Insights into HLA-G genetics provided by worldwide haplotype diversity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Disease resistance of pacu Piaractus mesopotamicus (Holmberg, 1887) fed with beta-glucan

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Diazepam, em dose única, inibe a migração celular, a estimulação macrofágica e a atividade de TNF-α na reação inflamatória aguda induzida por LPS em camundongos

Benzodiazepines are one of the most frequently prescribed drugs due to their anxiolytic properties. The aim of this study was to evaluate the effects of diazepam on lipopolysaccharide-induced peritoneal acute inflammatory responses. Swiss mice were treated with diazepam in a single dose of 1 or 10 mg/kg- subcutaneously 1 h before an intraperitoneal injection of lipopolysaccharide or sterile saline solution. The mice were killed 16 h after and the cells were washed from the peritoneal cavity to determine the total number of cells and the mononuclear and polimorfonuclear subpopulations, as well as the TNF-alpha activity and percentage of spread macrophages. Our results showed that the diazepam treatment (1 and 10 mg/kg) induced a significant reduction in the LPS-induced macrophage stimulation and TNF-α activity. Diazepam (10 mg/kg) also reduced the inflammatory cellular migration when compared to the control. It can be concluded that the diazepam treatment in a single dose is able to influence the inflammatory cellular influx, macrophage stimulation and TNF-α activity in the acute inflammatory response in mice, having possible implications on the anti-infectious response efficiency.

Chemical, enzymatic and cellular antioxidant activity studies of Agaricus blazei Murrill

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Skeletal muscle degeneration and regeneration after injection of bothropstoxin-II, a phospholipase A2 isolated from the venom of the snake Bothrops jararacussu

A myotoxic phospholipase A2, named bothropstoxin II (BthTX-II), was isolated from the venom of the South American snake Bothrops jararacussu and the pathogenesis of myonecrosis induced by this toxin was studied in mice. BthTX-II induced a rapid increase in plasma creatine kinase levels. Histological and ultrastructural observations demonstrate that this toxin affects muscle fibers by first disrupting the integrity of plasma membrane, as delta lesions were the earliest morphological alteration and since the plasma membrane was interrupted or absent in many portions. In agreement with this hypothesis, BthTX-II released peroxidase entrapped in negatively charged multilamellar liposomes and behaved as an amphiphilic protein in charge shift electrophoresis, an indication that its mechanism of action might be based on the interaction and disorganization of plasma membrane phospholipids. Membrane damage was followed by a complex series of morphological alterations in intracellular structures, most of which are probably related to an increase in cytosolic calcium levels. Myofilaments became hypercontracted into dense clumps which alternated with cellular spaces devoid of myofibrillar material. Later on, myofilaments changed to a hyaline appearance with a more uniform distribution. Mitochondria were drastically affected, showing high amplitude swelling, vesiculation of cristae, formation of flocculent densities, and membrane disruption. By 24 hr, abundant polymorphonuclear leucocytes and macrophages were observed in the interstitial space as well as inside necrotic fibers. Muscle regeneration proceeded normally, as abundant myotubes and regenerating myofibers were observed 7 days after BthTX-II injection. By 28 days regenerating fibers had a diameter similar to that of adult muscle fibers, although they presented two distinctive features: central location of nuclei and some fiber splitting. This good regenerative response may be explained by the observation that BthTX-II does not affect blood vessels, nerves, or basal laminae. © 1991.

Structural characterization of novel chemotactic and mastoparan peptides from the venom of the social wasp Agelaia pallipes pallipes by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The importance of myeloperoxidase in apocynin-mediated NADPH oxidase inhibition

Apocynin is widely used as an inhibitor of the NADPH oxidase. Since myeloperoxidase (MPO) has been considered as essential for the mechanism of action of apocynin, here we used cells with different levels of MPO and compared their sensitivity to apocynin. HL-60 cells were differentiated with DMSO or IFN γ /TNF α and compared with peripheral mononuclear (PBMC) and polymorphonuclear cells (PMN). The relative MPO activity was PBMC = HL60 DMSO < HL60 IFN γ < PMN. Apocynin inhibited the intracellular reactive oxygen species production by PMN (80%) and IFN γ /TNF α -differentiated HL-60 cells (45%) but showed a minor effect in PBMC and DMSO differentiated HL-60 cells (20%). The addition of azide decreased the efficiency of apocynin in PMN and the addition of peroxidase increased the inhibition in PBMC. We also determined the gene expression of the components gp91phox, p47phox, p22phox and p67phox in the resting cells. Apocynin did not change gp91phox, p47phox or p22phox gene expression in nonstimulated PBMC, HL60 DMSO, HL60 IFN γ /TNF α , and PMN and has a subtle increase in p67phox in HL60 IFN γ /TNF α . The results from this work suggest that a rational search for better inhibitors of NADPH oxidase in leukocytes should include a correlation with their affinity as substrates for MPO.

Anti-hyperalgesic and anti-inflammatory activity of Alternanthera maritima extract and 2″-O-α-L-rhamnopyranosylvitexin in mice

Alternanthera maritima are used in Brazilian popular medicine for the treatment of inflammatory and infectious diseases. Species of Alternanthera have demonstrated biological activities in previous scientific studies. The aim of this study was to determine whether the ethanol extract of the aerial parts of A. maritima (EEAM) and the isolated compound 2″-O-α-L-rhamnopyranosyl-vitexin inhibit mechanical hyperalgesia and parameters of inflammation in mice. The oral administration of EEAM significantly inhibited carrageenan (Cg)-induced paw edema and reduced leukocyte migration into the pleural cavity. 2″-O-α-L-rhamnopyranosylvitexin significantly inhibited paw edema and reduced both leukocyte migration and the leakage of protein into the pleural cavity. Both EEAM and 2″-O-α-L-rhamnopyranosylvitexin significantly prevented the Cg-induced hyperalgesia. Local administration of 2″-O-α-L-rhamnopyranosylvitexin significantly prevented the Cg- and tumor necrosis factor (TNF)-induced hyperalgesia. In conclusion, this study demonstrated that EEAM is an anti-inflammatory and anti-hyperalgesic agent, and the results suggested that 2″-O-α-L-rhamnopyranosylvitexin is responsible for the effects of EEAM and the mechanism involves the TNF pathway.

Protective effects of the galectin-1 protein on in vivo and in vitro models of ocular inflammation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The immune system is limited by oxidative stress: dietary selenium promotes optimal antioxidative status and greatest immune defense in pacu Piaractus mesopotamicus

Reactive oxygen species (ROS) are reactive molecules containing oxygen, that form as byproducts of aerobic metabolism, including immune system processes. Too much ROS may cause oxidative stress. In this study, we examined whether it can also limit the production of immune system compounds. To assess the relationship between antioxidant status and immunity we evaluated the effect of dietary supplementation with organic selenium, given at various levels for 10 days, on the antioxidant and immune system of the pacu fish (Piaractus mesopotamicus). Fish fed a diet containing 0.6 mg Se-yeast kg(-1) showed significant improvement in antioxidant status, as well as in hematological and immunological profiles. Specifically, they had the highest counts for catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), red blood cells, and thrombocytes; the highest leukocyte count (particularly for monocytes); and the highest serum lysozyme activity. There was also a positive correlation between GPx and lysozyme in this group of fish. These findings indicate that short-term supplementation with 0.6 mg Se-yeast kg(-1) reestablished the antioxidative status, allowing the production of innate components which can boost immunity without the risk of oxidative stress. This study shows a relationship between oxidative stress and immunity, and, from a practical perspective, shows that improving immunity and health in pacu through the administration of selenium could improve their growth performance.

Análise de inflamassoma induzido por urato monossódico em monócitos de gestantes portadoras de pré-eclampsia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação proteômica do conteúdo vaginal em resposta ao tratamento da vaginose bacteriana

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Terapia gênica com interferon-alfa no controle do câncer colorretal

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeito do plasma rico em glicose na apoptose de neutrófilos de cães

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Valor do teste de redução do Tetrazólio Nitroazul (NBT) no diagnóstico de processos inflamatórios caninos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)