DSpace Collection:
http://hdl.handle.net/1843/276
2024-03-28T17:33:09ZImunomodulação da resposta imune na artrite gotosa aguda murina através da reprogramação de macrófagos
http://hdl.handle.net/1843/65275
Title: Imunomodulação da resposta imune na artrite gotosa aguda murina através da reprogramação de macrófagos
Abstract: Gouty arthritis is an inflammation of the joints characterized by the deposition of MSU crystals (monosodium urate) within the joints. Within the context of gouty inflammation, macrophages play a paradoxical role, participating in both the pathogenesis and resolution of inflammation. These cells have the ability to adapt their activation profiles based on the tissue microenvironment and contribute to physiological and pathological processes in seeking to achieve homeostasis. The aim of this study was to investigate and evaluate the therapeutic potential of regulatory macrophages (Mreg), aiming to enhance the understanding and application of their effects in a gout model, focusing on reducing inflammatory symptoms and preventing joint damage. Consequently, in vitro studies were conducted using bone marrowderived macrophages (BMDMs) and in vivo experiments using gout models in mice. Reprogramming macrophages toward a regulatory profile led to a decrease in the release of IL-12 and an increase in the release of IL-10 compared to other macrophage subtypes. In in vitro studies, co-incubation of Mreg with LPS-primed macrophages and subsequent challenge with NLRP3 inflammasome agonists resulted in a reduction in the release of IL-1β, a key cytokine in gouty inflammation. Additionally, a decrease in IL-1β was observed in the model of acute peritonitis induced by MSU in mice upon injecting Mreg. Subsequently, MSU crystals were injected into the tibiofemoral joints of mice, resulting in tissue inflammation associated with a significant influx of leukocytes, mainly neutrophils. Administering Mreg therapy to the joints led to a reduction in the influx of neutrophils and the release of the chemokine CXCL1. These preliminary results provide perspectives for further investigations into the role of Mregs and IL-10 in the NLRP3 inflammasome pathway and inflammation reduction, as well as the potential for manipulating the macrophage phenotype. The study highlights macrophages as potential therapeutic targets in gout. Reprogramming macrophages towards an anti-inflammatory profile could be an effective approach in disease management. These findings have the potential to contribute to the development of innovative therapeutic strategies for gouty arthritis.
Type: Dissertação2023-11-14T00:00:00ZAspectos anatomoclínicos e laboratoriais de gestantes infectadas pelo HIV e expostas ao ZIKA vírus.
http://hdl.handle.net/1843/65274
Title: Aspectos anatomoclínicos e laboratoriais de gestantes infectadas pelo HIV e expostas ao ZIKA vírus.
Abstract: The Zika vírus (ZIKV) epidemic that occurred in Brazil from 2015 was followed by the identification of complications, the most impotant being related to the congenital syndrome associated with ZIKV (SCZ). Placentas from pregnant women exposed to the vírus may exhibit variable morphological changes. Such changes can be modified in immunosuppressed patients, in the context of co-infecctin, and may be associated with different neonatal outcomes. Objective: Characterize the morphological aspects of placentas from HIV-infected pregnant women and compare with placenta from ZIKV carriers, and in ZIKV-HIV co-infection. Methods: Thirty-seven HIV-positive pregnant women who were being followed up at a referral obstetric service and who had suspected symptoms of arbovirus infection were included. Clinical data of pregnancy, anatomopathological analysis and research of viral genetic material of the placentas were performed and compared with the histology of placentas from perenant women who were know to have ZIKV infection during pregnancy and with a control group. Results: The most observed antiretroviral regimen was the combination of lamivudine (3TC) + tenofovir (TDF) + efavirenz (EFZ) – 37,4%. The mean viral load at delivery was 836 copies/ml, with a reduction of 81,9% compared to admission (p=0,019). The mean gestational age at birth, birth weight and Apgar score of newborns did not differ from the population. The macroscopic analysis showed an average weight of 423.5g and identifiction of fone case of old infarction, one of retroplacental and suchorionic hematoma, in addition to signs of umbilical cord thrombosis and change in the color of the placenta in 16.2% of cases. The main microscopic finding was marked distal villous hypoplasia present in 88.8% of the placentas of pregnant women with ZIKV and moderate distal villous hypoplasia presente in 62.1% of the placentas of pregnant women with HIV. Other findings indentified were corangiosis, congestion and thickening of villous vessels. HIV genetic material was identified in 94,5% of the placentas in the group of patients with HIV and in 10.8% of these placentas the co-infection by ZIKV was also identified. No marked distal villous hypoplasia was identified in the ZIKV-HIV co-infection group. HIV and ZIKV viruses independently compromise the human placenta and, when associated, there is evidence of reduced impact of ZIKV.
Type: Dissertação2021-09-09T00:00:00ZEstudo clínico e histopatológico dos efeitos da radiação ionizante com dose subletal em camundongos
http://hdl.handle.net/1843/64962
Title: Estudo clínico e histopatológico dos efeitos da radiação ionizante com dose subletal em camundongos
Abstract: Ionizing radiation has been used in various disease treatments, mainly in the oncology area,
proving to be an interesting tool alongside chemotherapy for the cure or palliative treatment of
patients. On the other hand, radiation can also be used as a weapon of mass destruction, which
generates radioactive compounds that are difficult to trace, preventing adequate clinical control
of patients. Exposure to radiation, accidental or presumed by radiotherapy, can generate side
effects, characterized by the so-called acute radiation sickness and treatments aimed at
radiation-induced injuries depend on the symptoms, the dose of exposure as well as the tissue
irradiated. Due to the diverse possibilities of exposure to radiation and the varied forms of
presentation of diseases caused by radiation, experimental models capable of mimicking some
of these situations are important study tools. In this context, the animal model of radiation
disease used in this study evaluated the effects of exposure on the entire body of C57BL/6 mice,
during a period of approximately 30 days after lethal (7 Gray) and sublethal (5 Gray) doses at
a rate dose of 0.75 min1 of Gamma rays. The clinical data analyzed were: temperature and body
weight, mucosal changes and food consumption. The anatomopathological analyzes were
performed on the following organs: intestine, lung and bone marrow in the 5 Gy groups and the
control group without irradiation at the end of 30 days. Clinically, it was observed that the
survival of the 7 Gy group was reduced up to 11 days post-irradiation and the animals in the 5
Gy group survived approximately 30 days after irradiation. Changes in mucous membranes and
extremities (paws and snout) were more frequent in the 7 Gy group of animals compared to
animals in the 5 Gy group. Bone marrow analysis demonstrated hypoplasia of hematopoietic
progenitors and an increased number of adipocytes in the 5 Gy group. In the lung, an intense
inflammatory process with thickening of the alveolar septum was observed after 30 days of
irradiation. In the intestine, the goblet cells, as well as the architecture of the colon, were
preserved and without changes to the crypts or mucosa at the end of the experiment.
Type: Dissertação2022-07-13T00:00:00ZEstudo histológico qualitativo e quantitativo das alterações na matriz extracelular (MEC) e estudo imuno-histoquímico do infiltrado inflamatório em doenças granulomatosas infecciosas e não infecciosas
http://hdl.handle.net/1843/64694
Title: Estudo histológico qualitativo e quantitativo das alterações na matriz extracelular (MEC) e estudo imuno-histoquímico do infiltrado inflamatório em doenças granulomatosas infecciosas e não infecciosas
Abstract: Qualitative and quantitative histological study of alterations in the extracellular matrix (ECM)
and immunohistochemistry of the inflammatory infiltrate in infectious and non-infectious
granulomatous diseases.
Processes of organization and fibrosis (collagenogenesis) and/or elastic tissue synthesis or
degradation occur in infectious and non-infectious cutaneous granulomatous diseases
characterizing, profound Extracellular Matrix (ECM) alterations. Activity of macrophage
subtypes contributes to these ECM changes and to fibrosis processes arising from the
secretion of various cytokines, inflammatory activity, or ECM remodeling proteins such as
the metalloproteases MMPs, collagen secretion and others.
In view of the versatility and plasticity of this cell against agents, the mapping of macrophage
expressed proteins such as CD68 and CD163 are investigated. Additionally, some
mesenchymal markers such as alpha-actin and vimentin may indicate activation of cells with
fibroblastic potential, i.e. activated collagen-producing fibroblasts ("myofibroblast"). Some
quantitative techniques of specific components of the ECM such as reticular fibers (composed
mainly of collagens I and III) and elastic fibers, provide clues as to how the ECM behaves in
different models of granulomatous diseases of infectious causes such as tegumentary
American leishmaniasis - ATL, Virchowian leprosy and paracoccidioidomycosis and also
non-infectious diseases such as foreign body granuloma and sarcoidosis, establishing a
comparison between these models. Thus, our study demonstrated a higher expression of
alpha-actin, vimentin, and reticular fibers in the samples from the paracoccidioidomycosis and
foreign body granuloma groups, along with higher rates of M2 macrophages (CD163 positive
cells). Alterations in the elastic tissue occurred mainly in the samples from Virchowian
leprosy and ATL. However, differences between infectious and non-infectious granulomatous
diseases regarding the amount of M2 macrophages, reticular fibers, alpha-actin, and vimentin
were not observed.
Type: Dissertação2023-07-14T00:00:00Z