Navegando por Autor "Calsavara, Allan Jefferson Cruz"
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Item Anti-Inflammatory and antioxidant properties of black mulberry (Morus nigra L.) in a model of LPS-induced sepsis.(2018) Lúcio, Karine de Pádua; Rabelo, Ana Carolina Silveira; Araújo, Carolina Morais; Brandão, Geraldo Célio; Souza, Gustavo Henrique Bianco de; Silva, Regislainy Gomes da; Souza, Débora Maria Soares de; Silva, André Talvani Pedrosa da; Bezerra, Frank Silva; Calsavara, Allan Jefferson Cruz; Costa, Daniela CaldeiraSepsis is a complex disease and is the cause of many deaths worldwide. Sepsis pathogenesis involves a dysregulated inflammatory response with consequent production of inflammatory mediators and reactive species. The production and excessive release of these substances into the systemic circulation trigger various cellular and metabolic alterations that are observed during the disease evolution. Thus, more studies have been carried out to investigate the therapeutic potential of plants such as Morus nigra L., popularly known as black mulberry. Studies have shown that plants belonging to the Morus genus are rich in secondary metabolites such as flavonoids which are associated with important biological activities as antioxidant and anti-inflammatory actions. Based on this context, the objective of our study was to evaluate the anti-inflammatory and antioxidant properties of Morus nigra L. in a sepsis model induced by LPS. Male C57BL/6 mice were distributed in four groups: control, sepsis, sepsis treated with leaf extract of mulberry, and sepsis treated with mulberry pulp. The animals were treated with 100 μL of their respective treatments for twenty-one days. Sepsis was induced at the 21st day with lipopolysaccharide (LPS) by intraperitoneal injection. The animals were euthanized 24 hours after receiving the LPS injection. The data obtained were analyzed in GraphPad Prism 6.0 software. Our results showed that treatment with either extract significantly decreased the number of leukocytes in the bronchoalveolar lavage fluid and serum levels of TNF in septic animals. Regarding the redox status, the treatments significantly decreased the antioxidant activity of the enzyme glutathione peroxidase. Regarding metalloproteinase type 2, it was observed that the treatment with black mulberry pulp was able to significantly reduce the activity of this enzyme concerning the sepsis group. Finally, these results together promoted an increase in the animal’s survival that received the black mulberry leaf or pulp extract.Item Avaliação das propriedades anti-inflamatórias e antioxidantes de Morus nigra L. (blackberry) em um modelo murino de sepse induzido por LPS.(2018) Lúcio, Karine de Pádua; Costa, Daniela Caldeira; Calsavara, Allan Jefferson Cruz; Costa, Daniela Caldeira; Souza, Gustavo Henrique Bianco de; Cardoso, Leonardo MáximoA sepse é uma doença complexa, de alta incidência nas unidades de terapia intensiva (UTIs) sendo a causa de muitos óbitos no mundo inteiro. A patogênese da sepse envolve uma resposta inflamatória desregulada com consequente produção de mediadores inflamatórios e espécies reativas. A produção e liberação excessiva dessas substâncias na circulação sistêmica desencadeiam as diversas alterações celulares e metabólicas que são observadas durante a evolução da doença. Alguns trabalhos científicos tem investigado plantas como Morus nigra L., conhecida popularmente como amoreira-preta, pois sabe-se que as plantas desse gênero apresentam um grande potencial terapêutico. Estudos já mostraram que as plantas pertencentes a este gênero são ricas em metabólitos secundários como os flavonoides que apresentam atividades biológicas importantes. Com base nesse contexto, o objetivo do nosso estudo foi avaliar as propriedades anti-inflamatórias e antioxidantes de Morus nigra L. em modelo murino de sepse induzido por LPS. Para isso, camundongos machos da linhagem C57Bl/6, com oito semanas de idade e peso médio entre 20-25g foram distribuídos em quatro grupos experimentais, a saber: controle (C), sepse (S), sepse tratado com extrato das folhas da amoreira (SF) e sepse tratado com a polpa de amora (SP). Os animais foram tratados com 100μl de seus respectivos tratamentos, por gavagem, durante vinte e um dias. A sepse foi induzida no 21º através de injeção intraperitoneal com lipopolissacarídeo (LPS). Os animais foram eutanasiados 24 horas após receberem a injeção de LPS e amostras de plasma, fígado e lavado bronco-alveolar foram coletados e armazenados para análises posteriores. Os dados obtidos a partir das dosagens laboratoriais foram analisados no software GraphPad Prism 5.0 para Windows (San Diego, California, USA). Nossos resultados mostraram que os tratamentos com a polpa e o extrato das folhas diminuíram significativamente o infiltrado de leucócitos nos pulmões e os níveis séricos de TNF nos animais sépticos. Com relação aos marcadores de processos redox, ambos os tratamentos diminuíram significativamente a atividade antioxidante da enzima glutationa peroxidase (GPx). No que diz respeito à metaloproteinase do tipo 2 (MMP-2) observamos que o tratamento com a polpa da amora foi capaz de reduzir significativamente a atividade dessa enzima em relação ao grupo sepse. Por fim, esses resultados positivos em conjunto, promoveram o aumento na sobrevida dos animais sépticos que receberam o extrato das folhas ou a polpa de amora.Item Efeito da doxiciclina na melhora cognitiva de animais com sepse polimicrobiana : papel da metaloproteinase cerebral na regulação das vias neuro inflamatórias e oxidativas.(2023) Castro, Maria Laura da Cruz; Costa, Daniela Caldeira; Calsavara, Allan Jefferson Cruz; Costa, Daniela Caldeira; Calsavara, Allan Jefferson Cruz; Barichello, Tatiana; Santos, Orlando David Henrique dos; Gomes, Sílvia de PaulaIndivíduos que sobrevivem à sepse podem apresentar sequelas neurológicas com diminuição da função cognitiva. Um dos mecanismos responsáveis por esta diminuição da função cognitiva é o aumento da atividade das metaloproteinases da matriz (MMPs). A doxiciclina é um antibiótico da classe das tetraciclinas e um potente inibidor de MMPs. Assim, o objetivo desse trabalho foi avaliar o efeito da doxiciclina (um inibidor de MMPs) na possível melhora cognitiva de camundongos com sepse polimicrobiana e os seus mecanismos subjacentes. Foram utilizados 183 camundongos isogênicos C57BL/6 machos, com 8 a 12 semanas de idade distribuídos em cinco grupos: Grupo 1: animais submetidos à cirurgia branca e tratados com soro fisiológico 0,9% (SHAM) (n=27); Grupo 2: animais submetidos à cirurgia de ligadura e perfuração do ceco (CLP) e tratados com soro fisiológico 0,9% (n=49); Grupo 3: CLP tratados com doxiciclina (20 mg/kg/dia) (DOX20) (n=38); Grupo 4: CLP tratados com doxiciclina (40 mg/kg/dia) (DOX40) (n=32); Grupo 5: CLP tratados com ceftriaxona (400 mg/kg/dia) (CTX) (n=37). Os tratamentos foram realizados por meio de uma injeção subcutânea diária durante o período de cinco dias. No quarto dia de tratamento os animais foram submetidos aos testes cognitivos. O tratamento com a doxiciclina foi capaz de reduzir os níveis de TNF e VEGF no córtex cerebral, inibir MMP-9, melhorar o perfil redox, por meio do aumento da atividade de SOD e catalase e diminuição do dano oxidativo lipídico, além de aumentar os níveis de BDNF no hipocampo e melhorar a cognição dos animais. Além disso, a doxiciclina interagiu de maneira mais efetiva com a MMP-9 do que a ceftriaxona no estudo de modelagem molecular. Portanto, nossos resultados sugerem que a doxiciclina por meio da sua capacidade de inibir MMPs e dos seus mecanismos imunomoduladores e antioxidantes é um potencial fármaco para o tratamento do déficit cognitivo em indivíduos que sobrevivem à sepse.Item Factors associated with short and long term cognitive changes in patients with sepsis.(2018) Calsavara, Allan Jefferson Cruz; Costa, Priscila de Almeida; Nobre Junior, Vandack Alencar; Teixeira, Antônio LúcioThis study aimed to assess cognition in patients with severe sepsis or septic shock and whether cognitive impairment was associated with clinical and laboratory parameters. We conducted a cohort study of patients with severe sepsis and septic shock evaluated within 24 h and one year after ICU discharge. Demographic, clinical and laboratory data were analyzed, and the following neuropsychological tests were applied: Consortium to Establish Registry for Alzheimer’s Disease, Mini- Mental State Examination, and Trail Making Test forms A and B. We included 33 patients, mean age of 49, 19% were female. Patients underperformed on most measures 24 h after ICU discharge, with improvement on follow-up. IQCODE, APACHE II scores, NSE and IFN-γ levels at ICU discharge were associated with poor cognitive performance, while higher educational level was associated with good cognitive performance. The time to first antibiotic dose, accumulated dose of haloperidol during UCI stay and mean glycemia were also associated with poor cognitive outcome. In general, patients with severe sepsis or septic shock have cognitive impairment that can improve over time. This improvement was associated with factors identified during their ICU stay, such as cognitive reserve, educational level, mean glycemia during ICU stay and NSE level.Item High-fat diet increases mortality and intensifies immunometabolic changes in septic mice.(2023) Gomes, Sttefany Viana; Dias, Bruna Vidal; Machado Júnior, Pedro Alves; Pereira, Renata Rebeca; Souza, Débora Maria Soares de; Breguez, Gustavo Silveira; Lima, Wanderson Geraldo de; Magalhães, Cíntia Lopes de Brito; Cangussú, Silvia Dantas; Silva, André Talvani Pedrosa da; Queiroz, Karina Barbosa de; Calsavara, Allan Jefferson Cruz; Costa, Daniela CaldeiraImmunometabolic changes in the liver and white adipose tissue caused by high-fat (HF) diet intake may worse metabolic adaptation and protection against pathogens in sepsis. We investigate the effect of chronic HF diet (15 weeks) on mortality and immunometabolic responses in female mice after sepsis induced by cecum ligation and perforation (CLP). At week 14, animals were divided into four groups: sham C diet, sepsis C diet (C-Sp), sham HF diet (HF-Sh) and sepsis HF diet (HF-Sp). The surviving animals were euthanized on the 7th day. The HF diet decreased survival rate (58.3% vs. 76.2% C-Sp group), increased serum cytokine storm (IL-6 [1.41 ×; vs. HF-Sh], IL-1β [1.37 ×; vs. C-Sp], TNF [1.34 ×; vs. C-Sp and 1.72 ×; vs. HF-Sh], IL-17 [1.44 ×; vs. HF-Sh], IL-10 [1.55 ×; vs. C-Sp and 1.41 ×; HF-Sh]), white adipose tissue inflammation (IL-6 [8.7 ×; vs. C-Sp and 2.4 ×; vs. HF-Sh], TNF [5 ×; vs. C-Sp and 1.7 ×; vs. HF-Sh], IL-17 [1.7 ×; vs. C-Sp], IL-10 [7.4 ×; vs. C-Sp and 1.3 ×; vs. HF-Sh]), and modulated lipid metabolism in septic mice. In the HF-Sp group liver's, we observed hepatomegaly, hydropic degeneration, necrosis, an increase in oxidative stress (reduction of CAT activity [−81.7%; vs. HF-Sh]; increase MDA levels [82.8%; vs. HF-Sh], and hepatic IL-6 [1.9 ×; vs. HF-Sh], and TNF [1.3 × %; vs. HF-Sh]) production. Furthermore, we found a decrease in the total number of inflammatory, mononuclear cells, and in the regenerative processes, and binucleated hepatocytes in a HF-Sp group livers. Our results suggested that the organism under metabolic stress of a HF diet during sepsis may worsen the inflammatory landscape and hepatocellular injury and may harm the liver regenerative process.Item Post-sepsis cognitive impairment and associated risk factors : a systematic review.(2017) Calsavara, Allan Jefferson Cruz; Nobre Junior, Vandack Alencar; Barichello, Tatiana; Teixeira, Antônio LúcioIntroduction: Post-sepsis cognitive impairment is one of the major sequelae observed in survivors ofsepsis. This cognitive impairment can be global or may affect specific domains. A better understandingof these deficits and associated risk factors could influence the care of patients with sepsis.Objective: To perform a systematic review to investigate the presence of cognitive impairment and itsassociated risk factors among patients who survived sepsis.Methods: The search was conducted in MEDLINE (1966 to March 2017) and EMBASE (1988 to March 2017).We included studies with individuals who were 18 years or older with post-sepsis cognitive impairment.Results: We analysed 577 articles. Sixteen studies met the inclusion criteria. More than 74,000,000patients were evaluated in the selected studies. Significant variation was observed in the definitionof sepsis and cognitive impairment. Twelve studies used ACCP/SCCM criteria for sepsis, while cogni-tive impairment was defined per test used. Post-sepsis cognitive impairment was observed in 12.5 to21% of survivors of sepsis. Attention, cognitive flexibility, processing speed, associative learning, visualperception, work memory, verbal memory, and semantic memory were the specific domains affected.Depressive symptoms, central nervous system infection, length of hospitalisation due to infection, andtemporal proximity to the last period of infection were associated with cognitive impairment.Conclusion: The studies are heterogeneous, and there is urgent need for a common language, includ-ing definitions and neuropsychological tests, for the investigation of post-sepsis cognitive impairment.Despite this, there is mounting evidence for the clinical relevance of post-sepsis cognitive impairment.Item Prevalence and risk factors for post-traumatic stress, anxiety, and depression in sepsis survivors after ICU discharge.(2021) Calsavara, Allan Jefferson Cruz; Costa, Priscila de Almeida; Nobre Junior, Vandack Alencar; Teixeira, Antônio LúcioObjective: Sepsis survivors present a wide range of sequelae; few studies have evaluated psychiatric disorders after sepsis. The objective of this study was to define the prevalence of and risk factors for anxiety, depression and post-traumatic stress disorder (PTSD) symptoms in sepsis survivors. Method: Anxiety, depression and post-traumatic stress symptoms in severe sepsis and septic shock survivors 24 h and 1 year after intensive care unit (ICU) discharge were assessed using the Beck Anxiety/Depression Inventories and the PTSD Checklist-Civilian Version. Differences in psychiatric symptoms over time and the influence of variables on these symptoms were calculated with marginal models. Results: A total of 33 patients were enrolled in the study. The frequencies of anxiety, depression and PTSD 24 h after ICU discharge were 67%, 49%, and 46%, respectively and, among patients re evaluated 1 year after ICU discharge, the frequencies were 38%, 50%, and 31%, respectively. Factors associated with PTSD included serum S100B level, age, and Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) score. Factors associated with depression included patient age and cumulative dose of dobutamine. IQCODE score and cumulative dose of haloperidol in the ICU were associated with anxiety after ICU discharge. Conclusion: Patients who survive sepsis have high levels of psychiatric symptoms. Sepsis and asso ciated treatment-related exposures may have a role in increasing the risk of subsequent depression, anxiety, and PTSD.Item TNFR1 absence protects against memory deficit induced by sepsis possibly through.(2014) Calsavara, Allan Jefferson Cruz; Soriani, Frederico Marianetti; Vieira, Leda Quercia; Costa, Priscila de Almeida; Rachid, Milene Alvarenga; Teixeira Junior, Antonio LucioThe involvement of TNF-α type 1 receptor (TNFR1) in memory deficits induced by sepsis was explored by using TNFR1 knockout (KO) mice. We reported that wild type (WT) mice presented memory deficits in the novel object recognition test 10 days after sepsis induced by cecumligation and perforation (CLP). These deficits were not observed in TNFR1 KO mice. The involvement of serum and brain cytokines TNF-α, IL-1β, IL-6, IFN-γ and IL-10 was then investigated. TNFR1 KO mice had higher serum levels of TNF-α and IL-1β, and brain levels of TNF-α than WT mice. After CLP, the brain levels of TNF-α, IL-1β, IL-6 and IFN-γ increased in both WT and KO mice. Our next step was to determine the expression of inflammatory cytokines, BDNF and TrKb in the hippocampus. The absence of TNFR1 inmice subjected to polymicrobial sepsis resulted in higher BDNF expression in the hippocampus. In conclusion, after CLP, memory is preserved in the absence of TNFR1. This finding was associated with increased BDNF expression in the hippocampus.