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1.
Int J Mol Sci ; 20(16)2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31426434

RESUMO

Ischemic heart diseases (IHD) are the leading cause of death worldwide. Although the principal form of treatment of IHD is myocardial reperfusion, the recovery of coronary blood flow after ischemia can cause severe and fatal cardiac dysfunctions, mainly due to the abrupt entry of oxygen and ionic deregulation in cardiac cells. The ability of these cells to protect themselves against injury including ischemia and reperfusion (I/R), has been termed "cardioprotection". This protective response can be stimulated by pharmacological agents (adenosine, catecholamines and others) and non-pharmacological procedures (conditioning, hypoxia and others). Several intracellular signaling pathways mediated by chemical messengers (enzymes, protein kinases, transcription factors and others) and cytoplasmic organelles (mitochondria, sarcoplasmic reticulum, nucleus and sarcolemma) are involved in cardioprotective responses. Therefore, advancement in understanding the cellular and molecular mechanisms involved in the cardioprotective response can lead to the development of new pharmacological and non-pharmacological strategies for cardioprotection, thus contributing to increasing the efficacy of IHD treatment. In this work, we analyze the recent advances in pharmacological and non-pharmacological strategies of cardioprotection.


Assuntos
Cardiotônicos/uso terapêutico , Precondicionamento Isquêmico Miocárdico/métodos , Isquemia Miocárdica/terapia , Animais , Humanos , Isquemia Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/terapia , Miocárdio/patologia
2.
J Clin Immunol ; 32(2): 212-20, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22193914

RESUMO

CD40 ligand (CD40L) deficiency or X-linked hyper-IgM syndrome (X-HIGM) is a well-described primary immunodeficiency in which Pneumocystis jiroveci pneumonia is a common clinical feature. We have identified an unusual high incidence of fungal infections and other not yet described infections in a cohort of 11 X-HIGM patients from nine unrelated Brazilian families. Among these, we describe the first case of paracoccidioidomycosis (PCM) in X-HIGM. The molecular genetic analysis of CD40L was performed by gene sequencing and evaluation of CD40L protein expression. Nine of these 11 patients (82%) had fungal infections. These included fungal species common to CD40L deficiency (P. jiroveci and Candida albicans) as well as Paracoccidioides brasiliensis. One patient presented with PCM at age 11 years and is now doing well at 18 years of age. Additionally, one patient presented with a simultaneous infection with Klebsiella and Acinetobacter, and one with condyloma caused by human papilloma virus. Molecular analysis revealed four previously described CD40L mutations, two novel missense mutations (c.433 T > G and c.476 G > C) resulting in the absence of CD40L protein expression by activated CD4(+) cells and one novel insertion (c.484_485insAA) within the TNFH domain leading to a frame shift and premature stop codon. These observations demonstrated that the susceptibility to fungal infections in X-HIGM extends beyond those typically associated with X-HIGM (P. jiroveci and C. albicans) and that these patients need to be monitored for those pathogens.


Assuntos
Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/genética , Paracoccidioidomicose/complicações , Adolescente , Adulto , Idade de Início , Sequência de Aminoácidos , Sequência de Bases , Brasil/epidemiologia , Ligante de CD40/deficiência , Ligante de CD40/genética , Ligante de CD40/metabolismo , Criança , Pré-Escolar , Estudos de Coortes , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/diagnóstico , Isotipos de Imunoglobulinas/sangue , Isotipos de Imunoglobulinas/imunologia , Incidência , Lactente , Contagem de Linfócitos , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Masculino , Dados de Sequência Molecular , Mutação , Paracoccidioidomicose/epidemiologia , Paracoccidioidomicose/patologia , Linhagem , Alinhamento de Sequência , Adulto Jovem
3.
Acta Cir Bras ; 36(3): e360306, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33978062

RESUMO

PURPOSE: To evaluate the preventive cardioprotective effects of resveratrol and grape products, such as grape juice and red wine, in animal model of cardiac ischemia and reperfusion. METHODS: Male Wistar rats orally pretreated for 21-days with resveratrol and grape products were anesthetized and placed on mechanical ventilation to surgically induce cardiac ischemia and reperfusion by obstruction (ischemia) followed by liberation (reperfusion) of blood circulation in left descending coronary artery. These rats were submitted to the electrocardiogram (ECG) analysis to evaluate the effects of pretreatment with resveratrol and grape products on the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) resulting from cardiac ischemia and reperfusion. RESULTS: It was observed that the incidence of AVB was significantly lower in rats pretreated with resveratrol (25%), grape juice (37.5%) or red wine (12.5%) than in rats treated with saline solution (80%) or ethanol (80%). Similarly, incidence of LET was also significantly lower in rats pretreated with resveratrol (25%), grape juice (25%) or red wine (0%) than in rats treated with saline solution (62.5%) or ethanol (75%). CONCLUSIONS: These results indicate that the cardioprotective response stimulated by resveratrol and grape products prevents the lethal cardiac arrhythmias in animal model of ischemia and reperfusion, supporting the idea that this treatment can be beneficial for prevention of severe cardiac arrhythmias in patients with ischemic heart disease.


Assuntos
Estilbenos , Vitis , Animais , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/prevenção & controle , Humanos , Isquemia , Masculino , Ratos , Ratos Wistar , Reperfusão , Resveratrol/farmacologia , Estilbenos/farmacologia
4.
Acta Cir Bras ; 35(3): e202000306, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32692797

RESUMO

PURPOSE: To evaluate whether the attenuation of mitochondrial Ca2+ overload produced by pharmacological blockade of mitochondrial Ca2+ uniporter (MCU) protects the myocardium against injuries caused by cardiac ischemia and reperfusion (CIR). METHODS: CIR was induced in adult male Wistar rats (300-350 g) by occlusion of the left anterior descendent coronary artery (10 min), followed by reperfusion (120 min). Rats were treated with different doses of MCU blocker ruthenium red (RuR), administered 5 min before ischemia or reperfusion. RESULTS: In untreated rats, the incidences of ventricular arrhythmias (VA), atrioventricular block (AVB) and the lethality (LET) induced by CIR were 85%, 79% and 70%, respectively. In rats treated with RuR before ischemia, the incidences of VA, AVB and LET were significantly reduced to 62%, 25% and 25%, respectively. In rats treated with RuR after ischemia, the incidences of VA, AVB and LET were significantly reduced to 50%, 25% and 25%, respectively. CONCLUSION: The significant reduction of the incidence of CIR-induced VA, AVB and LET produced by the treatment with RuR indicates that the attenuation of mitochondrial Ca2+ overload produced by pharmacological blockade of MCU can protect the myocardium against injuries caused by CIR.


Assuntos
Canais de Cálcio , Isquemia Miocárdica , Traumatismo por Reperfusão Miocárdica , Animais , Cálcio , Canais de Cálcio/efeitos dos fármacos , Masculino , Isquemia Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Ratos , Ratos Wistar
5.
Acta Cir Bras ; 34(5): e201900505, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31166461

RESUMO

PURPOSE: To evaluate the cardioprotective response of the pharmacological modulation of ß-adrenergic receptors (ß-AR) in animal model of cardiac ischemia and reperfusion (CIR), in spontaneously hypertensive (SHR) and normotensive (NWR) rats. METHODS: CIR was induced by the occlusion of left anterior descendent coronary artery (10 min) and reperfusion (75 min). The SHR was treated with ß-AR antagonist atenolol (AT, 10 mg/kg, IV) 5 min before CIR, and NWR were treated with ß-AR agonist isoproterenol (ISO, 0.5 mg/kg, IV) 5 min before CIR. RESULTS: The treatment with AT increased the incidence of VA, AVB and LET in SHR, suggesting that spontaneous cardioprotection in hypertensive animals was abolished by blockade of ß-AR. In contrast, the treatment with ISO significantly reduced the incidence of ventricular arrhythmia, atrioventricular blockade and lethality in NWR (30%, 20% and 20%, respectively), suggesting that the activation of ß-AR stimulate cardioprotection in normotensive animals. Serum CK-MB were higher in SHR/CIR and NWR/CIR compared to respective SHAM group (not altered by treatment with AT or ISO). CONCLUSION: The pharmacological modulation of ß-AR could be a new cardioprotective strategy for the therapy of myocardial dysfunctions induced by CIR related to cardiac surgery and cardiovascular diseases.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Agonistas Adrenérgicos beta/farmacologia , Atenolol/farmacologia , Cardiotônicos/farmacologia , Isoproterenol/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Receptores Adrenérgicos beta/efeitos dos fármacos , Animais , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Creatina Quinase Forma MB/sangue , Testes de Função Cardíaca , Masculino , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Ratos Endogâmicos SHR , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
6.
Acta Cir Bras ; 33(7): 588-596, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30110060

RESUMO

PURPOSE: To investigate the cardioprotective effects of ischemic preconditioning (preIC) and postconditioning (postIC) in animal model of cardiac ischemia/reperfusion. METHODS: Adult rats were submitted to protocol of cardiac ischemia/reperfusion (I/R) and randomized into three experimental groups: cardiac I/R (n=33), preCI + cardiac I/R (n=7) and postCI + cardiac I/R (n=8). After this I/R protocol, the incidence of ventricular arrhythmia (VA), atrioventricular block (AVB) and lethality (LET) was evaluated using the electrocardiogram (ECG) analysis. RESULTS: After reestablishment of coronary blood flow, we observed variations of the ECG trace with increased incidence of ventricular arrhythmia (VA) (85%), atrioventricular block (AVB) (79%), and increase of lethality (70%) in cardiac I/R group. The comparison between I/R + preIC group with I/R group demonstrated significant reduction in VA incidence to 28%, AVB to 0% and lethality to 14%. The comparison of I/R + postIC group with I/R group was observed significance reduction in AVB incidence to 25% and lethality to 25%. CONCLUSION: The preconditioning strategies produce cardioprotection more efficient that postconditioning against myocardial dysfunctions and lethality by cardiac ischemia and reperfusion.


Assuntos
Pós-Condicionamento Isquêmico/métodos , Precondicionamento Isquêmico Miocárdico/métodos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Animais , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/prevenção & controle , Bloqueio Atrioventricular/fisiopatologia , Bloqueio Atrioventricular/prevenção & controle , Eletrocardiografia , Masculino , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
7.
Acta Cir Bras ; 33(6): 524-532, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-30020314

RESUMO

PURPOSE: To evaluate in vivo animal model of cardiac ischemia/reperfusion the cardioprotective activity of pancreatic lipase inhibitor of the orlistat. METHODS: Adult male Wistar rats were anesthetized, placed on mechanical ventilation and underwent surgery to induce cardiac I/R by obstructing left descending coronary artery followed by reperfusion to evaluation of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) with pancreatic lipase inhibitor orlistat (ORL). At the end of reperfusion, blood samples were collected for determination of triglycerides (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase-MB (CK-MB). RESULTS: Treatment with ORL has been able to decrease the incidence of VA, AVB and LET. Besides that, treatment with ORL reduced serum concentrations of CK and LDL, but did not alter the levels of serum concentration of TG, VLDL and HDL. CONCLUSION: The reduction of ventricular arrhythmias, atrioventricular block, and lethality and serum levels of creatine kinase produced by treatment with orlistat in animal model of cardiac isquemia/reperfusion injury suggest that ORL could be used as an efficient cardioprotective therapeutic strategy to attenuate myocardial damage related to acute myocardial infarction.


Assuntos
Cardiotônicos/farmacologia , Lactonas/farmacologia , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Animais , Arritmias Cardíacas/prevenção & controle , Bloqueio Atrioventricular/prevenção & controle , Creatina Quinase/sangue , Eletrocardiografia , L-Lactato Desidrogenase/sangue , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Lipoproteínas VLDL/sangue , Masculino , Infarto do Miocárdio/sangue , Traumatismo por Reperfusão Miocárdica/sangue , Orlistate , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Risco , Resultado do Tratamento , Triglicerídeos/sangue
8.
Acta Cir Bras ; 32(11): 964-972, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29236801

RESUMO

PURPOSE: To investigate the effects of atenolol in inflammatory mediator and oxidative stress in a myocardial injury by intestinal ischemia/reperfusion in rat model. METHODS: Adult Wistar male rats were randomly (n=8), anesthetized and divided in: Sham: submitted to operation only; group SS+IR: intravenous saline infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); group AT+IR: intravenous atenolol infusion (2 mg/kg) following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); and group AT+I+AT+R: intravenous atenolol infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and in the time 45 minutes other atenolol doses were administrated and the artery was open for 120 minutes (reperfusion), all animals were submitted to muscular relaxation for mechanical ventilation. In the end of experiment the animals were euthanized and the hearts tissue were morphology analyzed by histology and malondialdehyde by ELISA, and the plasma were analyzed for tumor necrosis factor-alpha by ELISA. RESULTS: The group SS+IR demonstrated the higher malondialdehyde levels when compared with the atenolol treated-groups (p=0.001) in the heart tissue. The tumor necrosis factor-alpha level in plasma decrease in the treated groups when compared with SS+IR group (p=0.001). Histology analyses demonstrate pyknosis, edema, cellular vacuolization, presence of inflammatory infiltrate and band contraction in the heart tissue of the rats. CONCLUSION: Atenolol significantly reduce the degree of cardiac damage after intestinal ischemia-reperfusion.


Assuntos
Anti-Hipertensivos/farmacologia , Atenolol/farmacologia , Coração/efeitos dos fármacos , Intestinos/irrigação sanguínea , Traumatismo por Reperfusão/patologia , Animais , Anti-Hipertensivos/farmacocinética , Anti-Hipertensivos/uso terapêutico , Atenolol/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Masculino , Artéria Mesentérica Superior , Ratos , Ratos Wistar
10.
Rev Bras Reumatol Engl Ed ; 56(1): 58-68, 2016.
Artigo em Inglês, Português | MEDLINE | ID: mdl-27267335

RESUMO

Primary immunodeficiency disorders (PID) represent a heterogeneous group of diseases resulting from inherited defects in the development, maturation and normal function of immune cells; thus, turning individuals susceptible to recurrent infections, allergy, autoimmunity, and malignancies. In this retrospective study, autoimmune diseases (AIDs), in special systemic lupus erythematosus (SLE) which arose associated to the course of PID, are described. Classically, the literature describes three groups of PID associated with SLE: (1) deficiency of Complement pathway components, (2) defects in immunoglobulin synthesis, and (3) chronic granulomatous disease (CGD). Currently, other PID have been described with clinical manifestation of SLE, such as Wiskott-Aldrich syndrome (WAS), autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), autoimmune lymphoproliferative syndrome (ALPS) and idiopathic CD4(+) lymphocytopenia. Also we present findings from an adult cohort from the outpatient clinic of the Rheumatology Division of Universidade Federal de São Paulo. The PID manifestations found by our study group were considered mild in terms of severity of infections and mortality in early life. Thus, it is possible that some immunodeficiency states are compatible with survival regarding infectious susceptibility; however these states might represent a strong predisposing factor for the development of immune disorders like those observed in SLE.


Assuntos
Proteínas do Sistema Complemento/deficiência , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/fisiopatologia , Lúpus Eritematoso Sistêmico/imunologia , Brasil , Hospitais Universitários , Humanos , Estudos Retrospectivos , Reumatologia
11.
Acta cir. bras ; 36(3): e360306, 2021. graf
Artigo em Inglês | LILACS | ID: biblio-1248539

RESUMO

ABSTRACT Purpose To evaluate the preventive cardioprotective effects of resveratrol and grape products, such as grape juice and red wine, in animal model of cardiac ischemia and reperfusion. Methods Male Wistar rats orally pretreated for 21-days with resveratrol and grape products were anesthetized and placed on mechanical ventilation to surgically induce cardiac ischemia and reperfusion by obstruction (ischemia) followed by liberation (reperfusion) of blood circulation in left descending coronary artery. These rats were submitted to the electrocardiogram (ECG) analysis to evaluate the effects of pretreatment with resveratrol and grape products on the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) resulting from cardiac ischemia and reperfusion. Results It was observed that the incidence of AVB was significantly lower in rats pretreated with resveratrol (25%), grape juice (37.5%) or red wine (12.5%) than in rats treated with saline solution (80%) or ethanol (80%). Similarly, incidence of LET was also significantly lower in rats pretreated with resveratrol (25%), grape juice (25%) or red wine (0%) than in rats treated with saline solution (62.5%) or ethanol (75%). Conclusions These results indicate that the cardioprotective response stimulated by resveratrol and grape products prevents the lethal cardiac arrhythmias in animal model of ischemia and reperfusion, supporting the idea that this treatment can be beneficial for prevention of severe cardiac arrhythmias in patients with ischemic heart disease.


Assuntos
Humanos , Animais , Masculino , Ratos , Estilbenos/farmacologia , Vitis , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/prevenção & controle , Reperfusão , Ratos Wistar , Resveratrol/farmacologia , Isquemia
13.
Acta cir. bras ; 35(3): e202000306, 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1130620

RESUMO

Abstract Purpose To evaluate whether the attenuation of mitochondrial Ca2+ overload produced by pharmacological blockade of mitochondrial Ca2+ uniporter (MCU) protects the myocardium against injuries caused by cardiac ischemia and reperfusion (CIR). Methods CIR was induced in adult male Wistar rats (300-350 g) by occlusion of the left anterior descendent coronary artery (10 min), followed by reperfusion (120 min). Rats were treated with different doses of MCU blocker ruthenium red (RuR), administered 5 min before ischemia or reperfusion. Results In untreated rats, the incidences of ventricular arrhythmias (VA), atrioventricular block (AVB) and the lethality (LET) induced by CIR were 85%, 79% and 70%, respectively. In rats treated with RuR before ischemia, the incidences of VA, AVB and LET were significantly reduced to 62%, 25% and 25%, respectively. In rats treated with RuR after ischemia, the incidences of VA, AVB and LET were significantly reduced to 50%, 25% and 25%, respectively. Conclusion The significant reduction of the incidence of CIR-induced VA, AVB and LET produced by the treatment with RuR indicates that the attenuation of mitochondrial Ca2+ overload produced by pharmacological blockade of MCU can protect the myocardium against injuries caused by CIR.


Assuntos
Animais , Masculino , Ratos , Canais de Cálcio/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Cálcio , Ratos Wistar
14.
Acta cir. bras ; 34(5): e201900505, 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1010872

RESUMO

Abstract Purpose: To evaluate the cardioprotective response of the pharmacological modulation of β-adrenergic receptors (β-AR) in animal model of cardiac ischemia and reperfusion (CIR), in spontaneously hypertensive (SHR) and normotensive (NWR) rats. Methods: CIR was induced by the occlusion of left anterior descendent coronary artery (10 min) and reperfusion (75 min). The SHR was treated with β-AR antagonist atenolol (AT, 10 mg/kg, IV) 5 min before CIR, and NWR were treated with β-AR agonist isoproterenol (ISO, 0.5 mg/kg, IV) 5 min before CIR. Results: The treatment with AT increased the incidence of VA, AVB and LET in SHR, suggesting that spontaneous cardioprotection in hypertensive animals was abolished by blockade of β-AR. In contrast, the treatment with ISO significantly reduced the incidence of ventricular arrhythmia, atrioventricular blockade and lethality in NWR (30%, 20% and 20%, respectively), suggesting that the activation of β-AR stimulate cardioprotection in normotensive animals. Serum CK-MB were higher in SHR/CIR and NWR/CIR compared to respective SHAM group (not altered by treatment with AT or ISO). Conclusion: The pharmacological modulation of β-AR could be a new cardioprotective strategy for the therapy of myocardial dysfunctions induced by CIR related to cardiac surgery and cardiovascular diseases.


Assuntos
Animais , Masculino , Atenolol/farmacologia , Cardiotônicos/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Receptores Adrenérgicos beta/efeitos dos fármacos , Agonistas Adrenérgicos beta/farmacologia , Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Isoproterenol/farmacologia , Ratos Endogâmicos SHR , Fatores de Tempo , Pressão Sanguínea/efeitos dos fármacos , Biomarcadores/sangue , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Traumatismo por Reperfusão Miocárdica/sangue , Reprodutibilidade dos Testes , Resultado do Tratamento , Creatina Quinase Forma MB/sangue , Testes de Função Cardíaca
15.
Arch Immunol Ther Exp (Warsz) ; 61(6): 427-43, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24057516

RESUMO

Toll-like receptors (TLRs) sense microbial products and play an important role in innate immunity. Currently, 11 members of TLRs have been identified in humans, with important function in host defense in early steps of the inflammatory response. TLRs are present in the plasma membrane (TLR1, TLR2, TLR4, TLR5, TLR6) and endosome (TLR3, TLR7, TLR8, TLR9) of leukocytes. TLRs and IL-1R are a family of receptors related to the innate immune response that contain an intracellular domain known as the Toll-IL-1R (TIR) domain that recruits the TIR-containing cytosolic adapters MyD88, TRIF, TIRAP and TRAM. The classical pathway results in the activation of both nuclear factor κB and MAPKs via the IRAK complex, with two active kinases (IRAK-1 and IRAK-4) and two non-catalytic subunits (IRAK-2 and IRAK-3/M). The classical pro-inflammatory TLR signaling pathway leads to the synthesis of inflammatory cytokines and chemokines, such as IL-1ß, IL-6, IL-8, IL-12 and TNF-α. In humans, genetic defects have been identified that impair signaling of the TLR pathway and this may result in recurrent pyogenic infections, as well as virus and fungi infections. In this review, we discuss the main mechanisms of microbial recognition and the defects involving TLRs.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Citocinas/imunologia , Infecções/imunologia , Mediadores da Inflamação/imunologia , Receptores Toll-Like/imunologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Predisposição Genética para Doença , Humanos , Infecções/genética , Mutação/genética , Polimorfismo Genético , Transdução de Sinais/genética
16.
Acta cir. bras ; 33(7): 588-596, July 2018. graf
Artigo em Inglês | LILACS | ID: biblio-949370

RESUMO

Abstract Purpose: To investigate the cardioprotective effects of ischemic preconditioning (preIC) and postconditioning (postIC) in animal model of cardiac ischemia/reperfusion. Methods: Adult rats were submitted to protocol of cardiac ischemia/reperfusion (I/R) and randomized into three experimental groups: cardiac I/R (n=33), preCI + cardiac I/R (n=7) and postCI + cardiac I/R (n=8). After this I/R protocol, the incidence of ventricular arrhythmia (VA), atrioventricular block (AVB) and lethality (LET) was evaluated using the electrocardiogram (ECG) analysis. Results: After reestablishment of coronary blood flow, we observed variations of the ECG trace with increased incidence of ventricular arrhythmia (VA) (85%), atrioventricular block (AVB) (79%), and increase of lethality (70%) in cardiac I/R group. The comparison between I/R + preIC group with I/R group demonstrated significant reduction in VA incidence to 28%, AVB to 0% and lethality to 14%. The comparison of I/R + postIC group with I/R group was observed significance reduction in AVB incidence to 25% and lethality to 25%. Conclusion: The preconditioning strategies produce cardioprotection more efficient that postconditioning against myocardial dysfunctions and lethality by cardiac ischemia and reperfusion.


Assuntos
Animais , Masculino , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Precondicionamento Isquêmico Miocárdico/métodos , Pós-Condicionamento Isquêmico/métodos , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/prevenção & controle , Fatores de Tempo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Distribuição Aleatória , Reprodutibilidade dos Testes , Resultado do Tratamento , Ratos Wistar , Eletrocardiografia , Bloqueio Atrioventricular/fisiopatologia , Bloqueio Atrioventricular/prevenção & controle
17.
Acta cir. bras ; 33(6): 524-532, June 2018. graf
Artigo em Inglês | LILACS | ID: biblio-949352

RESUMO

Abstract Purpose: To evaluate in vivo animal model of cardiac ischemia/reperfusion the cardioprotective activity of pancreatic lipase inhibitor of the orlistat. Methods: Adult male Wistar rats were anesthetized, placed on mechanical ventilation and underwent surgery to induce cardiac I/R by obstructing left descending coronary artery followed by reperfusion to evaluation of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) with pancreatic lipase inhibitor orlistat (ORL). At the end of reperfusion, blood samples were collected for determination of triglycerides (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase-MB (CK-MB). Results: Treatment with ORL has been able to decrease the incidence of VA, AVB and LET. Besides that, treatment with ORL reduced serum concentrations of CK and LDL, but did not alter the levels of serum concentration of TG, VLDL and HDL. Conclusion: The reduction of ventricular arrhythmias, atrioventricular block, and lethality and serum levels of creatine kinase produced by treatment with orlistat in animal model of cardiac isquemia/reperfusion injury suggest that ORL could be used as an efficient cardioprotective therapeutic strategy to attenuate myocardial damage related to acute myocardial infarction.


Assuntos
Animais , Masculino , Cardiotônicos/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Lactonas/farmacologia , Infarto do Miocárdio/prevenção & controle , Arritmias Cardíacas/prevenção & controle , Triglicerídeos/sangue , Traumatismo por Reperfusão Miocárdica/sangue , Distribuição Aleatória , Reprodutibilidade dos Testes , Fatores de Risco , Resultado do Tratamento , Ratos Wistar , Creatina Quinase/sangue , Eletrocardiografia , Bloqueio Atrioventricular/prevenção & controle , L-Lactato Desidrogenase/sangue , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Lipoproteínas VLDL/sangue , Infarto do Miocárdio/sangue
18.
Ann N Y Acad Sci ; 1250: 62-72, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22364447

RESUMO

Primary immunodeficiencies (PIDs) are genetic disorders of the immune system comprising many different phenotypes. Although previously considered rare, recent advances in their clinical, epidemiological, and molecular definitions are revealing how much we still need to learn about them. For example, geographical and ethnic variations as well as the impact of certain practices influence their frequency and presentation, making it necessary to consider their study in terms of regions. The Latin American Society for Immunodeficiencies was established as an organization dedicated to provide scientific support for basic and clinical research and to develop tools and educational resources to promote awareness in the medical community. Initiatives such as these are positively influencing the way PIDs are tackled in these countries, as shown by recent reports and publications. This paper provides a historical compilation and a current view of the many issues faced by scientists studying these diseases in these countries, highlighting the diverse scientific contributions and offering a promising perspective for the further developments in this field in Latin America.


Assuntos
Pesquisa Biomédica/tendências , Imunodeficiência de Variável Comum/epidemiologia , Imunodeficiência de Variável Comum/genética , Imunodeficiência de Variável Comum/imunologia , Sociedades Médicas , Imunodeficiência de Variável Comum/etnologia , Humanos , América Latina/epidemiologia , América Latina/etnologia
19.
Acta cir. bras ; 32(11): 964-972, Nov. 2017. graf
Artigo em Inglês | LILACS | ID: biblio-886186

RESUMO

Abstract Purpose: To investigate the effects of atenolol in inflammatory mediator and oxidative stress in a myocardial injury by intestinal ischemia/reperfusion in rat model. Methods: Adult Wistar male rats were randomly (n=8), anesthetized and divided in: Sham: submitted to operation only; group SS+IR: intravenous saline infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); group AT+IR: intravenous atenolol infusion (2 mg/kg) following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); and group AT+I+AT+R: intravenous atenolol infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and in the time 45 minutes other atenolol doses were administrated and the artery was open for 120 minutes (reperfusion), all animals were submitted to muscular relaxation for mechanical ventilation. In the end of experiment the animals were euthanized and the hearts tissue were morphology analyzed by histology and malondialdehyde by ELISA, and the plasma were analyzed for tumor necrosis factor-alpha by ELISA. Results: The group SS+IR demonstrated the higher malondialdehyde levels when compared with the atenolol treated-groups (p=0.001) in the heart tissue. The tumor necrosis factor-alpha level in plasma decrease in the treated groups when compared with SS+IR group (p=0.001). Histology analyses demonstrate pyknosis, edema, cellular vacuolization, presence of inflammatory infiltrate and band contraction in the heart tissue of the rats. Conclusion: Atenolol significantly reduce the degree of cardiac damage after intestinal ischemia-reperfusion.


Assuntos
Animais , Masculino , Ratos , Atenolol/farmacologia , Traumatismo por Reperfusão/patologia , Coração/efeitos dos fármacos , Intestinos/irrigação sanguínea , Anti-Hipertensivos/farmacologia , Atenolol/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Ratos Wistar , Artéria Mesentérica Superior , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacocinética
20.
Conscientiae saúde (Impr.) ; 16(2): 2017217223, jun. 2017.
Artigo em Português | LILACS | ID: biblio-875793

RESUMO

Introdução: A hipertensão arterial é um dos fatores de risco para doenças cardiovasculares, estando diretamente associada ao elevado consumo de sódio. Objetivo: Avaliar os níveis de marcadores de lesão hepática, renal e cardíaca em ratos hipertensos comparados aos seus controles normotensos, tratados com um salgante isento de sódio, água ou NaCl. Métodos: Ratos hipertensos (SHR) e seus controles normotensos (NWR) foram divididos em 3 grupos (n=7): G1 (água); G2 (solução aquosa contendo NaCl 70 mg/kg/dia); G3 (solução aquosa contendo salgante sem sódio 70 mg/kg/dia). Após 30 dias, o sangue dos animais foi processado. Resultados: Não houve diferença entre os níveis séricos de creatina quinase total, creatina quinase-MB, lactato desidrogenase, ácido úrico, aspartato aminotransferase e fosfatase alcalina tanto nos NWR como nos SHR tratados com NaCl ou Salgante. Houve diminuição da creatinina nos NWR e SHR tratados com NaCl e Salgante em relação aos controles (p<0,005). Conclusões: A suplementação diária com o Salgante e NaCl diminuiu os níveis séricos de creatinina nos grupos NWR e SHR. Contudo, não houve modificação nos níveis séricos de marcadores de lesão cardíaca e hepática. (AU)


Introduction: Hypertension is one of the risk factors for cardiovascular diseases, being directly associated with high consumption of sodium. Objective: To assess the levels of hepatic, renal and cardiac injury markers in hypertensive rats compared to their normotensive controls, treated with a salt free saline solution, water or NaCl. Methods: Hypertensive rats (SHR) and their normotensive controls (NWR) were divided into 3 groups (n = 7): G1 (water); G2 (aqueous solution containing NaCl 70 mg / kg / day); G3 (sodium salt-free aqueous solution 70 mg / kg / day). After 30 days, the animals' blood was processed. Results: There was no difference between serum levels of total creatine kinase, creatine kinase-MB, lactate dehydrogenase, uric acid, aspartate aminotransferase and alkaline phosphatase in both NWR and SHR1 treated NaCl or Salgante. There was a decrease in creatinine in NWR and SHR treated with NaCl and Salgante comparing to controls (p <0.005). Conclusions: Daily supplementation with sodium salt-free aqueous solution and NaCl decreases serum creatinine levels in NWR and SHR groups. However, there was no change in serum levels of cardiac and hepatic injury markers. (AU)


Assuntos
Animais , Masculino , Ratos , Cloreto de Sódio na Dieta , Aspartato Aminotransferases/sangue , Ácido Úrico/sangue , Biomarcadores , Ratos Wistar , Suplementos Nutricionais , Creatina Quinase/sangue , Fosfatase Alcalina/sangue , Frequência Cardíaca , L-Lactato Desidrogenase/sangue
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