACT
A rapid and sensitive procedure is described for the quantitation of levamisole in plasma using high-performance liquid chromatography (HPLC). The procedure involves sample preparation using a reverse-phase C18 cartridge prior to chromatography and quantitation using peak area ratios (UV absorbance detection, 225 nm) of levamisole to the internal standard, quinine. The limit of detection was 21 ng/ml and the limit of quantification was 72 ng/ml, both contained in 1 ml of plasma. The recoveries were sufficiently high (73.1%) and overall coefficient of variation of the procedure was 0.25%. This procedure has been used to determine levamisole levels in human and cattle plasma. A comparison of using two C18 columns (Nova-pak, Puresil) was also studied and discussed.
Subject(s)
Levamisole/blood , Administration, Cutaneous , Animals , Cattle , Chromatography, Gas , Chromatography, High Pressure Liquid , Humans , Levamisole/administration & dosage , Polarography , Spectrophotometry, UltravioletABSTRACT
The alkaloid composition of the aerial parts and roots of PHYSALIS PERUVIANA was analysed by capillary GC (GC (2)), GC (2)-MS and GC (2)-FTIR. Eight alkaloids were identified, three of those alkaloids are 3beta-acetoxytropane and two N-methylpyrrolidinylhygrine isomers, which were not previously found in the genus PHYSALIS. A reproduction of the identification of alkaloids detected in the plant by the use of retention indices has been proposed.
ABSTRACT
High working temperatures were used during the separation of benzodiazepines by capillary gas chromatography with Fourier transform infrared detection (FTIR). Spectral identification of these drugs give very good results with 10 micrograms of drug injected. On the contrary, the precision of the quantitative determination is poor.
Subject(s)
Benzodiazepines/analysis , Chromatography, Gas/methods , Spectrophotometry, Infrared/methods , Fourier AnalysisABSTRACT
Different chemical treatments were applied to solutions of Aflatoxin B1 in order to compare their efficacy for the detoxification of AfB1: sodium sulfite, sodium hydrogen sulfate, sodium hydroxide, ammonia, sodium hypochlorite, hydrogen peroxide. The rate of the detoxification of AfB1 has been followed by three experimental approaches: 1. Quantitative estimation of the unmodified AfB1 by HPLC chromatography. 2. Quantitative estimation of the most toxic metabolite. AfB1-epoxide by chemical transformation into the trishydroxy AfB1 derivative followed by HPLC analysis. 3. Determination of the bacterial mutagenic activity, following the Ames' test. Among the different detoxification methods that were compared, the treatment with sodium sulfite proved to be the most efficient and seems thus to be recommended for foods contaminated by AfB1.
Subject(s)
Aflatoxin B1/chemistry , Aflatoxin B1/toxicity , Animals , Chromatography, High Pressure Liquid , In Vitro Techniques , Mutagenicity Tests , Mutagens/toxicity , RatsABSTRACT
Capillary gas chromatography with infra-red detection (FTIR) was used for the qualitative determination of ten barbiturates. The identification is valid only for 1 microgram drug by injection. Comparison between usual and Fourier transform infra-red spectra is also provided.
Subject(s)
Barbiturates/analysis , Chromatography, Gas , Fourier Analysis , Spectrophotometry, InfraredABSTRACT
Different cassava products were found to contain mutagenic activities in the Ames test. This paper describes how the flavonol quercetin is released during the cooking of fresh cassava leaves, following a process very similar to culinary habits. The hydrolysis of the glucoside(s) and the release of free quercetin has been followed by the monitoring of mutagenic activities with a simultaneous isolation and purification by thin-layer chromatography. The fluorodensitometric method applied revealed that fresh leaves contained about 1300 mg quercetin per kg wet weight, of which 800 mg were released during a normal cooking process.
Subject(s)
Manihot/toxicity , Mutagens , Flavonoids/analysis , Flavonols , Hot Temperature , Hydrolysis , Manihot/analysis , Mutagenicity Tests , Plants, Edible , Quercetin/analysis , Salmonella typhimurium/genetics , SolventsABSTRACT
Explica sobre la instalación de bombas centrífugas, la puesta en marcha, operación, parada, supervisión de operación y mantenimiento y reparaciones. Presenta conocimientos básicos de las actividades de mantenimiento a nivel de taller. Enfoca el trabajo de topografía y trazos para el tendido de tuberías y trata sobre el transporte y almacenamiento de tubos, preparación y relleno de la zanja, herramientas y accesorios utilizados, empalme de tubos, bloques de anclaje de concreto, prueba de presión y conexión domiciliaria
Subject(s)
Centrifugal Pumps , Operators , Water SupplyABSTRACT
Informa sobre los conceptos y las fórmulas de la teoría hidráulica que se usan en el diseño de los sistemas de abastecimiento de agua y los aplica en el transporte de agua en tuberías a presión. Examina diagramas eléctricos, símbolos gráficos, componentes eléctricos de control e interpreta diagramas eléctricos y desarrollo de esquemas de control. Explica sobre el registro de datos operativos y recopilación de estadísticas del agua, la planificación del trabajo de inspección y mantenimiento y el control de existencias. Incluye instrucciones permanentes
Subject(s)
Operators , Water Distribution , Water Supply , Handbook , Operation and MaintenanceABSTRACT
Presenta información especializada sobre mantenimiento y reparación de: motores diesel, a gasolina, y eléctricos; sistemas simples de elevación, bombas, ventiladores y compresores. Explica el procedimiento para el tendido de tuberías y el desarrollo de pruebas de troncales de agua. Trata de operación general de sistemas de abastecimiento de agua, construcción de unidades de abastecimiento, seguridad industrial y protección contra accidentes, topografía básica y dibujo técnico
Subject(s)
Operators , Sewer Pipe Laying , Pipelines , Water SupplyABSTRACT
The mutagenic activity present in urine of animals treated with acrylonitrile (ACN) is tentatively related to the excretion of three urinary metabolites: thiocyanate (SCN-), hydroxyethylmercapturic acid (OH-MA), and cyanoethylmercapturic acid (CN-MA). It is shown that the route of administration and animal species affect SCN- excretion but not the excretion of hydroxyethyl- and cyanoethylmercapturic acids or the mutagenicity of urine from ACN-treated animals. Various pretreatments (phenobarbital, CoCl2, diethylmaleate, trichloroacetonitrile) decrease the mutagenicity of urine from ACN-treated animals and decrease the excretion of SCN- and OH-MA. None of the quantified urinary metabolites is responsible for urinary mutagenicity.
Subject(s)
Acrylonitrile/toxicity , Mutagens/urine , Nitriles/toxicity , Acrylonitrile/metabolism , Animals , Biotransformation , Male , Mixed Function Oxygenases/metabolism , Mutagenicity Tests , Rats , Salmonella typhimurium/drug effectsABSTRACT
The metabolism of N-nitrosopyrrolidine (NPyrr) via alpha-hydroxylation is modified by pretreatments of the animals with compounds which affect the microsomal level of cytochrome P-450 and by addition, in vitro, of 2-diethylaminoethyl-2,2-diphenyl valerate hydrochloride (SKF 525-A), an inhibitor of cytochrome P-450. This phenomenon is due exclusively to the induction or the inhibition of the enzymatic activity involved in the microsomal metabolism. After preincubation in liquid medium, the mutagenic activity of NPyrr towards the Salmonella typhimurium strain TA 1530 is similarly modified by these effectors. A similar effect is not observed when using the plate incorporation method. The mutagenic intermediate is formed by the microsomal fraction. The presence of the S. typhimurium strain TA 1530 decrease the transformation of NPyrr into its ultimate metabolite (1,4-butanediol); there is a relationship between the formation of 1,4-butanediol and the mutagenic activity of NPyrr. The S. typhimurium strain TA 1530 is able to partially transform 4-hydroxybutanal, the first identifiable microsomal metabolite of NPyrr, into its ultimate metabolite (1,4-butanediol).
Subject(s)
Microsomes, Liver/metabolism , N-Nitrosopyrrolidine/metabolism , Nitrosamines/metabolism , Animals , Biotransformation , Butylene Glycols/analysis , Cobalt/pharmacology , Hydroxylation , Male , Microsomes, Liver/drug effects , Mutagenicity Tests , N-Nitrosopyrrolidine/pharmacology , Phenobarbital/pharmacology , Proadifen/pharmacology , Rats , Rats, Inbred Strains , Salmonella typhimurium/drug effectsABSTRACT
The mutagenicity of N-nitrosodiethanolamine and its mono- and di-acetyl derivatives was tested in the S. typhimurium test system, in cytogenetic studies and in the micronucleus test. N-nitrosodiethanolamine had no mutagenic effects towards several strains of S. typhimurium either in the absence or in the presence of metabolic activating systems. Its diacetyl derivative exerted mutagenic effects towards the S. typhimurium strains TA1530 and TA100. Neither compound increased significantly the nubmer of chromosomal aberrations or of micronuclei in mice.
Subject(s)
Diethylnitrosamine/pharmacology , Mutagens , Nitrosamines/pharmacology , Animals , Cell Nucleus/drug effects , Chromosomes/drug effects , Diethylnitrosamine/analogs & derivatives , Male , Mutagenicity Tests , Rats , Salmonella typhimurium/geneticsABSTRACT
The mutagenicity of acrylonitrile (ACN) was tested with Salmonella typhimurium TA1530 after a preincubation period of the chemical with a rat liver post-mitochondrial fraction in liquid medium. Several pretreatments were applied to the animals before the preparation of the liver fractions and different compounds added to the incubation mixture, which were shown to modify the liver mediated mutagenic activity of ACN. Four metabolites: cyanoacetic acid, cyanoethanol, acetic acid and glycolaldehyde were identified after incubation of ACN with the rat liver homogenate. From both sets of results, an in vitro metabolic scheme is proposed to ACN, which postulates the intermediate formation of a radical species and an epoxide.
Subject(s)
Acrylonitrile/pharmacology , Mutagens , Nitriles/pharmacology , Acetaldehyde/analogs & derivatives , Acetaldehyde/metabolism , Acetates/metabolism , Acrylonitrile/analogs & derivatives , Acrylonitrile/metabolism , Animals , Biotransformation , Ethanol/analogs & derivatives , Ethanol/metabolism , Ferrous Compounds/pharmacology , Glutathione/pharmacology , In Vitro Techniques , Male , Metyrapone/pharmacology , Microsomes, Liver/metabolism , Nitriles/metabolism , RatsABSTRACT
Urines collected from rats injected with acrylonitrile (ACN) were mutagenic towards Salmonella typhimurium TA1530; this activity was reduced when the animals were pretreated by pyrazole (inhibitor of alcohol dehydrogenase) and suppressed after pretreatment either by CoCl2 and SKF 525-A (inhibitors of the mixed-function oxidases system) or by trichloroacetonitrile (radical trapping agent). On the other hand, two urinary metabolites (cyanoethanol and cyanoacetic acid) have been detected by gas chromatography. One possible scheme for the in vivo metabolism of ACN is presented which postulates the intermediate formation of a radical species and of an epoxide.
Subject(s)
Acrylonitrile/urine , Mutagens/metabolism , Nitriles/urine , Acetates/urine , Acetonitriles/pharmacology , Acrylonitrile/analogs & derivatives , Animals , Cobalt/pharmacology , Ethanol/analogs & derivatives , Ethanol/urine , Male , Models, Chemical , Proadifen/pharmacology , Pyrazoles/pharmacology , RatsABSTRACT
N-Nitrosopyrrolidine (NPyrr) and N-nitrosopiperidine (NPip) are carcinogenic and mutagenic cyclic nitrosamines. Their biotransformation by rat liver post-mitochondrial fraction into 1,4-butanediol and 1,5-pentanediol, respectively, is evaluated by determining these ultimate metabolites with a sensitive and suitable method. Their mutagenic activity towards the Salmonella typhimurium strain TA 1530 was simultaneously observed. A relationship exists between their metabolism and their mutagenicity. alpha-Hydroxylation is probably the critical metabolic metabolism of cyclic nitrosamines.