Exchange Communication Point Modeling in the context of the Enterprise Architecture

It is important to understand the performance and operation of an Internet Exchange Point to improve the management, and to reduce the cost associated with implementation and the information shared. Enterprise Architecture supports the design of systems, according to the business domain processes, network infrastructure and all the different applications running. Existing Enterprise Architecture modelling languages only provide a general concept of a network and do not represent specific information such as the protocols used, the internet protocols or the network addresses used for sharing information. This paper proposes a set of new concepts and attributes to the technology layer of reference language (ArchiMate) to enhance the representation and management of the network infrastructure. The ArchiMate language extensions are then used in modelling two Case Studies of Internet Exchange Point implementation in the Portuguese Public Administration. It was possible to compute which services will have impact in case of failure

Intrauterine Undernourishment Alters TH1/TH2 Cytokine Balance and Attenuates Lung Allergic Inflammation in Wistar Rats

IL-4 produced by Th2 cells can block cytokine production by Th1 cells, and Th1 IFN-gamma is known to counterregulate Th2 immune response, inhibiting allergic eosinophilia. As intrauterine undernutrition can attenuate lung inflammation, we investigated the influence of intrauterine undernourishment on the Th1/Th2 cytokine balance and allergic lung inflammation. Intrauterine undernourished offspring were obtained from dams fed 50% of the nourished diet of their counterparts and were immunized at 9 weeks of age. We evaluated the cell counts and cytokine protein expression in the bronchoalveolar lavage, mucus production and collagen deposition, and cytokine gene expression and transcription factors in lung tissue 21 days after ovalbumin immunization. Intrauterine undernourishment significantly reduced inflammatory cell airway infiltration, mucus secretion and collagen deposition, in rats immunized and challenged. Intrauterine undernourished rats also exhibited an altered cytokine expression profile, including higher TNF-alpha and IL-1 beta expression and lower IL-6 expression than well-nourished rats following immunization and challenge. Furthermore, the intrauterine undernourished group showed reduced ratios of the IL-4/IFN-gamma and the transcription factors GATA-3/T-Bet after immunization and challenge. We suggest that the attenuated allergic lung inflammation observed in intrauterine undernourished rats is related to an altered Th1/Th2 cytokine balance resulting from a reduced GATA-3/T-bet ratio. Copyright (C) 2012 S. Karger AG, BaselConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundo de Auxilio aos Docentes e Alunos (FADA-UNIFESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 São Paulo, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Imunol, Lab Imunol Transplantes, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nefrol, Lab Imunol Clin & Expt, BR-09972270 São Paulo, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Farmacol, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nefrol, Lab Imunol Clin & Expt, BR-09972270 São Paulo, BrazilFAPESP: 07/07139-3FAPESP: 09/09849-3FAPESP: 09/52119-6FAPESP: 10/01404-0FAPESP: 12/02270-2Web of Scienc

Mesenchymal Stem Cell Therapy Modulates the Inflammatory Response in Experimental Traumatic Brain Injury

Therapy with mesenchymal stem cells (MSCs) has showed to be promising due to its immunomodulatory function. Traumatic brain injury (TBI) triggers immune response and release of inflammatory mediators, mainly cytokines, by glial cells creating a hostile microenvironment for endogenous neural stem cells (NSCs). We investigated the effects of factors secreted by MSCs on NSC in vitro and analyzed cytokines expression in vitro in a TBI model. Our in vitro results show that MSC-secreted factors increase NSC proliferation and induce higher expression of GFAP, indicating a tendency toward differentiation into astrocytes. In vivo experiments showed that MSC injection at an acute model of brain injury diminishes a broad profile of cytokines in the tissue, suggesting that MSC-secreted factors may modulate the inflammation at the injury site, which may be of interest to the development of a favorable microenvironment for endogenous NSC and consequently to repair the injured tissue

Activation and Metabolic Shifting: An Essential Process to Mesenchymal Stromal Cells Function

To elucidate the basal metabolism of Mesenchymal Stromal Cells (MSCs), as well as knowing how they are activated, can bring important clues to a successful cell-based therapy. Naive MSCs, in their niche, mainly keep the local homeostasis and the pool of tissue stem cells. Once activated, by an injury, MSCs’ response leads to a lot of physiological differences in its metabolism that are responsible for its healing process. Since endogenous MSC seems to be ineffective in pathologic and aging conditions, cell-based therapy using MSC is focused on administration of exogenous MSC in patients to exert its healing functions. From quiescent to activated state, this “Metabolic Shifting” of MSC interferes directly in its secretion and cellular-derived particle generation. We will address here the differences between the MSCs activation phases and how they can modify the MSCs metabolism and its function. Moreover, understanding MSC in their niche and its damped function in pathologic and aging processes can improve stem cell-based therapies

Acute Kidney Injury Reduces Phagocytic and Microbicidal Capacities of Alveolar Macrophages

Background/Aims: Renal ischaemia-reperfusion injury (IRI) is a systemic inflammatory process in which Th1 responses predominate affecting other organs including the lungs. the present study explored the phagocytic and microbicidal capacity of macrophages in rats with lung inflammation that underwent IRI. Methods: the alveolar macrophages of rats sensitised to OVA were evaluated for phagocytosis and bacterial killing 24h after antigen challenge in animals with or without prior submission to 60 min of renal ischaemia. Results: Bronchoalveolar lavage had a high level of cellular infiltrate in immunised animals (420%) compared with control animals; IRI significantly reduced this infiltration (52%). Macrophages from animals immunised and challenged with OVA presented a 10x increase in phagocytic capacity compared to the control group, whereas immunised animals subjected to IRI showed a reduction in the phagocytic index of 68%. the killing of Klebsiella pneumoniae by macrophages from immunised animals was higher (56%) compared with the control group but reduced in animals submitted to IRI (45%). Immunised and challenged group showed an increase in gene expression levels of IL-10(450%), HO-1 (259%), INF-gamma (460%) and MCP-1 (370%) compared to the immunised group subjected to IRI. Conclusions: Renal ischaemia and reperfusion injury apparently alters the phagocytic and microbicidal capacity of macrophages, reducing lung inflammation to OVA. Copyright (C) 2013 S. Karger AG, BaselFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)INCT Complex FluidsFADA-UNIFESPUniversidade Federal de São Paulo, Disciplina Nefrol, Lab Imunol Clin & Expt, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Lab Inflamacao & Farmacol Vasc, BR-04023900 São Paulo, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Imunol, Lab Imunobiol Transplante, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Nefrol, Lab Imunol Clin & Expt, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Lab Inflamacao & Farmacol Vasc, BR-04023900 São Paulo, BrazilFAPESP: 07/07139-3FAPESP: 10/52180-4FAPESP: 10/01404-0FAPESP: 12/02270-0FAPESP: 12/51104-8Web of Scienc

Adipose Tissue-Derived Stem Cell Treatment Prevents Renal Disease Progression

Adipose tissue-derived stem cells (ASCs) are an attractive source of stem cells with regenerative properties that are similar to those of bone marrow stem cells. Here, we analyze the role of ASCs in reducing the progression of kidney fibrosis. Progressive renal fibrosis was achieved by unilateral clamping of the renal pedicle in mice for 1 h; after that, the kidney was reperfused immediately. Four hours after the surgery, 2 x 10(5) ASCs were intraperitoneally administered, and mice were followed for 24 h posttreatment and then at some other time interval for the next 6 weeks. Also, animals were treated with 2 x 10(5) ASCs at 6 weeks after reperfusion and sacrificed 4 weeks later to study their effect when interstitial fibrosis is already present. At 24 h after reperfusion, ASC-treated animals showed reduced renal dysfunction and enhanced regenerative tubular processes. Renal mRNA expression of IL-6 and TNF was decreased in ASC-treated animals, whereas IL-4. IL-10, and HO-1 expression increased despite a lack of ASCs in the kidneys as determined by SRY analysis. As expected, untreated kidneys shrank at 6 weeks, whereas the kidneys of ASC-treated animals remained normal in size, showed less collagen deposition, and decreased staining for FSP-1, type I collagen, and Hypoxyprobe. the renal protection seen in ASC-treated animals was followed by reduced serum levels of TNF-alpha, KC, RANTES, and IL-1 alpha. Surprisingly, treatment with ASCs at 6 weeks, when animals already showed installed fibrosis, demonstrated amelioration of functional parameters, with less tissue fibrosis observed and reduced mRNA expression of type I collagen and vimentin. ASC therapy can improve functional parameters and reduce progression of renal fibrosis at early and later times after injury, mostly due to early modulation of the inflammatory response and to less hypoxia, thereby reducing the epithelial-mesenchymal transition.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)DECIT/Ministerio do SaudeComplex Fluids INCTUniversidade Federal de São Paulo, Div Nephrol, Escola Paulista Med, Expt & Clin Immunol Lab, BR-04023900 São Paulo, BrazilUniv São Paulo, Dept Pathol, São Paulo, BrazilUniv Fed Triangulo Mineiro, Div Pathol, Uberaba, MG, BrazilUniv São Paulo, Dept Immunol, Lab Transplantat Immunobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Escola Paulista Med, Expt & Clin Immunol Lab, BR-04023900 São Paulo, BrazilFAPESP: 09/13251-6FAPESP: 07/07139-3CNPq: 473844/2009-5Web of Scienc

REDUCTION in INFLAMMATORY MARKERS EXPRESSION in SERUM IS RELATED TO IMPROVEMENT in RENAL FUNCTIONS in INTRAUTERINE UNDERNOURISHED RATS

Univ São Paulo, Inst Biomed Sci, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Nephrol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Nephrol, São Paulo, BrazilWeb of Scienc

Mesenchymal stem cells (MSC) prevented the progression of renovascular hypertension, improved renal function and architecture

Renovascular hypertension induced by 2 Kidney-1 Clip (2K-1C) is a renin-angiotensin-system (RAS)-dependent model, leading to renal vascular rarefaction and renal failure. RAS inhibitors are not able to reduce arterial pressure (AP) and/or preserve the renal function, and thus, alternative therapies are needed. Three weeks after left renal artery occlusion, fluorescently tagged mesenchymal stem cells (MSC) (2×10(5) cells/animal) were injected weekly into the tail vein in 2K-1C hypertensive rats. Flow cytometry showed labeled MSC in the cortex and medulla of the clipped kidney. MSC prevented a further increase in the AP, significantly reduced proteinuria and decreased sympathetic hyperactivity in 2K-1C rats. Renal function parameters were unchanged, except for an increase in urinary volume observed in 2K-1C rats, which was not corrected by MSC. The treatment improved the morphology and decreased the fibrotic areas in the clipped kidney and also significantly reduced renal vascular rarefaction typical of 2K-1C model. Expression levels of IL-1β, TNF-α angiotensinogen, ACE, and Ang II receptor AT1 were elevated, whereas AT2 levels were decreased in the medulla of the clipped kidney. MSC normalized these expression levels. In conclusion, MSC therapy in the 2K-1C model (i) prevented the progressive increase of AP, (ii) improved renal morphology and microvascular rarefaction, (iii) reduced fibrosis, proteinuria and inflammatory cytokines, (iv) suppressed the intrarenal RAS, iv) decreased sympathetic hyperactivity in anesthetized animals and v) MSC were detected at the CNS suggesting that the cells crossed the blood-brain barrier. This therapy may be a promising strategy to treat renovascular hypertension and its renal consequences in the near future.Coordenação de Aperfeiçoamento de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP