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1.
Biochem Genet ; 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38522064

RESUMO

Oxidative stress is a sophisticated situation that orignates from the accumulation of reactive free radicals within cellular compartments. The antioxidant mechanism of the MnSOD enzyme facilitates the removal of these lethal oxygen species from cellular components. The main goal of this pertained work is to study the contribution of the SOD2 (rs4880; p.Val16Ala) variant to the development of bronchial asthma among children. The study's design was carried out based on a total of 254 participants including 127 asthmatic children (91 atopic and 36 non-atopic) along with 127 unrelated healthy controls. Allelic discrimination analysis was executed using the T-ARMS-PCR protocol. This potential variant conferred a significant association with decreased risk of bronchial asthmatic children under allelic (OR = 0.56, P-value = 0.002), recessive (OR = 0.32, P-value = 0.011), and dominant (OR = 0.51, P-value = 0.040) models. Additionally, atopic and non-atopic asthmatic children indicated a protection against bronchial asthma development under allelic, and dominant models (p-value < 0.05). Our findings suggested that the SOD2*rs4880 variant was correlated with decreased risk of childhood bronchial asthma.

2.
FASEB J ; 34(2): 2595-2608, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31919918

RESUMO

Dendritic cells are an important link between innate and adaptive immune response. The role of dendritic cells in bone homeostasis, however, is not understood. Osteoporosis medications that inhibit osteoclasts have been associated with osteonecrosis, a condition limited to the jawbone, thus called medication-related osteonecrosis of the jaw. We propose that disruption of the local immune response renders the oral microenvironment conducive to osteonecrosis. We tested whether zoledronate (Zol) treatment impaired dendritic cell (DC) functions and increased bacterial load in alveolar bone in vivo and whether DC inhibition alone predisposed the animals to osteonecrosis. We also analyzed the role of Zol in impairment of differentiation and function of migratory and tissue-resident DCs, promoting disruption of T-cell activation in vitro. Results demonstrated a Zol induced impairment in DC functions and an increased bacterial load in the oral cavity. DC-deficient mice were predisposed to osteonecrosis following dental extraction. Zol treatment of DCs in vitro caused an impairment in immune functions including differentiation, maturation, migration, antigen presentation, and T-cell activation. We conclude that the mechanism of Zol-induced osteonecrosis of the jaw involves disruption of DC immune functions required to clear bacterial infection and activate T cell effector response.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Osso e Ossos/efeitos dos fármacos , Células Dendríticas/metabolismo , Homeostase/imunologia , Doenças Maxilomandibulares/imunologia , Osteonecrose/tratamento farmacológico , Ácido Zoledrônico/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Células Dendríticas/imunologia , Homeostase/efeitos dos fármacos , Imidazóis/farmacologia , Doenças Maxilomandibulares/tratamento farmacológico , Osteoclastos/efeitos dos fármacos , Osteoclastos/imunologia , Osteonecrose/imunologia , Extração Dentária/métodos , Cicatrização/efeitos dos fármacos
3.
BMC Anesthesiol ; 18(1): 46, 2018 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-29699477

RESUMO

BACKGROUND: Bacterial translocation (BT) has been proposed as a trigger for stimulation of the immune system with consequent hemodynamic alteration in patients with liver cirrhosis. However, no information is available regarding its hemodynamic and coagulation consequences during liver transplantation. METHODS: We screened 30 consecutive adult patients undergoing living-donor liver transplant for the presence of BT. Bacterial DNA, Anti factor Xa (aFXa), thromboelastometry, tumor necrosis factor-α TNF-α, and interleukin-17 (IL-17) values were measured in sera before induction of anesthesia. Systemic hemodynamic data were recorded throughout the procedures. RESULTS: Bacterial DNA was detected in 10 patients (33%) (bactDNA(+)). Demographic, clinical, and hemodynamic data were similar in patients with presence or absence of bacterial DNA. BactDNA(+) patients showed significantly higher circulating values of TNF-α and IL-17, and had significantly higher clotting times and clot formation times as well as significantly lower alpha angle and maximal clot firmness than bactDNA(-) patients, P < 0.05. We found no statistically significant difference in aFXa between the groups, P = 0.4. Additionally, 4 patients in each group needed vasopressor agents, P = 0.2. And, the amount of transfused blood and blood products used were similar between both groups. CONCLUSION: Bacterial translocation was found in one-third of patients at the time of transplantation and was largely associated with increased markers of inflammation along with decreased activity of coagulation factors. TRIAL REGISTRATION: Trial Registration Number: NCT03230214 . (Retrospective registered). Initial registration date was 20/7/2017.


Assuntos
Translocação Bacteriana/fisiologia , Coagulação Sanguínea/fisiologia , Hemodinâmica/fisiologia , Transplante de Fígado , DNA Bacteriano/sangue , Feminino , Humanos , Interleucina-17/sangue , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Tromboelastografia , Fator de Necrose Tumoral alfa/sangue
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