The inhibitory effect of MK886 on the inflammatory process caused by Paracoccidioidomycosis brasiliensis infection in genetically selected mice

Leukotrienes are classic inflammatory response mediators considered chemotactic agents and microbicidal activity regulators in cells of the innate immune system, playing a protective role against different infectious agents. In this study, we investigated the involvement of leukotrienes in the course of murine paracoccidioidomycosis based on the following immunologic parameters: cell influx, mieloperoxydase activity, NO production, cytokine production, and fungal recovery in lungs of mice selected according to the intensity of their low (AIRmin) and high (AIRmax) acute inflammatory response. Infection by P. brasiliensis induced considerable production of IL-6, IL-10, IFN-gamma and TNF-alpha cytokines, and led to cell recruitment, as well as NO production in lungs at different study periods. In animals treated with MK886, a leukotriene biosynthesis inhibitor, IFN-gamma, IL-6 and TNF-alpha production was lower, while neutrophil influx and NO production decreased. These results may explain the higher fungal load in lungs of animals in which leukotriene synthesis was inhibited, suggesting that leukotrienes have a possible protective role in experimental paracoccidioidomycosis. AIRmax animals had lower fungal load in comparison with AIRmin ones, which can be related to the AIR phenotype regarding neutrophil migration, besides lower production of NO and pro-inflammatory cytokines. Thus, mice presenting AIRmax background are more resistant to infection by P. brasiliensis.

Morphological alteration of peritoneal mast cells and macrophages in the mouse peritoneal cavity during the early phases of an allergic inflammatory reaction

We investigated the presence of mast cell granules in macrophages following an in vivo model of an allergic reaction. Injection of ovalbumin (100 mug) into the peritoneal cavity of sensitised mice produced a rapid (within 2 h) influx of neutrophils followed by a slower (after >4 h) eosinophil migration. Ovalbumin treatment induced a high incidence (similar to 50%) of mast cell degranulation compared to control phosphated-buffered saline-treated mice. The majority (similar to 90%) of peritoneal macrophages contained mast cell granules as early as 2 It post-ovalbumin, with lower values at later time-points, as determined by staining with Toluidine blue and Berberine sulphate. This was confirmed by electron microscopy which enabled us to identify the complex mast cell granule sub-structural components in macrophage phagosomes. In conclusion, we used histochemical and ultrastructural analyses to show that mast cell granules become internalised with macrophages during the early stages of an experimental allergic reaction. (C) 2001 Academic Press.

Functional and Ultrastructural Analysis of Annexin A1 and Its Receptor in Extravasating Neutrophils during Acute Inflammation

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

Reduced allergic lung inflammation in rats following formaldehyde exposure: Long-term effects on multiple effector systems

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

Purification, crystallization and preliminary X-ray diffraction analysis of crotamine, a myotoxic polypeptide from the Brazilian snake Crotalus durissus terrificus

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

Anti-Inflammatory Effects of Low-Level Light Emitting Diode Therapy on Achilles Tendinitis in Rats

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

Temporary fragmentation of a marginal lake and its effects on zooplankton community structure and organization

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

Manganese uptake and redistribution in soybean as affected by glyphosate

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

Formação, sustentação ou implosão de uma bolha imobiliária? A dinâmica de preços no mercado de imóveis de Natal no período 2005-2010

A motivação para a realização deste artigo foi a percepção de que o movimento de preços dos imóveis em Natal apresentava componentes que precisavam ser investigados, notadamente o influxo de capital estrangeiro, sobretudo para aplicação nos setores de turismo e imobiliário e o comportamento do crédito imobiliário. O objetivo do trabalho é examinar a evolução dos preços no mercado de imóveis da cidade no período 2005; 2010. Os indicadores levantados permitiram uma coleta de evidências suficiente para ampliar o grau de confiança nas hipóteses de que, de fato: a) ocorreu uma bolha no mercado de imóveis no triênio 2005; 2007; b) a bolha não implodiu no biênio 2009; 2010, após a crise financeira de 2008, pois o movimento de alta de preços se manteve tanto nos imóveis vendidos na planta quanto nos imóveis prontos.

Pulmonary neutrophil recruitment and bronchial reactivity in formaldehyde-exposed rats are modulated by mast cells and differentially by neuropeptides and nitric oxide

We have used a pharmacological approach to study the mechanisms underlying the rat lung injury and the airway reactivity changes induced by inhalation of formaldehyde (FA) (1% formalin solution, 90 min once a day, 4 days). The reactivity of isolated tracheae and intrapulmonary bronchi were assessed in dose-response curves to methacholine (MCh). Local and systemic inflammatory phenomena were evaluated in terms of leukocyte countings in bronchoalveolar lavage (BAL) fluid, blood, bone marrow lavage and spleen. Whereas the tracheal reactivity to MCh did not change, a significant bronchial hyporesponsiveness (BHR) was found after FA inhalation as compared with naive rats. Also, FA exposure significantly increased the total cell numbers in BAL, in peripheral blood and in the spleen, but did not modify the counts in bone marrow. Capsaicin hindered the increase of leukocyte number recovered in BAL fluid after FA exposure. Both compound 48/80 and indomethacin were able to prevent the lung neutrophil influx after FA, but indomethacin had no effect on that of mononuclear cells. Following FA inhalation, the treatment with sodium cromoglycate (SCG), but not with the nitric oxide (NO) synthase inhibitor L-NAME, significantly reduced the total cell number in BAL. Compound 48/80, L-NAME and SCG significantly prevented BHR to MCh after FA inhalation, whereas capsaicin was inactive in this regard. on the other hand, indomethacin exacerbated BHR. These data suggest that after FA inhalation, the resulting lung leukocyte influx and BHR may involve nitric oxide, airway sensory fibers and mast cell-derived mediators. The effect of NO seemed to be largely restricted to the bronchial tonus, whereas neuropeptides appeared to be linked to the inflammatory response, therefore indicating that the mechanisms responsible for the changes of airway responsiveness caused by FA may be separate from those underlying its inflammatory lung effects. (c) 2005 Elsevier B.V. All rights reserved.

Immune modulation induced by tuberculosis DNA vaccine protects non-obese diabetic mice from diabetes progression

We have described previously the prophylactic and therapeutic effect of a DNA vaccine encoding the Mycobacterium leprae 65 kDa heat shock protein (DNA-HSP65) in experimental murine tuberculosis. However, the high homology of this protein to the corresponding mammalian 60 kDa heat shock protein (Hsp60), together with the CpG motifs in the plasmid vector, could trigger or exacerbate the development of autoimmune diseases. The non-obese diabetic (NOD) mouse develops insulin-dependent diabetes mellitus (IDDM) spontaneously as a consequence of an autoimmune process that leads to destruction of the insulin-producing beta cells of the pancreas. IDDM is characterized by increased T helper 1 (Th1) cell responses toward several autoantigens, including Hsp60, glutamic acid decarboxylase and insulin. In the present study, we evaluated the potential of DNA-HSP65 injection to modulate diabetes in NOD mice. Our results show that DNA-HSP65 or DNA empty vector had no diabetogenic effect and actually protected NOD mice against the development of severe diabetes. However, this effect was more pronounced in DNA-HSP65-injected mice. The protective effect of DNA-HSP65 injection was associated with a clear shift in the cellular infiltration pattern in the pancreas. This change included reduction of CD4(+) and CD8(+) T cells infiltration, appearance of CD25(+) cells influx and an increased staining for interleukin (IL)-10 in the islets. These results show that DNA-HSP65 can protect NOD mice against diabetes and can therefore be considered in the development of new immunotherapeutic strategies.

Initial Development and Characterization of PLGA Nanospheres Containing Ropivacaine

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

PALEOCLIMATIC CONTROLS ON STABLE OXYGEN AND CARBON ISOTOPES IN CALICHE OF THE ABO FORMATION (PERMIAN), SOUTH-CENTRAL NEW-MEXICO, USA

The stable oxygen and carbon isotopic composition of caliche in fluvial and supratidal rocks of the Abo Formation (Permian), south-central New Mexico, is controlled by palecoclimate and depositional environment. Fluvial caliche consists of low-Mg calcite nodules and vertically oriented tubules that display stage II texture. Micrite matrix support, brecciation, ooids/pisoliths, aveolar-septal texture, and peloids are common in the fluvial caliche and, along with red color and slickensides in the host shale, indicate pedogenesis in a well-oxidized vadose zone. In contrast, periodic waterlogging of the supratidal paleosols, probably due to high water table, is indicated by drab colors, carbonaceous flecks, horizontal rhizoliths, and the paucity of vadose textures in the stage II caliche nodules.Stable oxygen isotopes are similar in the fluvial and supratidal caliches and range from 21.6 to 30.5 parts per thousand (SMOW). The data exhibit a crude bimodality and delta-O-18 enrichment with a decrease in age (higher in the section). Consideration of these data in the context of delta-temperature relations suggests that 1) surface waters responsible for caliche formation increased in delta-O-18 (from roughly -8 to + 1 parts per thousand) over the 18 m.y. time interval that separated the lowest stratigraphic nodule horizon from the highest, 2) the increasing delta-O-18 values also reflect a warming trend (approximately 15-degrees to nearly 30-degrees-C) in the mean monthly temperature over this same time period, with perhaps an associated increase in Permian ocean temperatures, and 3) the significant variation in delta-O-18 from oldest to youngest caliche was probably enhanced by the amount effect, such that as the temperature increased, the amount of precipitation decreased, resulting in high delta-O-18 values.Caliches in the Abo are enriched in heavy carbon (-7.2 to -1.5 part per thousand PDB) compared to that of soil carbonate derived exclusively from C3 plants (-12 part per thousand PDB), and the supratidal caliches contain somewhat heavier carbon compared to the fluvial caliche. The delta-C-13 values for both environments increase with a decrease in caliche age. These results indicate that as the temperature increased and rainfall decreased with time, the level of C3 plant productivity apparently declined, allowing a greater influx of atmospheric CO2 into the soil. This can only occur when soil respiration rates are quite low or at very shallow depths (less than 10 cm), or both. Atmospheric CO2 seems to have invaded the supratidal soils to a somewhat greater extent than the fluvial soils.

Antitumor effect of Bothrops jararaca venom

MANY experimental studies have been carried out using snake venoms for the treatment of animal tumors, with controversial results. While some authors have reported an antitumor effect of treatment with specific snake venom fractions, others have reported no effects after this treatment. The aim of this study was to evaluate the effect of Bothrops jararaca venom (BjV) on Ehrlich ascites tumor (EAT) cells in vivo and in vitro. In the in vivo study, Swiss mice were inoculated with EAT cells by the intraperitoneal (i.p.) route and treated with BjV venom (0.4 mg/kg, i.p.), on the 1st, 4th, 7th, 10th, and 13th days. Mice were evaluated for total and differential cells number on the 2nd, 5th, 8th, 11th and 14th days. The survival time was also evaluated after 60 days of tumor growth. In the in vitro study, EAT and normal peritoneal cells were cultivated in the presence of different BjV concentrations (2.5, 5.0, 10.0, 20.0, 40.0, and 80 mug) and viability was verified after 3, 6, 12 and 24 h of cultivation. Results were analyzed statistically by the Kruskal-Wallis and Tukey tests at the 5% level of significance. It was observed that in vivo treatment with BjV induced tumor growth inhibition, increased animal survival time, decreased mortality, increased the influx of polymorphonuclear leukocytes on the early stages of tumor growth, and did not affect the mononuclear cells number. In vitro treatment with BjV produced a dose-dependent toxic effect on EAT and peritoneal cells, with higher effects against peritoneal cells. Taken together, our results demonstrate that BjV has an important antitumor effect. This is the first report showing this in vivo effect for this venom.

Low intensity laser therapy (LILT) in vivo acts on the neutrophils recruitment and chemokines/cytokines levels in a model of acute pulmonary inflammation induced by aerosol of lipopolysaccharide from Escherichia coli in rat

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