Endangered Lymphocytes: The Effects of Alloxan and Streptozotocin on Immune Cells in Type 1 Induced Diabetes.

Alloxan (ALX) and streptozotocin (STZ) are extensively used to induce type 1 diabetes (T1D) in animal models. This study is aimed at evaluating the differences in immune parameters caused by ALX and STZ. T1D was induced either with ALX or with STZ, and the animals were followed for up to 180 days. Both ALX and STZ induced a decrease in the total number of circulating leukocytes and lymphocytes, with an increase in granulocytes when compared to control mice (CT). STZ-treated mice also exhibited an increase in neutrophils and a reduction in the lymphocyte percentage in the bone marrow. In addition, while the STZ-treated group showed a decrease in total CD3+, CD4-CD8+, and CD4+CD8+ T lymphocytes in the thymus and CD19+ B lymphocytes in the pancreas and spleen, the ALX group showed an increase in CD4-CD8+ and CD19+ only in the thymus. Basal levels of splenic interleukin- (IL-) 1ß and pancreatic IL-6 in the STZ group were decreased. Both diabetic groups showed atrophy of the thymic medulla and degeneration of pancreatic islets of Langerhans composed of inflammatory infiltration and hyperemia with vasodilation. ALX-treated mice showed a decrease in reticuloendothelial cells, enhanced lymphocyte/thymocyte cell death, and increased number of Hassall's corpuscles. Reduced in vitro activation of splenic lymphocytes was found in the STZ-treated group. Furthermore, mice immunized with ovalbumin (OVA) showed a more intense antigen-specific paw edema response in the STZ-treated group, while production of anti-OVA IgG1 antibodies was similar in both groups. Thereby, important changes in immune cell parameters in vivo and in vitro were found at an early stage of T1D in the STZ-treated group, whereas alterations in the ALX-treated group were mostly found in the chronic phase of T1D, including increased mortality rates. These findings suggest that the effects of ALX and STZ influenced, at different times, lymphoid organs and their cell populations.

Photobiomodulation associated to cellular therapy improve wound healing of experimental full thickness burn wounds in rats.

Adipose derived stromal vascular fraction (SVF) is a method of cell therapy potentially applicable for treatment of full thickness burns. Here we investigated if the association of photobiomodulation (PBM) with SVF therapy could improve wound healing in experimentally induced full thickness burn wounds in rats compared to the topical agent 2% silver sulfadiazine in a dose-dependent manner. Sixty-six male Wistar rats were divided in 4 groups containing 5 animals each which received the following treatments: 2% sulfadiazine (SD), SVF, SVF plus PBM at 30 mW (SVFL30), and SVF plus PBM at 100 mW (SVFL100). Two donor animals were used for each experimental series with 3, 7 and 30 days. Digital photography, microscopic analysis with Hematoxilin and Eosin (H&E), quantification of collagen type I by picrosirius red staining analysis and wound contraction evaluation were performed in order to quantify the results. At day 3 SVF alone or combined with PBM promoted increased early inflammatory response compared to SD. At day 7 SVFL30 and SVFL100 enhanced inflammatory cells infiltration, angiogenesis and fibroblast content compared to SVF and SD groups. At day 30 collagen concentration and wound contraction were higher in SVFL30 when compared to the other groups. In conclusion PBM promotes a synergistic outcome with SVF therapy with a dose dependent effect potentializing wound healing of experimental full thickness burns in rats through amplification of early inflammatory response, enhanced angiogenesis, fibroblast content, accentuated wound contraction and collagen concentration.

Taenia crassiceps antigens induce a Th2 immune response and attenuate injuries experimentally induced by neurotoxoplasmosis in BALB/c mice.

Toxoplasma gondii is a pathogenic agent responsible for causing both systemic and local disease which elicits a typically pro-inflammatory, Th1 immune response. Taenia crassiceps antigen induces a Th2 immune response that immunomodulates Th1 based infections. Therefore the aim of this study was to evaluate whether T. crassiceps cysticerci antigens are able to modulate the inflammatory response triggered in experimental neurotoxoplasmosis (NT). BALB/c mice were inoculated with T. gondii cysts and/or cysticerci antigens and euthanized at 60 and 90days after inoculation (DAI). The histopathology of the brains and cytokines produced by spleen cells culture were performed. The animals from the NT group, 90DAI (NT90), presented greater intensity of lesions such as vasculitis, meningitis and microgliosis and cytokines from Th1 profile characterized by high levels of IFN-gamma. While in the T. crassiceps antigens group, 60DAI, there were more discrete lesions and high levels of IL-4, a Th2 cytokine. In the NT co-inoculated with cysticerci antigens group the parenchyma lesions were more discrete with lower levels of IFN-gamma and higher levels of IL-4 when compared to NT90. Therefore the inoculation of T. crassiceps antigens attenuated the brain lesions caused by T. gondii inducing a Th2 immune response.

Polymethyl methacrylate (Linnea Safe) causes local inflammatory response after intramuscular implant in BALB/c mice but it is not observed in distant organs / Polimetilmetacrilato (Linnea Safe) provoca resposta inflamatória localizada após implante intramuscular em camundongos BALB/c, mas não é observado em órgãos a distância

ABSTRACT Introduction: Among its different therapeutic functions, the use of polymethyl methacrylate (PMMA) for more than a decade has has stood out in the replacement of the volumes lost with the aging process and filling in wrinkles and creases. It is considered a permanent biomaterial despite its reliability is widely discussed by health professionals. Objective: To analyze the size of the microspheres in of three different commercialized types of PMMA, and the inflammatory process generated by the implant, as well as to evaluate possible migration of the microspheres. Methods: The polymers of the brands Biossimetric®, MetaCrill® and Linnea Safe® were analyzed by scanning electron microscope (SEM) and had the dispersion and the size of its particles determined. After this analysis, it was decided to implant in BALB/c mice the polymer of the brand Linnea Safe®, which was the more homogeneous product. The animals submitted to polymer implantation were euthanized at 3, 7, 15, 30, 60, 90 and 120 days after implantation, allowing the weighing of the implanted paws and the histopathological analysis of some tissues. Results: It was observed that the implantation of Linnea Safe® PMMA microspheres in mice triggered an acute inflammatory process 3 to 15 days after the surgical procedure, evolving to chronic non-granulomatous inflammation with collagen deposition, tissue reorganization after 30 days of PMMA implantation up to 120 days; also, no microspheres were observed in distant organs. Conclusion: The Linnea Safe® PMMA behaved as a safe and stable biomaterial, once its microspheres were sized to prevents phagocytosis, and leads to local and controlled inflammation.

RESUMO Introdução: Entre suas diversas funções terapêuticas, há mais de uma década o polimetilmetacrilato (PMMA) vem se destacando na reposição de volumes perdidos com processo de envelhecimento e preenchimento de sulcos e rugas. É considerado um biomaterial permanente, apesar de sua confiabilidade ser amplamente discutida por profissinais da área da saúde. Objetivos: Analisar o tamanho das microesferas de três formas comercializadas de PMMA e o processo inflamatório gerado pelo implante, bem como avaliar a possível migração das microesferas. Métodos: Os polímeros das marcas Biossimetric®, MetaCrill® e Linnea Safe® foram analisados por microscópio eletrônico de varredura (MEV) e tiveram a dispersão e o tamanho de suas partículas determinados. Após essa análise, decidiu-se implantar em camundongos BALB/c o polímero da marca Linnea Safe®, o qual se apresentou mais homogêneo. Os animais submetidos ao implante do polímero foram eutanasiados aos 3, 7, 15, 30, 60, 90 e 120 dias após o implante, permitindo a realização da pesagem das patas implantadas e a análise histopatológica de alguns tecidos. Resultados: Observou-se que a implantação de microesferas de PMMA Linnea Safe® em camundongos desencadeou um processo inflamatório agudo de 3 a 15 dias após o procedimento cirúrgico, evoluindo para inflamação crônica não granulomatosa com deposição de colágeno e reorganização do tecido após 30 dias de implantação de PMMA até 120 dias; além disso, não foram observadas microesferas em órgãos a distância. Conclusão: O PMMA da marca Linnea Safe® comportou-se como um biomaterial seguro e estável, uma vez que as microesferas apresentaram tamanho que impedem sua fagocitose e provocam inflamação localizada e controlada.