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)

Mucina y Enfermedad Periodontal / Mucin and periodontal disease

La enfermedad periodontal (EP) es una patología que afecta principalmente los tejidos que rodean a la pieza dentaria (PD) y se caracteriza, en la mayoría de los casos, por una exposición bacteriana que favorece una respuesta destructiva e inflamatoria del huésped, que conduce a la pérdida de inserción periodontal de la PD, provocando una marcada reabsorción ósea y la posible pérdida de las PD. El diagnóstico de EP implica evaluaciones clínicas y radiográficas, en la actualidad se están realizando diversas investigaciones para evaluar posibles compuestos en los fluidos orales a través de lo cual puede ser posible evaluar la presencia y gravedad de estas enfermedades, como así también el riesgo en los pacientes. Hay evidencias de la interacción de macromoléculas salivales, como las mucinas, con microorganismos específicos. De esta manera las mucinas, junto con otros productos de la saliva, ayudan a modular tanto el número como el tipo de proliferación de ciertos organismos y provocar la disminución de otros. La revisión de la literatura actual concluye que las mucinas salivales pueden servir como un parámetro bioquímico de la inflamación del periodonto (AU)

Periodontal disease (PD) is a pathology that mainly affects the tissues surrounding the tooth (PD) and is characterized, in most cases, by a bacterial exposure that favors a destructive and inflammatory response of the host, which leads to the loss of periodontal insertion of the PD, causing a marked bone resorption and the possible loss of the PD. The diagnosis of PD involves clinical and radiographic evaluations, at present several investigations are being carried out to evaluate possible compounds in oral fluids through which it may be possible to evaluate the presence and severity of these diseases, as well as the risk in patients. There is evidence of the interaction of salivary macromolecules, such as mucins, with specific microorganisms. In this way, mucins, together with other saliva products, help modulate both the number and type of proliferation of certain organisms and cause the decrease of others. The review of the current literature concludes that salivary mucins can serve as a biochemical parameter of inflammation of the periodontium (AU)

Periodontitis y Alzheimer: posibles mecanismos de vinculación: revisión de la literatura / Periodontitis and Alzheimer: possible linking mechanisms: a review of the literature

La periodontitis es una enfermedad inflamatoria, crónica que afecta a los tejidos de soporte de los dientes y puede repercutir en la salud general, afectando la calidad de vida del paciente. La enfermedad de Alzheimer es una condición neurodegenerativa y progresiva que va disminuyendo la memoria, el lenguaje y aprendizaje de los pacientes. El objetivo de la investigación es realizar una revisión bibliográfica para comprender la posible vinculación entre la periodontitis y el Alzheimer. Los microorganismos periodontopatógenos producen una respuesta inflamatoria que, por vía sistémica, puede desencadenar un mecanismo inflamatorio dentro del sistema nervioso central. La respuesta del hospedero es liberar gran cantidad de moléculas proinflamatorias que comprometen la barrera hematoencefálica sobreestimulando a las células microgliales, esto conduce a la destrucción de neuronas vitales y al mantenimiento de la inflamación crónica que contribuye a la progresión del Alzheimer. Por otra parte, la periodontitis puede favorecer la formación de placas ateromatosas que afectan la integridad vascular siendo éste un factor a considerar en el desarrollo de la patología cerebrovascular. A pesar que son pocos los estudios clínicos experimentales, ya se puede sugerir la correlación entre ambas enfermedades (AU)

Periodontitis is a chronic inflammatory disease that affects the supporting tissues of teeth, affecting the systemic health and quality of life of the patient. Alzheimer's disease is a neurodegenerative and progressive condition that decreases memory, speech and learning of patients. The objective of this literature review was to report the possible link between periodontitis and Alzheimer's disease. Periodontopathogens produce an inflammatory response that, systemically, can trigger an inflammatory mechanism within the central nervous system. Due to this attack, the host releases a great quantity of proinflammatory molecules that compromise the blood-brain barrier by over- stimulation microglial cells, this produces destruction of vital neurons and maintenance the chronic inflammation in CNS and that contribute to the progression of Alzheimer's disease. On the other hand, periodontitis can favor the formation of atheromatous plaques that affect vascular integrity, being a factor to consider in the development of the cerebrovascular disease. Although there are few experimental clinical studies, the correlation between both diseases can already be suggested (AU)

Effect of Cold Water Immersion Performed on Successive Days on Physical Performance, Muscle Damage, and Inflammatory, Hormonal, and Oxidative Stress Markers in Volleyball Players.

de Freitas, VH, Ramos, SP, Bara-Filho, MG, Freitas, DGS, Coimbra, DR, Cecchini, R, Guarnier, FA, and Nakamura, FY. Effect of cold water immersion performed on successive days on physical performance, muscle damage, and inflammatory, hormonal, and oxidative stress markers in volleyball players. J Strength Cond Res 33(2): 502-513, 2019-The aim of this study was to investigate the effects of daily cold water immersion (CWI) on physical performance, muscle damage, and inflammatory, hormonal, and oxidative stress markers in volleyball. Six players were submitted to CWI and six players to a placebo, during 5 training days. Thigh circumference, squat jump, and agility were measured on the first, third, and sixth days. On the first and sixth days, blood and saliva were collected for analysis of oxidative stress, muscle damage, and inflammatory and hormonal levels. Muscle soreness and countermovement jump were quantified daily. The physical performance comparisons did not present differences and the only between group comparison with a large effect size (ES = -1.39) was in Δ% between day 1 and day 2 for countermovement jump. Delayed onset muscle soreness and creatine kinase increased in both groups and the ESs of between group comparisons of Δ% between moments were not more than moderate. Thigh circumference increased only in the placebo group (p = 0.04) and the ES of the between group comparisons of Δ% between moments was large (1.53). No differences were found in oxidative stress, or inflammatory markers. Cortisol decreased only in the CWI-group (p ≤ 0.05) and the ESs of the between group comparisons of Δ% between moments of the testosterone to cortisol ratio (-1.94) and insulin-like growth-1 (-1.34) were large. Despite the positive effects of daily CWI on muscle edema and hormonal status, the limited effects of CWI on performance, muscle damage, inflammation markers, and reactive oxygen species mediators signal the unimportance of the daily practice of this recovery method in volleyball players.

[Mediators of inflammatory response in asthma and its association with obesity]. / Mediadores de la respuesta inflamatoria en asma y su relación con obesidad.

There is an increase in the prevalence of asthma and obesity, constituting a public health problem at national and global levels. The association between the two pathologies has not been clearly determined; however, a certain synergy has been proposed, which leads to more severe bronchospasms, longer recovery time, and more prolonged use of medications in obese asthmatic patients. The discovery of leptin, an adipokine that is directly related to the amount of total body fat and the production of proinflammatory cytokines, has generated greater interest in white adipose tissue. Our objective was to describe the possible mechanisms involved and the association between obesity and asthma. A bibliographic search was conducted in the scientific literature using the National Biotechnology Information Center (NCBI) database of the USA as a search tool; keywords used were: asthma, leptin, obesity and inflammation. There are numerous clinical and experimental studies that explore the role of obesity as an inflammatory entity in asthma, some of which have evaluated the role of "shared" genetic polymorphisms in both pathologies. Apparently, the interaction between asthma and obesity is complex, there are mechanisms that link both pathologies, these can influence the improvement or exacerbation of symptoms.

El incremento en la prevalencia de asma y obesidad constituye un problema de salud pública en los ámbitos nacional y mundial. Se ha propuesto una sinergia entre estas patologías que genera broncoespasmos más severos, mayor tiempo de recuperación y uso de medicamentos por un lapso más prolongado en los pacientes asmáticos con obesidad. El descubrimiento de la leptina, relacionada directamente con la cantidad de grasa corporal total y la producción de citocinas proinflamatorias ha generado mayor interés en el tejido adiposo blanco. El objetivo de esta investigación fue describir la asociación entre obesidad, asma y los mecanismos fisiopatológicos involucrados. Se realizó una búsqueda bibliográfica en la literatura científica empleando el Centro Nacional de Información sobre Biotecnología (NCBI) de Estados Unidos como herramienta de búsqueda; las palabras claves utilizadas fueron asma, leptina, obesidad e inflamación. Numerosos estudios clínicos y experimentales exploran la participación de la obesidad como una entidad inflamatoria en el asma; algunos han evaluado el papel de polimorfismos genéticos "compartidos" por ambas patologías. Al parecer, existen mecanismos comunes a ambas patologías que pueden influir en la exacerbación de los síntomas del asma en pacientes con obesidad.

Blood-Brain Barrier Disruption Induced by Chronic Sleep Loss: Low-Grade Inflammation May Be the Link.

Sleep is a vital phenomenon related to immunomodulation at the central and peripheral level. Sleep deficient in duration and/or quality is a common problem in the modern society and is considered a risk factor to develop neurodegenerative diseases. Sleep loss in rodents induces blood-brain barrier disruption and the underlying mechanism is still unknown. Several reports indicate that sleep loss induces a systemic low-grade inflammation characterized by the release of several molecules, such as cytokines, chemokines, and acute-phase proteins; all of them may promote changes in cellular components of the blood-brain barrier, particularly on brain endothelial cells. In the present review we discuss the role of inflammatory mediators that increase during sleep loss and their association with general disturbances in peripheral endothelium and epithelium and how those inflammatory mediators may alter the blood-brain barrier. Finally, this manuscript proposes a hypothetical mechanism by which sleep loss may induce blood-brain barrier disruption, emphasizing the regulatory effect of inflammatory molecules on tight junction proteins.

Acute Respiratory Distress Syndrome: Role of Oleic Acid-Triggered Lung Injury and Inflammation.

Lung injury especially acute respiratory distress syndrome (ARDS) can be triggered by diverse stimuli, including fatty acids and microbes. ARDS affects thousands of people worldwide each year, presenting high mortality rate and having an economic impact. One of the hallmarks of lung injury is edema formation with alveoli flooding. Animal models are used to study lung injury. Oleic acid-induced lung injury is a widely used model resembling the human disease. The oleic acid has been linked to metabolic and inflammatory diseases; here we focus on lung injury. Firstly, we briefly discuss ARDS and secondly we address the mechanisms by which oleic acid triggers lung injury and inflammation.

Resistance to P. brasiliensis Experimental Infection of Inbred Mice Is Associated with an Efficient Neutrophil Mobilization and Activation by Mediators of Inflammation.

Paracoccidioidomycosis (PCM) is a systemic fungal infection, endemic in Brazil, that leads to severe morbidity and even mortality if not correctly treated. Patients may respond differently to PCM depending on the pattern of the acquired immune response developed. The onset of protective immune response is notably mediated by neutrophils (PMN) that play an important role through directly killing the fungi and also by interacting with other cell types to modulate the acquired protective immune response that may follow. In that way, this study aimed to present and compare different experimental models of PCM (intraperitoneal and subcutaneous) regarding PMN production and maturation inside femoral bone marrow and also PMN infiltration in peritoneal and subcutaneous exudates of resistant and susceptible mice. We also assessed the fungal colony forming units and the levels of soluble inflammatory mediators (LTB4, KC, IFN-γ, GM-CSF, and IL-10) inside subcutaneous air-pouches to compare the efficiency of the PMN present at this site in relation to the two main neutrophil functions: initial lysis of the invading pathogen and modulation of the acquired immune response. P. brasiliensis inoculated intraperitoneally was able to disseminate to the bone marrow of susceptible mice, causing a more marked alteration of PMN production and maturation than that observed after resistant mice infection by the same route. Subcutaneous air-pouch inoculation of P. brasiliensis elicited a controlled and limited infection that produced a PMN-rich exudate, thus favoring the study of the interaction between the fungus and the neutrophils. Susceptible mice produced higher numbers of PMN; however, these cells were less effective in killing the fungi. Inflammatory cytokines were more pronounced in resistant mice, which supports their PCM raised resistance.

Chronic granulomatous disease: why an inflammatory disease?

Chronic granulomatous disease is a primary immunodeficiency caused by mutations in the genes encoding subunits of the phagocytic NADPH oxidase system. Patients can present with severe, recurrent infections and noninfectious conditions. Among the latter, inflammatory manifestations are predominant, especially granulomas and colitis. In this article, we systematically review the possible mechanisms of hyperinflammation in this rare primary immunodeficiency condition and their correlations with clinical aspects.

Chronic granulomatous disease: why an inflammatory disease?

Chronic granulomatous disease is a primary immunodeficiency caused by mutations in the genes encoding subunits of the phagocytic NADPH oxidase system. Patients can present with severe, recurrent infections and noninfectious conditions. Among the latter, inflammatory manifestations are predominant, especially granulomas and colitis. In this article, we systematically review the possible mechanisms of hyperinflammation in this rare primary immunodeficiency condition and their correlations with clinical aspects.

Neuroimmunomodulation in depression: a review of inflammatory cytokines involved in this process.

Depression is a debilitating mental disease that affects a large number of people globally; however the pathophysiological mechanisms of this disease remain incompletely understood. Some studies have shown that depression is associated with inflammatory activity, and the mode of action of several antidepressants appears to involve immunomodulation. In this case, the induction of a pro-inflammatory state in healthy or depressive subjects induces a 'sickness behaviour' resembling depressive symptomatology. Potential mechanisms of pro-inflammatory cytokines are effects on monoamine levels, disruption of the hypothalamic-pituitary-adrenal axis, activation of the pathological microglial cells, such as the macrophages and alterations in neuroplasticity and brain functions. Thus, this review will highlight the role of inflammation in depression, the possible mechanisms involved, and also explore effective treatments that act on the immune system.

Novel aspects of glucocorticoid actions.

Normal hypothalamic-pituitary-adrenal (HPA) axis activity leading to the rhythmic and episodic release of adrenal glucocorticoids (GCs) is essential for body homeostasis and survival during stress. Acting through specific intracellular receptors in the brain and periphery, GCs regulate behaviour, as well as metabolic, cardiovascular, immune and neuroendocrine activities. By contrast to chronic elevated levels, circadian and acute stress-induced increases in GCs are necessary for hippocampal neuronal survival and memory acquisition and consolidation, as a result of the inhibition of apoptosis, the facilitation of glutamatergic neurotransmission and the formation of excitatory synapses, and the induction of immediate early genes and dendritic spine formation. In addition to metabolic actions leading to increased energy availability, GCs have profound effects on feeding behaviour, mainly via the modulation of orexigenic and anorixegenic neuropeptides. Evidence is also emerging that, in addition to the recognised immune suppressive actions of GCs by counteracting adrenergic pro-inflammatory actions, circadian elevations have priming effects in the immune system, potentiating acute defensive responses. In addition, negative-feedback by GCs involves multiple mechanisms leading to limited HPA axis activation and prevention of the deleterious effects of excessive GC production. Adequate GC secretion to meet body demands is tightly regulated by a complex neural circuitry controlling hypothalamic corticotrophin-releasing hormone (CRH) and vasopressin secretion, which are the main regulators of pituitary adrenocorticotrophic hormone (ACTH). Rapid feedback mechanisms, likely involving nongenomic actions of GCs, mediate the immediate inhibition of hypothalamic CRH and ACTH secretion, whereas intermediate and delayed mechanisms mediated by genomic actions involve the modulation of limbic circuitry and peripheral metabolic messengers. Consistent with their key adaptive roles, HPA axis components are evolutionarily conserved, being present in the earliest vertebrates. An understanding of these basic mechanisms may lead to novel approaches for the development of diagnostic and therapeutic tools for disorders related to stress and alterations of GC secretion.

Optical neuritis induced by different concentrations of myelin oligodendrocyte glycoprotein presents different profiles of the inflammatory process.

Optical neuritis (ON) is characterized by inflammation of the optic nerve, and is one of the first clinical signs of multiple sclerosis (MS). Experimental autoimmune encephalomyelitis (EAE) is the animal model used to study MS and ON. The present study evaluated the induction, development and progression of ON using an EAE model induced by 100 µg or 300 µg of MOG35-55. An EAE model was induced in C57BL/6 mice by tail base injection of 100 µg or 300 µg of MOG35-55 in complete Freund's adjuvant, supplemented with Mycobacterium tuberculosis. On the day of injection and 48 h later, animals received intraperitoneally 300 ng of pertussis toxin. On days 7, 10, 14, 21 and 58 the optic nerve was dissected for histological analysis, production of CCL5 and immunohistochemical detection of CD4 and CD8. The histological changes observed in the optic nerves consisted of inflammatory cell infiltrates showing varying degrees of ON in the two groups. The onset of ON in the 300 µg of MOG35-55 group was coincident with higher production of CCL5, on day 10 after induction. However, the 100 µg MOG35-55 group showed more intense inflammatory infiltrate on day 14 after induction, with higher amounts of CD4 and CD8, reaching an excessive demyelination process on days 21 and 58 after induction. The results suggest that two different concentrations of MOG35-55 lead to different forms of evolution of optic neuritis.

NF-κB activation mediates crystal translocation and interstitial inflammation in adenine overload nephropathy.

Adenine overload promotes intratubular crystal precipitation and interstitial nephritis. We showed recently that these abnormalities are strongly attenuated in mice knockout for Toll-like receptors-2, -4, MyD88, ASC, or caspase-1. We now investigated whether NF-κB activation also plays a pathogenic role in this model. Adult male Munich-Wistar rats were distributed among three groups: C (n = 17), receiving standard chow; ADE (n = 17), given adenine in the chow at 0.7% for 1 wk and 0.5% for 2 wk; and ADE + pyrrolidine dithiocarbamate (PDTC; n = 14), receiving adenine as above and the NF-κB inhibitor PDTC (120 mg·kg⁻¹·day⁻¹ in the drinking water). After 3 wk, widespread crystal deposition was seen in tubular lumina and in the renal interstitium, along with granuloma formation, collagen accumulation, intense tubulointerstitial proliferation, and increased interstitial expression of inflammatory mediators. Part of the crystals were segregated from tubular lumina by a newly formed cell layer and, at more advanced stages, appeared to be extruded to the interstitium. p65 nuclear translocation and IKK-α increased abundance indicated activation of the NF-κB system. PDTC treatment prevented p65 migration and normalized IKK-α, limited crystal shift to the interstitium, and strongly attenuated interstitial fibrosis/inflammation. These findings indicate that the complex inflammatory phenomena associated with this model depend, at least in part, on NF-κB activation, and suggest that the NF-κB system may become a therapeutic target in the treatment of chronic kidney disease.

Nutrition and sickle cell disease.

A common observation in sickle cell disease is growth retardation, in particular, wasting. Wasting is associated with increased hospitalization and possibly poorer clinical outcomes. Therefore understanding the mechanism of wasting is crucial and reducing the degree of wasting by improving the nutritional status, holds the potential for modifying the course of the disease.

La enfermedad periodontal asociada al paciente con síndrome de Down / Periodontal disease associated to the Down´s syndrome patient

El síndrome de Down es una de las condiciones de discapacidad más comunes. Dentro de las patologías bucales más prevalentes, la enfermedad periodontal es una de las asociadas con este síndrome. Se cxonsidera que la persona con síndrome de Down presenta una mayor susceptibilidad a contraer esta enfermedad. En este artículo se describen los factores etiológicos y las características clínicas de la enfermedad en este paciente.(AU)

La enfermedad periodontal asociada al paciente con síndrome de Down / Periodontal disease associated to the Down´s syndrome patient

El síndrome de Down es una de las condiciones de discapacidad más comunes. Dentro de las patologías bucales más prevalentes, la enfermedad periodontal es una de las asociadas con este síndrome. Se cxonsidera que la persona con síndrome de Down presenta una mayor susceptibilidad a contraer esta enfermedad. En este artículo se describen los factores etiológicos y las características clínicas de la enfermedad en este paciente.

Inflammatory mediators in epilepsy.

All common contributing factors to epilepsy such as trauma, malignancies and infections are accompanied by different levels of central nervous system inflammation that in turn have been associated with the occurrence of seizure. Emerging data from human brain tissue and experimental models of epilepsy support the proposed involvement of inflammation in epilepsy. Key mediators of this process include, among others: interleukin (IL) -1ß, IL-6, tumor necrosis factor-α, adhesion molecules and component of complement. Recent advances suggest the involvement of specific inflammatory pathways in the pathogenesis of seizures in patients with pharmacoresistant temporal lobe epilepsy, highlighting the potential for new therapeutic strategies. This review provides an overview of the current knowledge on the relationship between inflammatory mediators and epilepsy. We also describe experimental and clinical evidence of inflammation in epilepsy with special emphasis on clinical aspects once the epileptogenic focus has been resected. Further insight into the complex role of inflammation in epileptogenesis may provide new treatment options.