RESUMO
Both experimental and epidemiological studies suggest that patients with autoimmune and other chronic inflammatory diseases are more prone to develop cancer. The aim of the present investigation is to find some typical differences between the content of lipid-bound sialic acid (LSA) and the activity of superoxide dismutase (SOD) in sera from children with neoplastic diseases and juvenile chronic arthritis (JCA). Our results show 30% lower SOD activity in the sera from children with cancer compared with the sera from children with JCA. LSA levels 102% and 166% higher than in children with JCA were observed in the sera from children with blood and solid cancers, respectively. The relation LSA/SOD is about fivefold higher in children with cancers. A negative correlation (r = 0.720, P < 0.001) exists between LSA and SOD in sera from children with cancers. No such correlation was established in the group of children with JCA. We suppose that such differentiation disappears in the beginning of neoplastic process during prolonged therapy of autoimmune diseases. From our findings SOD and LSA appear to be putative markers of malignant disease with potential usefulness not only in JCA but also in other conditions associated with an increased risk of neoplastic development.
Assuntos
Artrite Juvenil/sangue , Neoplasias/sangue , Ácidos Siálicos/sangue , Superóxido Dismutase/sangue , Adolescente , Artrite Juvenil/patologia , Doenças Autoimunes/sangue , Doenças Autoimunes/patologia , Biomarcadores/sangue , Biomarcadores Tumorais/sangue , Transformação Celular Neoplásica/patologia , Criança , Pré-Escolar , Doença de Hodgkin/sangue , Humanos , Lactente , Linfoma não Hodgkin/sangue , Ácido N-Acetilneuramínico , Neoplasias/etiologia , Neoplasias/patologia , Neuroblastoma/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
The protein binding of sulindac (CAS 38194-50-2) was studied using circular dichroism (CD). By the new algorithm for the analysis of proposed data the association constants (k) and number of binding sites (N) were determined. The binding was found to go through separate stages, where the binding affinity tends to become lower; the first step characterized by kI = 7.6 x 10(6) l.mol-1 and NI = 1.4; while for the second step kII = 1.7 x 10(6) l.mol-1 and NII = 6.6. On the basis of the CD-data and using UV-spectra the nature of binding sites was studied. It may be stated that the binding sites are situated in the region of asymmetrically perturbed chromophore of the drug, which made a positive contribution to the Cotton effect. The results obtained suggest a mechanism of interaction which is consistent with the stepwise binding model.
Assuntos
Albumina Sérica/metabolismo , Sulindaco/metabolismo , Algoritmos , Sítios de Ligação , Dicroísmo Circular , Humanos , Modelos Químicos , Ligação Proteica , Espectrofotometria Ultravioleta , Sulindaco/químicaRESUMO
A new method for analysis of circular dichroism titration data used for drug-protein binding investigations is proposed. A square equation between molar ellipticity change and total drug concentration is obtained which is examined analytically. A new minimization algorithm for determining the binding sites and association constants of each type of drug-protein complexes is applied.
Assuntos
Algoritmos , Dicroísmo Circular , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismo , Ligação Proteica , Receptores de Droga/metabolismoRESUMO
The authors investigated the release of isoniazid from repository tablets as related to form, processing technology, strength constant and storage for 5 years. On determining the diffusion coefficient (D), the initial dissolution rate (Vo) and the time required for the diffusion of the releasing medium to the middle of the tablet (t1/2), it was found that the difference in release rate between the flat and the biconvex tablets is small. Furthermore, it was stated that the three-layer tablets have very high D and Vo values and very low t1/2 values, for what reason they are unsuited for repository tablets of the composition under investigation. Moreover, it was found that an increase of the strength constant does not affect the D, t1/2 and Vo values, and that the release of isoniazid is retarded only in flat tablets with the highest strength constant. Storage exerts no effect on the drug release from these tablets. The industrial production of these tablets is under way.
