Terapia biológica em artrite reumatoide: novas perspectivas no controle e remissão / Biological therapy in rheumatoide arthritis: new perspectives in control and remission

O tratamento das doenças autoimunes sofreu grande avanço nos últimos anos. A artrite reumatoide, de etiologia desconhecida, porém com uma desregulação do sistema imunológico relacionada à sua eclosão e evolução, é hoje passível de tratamento, visando à remissão tanto clínica quanto das lesões estruturais. Além dos anti-inflamatórios e analgésicos utilizados para alívio dos sintomas, várias outras drogas, rotuladas de modificadoras do curso da doença (DMCDs), que visam controlar este distúrbio imunológico expresso pela atividade de diversos mediadores inflamatórios, estão contribuindo para a melhoria da qualidade de vida e do prognóstico dos pacientes.

Autoimmune diseases, as rheumatoid arthritis (RA) had a strong development in their treatment last years. Over the past years, the knowledge about the pathophysiological mechanism of RA has advanced dramatically, with the development of new classes of drugs and the implementation of different strategies of treatment and follow-up. Beside this new drugs, the associated use of the anti-inflammatory drugs, corticoids, sintetic or traditionals disease-modifying antirheumatic drugs allow control or suppress the disease activity giving a better quality of life and prognosis to the patients.

Synthesis and antimicrobial activity of pyranobenzoquinones related to the pyranonaphthoquinone antibiotics.

The synthesis and antimicrobial activity of isochromane-type analogs of the pyranonaphthoquinone antibiotics are reported. Isochromane derivatives with (17a, b) and without (22a, b) a C-4 hydroxyl moiety and their corresponding quinones (19a and 23), were prepared. Both quinones exhibited antimicrobial activity against Staphylococcus aureus, Bacillus atrophaeus and Streptococcus agalactiae, while the related isochromanes were inactive. The results suggest that the quinone moiety is important for biological activity while the C-4 hydroxyl may not be essential.

Effect of gluconic acid as a secondary carbon source on non-growing L-lysine producers cells of Corynebacterium glutamicum. Purification and properties of 6-phosphogluconate dehydrogenase.

We studied the production of L-lysine in Corynebacterium glutamicum ATCC 21543 non growing cells obtained by nutrient limitation. Statistical analysis revealed significant differences in the L-lysine titers of glucose, gluconic acid or glucose-gluconic acid cultures. Higher L-lysine titer obtained in batch cultures with mixed carbon sources or gluconic acid alone were found to be associated with a high 6-phosphogluconate dehydrogenase activity (6PGDH, E.C.1.1.1.44). This enzyme is a pivotal enzyme within the hexose monophosphate pathway, and thus of importance for L-lysine production. 6PGDH was purified and characterized. The purified enzyme migrates as a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a molecular mass of 52.5 kDa. The molecular mass of the native enzyme was estimated to be 120 kDa by molecular exclusion chromatography, thus suggesting a homodimeric structure. The amino terminal sequence shows a strong similarity (a match of 86% of the first 20 amino acid) to the 6PGDH from other microorganisms such as, E. coli and B. subtilis. The pI of the dimeric native enzyme and the optimum pH were 6.2 and 8.0, respectively. For the oxidative decarboxylation of 6-phosphogluconate, K(m) of 71 &mgr;M and 43 &mgr;M were obtained for 6-phosphogluconate and NADP(+), respectively.

Premature infants respond to early-onset and late-onset sepsis with leukocyte activation.

OBJECTIVE: Leukocyte differentiation antigens are expressed on the cell membrane during activation. The purpose of this study was to evaluate leukocyte activation in premature neonates with sepsis. Paired blood samples from the same individual while sick and while convalescent were examined to quantify the expression of leukocyte antigens in these clinical states. METHODS: Mononuclear blood cells from 21 premature infants (24 to 30 weeks' gestation) were analyzed. The "sick" samples were drawn at the time of workup for sepsis; "convalescent" samples were drawn 20 days later. Samples were incubated with monoclonal antibodies to the lymphocyte antigens CD3, CD19, CD25, CD26, CD71, and CD69 and neutrophil antigens CD11b, CD11c, CD13, CD15, CD33, and CD66b. The cells were lysed, fixed, and analyzed by flow cytometry. RESULTS: Twenty-one infants enrolled in the study had multiple sepsis evaluations and had more than one sample available for a paired observation. CD33, CD66b, and CD19 levels were significantly elevated in both the presumed sepsis and culture-proven sepsis groups when compared with the samples drawn from those same patients when healthy. Expression of CD33 and expression of CD66b were correlated, and in a multivariate analysis the elevation of antigen expression was predictive of sepsis. CONCLUSIONS: Leukocytes from preterm newborn infants respond to infection with an increased expression of CD19, CD33, and CD66b on their cell surfaces.

Prenatal diagnosis by analysis of fetal cells in maternal blood.

The data accumulated thus far indicate that fetal NRBCs are the target cell type of choice in maternal blood for most investigators, although some groups continue to work with the trophoblast. Reports of persistent circulation of hematopoietic stem cells, lymphoid/myeloid progenitors, and lymphocytes mandate that removal of these cell types must occur before clinical diagnosis of the current pregnancy can be made. In selected cases, accurate detection of fetal aneuploidy has been made from fetal cells in maternal blood; the clinical evaluation sponsored by the National Institute of Child Health and Human Development will determine the sensitivity and specificity of cytogenetic diagnosis in a larger group of pregnant women, but this information will not be available for several years. At present, detection of uniquely fetal, paternally inherited gene polymorphisms or mutations such as the Rh(D) antigen is possible only because the mother lacks these genes; hence, maternal cell contamination does not hinder diagnosis. Currently the presence of large numbers of maternal cells in enriched samples precludes single-gene diagnosis for conditions in which the mother carries a mutant gene, because her cells are preferentially amplified and difficult to distinguish from those of the fetus. It is likely, however, that as techniques of individual fetal cell isolation are perfected, maternal cell contamination will no longer be an issue, and the entire fetal genome will become available for diagnosis and therapy. Pediatricians need to be aware of the progress of research in this field, because fetal cell isolation from maternal blood not only could change prenatal diagnosis but would change the amount of genetic information that arrives with a newborn infant at birth. The ultimate goal of this work is to diagnose noninvasively, in the first trimester, the common fetal aneuploidies and single-gene disorders, to permit in utero treatment, or to allow low-risk pregnant women carrying an abnormal fetus an opportunity for reproductive choice.

Bloqueo de bronquio fuente izquierdo con cateter de Fogarty / Bronchial blocking left source with Fogarty catheter

Se considera de interés la presentación de este caso, por ser la primera vez que se emplea en nuestro medio el catéter de Fogarty como bloqueador bronquial en presencia de hemoptisis masiva durante la cirugía de resección pulmonar en el niño (AU)

Bloqueo de bronquio fuente izquierdo con cateter de Fogarty / Bronchial blocking left source with Fogarty catheter

Se considera de interés la presentación de este caso, por ser la primera vez que se emplea en nuestro medio el catéter de Fogarty como bloqueador bronquial en presencia de hemoptisis masiva durante la cirugía de resección pulmonar en el niño