Different antithrombotic mechanisms among glycosaminoglycans revealed with a new fucosylated chondroitin sulfate from an echinoderm.

The antithrombotic activity of a fucosylated chondroitin sulfate extracted from the body wall of a sea cucumber was assessed using a stasis thrombosis model in rats. Intravenous administration of the polysaccharide reduced thrombosis in a dose-dependent manner. We also compared the antithrombotic action of the sea cucumber chondroitin sulfate with that of standard mammalian glycosaminoglycans, mainly heparin and dermatan sulfate. Intravascular injection of fucosylated chondroitin sulfate at the dose totally preventing thrombus formation produced a much more intense modification of the plasma anticoagulant activity than antithrombotic doses of unfractionated heparin, low-molecular-weight heparin and mammalian dermatan sulfate. Thus, it is possible that the mechanism of antithrombotic action of these polysaccharides are different. For fucosylated chondroitin sulfate, it depends mostly on modifications of the plasma anticoagulant activity, but it may involve additional effects in the case of mammalian glycosaminoglycans, perhaps modifications induced in the cells of the vessel wall. The anticoagulant and possibly the antithrombotic actions of fucosylated chondroitin sulfate are mostly dependent on heparin cofactor II activity, and both are markedly reduced with the decrease of the chain size of the polymer. Overall, the sulfated polysaccharide from the invertebrate revealed an unequivocal effect in preventing experimental venous thrombosis, is a useful tool to investigate the antithrombotic action in mammals and may offer an alternative for future development of a new therapeutic agent.

Histoarchitecture of schistosomal granuloma development and involution: morphogenetic and biomechanical approaches.

The authors present morphogenetic and biomechanical approaches on the concept of the Schistosoma mansoni granulomas, considering them as organoid structures that depend on cellular adhesion and sorting, forming rearrangement into hierarchical concentric layers, creating tension-dependent structures, aiming to acquire round form, since this is the minimal energy form, in which opposing forces pull in equally from all directions and are in balance. From the morphogenetic point of view, the granulomas function as little organs, presenting maturative and involutional stages in their development with final disappearance (pre-granulomatous stages, subdivided in: weakly and/or initial reactive and exudative; granulomatous stages: exudative-productive, productive and involutional). A model for the development of granulomas was suggested, according to the following stages: encapsulating, focal histolysis, fiber production, orientation and compacting and involution and disintegration. The authors concluded that schistosomal granuloma is not a tangled web of individual cells and fibers, but an organized structure composed by host and parasite components, which is not formed to attack the miracidia, but functions as an hybrid interface between two different phylogenetic beings.

Systemic modulation of peripheral eosinophilia (air pouch model) in Schistosoma mansoni infection

Schistosoma mansoni infection induces in their hosts a marked and sustained eosinophilia, which is influenced or modulated by complex mechanisms, that vary according to the phase of infection. To address this phenomenon, we used the air pouch (AP) model in control and infected Swiss webster mice, analyzing the cellular, tissue response and local expression of adhesion molecules [CD18 (ß2-chain), CD44, ICAM-1 (CD54), L-selectin (CD62L), CD49d (alpha4-chain), LFA1 (CD11a)]. Infected animals were studied at 3 (pre-oviposition phase), 7 (acute phase), and 14 (chronic phase) weeks after infection (5-6 mice/period of infection). Normal mice were age-matched. Results showed that after egg stimulation, compared with matched controls, the infected mice, at each point of infection, showed a lower eosinophil response in the acute (7 weeks) and chronic phase (14 weeks) of infection. However, when the infected mice were in pre-oviposition phase (3 weeks) their eosinophil response surpassed the control ones. In the AP wall of infected mice, a significant decrease in the expression of ICAM-1 and CD44 in fibroblastic-like cells and a reduction in the number of CD18 and CD11 a in migratory cells were observed. The other adhesion molecules were negative or weakly expressed. The results indicated that in the air pouch model, in S. mansoni-infected mice: (1) eosinophil response is strikingly down-regulated, during the acute ovular phase; (2) in the pre-oviposition phase, in contrast, it occurs as up-regulatory modulation of eosinophil responses, in which the mechanisms are completely unknown; (3) in the chronic phase of the infection, the down modulation of eosinophil response is less pronounced; (4) Down-regulation of adhesion molecules, specially of ICAM-1 appear to be associated with the lower eosinophil response.

Immunological system and Schistosoma mansoni: co-evolutionary immunobiology. What is the eosinophil role in parasite-host relationship?

Schistosomes, ancestors and recent species, have pervaded many hosts and several phylogenetic levels of immunity, causing an evolutionary pressure to eosinophil lineage expression and response. Schistosoma mansoni adult worms have capitalized on the apparent adversity of living within the mesenteric veins, using the dispersion of eggs and antigens to other tissues besides intestines to set a systemic activation of several haematopoietic lineages, specially eosinophils and monocytes/macrophages. This activation occurs in bone marrow, spleen, liver, lymph nodes, omental and mesenteric milky spots (activation of the old or primordial and recent or new lymphomyeloid tissue), increasing and making easy the migration of eosinophils, monocytes and other cells to the intestinal periovular granulomas. The exudative perigranulomatous stage of the periovular reaction, which present hystolitic characteristics, is then exploited by the parasites, to release the eggs into the intestinal lumen. The authors hypothesize here that eosinophils, which have a long phylogenic story, could participate in the parasite-host co-evolution, specially with S. mansoni, operating together with monocytes/macrophages, upon parasite transmission.

Systemic modulation of peripheral eosinophilia (air pouch model) in Schistosoma mansoni infection.

Schistosoma mansoni infection induces in their hosts a marked and sustained eosinophilia, which is influenced or modulated by complex mechanisms, that vary according to the phase of infection. To address this phenomenon, we used the air pouch (AP) model in control and infected Swiss webster mice, analyzing the cellular, tissue response and local expression of adhesion molecules [CD18 (beta(2)-chain), CD44, ICAm-1 (CD54), L-selectin (CD62L), CD49d (alpha(4)-chain), LFA1 (CD11 alpha)]. Infected animals were studied at 3 (pre-oviposition phase), 7 (acute phase), and 14 (chronic phase) weeks after infection (5-6 mice/period of infection). Normal mice were age-matched. Results showed that after egg stimulation, compared with matched controls, the infected mice, at each point of infection, showed a lower eosinophil response in the acute (7 weeks) and chronic phase (14 weeks) of infection. However, when the infected mice were in pre-oviposition phase (3 weeks) their eosinophil response surpassed the control ones. In the AP wall of infected mice, a significant decrease in the expression of ICAM-1 and CD44 in fibroblastic-like cells and a reduction in the number of CD18 and CD11 alpha in migratory cells were observed. The other adhesion molecules were negative or weakly expressed. The results indicated that in the air pouch model, in S. mansoni-infected mice: (1) eosinophil response is strikingly down-regulated, during the acute ovular phase; (2) in the pre-oviposition phase, in contrast, it occurs an up-regulatory modulation of eosinophil response, in which the mechanisms are completely unknown; (3) in the chronic phase of the infection, the down modulation of eosinophil response is less pronounced; 4) Down-regulation of adhesion molecules, specially of ICAM-1 appear to be associated with the lower eosinophil response.

Proteinograma sérico de novilhas sadias da raça Girolanda criadas no Município de Itaguaí (RJ) / Seric proteinogram in healthy crossbred heifers from Rio de Janeiro, Brazil

Thirteen clinicaly healthy crossbred (Holstein x Zebu) aged between 20 and 45 months, raised in Rio de Janeiro State, Brazil, were utilized. Samples of blood (2), without anticoagulant, were colected from each animal by jugular vein puncture. It was determined the values for total protein, albumin (commercial kits), globulins and albumin/globulins ratio by mathematics calculation. The observed limits, mean and respective standard deviation in g/dl were: 5.70 to 8.80 and 7.01 more or less 0.65 (total protein); 2.60 to 4.20 and 3.10 more or less 0.36 (albumin); 2.30 to 5.00 and 3.70 more or less 0.59 (globulins) and 0.60 to 3.50 and 2.25 more or less 0.87 (albumin/globulins ratio)

Dermato-polimiosite tumoral. / Tumoral dermatopolymyositis

Os autores compararam 14 pacientes portadores de dermato-polimiosite primaria (DP) com pacientes portadores de reumatismo tumoral nao invasivo (RTNI) e neoplasias malignas. As idades medias no DP, DS, RNTI e neoplasias malignas foram de 25,3 mais ou menos 19,0, 47,8 mais ou menos 10,8, 51,7 mais ou menos 14,1 e 58,2 mais ou menos 13,3 anos respectivamente.Houve preponderancia do sexo masculino no grupo RTNI e feminino do DS tumoral (DST). A terapeutica para a DST mostrou-se mais eficaz com o uso de quimioterapia, radioterapia do que com o uso de anti-inflamatorios. Os dados obtidos sugerem que as dermato-polimiosite tumorais possam surgir numa faixa etaria intermediaria entre a DP e tumores malignos. A incidencia de neoplasias em dermato-polimiosite foi de 28,5%, enquanto a incidencia de DST para uma populacao de portadores de RNTI e neoplasias foi respectivamente de 22,2% e 1,1%. Especula-se tambem a respeito de um possivel mecanismo imunopatologico da DST pelo qual o nucleo tumoral poderia ter a capacidade de desviar do tumor uma populacao de celulas capazes de reagir a antigenos tumorais de uma maneira tal que a reacao se daria a nivel do sistema muscular