RESUMEN
A sample of high-molar mass hyaluronan was oxidized by seven oxidative systems involving hydrogen peroxide, cupric chloride, ascorbic acid, and sodium hypochlorite in different concentrations and combinations. The process of the oxidative degradation of hyaluronan was monitored by rotational viscometry, while the fragments produced were investigated by size-exclusion chromatography, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry, and non-isothermal chemiluminometry. The results obtained imply that the degradation of hyaluronan by these oxidative systems, some of which resemble the chemical combinations present in vivo in the inflamed joint, proceeds predominantly via hydroxyl radicals. The hyaluronan fragmentation occurred randomly and produced species with rather narrow and unimodal distribution of molar mass. Oxidative degradation not only reduces the molecular size of hyaluronan but also modifies its component monosaccharides, generating polymer fragments that may have properties substantially different from those of the original macromolecule.
Asunto(s)
Ácido Hialurónico/química , Mediciones Luminiscentes , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Detección de Spin , ViscosidadRESUMEN
Changes in dynamic viscosity of the solutions of a high-molar-mass hyaluronan (HA) were monitored using a rotational viscometer. The degradative conditions generated in the HA solutions by a system comprising ascorbate plus Cu(II) plus H(2)O(2) were studied either in the presence or absence of a drug--naproxen or acetylsalicylic acid. Continual decrease of the dynamic viscosity of HA solution was indicative of the polymer degradation. Addition of the drug retarded/inhibited the HA degradation in a concentration-dependent manner. The characteristics of the fragmented polymers were investigated by FT-IR spectroscopy and by two different liquid chromatographic techniques, namely by size-exclusion chromatography equipped with a multi-angle light scattering photometric detector and by high-performance liquid chromatography connected on-line to a spectrofluorometer.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/química , Ácido Ascórbico/química , Aspirina/farmacología , Cobre/química , Ácido Hialurónico/antagonistas & inhibidores , Ácido Hialurónico/química , Naproxeno/farmacología , Antiinflamatorios no Esteroideos/química , Aspirina/química , Cationes Bivalentes/química , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Peróxido de Hidrógeno/química , Estructura Molecular , Peso Molecular , Naproxeno/química , Oxidantes/química , Oxidación-Reducción , Soluciones/química , Espectrometría de Fluorescencia , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Viscosidad/efectos de los fármacosRESUMEN
Many human diseases are associated with harmful action of reactive oxygen species (ROS). These species are involved in the degradation of essential tissue or related components. One of such components is synovial fluid that contains a high-molecular-weight polymer--hyaluronan (HA). Uninhibited and/or inhibited hyaluronan degradation by the action of various ROS has been studied in many in vitro models. In these studies, the change of the molecular weight of HA or a related parameter, such as HA solution viscosity, has been used as a marker of inflicted damage. The aim of the presented review is to briefly summarize the available data. Their correct interpretation could contribute to the implementation of modern methods of evaluation of the antioxidative capacity of natural and synthetic substances and prospective drugs--potential inflammatory disease modifying agents. Another focus of this review is to evaluate briefly the impact of different available analytical techniques currently used to investigate the structure of native high-molecular-weight hyaluronan and/or of its fragments.
Asunto(s)
Ácido Hialurónico/química , Sustancias Macromoleculares/química , Especies Reactivas de Oxígeno , Animales , Antioxidantes/química , Secuencia de Carbohidratos , Humanos , Inflamación , Modelos Biológicos , Modelos Químicos , Datos de Secuencia Molecular , Polímeros/química , Xenobióticos/químicaRESUMEN
Several major policy initiatives have been undertaken in Victoria, Australia's second-largest state, to address difficulties in providing accessible and culturally sensitive mental health services to ethnic minorities. These initiatives include the development and publication of a policy statement, alteration of funding formulas to take into account populations of persons with non-English-speaking backgrounds, incentive funding mechanisms, new funding specifically devoted to ethnic mental health, the establishment of service development positions in the major public hospital networks, and the establishment of a pilot project to employ bilingual staff as psychiatric case managers.
