Naringenin attenuates cerebral ischemia/reperfusion injury by inhibiting oxidative stress and inflammatory response via the activation of SIRT1/FOXO1 signaling pathway in vitro

Purpose: To explore the protection of naringenin against oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cell injury, a cell model of cerebral ischemia/reperfusion (I/R) injury in vitro, focusing on SIRT1/FOXO1 signaling pathway. Methods: Cytotoxicity, apoptosis, reactive oxygen species (ROS) generation, malondialdehyde (MDA) content, 4-hydroxynonenoic acid (4-HNE) level, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were measured by commercial kits. Inflammatory cytokines levels were determined by enzyme-linked immunosorbent assay (ELISA). The protein expressions were monitored by Western blot analysis. Results: Naringenin significantly ameliorated OGD/Rinduced cytotoxicity and apoptosis in HT22 cells. Meanwhile, naringenin promoted SIRT1 and FOXO1 protein expressions in OGD/R-subjected HT22 cells. In addition, naringenin attenuated OGD/R-induced cytotoxicity, apoptosis, oxidative stress (the increased ROS, MDA and 4-HNE levels, and the decreased SOD, GSH-Px and CAT activities) and inflammatory response (the increased tumor necrosis factor-α, interleukin [IL]-1ß, and IL-6 levels and the decreased IL-10 level), which were blocked by the inhibition of the SIRT1/FOXO1 signaling pathway induced by SIRT1-siRNA transfection. Conclusion: Naringenin protected HT22 cells against OGD/R injury depending on its antioxidant and anti-inflammatory activities via promoting the SIRT1/FOXO1 signaling pathway.

Caracterización clínica y epidemiológica de los pacientes con hepatitis alcohólica en el Hospital Regional de Talca: estudio retrospectivo de 5 años (2017-2022) / Clinical and epidemiological characterisation of patients with alcoholic hepatitis in the Regional Hospital of Talca - 5-year retrospective study (2017-2022)

Alcoholic Hepatitis (HA) represent to one of the pathological entities in the context of liver damage associated with excessive and prolonged alcohol consumption. Despite its high mortality, making the early diagnosis is still a challenge for physicians. The local information of this pathology is limited, so this work consists of conducting a retrospective study on the clinical and epidemiological characteristics of patients diagnosed with HA at the Regional Hospital of Talca (HRT); in order to make available to the treating doctors, the greatest amount of data contributing to decision-making for the benefit of patients. Methods: The clinical records of all patients discharged from the HRT with a diagnosis of HA during the period between January 2017 and August 2022 were reviewed. Background information such as: chief complaint, main symptoms, comorbidities, laboratory tests, treatment, evolution and survival, etc., was collected for analysis and to obtain the conclusions presented. Results: A total of 16 patients were studied; 93.75 % were male and 6.24 % female; with a mean age of 52. Of the patients, 87.5 % had a history of DHC. All had alcohol abuse for more than 5 years and 93.75% had active alcoholism. The most frequent laboratory findings included hyperbilirubinaemia (93.75 %), GOT/GPT ratio >2 (50 %) and leukocytosis (56.25 %). Of the total patients studied, 68.75% had a survival of more than 1 year after the event, while 12.5% died during hospitalisation.

Características del SARS-CoV-2, COVID-19 y su diagnóstico en el laboratorio / Characteristics of SARS-CoV-2, COVID-19, and laboratory diagnosis

La enfermedad COVID­19 es causada por el virus SARS-CoV-2, descrito por primera vez en diciembre del 2019 en Wuhan, China, y declarada en marzo del 2020 como una pandemia mundial. Actualmente existen diversos métodos diagnósticos para COVID-19, siendo el estándar de oro la detección del material genético mediante la reacción en cadena de la polimerasa (PCR), en su variante, la RT-PCR, que detecta el material genético de tipo ARN presente en el virus. Sin embargo, es necesario disponer de pruebas rápidas con alta sensibilidad y precisión para realizarlas a gran escala y brindar un diagnóstico oportuno. Adicionalmente, se debe disponer de otras herramientas que, si bien no van a establecer un diagnóstico, le van a permitir al profesional brindar un mejor manejo clínico y epidemiológico que ayuden a predecir el agravamiento del paciente y su posible ingreso a UCI, destacando entre estas los niveles de dímero D, linfocitos, ferritina, urea y creatinina, entre otras. En esta revisión se evalúa la utilidad y limitaciones de los diferentes métodos diagnósticos para COVID-19, al igual que las características, fisiopatología y respuesta inmune al SARS-CoV-2, así como algunos aspectos preanalíticos de importancia que ayudan a minimizar errores en el diagnóstico como consecuencia de procedimientos incorrectos en la toma, transporte y conservación de la muestra, y que permiten al profesional emitir resultados veraces y confiables. Lo anterior se realizó basado en artículos originales, revisiones y guías clínicas

COVID­19 is caused by the SARS-CoV-2 virus, first described in December 2019 in Wuhan, China, and declared a global pandemic in March 2020. Currently there are various diagnostic methods for COVID-19, the gold standard is the detection of genetic material through polymerase chain reaction (PCR) in its variant, RT-PCR, which detects RNA-type genetic material present in the virus. However, it is necessary to have rapid tests with high sensitivity and precision to be performed on a large scale and provide timely diagnosis. Furthermore, other tools must be available, and although they will not establish the diagnosis, will allow the professional to provide better clinical and epidemiological management that will help predict the worsening of the patient and possible admission to the ICU. Among these, levels of D-dimer, lymphocytes, ferritin, urea and creatinine. In this review, the usefulness and limitations of the different diagnostic methods for COVID-19 are evaluated, as well as the characteristics, pathophysiology and immune response to SARS-CoV-2, and some important preanalytical aspects that allow minimizing diagnostic errors as a consequence of incorrect procedures in the collection, transport and conservation of the sample, that allow the professional to yield accurate and reliable results. This article was completed based on original articles, reviews and clinical guidelines

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)

Cytotoxicity and inflammatory mediators release by macrophages exposed to real seal xt and sealapex xpress

Abstract This study evaluated the cytotoxicity of Sealapex Xpress and Real Seal XT and their effect on macrophage activation. J774.1 macrophages were incubated with Sealapex Xpress and Seal Real XT (0.1, 1.0, and 10 mg/mL) for 24 and 48 h. Cell viability was assessed by the MTT assay and macrophage activation was measured by pro- and anti-inflammatory cytokine production using ELISA. Data were analyzed using one-way ANOVA and Tukey's post-test (a=0.05). Cell viability was not affected with 0.1 or 1.0 mg/mL of extracts of Sealapex Xpress and Real Seal XT at 24 and 48 h (p>0.05), but was significantly lower when cells were exposed to 10 mg/mL of both sealers (p<0.05). Sealapex Xpress inhibited the production of TNF-a, whereas Real Seal XT induced TNF-a secretion at 24 h (p<0.05). IL-6 production was induced by Real Seal XT, but not by Sealapex Xpress (p<0.05). Real Seal XT and Sealapex Xpress induced the secretion of anti-inflammatory IL-10. IL-4 was not detected in any group. In conclusion, both sealers had low toxicity but differentially activated macrophages. Macrophage activation by Sealapex Xpress was characterized by inhibition of TNF-a and induction of IL-10, whereas Real Seal XT induced IL-6 solely.

Resumo O objetivo deste estudo foi avaliar in vitro a citotoxicidade dos cimentos endodônticos Sealapex Xpress e Real Seal XT pelo ensaio de MTT e a ativação de macrófagos J774.1. Os cimentos endodônticos Sealapex Xpress e Real Seal XT foram pesados e os extratos foram obtidos a partir da diluição em meio de cultura DMEM por 48 horas (10mg/mL, 1mg/m, e 0,1 mg/mL). A viabilidade celular foi avaliada pelo ensaio MTT e a produção de citocinas (TNF-a, IL-6 e IL-10) foi investigada pelo ensaio imunoenzimático (ELISA) em células de linhagem (macrofagos J774.1). Os dados obtidos foram analisados utilizando-se análise de variância de uma via e pós-teste de Tukey (a=0,05). A viabilidade celular após 24 ou 48 horas não foi afetada nas concentrações de 0,1 ou 1 mg/mL dos dois cimentos estudados (p>0,05). Por outro lado, na concentração 10 mg/mL, a viabilidade celular foi significativamente mais baixa (p <0,05). Observou-se que o Sealapex Xpress inibiu a produção de TNF-a, enquanto o Real Seal XT induziu a secreção de TNF-a às 24 h (p<0,05). A produção de IL-6 foi induzida pelo Real Seal XT, mas não pelo Sealapex Xpress (p<0,05). A secreção da citocina anti-inflamatória IL-10 foi induzida tanto pelo Real Seal XT quanto pelo Sealapex Xpress. IL-4 não foi detectada em nenhum grupo. Em conclusão, os dois cimentos obturadores apresentaram baixa toxicidade, mas ativaram os macrófagos de modo distinto. A ativação pelo Sealapex Xpress foi caracterizada pela inibição do TNF-a e indução da IL-10, enquanto o Real Seal XT induziu somente IL-6.

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)

A standardized extract of Centella asiatica (ECa 233) prevents temporomandibular joint osteoarthritis by modulating the expression of local inflammatory mediators in mice

Abstract Objectives To investigate the effect of a standardized extract of Centella asiatica (ECa 233), which has anti-inflammatory properties, on the local expression of the transient receptor potential vanilloid 1 (TRPV1), the acid-sensing ion channel subunit 3 (ASIC3), and the calcitonin gene-related peptide (CGRP) in the temporomandibular joint (TMJ) structure 21 days after injecting the TMJ with complete Freund's adjuvant (CFA). Methodology A mouse model was induced by analyzing the CFA-injected TMJ on days 7, 14, and 21. We assessed TMJ histology by the osteoarthritis cartilage grade score. Then, we observed the effect of different ECa 233 concentrations (30, 100, and 300 mg/kg) and of 140 mg/kg ibuprofen doses on TRPV1, ASIC3, and CGRP local expression on day 21. Results Osteoarthritis cartilage scores were 1.17±0.37 and 3.83±0.68 on days 14 and 21, respectively, in the CFA group (n=5). On day 21, TRPV1, ASIC3, and CGRP expression significantly increased in the CFA group. In the ibuprofen-treated group, TRPV1 expression significantly decreased, but ASIC3 and CGRP showed no significant difference. All ECa 233 doses reduced TRPV1 expression, but the 100 mg/kg ECa 233 dose significantly decreased ASIC3 expression. Conclusions TRPV1, ASIC3, and CGRP expression increased in mice with TMJ-OA on day 21. All ECa 233 and ibuprofen doses inhibited pathogenesis by modulating the local expression of TRPV1 and ASIC3. Therefore, ECa 233 was more effective than ibuprofen.

Análise clínico-patológica e qualitativa da expressão de mediadores inflamatórios teciduais no líquen plano oral / Clinicopathological and qualitative analysis of the expression of tissue inflammatory mediators in oral lichen planus

O líquen plano oral (LPO) é uma condição imuno-inflamatória mucocutânea crônica que ainda possui etiologia e patogênese desconhecidas. Estudos mostrando a participação de citocinas no LPO, em especial, interleucinas (IL)-6, IL-17 e IL-18, são escassos, assim como a correlação das características clínicas e histológicas das lesões de LPO com a presença destes mediadores inflamatórios. Todas as lesões de LPO e de lesões liquenoides orais (LLO) foram revisadas a partir do arquivo do laboratório de Patologia Bucal da Faculdade de Odontologia da Universidade do Estado do Rio de Janeiro e as características clínico-patológicas dos casos foram analisadas. Foram selecionados 40 casos de LPO para realização adicional de reações imuno-histoquímicas para IL-6, IL-17 e IL-18. A amostra total foi composta por 221 casos e mostrou que o LPO apresentou predileção por mulheres adultas, mais frequentemente acometidas pelo padrão reticular e com lesões localizadas predominantemente na mucosa jugal. Os 40 casos selecionados para a avaliação imuno-histoquímica incluíram pacientes com média de idade de 53 anos, sem predileção por gênero, e com lesões localizadas preferencialmente na mucosa jugal (85%), na gengiva/mucosa alveolar (47%) e na língua (42%). Quanto ao padrão clínico, 14 pacientes (35%) mostravam lesões exclusivamente reticulares e 26 (65%) mostravam lesões reticulares associadas a lesões atrófico-erosivas. Sintomas foram relatados por 53% dos pacientes e incluíram principalmente ardência e desconforto local. A análise histológica mostrou que o epitélio das lesões mostrava espessura normal, atrófica ou hiperplásica em, respectivamente, 17 (43%), 9 (22%) e 14 (35%) casos. A presença de hiperqueratose foi observada em 21 casos (53%) e exocitose de linfócitos T CD4+ e T CD8+ estava presente em, respectivamente, 17 (42%) e 30 (75%) casos. A análise imuno-histoquímica revelou que a IL-6 foi, de forma geral, a mais expressa, tanto no epitélio, quanto no conjuntivo. A expressão de IL-17 se mostrou intensa no tecido conjuntivo, em 40% dos casos. A IL-18 mostrou intensidade mais frequente leve/moderada tanto no epitélio (40%), quanto no tecido conjuntivo (45%). A presença de exocitose mostrou relação com a maior expressão das ILs e a expressão de IL-17 foi maior no epitélio mostrando hiperqueratose. Os resultados do presente estudo mostraram que as características clínicas das lesões de LPO e de LLO são distintas e podem ser utilizadas para diferenciação entre as duas entidades. Os achados histológicos e imunohistoquímicos sugerem que as ILs estudadas mostram-se mais presentes quando há exocitose linfócitos T CD4+ e T CD8+ e que sua expressão pode ter relação com as alterações epiteliais encontradas no LPO, participando da patogênese e da modulação da expressão da doença.

Oral lichen planus (OLP) is a chronic immunoinflammatory mucocutaneous condition of unknown etiology and pathogenesis. Studies focusing on the presence of cytokines in OLP, especially interleukin (IL)-6, IL-17 and IL-18, are scarce, as well as the correlation of clinical and histological characteristics with the presence of inflammatory mediators. All lesions diagnosed as OLP and oral lichenoid lesions (OLL) were reviewed from the files of the Oral Pathology laboratory, Dental School, Rio de Janeiro State University, and their clinicopathological characteristics were analyzed. Forty cases diagnosed as OLP were selected for additional immunohistochemical reactions directed against IL-6, IL-17 e IL-18. The total sample was composed by 221 cases and showed that OLP presented a predilection for adult females, mostly affected by lesions with the reticular pattern and located in the buccal mucosa. The 40 cases selected for the immunohistochemical reactions included patients with a mean age of 53 years, with no gender predilection, and with lesions located mostly in the buccal mucosa (85%), gingiva/alveolar mucosa (47%) and tongue (42%). The clinical pattern showed reticular lesions in 14 patients (35%) and reticular and atrophic/erosive lesions in 26 patients (65%). Symptoms were reported by 53% of the patients and included mostly burning sensation and local discomfort. Histological analysis showed that the epithelial thickness was normal, atrophic, or hyperplastic in, respectively, 17 (43%), 9 (22%) and 14 (35%) cases. The presence of hyperkeratosis was observed in 21 cases (53%), and exocytosis of T CD4+ and T CD8+ lymphocytes was present in, respectively, 17 (42%) and 30 (75%) cases. Immunohistochemical analysis showed that, in general, IL-6 was the most expressed IL both in epithelium and connective tissue. IL-17 expression was considered intense in the connective tissue from 40% of the cases. IL-18 expression was considered mostly mild/moderate both in epithelium (40% of the cases) and connective tissue (45% of the cases). The presence of exocytosis was associated with a higher expression of the ILs and expression of IL-17 was higher in epithelium showing hyperkeratosis. The results from the present study showed that the clinical characteristics of OLP and OLL are distinct and can be useful in differentiating these two diagnostic entities. The histological and immunohistochemical features suggest that the studied ILs are more expressed when there is exocytosis of both T CD4+ and T CD8+ lymphocytes. Expression of the ILs can be associated with the epithelial alterations encountered in OLP, participating in the pathogenesis and modulating the expression of the disease.

Asociación entre los niveles séricos de vitamina D y marcadores inflamatorios en pacientes en hemodiálisis / Association between vitamin D serum levels and inflammatory markers in patients on hemodialysis

Resumen Introducción: La relación entre 25-OH-vitamina D y el sistema inmune en pacientes con enfermedad renal crónica es objeto de atención. Objetivos: Evaluar la prevalencia de la deficiencia de vitamina D en pacientes en hemodiálisis e investigar la asociación entre la vitamina D y proteína C reactiva ultrasensible (PCRus), índice neutrófilo/linfocito (INL) e índice plaqueta/linfocito (IPL). Método: Estudio transversal de 80 pacientes en hemodiálisis, divididos en dos grupos: un nivel sérico de 25-OH-vitamina D < 20 ng/mL se consideró como deficiencia de vitamina D y ≥ 20 ng/mL, como normal. Con el análisis de correlación de Spearman se definió la relación entre los parámetros. Resultados: 40 % de los pacientes presentó deficiencia de vitamina D. Hubo diferencias significativas entre los grupos en PCRus (p = 0.047), INL (p = 0.039), IPL (p = 0.042) y tratamiento con análogos de vitamina D (p = 0.022). La vitamina D tuvo una correlación negativa significativa con PCRus (p = 0.026), INL (p = 0.013) e IPL (p = 0.022). Conclusiones: La deficiencia de vitamina D fue de 40 %. Los niveles de PCRus, INL e IPL fueron significativamente más altos ante deficiencia de vitamina D. Se encontró correlación inversa significativa entre vitamina D y PCRus, INL e IPL.

Abstract Introduction: The relationship between 25-OH-vitamin D and the immune system in patients with chronic kidney disease is a subject of attention. Objectives: To assess the prevalence of vitamin D deficiency in patients on hemodialysis and to investigate the association between vitamin D, ultra-sensitive C-reactive protein (US-CRP), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Method: Cross-sectional study of 80 patients on hemodialysis, divided into two groups: a serum 25-OH-vitamin D level < 20 ng/mL was considered to be vitamin D deficiency and a serum level ≥ 20 ng/mL was regarded as normal. The relationship between the parameters was defined with Spearman’s correlation analysis. Results: 40 % of the patients had vitamin D deficiency. There were significant differences between groups in US-CRP (p = 0.047), NLR (p = 0.039), PLR (p = 0.042) and treatment with vitamin D analogues (p = 0.022). Vitamin D had a significant negative correlation with US-CRP (p = 0.026), NLR (p = 0.013) and PLR (p = 0.022). Conclusions: The prevalence of vitamin D deficiency was 40 %. The values of US-CRP, NLR and PLR were significantly higher in the presence of vitamin D deficiency. A significant inverse correlation was found between vitamin D levels and US-CRP, NLR and PLR.

Induction of selective liver hypothermia prevents significant ischemia/reperfusion injury in Wistar rats after 24 hours

Purpose To investigate the effects of induction of selective liver hypothermia in a rodent model. Methods Seven male Wistar rats were subjected to 90 minutes of partial 70% liver ischemia and topic liver 26°C hypothermia (H group). Other seven male Wistar rats were subjected to 90 minutes of partial 70% normothermic liver ischemia (N group). Five additional rats underwent a midline incision and section of liver ligaments under normothermic conditions and without any liver ischemia (sham group). All animals were sacrificed 24-h after reperfusion, and livers were sampled for analyses. Pathology sections were scored for sinusoidal congestion, ballooning, hepatocelllular necrosis and the presence of neutrophilic infiltrates. Results At the end of the experiment, liver tissue expressions of TNF-ɑ, IL-1β, iNOS and TNF-ɑ/IL-10 ratio were significantly reduced in the H group compared to N group, whereas IL-10 and eNOS were significantly increased in H group. Histopathological injury scores revealed a significant decrease in ischemia/reperfusion (I/R) injuries in H group. Conclusion Selective liver hypothermia prevented I/R injury by inhibiting the release of inflammatory cytokines, preserves microcirculation, prevents hepatocellular necrosis and leukocyte infiltration, allowing maintenance of the liver architecture.

Involvement of HSP90 in ischemic postconditioning-induced cardioprotection by inhibition of the complement system, JNK and inflammation

Abstract Purpose To investigate whether heat shock protein 90 (HSP90) is involved in complement regulation in ischemic postconditioning (IPC). Methods The left coronary artery of rats underwent 30 min of occlusion, followed by 120 min of reperfusion and treatment with IPC via 3 cycles of 30s reperfusion and 30s occlusion. The rats were injected intraperitoneally with 1 mg/kg HSP90 inhibitor geldanamycin (GA) after anesthesia. Eighty rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R), IPC and IPC + GA. Myocardial infarct size, apoptosis index and the expression of HSP90, C3, C5a, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1β and c-Jun N-terminal kinase (JNK) were assessed. Results Compared with the I/R injury, the IPC treatment significantly reduced infarct size, release of troponin T, creatine kinase-MB, and lactate dehydrogenase, and cardiomyocyte apoptosis. These beneficial effects were accompanied by a decrease in TNF-α, IL-1β, C3, C5a and JNK expression levels. However, all these effects were abrogated by administration of the HSP90 inhibitor GA. Conclusion HSP90 exerts a profound effect on IPC cardioprotection, and may be linked to the inhibition of the complement system and JNK, ultimately attenuating I/R-induced myocardial injury and apoptosis.

Association of measures of central fat accumulation indices with body fat distribution and metabolic, hormonal, and inflammatory parameters in women with polycystic ovary syndrome

ABSTRACT Objective To investigate the associations among visceral adiposity index (VAI), lipid accumulation product (LAP), body fat percentage (%), and android/gynoid ratio (A/G ratio) in women with polycystic ovary syndrome (PCOS) and verify if the parameters representative of visceral obesity correlate with and exhibit the same frequency as body composition variables; anthropometric indices; and metabolic, hormonal, and inflammatory parameters. Subjects and methods This was a cross-sectional study that included 94 women with PCOS. Hormonal, metabolic, and inflammatory parameters were analyzed in all women. Free androgen index (FAI) and homeostasis model assessment (HOMA-IR), as well as LAP, VAI, and anthropometric indices, were calculated. The regions of interest (ROIs) in body composition and body composition indices were evaluated using a dual X-ray absorptiometry (DXA). Overall, 32 variables were selected as markers of body fat distribution. Results Among the 32 markers evaluated, 29 correlated with LAP, whereas 25 correlated with VAI, 19 with body fat (%), and 30 with A/G ratio. Additionally, some markers correlated with the four adiposity indices evaluated: ROIs, except for total mass and leg fat (%); body composition (body mass index, waist circumference, and hip circumference) indices; fasting insulin; and C-reactive protein. Conclusion LAP and VAI may be sensitive measures for screening and preventing metabolic syndrome and insulin resistance in PCOS, with LAP being more sensitive than VAI, and the A/G ratio may be more sensitive than body fat percentage.

Niveles Plasmáticos de Citoquinas Proinflamatorias en Cáncer de Próstata / Serum levels of proinflammatory cytokines in prostate cancer

INTRODUCTION: Prostate cancer has become an important public health problem affecting millions of men worldwide every year. Like other malignant tumors, prostate cancer shows evidence of a strong inflammatory component that is dependent on the release of pro-inflammatory cytokines, which might play a major role in the development and progression of the tumor, helping in its early stage, progression and aggressiveness. AIMS: The goal of this study was to determine the relationships between the serum levels of pro-inflammatory cytokines and the different stages of prostate cancer. To this end, sera from patients enrolled by The Laboratory of Metabolic Diseases and Cancer of the Faculty of Pharmacy and Biochemistry at the University Juan Agustín Maza in Argentina, were analyzed through ELISA and their pro-inflammatory cytokines (IL-6, TNF-α and MCP-1) quantified. Patients were first classified into three groups (Control, at Risk, and Cancer subjects) and anthropometric, biochemical and histological parameters of prostate were then determined for all groups. RESULTS AND CONCLUSIONS: Despite displaying elevated serum concentrations of IL-6 and TNF-α in the Cancer and the Risk groups compared to the Control group, the differences did not reach significance. However, there was a positive correlation between these cytokines only in the Risk and Cancer groups, showing a general inflammatory behavior in these patients. The results obtained provide general data about the behavior of pro-inflammatory cytokines in prostate cancer. However, they do not demonstrate a direct correlation between serum levels and neoplastic progression. Nevertheless, these findings do not rule out a possible relationship between prostate cancer and serum levels of pro-inflammatory cytokines.

Intravitreal neurodegenerative and inflammatory mediators in proliferative diabetic retinopathy / Mediadores intravítreos da neurodegeneração e inflamação na retinopatia diabética proliferativa

ABSTRACT Purpose: To compare the intravitreal concentrations of cellular mediators involved in neurodegeneration, inflammation, and angiogenesis in patients with proliferative diabetic retinopathy and other vitreoretinal diseases. Methods: A multiplex bead immunoassay was used to measure vitreous levels of pigment epithelium-derived factor, serum amyloid P, C-reactive protein, complement C4, alpha-1 antitrypsin, vascular endothelial growth factor, platelet-derived growth factor-AA, platelet-derived growth factor-BB, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor alpha and beta in patients undergoing 23-gauge vitrectomy for proliferative diabetic retinopathy and other diagnoses (control group). Results: We evaluated 55 patients, of whom 24 had proliferative diabetic retinopathy and 31 had other diagnoses including vitreous hemorrhage, retinal detachment, macular hole, and epiretinal membrane. Patients with proliferative diabetic retinopathy demonstrated increased levels of serum amyloid P (85.49 vs. 31.38 ng/mL); C-reactive protein (59.89 vs. 41.75 ng/mL), vascular endothelial growth factor (2,330.11 vs. 554.25 pg/mL; p<0.001), platelet-derived growth factor A (127.32 vs. 39.11 pg/mL), platelet-derived growth factor B (29.37 vs. 7.12 pg/mL), interleukin-6 (69.37 vs. 33.58 pg/mL), interleukin-8 (175.25 vs. 59.71 pg/mL), and interleukin-10 (3.70 vs. 1.88 pg/mL); all p<0.004 when compared with the control group. Levels of pigment epithelium-derived factor (30.06 vs. 27.48 ng/mL; p=0.295), complement C4 (570.78 vs. 366.24 ng/mL; p=0.069), and alpha-1-antitrypsin (359.27 vs. 522.44 ng/mL; p=0.264) were not significantly different between the groups. Intravitreal levels of tumor necrosis factor-alpha and tumor necrosis factor-beta were undetectable. Serum Amyloid P, C-reactive protein, platelet-derived growth factor A, platelet-derived growth factor B, interleukin-6, and interleukin-8 were correlated positively with vascular endothelial growth factor. Conclusions: Cellular mediators involved in neurodegeneration and inflammation demonstrated increased levels in the vitreous humor of patients with proliferative diabetic retinopathy and may be part of the pathogenesis of diabetic retinopathy.

RESUMO Objetivo: Comparar as concentrações intravítreas de mediadores celulares envolvidos na neurodegeneração, inflamação e angiogênese em pacientes com retinopatia diabética proliferativa e outras doenças vítreo-retinianas. Métodos: Um ensaio imunomagnético foi utilizado para medir os níveis vítreos do fator derivado do epitélio pigmentar, amilóide P sérico, proteína-C-reativa, complemento C4, e alfa-1-antitripsina, fator de crescimento do endotélio vascular, fator de crescimento derivado das plaquetas AA, fator de crescimento derivado das plaquetas BB, interleucina-6, interleucina-8, interleucina-10, fator de necrose tumoral alfa e beta em pacientes submetidos à vitrectomia 23-gauge para retinopatia diabética proliferativa ou outros diagnósticos (grupo controle). Resultados: Foram avaliados 55 pacientes, dos quais 24 tinham retinopatia diabética proliferativa e 31 tinham outros diagnósticos, incluindo hemorragia vítrea, descolamento de retina, buraco macular e membrana epirretiniana. Pacientes com retinopatia diabética proliferativa demonstraram níveis aumentados de amilóide P sérico (85,49 vs 31,38 ng/mL), proteína-C-reativa (59,89 vs 41,75 ng/mL), fator de crescimento do endotélio vascular (2.330,11 vs 554,25 pg/mL, p<0.001), fator de crescimento derivado das plaquetas-A: (127,32 vs 39,11 pg/mL), fator de crescimento derivado das plaquetas-B (29,37 vs 7,12 pg/mL), interleucina-6 (69,37 vs 33,58 pg/mL), interleucina-8 (175,25 vs 59,71 pg/mL) e interleucina-10 (3,70 vs 1,88 pg/mL), todos com p<0,004 quando comparados ao grupo controle. Níveis de fator derivado do epitélio pigmentar (30,06 vs 27,48 ng/mL; p=0,295), complemento C4 (570,78 vs 366,24 ng/mL; p=0,069), alfa-1 antitripsina (359,27 vs 522,44 ng/mL; p=0,264) não foram significativamente diferente entre os grupos. Níveis intravítreos de fator de necrose tumoral alfa e fator de necrose tumoral beta foram indetectáveis. O amilóide P sérico, a proteína C-reativa, o fator de crescimento derivado das plaquetas A e B, a interleucina-6 e a interleucina-8 correlacionaram-se positivamente com o fator de crescimento do endotélio vascular. Conclusões: Os medidores celulares envolvidos na neurodegeneração e inflamação demonstraram níveis aumentados no humor vítreo de pacientes com retinopatia diabética proliferativa e podem ser parte da patogênese da retinopatia diabética.

Hematologic parameters and neutrophil / lymphocyte ratio in the prediction of urethroplasty success

ABSTRACT Objective: The pathophysiology of urethral stricture and its recurrence remains vague and one of the important causes is progressive inflammation. It has been shown in recent years that the neutrophil / lymphocyte ratio is a marker of systemic inflammation and is associated with prognosis in many cardiovascular diseases, malignancies and chronic inflammatory diseases. We assessed simple systemic inflammation markers preoperatively and surgical techniques for urethral stricture recurrence after urethroplasty. Patients and Methods: After exclusion criteria applied, a total of 117 male cases operated with urethroplasty in our clinic between January 2012 and June 2017 were included in the study and analyzed retrospectively. Localization and length of the strictures of the patients, neutrophil counts and percentages, lymphocyte counts and percentages, and neutrophil / lymphocyte ratios in preoperative peripheral blood samples were statistically analyzed. Recurrent stricture during first 12 months follow-up after the surgery has been assessed as recurrence. Results: The mean age of the patients was 54.12 ± 16.35 and the mean urethral stricture length was 3.44 ± 1.83 cm. Recurrence was observed in 30.1% of cases who received buccal graft, 30% in penile skin applied cases and 26.1% of cases treated with end-to-end anastomosis and there was no statistically significant difference between neutrophil, lymphocyte, neutrophil / lymphocyte ratio and average stricture segment length between recurrent and non-recurrent cases (p > 0.005). Conclusions: We consider that neutrophil, lymphocyte counts and their ratio prior to urethroplasty and the technique performed are not parameters that can be used to predict stricture recurrence. Prospective and randomized new trials with larger patient populations are needed to make more accurate judgments about the role of these inflammatory parameters.

Efeitos clínicos e imunológicos de ácidos graxos poli-insaturados de ômega-3 e aspirina em baixa dosagem como adjuvantes ao debridamento periodontal em pacientes com diabetes tipo 2: estudo clínico randomizado / Clinical and immunological effects of omega-3 polyunsaturated fatty acids and low-dose aspirin as adjuncts to periodontal debridement in patients with type 2 diabetes: randomized clinical trial

A suplementação diária com ácidos graxos poli-insaturados de ômega-3 (ω-3) e a aspirina em baixa dosagem foram propostas como terapia de modulação do hospedeiro para o tratamento de doenças inflamatórias crônicas. O objetivo deste estudo foi investigar as ações clínicas e imunológicas do ω-3 e da aspirina (AAS) como terapia adjunta ao debridamento periodontal de boca toda para o tratamento da periodontite em pacientes com diabetes tipo 2. Setenta e cinco pacientes (n=25/grupo) que atendiam aos critérios de inclusão foram randomicamente designados para receber placebo e debridamento periodontal (GC), ω-3 (3g de óleo de peixe/dia por 60 dias) e AAS (100mg/dia por 60 dias) após o debridamento periodontal (GT1), e (3g de óleo de peixe/dia por 60 dias) e AAS (100mg/dia por 60 dias) antes do debridamento periodontal (GT2). Parâmetros clínicos periodontais e fluido gengival crevicular (FGC) foram coletados no baseline (t0), 90 dias (GT1 e GC) (t1), após a suplementação/medicação com ω-3 e AAS (t1), e 180 dias após o debridamento periodontal (todos os grupos) (t2). Dez pacientes (40%) no GT1 e nove pacientes (36%) no GT2 alcançaram o endpoint clínico para o tratamento (≤4 bolsas periodontais com profundidade de sondagem (PS)≥ 5mm), em contraste com quatro (16%) no GC. Houve ganho de inserção em bolsas moderadas e em bolsas profundas entre t0 e t2 para o GT1. Os níveis de concentração de IFN-γ, IL-1ß e IL-8 apresentaram redução em t2 para os dois grupos teste, com mudanças significantes prévias (t1) para o GT1. Os níveis de IL-6 apresentaram redução em t1 e em t2 para o GT1, e a MIP-1α reduziu em t2 no GT2. No GC a IL-1ß foi a única citocina a apresentar diferença estatisticamente significante na comparação entre tempos. Os resultados deste estudo clínico sugerem que a terapia adjuvante de ω-3 a AAS após o debridamento periodontal promove maiores benefícios clínicos e imunológicos ao tratamento da periodontite em pacientes com diabetes tipo 2 quando comparado aos demais protocolos avaliados(AU)

Daily dietary supplementation with omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) and low-dose aspirin (ASA) have been proposed as a host modulation therapy for the treatment of chronic inflammatory diseases. The aim of this study was to investigate the clinical and immunological actions of ω-3 PUFAs and ASA as an adjunct therapy to full-mouth periodontal debridement for the treatment of periodontitis in patients with type 2 diabetes. Seventy-five patients (n=25/group) meeting the inclusion criteria were randomly assigned to receive placebo and periodontal debridement (CG), ω-3 (3g of fish oil/day for 60 days) and ASA (100mg/day for 60 days) after periodontal debridement (TG1), and ω-3 (3g of fish oil/day for 60 days) and ASA (100mg/day for 60 days) before periodontal debridement (TG2). Periodontal clinical parameters and gingival crevicular fluid (GCF) were collected at baseline (t0), 90 days (TG1 and CG) (t1), after ω-3 and ASA only (TG2) (t1), and 180 days after periodontal debridement (all groups) (t2). Ten patients (40%) in TG1 and nine patients (36%) in TG2 achieved the clinical endpoint for treatment (≤4 periodontal pockets with probing depth (PD)≥ 5mm), as opposed to four (16%) in CG. There was clinical attachment gain in moderate and deep pockets between t0 and t2 for TG1. Concentration levels of IFN-γ, IL-1ß, and IL-8 decreased over time for both test groups, with early (t1) significant changes for TG1. IL-6 levels were lower at t1 and t2 for TG1, and MIP-1α decreased at t2 for TG2. In the CG, IL1ß was the only marker presenting statistically significant changes over time. The results of this clinical study suggest that the adjunctive use of ω-3 and ASA after periodontal debridement provides clinical and immunological benefits to the treatment of periodontitis in patients with type 2 diabetes when compared to the other treatment protocols evaluated(AU)