HIDROXICLOROQUINA: USO POTENCIAL EM CORONAVIROSES?

A hidrocloroquina (HCQ) é um análogo da cloroquina, que foi projetada para terapêutica da malária. A longo das últimas décadas têm se observado o potencial de aplicação em outras patologias, como doenças autoimunes, oncologia e infecções virais. Neste ultimo grupo, enquadra-se o desafio da pandemia de coronavírus 2019 (COVID-19) que têm infectado centenas de milhares de pessoas e acarretado em milhares de mortes em todo mundo. Nesta conjuntura, objetivou-se discorrer acercar do uso potencial da hidrolcloroquina em infecções do coronovavírus. Através dos dados coletados, observou-se que a HCQ pode inibir a replicação viral pelo seu acúmulo no lisossoma e complexo de golgi celular, apresentando baixo custo e auxiliado na estabilização de pacientes graves com COVID-19. Entretanto, não evidência quanto a sua eficácia como droga profilática, existem diversas reações adversas e contra-indicações clínicas, de forma que seu uso deve ser devidamente prescrita por profissional de saúde. Além disso, ensaios clínicos randomizados, cegos, de tratamentos de coronoviroses devem ser estabelecidos, de forma que protocolos clínicos possam ser adequamente utilizados para a HCQ

Coronavirus Outbreaks: Literature Review

Coronaviruses are observed in birds and mammals and can be transmitted to humans, leading to outbreaks and pandemics. Among the most recent ones are SARS-CoV, MERS-CoV, and COVID 19. Thus, the objective was to describe a discussion about coronaviruses, with an emphasis on Sars-Cov-2. From the data collected, it can be seen that the current pandemic has had impacts on public health and socioeconomic life in more than 170 countries worldwide, to date, with tens of millions of people infected and hundreds of thousands of deaths. In this regard, prevention actions must be intensified, especially among the most vulnerable patients (the elderly and those with comorbidities that affect immunity). In addition, new studies should be carried out so that vaccines and antivirals can be implemented for application to COVID-19

Antibacterial Effect of Silver Nanoparticles on Klebsiella spp

Silver nanoparticles (AgNP) can be incorporated into medical devices, such as tissues, to circumvent bacterial resistance such as Klebsiella spp, which can lead to skin and mucosal infections. Thus, the aim of the present study was to synthesize silver nanoparticles for later incorporation into cotton fabrics and in vitro tests against Klebsiella spp. The AgNP colloidal solution was synthesized (AgNO3 - 0.1 mM, 100 mM trisodium citrate, polyvinylpyrrolidone - 0.24 g, H2OH2) and then impregnated into the cotton fabric pretreated with poly diallyl dimethylammonium chloride (PDDA) of 100/500 tissue, shaken for 30 minutes). The material produced was analyzed by the FTIR; DLS and reflectance spectroscopy. The tests of the antimicrobial activities were by the microdilution technique against Klebsiella spp, in tubes containing Brain Heart Infusion (BHI), with the solution of silver (1); Tissue containing AgNP - 4 mm (2); Negative control (3) and positive control - ceftriaxone (4). Regarding MIC, the inhibitory activity occurred of the dilutions between 1/2 and 1/16. The AgNP particles had an average size of 24.75 nm. As synthesized AgNPs demonstrate the excellent antimicrobial activity against Klebsiella spp, with special emphasis on applications in nanotechnology and nanomedicine, targeting multiresistant antibiotic bacteria

Coronavirus in Pregnant Women: Literature Review

The coronavirus viruses cause infectious conditions that evolve with greater severity in patients with reduced immunity, a fact that can be observed in pregnant women. In these, anatomical and physiological changes occur that can compromise immunity, which can lead to complications. Faced with the pandemic by COVID-19, the present study aimed to discuss the possible risk of the pregnant woman and the fetus facing infection with this virus, which initially presents respiratory symptoms and with lower gastrointestinal prevalence. . Based on the data collected, it was observed that, in many cases, pregnant women develop respiratory, renal and cardiovascular complications, requiring ICU admission and mechanical ventilation. This can lead to fetal distress, placental detachment, spontaneous abortion, reduced fetal growth and risk of maternal-fetal death. Thus, attention must be redoubled in health surveillance and education for this group, as well as the availability of the health care system and clinical, epidemiological and laboratory diagnosis is required, since most patients tend to evolve with clinical complications

Correlação entre a expressão de receptores da resposta imune inata e as formas clínicas na doença de Chagas humana

Exportado OPUSMade available in DSpace on 2019-08-12T11:32:57Z (GMT). No. of bitstreams: 1 disserta__o_ap_s_corre__o_nathalie_sena.pdf: 2039326 bytes, checksum: 1a10518c7a56472ee26707fecbaa61ac (MD5) Previous issue date: 15Estudos recentes demonstraram a importância de receptores do tipo Toll Like Receptors (TLRs) e do tipo NOD Like Receptors (NLRs) durante a resistência à infecção experimental pelo Trypanosoma cruzi. Entretanto, não existem estudos que correlacionem a expressão destas moléculas às formas clínicas crônicas da doença de Chagas humana. Neste estudo, foi avaliada a expressão de receptores da imunidade inata (TLRs e NLRs), suas moléculas adaptadoras, citocinas e -defensinas, em pacientes chagásicos crônicos com as formas clínicas indeterminada (n=18), cardíaca (n=17), digestiva (n=9) e cardiodigestiva (n=10) da doença. Amostras de indivíduos não infectados da mesma região geográfica foram utilizadas como controle (n=9). A partir das células mononucleares do sangue periférico (PBMC) foi realizada a quantificação da expressão de RNA mensageiro (RNAm) por PCR em tempo real, dos TLRs (TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9), NLRs (NOD1 e NOD2), de moléculas adaptadoras RIP2 (Receptor-interacting protein kinase 2), TRIF (Toll/IL-1 Receptor Domain-ContainingAdaptor-Inducing IFN-) e Myd88 (Myeloid Differentiation Primary Response Gene 88), citocinas (IL-1, IL-6, IL-12, IL-18 e IFN-) e -defensinas (5 e 6). Não houve diferença na expressão de RNAm para os TLRs (TLR1, 2,3,4,5,6,7 e 9) e para a molécula adaptadora TRIF entre os pacientes com as diferentes formas clínicas da doença de Chagas. Entretanto, pacientes com a forma clínica cardiodigestiva expressaram maior quantidade de RNAm de TLR8 e Myd88, quando comparado aos pacientes com as formas clínicas cardíaca e indeterminada. Os pacientes com a forma cardíaca apresentaram elevada expressão de RNAm de IL-1 e IL-12 que aqueles com a forma indeterminada, que estão associadas ao desenvolvimento de doença cardíaca grave. Além disso, não houve diferença entre a expressão das citocinas (IL-6, IL-18 e IFN-). Os pacientes com a forma digestiva da doença apresentaram menor expressão de NOD2 e maior expressão de RIP2, quando comparado aos pacientes com a forma indeterminada. Houve uma correlação negativa entre a expressão de RNAm de NOD2 e o grau de dilatação do esôfago (R=-0,7859, p=0,0172) e a dimensão do sigmóide (R=-0,7859, p=0,0172). Os pacientes com a forma digestiva apresentaram elevada expressão de -defensina 6. Estes dados indicam que a elevada expressão de RNAm para IL1- e IL-12 está relacionada à cardiomiopatia chagásica crônica e, a ausência ou baixa expressão de NOD2, correlacionada à gravidade na forma digestiva da doença de Chagas.Recent studies have established the importance of Toll Like Receptors (TLRs) and Nod Like Receptors (NLRs) in resistance for Trypanosoma cruzi infection in experimental models. However, there are not studies correlating the expression of these molecules to clinical forms of chronic human Chagas disease. In this study, we aim to evaluate the expression of innate immunity receptors (Toll and Nod), signaling molecules, cytokines and -defensins in patients with chronic Chagas disease that displayed indeterminate (n=18), cardiac (n=17), digestive (n=9) and cardiodigestive (n=10) clinical forms. Uninfected individuals from the same geographical region were used as control (n=9). The quantification of mRNA expression was performed by real-time PCR, from peripheral blood mononuclear cells (PBMC), TLRs (TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9), NLRs (NOD1 and NOD2), the adapter molecules RIP2 (Receptor-interacting protein kinase 2), TRIF (Toll/IL-1 Receptor Domain-Containing Adaptor-Inducing IFN-), Myd88 (Myeloid Differentiation Primary Response Gene 88), cytokines (IL-1, IL-6, IL-12, IL-18 and IFN-) and -defensins (5 and 6). There was no difference in the expression of mRNA for TLRs (TLR1, 2, 3, 4, 5, 6, 7 and 9) and the adapter molecule TRIF between patients presenting different clinical forms of Chagas disease. However, patients with cardiodigestive form displayed highest expression of TLR8 and Myd88 mRNA compared to cardiac and indeterminate clinical forms. Patients with cardiac form showed higher mRNA expression of IL-1 and IL12, which is associated with the development of severe cardiac disease. Furthermore, there was no difference between the expression of other cytokines analyzed (IL-6, IL-18 and IFN-). Patients with digestive form of the disease showed lower expression of NOD2 and higher expression of RIP2 compared with indeterminate form. Also, there was a negative correlation between the expression of NOD2 and the degree of dilation of the esophagus (R=-0.7859, p=0.0172) and sigmoid (R=-0.7859, p=0, 0172). Patients with digestive form showed higher expression of -defensin 6. The results indicate that high mRNA expression of IL1- and IL-12 is correlated to chronic Chagas cardiomyopathy, and the absence or low NOD2 mRNA expression is correlated with the severity of digestive clinical form of Chagas disease

Innate immune receptors over expression correlate with chronic chagasic cardiomyopathy and digestive damage in patients.

Chronic chagasic cardiomyopathy (CCC) is observed in 30% to 50% of the individuals infected by Trypanosoma cruzi and heart failure is the important cause of death among patients in the chronic phase of Chagas disease. Although some studies have elucidated the role of adaptive immune responses involving T and B lymphocytes in cardiac pathogenesis, the role of innate immunity receptors such as Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in CCC pathophysiology has not yet been determined. In this study, we evaluated the association among innate immune receptors (TLR1-9 and nucleotide-binding domain-like receptor protein 3/NLRP3), its adapter molecules (Myd88, TRIF, ASC and caspase-1) and cytokines (IL-1β, IL-6, IL-12, IL-18, IL-23, TNF-α, and IFN-β) with clinical manifestation, digestive and cardiac function in patients with different clinical forms of chronic Chagas disease. The TLR8 mRNA expression levels were enhanced in the peripheral blood mononuclear cells (PBMC) from digestive and cardiodigestive patients compared to indeterminate and cardiac patients. Furthermore, mRNA expression of IFN-β (cytokine produced after TLR8 activation) was higher in digestive and cardiodigestive patients when compared to indeterminate. Moreover, there was a positive correlation between TLR8 and IFN-β mRNA expression with sigmoid and rectum size. Cardiac and cardiodigestive patients presented higher TLR2, IL-12 and TNF-α mRNA expression than indeterminate and digestive patients. Moreover, cardiac patients also expressed higher levels of NLRP3, ASC and IL-1β mRNAs than indeterminate patients. In addition, we showed a negative correlation among TLR2, IL-1β, IL-12 and TNF-α levels with left ventricular ejection fraction, and positive correlation between NLRP3 with cardiothoracic index, and TLR2, IL-1β and IL-12 with left ventricular mass index. Together, our data suggest that high expression of innate immune receptors in cardiac and digestive patients may induce an enhancement of cytokine expression and participate of cardiac and digestive dysfunction

Innate immune receptors over expression correlate with chronic chagasic cardiomyopathy and digestive damage in patients

Submitted by Sandra Infurna ([email protected]) on 2019-01-30T10:27:25Z No. of bitstreams: 1 adelaideV_Motta_etal_IOC_2018.pdf: 4348852 bytes, checksum: 2a6663ea033f9812085adebf92dec5ce (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-01-30T10:46:20Z (GMT) No. of bitstreams: 1 adelaideV_Motta_etal_IOC_2018.pdf: 4348852 bytes, checksum: 2a6663ea033f9812085adebf92dec5ce (MD5)Made available in DSpace on 2019-01-30T10:46:20Z (GMT). No. of bitstreams: 1 adelaideV_Motta_etal_IOC_2018.pdf: 4348852 bytes, checksum: 2a6663ea033f9812085adebf92dec5ce (MD5) Previous issue date: 2018Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brasil / Universidade Federal do Rio Grande do Norte. Departamento de Microbiologia e Parasitologia. Natal, RN, Brasil / Universidade Potiguar. Escola de Saúde. Natal, RN, Brasil.Universidade Federal do Rio Grande do Norte. Departamento de Microbiologia e Parasitologia. Natal, RN, Brasil.Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brasil.Universidade do Estado do Rio Grande do Norte. Departamento de Ciências Biomédicas. Mossoró, RN, Brasil.Instituto Internacional de Neurociências Edmond e Lilly Safra. Macaíba, RN, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio Grande do Norte. Departamento de Análises Clínicas e Toxicológicas. Natal, RN, Brasil.Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brasil.Universidade Federal do Rio Grande do Norte. Departamento de Microbiologia e Parasitologia. Natal, RN, Brasil.Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, BrasilChronic chagasic cardiomyopathy (CCC) is observed in 30% to 50% of the individuals infected by Trypanosoma cruzi and heart failure is the important cause of death among patients in the chronic phase of Chagas disease. Although some studies have elucidated the role of adaptive immune responses involving T and B lymphocytes in cardiac pathogenesis, the role of innate immunity receptors such as Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in CCC pathophysiology has not yet been determined. In this study, we evaluated the association among innate immune receptors (TLR1-9 and nucleotide-binding domain-like receptor protein 3/NLRP3), its adapter molecules (Myd88, TRIF, ASC and caspase- 1) and cytokines (IL-1β, IL-6, IL-12, IL-18, IL-23, TNF-α, and IFN-β) with clinical manifestation, digestive and cardiac function in patients with different clinical forms of chronic Chagas disease. The TLR8 mRNA expression levels were enhanced in the peripheral blood mononuclear cells (PBMC) from digestive and cardiodigestive patients compared to indeterminate and cardiac patients. Furthermore, mRNA expression of IFN-β (cytokine produced after TLR8 activation) was higher in digestive and cardiodigestive patients when compared to indeterminate. Moreover, there was a positive correlation between TLR8 and IFN-β mRNA expression with sigmoid and rectum size. Cardiac and cardiodigestive patients presented higher TLR2, IL-12 and TNF-α mRNA expression than indeterminate and digestive patients. Moreover, cardiac patients also expressed higher levels of NLRP3, ASC and IL-1β mRNAs than indeterminate patients. In addition, we showed a negative correlation among TLR2, IL-1β, IL-12 and TNF-α levels with left ventricular ejection fraction, and positive correlation between NLRP3 with cardiothoracic index, and TLR2, IL-1β and IL-12 with left ventricular mass index. Together, our data suggest that high expression of innate immune.receptors in cardiac and digestive patients may induce an enhancement of cytokine expression and participate of cardiac and digestive dysfunction

Inflammation Enhances the Risks of Stroke and Death in Chronic Chagas Disease Patients

Submitted by sandra infurna ([email protected]) on 2016-06-19T18:59:10Z No. of bitstreams: 1 mariaadelaide_matta_etal_IOC_2016.pdf: 749988 bytes, checksum: 989d8777a371bcd276efecde9a5d4214 (MD5)Approved for entry into archive by sandra infurna ([email protected]) on 2016-06-19T19:21:52Z (GMT) No. of bitstreams: 1 mariaadelaide_matta_etal_IOC_2016.pdf: 749988 bytes, checksum: 989d8777a371bcd276efecde9a5d4214 (MD5)Made available in DSpace on 2016-06-19T19:21:52Z (GMT). No. of bitstreams: 1 mariaadelaide_matta_etal_IOC_2016.pdf: 749988 bytes, checksum: 989d8777a371bcd276efecde9a5d4214 (MD5) Previous issue date: 2016Made available in DSpace on 2016-07-08T12:21:49Z (GMT). No. of bitstreams: 3 mariaadelaide_matta_etal_IOC_2016.pdf.txt: 58546 bytes, checksum: d1a8f1e931ab9591fce414aa980fdaa1 (MD5) mariaadelaide_matta_etal_IOC_2016.pdf: 749988 bytes, checksum: 989d8777a371bcd276efecde9a5d4214 (MD5) license.txt: 2991 bytes, checksum: 5a560609d32a3863062d77ff32785d58 (MD5) Previous issue date: 2016Universidade Federal do Rio Grande do Norte. Departamento de Microbiologia e Parasiologia. Natal, RN, BrasilUniversidade do Estado do Rio Grande do Norte. Departamento de Ciências Biomédicas. Mossoró, RN, Brasil.Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brasil.Universidade Federal do Rio Grande do Norte. Departamento de Microbiologia e Parasiologia. Natal, RN, Brasil / Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brasil.Universidade Federal do Rio Grande do Norte. Departamento de Microbiologia e Parasiologia. Natal, RN, BrasilUniversidade Federal de Ouro Preto. Escola de Medicina. Ouro Preto, MG, Brasil.Univrsidade de São Paulo. Escola de Medicina de Ribeirão Preto. Ribeirão Preto, SP, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório deUltraestrutura Celular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio Grande do Norte. Departmaneto de Análises Clínicas e Toxicológicas. Natal, RN, Brasil.Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brasil.Ischemic strokes have been implicated as a cause of death in Chagas disease patients. Inflammation has been recognized as a key component in all ischemic processes, including the intravascular events triggered by vessel interruption, brain damage and repair. In this study, we evaluated the association between inflammatory markers and the death risk (DR) and stroke risk (SR) of patients with different clinical forms of chronic Chagas disease. The mRNA expression levels of cytokines, transcription factors expressed in the adaptive immune response (Th1, Th2, Th9, Th17, Th22 and regulatory T cell), and iNOS were analyzed by realtime PCR in peripheral blood mononuclear cells of chagasic patients who exhibited the indeterminate, cardiac, digestive and cardiodigestive clinical forms of the disease, and the levels of these transcripts were correlated with the DR and SR. Cardiac patients exhibited lowermRNA expression levels of GATA-3, FoxP3, AHR, IL-4, IL-9, IL-10 and IL-22 but exhibited higher expression of IFN-γ and TNF-α compared with indeterminate patients. Digestive patients showed similar levels of GATA-3, IL-4 and IL-10 than indeterminate patients. Cardiodigestive patients exhibited higher levels of TNF-α compared with indeterminate and digestive patients. Furthermore, we demonstrated that patients with high DR and SR exhibited lower GATA-3, FoxP3, and IL-10 expression and higher IFN-γ, TNF-α and iNOS mRNA expression than patients with low DR and SR. A negative correlation was observed between Foxp3 and IL-10 mRNA expression and the DR and SR. Moreover, TNF-α and iNOS expression was positively correlated with DR and SR. Our data suggest that an inflammatory imbalance in chronic Chagas disease patients is associated with a high DR and SR. This study provides a better understanding of the stroke pathobiology in the general population and might aid the development of therapeutic strategies for controlling the morbidity and mortality of Chagas disease

High NLRP3 expression is correlated with high cardiothoracic index (CI).

<p>The mRNA expression levels of NLRP3 (A), TLR2 (B), IL-1β (C) and IL-12 (D) were determined by real-time PCR in peripheral blood mononuclear cells of patients with the indeterminate (n = 18), cardiac (n = 17), digestive (n = 15) and cardiodigestive (n = 15) clinical forms of Chagas disease and correlated with cardiothoracic index (CI). The expression levels were normalized to the expression level of β-actin. Spearman test was used.</p

High left ventricle mass index (LVMI) is correlated with high TLR-2, IL-1β and TNF-α mRNA expression.

<p>The mRNA expression levels of NLRP3 (A), TLR2 (B), IL-1β (C) and IL-12 (D) were determined by real-time PCR in PBMC of indeterminate (n = 18), cardiac (n = 17), digestive (n = 15) and cardiodigestive (n = 15) patients and correlated with LVMI. Spearman test was used.</p