Leukocyte adhesion - a fundamental process in leukocyte physiology

Leukocyte adhesion is of pivotal functional importance. The adhesion involves several different adhesion molecules, the most important of which are the leukocyte ß2-integrins (CD11/CD18), the intercellular adhesion molecules, and the selectins. We and others have extensively studied the specificity and binding sites in the integrins and the intercellular adhesion molecules for their receptors and ligands. The integrins have to become activated to exert their functions but the possible mechanisms of activation remain poorly understood. Importantly, a few novel intercellular adhesion molecules have been recently described, which seem to function only in specific tissues. Furthermore, it is becoming increasingly apparent that changes in integrins and intercellular adhesion molecules are associated with a number of acute and chronic diseases.

Thalidomide and pentoxifylline block the renal effects of supernatants of macrophages activated with Crotalus durissus cascavella venom

Because thalidomide and pentoxifylline inhibit the synthesis and release of tumor necrosis factor-alpha (TNF-alpha), we determined the effect of these drugs on the renal damage induced by supernatants of macrophages activated with Crotalus durissus cascavella venom in order to identify the role of TNF-alpha in the process. Rat peritoneal macrophages were collected with RPMI medium and stimulated in vitro with C.d. cascavella venom (10 µg/ml) in the absence and presence of thalidomide (15 µM) or pentoxifylline (500 µM) for 1 h and washed and kept in culture for 2 h. Supernatant (1 ml) was tested on an isolated perfused rat kidney (N = 6 for each group). The first 30 min of each experiment were used as control. The supernatant was added to the perfusion system. All experiments lasted 120 min. The toxic effect of the preparation of venom-stimulated macrophages on renal parameters was determined. At 120 min, thalidomide (Thalid) and pentoxifylline (Ptx) inhibited (P < 0.05) the increase in perfusion pressure caused by the venom (control = 114.0 ± 1.3; venom = 137.1 ± 1.5; Thalid = 121.0 ± 2.5; Ptx = 121.4 ± 4.0 mmHg), renal vascular resistance (control = 4.5 ± 0.2; venom = 7.3 ± 0.6; Thalid = 4.5 ± 0.9; Ptx = 4.8 ± 0.6 mmHg/ml g-1 min-1), urinary flow (control = 0.23 ± 0.001; venom = 0.44 ± 0.01; Thalid = 0.22 ± 0.007; Ptx = 0.21 ± 0.009 ml g-1 min-1), glomerular filtration rate (control = 0.72 ± 0.06; venom = 1.91 ± 0.11; Thalid = 0.75 ± 0.04; Ptx = 0.77 ± 0.05 ml g-1 min-1) and the decrease in percent tubular sodium transport (control = 77.0 ± 0.9; venom = 73.9 ± 0.66; Thalid = 76.6 ± 1.1; Ptx = 81.8 ± 2.0%), percent tubular chloride transport (control = 77.1 ± 1.2; venom = 71.4 ± 1.1; Thalid = 77.6 ± 1.7; Ptx = 76.8 ± 1.2%), and percent tubular potassium transport (control = 72.7 ± 1.1; venom = 63.0 ± 1.1; Thalid = 72.6 ± 1.0; Ptx = 74.8 ± 1.0%), 30 min before and during the stimulation of macrophages with C.d. cascavella venom. These data suggest the participation of TNF-alpha in the renal effects induced by supernatant of macrophages activated with C.d. cascavella venom.

Increased expression of tissue factor and protease-activated receptor-1 does not correlate with thrombosis in human lung adenocarcinoma

A correlation between cancer and hypercoagulability has been described for more than a century. Patients with cancer are at increased risk for thrombotic complications and the clotting initiator protein, tissue factor (TF), is possibly involved in this process. Moreover, TF may promote angiogenesis and tumor growth. In addition to TF, thrombin seems to play a relevant role in tumor biology, mainly through activation of protease-activated receptor-1 (PAR-1). In the present study, we prospectively studied 39 lung adenocarcinoma patients in relation to the tumor expression levels of TF and PAR-1 and their correlation with thrombosis outcome and survival. Immunohistochemical analysis showed TF positivity in 22 patients (56%), most of them in advanced stages (III and IV). Expression of PAR-1 was found in 15 patients (39%), most of them also in advanced stages (III and IV). Remarkably, no correlation was observed between the expression of TF or PAR-1 and risk for thrombosis development. On the other hand, patients who were positive for TF or PAR-1 tended to have decreased long-term survival. We conclude that immunolocalization of either TF or PAR-1 in lung adenocarcinoma may predict a poor prognosis although lacking correlation with thrombosis outcome.

Physicochemical and sensory changes in aged sugarcane spirit submitted to filtering with activated carbon filter

Sugarcane spirit is a drink considered as a national symbol of Brazil. It is produced by large producers and by about 30 thousand small and medium home-distilling producers dispersed throughout the country. The copper originating from the home-distillers can become a serious problem since at high concentrations in beverages it may cause serious human health problems. Therefore, the objective of this study was to investigate the influence of the activated carbon used in commercial filters on the physicochemical and sensory characteristics of aged sugarcane spirit. Analyses of copper, dry extract, alcoholic degree, higher alcohols, volatile acids, aldehydes, esters, furfural, and methanol were performed. The sensory evaluation was performed by seven selected trained judges, who analyzed the yellow color, woody aroma and flavor, and intensity of alcoholic aroma and flavor of the cane spirit before and after the filtration process. The sensory tests were carried out using a 9 cm non-structured intensity scale. A reduction was observed in all compounds analyzed physicochemically, except for the esters, which increased after filtration. This increase is probably due to the esterification of the alcohols and acids present. According to the sensory results obtained, a reduction was observed in the intensity of the yellow color, aroma, and wood flavor characteristics, the major characteristics of the aging process.

China's proposing behavior in Global Governance: the cases of the WTO Doha Round negotiation and G-20 process

This article examines China's proposals on the reform of global governance, and discusses the main features of China's proposing behavior in the cases of the WTO Doha Round negotiation and G-20 Process. The main findings are: (1) in the critical junctures of global governance reform, China engaged the reform of the global governance institutions proactively, and put forward a series of reform proposals; (2) in proposing behavior, China argued the global governance institutions should be properly adjusted without intention to change the basic principles, refrained from playing a leadership role while proposing jointly with other countries, and upheld the principled idea of pro-development.

The UN peacebuilding process: an analysis of its shortcomings in Timor-Leste

This paper brings a comprehensive analysis of the peacebuilding process conducted by the UN in Timor-Leste. Drawing on fieldwork, interviews, and secondary sources, the paper brings light to the main fragilities of this process. Firstly, the paper briefly outlines the scholarly debate around UN peacebuilding process. Then, the paper brings an overview of the UN missions deployed to Timor-Leste. Finally, the paper identifies the major limitations of such engagement. By highlighting the main flaws of this peacebuilding process, the paper opens the space for (re)thinking alternative ways of building peace in post-conflict scenarios.

Chemical sterilization in in vitro propagation of Arundina bambusifolia Lindl. and Epidendrum ibaguense Kunth

There is a great demand for simpler and less costly laboratory techniques and for more accessible procedures for orchid breeders who do not have the necessary theoretical basis to use the traditional seed and clone production methods of orchids in vitro. The aim of this study was to assess the use of sodium hypochlorite (NaClO) as a decontaminant in the process of inoculating adult orchid explants of Arundina bambusifolia and Epidendrum ibaguenses. Solutions of NaClO (1.200, 2.400, 3.600, 4.800 and 6.000 mg L-1 - equivalent to 50, 100, 150, 200 and 250 mL L-1 of commercial bleach - CB) were sprayed on the explants (1.0 mL) and the culture medium (GB5), in the presence or absence of activated charcoal (2 g L-1). The explants used were nodal segments of field-grown adult plants. The procedures for inoculating the explants were conducted outside the laminar flow chamber (LFC), except for the control treatment (autoclaved medium and explant inoculation inside the LFC). The best results for fresh weight yield, height and number of shoots were obtained using NaClO in solution at 1.200 mg L-1 (equivalent to 50 mL L-1 commercial bleach) with activated charcoal in the culture medium. Fresh weight figures were 1.10 g/jar for Arundina bambusifolia and 0.16 g/jar for Epidendrum ibaguenses. Spraying the NaClO solutions controls the contamination of the culture medium already inoculated with the explants.

How middle managers contribute to strategy formation process: connection of strategy processes and strategy practices

The role of middle management is essential when managing integrative and emergent strategy formation processes. We stand out the importance of its role connecting micro and macro organizational level offering a very important contribution when examining the strategy-as-practice perspective and integrative strategy formation process. The main goal of this research is to analyse the relationship between the integrative strategy formation process and the roles of middle management under the strategy-as-practice perspective. To check it out we adopted a qualitative methodology droving a case analysis in a Spanish University. Data was collected by means of personal interviews with members of different levels of the Institution, documents analysis and direct observation. In advance of some results we find out that the University develops an integrative strategy formation process and confers to middle management an important role extended all over the organization.

The process of implementing answerability in contemporary Brazil

Abstract: The aim of this study was to characterize the trajectory of answerability in Brazil. In the light of studies based on the historical neo-institutionalism approach, formal institutional changes adopted at federal level between 1985 and 2014, and which favor the typical requirements of answerability - information and justification - were identified and analyzed through the content analysis technique. The conclusion is that the trajectory of answerability in contemporary Brazil can be characterized as continuous, primarily occurring through the layering strategy, and whose leitmotif, since its origin, has consisted of matters of financial and budgetary nature. Nevertheless, a recent influence of deeper democratic subjects on it has been observed.

Avaliação de operadoras de saúde por usuários pelo método Analytic Hierarchy Process

OBJETIVO: Analisar a qualidade dos serviços oferecidos por empresas operadoras de planos de saúde, segundo a percepção de usuários. MÉTODOS: Estudo transversal com 360 usuários de sete operadoras de planos de saúde da cidade de Curitiba, PR, e região metropolitana em 2008. Foi aplicado questionário sobre as preferências dos usuários em relação a seis atributos (localização dos pontos de atendimento; efetividade da ação dos médicos, clínicas e hospitais; rapidez e amabilidade no atendimento; facilidade na liberação de guias; preço; abrangência da rede credenciada) de cada uma das empresas operadoras. Para a análise das respostas foi utilizado o método Analytic Hierarchy Process (AHP, ou Processo Analítico de Hierarquia), ferramenta de análise de decisão e planejamento de múltiplos critérios. RESULTADOS: O atributo mais valorizado pelos usuários foi "preço". As empresas foram agrupadas em dois conjuntos de preferências em relação aos atributos: dos sete planos de saúde, dois apresentaram menor preferência (entre 23% e 19%) e cinco, maior preferência (em torno de 10%). CONCLUSÕES: Com esse tipo de pesquisa, as empresas operadoras de planos de saúde poderiam reformular suas estruturas, processos, preços e redes credenciadas com o objetivo de melhorar seu posicionamento no mercado.

Role of iron in the nitric oxide-mediated fungicidal mechanism of IFN-gamma-activated murine macrophages against Paracoccidioides brasiliensis conidia

Iron is an essential growth element of virtually all microorganisms and its restriction is one of the mechanisms used by macrophages to control microbial multiplication. Paracoccidioides brasiliensis, the agent of paracoccidioidomycosis, an important systemic mycosis in Latin America, is inhibited in its conidia-to-yeast conversion in the absence of iron. We studied the participation of iron in the nitric oxide (NO)-mediated fungicidal mechanism against conidia. Peritoneal murine macrophages activated with 50U/mL of IFN-gamma or treated with 35 µM Deferoxamine (DEX) and infected with P. brasiliensis conidia, were co-cultured and incubated for 96 h in the presence of different concentrations of holotransferrin (HOLO) and FeS0(4). The supernatants were withdrawn in order to assess NO2 production by the Griess method. The monolayers were fixed, stained and observed microscopically. The percentage of the conidia-to-yeast transition was estimated by counting 200 intracellular propagules. IFN-gamma-activated or DEX-treated Mthetas presented marked inhibition of the conidia-to-yeast conversion (19 and 56%, respectively) in comparison with non-activated or untreated Mthetas (80%). IFN-gamma-activated macrophages produced high NO levels in comparison with the controls. Additionally, when the activated or treated-macrophages were supplemented with iron donors (HOLO or FeSO4), the inhibitory action was reversed, although NO production remained intact. These results suggest that the NO-mediated fungicidal mechanism exerted by IFN-gamma-activated macrophages against P. brasiliensis conidia, is dependent of an iron interaction.

Lysozyme plays a dual role against the dimorphic fungus Paracoccidioides brasiliensis

In order to determine the role of lysozyme, an antimicrobial peptide belonging to the innate immune system, against the dimorphic fungus Paracoccidioides brasiliensis, co-cultures of the MH-S murine alveolar macrophages cell line with P. brasiliensis conidia were done; assays to evaluate the effect of physiological and inflammatory concentrations of lysozyme directly on the fungus life cycle were also undertaken. We observed that TNF-α-activated macrophages significantly inhibited the conidia to yeast transition (p = 0.0043) and exerted an important fungicidal effect (p = 0.0044), killing 27% more fungal propagules in comparison with controls. Nonetheless, after adding a selective inhibitor of lysozyme, the fungicidal effect was reverted. When P. brasiliensis propagules were exposed directly to different concentrations of lysozyme, a dual effect was observed. Physiologic concentrations of the enzyme facilitated the conidia-to-yeast transition process (p < 0.05). On the contrary, inflammatory concentrations impaired the normal temperature-dependant fungal transition (p < 0.0001). When yeast cells were exposed to lysozyme, irrespective of concentration, the multiple-budding ability was badly impaired (p < 0.0001). In addition, ultra-structural changes such as subcellular degradation, fusion of lipid vacuoles, lamellar structures and interruption of the fibrilar layer were observed in lysozyme exposed conidia. These results suggest that lysozyme appears to exert a dual role as part of the anti-P. brasiliensis defense mechanisms.

THE RELEVANCE OF NUTRITIONAL STATUS AND HISTOPATHOLOGICAL FINDINGS ON THE INFECTIOUS PROCESS OF BALB/C MICE INOCULATED WITH Lacazia loboi

SUMMARY The aim of this study was to evaluate the effects of the protein-calorie malnutrition in BALB/c isogenic mice infected with Lacazia loboi, employing nutritional and histopathological parameters. Four groups were composed: G1: inoculated with restricted diet, G2: not inoculated with restricted diet, G3: inoculated with regular diet, G4: not inoculated with regular diet. Once malnutrition had been imposed, the animals were inoculated intradermally in the footpad and after four months, were sacrificed for the excision of the footpad, liver and spleen. The infection did not exert great influence on the body weight of the mice. The weight of the liver and spleen showed reduction in the undernourished groups when compared to the nourished groups. The macroscopic lesions, viability index and total number of fungi found in the footpads of the infected mice were increased in G3 when compared to G1. Regarding the histopathological analysis of the footpad, a global cellularity increase in the composition of the granuloma was observed in G3 when compared to G1, with large numbers of macrophages and multinucleated giant cells, discrete numbers of lymphocytes were present in G3 and an increase was observed in G1. The results suggest that there is considerable interaction between Jorge Lobo's disease and nutrition.