High-intensity interval training (treadmill) effects in myokines and endoplasmic reticulum stress of calf muscles in obese mice / Efectos del entrenamiento interválico de alta intensidad (trotadora) en miocinas y estrés del retículo endoplasmático de los músculos surales en ratones obesos

SUMMARY: Obesity is commonly associated with chronic tissue inflammation and skeletal muscle dysfunction. The study aimed to investigate the effects of High-Intensity Interval training (HIIT) on myokines and endoplasmic reticulum (ER) stress of diet- induced obese (DIO) mice. Three-month-old C57BL/6 male mice were fed a control (C) diet (n=20) or a high-fat (HF) diet (n=20) for 16 weeks. Then, half of the groups underwent HIIT (treadmill running) for an additional four weeks. HIIT increased calf muscles' contribution to BW (+24 %) and reduced weight gain in HF/HIIT than in HF (-120 %). Intramuscular fat accumulation was observed in HF and HF/ HIIT. Peak velocity was higher in HF/HIIT compared to HF (+26 %). Plasma insulin did not change, but glycemia was lower in HF/HIIT than in HF (-30 %). Fndc5 (+418 %) and Irisin (+72 %) were higher in HF/HIIT than in HF. Muscle Fgf21 was higher in HF/HIIT compared to HF (+30 %). In addition, NfKb (-53 %) and Tnfa (-63 %) were lower in HF/HIIT than in HF. However, Il1b (-86 %), Il6 (- 48 %), Il7 (-76 %), and Il15 (-21 %) were lower in HF/HIIT than in HF. Finally, HIIT reduced ER stress in HF/HIIT compared to HF: Atf4, -61 %; Chop, -61 %; Gadd45, -95 %. In conclusion, HIIT leads to weight loss and avoids muscle depletion. HIIT improves blood glucose, Irisin-Fndc5, and peak velocity. In addition, HIIT mitigates muscle inflammation and ER stress.

La obesidad es asociada comúnmente con inflamación tisular crónica y disfunción del músculo esquelético. El estudio tuvo como objetivo investigar los efectos del entrenamiento de intervalos de alta intensidad (HIIT) en las mioquinas y el estrés del retículo endoplásmico (ER) de ratones obesos inducidos por dieta (DIO). Se alimentó a ratones macho C57BL/6 de tres meses de edad con una dieta control (C) (n=20) o una dieta rica en grasas (HF) (n=20) durante 16 semanas. Luego, la mitad de los grupos se sometieron a HIIT (carrera en una trotadora) durante cuatro semanas más. HIIT aumentó la contribución de los músculos de la pantorrilla al BW (+24 %) y redujo el aumento de peso en HF/HIIT en HF (-120 %). Se observó acumulación de grasa intramuscular en HF y HF/HIIT. La velocidad máxima fue mayor en HF/HIIT en comparación con HF (+26 %). La insulina plasmática no cambió, pero la glucemia fue menor en HF/HIIT que en HF (-30 %). Fndc5 (+418 %) e Irisin (+72 %) fueron mayores en HF/HIIT que en HF. El Fgf21 muscular fue mayor en HF/ HIIT en comparación con HF (+30 %). Además, NfKb (-53 %) y Tnfa (-63 %) fueron menores en HF/HIIT que en HF. Sin embar- go, Il1b (-86 %), Il6 (-48 %), Il7 (-76 %) e Il15 (-21 %) fueron más bajos en HF/HIIT que en HF. Finalmente, HIIT redujo el estrés de RE en HF/HIIT en comparación con HF: Atf4, -61 %; Picar, - 61 %; Gadd45, -95 %. En conclusión, HIIT conduce a la pérdida de peso y evita el agotamiento muscular. HIIT mejora la glucosa en sangre, Irisin-Fndc5 y la velocidad máxima. Además, HIIT mitiga la inflamación muscular y el estrés ER.

La inflamación como el nexo entre la enfermedad periodontal y la enfermedad cardiovascular / Inflammation as a link between periodontal disease and cardiovascular disease

La periodontitis es una enfermedad no transmisible, con una alta prevalencia, que oscila entre el 45% y el 50% de la población mundial, ocupando el sexto lugar entre las enfermedades más frecuentes de la huma-nidad. Existe suficiente evidencia que avala la relación entre la enfermedad periodontal y la enfermedad car-diovascular, responsable de aproximadamente el 45% de las muertes en países desarrollados, compren-diendo en su causalidad al infarto de miocardio, el accidente cerebrovascular, la insuficiencia cardíaca y las arritmias, que causan alrededor del 95 % de las muertes relacionadas con la enfermedad cardiovas-cular. Ambas patologías presentan factores de riesgo comunes ampliamente reconocidos, como la diabetes y el tabaquismo, pero además manifiestan caracte-rísticas genéticas y epigenéticas que avalan distintos mecanismos etiopatológicos. Más allá de los factores de riesgo comunes, se han propuesto dos mecanis-mos para explicar la relación entre la enfermedad periodontal y las cardiovasculares. Uno de ellos, constituye la invasión directa de patógenos periodontales en las células endoteliales. El otro mecanismo sugerido (vía indirecta), ocasionado por la respuesta inflamatoria sistémica que resulta en niveles cróni-camente elevados de diferentes citoquinas, también relacionadas con la enfermedad vascular aterosclerotica como IL-1ß, IL-6, IL-8, TNF-α, PCR y la proteína quimioatrayente de monocitos, podría estar mediado por productos bacterianos, como los lipopolisacári-dos que alcanzarían la circulación induciendo una potente respuesta inmunitaria. Estos mecanismos pueden actuar inflamando las células endoteliales, modulando el metabolismo de los lípidos y aumentan-do el estrés oxidativo, favoreciendo la aterosclerosis, conformando la expresión de un fenotipo arterial in-flamatorio, generando el nexo entre la enfermedad periodontal y las patologías cardiovasculares (AU))

Periodontitis is a non-communicable disease which is highly prevalent worldwide. It was reported to range from 45% to 50% around the world and it was the sixth most prevalent condition of humanity. Consistent body of evidence explains the relationship between periodontal disease and other common systemic conditions such as cardiovascular disease. Periodontitis is likely to cause a 45% of deaths in developed countries, including myocardial infarction, stroke, heart failure and arrhythmias that cause about a 95% of deaths related to cardiovascular disease.Both diseases share many risk factors, such as diabetes and smoking; but also, genetic, and epigenetic characteristics support several etiopathological mechanisms. Beyond the common risk factors, two mechanisms have been proposed to elucidate the relationship between the periodontal disease and cardiovascular diseases. One of them supports the concept that periodontal pathogens are capable of the direct invasion of endothelial cells. The other mechanism suggested (indirect pathway), caused by the disease resulting in chronically elevation of CRP, inflammatory cytokines, the monocyte chemoattractant protein, could be mediated by bacterial products, such as lipopolysaccharides, wich induce a potent immune response and can accelerate endothelial dysfunction. These mechanisms may act by inflaming endothelial cells, modulating lipid metabolism and increasing oxidative stress, favoring atherosclerosis, determining the expression of an inflammatory arterial phenotype, generating the link between periodontal disease and cardiovascular pathologies (AU)

Otro desafío de la naturaleza: el nuevo coronavirus virología y fisiopatología del SARS-COV-2 / Another challenge of nature: the new coronavirus virology and physiopathology of SARS-CoV-2

The recent outbreak of emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has been brought to global attention in the search of knowledge about the virus and its pathogenesis. The immune response is essential to control and eliminate the infection, however, maladjusted immune responses may result in severe disease fisiopathology. Gaining a deeper understanding of the interaction between SARS-CoV-2 and the immune systems of the hosts may help us anticipate the development of persistent pulmonary inflammation and, why not, be the first step to therapeutic success and trying to save more lives. In this review, we provide an update on CoV virology and our vision of pathogenesis understanding it from the stages of infection, without forgetting the cytokine storm resulting from the interaction of the virus with ACE2 receptors widely distributed in the body.

La reciente emergencia de síndrome de distrés respiratorio agudo producido por coronavirus 2 (SARS-CoV-2), enfermedad denominada COVID-19 ha traído la atención mundial a la búsqueda de conocimiento sobre este virus y su patogenia. La respuesta inmune es esencial para controlar y erradicar la infección, sin embargo, las respuestas inmunes descontroladas pueden resultar en la fisiopatología de la enfermedad grave. Lograr una comprensión más profunda de la interacción entre SARS-COV-2 y el sistema inmune de los huéspedes podría ayudar a anticiparnos al desarrollo de una inflamación pulmonar persistente causada por el SARS-CoV-2, y por qué no, ser la puerta de entrada al éxito terapéutico e intentar salvar mayor número de vidas. En esta revisión, proporcionamos una actualización sobre la virología y nuestra visión de la patogenia, entendiéndola desde las fases o etapas de la infección, sin olvidar el estallido de citoquinas resultantes de la interacción del virus con los receptores ACE2 ampliamente distribuidos en el organismo.

Preliminary findings on the possible role of B-lymphocyte stimulator (BLyS) on diabetes-related periodontitis

Abstract The possible role of B-cell growth and differentiation-related cytokines on the pathogenesis of diabetes-related periodontitis has not been addressed so far. The aim of this study was to evaluate the effects of diabetes mellitus (DM) on the gene expression of proliferation-inducing ligand (APRIL) and B-lymphocyte stimulator (BLyS), two major cytokines associated to survival, differentiation and maturation of B cells in biopsies from gingival tissue with periodontitis. Gingival biopsies were obtained from subjects with periodontitis (n = 17), with periodontitis and DM (n = 19) as well as from periodontally and systemically healthy controls (n = 10). Gene expressions for APRIL, BLyS, RANKL, OPG, TRAP and DC-STAMP were evaluated using qPCR. The expressions APRIL, BLyS, RANKL, OPG, TRAP and DC-STAMP were all higher in both periodontitis groups when compared to the control group (p < 0.05). Furthermore, the expressions of BLyS, TRAP and RANKL were significantly higher in the subjects with periodontitis and DM when compared to those with periodontitis alone (p < 0.05). The mRNA levels of BLyS correlated positively with RANKL in the subjects with periodontitis and DM (p < 0.05). BLyS is overexpressed in periodontitis tissues of subjects with type 2 DM, suggesting a possible role of this cytokine on the pathogenesis DM-related periodontitis.

Expression of dNK cells and their cytokines in twin pregnancies with preeclampsia

OBJECTIVES: To assess the expression of decidual natural killer (dNK) cells and their cytokines in twin pregnancies with preeclampsia. METHODS: This was a prospective case-control study. The inclusion criteria were diamniotic (monochorionic or dichorionic) twin pregnancies in the third trimester with negative serological results for infectious diseases; absence of major fetal abnormalities or twin-twin transfusion syndrome; and no history of administration of corticosteroids in this pregnancy. The control group (CG) included uncomplicated twin pregnancies, and the preeclampsia group (PEG) included twin gestations with clinical and laboratory confirmation of the disease according to well-established criteria. Samples of the decidua were obtained and analyzed by immunohistochemistry for the expression of dNK cells and interleukins (ILs) 10, 12 and 15. In addition, maternal serum samples were collected to determine the levels of these interleukins. RESULTS: Thirty twin pregnancies were selected: 20 in the control group (CG) and 10 in the preeclampsia group (PEG). The PEG showed strong placental immunostaining for IL-15 (p=0.001) and high maternal serum levels of IL-10 (22.7 vs. 11.9 pg/mL, p=0.024) and IL-15 (15.9 vs. 7.4 pg/mL, p=0.024). CONCLUSION: A higher maternal serum concentration of both pro- and anti-inflammatory factors was observed in the twin pregnancies in the PEG. However, no difference in placental expression of IL-10 was found between the groups. These findings may suggest that maternal attempts to balance these interleukins were not sufficient to cause a placental response, and this failure may contribute to the development of preeclampsia.

The role of visfatin levels in gingival crevicular fluid as a potential biomarker in the relationship between obesity and periodontal disease

Abstract Objectives Visfatin is an adipokine that plays an important role in immune functions as a growth factor, enzyme, and pro-inflammatory mediator. We aimed to determine the levels of visfatin, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in gingival crevicular fluid (GCF) in both obese/non-obese patients, with/without generalized chronic periodontitis (GCP). Methodology Patients were categorized as obese (O) (n=31) or non-obese (nO) (n=19). Groups were divided into four subgroups according to periodontal conditions: (1) periodontally healthy without obesity (nO-Ctrl); (2) GCP without obesity (nO-CP); (3) periodontally healthy with obesity (O-Ctrl); and (4) GCP with obesity (O-CP). Demographic variables, anthropometric and laboratory data were recorded. Periodontal parameters were measured at baseline and 3rd months after either non-surgical periodontal treatment or calorie -restricted diet therapy. At the same time, GCF samples were taken from patients to analyze TNF-alpha, IL-6,and visfatin levels. Results Periodontal parameters were significantly higher in the O group than in the nO group (P<0.05). IL-6 levels were higher in the O group than in the nO group (P<0.001). The visfatin levels of the obese patients were reduceddecreased following the treatments (P<0.05). Cholesterol levels were higher in the O group than in the nO groups (P<0.05). IL-6 levels were higher in O-CP and O-Ctrl groups than in the nO-Ctrl group (P<0.05). Compared to the other groups, visfatin levels were significantly higher in the O-CP group but decreased following treatment (P<0.05). Conclusions Our findings suggest that visfatin and IL-6 levels in GCF are associated with the pathogenesis of obesity and periodontitis. Within the limits of this study, we considered that there might be an association between the lipid profile and periodontitis on systemically healthy individuals.

Etiologic role of root canal infection in apical periodontitis and its relationship with clinical symptomatology

Abstract: Evidence shows the polymicrobial etiology of endodontic infections, in which bacteria and their products are the main agents for the development, progression, and dissemination of apical periodontitis. Microbial factors in necrotic root canals (e.g., endotoxin) may spread into apical tissue, evoking and supporting a chronic inflammatory load. Thus, apical periodontitis is the result of the complex interplay between microbial factors and host defense against invasion of periradicular tissues. This review of the literature aims to discuss the complex network between endodontic infectious content and host immune response in apical periodontitis. A better understanding of the relationship of microbial factors with clinical symptomatology is important to establish appropriate therapeutic procedures for a more predictable outcome of endodontic treatment.

Three-dimensional structure and cytokine distribution of platelet-rich fibrin

OBJECTIVES: Previous reports have revealed that several cytokines (including platelet-derived growth factor-BB, transforming growth factors-β1 and insulin-like growth factor-1) can enhance the rate of bone formation and synthesis of extracellular matrix in orthopaedics or periodontology. This study aimed to determine the concentration of cytokines within platelet-rich fibrin microstructures and investigate whether there are differences in the different portions of platelet-rich fibrin, which has implications for proper clinical use of platelet-rich fibrin gel. METHODS: Whole blood was obtained from six New Zealand rabbits (male, 7 to 39 weeks old, weight 2.7-4 kg); it was then centrifuged for preparation of platelet-rich fibrin gels and harvest of plasma. The resultant platelet-rich fibrin gels were used for cytokine determination, histological analyses and scanning electron microscopy. All plasmas obtained were subject to the same cytokine determination assays for the purpose of comparison. RESULTS: Cytokines platelet-derived growth factor-BB and transforming growth factor-β1 formed concentration gradients from high at the red blood cell end of the platelet-rich fibrin gel (p=1.88×10-5) to low at the plasma end (p=0.19). Insulin-like growth factor-1 concentrations were similar at the red blood cell and plasma ends. The porosities of the platelet-rich fibrin samples taken in sequence from the red blood cell end to the plasma end were 6.5% ± 4.9%, 24.8% ± 7.5%, 30.3% ± 8.5%, 41.4% ± 12.3%, and 40.3% ± 11.7%, respectively, showing a gradual decrease in the compactness of the platelet-rich fibrin network. CONCLUSION: Cytokine concentrations are positively associated with platelet-rich fibrin microstructure and portion in a rabbit model. As platelet-rich fibrin is the main entity currently used in regenerative medicine, assessing cytokine concentration and the most valuable portion of PRF gels is essential and recommended to all physicians.

Omentina: papel en la resistencia a la insulina, inflamación y protección cardiovascular / Omentin: Role in insulin resistance, inflammation and cardiovascular protection

La omentina es una nueva adipocina a la que se le ha atribuido la capacidad de regular actividades metabólicas (sensibilidad a la insulina) y antiinflamatorias, ofreciendo protección cardiovascular en la obesidad y diabetes mellitus tipo 2. Por lo anterior, es importante conocer los mecanismos a través de los cuales confiere protección cardiovascular, con el objetivo de considerar la omentina como blanco o agente terapéutico en este escenario.

The omentin is an adipokine, which role is due to the capacity of regulate metabolic (insulin sensitivity) and anti-inflammatory activities, thus conferring vascular protection during obesity and diabetes mellitus type 2. By this, it is important to know the mechanisms by which omentin confers cardiovascular protection, with the purpose of establish omentin a possible therapeutic target or molecule on this scenario.

Papel das citocinas inflamatórias na nefropatia diabética / Role of inflammatory cytokines in diabetic nephropathy

A nefropatia diabética consiste na principal causa de doença renal terminal e está associada a um risco aumentado de doença cardiovascular. O estudo dos mecanismos responsáveis pelo desenvolvimento da nefropatia diabética possui extrema importância, já que pode contribuir para o desenvolvimento de terapias mais eficazes para a prevenção e o tratamento dessa complicação. Alguns estudos têm demonstrado que os processos inflamatórios devem desempenhar um papel significativo no desenvolvimento e na progressão da nefropatia diabética. Citocinas inflamatórias, como interleucina 1, fator de necrose tumoral alfa e interleucina 6, têm sido associadas com o desenvolvimento e a evolução da disfunção renal em pacientes diabéticos tipos 1 e 2. O reconhecimento das citocinas inflamatórias como fatores patogênicos significativos da nefropatia diabética pode fornecer novos alvos terapêuticos. Neste contexto, o uso de anti-inflamatórios para o tratamento da doença renal no diabetes tem se mostrado estratégia bastante promissora

Diabetic nephropathy is the most important cause of endstage renal disease, and is associated with an increased risk of cardiovascular disease. The study of the mechanisms involved with the development of diabetic nephropathy is extremely relevant, since it can contribute to the development of more effective therapies for the prevention and treatment of this complication. Some studies have demonstrated that the inflammatory processes play a significant role in the development and progression of diabetic nephropathy. Inflammatory cytokines, such as interleukin-1, tumor necrosis factor alpha and interleukin-6, have been associated with the development and evolution of renal dysfunction in type 1 and type 2 diabetic patients. The recognition of inflammatory cytokines as significant pathogenic factors of diabetic nephropathy can provide new therapeutic targets. In this context, the use of antiinflammatories for the treatment of renal disease in diabetes has been shown to be a very promising strategy

El inflamasoma: mecanismos de activación / Inflammasome: activation mechanisms

La inflamación es una respuesta biológica rápida del sistema inmune en tejidos vasculares, dirigida a eliminar estímulos capaces de producir daño y a iniciar la curación y la reparación. Los complejos macromoleculares denominados inflamasomas están constituidos por un receptor NOD (NLR), un receptor de AIM2 (ausente en melanoma 2) el ALR, la proteína tipo punto asociada a apoptosis (ASC) y la procaspasa-1, los cuales pueden ser activados por variación en la concentración iónica y de ATP intracelular y extracelular, por desestabilización del fagolisosoma, por internalización de cristales insolubles y por mecanismos de oxidoreducción, lo cual permitirá la activación de la plataforma molecular y el consiguiente procesamiento de las prointerleuquinas inflamatorias a sus formas activas. En la actualidad existen dos nodos de señalización utilizados por los inflamasomas: canónica y no canónica para generar respuestas efectoras. Datos recientes vinculan al inflamasoma NLRP3, la IL-1b y a la IL-18, en el desarrollo y evolución de enfermedades tales como: ateroesclerosis, diabetes tipo II, hiperhomocisteinemia, gota, malaria e hipertensión arterial e identificaron esta cascada, como un blanco quimioterapéutico ideal para la prevención de estas patologías. En esta revisión se discutirán los mecanismos de activación y regulación del inflamasoma que estimulan, modulan y resuelven los procesos inflamatorios.

Inflammation is a rapid biologic response of the immune system in vascular tissues, directed to eliminate stimuli capable of causing damage and begin the process of repair. The macromolecular complexes known as “inflammasomes” are formed by a receptor, either NOD (NLR) or ALR, the receptor absent in melanoma 2 (AIM2). In addition, the inflammasome is formed by the speck-like protein associated to apoptosis (ASC) and procaspase-1, that may be activated by variations in the ionic and intracellular and extracellular ATP concentrations; and the loss of stabilization of the fagolisosomme by internalization of insoluble crystals and redox mechanisms. As a result, there is activation of the molecular platform and the processing of inflammatory prointerleukins to their active forms. There are two modalities of activation of the inflammasome: canonical and non-canonical, both capable of generating effector responses. Recent data associate NLRP 3, IL-1b and IL-18 in the pathogenesis of a variety of diseases, including atherosclerosis, type II diabetes, hyperhomocysteinemia, gout, malaria and hypertension. The inflammasome cascade is emerging as a new chemotherapeutic target in these diseases. In this review we shall discuss the mechanisms of activation and regulation of the inflammasome that stimulate, modulate and resolve inflammation.

Absenteísmo-doença no serviço público municipal de Goiânia / Sickness absence in a municipal public service of Goiânia, Brazil

INTRODUÇÃO: O absenteísmo-doença, enquanto falta ao trabalho justificada por licença médica, é um importante indicador das condições de saúde dos trabalhadores. Em geral, características sociodemográficas e ocupacionais situam-se entre os principais fatores associados ao absenteísmo-doença. A administração pública é responsável por 21,8% dos empregos formais no Brasil. Esta população permite o estudo de uma grande variedade de categorias profissionais. OBJETIVO: Analisar o perfil e os indicadores de absenteísmo-doença entre servidores municipais de Goiânia, no Estado de Goiás, Brasil. Métodos: Estudo transversal das licenças certificadas para tratamento de saúde superiores a três dias, de todos os servidores, desde janeiro de 2005 a dezembro de 2010. Foram calculadas as prevalências, utilizando como critérios o número de indivíduos, os episódios e os dias de afastamento. RESULTADOS: Foram concedidas 40.578 licenças certificadas para tratamento de saúde a 13.408 servidores numa população média anual de 17.270 pessoas, o que resultou em 944.722 dias de absenteísmo. A prevalência acumulada de licença no período foi de 143,7%, com média anual de 39,2% e duração de 23 dias por episódio. A prevalência acumulada de absenteísmo-doença foi maior entre mulheres (52,0%) com idade superior a 40 anos (55,9%), com companheiro (49,9%), de baixa escolaridade (54,4%), profissionais de educação (54,7%), > 10 anos de serviço (61,9%) e múltiplos vínculos profissionais (53,7%). Os grupos de diagnósticos (CID-10) com as maiores prevalências acumuladas de licenças foram os do capítulo de transtornos mentais (26,5%), doenças osteomusculares (25,1%) e lesões (23,6%). CONCLUSÕES: Os indicadores de absenteísmo-doença expressam a magnitude desse fenômeno no serviço público e podem auxiliar no planejamento das ações de saúde do trabalhador, priorizando os grupos ocupacionais mais vulneráveis. .

BACKGROUND: Sickness absence, as work absenteeism justified by medical certificate, is an important health status indicator of the employees and, overall, sociodemographic and occupational characteristics are among the main factors associated with sickness absence. Public administration accounts for 21.8% of the formal job positions in Brazil. This population allows the study of a wide range of professional categories. OBJECTIVE: To assess the profile and indicators of sickness absence among public workers from the municipality of Goiania, in the State of Goiás, Brazil. METHODS: A cross-sectional study on certified sick leaves, lasting longer than three days, of all civil servants from January 2005 to December 2010. Prevalence rates were calculated using as main criteria the number of individuals, episodes and sick days. RESULTS: 40,578 certified sick leaves were granted for health treatment among 13,408 public workers, in an annual average population of 17,270 people, which resulted in 944,722 days of absenteeism. The cumulative prevalence of sick leave for the period was of 143.7%, with annual average of 39.2% and duration of 23 days per episode. The cumulative prevalence of sickness absence was higher among women (52.0%), older than 40 years old (55.9%), with a partner (49.9%), low schooling (54.4%), education professionals (54.7%), > 10 years of service (61.9%), and with multiple work contracts (53.7%). Diagnoses groups (ICD-10) with higher cumulative prevalence of sick leaves were those with mental disorders (26.5%), musculoskeletal diseases (25.1%), and injuries (23.6%). CONCLUSIONS: Indicators of sickness absence express the magnitude of this phenomenon in the public sector and can assist in planning health actions for the worker, prioritizing the most vulnerable occupational groups. .

Relationship between retinal sensitivity and disease activity in patients with psoriasis vulgaris

OBJECTIVES: Psoriasis is a hyperproliferative chronic inflammatory skin disease of unknown etiology and ocular structures and visual pathways can also be affected during the course of this disease. Subclinical optic neuritis has previously been observed in psoriatic patients in visual evoked potential studies. This trial was designed to evaluate retinal sensitivity in patients with psoriasis vulgaris. METHODS: A total of 40 eyes of 40 patients with chronic plaque-type psoriasis and 40 eyes of 40 age- and sex-matched control subjects were included in this study. The diagnosis of psoriasis was confirmed by skin biopsy. The severity was determined using the Psoriasis Area and Severity Index and the duration of the disease was recorded. After a full ophthalmological examination, including tests for color vision and pupil reactions, the visual field of each subject was assessed using both standard achromatic perimetry and short wavelength automated perimetry. RESULTS: The mean Psoriasis Area and Severity Index was 22.05±6.40′. There were no significant differences in the visual field parameters of subjects versus controls using either method. There were correlations between disease severity and the mean deviations in standard achromatic perimetry and short wavelength automated perimetry and between disease severity and the corrected pattern standard deviation and pattern standard deviation of short wavelength automated perimetry (r = -0.363, r = -0.399, r = 0.515 and r = 0.369, respectively). CONCLUSIONS: Retinal sensitivity appears to be affected by the severity of psoriasis vulgaris. .

Pathophysiology of bacterial infection of the central nervous system and its putative role in the pathogenesis of behavioral changes

Invasion of the central nervous system (CNS) by microorganisms is a severe and frequently fatal event during the course of many infectious diseases. It may lead to deafness, blindness, cerebral palsy, hydrocephalus, cognitive impairment or permanent neurological dysfunction in survivors. Pathogens can cross the blood-brain barrier by transcellular migration, paracellular migration and in infected macrophages. Pathogens may breach the blood-brain barrier and be recognized by antigen-presenting cells through the binding of Toll-like receptors. This induces the activation of nuclear factor kappa B or mitogen-activated protein kinase pathways and subsequently induces leukocyte infiltration and proliferation and the expression of numerous proteins involved in inflammation and the immune response. Many brain cells can produce cytokines, chemokines and other pro-inflammatory molecules in response to bacteria stimuli; as a consequence, polymorphonuclear cells are attracted and activated, and release large amounts of superoxide anion and nitric oxide, leading to peroxynitrite formation and oxidative stress. This cascade leads to lipid peroxidation, mitochondrial damage and blood-brain barrier breakdown, contributing to cellular injury during neuronal infection. Current evidence suggests that bacterial CNS infections can play a role in the etiopathogenesis of behavioral disorders by increasing pro-inflammatory cytokines and bacterial virulence factors. The aim of this review is to summarize the current knowledge of the relevant pathophysiologic steps in CNS infections.

Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications / Leptina: mecanismos moleculares, efeitos pró-inflamatórios sistêmicos e implicações clínicas

Leptin, the adipokine produced mainly by the white adipose tissue, plays important roles not only in the regulation of food intake, but also in controlling immunity and inflammation. It has been widely demonstrated that the absence of leptin leads to immune defects in animal and human models, ultimately increasing mortality. Leptin also regulates inflammation by means of actions on its receptor, that is widely spread across different immune cell populations. The molecular mechanisms by which leptin determines its biological actions have also been recently elucidated, and three intracellular pathways have been implicated in leptin actions: JAK-STAT, PI3K, and ERK 1/2. These pathways are closely regulated by intracellular proteins that decrease leptin biological activity. In this review, we discuss the molecular mechanisms by which leptin regulates immunity and inflammation, and associate those mechanisms with chronic inflammatory disorders. Arq Bras Endocrinol Metab. 2012;56(9):597-607.

A leptina, uma adipocina produzida principalmente pelo tecido adiposo branco, tem um papel importante não somente na regulação da ingestão alimentar, mas também no controle da imunidade e da inflamação. Já foi amplamente demonstrado que a ausência de leptina causa deficiências imunológicas em modelos animais e em humanos, levando ao aumento da mortalidade. A leptina também regula a inflamação por meio da ação em seu receptor, amplamente distribuído em diversos tipos de células do sistema imunológico. Os mecanismos moleculares pelos quais a leptina determina suas ações biológicas foram recentemente elucidados, e três cascatas intracelulares são ativadas pela leptina: JAK-STAT, PI3K e ERK 1/2. Essas cascatas são reguladas por proteínas intracelulares, reduzindo as ações da leptina. Nesta revisão, são discutidos os mecanismos moleculares pelos quais a leptina regula a imunidade e a inflamação, associando-os a enfermidades inflamatórias crônicas. Arq Bras Endocrinol Metab. 2012;56(9):597-607.

Tumor necrosis factor-alpha and the cytokine network in psoriasis / Fator de necrose tumoral-alfa e a rede de citocinas na psoriase

New molecular methods of research have greatly expanded the knowledge about the role of cytokines in several diseases, including psoriasis. The work orchestrated by these peptides is essential for the communication between resident inflammatory cells (keratinocytes and endothelial cells) and infiltrating cells (neutrophils, lymphocytes, Langerhans cells). This is a complex network due to redundancy, synergism and, sometimes, the antagonism of cytokines, which prevents full understanding of the pathogenesis of the disease. Currently, it seems premature to try to establish a main actor, but TNFalpha participates in all stages of psoriatic plaque development, as we shall see.

A introdução de novos métodos moleculares de investigação ampliou muito o conhecimento sobre o papel das citocinas em diversas doenças, entre elas a psoríase. O trabalho orquestrado desses polipeptídeos é fundamental na comunicação entre as células inflamatórias residentes (queratinócitos e células endoteliais) e infiltrantes (neutrófilos, linfócitos, células de Langerhans). Trata-se de uma rede complexa devido à redundância, ao sinergismo e, por vezes, ao antagonismo das citocinas, o que dificulta a compreensão da fisiopatogenia da doença a partir de um mecanismo linear. No momento atual, parece precoce tentar estabelecer um regente, mas o TNF-alfa se destaca em todos os passos do desenvolvimento da placa psoriásica, como veremos a seguir.

Glaucomatous neurodegeneration An eye on tumor necrosis factor-alpha.

Glaucoma, a neurodegenerative disease, is currently being treated by modulation of one of its primary risk factors, the elevated intraocular pressure. Newer therapies that can provide direct neuroprotection to retinal ganglion cells are being extensively investigated. Tumor necrosis factor-α, a cytokine, has been recognized to play an important role in pro and antiapoptotic cellular events. In this paper we review the relevant literature to understand (1) The association of increased expression of tumor necrosis factor-α with glaucomatous neurodegeneraion, (2) Modulation of tumor necrosis factor-α expression by exposure to various risk factors of glaucoma, (3) Downstream cellular signaling mechanisms following interaction of tumor necrosis factor-α with its receptors and (4) Role of tumor necrosis factor-α as a possible target for therapeutic intervention in glaucoma. Literature was reviewed using PubMed search engine with relevant key words and a total of 82 English language papers published from 1990 to 2010 are included in this review.

Inflamação na doença renal crônica: papel de citocinas / Inflammation in chronic kidney disease: the role of cytokines

A doença renal crônica (DRC) é um grave problema de saúde pública cuja prevalência tem aumentado nos últimos anos. Apresenta caráter progressivo e está associada à elevada morbidade e mortalidade. Inúmeros fatores estão associados à instalação e progressão da DRC, tais como obesidade, hipertensão arterial e diabetes mellitus. Além desses fatores, existem evidências de inflamação na fisiopatologia da DRC. Diversas citocinas e quimiocinas têm sido detectadas no plasma e urina de pacientes em estágios precoces da DRC e também relacionadas às complicações da doença. A expressão desses mediadores e a lesão renal sofrem interferência de fármacos como inibidores de enzima conversora de angiotensina (ECA), estatinas e antagonistas de receptores de citocinas. A modulação da resposta imuno-inflamatória pode se tornar alvo para tratamento da DRC. O objetivo deste artigo de revisão foi resumir as evidências científicas do pa-pel da inflamação na DRC, destacando-se os efeitos de citocinas e quimiocinas.

Chronic kidney disease (CKD) is a serious public health problem whose prevalence has increased in the last few years. Its progression is associated with high morbidity and mortality. Several factors are associated with the onset and progression of CKD, such as obesity, hypertension and diabetes mellitus. Beyond these factors, there is evidence of a pathophysiological role for inflammation in CKD. Several cytokines and chemokines have been detected in the plasma and urine of patients at early stages of CKD, and have also been related to CKD complications. The expression of these mediators and renal injury may be influenced by drugs such as angiotensin-converting enzyme inhibitors, statins and antagonists of cytokine receptors. Modulation of the immune-inflammatory response can become a target for CKD treatment. The aim of this study was to review the scientific evidence on the role of inflammation in CKD, especially the effects of cytokines and chemokines.

Inmunología del embarazo / Immunology of pregnancy

Uno de los fenómenos que abre más interrogantes en la Inmunología es ¿Por qué el embrión, comportándose como un injerto semialogénico, no es rechazado por la madre? Se sabe que la madre produce una activa respuesta inmunológica frente al feto y sin embargo, en condiciones normales, el rechazo inmunológico no se produce. En el presente trabajo de revisión, se describen algunos mecanismos por medio de los cuales se genera la tolerancia inmunológica específica de la madre hacia el embrión. Todos estos mecanismos son interdependientes, y en conjunto constituyen una trama para evitar el rechazo fetal. Aquí se detalla la acción de las hormonas sexuales femeninas sobre el sistema inmunológico, el cambio del perfil de citoquinas, la generación de proteínas inmunomoduladoras y de anticuerpos bloqueantes, el efecto de la expresión de los HLA-G y el papel de algunas células inmunocompetentes como los linfocitos T reguladores, las células dendríticas y las células asesinas naturales o Natural Killer. Asimismo se detallan otras vías por las cuales el embrión se defiende del ataque inmunológico materno como la inducción de la apoptosis en el endometrio y en los leucocitos, el metabolismo de hierro y triptofano, la inhibición del sistema del complemento y la expresión de anexinas.

One of the phenomena that offers more questions in Immunology is: Why the embryo, behaving like a semialogenic graft, is not rejected by the mother? It is known that the mother produces an active immunological response against the fetus and, nevertheless, in normal conditions, the immunological rejection does not take place. In the present work of revision, some mechanisms are described by means of which the specific immunological tolerance of the mother is generated towards the embryo. All these mechanisms are interdependent and altogether they constitute a safety network to avoid the fetal rejection. Here the effects of female sex hormones on the immunological system, the change of the profile of cytokines, the generation of immunomodulating proteins and blocking antibodies, the effect of the expression of the HLA-G and the paper of some cells, like Regulatory T lymphocytes, dendritic and Natural Killer cells, are detailed. Also other routes by which the embryo defends itself of the maternal immunological attack are described, like the induction of apoptosis in the endometrium and leukocytes, the tryptophan and iron metabolisms, the inhibition of the complement system and the expression of annexins.

Receptores tipo Toll, patogénesis y respuesta inmune a Helicobacter pylori / Toll-like receptors, pathogenesis and immune response to Helicobacter pylori

Helicobacter pylori coloniza el epitelio gástrico y la mayoría de las personas infectadas es asintomática, de 10 al 20 por ciento desarrolla gastritis atrófica, úlcera péptica, y menos de 3 por ciento genera cáncer gástrico. Estas patologías están determinadas por la relación entre los factores de virulencia de la bacteria y los factores del hospedero como predisposición genética y respuesta inmune. La inmunidad innata, representada principalmente por los receptores tipo Toll y tipo Nod, reconocen a sus ligandos específicos y activan factores de transcripción como NF-kB, AP-1, CREB-1, induciendo la producción de citocinas inflamatorias como IL-8, IL-12, IL-6, IL-1β, IL-18 y TNF-α, e IL-10. La inflamación crónica favorece los cambios de morfología gástrica, evita la apoptosis y favorece la angiogénesis, ocasionando lesiones neoplásicas y cáncer. El objetivo de esta revisión es analizar los mecanismos propuestos a la fecha de la respuesta inmune innata y adaptativa, involucrados en la infección por H. pylori, y se puntualiza en los mecanismos de eliminación o persistencia de la infección.

Helicobacter pylori colonize the gastric epithelial, most infected people are asymptomatic, 10 to 20 percent develop atrophic gastritis, peptic ulcer and less than 3 percent gastric cancer. These diseases are determined by the relationship between virulence factors of bacteria, host factors such as, genetic predisposition, and immune response. The innate immune response mainly represented by Toll-like receptors and Nod-like receptors that recognize their specific ligands, activate transcription factors as NF-kB, AP-1, CREB-1, inducing production of inflammatory cytokines such as IL -8, IL-12, IL-6, IL-1β, IL-18, TNF-α and IL-10. Chronic inflammation promotes gastric morphological changes, prevents apoptosis and allows angiogenesis generating neoplasic lesions and cancer. The aim of this review is to analyze the mechanisms proposed to date of the innate and adaptative immune response involved in H. pylori infection; remarking the mechanisms related in the elimination or persistence.