Paracoccidioides brasilinsis-Induced Migration of Dendritic Cells and Subsequent T-Cell Activation in the Lung-Draining Lymph Nodes

Paracoccidioidomycosis is a mycotic disease caused by a dimorphic fungus, Paracoccidioides brasiliensis (Pb), that starts with inhalation of the fungus; thus, lung cells such as DC are part of the first line of defense against this microorganism. Migration of DC to the lymph nodes is the first step in initiating T cell responses. The mechanisms involved in resistance to Pb infection are poorly understood, but it is likely that DC play a pivotal role in the induction of effector T cells that control Pb infection. In this study, we showed that after Pb Infection, an important modification of lung DC receptor expression occurred. We observed an increased expression of CCR7 and CD103 on lung DC after infection, as well as MHC-II. After Pb infection, bone marrow-derived DC as well lung DC, migrate to lymph nodes. Migration of lung DC could represent an important mechanism of pathogenesis during PCM infection. In resume our data showed that Pb induced DC migration. Furthermore, we demonstrated that bone marrow-derived DC stimulated by Pb migrate to the lymph nodes and activate a T helper (Th) response. To the best of our knowledge, this is the first reported data showing that Pb induces migration of DC and activate a T helper (Th) response.

Integration and visualization of systems biology data in context of the genome

Background: High-density tiling arrays and new sequencing technologies are generating rapidly increasing volumes of transcriptome and protein-DNA interaction data. Visualization and exploration of this data is critical to understanding the regulatory logic encoded in the genome by which the cell dynamically affects its physiology and interacts with its environment. Results: The Gaggle Genome Browser is a cross-platform desktop program for interactively visualizing high-throughput data in the context of the genome. Important features include dynamic panning and zooming, keyword search and open interoperability through the Gaggle framework. Users may bookmark locations on the genome with descriptive annotations and share these bookmarks with other users. The program handles large sets of user-generated data using an in-process database and leverages the facilities of SQL and the R environment for importing and manipulating data. A key aspect of the Gaggle Genome Browser is interoperability. By connecting to the Gaggle framework, the genome browser joins a suite of interconnected bioinformatics tools for analysis and visualization with connectivity to major public repositories of sequences, interactions and pathways. To this flexible environment for exploring and combining data, the Gaggle Genome Browser adds the ability to visualize diverse types of data in relation to its coordinates on the genome. Conclusions: Genomic coordinates function as a common key by which disparate biological data types can be related to one another. In the Gaggle Genome Browser, heterogeneous data are joined by their location on the genome to create information-rich visualizations yielding insight into genome organization, transcription and its regulation and, ultimately, a better understanding of the mechanisms that enable the cell to dynamically respond to its environment.

Changes in Management Strategies After Spontaneous Migration of a Retained Intraorbital Metallic Foreign Body

Purpose: Because of the controversial biologic tolerance and management, retained intraorbital metallic foreign body (RIMFb) poses a formidable challenge to surgeons. Besides location of the foreign body, indications for surgical management include neurologic injury, mechanical restriction of the eye movement, and development of local infection or draining fistula. The authors describe an unusual case of spontaneous migration of a RIMFb. Methods: A 26-year-old man had a gunshot injury on the left orbit. The patient was initially managed conservatively because of the posterior position of the bullet fragment. Thereafter, because of the clinical impairments and anterior migration of projectile, surgical treatment was considered. Results: Spontaneous anterior migration has led to mechanical disturbances and inflammatory complications that comprise explicit surgical indications for removal. The patient underwent surgery with complete relief of symptoms. We suppose that extrinsic ocular muscles might play a role in shifting large RIMFb over time, leading to change in the management strategies. Conclusions: Spontaneous migration of RIMFb is a rare clinical situation that can lead to pain, local deformity, as well as changes in the management strategies of the affected patients even in the late phase of follow-up.

Phase equilibria study of systems composed of refined babassu oil, lauric acid, ethanol, and water at 303.2 K

Deacidification of vegetable oils can be performed using liquid-liquid extraction as an alternative method to the classical chemical and physical refining processes. This paper reports experimental data for systems containing refined babassu oil, lauric acid, ethanol, and water at 303.2 K with different water mass fractions in the alcoholic solvent (0, 0.0557, 0.1045, 0.2029, and 0.2972). The dilution of solvent with water reduced the distribution coefficient values, which indicates a reduction in the loss of neutral oil. The experimental data were used to adjust the NRTL equation parameters. The global deviation between the observed and the estimated compositions was 0.0085, indicating that the model can accurately predict the behavior of the compounds at different levels of solvent hydration. (C) 2011 Elsevier Ltd. All rights reserved.

The effect of DMSA-functionalized magnetic nanoparticles on transendothelial migration of monocytes in the murine lung via a beta(2) integrin-dependent pathway

Magnetic nanoparticles surface-functionalized with meso-2,3-dimercaptosuccinic acid (MNPs-DMSA) constitute an innovative and promising approach for tissue- and cell-targeted delivery of therapeutic drugs in the lung. Transendothelial migration of leukocytes in the lung is a side effect of endovenous administration of MNPs-DMSA. Using cytologic and phenotypic analysis of murine bronchoalveolar lavage cells, we identified monocytes/macrophages as the main subpopulation of leukocytes involved in this process. Moreover, ultrastructural analysis revealed the presence of nanoparticles inside of numerous macrophages from bronchoalveolar lavage. MNPs-DMSA at concentrations as high as 1 X 10(15) nanoparticles/mL had no toxic effects on macrophages, as evidenced by 3-(4, 5-dimethylthiazolyi-2)-2,5-diphenyltetrazolium bromide (MTT) assay. Notably, MNPs-DMSA up-regulated the mRNA expression of E, L- and P-selectin and macrophage-1 antigen in the murine lung. Upregulation of these cell adhesion molecules was associated with an increased concentration of tumor necrosis factor-alpha in lung. Finally, the critical relevance of the beta(2) integrin-dependent pathway in leukocyte transmigration elicited by MNPs-DMSA was demonstrated by use of knockout mice. Our results characterize mechanisms of the pro-inflammatory effects of MNPs-DMSA in the lung, and identify beta(2) integrin-targeted interventions as promising strategies to reduce pulmonary side effects of MNPs-DMSA during biomedical applications. (C) 2009 Elsevier Ltd. All rights reserved.

Short-chain fatty acids stimulate the migration of neutrophils to inflammatory sites

SCFAs (short-chain fatty acids) are produced by anaerobic bacterial fermentation. Increased concentrations of these fatty acids are observed in inflammatory conditions, such as periodontal disease, and at sites of anaerobic infection. In the present study, the effect of the SCFAs acetate, propionate and butyrate on neutrophil chemotaxis and migration was investigated. Experiments were carried out in rats and in vitro. The following parameters were measured: rolling, adherence, expression of adhesion molecules in neutrophils (L-selectin and beta 2 integrin), transmigration, air pouch influx of neutrophils and production of cytokines [CINC-2 alpha beta (cytokine-induced neutrophil chemoattractant-2 alpha beta), IL-1 beta (interleukin-1 beta), MIP-1 alpha (macrophage inflammatory protein-1 alpha) and TNF-alpha (tumour necrosis factor-alpha)]. SCFAs induced in vivo neutrophil migration and increased the release of CINC-2 alpha beta into the air pouch. These fatty acids increased the number of rolling and adhered cells as evaluated by intravital microscopy. SCFA treatment increased L-selectin expression on the neutrophil surface and L-selectin mRNA levels, but had no effect on the expression of beta 2 integrin. Propionate and butyrate also increased in vitro transmigration of neutrophils. These results indicate that SCFAs produced by anaerobic bacteria raise neutrophil migration through increased L-selectin expression on neutrophils and CINC-2 alpha beta release.

Cross talk Initiated by Endothelial Cells Enhances Migration and Inhibits Anoikis of Squamous Cell Carcinoma Cells through STAT3/Akt/ERK Signaling

It is well known that cancer cells secrete angiogenic factors to recruit and sustain tumor vascular networks. However, little is known about the effect of endothelial cell-secreted factors on the phenotype and behavior of tumor cells. The hypothesis underlying this study is that endothelial cells initiate signaling pathways that enhance tumor cell survival and migration. Here, we observed that soluble mediators from primary human dermal microvascular endothelial cells induce phosphorylation of signal transducer and activator of transcription 3 (STAT3), Akt, and extracellular signal-regulated kinase (ERK) in a panel of head and neck squamous cell carcinoma (HNSCC) cells (OSCC-3, UM-SCC-1, UM-SCC-17B, UM-SCC-74A). Gene expression analysis demonstrated that interleukin-6 (IL-6), interleukin-8 (CXCL8), and epidermal growth factor (EGF) are upregulated in endothelial cells cocultured with HNSCC. Blockade of endothelial cell-derived IL-6, CXCL8, or EGF by gene silencing or neutralizing antibodies inhibited phosphorylation of STAT3, Akt, and ERK in tumor cells, respectively. Notably, activation of STAT3, Akt, and ERK by endothelial cells enhanced migration and inhibited anoikis of tumor cells. We have previously demonstrated that Bcl-2 is upregulated in tumor microvessels in patients with HNSCC. Here, we observed that Bcl-2 signaling induces expression of IL-6, CXCL8, and EGF, providing a mechanism for the upregulation of these cytokines in tumor-associated endothelial cells. This study expands the contribution of endothelial cells to the pathobiology of tumor cells. It unveils a new mechanism in which endothelial cells function as initiators of molecular crosstalks that enhance survival and migration of tumor cells.

Synthesis of PID controllers for a class of time delay systems

In this paper we use the Hermite-Biehler theorem to establish results on the design of proportional plus integral plus derivative (PID) controllers for a class of time delay systems. Using the property of interlacing at high frequencies of the class of systems considered and linear programming we obtain the set of all stabilizing PID controllers. As far as we know, previous results on the synthesis of PID controllers rely on the solution of transcendental equations. This paper also extends previous results on the synthesis of proportional controllers for a class of delay systems Of retarded type to a larger class of delay systems. (C) 2009 Elsevier Ltd. All rights reserved.

Rheological, mechanical and mucoadhesive properties of thermoresponsive, bioadhesive binary mixtures composed of poloxamer 407 and carbopol 974P designed as platforms for implantable drug delivery systems for use in the oral cavity

This study described the formulation and characterisation of the viscoelastic, mechanical and mucoadhesive properties of thermoresponsive, binary polymeric systems composed of poloxamer (P407) and poly(acrylic acid, C974P) that were designed for use as a drug delivery platform within the oral cavity. Monopolymeric and binary polymeric formulations were prepared containing 10, 15 and 20% (w/w) poloxamer (407) and 0.10-0.25% (w/w) poly(acrylic acid, 934P). The flow theological and viscoelastic properties of the formulations were determined using controlled stress and oscillatory rheometry, respectively, the latter as a function of temperature. The mechanical and mucoadhesive properties (namely the force required to break the bond between the formulation and a pre-hydrated mucin disc) were determined using compression and tensile analysis, respectively. Binary systems composed of 10% (w/w) P407 and C934P were elastoviscous, were easily deformed under stress and did not exhibit mucoadhesion. Formulations containing 15 or 20% (w/w) Pluronic P407 and C934P exhibited a sol-gel temperature T(sol/gel), were viscoelastic and offered high elasticity and resistance to deformation at 37 degrees C. Conversely these formulations were elastoviscous and easily deformed at temperatures below the sol-gel transition temperature. The sol-gel transition temperatures of systems containing 15% (w/w) P407 were unaffected by the presence of C934P; however, increasing the concentration of C934P decreased the T(sol/gel) in formulations containing 20%(w/w) P407. Rheological synergy between P407 and C934P at 37 degrees C was observed and was accredited to secondary interactions between these polymers, in addition to hydrophobic interactions between P407 micelles. Importantly, formulations composed of 20% (w/w) P407 and C934P exhibited pronounced mucoadhesive properties. The ease of administration (below the T(sol/gel)) in conjunction with the viscoelastic (notably high elasticity) and mucoadhesive properties (at body temperature) render the formulations composed of 20% (w/w) P407 and C934P as potentially useful platforms for mucoadhesive, controlled topical drug delivery within the oral cavity. (c) 2009 Published by Elsevier B.V.

Approximate controllability of second-order distributed implicit functional systems

In this paper we study the approximate controllability of control systems with states and controls in Hilbert spaces, and described by a second-order semilinear abstract functional differential equation with infinite delay. Initially we establish a characterization for the approximate controllability of a second-order abstract linear system and, in the last section, we compare the approximate controllability of a semilinear abstract functional system with the approximate controllability of the associated linear system. (C) 2008 Elsevier Ltd. All rights reserved.

A Randomized Trial of a Skin Sealant to Reduce the Risk of Incision Contamination in Cardiac Surgery

Background. Immobilizing skin microbes is a rational approach to reducing contamination of surgical sites by endogenous microorganisms. Methods. This randomized, controlled, parallel-group, multicenter, open-label clinical trial (ClinicalTrials.gov NCT00467857) enrolled 300 adults scheduled for elective coronary artery bypass graft surgery. Patients received iodine-based skin preparations followed by a cyanoacrylate-based skin sealant or skin preparations alone. Microbiological samples collected from sternal and graft incision sites immediately before any skin preparation, at the wound border after skin incision, and at the incision after fascial closure were evaluated quantitatively. Results. In evaluable patients, mean microbial counts in collected samples increased at the sternal site after fascial closure compared with after skin incision by 0.37 log(10) colony-forming units (CFU)/mL in the skin sealant group (n = 120) and by 0.57 log10 CFU/mL in the control group (n = 132) (p = 0.047, Wilcoxon rank sum test). At the graft site, mean microbial counts increased by 0.09 (n = 119) and 0.27 (n = 127) log(10) CFU/mL, respectively (p = 0.037). There was a 35.3% relative risk reduction in surgical site infection (SSI) occurring in the skin sealant group (9 of 146 patients, 6.2%) versus the control group (14 of 147 patients, 9.5%). In obese patients (body mass index [BMI] > 30.0 to <= 37.0 kg/m(2)), the relative risk reduction for SSI associated with skin sealant was 83.3%. Conclusions. Pretreatment with skin sealant protects against contamination of the surgical incision by migration of skin microbes. Further data are needed to confirm the impact of this technology on SSI rates in clinical practice. (Ann Thorac Surg 2011;92:632-7) (C) 2011 by The Society of Thoracic Surgeons ADULT CARDIAC

Talc pleurodesis: Evidence of systemic Inflammatory response to small size talc particles

The mechanisms of the systemic response associated with talc-induced pleurodesis are poorly understood. The aim of this study was to assess the acute inflammatory response and migration of talc of small. size particles injected in the pleural space. Rabbits were injected intrapleurally with talc solution containing small. or mixed particles and blood and pleural fluid samples were collected after 6, 24 or 48 h and assayed for leukocytes, neutrophils, lactate dehydrogenase, IL-8, VEGF, and TGF-beta. The lungs, spleen, liver and kidneys were assessed to study deposit of talc particles. Both types of talc produced an acute serum inflammatory response, more pronounced in the small particles group. Pleural fluid IL-8 and VEGF levels were higher in the small particle talc group. Correlation between pleural VEFG and TGF-beta levels was observed for both groups. Although talc particles were demonstrated in the organs of both groups, they were more pronounced in the small talc group. In conclusion, intrapleural injection of talc of small size particles produced a more pronounced acute systemic response and a greater deposition in organs than talc of mixed particles. (C) 2008 Elsevier Ltd. All rights reserved.

Reduction of ICAM-1 expression by carbon monoxide via soluble guanylate cyclase activation accounts for modulation of neutrophil migration

Previously, it was demonstrated that the heme/heme oxygenase (HO)/carbon monoxide (CO) pathway inhibits neutrophil recruitment during the inflammatory response. Herein, we addressed whether the inhibitory effect of the HO pathway on neutrophil adhesion and migration involves the reduction of intracellular adhesion molecule type (ICAM)-1 and beta(2)-integrin expression. Mice pretreated with a specific inhibitor of inducible HO (HO-1), zinc protoporphyrin (ZnPP) IX, exhibit enhanced neutrophil adhesion and migration induced by intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS). These findings are associated with an increase in ICAM-1 expression on mesentery venular endothelium. In accordance, HO-1 inhibition did not enhance LPS-induced neutrophil migration and adhesion in ICAM-1-deficient mice. Furthermore, the treatment with a CO donor (dimanganese decacarbonyl, DMDC) that inhibits adhesion and migration of the neutrophils, reduced LPS-induced ICAM-1 expression. Moreover, neither DMDC nor ZnPP IX treatments changed LPS-induced beta(2)-integrin expression on neutrophils. The effect of CO on ICAM-1 expression seems to be dependent on soluble guanylate cyclase (sGC) activation, since 1H-(1,2,4)oxadiazolo (4,3-a)quinoxalin-1-one (sGC inhibitor) prevented the observed CO effects. Finally, it was observed that the nitric oxide (NO) anti-inflammatory effects on ICAM-1 expression appear to be indirectly mediated by HO-1 activation, since the inhibition of HO-1 prevented the inhibitory effect of the NO donor (S-nitroso-N-acetylpenicillamine) on LPS-induced ICAM-1 expression. Taken together, these results suggest that CO inhibits ICAM-1 expression on endothelium by a mechanism dependent on sGC activation. Thus, our findings identify the HO-1/CO/guanosine 3`5`-cyclic monophosphate pathway as a potential target for the development of novel pharmacotherapy to control neutrophil migration in inflammatory diseases.

Liquid-liquid equilibria for systems composed of refined soybean oil, free fatty acids, ethanol, and water at different temperatures

Soybean oil can be deacidified by liquid-liquid extraction with ethanol. In the present paper, the liquid-liquid equilibria of systems composed of refined soybean oil, commercial linoleic acid, ethanol and water were investigated at 298.2 K. The experimental data set obtained from the present study (at 298.2 K) and the results of Mohsen-Nia et al. [1] (at 303.2 K) and Rodrigues et al. [2] (at 323.2 K) were correlated by applying the non-random two liquid (NRTL) model. The results of the present study indicated that the mutual solubility of the compounds decreased with an increase in the water content of the solvent and a decrease in the temperature of the solution. Among variables, the water content of the solvent had the strongest effect on the solubility of the components. The maximum deviation and average variance between the experimental and calculated compositions were 1.60% and 0.89%, indicating that the model could accurately predict the behavior of the compounds at different temperatures and degrees of hydration. (C) 2010 Elsevier B.V. All rights reserved.

Evidences of the cooperative role of the chemokines CCL3, CCL4 and CCL5 and its receptors CCR1+and CCR5+in RANKL+ cell migration throughout experimental periodontitis in mice

Periodontal disease (PD) is characterized by the inflammatory bone resorption in response to the bacterial challenge, in a host response that involves a series of chemokines supposed to control cell influx into periodontal tissues and determine disease outcome. In this study, we investigated the role of chemokines and its receptors in the immunoregulation of experimental PD in mice. Aggregatibacter actinomycetemcomitans-infected C57BI/6 (WT) mice developed an intense inflammatory reaction and severe alveolar bone resorption, associated with a high expression of CCL3 and the migration of CCR5+, CCR1+ and RANKL+ cells to periodontal tissues. However, CCL3KO-infected mice developed a similar disease phenotype than WT strain, characterized by the similar expression of cytokines (TNF-alpha, IFN-gamma and IL-10), osteoclastogenic factors (RANKL and OPG) and MMPs (MMP-1, MMP-2, MMP-3, TIMP-1 and TIMP-3), and similar patterns of CCR1+, CCR5+ and RANKL+ cell migration. The apparent lack of function for CCL3 is possible due the relative redundancy of chemokine system, since chemokines such as CCL4 and CCL5, which share the receptors CCR1 and CCR5 with CCL3, present a similar kinetics of expression than CCL3. Accordingly, CCL4 and CCL5 kinetics of expression after experimental periodontal infection remain unaltered regardless the presence/absence of CCL3. Conversely, the individual absence of CCR1 and CCR5 resulted in a decrease of leukocyte infiltration and alveolar bone loss. When CCR1 and CCR5 were simultaneously inhibited by met-RANTES treatment a significantly more effective attenuation of periodontitis progression was verified, associated with lower values of bone loss and decreased counts of leukocytes in periodontal tissues. Our results suggest that the absence of CCL3 does not affect the development of experimental PD in mice, probably due to the presence of homologous chemokines CCL4 and CCL5 that overcome the absence of this chemokine. In addition, our data demonstrate that the absence of chemokine receptors CCR1+ and CCR5+ attenuate of inflammatory bone resorption. Finally, our data shows data the simultaneous blockade of CCR1 and CCR5 with MetRANTEs presents a more pronounced effect in the arrest of disease progression, demonstrating the cooperative role of such receptors in the inflammatory bone resorption process throughout experimental PD. (C) 2009 Elsevier Inc. All rights reserved.