RESUMO
An isocratic high-performance liquid chromatography with electrochemical detection (HPLC-ED) method for the determination of total plasma homocysteine [H(e)] has been developed. The electrochemical detection is performed using a glassy-carbon electrode that is not specific for thiol groups. We have tried to solve the problem of specificity focusing our work on chromatographic resolution and have obtained good results without coelution of other thiol compounds or any substances mentioned as common interferences for carbon electrode methods: uric acid, ascorbic acid and salicylates. Thirty samples a day can be assayed for total homocysteine with a lower limit of detection of 2 pmol, and a limit of quantification of 1.0 micromol/l, with a coefficient of variation (C.V.) <20%. For a concentration of total plasma homocysteine of 9.36 micromol/l, the intra- and inter-assay C.V.s were of 3.86% and 5.55% respectively. The analytical recovery achieved in the preparation of the samples ranged from 85.0% to 98.3% and the electrochemical response was linear up to 100 micromol/l.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Homocisteína/sangue , Carbono , Eletroquímica/instrumentação , Eletrodos , Humanos , Padrões de Referência , Sensibilidade e EspecificidadeRESUMO
La determinación de los niveles de homocisteína plasmática total se ha convertido en un estudio de gran utilidad debido a que los valores moderadamente elevados de homocisteína circulantes pueden causar aterosclerosis y obstrucción de las arterias coronarias. Se sabe que son varios los factores que causan el aumento de homocisteína plasmática; éstos incluyen afecciones metabólicas hereditarias, estado nutricional y el tratamiento con ciertos fármacos. Los posibles mecanismos por los cuales los niveles elevados de homocisteína causan afecciones vasculares incluyen efectos sobre las plaquetas, los factores de coagulación y el endotelio. Las lesiones ateroscleróticas y la trombosis relacionadas con la hiperhomocisteinemia podrían ser prevenidas con una dieta rica en vitaminas, aunque esto hasta el presente no ha sido comprobado
Assuntos
Homocisteína/metabolismo , Metionina/metabolismo , Doenças Vasculares/enzimologia , Fatores de Risco , Trombose , Vitaminas , Vitaminas/uso terapêuticoRESUMO
La determinación de los niveles de homocisteína plasmática total se ha convertido en un estudio de gran utilidad debido a que los valores moderadamente elevados de homocisteína circulantes pueden causar aterosclerosis y obstrucción de las arterias coronarias. Se sabe que son varios los factores que causan el aumento de homocisteína plasmática; éstos incluyen afecciones metabólicas hereditarias, estado nutricional y el tratamiento con ciertos fármacos. Los posibles mecanismos por los cuales los niveles elevados de homocisteína causan afecciones vasculares incluyen efectos sobre las plaquetas, los factores de coagulación y el endotelio. Las lesiones ateroscleróticas y la trombosis relacionadas con la hiperhomocisteinemia podrían ser prevenidas con una dieta rica en vitaminas, aunque esto hasta el presente no ha sido comprobado (AU)
Assuntos
Homocisteína/metabolismo , Metionina/metabolismo , Doenças Vasculares/enzimologia , Vitaminas/administração & dosagem , Vitaminas/uso terapêutico , Fatores de Risco , Trombose/prevenção & controleRESUMO
In comparative clinical studies of auranofin (AF, oral gold) and parenteral gold in the treatment of rheumatoid arthritis, no difference in efficacy was detected. Since the pharmacologic profiles of these compounds are different, we studied their combined effect on adjuvant arthritis (AA). The effect of AF alone and combined with gold sodium thiomalate (GTM) or gold sodium thiosulfate (GTS) on the excretion of urinary hydroxyproline (UHP) and urinary calcium (UCa), and the articular index of arthritic rats was followed during five weeks of treatment. The excretion of UHP and UCa was significantly inhibited (P less than 0.005) in rats treated with AF combined with GTM or GTS as compared with animals treated with the individual gold compounds. However, the articular index only decreased significantly (P less than 0.02) in the group of rats treated with AF + GTS. The present studies open the possibility that combined treatment with oral and injectable gold provide a new approach for chrysotherapy with an increased antiarthritic potency.
Assuntos
Artrite Experimental/tratamento farmacológico , Artrite/tratamento farmacológico , Auranofina/uso terapêutico , Tiomalato Sódico de Ouro/uso terapêutico , Tiossulfato Sódico de Ouro/uso terapêutico , Ouro/uso terapêutico , Administração Oral , Animais , Auranofina/administração & dosagem , Sinergismo Farmacológico , Quimioterapia Combinada , Tiomalato Sódico de Ouro/administração & dosagem , Tiossulfato Sódico de Ouro/administração & dosagem , Injeções Intramusculares , RatosRESUMO
We have observed an antiarthritic effect of combined chrysotherapy in adjuvant arthritis. Since superoxide radicals (O2-) are potent mediators of rheumatoid inflammation, we studied the combined effect of auranofin (AF) and injectable golds on luminol-dependent chemiluminescence (LDCL) and O2- generation by cytochrome-c reduction of activated leukocytes by different receptor-mediated stimuli: phorbol myristic acetate, 10(-6) M; f-Met-Leu-Phe, 10(-6) M; and poly-L-histidine, 10(-5) M. AF, 0.6 and 0.9 micrograms Au/ml, inhibited 34 and 58% of O2- generation, respectively; the addition to AF of 0.3 micrograms Au/ml of gold thiosulfate (GTS) increased this inhibition to 84 and 97% of the oxygen burst. Similar synergistic potentiation inhibition was obtained by LDCL. When the inhibition of O2- generation by the combined action of AF and GTS was compared with AF + gold sodium thiomalate (GTM), only GTS showed an activation on AF's inhibition of the oxygen burst of human leukocytes. The ligand thiosulfate in equimolar concentrations to GTS had a statistically significant (P less than 0.01) inhibitory effect on AF's blockade of O2- generation during the first 5 min of the interaction with the PMNs; thiomalate had no effect. Sequential pretreatment of PMNs with AF and GTS on O2- generation revealed that for synergism of combined gold action to take place, the cell membrane had to be subjected first to the action of oral gold or to the simultaneous combined action of oral and parenteral gold.(ABSTRACT TRUNCATED AT 250 WORDS)