72 research outputs found
The Role Of Inclusive Schools In Developing Social Interactions Of Children With Special Needs (Autism)
Sekolah inklusi adalah layanan pendidikan yang diberikan kepada anak berkebutuhan khusus untukmemperoleh pendidikan yang layak. Kebijakan pemerintah sebagaimana tertuang dalam Undang-UndangNomor 20 Tahun 2003 dalam Pasal 32 dan Permendiknas Nomor 70 Tahun 2009 adalah memberikankesempatan dan kesempatan kepada anak berkebutuhan khusus untuk memperoleh pendidikan di sekolahreguler. Di sekolah inklusi, anak berkebutuhan khusus dimungkinkan belajar bersama dengan anak normal,dan diperlakukan seperti anak normal. Hal ini menunjukkan dampak positif sekolah inklusi terhadap anakberkebutuhan khusus dari segi psikologis. Tujuan dari penelitian ini adalah untuk memperoleh informasitentang peran sekolah inklusi dalam mengembangkan interaksi sosial bagi anak berkebutuhan khusus(autisme). Penelitian ini dilakukan dengan menggunakan studi kepustakaan atau studi dokumentasi. Hasilpenelitian ini menyebutkan pendidikan inklusi merupakan salah satu upaya pemerintah untukmengoptimalkan kualitas pendidikan di Indonesia. Melalui penyelenggaraan pendidikan inklusi diharapkanmampu menanamkan rasa saling menghargai, kasih sayang, dan yang terpenting, saling menghargai terhadappeserta didik, sehingga anak normal dan anak berkebutuhan khusus dapat berkembang dengan baik
AVALIAÇÃO DE APRENDIZAGEM COM VISTAS AO REDESENHO DO MATERIAL DIDÁTICO UTILIZADO NA FORMAÇÃO DE AGENTES INTERVENTORES PARA O CURSO DE PREVENÇÃO AO USO DE DROGAS
Os resultados das pesquisas sobre o uso de drogas no país nos obrigam a refletir sobre uma questão que envolve crianças, adolescentes e adultos. Nesse sentido, faz-se necessário reavaliar valores, costumes, o papel da família e do próprio Estado na formação do cidadão. Destaca-se, entre outras ações, o compromisso do Estado e da sociedade civil em ofertar cursos que informem e capacitem agentes interventores, formadores e multiplicadores no que diz respeito ao assunto. A partir desse pensamento, um grupo de professores da Universidade do Extremo Sul Catarinense (Unesc), juntamente com o Setor de Educação a Distância, planejou, desenvolveu e executou um curso de extensão, com uma carga horária de 60 h/a, intitulado: .Drogas, saiba como evitar: educando para a vida e formando cidadãos.
Purinergic mechanism in the immune system: A signal of danger for dendritic cells
There is increasing appreciation that injured or stressed cells release molecules endowed with the ability to modulate dendritic cell maturation. The role of these molecules is thought to be that of alerting the body of an impending danger, and initiate and shape the subsequent immune response. Nucleotides are perfectly suited for this task as they are easily released upon damage of the cell membrane, rapidly diffuse in the extracellular environment and ligate specific plasma membrane receptors expressed by dendritic cells and other mononuclear phagocytes. A better knowledge of the modulation of dendritic cell responses by extracellular nucleotides may provide novel routes to enhance the immune response and increase the efficacy of vaccination
Lack of the purinergic receptor P2X7 results in resistance to contact hypersensitivity
Engagement of P2X7 on mouse dendritic cells, presumably by ATP released in response to contact allergen, is needed for IL-1β production and the sensitization phase of contact hypersensitivity
Activation of P2X7-mediated apoptosis Inhibits DMBA/TPA-induced formation of skin papillomas and cancer in mice
<p>Abstract</p> <p>Background</p> <p>The study tested the hypothesis that apoptosis can prevent and control growth of neoplastic cells. Previous studies in-vitro have shown that the pro-apoptotic P2X<sub>7 </sub>receptor regulates growth of epithelial cells. The specific objective of the present study was to understand to what degree the P2X<sub>7 </sub>system controls development and growth of skin cancer in vivo, and what cellular and molecular mechanisms are involved in the P2X<sub>7 </sub>action.</p> <p>Methods</p> <p>Skin neoplasias in mice (papillomas, followed by squamous spindle-cell carcinomas) were induced by local application of DMBA/TPA. Experiments in-vitro utilized cultured epidermal keratinocytes generated from wild-type or from P2X<sub>7</sub>-null mice. Assays involved protein immunostaining and Western blots; mRNA real-time qPCR; and apoptosis (evaluated in situ by TUNEL and quantified in cultured keratinocytes as solubilized DNA or by ELISA). Changes in cytosolic calcium or in ethidium bromide influx (P2X<sub>7 </sub>pore formation) were determined by confocal laser microscopy.</p> <p>Results</p> <p>(a) Co-application on the skin of the P2X<sub>7 </sub>specific agonist BzATP inhibited formation of DMBA/TPA-induced skin papillomas and carcinomas. At the completion of study (week 28) the proportion of living animals with cancers in the DMBA/TPA group was 100% compared to 43% in the DMBA/TPA+BzATP group. (b) In the normal skin BzATP affected mainly P2X<sub>7</sub>-receptor – expressing proliferating keratinocytes, where it augmented apoptosis without evoking inflammatory changes. (c) In BzATP-treated mice the degree of apoptosis was lesser in cancer than in normal or papilloma keratinocytes. (d) Levels of P2X<sub>7 </sub>receptor, protein and mRNA were 4–5 fold lower in cancer tissues than in normal mouse tissues. (e) In cultured mouse keratinocytes BzATP induced apoptosis, formation of pores in the plasma membrane, and facilitated prolonged calcium influx. (f) The BzATP-induced apoptosis, pore-formation and augmented calcium influx had similar dose-dependence for BzATP. (g) Pore formation and the augmented calcium influx were depended on the expression of the P2X<sub>7 </sub>receptor, while the BzATP-induced apoptosis depended on calcium influx. (h) The BzATP-induced apoptosis could be blocked by co-treatment with inhibitors of caspase-9 and caspase-3, but not of caspase-8.</p> <p>Conclusion</p> <p>(a) P2X<sub>7</sub>-dependent apoptosis is an important mechanism that controls the development and progression of epidermal neoplasia in the mouse. (b) The P2X<sub>7</sub>-dependent apoptosis is mediated by calcium influx via P2X<sub>7 </sub>pores, and involves the caspase-9 (mitochondrial) pathway. (c) The diminished pro-apoptotic effect of BzATP in mouse cancer keratinocytes is possibly the result of low expression of the P2X<sub>7 </sub>receptor. (d) Activation of P2X<sub>7</sub>-dependent apoptosis, e.g. with BzATP could be a novel chemotherapeutic growth-preventive modality for papillomas and epithelial cancers in vivo.</p
Shaping immune responses through the activation of dendritic cells–P2 receptors
Dendritic cells (DCs) activate and shape the adaptive immune response by capturing antigens, migrating to peripheral lymphoid organs where naïve T cells reside, expressing high levels of MHC and costimulatory molecules and secreting cytokines and chemokines. DCs are endowed with a high degree of functional plasticity and their functions are tightly regulated. Besides initiating adaptive immune responses, DCs play a key role in maintaining peripheral tolerance toward self-antigens. On the basis of the information gathered from the tissue where they reside, DCs adjust their functional activity to ensure that protective immunity is favoured while unwanted or exaggerated immune responses are prevented. A wide variety of signals from neighbouring cells affecting DC functional activity have been described. Here we will discuss the complex role of extracellular nucleotides in the regulation of DC function and the role of P2 receptors as possible tools to manipulate immune responses
P2 purinergic receptor modulation of cytokine production
Cytokines serve important functions in controlling host immunity. Cells involved in the synthesis of these polypeptide mediators have evolved highly regulated processes to ensure that production is carefully balanced. In inflammatory and immune disorders, however, mis-regulation of the production and/or activity of cytokines is recognized as a major contributor to the disease process, and therapeutics that target individual cytokines are providing very effective treatment options in the clinic. Leukocytes are the principle producers of a number of key cytokines, and these cells also express numerous members of the purinergic P2 receptor family. Studies in several cellular systems have provided evidence that P2 receptor modulation can affect cytokine production, and mechanistic features of this regulation have emerged. This review highlights three separate examples corresponding to (1) P2Y6 receptor mediated impact on interleukin (IL)-8 production, (2) P2Y11 receptor-mediated affects on IL-12/23 output, and (3) P2X7 receptor mediated IL-1β posttranslational processing. These examples demonstrate important roles of purinergic receptors in the modulation of cytokine production. Extension of these cellular observations to in vivo situations may lead to new therapeutic strategies for treating cytokine-mediated diseases
P2X7 in Cancer: From Molecular Mechanisms to Therapeutics
P2X7 is a transmembrane receptor expressed in multiple cell types including neurons, dendritic cells, macrophages, monocytes, B and T cells where it can drive a wide range of physiological responses from pain transduction to immune response. Upon activation by its main ligand, extracellular ATP, P2X7 can form a nonselective channel for cations to enter the cell. Prolonged activation of P2X7, via high levels of extracellular ATP over an extended time period can lead to the formation of a macropore, leading to depolarization of the plasma membrane and ultimately to cell death. Thus, dependent on its activation state, P2X7 can either drive cell survival and proliferation, or induce cell death. In cancer, P2X7 has been shown to have a broad range of functions, including playing key roles in the development and spread of tumor cells. It is therefore unsurprising that P2X7 has been reported to be upregulated in several malignancies. Critically, ATP is present at high extracellular concentrations in the tumor microenvironment (TME) compared to levels observed in normal tissues. These high levels of ATP should present a survival challenge for cancer cells, potentially leading to constitutive receptor activation, prolonged macropore formation and ultimately to cell death. Therefore, to deliver the proven advantages for P2X7 in driving tumor survival and metastatic potential, the P2X7 macropore must be tightly controlled while retaining other functions. Studies have shown that commonly expressed P2X7 splice variants, distinct SNPs and post-translational receptor modifications can impair the capacity of P2X7 to open the macropore. These receptor modifications and potentially others may ultimately protect cancer cells from the negative consequences associated with constitutive activation of P2X7. Significantly, the effects of both P2X7 agonists and antagonists in preclinical tumor models of cancer demonstrate the potential for agents modifying P2X7 function, to provide innovative cancer therapies. This review summarizes recent advances in understanding of the structure and functions of P2X7 and how these impact P2X7 roles in cancer progression. We also review potential therapeutic approaches directed against P2X7
Purinergic signalling and immune cells
This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells
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