Las citoquinas en el absceso hepático amebiano: un ejemplo de investigación inmunología en el ámbito clínico / Cytokines in amoebic liver abscess: an example of immunological research within the clinical scope

Resumen El propósito de esta revisión es resaltar la importancia de la investigación en el área de la inmunología y su aplicación en el ámbito clínico. En una primera parte se presentan los descubrimientos más importantes que ayudaron a dilucidar los principales procesos fisiológicos involucrados en las enfermedades y de esta manera ayudaron a redireccionar la investigación en el área de la inmunología. Seguido, se describe un ejemplo de investigación básica relacionada con el papel de las citocinas en el absceso hepático amebiano, mostrando el trabajo de varios grupos de investigación en el mundo, con el objetivo de entender la respuesta inmune contra el parásito. Lo anterior nos permite argumentar la relevancia que tiene la investigación inmunológica dentro del contexto clínico.

Abstract The purpose of this review is to highlight the importance of research in immunology and its application in the clinical setting. The first part presents the most important discoveries that helped to elucidate the main physiological processes involved in the diseases and in this way helped to redirect research in immunology. Then, we describe an example of basic research related to the role of cytokines in the amoebic liver abscess, showing the work of several research groups in the world, with the aim of understanding the immune response against the parasite. This allows us to argue the relevance of immunological research within the clinical context.

Microbiota Evaluation and Extracellular Cytokine Profile in Patients Affected with Intraabdominal Infection.

Failures in the control of infectious focus may be associated with Intra-abdominal infections (IAI)-driven sepsis. We evaluated the bacterial antimicrobial profile and the cytokine production in patients with IAI in Belo Horizonte, Brazil. To the analyses, Vitek 2 bioMérieux and BD-CBA Human Inflammatory Cytokines were used. Escherichia coli, Enterococcus faecalis and Bacteroides fragilis were predominant in this cohort. Enterobacteriaceae was resistant to at least 4 different antimicrobial classes and 80.0% of Acintobacter baumannii strains to imipenem. 81.8% of Staphylococcus spp. were methicillin-resistant. Penicillin and clindamycin resistance were found in 80.0% and 26.7% of anaerobes, respectively. IL-8 was found in all IAI secretions and in 93.5% of analyzed sera; while IL-6 was identified in 93.5% of patient’s serum and in 51.6% analyzed secretions. IL-10 was detected in 53.3% of patient’s serum. Our data indicates the relevance of further cytokine profile studies to better understanding the evolution of these processes.

Inflammatory mediators of neuropathic pain / Mediadores inflamatórios na dor neuropática

ABSTRACT BACKGROUND AND OBJECTIVES: Pro-inflammatory chemical mediators and algogenic substances seem to be confused by the sharing of their actions and by interactions in painful and inflammatory presentation. This study aimed at presenting a review of major inflammatory chemical mediators and place them in neuropathic pain pathophysiology. CONTENTS: Inflammation is the homeostatic response of vascularized tissues to remove harmful agents and restore their normal functions. Nervous system (central and/or peripheral) diseases and injuries may induce neuropathic pain and may also modify inflammatory process nervous mediation. In such pathological conditions, there might be pain without restrict link with admitedly harmful or painful stimuli, as well as there might be inflammation without restrict link with the presence of harmful agents and the need to remove them. Chemical mediators involved in neuropathic pain and inflammation pathophysiology modulate the presentation of both. CONCLUSION: Studies on inflammation offer evidences to support the important role of their chemical mediators in neuropathic pain pathogenesis. In peripheral and central sensitization, a thin borderline between reversibility or not of neuropathic pain may be respected or exceeded by inflammatory mediators actions.

RESUMO JUSTIFICATIVA E OBJETIVOS: Mediadores químicos pró-inflamatórios e substâncias algogênicas parecem se confundir pelo compartilhamento de suas ações e pelas interações no quadro doloroso e inflamatório. O objetivo deste estudo foi apresentar uma revisão sobre os principais mediadores químicos inflamatórios e situá-los na fisiopatologia da dor neuropática. CONTEÚDO: A inflamação é a resposta homeostática de tecidos vascularizados no sentido de remoção de agentes lesivos e restauro de suas funções normais. Doenças e lesões no sistema nervoso (central e/ou periférico) podem causar dor neuropática, e, também modificar a mediação nervosa do processo inflamatório. Nessas condições patológicas a dor pode ocorrer sem o vínculo restrito com estímulo reconhecidamente nocivo ou doloroso, assim como ocorrer quadro inflamatório sem o vínculo restrito com a presença de agentes lesivos e a necessidade de removê-los. Os mediadores químicos envolvidos na fisiopatologia da dor neuropática e da inflamação modulam o quadro de ambas. CONCLUSÃO: Os estudos sobre inflamação oferecem evidências para embasar a importância do papel dos seus mediadores químicos na patogênese da dor neuropática. Na sensibilização periférica e, também na central uma fronteira tênue entre a reversibilidade ou não do quadro neuropático pode ser respeitada ou ultrapassada pelas ações de mediadores inflamatórios.

Avaliação da eficácia da terapia periodontal não cirúrgica em indivíduos obesos: revisão da literatura / Evaluation of the efficacy of non-surgical periodontal therapy effectiveness in obese individuals: literature review

A obesidade vem sendo considerada um dos maiores problemas de saúde pública da era moderna. A doença influencia negativamente a saúde geral do indivíduo, desencadeando ou agravando inúmeras doenças e comorbidades. Estudos sugerem que a obesidade pode influenciar a severidade e a progressão da doença periodontal, através do aumento de citocinas inflamatórias como o TNF-α, IL-6 e IL-8 secretadas pelo tecido adiposo na corrente sanguínea. Por isso, a presente revisão de literatura objetivou avaliar se a terapia não cirúrgica é eficaz no tratamento da doença periodontal em indivíduos obesos. Utilizando-se Obesity AND Periodontitis AND Periodontal Therapy como palavras chave, foram levantados artigos na base de dados Pubmed, publicados entre os anos de 2011 e 2016, na língua inglesa. A maior parte dos estudos investigou o modelo de tratamento convencional e monitorou parâmetros clínicos. Os resultados demonstraram que clinicamente os obesos respondem favoravelmente a raspagem e alisamento radicular, incluindo diminuição de profundidade de sondagem e melhora na condição gengival. Os estudos que incluíram parâmetros bioquímicos também demonstraram resultados favoráveis. Entretanto, outros parâmetros devem ser monitorados como desfechos e outras modalidades terapêuticas precisam ser testadas para que se possa avaliar melhor a real eficácia do tratamento em obesos. Considerando-se que os dados disponíveis ainda são limitados, a literatura permitiu-nos concluir que a terapia periodontal convencional é efetiva em indivíduos obesos

Obesity has been considered one of the greatest public health problems of the modern era. The disease adversely affects the overall health of the individual, triggering or worsening numerous diseases and comorbidities. Studies suggest that obesity can influence the severity and progression of periodontal disease by the increase of inflammatory cytokines such as TNF-α, IL-6 and IL-8 secreted by adipose tissue in the bloodstream. Therefore, the aim of this literature review is to assess the efficacy of non-surgical periodontal therapy in obese individuals. Using Obesity AND Periodontitis AND Periodontal Therapy as keywords, articles published between 2011 and 2016 in the English language were searched in Pubmed database. Most studies had focused on conventional treatment and monitored clinical parameters. Obese showed good clinical response to scaling and root planing, including a decrease in pocket depth and improvement in the gingival condition. Studies that included biochemical parameters also showed favorable results. However, other parameters should be monitored as outcomes and other therapeutic modalities need to be tested so that the real effectiveness of treatment in obese patients can be better evaluated. Considering the limitation of available data, the literature enabled us to conclude that periodontal therapy is effective in obese individuals

Variabilidad de la síntesis de citoquinas por células dendríticas humanas estimuladas con los distintos serotipos de Aggregatibacter actinomycetecomitans / Variability in the cytokine synthesis by human dendritic cells in response to different Aggregatibacter actinomycetemcomitans serotypes

Objetivo: Sobre la base de la antigenicidad del polisacárido O del LPS, en A. actinomycetemcomitans se describen distintos serotipos bacterianos y entre ellos se ha especulado una patogenicidad e inmunogenicidad diferente. El objetivo de este trabajo es analizar las diferencias en la síntesis de citoquinas producidas por células dendríticas cuando son estimuladas con los distintos serotipos de A. actinomycetemcomitans. Metodología: Células dendríticas diferenciadas a partir de monocitos circulantes periféricos humanos fueron estimuladas a MOIs=10-1-10-2 con los serotipos a, b y c de A. Actinomycetemcomitans. Mediante PCR y ELISA se evaluaron los niveles de expresión y secreción de citoquinas. Resultados: En las células dendríticas, la producción de citoquinas fue diferente ante los distintos serotipos de A. actinomycetemcomitans, con mayores niveles de secreción de IL-1beta, IL-6, IL-12, IL-23, IFN-gamma y TNF-alfa cuando el microorganismo estimulante fue la cepa ATCC® 43718™ (serotipo b). Conclusión: El serotipo b de A. actinomycetemcomitans posee un mayor potencial inmuno-estimulador de células dendríticas comparado con los otros serotipos bacterianos y potencialmente contribuiría a inducir un patrón de respuesta inmune tipo Th1 y/o Th17 durante las periodontitis.

Objective: A. actinomycetemcomitans expresses a number of virulence factors that contribute to direct tissue damage and, based on the antigenicity of LPS O-polysaccharide, distinct serotypes have been described. The aim of this study was to determine the pattern of cytokine expression and secretion on dendritic cells stimulated with A. actinomycetemcomitans serotypes a, b and c. Methods: Using different multiplicity of infections of the serotypes a, b, and c of A. actinomycetemcomitans, the mRNA expression and secretion levels for cytokines IL-1beta, IL-5, IL-6, IL-10, IL-12, IL-23, TNF-alpha, and IFN-gamma were determined in stimulated dendritic cells using PCR and ELISA. Results: A dose-dependent increase in the secretion levels for IL-1beta, IL-5, IL-6, IL-10, IL-12, IL-23, TNF-alpha, and IFN-gamma was elicited on dendritic cells following stimulation with each of the serotypes of A. actinomycetemcomitans. In addition, A. actinomycetemcomitans serotype b (ATCC® 43718™) induced higher levels of IL-1beta, IL-6, IL-12, IL-23, IFN-gamma y TNF-alpha compared with the other strains. Conclusion: These data demonstrate that the distinct A. actinomycetemcomitans LPS O-polysaccharide serotypes induce both quantitative and qualitative differences in the dendritic cell response. Furthermore, the observed dendritic cell response to A. actinomycetemcomitans b serotype was characteristic of a Th1 and Th17 pattern of cytokine expression.

Manifestaciones clínicas y cambios en la química sérica y tisular en ratas tratadas con vitamina D3 (calciferol) / Clinical signs and changes in serum and tissue chemistry in rats treated with vitamin D3 (calciferol)

En el presente trabajo se estudió el efecto de la administración subcutánea de 250, 500 y 750 μg (10.000, 20.000 y 30.000 UI, respectivamente) de vitamina D3 (calciferol)/día durante 8 días, sobre las concentraciones séricas de vitamina D3 y de 25-hidroxivitamina D3 (25-OH-D3) y sobre las concentraciones séricas y tisulares de Ca, Zn, Cu y Fe en 45 ratas macho Wistar, de 12 semanas de edad y con pesos entre 180 y 200 gramos. El grupo control estuvo integrado por 15 ratas Wistar sanas, con género, edad y peso similares a los animales tratados. La administración del calciferol a dosis altas produjo una hipervitaminosis D que se caracterizo por un aumento en el contenido sérico de la vitamina D3 y de 25-OH-D3, diversos signos clínicos (por ejemplo, anorexia, pérdida marcada de peso, diarreas sanguinolentas, conjuntivitis bilateral y muerte), hipercalcemia, hipocincemia, hipercupremia, hipoferremia y una alteración en la distribución tisular de Ca, Zn, Cu y Fe en comparación con los controles no tratados. La hipercalcemia y la inflamación son un hallazgo prominente en la hipervitaminosis D. La inflamación o la infección inducen cambios sistémicos, conocidos colectivamente como la respuesta de fase aguda. Entre las variadas alteraciones que produce esta respuesta encontramos hipoferremia, hipocincemia e hipercupremia. Es probable que estas respuestas estén mediadas, en parte, por la producción y liberación de citocinas como la interleucina 1, interferones (IFN-alfa), la interleucina 6 (Il-6) y el factor de necrosis tumoral (TNF). El desarrollo de la hipoferremia durante la inflamación requiere de hepcidina, un péptido rico en enlaces disulfuro, regulador del metabolismo del hierro, sintetizado en el hígado en respuesta a la liberación de Il-6 durante la inflamación/infección. En conclusión, nuestros resultados proporcionan evidencias que la administración de altas dosis de vitamina D, a corto plazo, determina diversos signos clínicos, produce un marcado aumento de las concentraciones séricas de la vitamina D3 y de 25-OH-D3 y una marcada alteración en las concentraciones séricas y tisulares de Ca, Zn, Cu y Fe, que dependen de las dosis inyectadas de vitamina D.

In the present work the effect of subcutaneous administration of 250, 500 and 750 ìg (10.000, 20.000 and 30.000 IU, respectively) of vitamin D3 (calciferol) daily for eight days, on serum concentrations of vitamin D3 and 25- hydroxyvitamin D3 (25-OH-D3) and on serum and tissue concentrations of Ca, Zn, Cu and Fe in 45 white male Wistar rats, aged 12 weeks and weighing 180-200 g, have been studied. The group control was integrated by 15 healthy rats with similar characteristics (strain, gender, age and weight) that treated animals. Administration of high doses of calciferol produced a hypervitaminosis D characterized by a significant (p3 and 25-OH-D3, diverse clinical signs (such as, anorexia, marked loss of body weight, bloody diarrhea, bilateral conjunctivitis, and death), hypercalcemia, hypozincaemia, hypercupremia, hypoferraemia and an alteration in the tissue distribution of Ca, Zn, Cu and Fe as compared with untreated controls. Hypercalcemia and inflammation are prominent findings in hypervitaminosis D. Inflammation or infection induce systemic changes, collectively known as the acute phase response. Among the varied alterations that together produce this response are hypoferraemia, hypozincaemia and hypercupremia. It is likely that these responses are mediated, in part, by production and release of cytokines such as interleukin 1, interferons (IFN-alpha), interleukin 6 (Il-6) and tumor necrosis factor (TNF). The development of hypoferraemia during inflammation requires hepcidin, an iron regulatory hormone, a disulfide-rich peptide, produced in the liver in response to the release of Il-6 during inflammation/ infection. In conclusion, our results provide evidence that short-term administration of high doses of vitamin D determined diverse clinical signs and produced a marked increase of serum vitamin D3 and 25-OH-D3 and a marked alteration in the serum and tissue concentrations of Ca, Zn, Cu, and Fe. These changes depend on the doses given of vitamin D.

Desde la infección focal hasta la medicina periodontal / From focal infection to periodontal medicine

La participación de las bacterias de la cavidad bucal en la etiopatogenia de otras enfermedades puede ocurrir por medio de la migración de la propia bacteria hasta el foco de infección extraoral o por medio del establecimiento de un cuadro inflamatorio crónico que empieza en la infección ubicada en la boca. Evidencias científicas recientes sugieren que las enfermedades periodontales pueden interferir en la salud sistémica por medio de eses dos mecanismos, principalmente por medio de la liberación continua de diversos mediadores químicos y subproductos de la inflamación. Concentraciones plasmáticas elevadas de esas substancias durante periodos prolongados pueden influenciar el inicio o la progresión de otras enfermedades, como eventos adversos en el embarazo y enfermedades cardiovasculares. Este artigo presenta un breve histórico sobre la influencia de bacterias orales en la salud sistémica, desde la teoría de la Infección Focal hasta el concepto actual de Medicina Periodontal. Son abordados incluso los mecanismos de interacción entre la microbiota periodontopatogénica y la respuesta del hospedero.

The role of oral bacteria on the etiopathogenesis of other body diseases can occur through the migration ofthe microorganism to extra-oral infection site or by the establishment of a chronic inflammatory systemic environment from the localized infection on the mouth. Recent scientific evidences suggest that periodontal diseases might interfere with systemic health through these two mechanisms,mostly by the continual release of several chemical mediators and by-products of the inflammation. Highserum concentrations of these substances for prolonged periods of time might influence the beginning or the progression of other disorders, such as adverse pregnancy outcomesand cardiovascular diseases. This manuscript presents a brief historical perspective about the influence oforal bacteria on the systemic health, from the Focal Infection theory to the current concept of Periodontal Medicine. The mechanisms of interaction between periodontopathogenic microbiota and host response are also addressed.

Leucocitos e inflamação em pacientes com anemia falciforme / Leukocytes and inflammation in sickle cell disease patients

Os pacientes com anemia falciforme sofrem repetidos episódios de vasooclusâo caracterizados por lesão de isquemia-reperfusão e inflamação. Por esse motivo, a anemia falciforme é considerada um modelo de doença da microvasculatura, no qual há interação entre o endotélio, plaquetas, hemácias e leucócitos. Os objetivos deste trabalho foram investigar o papel de leucócitos mononucleares no processo inflamatório da anemia falciforme e a liberação de citocinas relacionadas à ativação do sistema NADPH oxidase em monócitos de pacientes com anemia falciforme estáveis. TNF-a, IFN-y e IL-10 foram detectados por meio de técnica de ensaio imunoenzimático (ELISA), utilizando kits comerciais. Após 24 horas de cultura com PHA; leucócitos mononucleares (PBMCs) de controles sadios liberaram quantidades significativamente maiores de TNFct, em relação aos de pacientes falciformes (p=0,02). Após 8 horas de cultura com LPS, também observamos maior liberação de TNF-a por PBMCs de controles sadios em relação aos pacientes falciformes (p=0,04). A liberação de TNF-a por monócitos de pacientes com doença falciforme e de controles sadios foi similar quando as células foram cultivadas em condições basais por 24 horas (p=0,25) ou após 24h (p=0,48) ou 48 horas de cultura com LPS (p=0,47). Após 48 horas de cultura com PFIA, a liberação de TNF-y por linfócitos de pacientes com doença falciforme foi...

Sickle cell disease patients suffer repeated episodes of vaso-occlusion. These episodes are characterized by ischemia-reperfusion injury and inflammation. Thus, sickle cell disease is considered a model of microvessel disease and a complex interaction among endothelial cells, platelets, erythrocytes and leukocytes. The aim of this study was to investigate the role of mononuclear leukocytes in the inflammatory process of sickle cell disease and the release of cytokines related to the NADPH oxidase components activation in mononuclear leukocytes from patients with sickle cell disease (SCD). TNF-a, IFN-y and IL-10 were detected in culture supernatants by standard commercial ELISA immunoassay kits. There was significant higher release of TNF-a by PBMC from healthy controls compared to SCD patients after 24h PHA stimulus (p-0.02) or 8h LPS stimulus (p=0.04). There was no significant difference in the release of TNF-a by monocytes from SCD patients compared to healthy controls. INF-y release by lymphocytes from SCD patients was significantly higher compared to healthy controls...