RESUMO
Arthritogenic alphaviruses are mosquito-borne viruses that cause a debilitating rheumatic disease characterized by fever, headache, rash, myalgia, and polyarthralgia with the potential to evolve into a severe and very prolonged illness. Although these viruses have been geographically restricted by vector hosts and reservoirs, recent epidemics have revealed the risks of their spread worldwide. In this review, we aim to discuss the protective and pathological roles of macrophages during the development of arthritis caused by alphaviruses. The progression to the chronic phase of the disease is related to the extension of viral replication and the maintenance of articular inflammation, in which the cellular infiltrate is predominantly composed of macrophages. We explore the possible implications of macrophage polarization to M1/M2 activation phenotypes, drawing a parallel between alphavirus arthritis and rheumatoid arthritis (RA), a chronic inflammatory disease that also affects articular tissues. In RA, it is well established that M1 macrophages contribute to tissue damage and inflammation, while M2 macrophages have a role in cartilage repair, so modulating the M1/M2 macrophage ratio is being considered as a strategy in the treatment of this disease. In the case of alphavirus-induced arthritis, the picture is more complex, as proinflammatory factors derived from M1 macrophages contribute to the antiviral response but cause tissue damage, while M2 macrophages may contribute to tissue repair but impair viral clearance.
Assuntos
Infecções por Alphavirus , Alphavirus , Artrite Reumatoide , Animais , Humanos , Macrófagos , InflamaçãoRESUMO
SUMMARY: Fifty male Wistar albino rats were divided into 5 groups; Group 1 as a sham group. Group 2 as a control group, Group 3 as 100 mg/kg CDP-choline administered group, Group as 200 mg/kg CDP-choline administered group, and Group 5 as sepsis group. The sepsis model was performed by ligating and perforating the caecum of rats. Liver and small intestine tissues were assessed either histologically or quantitatively and qualitatively. There was a significant difference between the sepsis and CDP-choline groups for liver and intestinal damage evaluated in tissue samples. (p <0.001). CDP-choline treatment partially improved dose-dependent the clinical parameters of sepsis and septic shock, reversed micro-anatomical damage caused by sepsis.
Cincuenta ratas albinas Wistar macho se dividieron en 5 grupos; Grupo 1 como grupo control simulador, el grupo 2 como grupo de control, el grupo 3 como grupo al que se administró 100 mg/kg de CDP-colina, el grupo 4 como grupo al que se administró 200 mg/kg de CDP-colina y el grupo 5 como grupo con sepsis. El modelo de sepsis se realizó ligando y perforando el intestino ciego de las ratas. Los tejidos del hígado y del intestino delgado se evaluaron histológicamente o cuantitativa y cualitativamente. Hubo una diferencia significativa entre los grupos de sepsis y CDP-colina para el daño hepático e intestinal evaluado en muestras de tejido (p<0,001). El tratamiento con CDP-colina mejoró parcialmente, según la dosis, los parámetros clínicos de sepsis y shock séptico y revirtió el daño micro anatómico causado por la sepsis.
Assuntos
Animais , Ratos , Sepse/tratamento farmacológico , Citidina Difosfato Colina/administração & dosagem , Intestino Delgado/efeitos dos fármacos , Fígado/efeitos dos fármacos , Ratos Wistar , Citidina Difosfato Colina/farmacologia , Modelos Animais de Doenças , Intestino Delgado/patologia , Fígado/patologiaRESUMO
Coronaviruses are the etiologic agents of several diseases. Coronaviruses of critical medical importance are characterized by highly inflammatory pathophysiology, involving severe pulmonary impairment and infection of multiple cell types within the body. Here, we discuss the interplay between coronaviruses and autophagy regarding virus life cycle, cell resistance, and inflammation, highlighting distinct mechanisms by which autophagy restrains inflammatory responses, especially those involved in coronavirus pathogenesis. We also address different autophagy modulators available and the rationale for drug repurposing as an attractive adjunctive therapy. We focused on pharmaceuticals being tested in clinical trials with distinct mechanisms but with autophagy as a common target. These autophagy modulators act in cell resistance to virus infection and immunomodulation, providing a double-strike to prevent or treat severe disease development and death from coronaviruses diseases.
Assuntos
Infecções por Coronavirus , Coronavirus , Autofagia/fisiologia , Coronavirus/fisiologia , Infecções por Coronavirus/patologia , Humanos , Inflamação , Carga Viral , Replicação Viral/fisiologiaRESUMO
SUMMARY: This study aimed to evaluate the effects of six weeks of HIIT on tissue and oxidative damage markers in rats supplemented with Coutoubea spicata fraction. Thirty-two male Wistar rats were divided into 4 groups: Baseline (GB); supplemented with 100 mg/kg of Coutoubea spicata fraction (GSCS); exercised for 6 weeks with the HIIT protocol (GH); supplemented with 100 mg/kg of Coutoubea spicata fraction + HIIT for 6 weeks (GHCS). Exercised animals performed the HIIT protocol (2 x 2). Tissue damage CK, LDH, ALT and AST markers in plasma were analyzed, as well as oxidative stress MDA and SH biomarkers in plasma and in cardiac, hepatic and muscle tissues. The results showed that CK, LDH, AST and ALT enzymes showed increase in GH when compared to GB (p<0.0001). However, CK, AST and ALT markers reduced their concentrations in GHCS when compared to GH (p<0.0001), indicating that Coutoubea spicata supplementation attenuated the damage in muscle and liver tissues induced by HIIT. Plasma, liver and muscle MDA showed increase in GH after HIIT sessions; however, when compared to GHCS, it showed reduced levels (p<0.0001). SH was elevated in the GH group when compared to GB in plasma and liver tissues (p<0.0001); in contrast, reduction in GHCS when compared to GH was observed in plasma, liver and cardiac tissues, demonstrating the redox effect of HIIT on some tissues. Thus, our findings showed that Coutoubea spicata has antioxidant activity, reducing oxidative damage markers and consequently tissue damage in healthy Wistar rats after HIIT protocol, but it also demonstrated redox balance after analyzing oxidative stress markers.
RESUMEN: Este estudio tuvo como objetivo evaluar los efectos de HIIT en los marcadores de daño tisular y oxidativo en ratas suplementadas con Coutoubea spicata durante seis semanas. Treinta y dos ratas Wistar macho se dividieron en 4 grupos: línea de base (GB); suplementados con 100 mg/kg de fracción de Coutoubea spicata (GSCS); ejercitados durante 6 semanas con el protocolo HIIT (GH); suplementado con 100 mg/kg de fracción de Coutoubea spicata + HIIT durante 6 semanas (GHCS). Los animales ejercitados realizaron el protocolo HIIT (2x2). Se analizaron los marcadores de daño tisular CK, LDH, ALT y AST en plasma, así como los biomarcadores de estrés oxidativo MDA y SH en plasma y en tejidos cardiaco, hepático y muscular. Los resultados indicaron que las enzimas CK, LDH, AST y ALT mostraron aumento en GH en comparación con GB (p<0,0001). Sin embargo, los marcadores CK, AST y ALT redujeron sus concentraciones en GHCS en comparación con GH (p<0,0001), lo que indica que la suplementación con Coutoubea spicata atenuó el daño en los tejidos musculares y hepáticos inducido por HIIT. La MDA de plasma, hígado y músculo mostró un aumento en la GH después de las sesiones de HIIT; sin embargo, en comparación con GHCS, mostró niveles reducidos (p<0,0001). Se observó SH elevado en el grupo de GH en comparación con GB en plasma y tejidos hepáticos (p<0,0001); en contraste, se observó una reducción en GHCS en comparación con GH en plasma, hígado y tejidos cardíacos, lo que demuestra el efecto redox de HIIT en algunos tejidos. Por lo tanto, nuestros hallazgos mostraron que Coutoubea spicata tiene actividad antioxidante, con reducción de los marcadores de daño oxidativo y, en consecuencia, el daño tisular en ratas Wistar sanas después del protocolo HIIT, pero además demostró el equilibrio redox después de analizar los marcadores de estrés oxidativo.
Assuntos
Animais , Masculino , Ratos , Extratos Vegetais/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Gentianaceae/química , Treinamento Intervalado de Alta Intensidade , Biomarcadores , Ratos WistarRESUMO
The lack of proper gastrointestinal models assessing the inter-strain virulence variability of foodborne pathogens and the effect of the vehicle (food matrix) affects the risk estimation. This research aimed to propose a dynamic and integrated in vitro/ex vivo gastrointestinal model to evaluate the probability and severity of infection of foodborne pathogens at different matrices. An everted gut sac was used to determine the adhesion and invasion of Salmonella enterica and tissue damage. S. Typhimurium ATCC 14028 was used as a representative bacterium, and two matrices (water and cheese) were used as vehicles. No differences (p > 0.05) in the probability of infection (Pinf) were found for intra-experimental repeatability. However, the Pinf of cheese-vehiculated S. Typhimurium was different compared to water- vehiculated S. Typhimurium, 7.2-fold higher. The histological analysis revealed Salmonella-induced tissue damage, compared with the control (p < 0.05). In silico proposed interactions between two major Salmonella outer membrane proteins (OmpA and Rck) and digested peptides from cheese casein showed high binding affinity and stability, suggesting a potential protective function from the food matrix. The results showed that the everted gut sac model is suitable to evaluate the inter-strain virulence variability, considering both physiological conditions and the effect of the food matrix.
Assuntos
Doenças Transmitidas por Alimentos/microbiologia , Trato Gastrointestinal/microbiologia , Salmonella typhimurium/fisiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Queijo/microbiologia , Água Doce/microbiologia , Humanos , Modelos Biológicos , Probabilidade , Salmonella typhimurium/genética , Salmonella typhimurium/patogenicidade , VirulênciaRESUMO
COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. Angiotensin-converting enzyme 2 (ACE2) is not only an enzyme but also a functional receptor on cell surfaces through which SARS-CoV-2 enters the host cells and is highly expressed in the heart, kidneys, and lungs and shed into the plasma. ACE2 is a key regulator of the renin-angiotensin-aldosterone system (RAAS). SARS-CoV-2 causes ACE/ACE2 balance disruption and RAAS activation, which leads ultimately to COVID-19 progression, especially in patients with comorbidities, such as hypertension, diabetes mellitus, and cardiovascular disease. Therefore, ACE2 expression may have paradoxical effects, aiding SARS-CoV-2 pathogenicity, yet conversely limiting viral infection. This article reviews the existing literature and knowledge of ACE2 in COVID-19 setting and focuses on its pathophysiologic involvement in disease progression, clinical outcomes, and therapeutic potential.
Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/patologia , SARS-CoV-2/patogenicidade , Enzima de Conversão de Angiotensina 2/genética , Anticorpos Monoclonais/uso terapêutico , COVID-19/epidemiologia , COVID-19/terapia , Comorbidade , Humanos , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Polimorfismo Genético , Sistema Renina-Angiotensina/fisiologia , Glicoproteína da Espícula de Coronavírus/imunologiaRESUMO
Resumen El objetivo del estudio fue identificar la presencia de daño muscular en deportistas de la Provincia de Azuay, Ecuador, a través de la medición de la actividad enzimática. Para esto se realizó una investigación clínica, descriptiva y de corte transversal en 220 deportistas con edades comprendidas entre 14 y 18 años (media 17,3 años), predominantemente del sexo masculino (64,1%), pertenecientes a 11 disciplinas deportivas, a quienes se les determinaron los valores sanguíneos de lactato deshidrogenasa, creatina quinasa y creatina quinasa isoenzima MB. Los principales resultados mostraron, que con un tiempo de práctica deportiva entre uno y tres años (39,1%) y con una frecuencia de entrenamiento de tres veces por semana (54,5%), predominaron los deportistas con valores normales de los marcadores musculares. La natación fue el deporte en el cual se identificó un mayor número de atletas con alteraciones de los valores séricos de creatina quinasa y creatina quinasa isoenzima MB. Se concluye que el sexo femenino, la práctica de actividad física sistemática por un período menor de un año y con una frecuencia de entrenamiento inferior a tres veces por semana fueron las características generales que no provocaron aumento de los valores séricos de los marcadores de daño muscular identificados.
Abstract The objective of the study was to identify the presence of muscle damage in athletes from the Azuay Province, Ecuador, by measuring enzyme activity. To this aim, a clinical, descriptive and cross-sectional investigation was carried out on 220 athletes aged between 14 and 18 years (average 17.3 years), predominantly male (64.1%), belonging to 11 sports disciplines, whose blood values for lactate dehydrogenase, creatine kinase and creatine kinase isoenzyme MB were determined. The main results showed that, with a length of sports practice between one and three years (39.1%) and a training frecuency of three times per week (54.5%), athletes with normal values of muscle markers predominated. Swimming was the sport in which a greater number of athletes with alterations in serum creatine kinase and preparatocreatine kinase isoenzyme MB values were identified. It is concluded that female sex and the practice of systematic physical activity for a period of less than one year and with a training frequency less than three times a week were the general characteristics that had a negative impact on the serum values of the identified muscle damage markers.
Resumo O objetivo do estudo foi identificar a presença de lesão muscular em atletas da Província de Azuay, Equador, por meio da medição da atividade enzimática. Para isso foi realizada uma pesquisa clínica, descritiva e transversal em 220 atletas com idades entre 14 e 18 anos (média de 17,3 anos), predominantemente do sexo masculino (64,1%), pertencentes a 11 modalidades esportivas cujos valores sanguíneos para lactato desidrogenase, creatina quinase e creatina quinase isoenzima MB foram determinados. Os principais resultados mostraram que com tempo de prática esportiva entre um e três anos (39,1%) e com frequência de três vezes por semana (54,5%), predominaram os atletas com valores normais dos marcadores musculares. A natação foi o esporte em que se identificou maior número de atletas com alterações nos valores séricos de creatina quinase e creatina quinase isoenzima MB. Conclui-se que o sexo feminino, a prática de atividade física sistemática por período inferior a um ano e com frequência de treinamento inferior a três vezes por semana foram as características gerais que não produziram aumento dos valores séricos dos marcadores de lesão muscular identificados.
RESUMO
INTRODUCTION: In 2006 and 2009, we reported the levels of acute and chronic tissue damage after cordectomy associated with use of the microlectrodes using high frequency energy. In 2010, we shifted to radiofrequency rather than high frequency electrogenerators. OBJECTIVE: The aim of this study is to evaluate acute tissue damage in the larynx after cordectomy using microelectrodes coupled to a radiofrequencygenerator. METHODS: We studied 22 patients with a stage T1 glottic squamous cell carcinoma. The patients were randomly assigned to the two operating mode: cutting or coagulation (11 patients each mode). The strength of the study is that there are no previous studies on the effect of radiofrequency in human vocal cord. RESULTS: Tissue damage was milder when microelectrodes were coupled to a 4â¯MHz generator operating in the cutting mode. Thus, when using microelectrodes and radiofrequency, we recommend that the cutting mode be used for epithelial incision and the coagulation mode to treat the stroma and muscle and for final hemostasis. CONCLUSION: Microelectrodes and radiofrequency in transoral laryngeal surgery produced mild tissue damage and offer an excellent alternative to the use of high frequency energy.
Assuntos
Neoplasias Laríngeas , Terapia a Laser , Glote/cirurgia , Humanos , Neoplasias Laríngeas/cirurgia , Microeletrodos , Prega Vocal/cirurgiaRESUMO
This study aimed to evaluate the essential oil of Ocimum gratissimum L. (EOOG) for anesthesia and in the transport of Oreochromis niloticus. Experiment I determined the time of anesthesia induction and recovery during anesthesia of O. niloticus exposed to different concentrations of EOOG (0, 30, 90, 150, and 300 mg L-1). Based on data from Experiment I, Experiment II evaluated the effect of 0, 30, and 90 mg L-1 EOOG on blood parameters and oxidative stress immediately after anesthesia induction and 1 h after recovery. Experiment III evaluated the effect of 0, 5, and 10 mg L-1 EOOG on blood variables immediately after 4.5 h of transport of juveniles. Concentrations between 90 and 150 mg L-1 EOOG were efficient for anesthesia and recovery. The use of 90 mg L-1 of EOOG prevented an increase in plasma glucose. Other changes in blood parameters and oxidative stress are discussed. The use of 10 mg L-1 EOOG in transport increased plasma glucose and decreased hematocrit values immediately after transport. It is concluded that the use of 90 and 150 mg L-1 EOOG causes anesthesia and recovery in O. niloticus within the time intervals considered ideal. The use of 90 mg L-1 EOOG favored stable plasma glucose soon after anesthesia induction and 1 h after recovery, but caused changes in the antioxidant defense system by increasing hepatic and kidney ROS. The transport of 12 g O. niloticus for 4.5 h can be performed with concentration of 5 mg L-1 of EOOG.
Assuntos
Anestésicos , Ciclídeos , Ocimum , Óleos Voláteis , Óleos de Plantas , Anestesia , Animais , Glicemia , Encéfalo/metabolismo , Proteínas de Peixes/metabolismo , Brânquias/metabolismo , Rim/metabolismo , Fígado/metabolismo , Estresse Oxidativo , Folhas de Planta , Espécies Reativas de Oxigênio , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
We investigated the ability of tannic acid (TA) to prevent oxidative and nitrosative damage in the brain, liver, kidney, and serum of a rat model of acute hypermethioninemia. Young Wistar rats were divided into four groups: I (control), II (TA 30 mg/kg), III (methionine (Met) 0.4 g/kg + methionine sulfoxide (MetO) 0.1 g/kg), and IV (TA/Met + MetO). Rats in groups II and IV received TA orally for seven days, and rats of groups I and III received an equal volume of water. After pretreatment with TA, rats from groups II and IV received a single subcutaneous injection of Met + MetO, and were euthanized 3 h afterwards. In specific brain structures and the kidneys, we observed that Met + MetO led to increased reactive oxygen species (ROS), nitrite, and lipid peroxidation levels, followed by a reduction in thiol content and antioxidant enzyme activity. On the other hand, pretreatment with TA prevented both oxidative and nitrosative damage. In the serum, Met + MetO caused a decrease in the activity of antioxidant enzymes, which was again prevented by TA pretreatment. In contrast, in the liver, there was a reduction in ROS levels and an increase in total thiol content, which was accompanied by a reduction in catalase and superoxide dismutase activities in the Met + MetO group, and pretreatment with TA was able to prevent only the reduction in catalase activity. Conclusively, pretreatment with TA has proven effective in preventing oxidative and nitrosative changes caused by the administration of Met + MetO, and may thus represent an adjunctive therapeutic approach for treatment of hypermethioninemia.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/tratamento farmacológico , Glicina N-Metiltransferase/deficiência , Estresse Nitrosativo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Taninos/farmacologia , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Erros Inatos do Metabolismo dos Aminoácidos/patologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Glutationa Peroxidase/genética , Glicina N-Metiltransferase/metabolismo , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estresse Nitrosativo/genética , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/genética , Ratos , Espécies Reativas de Oxigênio/metabolismo , Soro/efeitos dos fármacos , Soro/metabolismo , Superóxido Dismutase/genéticaRESUMO
Cutaneous leishmaniasis (CL) is caused by the bite of the infected sand fly, which inoculates parasites of Leishmania spp and triggers an immune response. An exacerbated cutaneous inflammatory response is crucial for controlling parasite burden but can also promote tissue damage. This study aimed to characterize the populations of natural killer (NK), CD57+, CD4+, and CD8+ T cells, CD20+ B cells, as well as CD68+ macrophages, in biopsies of ulcerated CL lesions, and quantify the production of perforin+, grazyme B+, interleukin 1 beta (IL-1ß+) and Tumor Necrosis Factor (TNF-α+ cells). We then correlated these parameters with necrosis, inflammation and the number of amastigotes. CD4+ T cells were positively correlated to the extent of inflammation, B cells and IL-1ß+ were associated with the extent of necrosis, CD68+ macrophages and perforin were correlated with the number of amastigotes, and CD57+ NK cells was correlated to CD68+ macrophages and amastigotes. In sum, the finding suggests that the production of cytotoxic granules and cytokines by inflammatory cells contributes to tissue damage in CL lesions.
Assuntos
Leishmania , Leishmaniose Cutânea , Linfócitos T CD8-Positivos , Citocinas , Humanos , PeleRESUMO
Snake bite envenoming is a public health problem that was recently included in the list of neglected tropical diseases of the World Health Organization. In the search of new therapies for the treatment of local tissue damage induced by snake venom metalloproteinases (SVMPs), we tested the inhibitory activity of peptidomimetic compounds designed as inhibitors of matrix metalloproteinases on the activities of the SVMP Batx-I, from Bothrops atrox venom. The evaluated compounds show great potential for the inhibition of Batx-I proteolytic, hemorrhagic and edema-forming activities, especially the compound CP471474, a peptidomimetic including a hydroxamate zinc binding group. Molecular dynamics simulations suggest that binding of this compound to the enzyme is mediated by the electrostatic interaction between the hydroxamate group and the zinc cofactor, as well as contacts, mainly hydrophobic, between the side chain of the compound and amino acids located in the substrate binding subsites S1 and S1 ' . These results show that CP471474 constitutes a promising compound for the development of co-adjuvants to neutralize local tissue damage induced by snake venom metalloproteinases.
Assuntos
Bothrops , Venenos de Crotalídeos/enzimologia , Venenos de Crotalídeos/toxicidade , Inibidores de Metaloproteinases de Matriz/uso terapêutico , Metaloproteases/toxicidade , Fosfolipases A2/toxicidade , Mordeduras de Serpentes/tratamento farmacológico , Animais , Edema/induzido quimicamente , Edema/prevenção & controle , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Ácidos Hidroxâmicos/química , Ácidos Hidroxâmicos/farmacologia , Masculino , Camundongos , Modelos Moleculares , Simulação de Dinâmica Molecular , Peptidomiméticos/uso terapêutico , Inibidores de Proteases/farmacologia , Inibidores de Proteases/uso terapêutico , Mordeduras de Serpentes/patologia , Zinco/química , Zinco/farmacologiaRESUMO
The human respiratory syncytial virus (hRSV) remains one of the leading pathogens causing acute respiratory tract infections (ARTIs) in children younger than 2 years old, worldwide. Hospitalizations during the winter season due to hRSV-induced bronchiolitis and pneumonia increase every year. Despite this, there are no available vaccines to mitigate the health and economic burden caused by hRSV infection. The pathology caused by hRSV induces significant damage to the pulmonary epithelium, due to an excessive inflammatory response at the airways. Cytokines are considered essential players for the establishment and modulation of the immune and inflammatory responses, which can either be beneficial or harmful for the host. The deleterious effect observed upon hRSV infection is mainly due to tissue damage caused by immune cells recruited to the site of infection. This cellular recruitment takes place due to an altered profile of cytokines secreted by epithelial cells. As a result of inflammatory cell recruitment, the amounts of cytokines, such as IL-1, IL-6, IL-10, and CCL5 are further increased, while IL-10 and IFN-γ are decreased. However, additional studies are required to elicit the mediators directly associated with hRSV damage entirely. In addition to the detrimental induction of inflammatory mediators in the respiratory tract caused by hRSV, reports indicating alterations in the central nervous system (CNS) have been published. Indeed, elevated levels of IL-6, IL-8 (CXCL8), CCL2, and CCL4 have been reported in cerebrospinal fluid from patients with severe bronchiolitis and hRSV-associated encephalopathy. In this review article, we provide an in-depth analysis of the role of cytokines secreted upon hRSV infection and their potentially harmful contribution to tissue damage of the respiratory tract and the CNS.
Assuntos
Citocinas/fisiologia , Infecções por Vírus Respiratório Sincicial/patologia , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Linhagem Celular , Sistema Nervoso Central/patologia , Criança , Pré-Escolar , Citocinas/líquido cefalorraquidiano , Células Epiteliais/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Lactente , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Muco/metabolismo , Prevalência , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/metabolismo , Vírus Sincicial Respiratório Humano/imunologia , Vírus Sincicial Respiratório Humano/patogenicidade , Vírus Sincicial Respiratório Humano/fisiologia , Sistema Respiratório/metabolismo , Sistema Respiratório/patologia , Sistema Respiratório/virologia , Replicação ViralRESUMO
L. (viannia) braziliensis infection causes American Tegumentary Leishmaniasis (ATL), with prolonged time to healing lesions. The potent inflammatory response developed by the host is important to control the parasite burden and infection however an unbalanced immunity may cooperate to the tissue damage observed. The range of mechanisms underlying the pathological responses associated with ATL still needs to be better understood. That includes epigenetic regulation by non-coding MicroRNAs (miRNAs), non-coding sequences around 22 nucleotides that act as post-transcriptional regulators of RNAs encoding proteins. The miRNAs have been associated with diverse parasitic diseases, including leishmaniasis. Here we evaluated miRNAs that targeted genes expressed in cutaneous leishmaniasis lesions (CL) by comparing its expression in both CL and normal skin obtained from the same individual. In addition, we evaluated if the miRNAs expression would be correlated with clinical parameters such as therapeutic failure, healing time as well as lesion size. The miR-361-3p and miR-140-3p were significantly more expressed in CL lesions compared to normal skin samples (p = 0.0001 and p < 0.0001, respectively). In addition, the miR-361-3p was correlated with both, therapeutic failure and healing time of disease (r = 0.6, p = 0.003 and r = 0.5, p = 0.007, respectively). In addition, complementary analysis shown that miR-361-3p is able to identify with good sensitivity (81.2%) and specificity (100%) patients who tend to fail initial treatment with pentavalent antimonial (Sbv). Finally, the survival analysis considering "cure" as the endpoint showed that the higher the expression of miR-361-3p, the longer the healing time of CL. Overall, our data suggest the potential of miR-361-3p as a prognostic biomarker in CL caused by L. braziliensis.
Assuntos
Leishmania braziliensis/fisiologia , Vacinas contra Leishmaniose/imunologia , Leishmaniose Cutânea/genética , MicroRNAs/genética , Pele/patologia , Adolescente , Adulto , Biomarcadores , Feminino , Granzimas/genética , Humanos , Leishmaniose Cutânea/mortalidade , Leishmaniose Cutânea/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Pele/parasitologia , Análise de Sobrevida , Resultado do Tratamento , Fator de Necrose Tumoral alfa/genética , Cicatrização/genética , Adulto JovemRESUMO
Most of the snakebite envenomations in Central and South America are caused by species belonging to Bothrops genus. Their venom is composed mainly by zinc-dependent metalloproteinases, responsible of the hemorrhage characteristic of these envenomations. The aim of this study was to determine the inhibitory ability of ten flavonoids on the in-vitro proteolytic activity of Bothrops atrox venom and on the hemorrhagic, edema-forming and myonecrotic activities of Batx-I, the most abundant metalloproteinase isolated from this venom. Myricetin was the most active compound, exhibiting an IC 50 value of 150 µ M and 1021 µ M for the inhibition of proteolytic and hemorrhagic activity, respectively. Independent injection experiments, with a concentration of 1600 µ M of myricetin administered locally, immediately after toxin injection, demonstrated a reduction of 28 ± 6 % in the hemorrhagic lesion. Additionally, myricetin at concentrations 800, 1200 and 1600 µ M promoted a reduction in plasma creatine kinase activity induced by Batx-I of 21 ± 2 % , 60 ± 5 % and 63 ± 2 % , respectively. Molecular dynamics simulations coupled with the adaptive biasing method suggest that myricetin can bind to the metalloproteinase active site via formation of hydrogen bonds between the hydroxyl groups 3', 4' and 5' of the benzyl moiety and amino acid Glu143 of the metalloproteinase. The hydroxyl substitution pattern of myricetin appears to be essential for its inhibitory activity. Based on this evidence, myricetin constitutes a candidate for the development of inhibitors to reduce local tissue damage in snakebite envenomations.
Assuntos
Venenos de Crotalídeos/antagonistas & inibidores , Edema/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Hemorragia/tratamento farmacológico , Metaloproteases/antagonistas & inibidores , Animais , Bothrops/metabolismo , Domínio Catalítico , Creatina Quinase/sangue , Venenos de Crotalídeos/química , Venenos de Crotalídeos/enzimologia , Venenos de Crotalídeos/toxicidade , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Inibidores Enzimáticos/química , Flavonoides/química , Hemorragia/induzido quimicamente , Ligação de Hidrogênio , Concentração Inibidora 50 , Metaloproteases/química , Camundongos , Modelos Moleculares , Simulação de Dinâmica MolecularRESUMO
Caulerpin (CLP), an alkaloid from algae of the genus Caulerpa, has shown anti-inflammatory activity. Therefore, this study aimed to analyze the effect of CLP in the murine model of peritonitis and ulcerative colitis. Firstly, the mice were submitted to peritonitis to evaluate which dose of CLP (40, 4, or 0.4 mg/kg) could decrease the inflammatory infiltration in the peritoneum. The most effective doses were 40 and 4 mg/kg. Then, C57BL/6 mice were submitted to colitis development with 3% dextran sulfate sodium (DSS) and treated with CLP at doses of 40 and 4 mg/kg. The disease development was analyzed through the disease activity index (DAI); furthermore, colonic tissue samples were submitted to histological analysis, NFκB determination, and in vitro culture for cytokines assay. Therefore, CLP at 4 mg/kg presented the best results, triggering improvement of DAI and attenuating the colon shortening and damage. This dose was able to reduce the TNF-α, IFN-γ, IL-6, IL-17, and NFκB p65 levels, and increased the levels of IL-10 in the colon tissue. Thus, CLP mice treatment at a dose of 4 mg/kg showed promising results in ameliorating the damage observed in the ulcerative colitis.
Assuntos
Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Caulerpa/metabolismo , Colite Ulcerativa/tratamento farmacológico , Indóis/farmacologia , Alga Marinha/metabolismo , Alcaloides/isolamento & purificação , Alcaloides/uso terapêutico , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Humanos , Indóis/isolamento & purificação , Indóis/uso terapêutico , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Peritonite/patologia , Resultado do Tratamento , Zimosan/toxicidadeRESUMO
Introducción: Entre el lugar del daño tisular y la percepción del dolor, ocurre una serie de eventos electroquímicos que se conocen como nocicepción y comprenden cuatro procesos neurofisiológicos conocidos como: transducción, transmisión, modulación y percepción. Objetivo: Aportar información actualizada sobre las regiones del encéfalo vinculadas a la interpretación del dolor. Material y Método: Se realizó una revisión bibliográfica, con vistas a esclarecer la interpretación de la señal nociceptiva. Se consultaron treinta y cinco artículos científicos, se determinó escoger un total de veintinueve por su relación directa con el propósito de la búsqueda, veintitrés de los cuales corresponden a los últimos 5 años publicados en revistas internacionales y nacionales. Desarrollo: Los axones nociceptivos se clasifican como A δ; y C, participan en la conducción de los potenciales de acción de la periferia al sistema nervioso central. La transmisión de la señal en forma de potenciales de acción se descodifica en áreas relacionadas con aspectos cognoscitivos, afectivo, emocional y conductual del dolor. Este disímil conjunto de estructuras se reconoce en la actualidad como matriz encefálica del dolor. Conclusiones: La matriz del dolor, corresponde a áreas encefálicas como las cortezas somestésicas SI y SII, implicadas en el aspecto discriminativo del dolor. La corteza cingulada anterior y la corteza insular están asociadas al componente afectivo emocional del dolor(AU)
Introduction: A series of electrochemical events called nociception occur between the tissue damage and the perception of pain. They include four neurophysiological processes known as: transduction, transmission, perception, and modulation. Objective: To provide up-to-date information about the regions of the brain involved with the interpretation of pain. Material and Method: A bibliographic review was carried out with the aim of clarifying the interpretation of the nociceptive signal. Thirty-five scientific articles were consulted, and a total of twenty-nine were chosen due to their direct relationship with the aim of the search, twenty-three of which correspond to the last five years of publication in national and international journals. Development: Nociceptive axons are classified as Aδ; and C, and participate in the conduction of action potential of the peripheral nervous system (PNS). The transmission of the signal in the form of action potential is decoded in areas related to cognoscitive, affective, and emotional aspects, and the behavioral area of pain. This dissimilar group of structures is recognized at present as the brain matrix of pain. Conclusions: The pain matrix corresponds to brain areas such as SI and SII somatosensory cortices, implied in the discriminative aspect of pain. Both the anterior cingulate cortex (ACC) and the anterior insular cortex (AIC) are associated with the emotional and affective component of pain(AU)
Assuntos
Humanos , Masculino , Feminino , Dor , Encéfalo , Percepção da Dor/fisiologia , Nociceptividade/fisiologiaRESUMO
Septic arthritis is an inflammatory joint disease that is induced by pathogens such as Staphylococcus aureus. Infection of the joint triggers an acute inflammatory response directed by inflammatory mediators including microbial danger signals and cytokines and is accompanied by an influx of leukocytes. The recruitment of these inflammatory cells depends on gradients of chemoattractants including formylated peptides from the infectious agent or dying cells, host-derived leukotrienes, complement proteins and chemokines. Neutrophils are of major importance and play a dual role in the pathogenesis of septic arthritis. On the one hand, these leukocytes are indispensable in the first-line defense to kill invading pathogens in the early stage of disease. However, on the other hand, neutrophils act as mediators of tissue destruction. Since the elimination of inflammatory neutrophils from the site of inflammation is a prerequisite for resolution of the acute inflammatory response, the prolonged stay of these leukocytes at the inflammatory site can lead to irreversible damage to the infected joint, which is known as an important complication in septic arthritis patients. Thus, timely reduction of the recruitment of inflammatory neutrophils to infected joints may be an efficient therapy to reduce tissue damage in septic arthritis.
Assuntos
Artrite Infecciosa/terapia , Articulações/efeitos dos fármacos , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Infecções Estafilocócicas/terapia , Antibacterianos/uso terapêutico , Artrite Infecciosa/imunologia , Artrite Infecciosa/microbiologia , Artrite Infecciosa/cirurgia , Artrocentese/métodos , Artroscopia/métodos , Movimento Celular/imunologia , Quimiocinas/imunologia , Quimiocinas/metabolismo , Humanos , Inflamação , Articulações/imunologia , Articulações/microbiologia , Articulações/cirurgia , Leucotrienos/imunologia , Leucotrienos/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/cirurgia , Staphylococcus aureus , Sucção/métodosRESUMO
The placenta plays a major role in embryo-fetal defects and intrauterine growth retardation after maternal alcohol consumption. Our aims were to determine the oxidative status and cellular and molecular oxidative stress effects on uterine myometrium and trophoblast-decidual tissue following perigestational alcohol intake at early organogenesis. CF-1 female mice were administered with 10% alcohol in drinking water for 17 days prior to and up to day 10 of gestation. Control females received ethanol-free water. Treated mice had smaller implantation sites compared to controls (p < 0.05), diminished maternal vascular lumen, and irregular/discontinuous endothelium of decidual vessels. The trophoblast giant cell layer was disorganized and presented increased abnormal nuclear frequency. The myometrium of treated females had reduced nitrite content, increased superoxide dismutase activity, and reduced glutathione (GSH) content (p < 0.05). However, the trophoblast-decidual tissue of treated females had increased nitrite content (p < 0.05), increased GSH level (p < 0.001), increased thiobarbituric acid-reactive substance concentration (p < 0.001), higher 3-nitrotyrosine immunoreaction, and increased apoptotic index (p < 0.05) compared to controls. In summary, perigestational alcohol ingestion at organogenesis induced oxidative stress in the myometrium and trophoblast-decidual tissue, mainly affecting cells and macromolecules of trophoblast and decidual tissues around early organogenesis, in CF-1 mouse, and suggests that oxidative-induced abnormal early placental formation probably leads to risk of prematurity and fetal growth impairment at term.