Antifungal activity of poly(ε-caprolactone) nanoparticles incorporated with Eucalyptus essential oils against Hemileia vastatrix.

Coffee (Coffea L.) is one of the main crops produced globally. Its contamination by the fungus Hemileia vastatrix Berkeley and Broome has been economically detrimental for producers. The objective of this work was to extract and characterize the essential oils from Eucalyptus citriodora Hook, Eucalyptus camaldulensis Dehn and Eucalyptus grandis Hill ex Maiden, produce and characterize nanoparticles containing these essential oils and evaluate the in vivo and in vitro antifungal activity of free and nanoencapsulated essential oils. The principal constituent of the essential oil from E. citriodora was citronellal; that from E. grandis was α-pinene; and that from E. camaldulensis was 1,8-cineol. The in vitro antifungal activity against the fungus H. vastatrix was 100% at a concentration of 1000 µl l-1 for all the oils and nanoparticles containing these natural products. The sizes of the nanoparticles produced with the essential oils from E. citriodora, E. camaldulensis and E. grandis were 402·13 nm, 275·33 nm and 328·5 nm, respectively, with surface charges of -11·8 mV, -9·24 mV and - 6·76 mV, respectively. Fourier transform infrared analyses proved that the encapsulation of essential oils occurred in the polymeric matrix of poly(ε-caprolactone). The incorporation of essential oils into biodegradable poly(ε-caprolactone) nanoparticles increased their efficiency as biofungicides in the fight against coffee rust, decreasing the severity of the disease by up to 90·75% after treatment with the nanoparticles containing the essential oil from E. grandis.

Antifungal and antiocratoxigenic potential of Alpinia speciosa and Cymbopogon flexuosus essential oils encapsulated in poly(lactic acid) nanofibres against Aspergillus fungi.

Essential oils encapsulated in a polymeric matrix can be used as an alternative method to control fungi and mycotoxins. The essential oils were extracted by hydrodistillation and characterized by gas chromatography. The nanofibres were produced from poly (acid lactic) (PLA) containing essential oils by the Solution Blow Spinning method. The antifungal and antimicotoxygenic properties were evaluated against Aspergillus ochraceus and Aspergillus westerdijkiae by the fumigation method. Terpinen-4-ol (20·23%), sabinene (20·18%), 1·8-cineole (16·69%) and γ-terpinene (11·03%) were the principal compounds present in the essential oil from Alpinia speciosa, whereas citral (97·67%) was dominant from Cymbopogon flexuosus. Microscopy images showed that the addition of essential oils caused an increase in the diameter of the nanofibres. The infrared spectroscopy results indicated the presence of essential oils in the PLA nanofibres. Differential scanning calorimetry curves also indicated the existence of interactions between the essential oils and polymeric macromolecules through their plasticizing action. The hydrophobic character of nanofibres was revealed by the contact angle technique. An antifungal effect was observed, the mycelial growths (3·25-100%) and the synthesis of ochratoxin A (25·94-100%) were inhibited by the presence of the nanofibres. The results suggest that bioactive nanofibres hold promise for application to control toxigenic fungi.

Chemical characterization of the Allium sativum and Origanum vulgare essential oils and their inhibition effect on the growth of some food pathogens / Caracterização química e efeito inibitório dos óleos essenciais de Allium sativum e Origanum vulgare frente ao crescimento de alguns patógenos de alimentos

This study sought to evaluate the chemical composition of the Allium sativum and Origanum vulgare essential oils and their effect on the growth inhibition of microorganisms, such as P. aeruginosa, S. Choleraesuis, A. flavus, A. niger and P. simplicissimum, important food contaminants. The main constituents of the oregano essential oil were 4-terpineol (27.03%), γ-terpinene (20.04%), and β-cymene (6.34%), and the main constituents of the garlic essential oil were diallyl trisulfide (38, 81%), diallyl disulfide (25.23%), and methyl allyl trisulfide (12.52%). Inhibition zones were formed in in vitro tests on the bacteria S. Choleraesuis and P. aeruginosa, except for A. sativum against P. aeruginosa. The inhibition of mycelial growth caused by the oregano essential oil occurred with the concentrations of 0.10, 0.03 and 0.05 mg mL-1 for the A. flavus, A. niger and P. simplicissimum fungi, respectively. The CMI for the garlic oil began at the 0.03 mg mL-1 concentration for all species of fungi. The oils presented an inhibitory effect against the microorganisms studied and constitute an alternative for microbiological control in food.

Objetivou-se avaliar a composição química e o efeito inibitório dos óleos essenciais de Allium sativum e Origanum vulgare frente ao crescimento dos micro-organismos Pseudomonas aeruginosa, Salmonella Choleraesuis, Aspergillus flavus, Aspergillus niger e Penicillium simplicissimum, importantes patógenos causadores de contaminações em alimentos. Para quantificação e identificação dos constituintes químicos dos óleos, utilizou-se cromatógrafo gasoso acoplado a espectrômetro de massas. Os principais constituintes do óleo essencial de orégano foram o 4-terpineol (27,03%), γ-terpineno (20,04%), β-cimeno (6,34%), e do alho, o dialil trissulfeto (38,81%), dialil dissulfeto (25,23%), metil alil trissulfeto (12,52%). Os resultados dos testes in vitro sobre as bactérias S. Choleraesuis e P. aeruginosa indicaram a formação de halo de inibição e revelaram o efeito inibitório para os referidos óleos, exceto para o óleo de A. sativum frente a P. aeruginosa. Para os fungos A. flavus, A. niger e P. simplicissimum a inibição do crescimento micelial provocada pelo óleo essencial de orégano ocorreu a partir das concentrações de 0,10, 0,03 e 0,05 µg mL-1, respectivamente, sendo que a CMI para o óleo de alho iniciou-se a partir da concentração 0,03 µg mL-1 para todas as espécies de fungos. Foi possível verificar que os óleos possuem efeito inibitório sobre os microrganismos estudados, sendo, portanto, uma alternativa no controle microbiológico de alimentos.

Avaliação da qualidade da casca dos ovos provenientes de matrizes pesadas com diferentes idades / Evaluation of eggshell quality from broiler breeder hens with different ages

Foi realizado um estudo sobre qualidade da casca dos ovos incubáveis provenientes de matrizes pesadas com diferentes idades, por meio da avaliação da relação entre peso da casca e peso do ovo e análises de peso específico, espessura, porosidade, resistência e microscopia eletrônica. Os dois tratamentos foram definidos pela idade da matriz, sendo considerados ovos de matrizes novas - 33 semanas - e de matrizes velhas - 63 semanas. Os ovos de matrizes com 33 semanas foram mais leves, e o número de poros por cm² foi menor que o de ovos das aves mais velhas. Ovos de aves com 63 semanas apresentaram menor percentual de casca em relação ao peso do ovo, menor peso específico e menores resistência e espessura da casca. A proporção das membranas da casca em relação à sua espessura total foi maior nas matrizes mais novas. Concluiu-se que ovos de matrizes velhas têm qualidade de casca inferior aos ovos das matrizes novas e que as membranas da casca nos ovos de matrizes novas desempenham papel relevante em sua estrutura.

We conducted a study on eggshell quality from Cobb® broiler breeders at different ages by assessing the relationship between eggshell weight and egg weight and analysis of specific weight, thickness, porosity, strength and electron microscopy. Both treatments were defined by broiler breeder age, considering eggs from young breeders (33 weeks) and eggs from old breeders (63 weeks). It was observed that eggs from breeders at 33 weeks have lower weight and number of pores per cm² compared with eggs from older birds. 63 weeks broiler breeders had lower percentage of eggshell in relation to egg weight, lower specific weight, strength and thickness, when compared with eggs from young breeders. The proportion of shell membranes in relation to its total thickness was significantly higher in young breeders. It was concluded that eggs from older broiler breeders have lower eggshell quality than the young breeders. The shell membranes in young breeder's eggs play a significant role in its structure, making it necessary to focus on this layer in future studies on eggshell quality and their relationship between breeder age and incubation yield.

Avaliação da qualidade da casca dos ovos provenientes de matrizes pesadas com diferentes idades / Evaluation of eggshell quality from broiler breeder hens with different ages

Foi realizado um estudo sobre qualidade da casca dos ovos incubáveis provenientes de matrizes pesadas com diferentes idades, por meio da avaliação da relação entre peso da casca e peso do ovo e análises de peso específico, espessura, porosidade, resistência e microscopia eletrônica. Os dois tratamentos foram definidos pela idade da matriz, sendo considerados ovos de matrizes novas - 33 semanas - e de matrizes velhas - 63 semanas. Os ovos de matrizes com 33 semanas foram mais leves, e o número de poros por cm² foi menor que o de ovos das aves mais velhas. Ovos de aves com 63 semanas apresentaram menor percentual de casca em relação ao peso do ovo, menor peso específico e menores resistência e espessura da casca. A proporção das membranas da casca em relação à sua espessura total foi maior nas matrizes mais novas. Concluiu-se que ovos de matrizes velhas têm qualidade de casca inferior aos ovos das matrizes novas e que as membranas da casca nos ovos de matrizes novas desempenham papel relevante em sua estrutura.(AU)

We conducted a study on eggshell quality from Cobb® broiler breeders at different ages by assessing the relationship between eggshell weight and egg weight and analysis of specific weight, thickness, porosity, strength and electron microscopy. Both treatments were defined by broiler breeder age, considering eggs from young breeders (33 weeks) and eggs from old breeders (63 weeks). It was observed that eggs from breeders at 33 weeks have lower weight and number of pores per cm² compared with eggs from older birds. 63 weeks broiler breeders had lower percentage of eggshell in relation to egg weight, lower specific weight, strength and thickness, when compared with eggs from young breeders. The proportion of shell membranes in relation to its total thickness was significantly higher in young breeders. It was concluded that eggs from older broiler breeders have lower eggshell quality than the young breeders. The shell membranes in young breeder's eggs play a significant role in its structure, making it necessary to focus on this layer in future studies on eggshell quality and their relationship between breeder age and incubation yield.(AU)

Óleo essencial de Baccharis tridentata Vahl: composição química, atividade antioxidante e fungitóxica, e caracterização morfológica das estruturas secretoras por microscopia eletrônica de varredura / Baccharis tridentata Vahl essential oil: chemical composition, and antioxidant and fungitoxic activities and morphological characterization of secretory structures by scanning electron microscopy

Este trabalho teve como objetivos avaliar a composição química do óleo essencial de Baccharis tridentata Vahl, as atividades antioxidante e fungitóxica, e estudar a morfologia das estruturas secretoras do óleo essencial presentes na superfície foliar por meio de microscopia eletrônica de varredura (MEV). A extração do óleo essencial foi realizada por hidrodestilação, as análises quantitativas e qualitativas foram executadas por meio de cromatografia em fase gasosa com detector de ionização de chamas (FID) e acoplada à espectrometria de massas, respectivamente. A atividade antioxidante foi realizada empregando-se os métodos de redução do radical estável DPPH e o ensaio de oxidação do sistema β-caroteno/ácido linoleico. As atividades fungitóxicas foram avaliadas utilizando o teste bioanalítico in vitro, sobre a inibição do crescimento micelial dos fitopatógenos Fusarium oxysporum, Colletotrichum gloeosporioides e Rhizoctonia solani. A composição química revelou a presença de 28 compostos, sendo o α-tujeno (22,93 por cento) o constituinte majoritário; não foi observada atividade antioxidante por meio dos ensaios utilizados, no entanto, observou-se atividade fungitóxica sobre o crescimento micelial dos fitopatógenos estudados. Já os estudos da superfície foliar por MEV revelaram a presença de tricomas glandulares em ambas as superfícies abaxial e adaxial.

This study aimed to evaluate the chemical composition and the antioxidant and fungitoxic activities of Baccharis tridentata essential oil, as well as to study the morphology of its secretory structures present on the leaf surface by scanning electron microscopy (SEM). The essential oil was extracted by hydrodistillation; the quantitative and qualitative analyses were performed on a gas chromatograph equipped with a flame ionization detector (FID) and coupled to a mass spectrometer, respectively. The antioxidant activity was determined by the methods of reduction of the DPPH stable radical and oxidation of the β-carotene/linoleic acid system. Fungitoxic activities were assessed by the in vitro bioanalytical test on the inhibition of the mycelial growth of the plant pathogens Fusarium oxysporum, Colletotrichum gloeosporioides and Rhizoctonia solani. The chemical composition revealed the presence of 28 compounds, with α-thujene (22.93 percent) as the major constituent. No antioxidant activity was observed in the tests used; however, there was fungitoxic activity against the mycelial growth of plant pathogens. Leaf surface studies by SEM revealed the presence of glandular trichomes on both abaxial and adaxial surfaces.

Effect of aging on bioactive amines, microbial flora, physico-chemical characteristics, and tenderness of broiler breast meat.

The objective of this study was to investigate the influence of aging on the levels of bioactive amines, microbial flora, physico-chemical characteristics, and tenderness of broiler breast. Forty-five 1-d-old Cobb broilers were aged at temperatures from 1.0 to 5.7 degrees C for 8 h. Nonaged broiler breast contained spermine, spermidine, and low levels of putrescine. There was prevalence of aerobic mesophiles followed by Pseudomonas. Mean pH, nonprotein N, weight loss after roasting, and shear force were 5.92, 0.46 g of N/100 g, 19.4%, and 5.57 kg, respectively. During aging, there was a significant increase in Pseudomonas and on the levels of amines. Two different amines were detected - tyramine and histamine. Aging resulted in a significant increase in tenderness without affecting pH, non-protein N, and weight loss after roasting. There was significant correlation between aging temperature and total bioactive amine levels. Aging above 4.9 degrees C induced the formation of histamine; therefore, aging should be performed at temperatures < or = 4.9 degrees C to prevent the formation of this amine, which has been associated with human health hazards. During storage of aged broiler breast at -18 +/- 1 degrees C for 89 d, there was no significant difference on pH, nonprotein N, and weight loss after roasting; however, there was a significant decrease on spermine, spermidine, putrescine, and tyramine levels. On the 89th day of storage, histamine was detected, and the shear force was significantly lower when compared with the samples immediately after aging. Therefore, the storage time of aged breast should not exceed 64 d to prevent histamine formation and to avoid excessive softening of the meat. Histamine in aged broiler breast could be used as an index of aging temperatures above 4.9 degrees C and also of frozen storage for more than 64 d.

Inheritance of acylsugar contents in tomatoes derived from an interspecific cross with the wild tomato Lycopersicon pennellii and their effect on spider mite repellence

Acylsugars present in Lycopersicon pennellii are responsible for the high levels of pest resistance often found in this wild tomato taxon. We investigated the inheritance of acylsugar contents in segregating populations of the interspecific tomato cross L. esculentum x L. pennellii and estimated correlations between leaflet acylsugar contents and the levels of mite repellence. Acylsugar contents were quantified with the Sommogy-Nelson colorimetric method in the acessions L. esculentum 'TOM-584' (P(1), low acylsugars), L. pennellii 'LA-716' (P(2), high acylsugars), in the interspecific F(1) (P(1) x P(2)) and in the F(2 )(P(1) x P(2)) generations. Mite resistance was assessed by a repellence test. Broad-sense heritability of acylsugar contents was moderately high (h(2)(b) = 0.476). Frequency distributions in the P(1), P(2), F(1) and F(2) can be explained by the action of a single major locus, with near-complete dominance of the L. esculentum allele for low-acylsugar content over the L. pennellii allele for high content. Indirect selection for high levels of acylsugars in leaflets led to correlated increases in the levels of mite repellency, indicating that acylsugars may be the main factor involved in mite resistance

The combination of zidovudine and interferon alpha-2B in the treatment of adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATL) is frequently a very aggressive malignancy with a poor survival despite aggressive multiagent chemotherapy. The combination of the antiretroviral drug zidovudine (AZT) and interferon alpha (IFNalpha) has been reported to induce remissions in patients with ATL. The purpose of this study was to evaluate the clinical response and toxicity following administration of a combination of IFNalpha-2b and AZT in patients with human T-cell lymphotropic virus type I (HTLV-I)-associated ATL. Eighteen patients with ATL (chronic. crisis, acute or lymphoma type) were treated with the combination of AZT (50 - 200 mg orally 5 times a day) and IFNalpha-2b (2.5 - 10 million units subcutaneously daily). Three patients had objective responses lasting more than one month. One patient had a clinical complete remission, lasting 21.6 months and two patients had partial remissions lasting 3.7 and 26.5 months. Six patients were not considered evaluable for response due to short and/or interrupted periods of treatment. Seventeen patients have died with a median survival time after initiation of therapy of 6 months. Neutropenia and thrombocytopenia were the dose limiting toxicities. In conclusion, the response rate in this study was lower than noted in the two previous published series. This may be due to the amount and type of prior treatment our patients had received.

The radioprotective effect of a new aminothiol (20-PRA).

We examined the radioprotective effect of aminothiol 2-N-propylamine-cyclo-hexanethiol (20-PRA) on a human leukemic cell line (K562) following various radiation doses (5, 7.5 and 20 Gy) using a source of 60Co gamma-rays. At 5 Gy and 1 nM 20-PRA, a substantial protective effect (58%) was seen 24 h after irradiation, followed by a decrease at 48 h (11%). At the high radiation dose (20 Gy) a low protective effect was also seen (35%). In addition, the antitumorigenic potential of 10 nM 20-PRA was shown by the inhibition of crown gall formation induced by Agrobacterium tumefaciens. The radioprotective potency of 20-PRA is 10(5)-10(6) times higher than that of the aminothiol WR-1065 (N-(2-mercaptoethyl)-1,3-diaminopropane) whose protective effect is in the 0.1 to 1.0 mM range.

The radioprotective effect of a new aminothiol (20-PRA)

We examined the radioprotective effect of aminothiol 2-N-propylamine-cyclo-hexanethiol (20-PRA) on a human leukemic cell line (K562) following various radiation doses (5, 7.5 and 20 Gy) using a source of (60)Co gamma-rays. At 5 Gy and 1 nM 20-PRA, a substantial protective effect (58 per cent) was seen 24 h after irradiation, followed by a decrease at 48 h (11 per cent). At the high radiation dose (20 Gy) a low protective effect was also seen (35 per cent). In addition, the antitumorigenic potential of 10 nM 20-PRA was shown by the inhibition of crown gall formation induced by Agrobacterium tumefaciens. The radioprotective potency of 20-PRA is 10(5)-10(6) times higher than that of the aminothiol WR-1065 N-(2-mercaptoethyl) - 1,3-diaminopropane) whose protective effect is in the 0.1 to 1.0 mM range.

Metabolism by Schistosoma mansoni of a new schistosomicide: 2-[(1-methylpropyl)amino]-1-octanethiosulphuric acid.

In order to investigate the mode of action of a new class of schistosomicides, the N-alkylaminoalkanethiosulphuric acids, the [outer 25S] 2-[(1-methylpropyl)amino]-1-octanethiosulphuric acids was synthesized. Labelling studies of adult Schistosoma mansoni were performed in infected mice and in in vitro incubations. After a single oral dose of the drug to infected mice, 5 metabolites were detected by thin-layer chromatogrpahy in organic extracts of male and female adult schistosomes. In vitro studies showed that the same compounds were present in organic extracts obtained from adult male and female worms. One of these metabolites was identified by mass spectroscopy as being the dimeric disulphide derivative of the parent labelled thiosulphuric acid.

Schistosomicidal activity of alkylaminooctanethiosulfuric acids.

The schistosomicidal activity of a new series of alkylaminooctanethiosulfuric acids was studied in white Swiss mice infected with the L.E. strain of Schistosoma mansoni (Belo Horizonte, MG, Brazil). In a preliminary screening of six compounds, two derivatives - 2-[(1-methylpropyl)amino]-1-octanethiosulfuric acid and 2-[(1-methylethyl)-amino]-1-octanethiosulfuric acid - given orally in doses of 300 mg/kg/day for five consecutive days, caused interruption of the oviposition and the hepatic shift of more than 90% of the worms. Both compounds caused a significant reduction in worm burden and, interestingly, the female schistosomes were more susceptible. With the therapeutic schedule of two doses of 800 mg/kg over a 20 day interval, the death of almost all the females and about 50% of the males was observed. Female worms recovered from treated mice showed scattered vitteline glands. Results of in vitro experiments against different developmental stages of the parasite revealed the induction of paralysis and damage to the tegument membrane. The drugs presented no toxic effects on the animals.

Application of gravitational sedimentation to efficient cellular recycling in continuous alcoholic fermentation.

A mathematical model for the sedimentation velocity in an inclined parallel plate sedimenter is proposed. The parameters of the alcoholic fermentation broth (cell density of Saccharomyces cerevisiae, density of the fermentation medium, viscosity of the broth at various alcohol and biomass contents) were determined experimentally. The sedimentation velocities were predicted under the various operational conditions and parameters, both of the broth (the alcohol concentration and cell content) and the sedimenter prototype (length, distance between the plates, and slope). The proposed model for the sedimentation velocity presented a good correlation with the experimental results of continuous sedimentation. These sedimenter prototypes were assembled and tested for efficiency of separation of yeast cell under conditions considered for interest for continuous alcoholic fermentation. A selective filter for the overflow composed of calcium alginate gel improved operation. A high operational stability, high separation efficiency (over 98%), and adequate settler residence times (about 20 min) were attained. The operational results permitted the operation of continuous alcoholic fermentation with cellular recycling effected exclusively by gravitational sedimentation, this characterizing a process of enormous industrial interest because of the operational simplicity and low operational and maintenance costs.

Cloning of human and bovine homologs of SNF2/SWI2: a global activator of transcription in yeast S. cerevisiae.

We performed positional cloning of genes carried on yeast artificial chromosomes that span a human translocation breakpoint associated with a human disease and isolated by chance human and bovine genes with strong homology to the S. cerevisiae genes, SNF2/SWI2 and STH1, and the D. melanogaster gene brahma. We report here sequence analysis, expression data, and functional studies for this human SNF2-like gene (hSNF2L) and its bovine homolog (bovSNF2L). Despite strong homology at the amino acid level, hSNF2L is not capable of complementing the yeast mutations snf2 or sth1 in S. cerevisiae. Furthermore, in contrast to SNF2 itself, a fusion protein consisting of the DNA binding domain of LexA and hSNF2L did not transactivate a reporter gene downstream of LexA binding sites in a yeast expression system. The strong similarity between hSNF2L and these yeast and drosophila genes suggest that the mammalian genes are part of an evolutionarily conserved family that has been implicated as global activators of transcription in yeast and fruitflies but whose function in mammals remains unknown.

Pharmacokinetic profile of tert-butylaminoethanethiol

A preliminary study of the pharmacokinetic parameters of t-Butylaminoethanethiol (TBAESH) was performed after administration of a single dose (35 mg/kg) either orally or intravenously. Plasma or blood samples were treated with dithiothreitol, perchloric acid and, after filtration, submitted to further purification with anionic resin. In the final step the drug was retained on a cationic resin column, eluted with NaCl lM and detected according to the method of Ellman (1958). The results suggested a pharmacokinetic behavior related to a one open compartment model with the following values for the total drug: area under the intravenous curve (AUC i.v.): 443(+ ou -) 24.0; AUC oral: 85.5(+ ou -) 14.5 ug min.ml(elevado a -1); elimination rate constant: 0.069(+ ou -) 0.0055 min(elevado a -1), biological half-life: 10.0(+ ou -) 0.80 min; distribution volume 1.15(+ ou -) 0.15 ml/g; biodisponibility: 0.19(+ ou -) 0.02. From a pharmacokinetic standpoint, TBAESH seems to have no advantage over the analogous disulfide compound

Pharmacokinetic profile of tert-butylaminoethanethiol.

A preliminary study of the pharmacokinetic parameters of t-Butylaminoethanethiol (TBAESH) was performed after administration of a single dose (35 mg/kg) either orally or intravenously. Plasma or blood samples were treated with dithiothreitol, perchloric acid and, after filtration, submitted to further purification with anionic resin. In the final step the drug was retained on a cationic resin column, eluted with NaCl lM and detected according to the method of Ellman (1958). The results suggested a pharmacokinetic behavior related to a one open compartment model with the following values for the total drug: area under the intravenous curve (AUCi.v.): 443 +/- 24.0; AUCoral: 85.5 +/- 14.5 micrograms min.ml-1; elimination rate constant: 0.069 +/- 0.0055 min-1, biological half-life: 10.0 +/- 0.80 min; distribution volume 1.15 +/- 0.15 ml/g; biodisponibility: 0.19 +/- 0.02. From a pharmacokinetic standpoint, TBAESH seems to have no advantage over the analogous disulfide compound.

Pharmacokinetic aspects of Tert-Butylaminoethyl disulfide, an experimental drug against schistosomiasis in mice

Um estudo preliminar da farmacocinética do t-butilamino-etil-dissulfeto foi conduzido utilizando droga fria ou radioativa em duas diferentes doses (35 e 300 mg/Kg). Amostras de plasma ou sangue foram tratadas com ditiotreiol, ácido perclórico, e, após filtraçäo, submetidas a uma subseqüente purificaçäo em um "batch" de resina aniônica. Na etapa final, a droga foi retida em coluna de resina catiônica, eluída com NaCl 1 M e detectada pelo método de Ellman (1958). Alternativamente, a droga radioativa foi detectada por cintilaçäo líquida. Os resultados correspondentes a droga total administrada na menor dose sugeriram um comportamento farmacocinético relacionado ao modelo de um compartimento aberto, com os seguintes parâmetros: área sob a curva intravenosa (ASCI.V.): 671 ñ 14; ASCoral: 150 ñ 40 microng.min.ml-1; constante de eliminaçäo: 0,07 min-1; meia-vida biológica: 9,8 min; volume de distribuiçäo: 0,74 ml/g. Para a dose mais alta, os resultados indicaram aparentemente a ocorrência de um modelo mais complexo e näo adequadamente classificado. Analisados em conjunto os resultados sugerem a ocorrência de um comportamento farmacocinético dose-dependente. A droga é absorvida e eliminada rapidamente, sendo este último processo relacionado principalmente a metabolizaçäo. A droga parece mais tóxica quando administrada via I.V. porque por esta via ela näo sobre metabolismo de primeira passagem e, é, por outro lado rapidamente distribuída para os tecidos. O nível sanguíneo máximo tolerado pelos animais parece ser de 16 microng/ml