Potential Comparison of Anti-inflammatory Activities of Quercetin and Diclofenac Mouthwash Formulations

Introduction: Periodontitis is a pandemic, with about 14% of people worldwide already suffering from severe periodontitis. Early intervention in the disease could probably reduce its progression and eliminate the need for the extraction of affected teeth. Quercetin is a probable candidate as it has exemplary anti-inflammatory properties. The presence of phenolic hydroxyl groups in them greatly contributes to their antioxidant and anti-inflammatory activities. Objectives: The study introduces the formulation of Quercetin mouthwash and assesses its anti-inflammatory properties in comparison to Diclofenac sodium. Methods: Quercetin mouthwash was prepared using a commercially procured bioactive agent. One standard nonsteroidal anti-inflammatory drug, Diclofenac was used as a reference drug. The percentage inhibition of protein denaturation was calculated and its anti-inflammatory properties were evaluated through Bovine Serum Albumin Assay and Egg Albumin Assay. Results: Quercetin mouthwash showed parallel anti-inflammatory properties and showed a proportionate increase in anti-inflammatory properties with the increase in the concentration of the mouthwash. Comparable inhibition of protein denaturation at 10µl and 50µl concentrations with a proportionate variation of 1% (p>0.05) to the control in Egg Albumin Assay and 47% and 83% denaturation at 10µl and 50µl of Bovine Serum Albumin Assay were observed. Conclusion: Quercetin mouthwash has shown significant anti-inflammatory activity and hence is considered a potent anti-inflammatory agent comparable to Diclofenac sodium. It is found to be a suitable agent as an oral formulation for reducing the progression of inflammatory conditions.

Introducción: La periodontitis es una pandemia, ya que alrededor del 14 % de las personas en todo el mundo padecen periodontitis grave. Una intervención precoz en la enfermedad podría, probablemente, reducir su progresión y eliminar la necesidad de extraer los dientes afectados. La quercetina es un candidato probable, ya que tiene propiedades antiinflamatorias ejemplares. Su presencia de grupos hidroxilos fenólicos contribuye en gran medida a sus actividades antioxidantes y antiinflamatorias. Objetivos: El estudio presenta la formulación del colutorio de quercetina y evalúa sus propiedades antiinflamatorias en comparación con el diclofenaco sódico. Métodos: Se preparó un colutorio de quercetina, utilizando un agente bioactivo obtenido comercialmente. Se utilizó como fármaco de referencia un antiinflamatorio no esteroideo estándar, el diclofenaco. Se calculó el porcentaje de inhibición de la desnaturalización de proteínas y se evaluaron sus propiedades antiinflamatorias mediante ensayo con albúmina de suero bovino y con albúmina de huevo. Resultados: El colutorio de quercetina mostró propiedades antiinflamatorias paralelas y mostró un aumento proporcional de las propiedades antiinflamatorias con el aumento de la concentración del colutorio. Se observó una inhibición comparable de la desnaturalización de proteínas a concentraciones de 10µl y 50µl con una variación proporcional del 1 % (p > 0,05), respecto al control en el ensayo de albúmina de huevo y una desnaturalización del 47 % y 83 % a 10µl y 50µl del ensayo de albúmina de suero bovino. Conclusiones: El enjuague bucal de quercetina ha mostrado una actividad antiinflamatoria significativa, por lo que se considera un potente agente antiinflamatorio comparable al diclofenaco sódico. Se considera un agente adecuado como formulación oral para reducir la progresión de las afecciones inflamatorias.

Aplicação de ácido hialurônico e corticoide através de uma punção guiada por ultrassonografia no tratamento de disfunção da articulação temporomandibular: relato de caso / Hyaluronic and corticoid application through an ultrasound-guided puncture in the treatment of temporomandibular joint dysfunctions: case report / Aplicación de ácido hialurónico y corticoide a través de una punción guiada por ecografía en el tratamiento de la disfunción de la articulación temporomandibular: informe de un caso

Introdução: As Disfunções temporomandibulares (DTM) incluem desordens dos músculos da mastigação, das articulações temporomandibulares e da inervação local, frequentemente associadas a dor orofacial e que resultam em mioartropatias do Sistema Mastigatório. A tendência atual tende a começar com tratamento conservador e progredir a procedimentos mais invasivos na falha dos tratamentos iniciais. Relato de caso: O presente relato visa mostrar o resultado de uma técnica invasiva para o tratamento de uma DTM grave, com a aplicação do ácido hialurônico e de corticoide através de uma punção guiado por ultrassonografia. A paciente apresentava dor crônica e perda importante de peso devido a limitação da abertura da boca. A RM demonstrou disfunção das ATMs, com sinais de deslocamento parcial do disco direito anteromedialmente. Foi realizada a aplicação bilateral intra-articular de ácido hialurônico e de corticoide através de uma punção guiado por ultrassonografia. Considerações Finais: A associação destas classes na punção de ATMs ainda não está bem estabelecida havendo necessidade de estudos complementares para avaliar eficácia, como este relato de caso, que se mostrou favorável com grande melhora clínica da paciente... (AU)

Introduction: Temporomandibular dysfunctions (TMD) include disorders of the masticatory muscles, temporomandibular joints, and local innervation, often associated with orofacial pain and resulting in myoarthropathies of the masticatory system. The current trend tends to begin with conservative treatment and progress to more invasive procedures if the initial treatments fail. Case Report: The present report aims to show the result of an invasive technique for the treatment of a severe TMD, with the application of hyaluronic acid and corticoid through an ultrasound-guided puncture. The patient presented with chronic pain and significant weight loss due to limited mouth opening. MRI demonstrated TMJ dysfunction, with signs of partial anteromedial dislocation of the right disc. Bilateral intra-articular application of hyaluronic acid and corticoid was performed through an ultrasound guided puncture. Final considerations: The association of these classes in TMJ puncture is still not well established, and further studies are needed to evaluate efficacy, as in this case report, which proved favorable, with great clinical improvement for the patient... (AU)

Introducción: Los trastornos temporomandibulares (TTM) incluyen trastornos de los músculos masticatorios, de las articulaciones temporomandibulares y de la inervación local, a menudo asociados a dolor orofacial y que dan lugar a mioartropatías del sistema masticatorio. La tendencia actual es comenzar con un tratamiento conservador y progresar hacia procedimientos más invasivos al fracasar los tratamientos iniciales. Informe de un caso: El presente informe pretende mostrar el resultado de una técnica invasiva para el tratamiento de un TTM severo, con la aplicación de ácido hialurónico y corticoide a través de una punción guiada por ecografía. El paciente presentaba dolor crónico y una importante pérdida de peso debido a la limitación de la apertura bucal. La RMN demostró una disfunción de la ATM, con signos de dislocación parcial del disco derecho anteromedialmente. Se realizó la aplicación intraarticular bilateral de ácido hialurónico y corticoide mediante una punción guiada por ecografía. Consideraciones finales: La asociación de estas clases en la punción de la ATM aún no está bien establecida y se necesitan más estudios para evaluar la eficacia, como en el reporte de este caso, que resultó favorable con gran mejoría clínica del paciente... (AU)

Role of cystatin C levels as an inflammatory marker in predicting endometriosis

SUMMARY OBJECTIVE: Endometriosis is a common chronic inflammatory disease associated with infertility and pelvic pain. Diagnosis is based on the appearance of endometriotic lesions at the time of surgery. Our study aimed to determine whether cystatin C can be used as a predictor of endometriosis and to investigate its potential role in doing so. METHODS: The study included 45 patients with endometriosis between the ages of 18 and 40 years whose pathology results were compatible with endometriosis and were operated on, and a control group of 45 healthy women. These two groups were compared in terms of serum cystatin C levels, demographic-clinical characteristics, operation results, and other laboratory values. RESULTS: The cystatin C and hs-CRP levels of the endometriosis patients were found to be significantly higher than the control subjects (p<0.005). Whether the endometriosis disease could be detected for serum cystatin C levels was determined by the receiver operating characteristic analysis and the most appropriate positive cutoff value for cystatin C was found to be 5.14 ng/mL (86.7% sensitivity and 77.8% specificity). In the linear regression analysis, it was observed that the probability of endometriosis increased 2.5 times when cystatin C levels increased above the threshold value of 5.14 ng/mL (OR: 2.5; 95%CI 2.24-2.76). CONCLUSION: Our study shows that the serum cystatin C levels can be used as a guide for diagnosis in patients with advanced endometriosis. However, more research is needed to prove its reliability and accuracy in order to put it into practice.

Anti-inflammatory treatment after selective laser trabeculoplasty: a systematic review of the literature and meta-analysis of randomized control trials / Tratamento anti-inflamatório após trabeculoplastia seletiva a laser: revisão sistemática da literatura e meta-análise de ensaios clínicos randomizados controlados

ABSTRACT We assessed the effects of anti-inflammatory treatment after selective laser trabeculoplasty through a systematic search of the MEDLINE, COCHRANE, and ClinicalTrials.gov. The outcome measures were intraocular pressure, anterior chamber inflammation, and discomfort. Evidence synthesis was performed using fixed effects or random-effects model according to the heterogeneity of the included studies. Heterogeneity was assessed using Q-statistic and I2. For an overall estimate of continuous outcomes, the mean differences and their 95% confidence intervals were applied, while odds ratios and their 95% confidence intervals were applied for dichotomous outcomes. Six studies were included in all. No significant difference was noted in the patients for intraocular pressure and discomfort when treated with anti-inflammatory drops. However, the patients showed benefit from reduced anterior chamber inflammation in the first postoperative week [FE OR=0.43, 95% CI=(0.19, 0.95), PQ=0.97, I2=0%], with no significant difference between the outcomes of non-steroidal anti-inflammatory drugs and steroids [FE OR=0.75, 95% CI=(0.20, 2.82), PQ=0.37, I2=0%]. Anti-inflammatory drops reduce anterior chamber inflammation after selective laser trabeculoplasty but showed no effect on the intraocular pressure.

RESUMO O objetivo deste estudo é avaliar os efeitos do tratamento anti-inflamatório após a trabeculoplastia seletiva a laser. Uma busca sistemática foi feita no MEDLINE, COCHRANE e ClinicalTrials.gov. As medidas de resultado foram pressão intraocular, inflamação da câmara anterior e desconforto. A síntese de evidência foi realizada utilizando-se modelo de efeitos fixos ou efeitos aleatórios, de acordo com a heterogeneidade dos estudos incluídos. A heterogeneidade foi avaliada utilizando-se Q-statistic e I². Para uma estimativa global dos resultados contínuos, foram usadas diferenças médias e seus intervalos de confiança de 95% enquanto para resultados dicótomos, usou-se odds ratios e seus intervalos de confiança de 95%. Seis estudos foram incluídos. Nenhuma diferença significativa foi encontrada em pacientes tratados com gotas anti-inflamatórias em termos de pressão intraocular e desconforto. No entanto, eles se beneficiaram da redução da inflamação da câmara anterior na primeira semana pós-operatória [FE OR=0,43, IC 95% = (0,19, 0,95), PQ=0,97, I2=0%], sem diferença significativa entre anti-inflamatórios não esteroidais e esteroidais [FE OR=0,75, IC 95% = (0,20, 2,82), PQ=0,37, I2=0%]. Gotas anti-inflamatórias reduzem a inflamação da câmara anterior após trabeculoplastia seletiva a laser, não afetando a pressão intraocular.

Anti-inflammatory effects of cannabinoids / Efeitos anti-inflamatórios dos canabinoides

ABSTRACT BACKGROUND AND OBJECTIVES: The use of cannabinoids for epileptic syndrome and control of side effects associated with chemotherapy is already widespread and supported by several well-controlled clinical trials. However, the use of these drugs in inflammatory pathologies is sometimes underestimated due to lack of scientific knowledge with a high degree of evidence, non-recognition of the endocannabinoid system as an active participant in these diseases, as well as fear of the stereotype surrounding the use of cannabis derivatives. The purpose of this study was to examine the anti-inflammatory and antioxidant effects of endogenous and exogenous cannabinoids on various physiological systems in which these ligands interact. CONTENTS: Studies cited in this review were obtained by searching Pubmed, Medline, Google Scholar, Scielo, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, and through the authors' familiarity with the published literature in this area of interest. Clinical, observational and intervention, experimental, qualitative studies and review articles were all included in the search. Articles were identified using the following descriptors: cannabis and tetrahydrocannabinol and cannabidiol and endocannabinoids and anti-inflammatory inflammation and oxidative stress. In addition, a manual revision of relevant references was also performed to capture articles that may not have been picked up through the initial search. The literature investigation was conducted from March 22 to May 2022. CONCLUSION: Cannabinoids show to be a promising therapeutic option in the context of inflammatory diseases, given the complete and complex relationship between the endocannabinoid system and the immune system. The setback to be overcome in the use of cannabinoids as anti-inflammatory drugs includes the synthesis of non-psychoactive cannabinoid receptor agonists while maintaining potent anti-inflammatory activity. Further studies are needed to increase our understanding of cannabinoids and their intricate effects on immune system disorders.

RESUMO JUSTIFICATIVA E OBJETIVOS: O uso de canabinoides para síndrome epiléptica e controle de efeitos adversos associados à quimioterapia já é amplamente difundido e apoiado por vários ensaios clínicos bem controlados. Entretanto, o uso destes fármacos em doenças inflamatórias é, por vezes, subestimado pela falta de conhecimento científico com alto grau de evidência, pelo não reconhecimento do sistema endocanabinoide como participante ativo destas doenças, bem como por receio do estereótipo que envolve o uso dos derivados da cannabis. O objetivo deste estudo foi analisar os efeitos anti-inflamatórios e antioxidantes de canabinoides endógenos e exógenos em vários sistemas fisiológicos nos quais esses ligantes interagem. CONTEÚDO: Estudos citados nesta revisão foram obtidos por meio de buscas feitas nas bases de dados Pubmed, Medline, Google Acadêmico, Scielo, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, e através da familiaridade dos autores com a literatura publicada nesta área de interesse. Estudos clínicos, observacionais e de intervenção, experimentais, qualitativos e artigos de revisão foram todos incluídos na pesquisa. Os artigos foram identificados usando os seguintes descritores: cannabis , tetraidrocanabinol e canabidiol e endocanabinoides e inflamação anti-inflamatório e estresse oxidativo. Ademais, uma revisão manual nas referências relevantes também foi realizada para captura de artigos que podem não ter sido captados por meio da busca inicial. A investigação na literatura foi realizada no período de 22 de março a 17 de maio de 2022. CONCLUSÃO: Os canabinoides demonstram ser uma opção terapêutica promissora no contexto das doenças inflamatórias, haja vista a completa e complexa relação entre o sistema endocanabinoide e o sistema imune. O revés a ser vencido no uso de canabinoides como fármacos anti-inflamatórios inclui a síntese de agonistas de receptores canabinoides que não sejam psicoativos, mantendo a potente atividade anti-inflamatória. Novos estudos são necessários para aumentar a compreensão dos canabinoides e seus efeitos intrincados sobre distúrbios do sistema imunológico.

Macroporous latex biomembrane from Hancornia speciosa modulates the inflammatory process and has a debridement effect on wound healing in rats

Purpose: The angiogenic, osteogenic and anti-inflammatory activity of latex of Hancornia speciosa has been evidenced and indicates pharmacological potential with great applicability in the health area, especially in the wound healing process. The present work aimed to compare the effects of the H. speciosa macroporous latex biomembrane with saline on wound healing. Methods: Forty-three Wistar rats were submitted to excisional wound induction procedure and divided into groups according to treatment: saline (G1), and macroporous biomembrane (G2). The animals were euthanized at three, seven, 14, and 21 days after injury induction (DAI), and three animals were used for the debridement test. Morphometric, macroscopic, and microscopic analyses of general pathological processes were performed. Results: The macroporous biomembrane minimized necrosis and inflammation during the inflammatory and proliferative phases of the healing process, confirmed by the lower intensity of the crust and the debridement effect. In addition, the wounds treated with the macroporous biomembrane presented greater contraction rates in all the experimental periods analyzed. Conclusions: The macroporous biomembrane presents angiogenic, anti-inflammatory and debridement effects, contributing to the healing process, and can be considered a potentially promising new biomaterial to be used as a dressing.

The antiinflammatory and electrophysiological effects of fingolimod on penicillin-induced rats / Os efeitos antiinflamatórios e eletrofisiológicos do fingolimode em ratos induzidos pela penicilina

Abstract Background The fact that inflammation triggers epileptic seizures brings to mind the antiepileptic properties of anti-inflammatory drugs. Objective To investigate the electrophysiological and anti-inflammatory effects of fingolimod on an experimental penicillin-induced acute epileptic seizure model in rats. Methods Thirty-two male Wistar rats were divided into four groups: control (penicillin), positive control (penicillin + diazepam [5 mg/kg]), drug (penicillin + fingolimod [0.3 mg/kg]) and synergy group (penicillin + diazepam + fingolimod). The animals were anesthetized with urethane, and epileptiform activity was induced by intracortical injection of penicillin (500,000 IU). After electrophysiological recording for 125 minutes, IL-1β, TNF-α, and IL-6 were evaluated by ELISA in the serum of sacrificed animals. Results During the experiment, animal deaths occurred in the synergy group due to the synergistic negative chronotropic effect of diazepam and fingolimod. Although not statistically significant, fingolimod caused a slight decrease in spike-wave activity and spike amplitudes in the acute seizure model induced by penicillin (p > 0.05). Fingolimod decreased serum IL-1β (p < 0.05); fingolimod and diazepam together reduced IL-6 (p < 0.05), but no change was observed in serum TNF-α values. Conclusion Even in acute use, the spike-wave and amplitude values of fingolimod decrease with diazepam, anticonvulsant and anti-inflammatory effects of fingolimod will be more prominent in chronic applications and central tissue evaluations. In addition, concomitant use of fingolimod and diazepam is considered to be contraindicated due to the synergistic negative inotropic effect.

Resumo Antecedentes O fato de a inflamação desencadear crises epilépticas traz à mente as propriedades antiepilépticas dos anti-inflamatórios. Objetivo Investigar os efeitos eletrofisiológicos e anti-inflamatórios do fingolimode em um modelo experimental de crise epiléptica aguda induzida por penicilina em ratos. Métodos Trinta e dois ratos Wistar machos foram divididos em quatro grupos: controle (penicilina), controle positivo (penicilina + diazepam [5 mg/kg]), droga (penicilina + fingolimode [0,3 mg/kg]) e grupo sinergia (penicilina + diazepam + fingolimode). Os animais foram anestesiados com uretano, e a atividade epileptiforme foi induzida por injeção intracortical de penicilina (500.000 UI). Após registro eletrofisiológico por 125 minutos, IL-1β, TNF-α e IL-6 foram avaliados por ELISA no soro dos animais sacrificados. Resultados Durante o experimento, ocorreram mortes de animais no grupo sinérgico devido ao efeito cronotrópico negativo sinérgico do diazepam e do fingolimode. Embora não seja estatisticamente significativo, o fingolimode causou uma ligeira diminuição na atividade pico-onda e nas amplitudes pico no modelo de convulsão aguda induzida pela penicilina (p > 0,05). O fingolimode diminuiu a IL-1β sérica (p < 0,05); fingolimode e diazepam juntos reduziram a IL-6 (p < 0,05), mas não foi observada alteração nos valores séricos de TNF-α. Conclusão Pensa-se que o efeito anticonvulsivante leve de uma dose única de fingolimode será mais proeminente em aplicações crônicas e em avaliações de tecidos centrais. Além disso, o uso concomitante de fingolimode e diazepam é considerado contraindicado devido ao efeito inotrópico negativo sinérgico.

Atualização em reações de hipersensibilidade aos anti-inflamatórios não esteroidais ­ Parte 1: definições, farmacologia, epidemiologia, fisiopatologia e fatores genéticos / Update on hypersensitivity reactions to nonsteroidal anti-inflammatory drugs ­ Part 1: definitions, pharmacology, epidemiology, pathophysiology, and genetics

Os anti-inflamatórios não esteroidais (AINE) estão entre os medicamentos mais utilizados no mundo e são os fármacos mais frequentemente associados à ocorrência de reações de hipersensibilidade na América Latina. As reações têm grande variabilidade de apresentações clínicas e, consequentemente, com abordagem terapêutica difícil. Nesta revisão, abordamos aspectos farmacológicos dos AINE, bem como as definições, epidemiologia e fisiopatologia das reações de hipersensibilidade aos AINE. Por fim, discutimos aspectos genéticos associados à intolerância e alergia a esses fármacos.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used medications worldwide and the drugs most frequently associated with the occurrence of hypersensitivity reactions in Latin America. The clinical presentation of the reactions varies widely, which makes them difficult to treat. In this review, we address pharmacological aspects of NSAIDs, as well as the definitions, epidemiology, and pathophysiology of hypersensitivity reactions to NSAIDs. Finally, we discuss genetic factors associated with intolerance and allergy to these drugs.

Una mirada al tratamiento actual de la estomatitis aftosa recurrente. Revisión de la literatura / A look at the current management of recurrent aphthous stomatitis: scoping review

Resumen La estomatitis aftosa recurrente (EAR) es una patología ulcerativa crónica idiopática, que, aunque no llega a comprometer la vida de los pacientes, si puede desmejorar su calidad de vida. Presenta una alta incidencia en la población con un alto porcentaje de recurrencia. Atendiendo a su importancia, el objetivo de esta revisión es brindar una actualización respecto a las terapias farmacológicas y con láser para el manejo de la estomatitis aftosa recurrente. Se realizó una búsqueda bibliográfica en las bases de datos PubMed, Science Direct, EBSCO HOST y LILACS desde enero de 2010 a octubre de 2020, identificando publicaciones en inglés y español. Los artículos que fueron incluidos debían estar relacionadas con la estomatitis aftosa y su tratamiento, enfocándose en el manejo farmacológico o con láser. La estrategia de búsqueda arrojó 4536 citas bibliográficas, de las cuales fueron incluidas 19 en esta presente revisión. La mayoría de los estudios fueron ensayos clínicos aleatorizados donde la población objeto fueron adultos que demostraron el uso de antiinflamatorios, inmunomoduladores, anticuerpos monoclonales, antisépticos, anestésicos, entre otros, para el manejo de la estomatitis aftosa recurrente. De los artículos analizados se pudo concluir que la terapia farmacológica debe ser instaurada de manera particular, de acuerdo a la clínica y antecedentes del paciente. Los fármacos de primera elección son de uso tópico, reservando los de uso sistémico para casos moderados o severos y para pacientes con tratamiento refractarios, asimismo, las recomendaciones coadyuvantes como alimentación e higiene pueden ayudar a la resolución de la enfermedad. La terapia láser surge como alternativa de tratamiento con bajo riesgo y buenos resultados para la EAR.

Abstract Recurrent Aphthous Stomatitis (RAS) is an idiopathic chronic ulcerative pathology. Although it does not compromise the life of the patients, it can impair their quality of life. It presents a high incidence in the population and a high percentage of recurrence. In view of its importance, the aim of this review is to provide an update on pharmacological and laser therapies that are being implemented for the management of RAS. A bibliographic search of literature that was published between January 2010 and October 2020 was performed in PubMed, Science Direct, EBSCOhost, and LILACS databases, identifying publications in English and Spanish languages. The articles that were included had to be related to aphthous stomatitis and its treatment, focusing on pharmacological or laser management. 4536 bibliographic citations were found and 19 of them were included in this review. Most of the studies were randomized clinical trials in which the target population were adults that reported the use of anti-inflammatory drugs, immunomodulators, monoclonal antibodies, antiseptics, anesthetics, among others for the treatment of recurrent aphthous stomatitis. From the articles analyzed, it was possible to conclude that pharmacological therapy should be established in a particular way according to the patient's symptoms and medical record. The first-choice drugs are of topical use, reserving those of systemic use for moderate or severe cases and for patients with refractory treatment. Likewise, adjuvant recommendations such as nutrition and hygiene can help in the resolution of the disease. Laser therapy emerges as an alternative treatment with low risk and positive results for recurrent aphthous stomatitis.

Rapamycin and Paclitaxel Affect Human Aortic Smooth Muscle Cells-Derived Foam Cells Viability and Proliferation

Abstract Introduction: Drug-eluting stents (DES) coated with rapamycin or paclitaxel as antiproliferative substances significantly reduced the incidence of clinical restenosis and had fewer side effects after percutaneous coronary intervention. However, DES coated with rapamycin or paclitaxel still cause restenosis due to abnormal tissue growth which remained a therapeutic problem, particularly in certain subgroups, possibly due to drug concentrations. This study examined the impact of different concentrations of rapamycin and paclitaxel on cytokine, cell viability and proliferation in human aortic smooth muscle cells (HASMC)-derived foam cells. Methods: The foam cell model was established in vitro by incubating HASMC with 20 µg/mL oxidized low-density lipoprotein (ox-LDL) for 48 hours. Subsequently, foam cells were treated with different concentrations (0.01 µg/mL, 0.1 µg/mL, 0.5 µg/mL, 1 µg/mL, 5 µg/mL and 10 µg/mL) of rapamycin or paclitaxel for 48 hours, to measure cytokine, cell viability and proliferation by ELISA and MTT, respectively. Finally, viability and proliferation were measured by MTT after the foam cells were treated with 1 µg/mL rapamycin or paclitaxel combined with cytokine antibody for 48 hours. Results: After incubation of HASMC with ox-LDL, the ratios of cholesterol ester and total cholesterol increased significantly (55.29%) (P<0.01). Lipid staining with Oil Red O showed many lipid vacuoles and red dye particles in the cells. Meanwhile, cell viability and proliferation significantly increased compared with the control. This indicated that HASMC had been transformed into foam cells (P<0.01) while rapamycin or paclitaxel concentrations ≥0.1 µg/mL can significantly decrease the foam cell proliferation (P<0.05 or P<0.01), and 1 µg/mL of rapamycin or paclitaxel appeared the most effective concentration. As for cytokines, rapamycin or paclitaxel concentrations ≥1 ug/mL could significantly increase the level of inflammatory cytokines IL-6 (P<0.05 or P<0.01), which was enhanced with the increase of drug concentration. However, rapamycin or paclitaxel concentrations ≥1 µg/mL could significantly reduce the levels of anti-inflammatory cytokines IL-35 and transforming growth factor beta (TGF-β) (P<0.05 or P<0.01), which decreased with the increase of drug concentration. In addition, rapamycin or paclitaxel combined with anti-IL-1β, anti-IL-6, anti- TNF-α or anti-IL-35 had no significant effect on foam cell proliferation compared to the drug alone. However, rapamycin or paclitaxel combined with anti-IL-10 or anti-TGF-β can significantly enhance foam cell proliferation (P<0.01). In addition, there was no difference in the effects of the same concentrations of rapamycin and paclitaxel on foam cells. Conclusion: Although rapamycin or paclitaxel can reduce foam cell proliferation, too high or too low concentrations could decrease effectiveness. In particular, a high dose can induce foam cells to increase inflammatory cytokines secretion, reduce anti-inflammatory cytokines secretion, and thus affect the inhibiting proliferation. For rapamycin- and paclitaxel-eluting stents, this conclusion may explain the clinical observation of in-stent restenosis after percutaneous coronary intervention. DES coated with an appropriate concentration of rapamycin or paclitaxel may, at least to some extent, contribute significantly to reducing incidence of late in-stent restenosis.

Radioprotective Effect of Nigella Sativa Oil on Heart Tissues of Rats Exposed to Irradition

Abstract Background Various studies are ongoing related to the radioprotective agents. Herbal preparations are currently becoming popular because of their beneficial effects with fewer side effects compared to the synthetic/semi-synthetic medicines, and Nigella sativa oil (NSO) is only one of them. Objective To investigate NSO for its antioxidant effects on the heart tissue of rats exposed to ionizing radiation (IR). Methods Thirty six male albino Wistar rats, divided into four groups, were designated to group I (IR plus NSO group) that received both 5 Gray of gamma IR to total cranium and NSO; group II (IR alone group) that received IR plus saline, group III (control group of NSO) that received saline and did not receive NSO or IR; group IV (control group) that received only sham IR. Alterations in Total antioxidant status (TAS) and Total oxidant status (TOS), Oxidative stres index (OSI), Sulhydryl group (SH), Lipid hydroperoxide (LOOH), Paraoxonase (PON) levels, Arylesterase (ARE) and Ceruloplasmin (CER) activities in homogenized heart tissue of rats were measured by biochemical methods. Results In heart tissue of the rats in the IR alone group (group II) LOOH, TOS and OSI levels were found to be higher, ARE activity and TAS level were found to be lower than all of the other groups (p < 0.01). These results also support that IR increases oxidative stress and NSO's protective effect. Conclusion NSO would reduce the oxidative damage in the irradiated heart tissue in the experimental rat model.

Níveis mais Baixos de Fetuína-A Sérica estão Associados a um Maior Risco de Mortalidade em Dez Anos em Pacientes com Infarto do Miocárdio por Supradesnivelamento do Segmento ST / Lower Serum Fetuin-A Levels are Associated with a Higher Ten-Year Mortality Risk in Patients with ST-Elevation Myocardial Infarction

Resumo Fundamento A fetuína-A é um fator anti-inflamatório e anticalcificação envolvido no curso da doença arterial coronariana (DAC). Em alinhamento com essas funções, investigou-se a fetuína-A como marcador de risco cardiovascular em vários estudos. Porém, a associação entre a fetuína-A e o prognóstico dos pacientes com DAC ainda é controversa. Objetivos O presente estudo foi conduzido para identificar a associação entre o nível de fetuína-A sérica e doença cardiovascular (DCV) de longo prazo e a mortalidade global por infarto do agudo do miocárdio por supradesnivelamento do segmento ST (STEMI). Métodos Foram cadastrados no estudo cento e oitenta pacientes consecutivos com STEMI. A população do estudo foi dividida em subgrupos (mais baixo, ≤288 µg/ml; e mais alto, >288 µg/ml) de acordo com a mediana do nível de fetuína-A. Dados de acompanhamento clínico foram obtidos por contato telefônico anual com pacientes ou familiares. As causas das mortes também foram confirmadas pelo banco de dados de saúde nacional. P-valores bilaterais <0,05 foram considerados estatisticamente significativos. Resultados Durante um acompanhamento médio de 10 anos, foram registradas 71 mortes, das quais 62 foram devidas a DCV. Identificou-se um índice de mortalidade global e por DCV significativamente mais alto no grupo com nível de fetuína-A mais baixo que no grupo com nível de fetuína-A mais alto (44% versus 24%, p= 0,005; 48% versus 31%, p= 0,022, respectivamente). Nas análises de risco proporcionais por regressão de Cox, detectou-se que a fetuína-A era um preditor independente de mortalidade global e por DCV. Conclusões A baixa concentração de fetuína-A está associada ao prognóstico de longo prazo ruim pós-STEMI, independentemente de fatores de risco cardiovascular tradicionais. Nossos achados fortaleceram estudos prévios demonstrando consistentemente o papel determinante dos mediadores anti-inflamatórios em síndromes coronárias agudas.

Abstract Background Fetuin-A is an anti-inflammatory and anti-calcification factor involved in the course of coronary artery disease (CAD). In line with these functions, fetuin-A has been investigated as a cardiovascular risk marker in many studies. However, the association between fetuin-A and the prognosis of CAD patients is still controversial. Objectives The present study was conducted to identify the association between serum fetuin-A level and long-term cardiovascular disease (CVD) and all-cause mortality of ST-elevation acute myocardial infarction (STEMI). Methods One hundred eigthy consecutive patients with STEMI were enrolled in the study. The study population was divided into subgroups (lower, ≤288 µg/ml; and higher, >288 µg/ml) according to the median fetuin-A level. Clinical follow-up data was obtained by annual contact with the patients or family members by telephone. The causes of death were also confirmed by the national health database. Two-sided p-values<0.05 were considered statistically significant. Results During a median follow-up of 10 years, 71 deaths were recorded , 62 of whom died from CVD. Both CVD and all-cause mortality were found to be significantly higher in the lower fetuin-A group than the higher fetuin-A group (44% vs 24%, p= 0.005; 48% vs 31%, p= 0.022, respectively). In Cox regression proportional hazard analyses, fetuin-A was found to be an independent predictor of CVD and all-cause mortality. Conclusions Low fetuin-A concentration is associated with a poor long-term prognosis after STEMI, regardless of the traditional cardiovascular risk factors. Our findings have strengthened previous studies that consistently demonstrate the determining role of anti-inflammatory mediators in acute coronary syndromes.

Salvadora persica extract attenuates cyclophosphamide-induced hepatorenal damage by modulating oxidative stress, inflammation and apoptosis in rats / 中西医结合学报

OBJECTIVE@#Salvadora persica (SP) is used as a food additive and is a common ingredient in folk medicine. This study investigates the antioxidant, anti-inflammatory, and beneficial effects of SP against cyclophosphamide (CYP) toxicity in rats.@*METHODS@#In a 10-day study, 32 male rats were equally allocated into 4 groups (8 rats/group) as follows: the normal control (NC group), normal rats that only received oral aqueous extract of SP (100 mg/[kg·d]; SP group), animals treated with intraperitoneal CYP injections (30 mg/[kg·d]; CYP group), and the CYP + SP group that concurrently received CYP with SP aqueous extract. Serum samples were collected to measure the liver and renal biochemical profiles, as well as antioxidant and oxidative stress markers and the concentrations of interleukin-1β (IL-1β), IL-6, IL-10, tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) and adenosine 5'-monophosphate-activated protein kinase (AMPK). Hepatic and renal tissues were also harvested for histopathology and to measure apoptosis using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique, alongside tissue levels of oxidative stress markers.@*RESULTS@#Liver enzymes, total bilirubin, creatinine and urea, as well as serum IL-1β, IL-6, TNF-α and NF-κB increased significantly, whilst total protein, albumin, calcium, IL-10 and AMPK declined in serum of the CYP group relative to the NC group. The hepatorenal concentrations of glutathione, glutathione peroxidase and catalase declined markedly in the CYP group, whereas malondialdehyde, protein adducts, and apoptosis index increased compared with the NC group. By contrast, the hepatorenal biochemistry and apoptosis index of the SP group were comparable to the NC group. Interestingly, the CYP + SP group had significant improvements in the liver and renal biochemical parameters, enhanced anti-oxidative and anti-inflammatory effects, and marked declines in hepatic and renal apoptosis relative to the CYP group. Moreover, all monitored parameters were statistically indistinguishable between the CYP + SP group and the NC group.@*CONCLUSION@#This study suggests that the aqueous extract of SP could be a potential remedy against CYP-induced hepatorenal damage and may act by modulating the AMPK/NF-κB signaling pathway and promoting anti-oxidative and anti-inflammatory activities.

Is rosuvastatin protective against sepsis-associated encephalopathy? A secondary analysis of the SAILS trial / 世界急诊医学杂志（英文）

@#BACKGROUND: Sepsis is a common cause of death in emergency departments and sepsis-associated encephalopathy (SAE) is a major complication. Rosuvastatin may play a neuroprotective role due to its protective effects on the vascular endothelium and its anti-inflammatory functions. Our study aimed to explore the potential protective function of rosuvastatin against SAE. METHODS: Sepsis patients without any neurological dysfunction on admission were prospectively enrolled in the “Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome” study (SAILS trial, ClinicalTrials.gov number: NCT00979121). Patients were divided into rosuvastatin and placebo groups. This is a secondary analysis of the SAILS dataset. Baseline characteristics, therapy outcomes, and adverse drug events were compared between groups. RESULTS: A total of 86 patients were eligible for our study. Of these patients, 51 were treated with rosuvastatin. There were significantly fewer cases of SAE in the rosuvastatin group than in the placebo group (32.1% vs. 57.1%, P=0.028). However, creatine kinase levels were significantly higher in the rosuvastatin group than in the placebo group (233 [22-689] U/L vs. 79 [12-206] U/L, P=0.034). CONCLUSION: Rosuvastatin appears to have a protective role against SAE but may result in a higher incidence of adverse events.

Síndrome de intolerancia a múltiples medicamentos / Syndrome of intolerance to multiple medicines

El síndrome de intolerancia a múltiples medicamentos (MDIS, por sus siglas en inglés) se caracteriza por la intolerancia a dos o más medicamentos no relacionados. Tiene una prevalencia baja y es común en pacientes con polifarmacia. A pesar de que las reacciones adversas a los medicamentos son muy frecuentes, es raro que los pacientes debuten con este síndrome, el cual tiene implicaciones clínicas de leves a graves que afectan su vida; de acuerdo con esto varían el abordaje y su manejo. La sintomatología presentada varía desde síntomas gastrointestinales como reflujo gastroesofágico, dolores musculares y cefalea, hasta síntomas cutáneos; estos son los más frecuentes, tales como urticaria y erupciones maculopapulares o presentaciones menos comunes como el síndrome de Stevens-Johnson. El MDIS es causado por una amplia variedad de fármacos; por ello el conocimiento del síndrome, así como un adecuado interrogatorio de los antecedentes del paciente, es necesario para realizar un diagnóstico oportuno e instaurar un manejo adecuado y preventivo, evitando reacciones adversas que pongan en riesgo su vida. Con los hallazgos del cuadro clínico en la paciente, y basados en los antecedentes alérgicos presentados anteriormente a diferentes medicamentos no relacionados entre ellos, más la presentación de un rash maculopapular generalizado posterior a la administración de trimetoprim/sulfametoxazol se realiza el diagnóstico de MDIS. Se decide cambiar de medicamento por fosfomicina, con una consecuente evolución favorable. (AU)

Eficácia da terapia a laser de tecidos profundos na cicatrização de úlceras por pressão em paciente com tetraplegia: relato de caso / Efficacy of deep tissue laser therapy in pressure ulcer healing in patient with quadriplegia: Case Report

CONTEXTO: Úlceras por pressão (UP) são a complicação mais comum observada em pacientes acamados. O objetivo deste relato de caso é explorar a eficácia da terapia a laser no infravermelho próximo de classe IV no tratamento de úlceras de pressão grandes e graves. DADOS: Um homem de 53 anos com diagnóstico de tetraplegia devido à tuberculose da coluna cervical no nível C5-C6 foi admitido em um hospital com úlcera por pressão instável sobre o sacro e úlceras de pressão do National Pressure Ulcer Advisory Panel estágio 3 sobre a área trocantérica direita para lesão por pressão. Não havia comorbidades associadas, como diabetes mellitus e hipertensão. Utilizou-se o Lite Cure Gallium-Aluminium-Arsenide (GaAlAs) classe IV laser próximo ao infravermelho, sem contato, emissão de feixe contínuo (não pulsante) no comprimento de onda de 980 nm. Os parâmetros de dosagem usados foram: 7,5 - 10 watts de potência; faixa de dosagem 7 J / cm2 - 9 J / cm2; área sacral (13 × 9) cm2 e área trocantérica (10 × 8) cm2; em diferentes densidades de energia; o tempo de tratamento varia entre 8 a 15 minutos para cada úlcera. No total, 19 sessões durante um período de 6 semanas foram administradas para tratar úlceras de pressão. Dimensões (área) e estágio de gravidade da úlcera por pressão foram anotados antes da intervenção e após a conclusão da intervenção. Os dados pós-tratamento revelaram melhora clínica em ambos os desfechos. CONCLUSÃO / SIGNIFICADO CLÍNICO: Este relato de caso demonstra um efeito anti-inflamatório, analgésico e bioestimulante de cicatrização do tratamento com laserterapia Classe IV, apresentando redução nas dimensões e gravidade das úlceras por pressão.

CONTEXT: Pressure ulcers (PU) are the most common complication noted in bed-ridden patients. The purpose of this case report is to explore the efficacy of class IV near-infrared laser therapy in the treatment of large and severe pressure ulcers. FINDINGS: A 53-years-old male diagnosed with quadriplegia due to cervical spine tuberculosis at level C5- C6 was admitted to a hospital with an unstageable pressure ulcer over the sacrum and National Pressure Ulcer Advisory Panel Pressure stage 3 ulcers over the right trochanteric area for pressure injury. No associated comorbidities like diabetes mellitus and hypertension were present. The Lite Cure Gallium-Aluminum-Arsenide (GaAlAs) class IV near-infrared laser, non-contact, continuous beam emission (non-pulsing) at 980nm wavelength, was used. The dosage parameters used were: 7.5 - 10 watts power; dose range 7 J/cm2 - 9 J/cm2; sacral area (13×9) cm2 and trochanteric area (10×8) cm2; at varying energy densities; treatment time ranges between 8 to 15 minutes for each ulcer. Total 19 sessions over 6 weeks were given to treat pressure ulcers. Dimensions (area) and severity stage of pressure ulcer were noted pre-intervention and after the intervention. The post-treatment data revealed the clinical improvement in both outcomes. CONCLUSION/ CLINICAL SIGNIFICANCE: This case report demonstrates the anti-inflammatory, analgesic, and bio-stimulative healing effects of Class IV laser therapy treatment showing a reduction in the dimensions and severity of pressure ulcers.

Influência do Consumo de Suco de Laranja (Citrus Sinensis) na Remodelação Cardíaca de Ratos Submetidos a Infarto do Miocárdio / Influence of Consumption of Orange Juice (Citrus Sinensis) on Cardiac Remodeling of Rats Submitted to Myocardial Infarction

Resumo Fundamento O suco de laranja (SL) é rico em polifenóis com propriedades anti-inflamatórias e antioxidantes. Após o infarto do miocárdio (IM), mudanças complexas ocorrem na estrutura e na função cardíacas, processo conhecido como remodelação cardíaca (RC). O estresse oxidativo e a inflamação podem modular esse processo. Nossa hipótese foi a de que o consumo de SL atenua a RC após o IM. Objetivos Avaliar a influência do SL sobre a RC após IM pela análise de variáveis funcionais, morfológicas, de estresse oxidativo, de inflação, e de metabolismo energético. Métodos Um total de 242 ratos machos pesando entre 200 e 250g foram submetidos a um procedimento cirúrgico (ligação da artéria coronária ou cirurgia simulada). Sete dia após a cirurgia, os animais sobreviventes foram divididos para um dos quatro grupos: 1) SM, animais sham que receberam água e maltodextrina (n= 20); 2) SSL, animais sham que receberam SL (n= 20); 3) IM, animais infartados que receberam água e maltodextrina (n= 40); e 4) ISL, animais infartados que receberam SL (n = 40). A análise estatística foi realizada pelo teste de ANOVA com dois fatores com o teste de Holm-Sidak. Os resultados foram apresentados em média ± desvio padrão, e o nível de significância adotado foi de 5%. Resultados Três meses depois, o IM levou à hipertrofia do ventrículo esquerdo (VE), com disfunção sistólica e diastólica, e aumento nos mediadores inflamatórios e de estresse oxidativo. Os animais que consumiram SL apresentaram menor atividade da glutationa peroxidase e maior expressão da heme-oxigenase-1 (HO-1). Conclusão O SL atenuou a RC, e a HO-1 pode exercer um importante papel nesse processo.

Abstract Background Orange juice (OJ) is rich in polyphenols with anti-inflammatory and antioxidant properties. After myocardial infarction (MI), complex changes occur in cardiac structure and function, which is known as cardiac remodeling (CR). Oxidative stress and inflammation can modulate this process. We hypothesized that the consumption of OJ attenuates the CR after MI. Objectives To evaluate the influence of OJ on CR after MI by analysis of functional, morphological, oxidative stress, inflammation, and energy metabolism variables. Methods A total of 242 male rats weighing 200-250 g were submitted to a surgical procedure (coronary artery ligation or simulated surgery). Seven days after surgery, survivors were assigned to one of the four groups 1) SM, sham animals with water and maltodextrin (n= 20); 2) SOJ, sham animals with OJ (n= 20); 3) IM, infarcted animals with water and maltodextrin (n= 40); and 4) IOJ, infarcted animals with OJ (n = 40). Statistical analysis was performed by the two-way ANOVA supplemented by Holm-Sidak. Results are presented as mean ± standard deviation, the level of significance adopted was 5%. Results After 3 months, MI led to left ventricular (LV) hypertrophy, with systolic and diastolic dysfunction, and increased oxidative stress and inflammatory mediators. OJ intake reduced LV cavity and improved systolic and diastolic function. The OJ animals presented lower activity of glutathione peroxidase and higher expression of heme-oxygenase-1 (HO-1). Conclusion OJ attenuated CR in infarcted rats and HO-1 may be play an important role in this process.