Influencia das lectinas PHA, de Phaseolus vulgaris, WGA, de germe de trigo e jacalina, de Artocarpus integrifolia, no processo de reparação tecidual da pele de ratos

Orientador: Celso Paulino da CostaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: A reparação é caracterizada por diversos eventos celulares e humorais que ocorrem de forma integrada. As lectinas são glicoproteínas com diversas atividades biológicas, tais como a ativação de células inflamatórias e a secreção de citocinas ''I' que ativam fibroblastos, as quais podem influenciar o reparo. Este trabalho teve como objetivo avaliar a influência das lectinas PHA, WGA e jacalina na reparação tecidual. As respostas inflamatórias in vivo e a influência das lectinas sobre a proliferação de fibroblastos in vitro, também foram avaliadas. Para avaliar a reparação, 300 J.1g1mL de cada lectina foram aplicados sobre as feridas provocadas no dorso de ratos Wistar, com punch de biópsia de 8 milímetros. A retração das feridas foi medida diariamente, após a aplicação. Nos dias 3, 7, 11 e 15 foram realizadas as análises histológicas, em cortes corados com hematoxilina eosina e impregnados pela prata. Os efeitos inflamatórios foram avaliados após injeção intradérmica das lectinas. A proliferação de fibroblastos, na presença das lectinas, foi avaliada por técnica colorimétrica. PHA acelerou a reparação. Aumentou o depósito e a maturação das fibras de colágeno e antecipou a reepitelização. As análises histológicas revelaram reação inflamatória, com predominância de células mononucleares. Quando adicionado ao meio de cultura, PHA inibiu a proliferação dos fibroblastos nas concentrações acima de 20 J.1g1mL. WGA retardou a reparação, o que foi evidenciado pelo atraso no desenvolvimento do tecido de granulação e na formação do epitélio. Induziu fraca reação inflamatória no local de aplicação e, acima de 20 J.1g1mL, inibiu a proliferação dos fibroblastos. A jacalina não influenciou o reparo tecidual ou a proliferação dos fibroblastos. Entretanto, induziu reação inflamatória local com predominância de células mononucleares. Possivelmente, a agregação de células inflamatórias pela ação de PHA foi benéfica. Linfócitos e macrófagos ativados secretam citocinas e fatores de crescimento importantes na reparação. Ao interagir com os receptores para a fibronectina e outras proteínas, WGA impediria a interação das células com a matriz, retardando a reparação. Apesar da jacalina exercer ação mitogênica sobre os linfócitos T, estimular a secreção de INFye produzir reação inflamatória local, esta lectina não influenciou a reparaçãoAbstract: Wound healing is a complex and dynamic process, characterized by the integrated actions of different cells. Lectins are glycoproteins which can present several biological activities. Many of lectin activities may contribute to repair including increased production of cytokines, and activation of inflammatory cells and fibroblasts. The purpose of this work was to evaluate in vivo effects of PHA (Phaseolus vulgaris phytohemaglutinin), WGA (Triticum vulgare lectin) and jacalin (Artocarpus integrifolia lectin) on wound healing in vivo. Male rats were anesthetized and excisions of 8 mm in diameter were performed in their dorsal skin. The lectins (300uglmL) were then placed Qn the wound. Changes in the surface area were recorded everyday as compared to the initial wound size. The rats were then killed at the 3rd, 7th, 11th, or 15th day. The specimens were harvested for histological examination, and stained with hematoxylin-eosin or silver impregnation. The inflammatory reaction was histologically evaluated around the area of lectin injection. The direct fibroblast proliferation induced by theses lectins were analyzed. PHA accelerated tis sue repair and enhanced the rate of wound contraction when applied to wound sites. Furthermore, PHA increased the reepithelization, collagen deposition and also promoted inflammatory reaction. PHA decreased fibroblast proliferation in vitro. WGA delayed wound repair when applied locally on the wound. WGA promoted weak inflammatory reaction and reduced the granulation tissue maturation. Significant decreased fibroblast proliferation were observed. Jacalin did not have a significant effect on repair and fibroblast proliferation. Jacalin promoted inflammatory Feaction when applied locally. PHA may induce wound healing due to the activation of inflammatory cells. Activated leukocytes release growth factors, such as ILs, INFy and F AFs, which have an important role in the repair processo WGA interact with different glycoproteins, such as plasma fibronectin receptor, and modify the cell and extracellular matrix interaction. Although jacalrn induced the proliferation of human lymphocytes and production of lymphokines, itt did not influence the cicatrization processoDoutoradoBiologia e Patologia Buco-DentalDoutor em Ciência

Immunogenetics of MHC and KIR in the Leprosy

Several genetic polymorphisms in immune response genes have been associated to leprosy. This fact converges on the main hypothesis that genetic factors are involved in the disease susceptibility in two distinct steps: leprosy per se and their clinical forms. These genes play an important role in the recognition process, in the activation of the main metabolic pathway of the immune response and in the evolution of the disease. The scope of this project was to highlight the role of the immune response genes in the context of leprosy, emphasizing the participation of some of them in the signaling and targeting processes in response to bacillus infection and on disease evolution, such as HLA, KIR and MIC genes. Some environmental and genetic factors are important when the exposure to the bacillus occurs, leading to cure or not. Factors that favor a cellular or humoral immune response may influence the clinical manifestations after the infection inducting to one of extreme poles. Furthermore, some genetic factors were associated to the type of reaction that some individuals present during the disease development. Thus, it is very important to highlight the participation of some genetic factors in the immunopathogenesis of leprosy

Application of Nanoparticles in Cancer Treatment: A Concise Review

Timely diagnosis and appropriate antitumoral treatments remain of utmost importance, since cancer remains a leading cause of death worldwide. Within this context, nanotechnology offers specific benefits in terms of cancer therapy by reducing its adverse effects and guiding drugs to selectively target cancer cells. In this comprehensive review, we have summarized the most relevant novel outcomes in the range of 2010–2023, covering the design and application of nanosystems for cancer therapy. We have established the general requirements for nanoparticles to be used in drug delivery and strategies for their uptake in tumor microenvironment and vasculature, including the reticuloendothelial system uptake and surface functionalization with protein corona. After a brief review of the classes of nanovectors, we have covered different classes of nanoparticles used in cancer therapies. First, the advances in the encapsulation of drugs (such as paclitaxel and fisetin) into nanoliposomes and nanoemulsions are described, as well as their relevance in current clinical trials. Then, polymeric nanoparticles are presented, namely the ones comprising poly lactic-coglycolic acid, polyethylene glycol (and PEG dilemma) and dendrimers. The relevance of quantum dots in bioimaging is also covered, namely the systems with zinc sulfide and indium phosphide. Afterwards, we have reviewed gold nanoparticles (spheres and anisotropic) and their application in plasmon-induced photothermal therapy. The clinical relevance of iron oxide nanoparticles, such as magnetite and maghemite, has been analyzed in different fields, namely for magnetic resonance imaging, immunotherapy, hyperthermia, and drug delivery. Lastly, we have covered the recent advances in the systems using carbon nanomaterials, namely graphene oxide, carbon nanotubes, fullerenes, and carbon dots. Finally, we have compared the strategies of passive and active targeting of nanoparticles and their relevance in cancer theranostics. This review aims to be a (nano)mark on the ongoing journey towards realizing the remarkable potential of different nanoparticles in the realm of cancer therapeutics.info:eu-repo/semantics/publishedVersio

Immunopathogenesis of Chronic Periodontitis

Periodontitis is a chronic inflammatory condition characterized by destruction of non-mineralized and mineralized connective tissues. The pathogenesis of periodontitis involves a complex interplay between periodontopathogens and the host immunity, greatly influenced by genetic and environmental factors. Failure in the inflammation resolving mechanism leads to establishment of a chronic inflammatory process, resulting in the progressive destruction of bone and soft tissue. The aim of this chapter is to summarize the role of innate and specific immune response involved in pathogenesis of periodontitis. Cells and inflammatory mediators, those participating in inflammatory process of the ligamentous supporting structure and in resorption of alveolar bone, will be presented

Genetic polymorphisms of Rh, Kell, Duffy and Kidd systems in a population from the State of Paraná, southern Brazil

BACKGROUND: Red blood group genes are highly polymorphic and the distribution of alleles varies among different populations and ethnic groups. AIM: To evaluate allele polymorphisms of the Rh, Kell, Duffy and Kidd blood group systems in a population of the State of Paraná METHODS: Rh, Kell, Duffy and Kidd blood group polymorphisms were evaluated in 400 unrelated blood or bone marrow donors from the northwestern region of Paraná State between September 2008 and October 2009. The following techniques were used: multiplex-polymerase chain reaction genotyping for the identification of the RHD gene and RHCE*C/c genotype; allele-specific polymerase chain reaction for the RHDΨ and restriction fragment length polymorphism polymerase chain reaction for the RHCE*E/e, KEL, FY-GATA and JK alleles. RESULTS: These techniques enabled the evaluation of the frequencies of Rh, Kell, Duffy and Kidd polymorphisms in the population studied, which were compared to frequencies in two populations from the eastern region of São Paulo State. CONCLUSION: The RHCE*c/c, FY*A/FY*B, GATA-33 T/T, JK*B/JK*B genotypes were more prevalent in the population from Paraná, while RHCE*C/c, FY*B/FY*B, GATA-33 C/C, JK*A/JK*B genotypes were more common in the populations from São Paulo.212

Associação de HLA-DR2 com cardiopatia crônica em uma população da região noroeste do Estado do Paraná, Brasil

A doença de Chagas é um dos maiores problemas que afetam a saúde pública no Brasil e outros países latino americanos. No entanto, poucos trabalhos avaliaram a susceptibilidade genética a esta doença. Como genes de resposta imune estão localizados no Complexo de Histocompatibilidade HLA, decidimos estudar a associação entre os antígenos HLA e a forma cardíaca da doença de Chagas, que parece apresentar um componente auto-imune importante. Trinta e cinco pacientes e 72 controles residentes na região noroeste do estado do Paraná foram utilizados neste estudo. Métodos estatísticos clássicos foram usados para comparar as freqüências HLA entre pacientes e controles. Os dados confirmam uma associação primária com HLA-DR2 (48.4%vs12.3%; Pc=0,0011) e secundária com HLA-B7 (31.4%vs8.3%; Pc=0.033). Concluindo, uma associação positiva entre DR2 e cardiopatia chagásica crônica foi demonstrada numa população de brancos brasileiros, reforçando a hipótese do envolvimento de fatores genéticos na susceptibilidade à forma cardíaca da doença de Chaga

Role of cytokines in the immunopathogenesis of Graft-versus-Host Disease

Stem cell transplantation is the first line treatment of many hematological diseases and primary immunodeficiencies. Graft-versus-host disease (GVHD) is still a severe complication after allogeneic transplantation and the main cause of mortality and morbidity. The study of the pathogenesis of GVHD may help to develop ways to prevent the disease, as well as to choose adequate immunosuppressant therapies. This study discusses the main immunological components involved in the pathogenesis of acute and chronic GVHD, with emphasis on the participation of cytokines and their control.O transplante de células progenitoras hematopoéticas é o tratamento de escolha para muitas doenças hematológicas e imunodeficiências primárias. A doença do enxerto contra o hospedeiro (DECH) é ainda uma grave complicação após o transplante alogênico e a principal causa de mortalidade e morbidade. O estudo da patogênese da DECH auxilia no desenvolvimento de medidas preventivas da doença, assim como na escolha de terapias imunossupressoras adequadas de tratamento. Este estudo discute os principais componentes imunológicos envolvidos na patogênese da DECH aguda e crônica, com ênfase à participação das citocinas e seu controle.14215