Pharmacotherapeutic potential of Vitis vinifera(grape) in age-related neurological diseases / Potencial farmacoterapéutico de Vitis vinifera(uva) en enfermedades neurológicas asociadas a la edad

Age-related neurological disorders (ANDs), including neurodegenerative diseases, are complex illnesses with an increasing risk with advancing years. The central nervous system's neuropathological conditions, including oxidative stress, neuroinflammation, and protein misfolding, are what define ANDs. Due to the rise in age-dependent prevalence, efforts have been made to combat ANDs. Vitis viniferahas a long history of usageto treat a variety of illness symptoms. Because multiple ligand sites may be targeted, Vitis viniferacomponents can be employed to treat ANDs. This is demonstrated by the link between the structure and action of these compounds. This review demonstrates that Vitis viniferaand its constituents, including flavonoids, phenolic compounds, stilbenoidsandaromatic acids, are effective at reducing the neurological symptoms and pathological conditions of ANDs. This is done by acting as an antioxidant and anti-inflammatory. The active Vitis vinifera ingredients have therapeutic effects on ANDs, as this review explains.

Las enfermedades neurológicas asociadas a la edad (AND, por su sigla en inglés) incluyendo las enfermedades neurodegenerativas, son enfermedades complejas con un riesgo creciente con la edad. Las condiciones neuropatológicas del sistema nervioso central, que incluyen el estrés oxidativo, la neuro inflamación, y el plegado erróneo de proteínas, son lo que define las AND. Debido al aumento en la prevalencia dependiente de la edad, se han hecho esfuerzos para combatir las AND. Vitis vinifera tiene una larga historia de uso para el tratamiento de síntomas. Puesto que puede hacer objetivo a muchos sitios ligando, los componentes de Vitis viniferase pueden utilizar para tratar AND. Esto se demuestra por el vínculo entre la estructura y la acción de estos compuestos. Esta revisión demuestra que la Vitis viniferay sus constituyentes, incluídos los flavonoides, componentes fenólicos, estilbenoides, y ácidos aromáticos, son efectivos para reducir los síntomas neurológicos y las condiciones patológicas de AND. Esto se produce por su acción como antioxidante y antiinflamatorio. Los ingredientes activos de Vitis vinifera tienen efectos terapéuticos en AND, y esta revisión lo explica.

Enfermedad de Caffey: reporte de un caso clínico / Caffey's disease: report of a clinical case / Doença de Caffey: relato de um caso clínico

Introducción: La enfermedad de Caffey es una patología ósea inflamatoria, rara, autolimitada, casi exclusiva de lactantes. Objetivos: Jerarquizar el abordaje diagnóstico de una patología poco frecuente. Caso clínico: 4 meses 22 días, varón, consulta por irritabilidad y edema de miembro inferior izquierdo de 4 días de evolución. Sin traumatismos ni fiebre. Examen físico: edema indurado en tercio medio e inferior de pierna izquierda, no rubor ni calor local. Dolor a la palpación de cara anterior y lateral de tibia y peroné. Limitación funcional, no resaltos óseos. Radiografía: engrosamiento del periostio en tibia y peroné a nivel diafisario. Hemograma: Glóbulos blancos 15.380 KU/L, Hemoglobina 10,8 g/dL, Plaquetas 816.400 10/ul, proteína C reactiva 13,90 mg/dl. Con planteo de probable infección osteoarticular se inicia clindamicina ( gentamicina e ingresa a cuidados moderados. Dada la persistencia de edema e irritabilidad, al quinto día se solicita resonancia magnética: hallazgos sugerentes de un probable proceso inflamatorio- infeccioso de partes blandas con compromiso óseo. Completa 14 días de clindamicina y 7 días de gentamicina intravenosa, hemocultivo negativo. Persiste con edema, irritabilidad y dolor. A los 21 días, se revalora la presentación clínica-imagenológica, se plantea enfermedad de Caffey. Se inicia anti-inflamatorio con buena evolución. Conclusiones: La enfermedad de Caffey es una colagenopatía rara, que afecta lactantes. El diagnóstico es clínico - radiológico (irritabilidad, tumefacción de partes blandas y alteraciones radiológicas). El pronóstico a largo plazo suele ser favorable. Es importante considerar el diagnóstico en lactantes que se presentan con esta sintomatología para evitar retrasos diagnósticos e instauración de tratamientos innecesarios.

Introduction: Caffey's disease is a rare disease that is reported almost exclusively in infants. Objective: Describe the case of a rare pathology, prioritizing the diagnostic approach. Clinical case: 4 month -old, healthy male. Consultation due to irritability and edema of the left lower limb for 4 days. No trauma or fever. Physical examination: indurated edema in the left leg, no redness or local heat. Pain on palpation of the anterior and lateral aspect of the tibia and fibula. Functional limitation, no bony protusions. Leg x-ray: thickening of the periosteum in the tibia and fibula at the diaphyseal level. Hemogram: White Blood Cells 15,380 KU/L Hemoglobin: 10.8 g/dL. Platelets: 816,400 10/ul, C-reactive protein: 13.90 mg/dl. He was admitted with a suggestion of probable osteoarticular infection. Clindamycin ( gentamicin is started. Given the persistence of edema and irritability despite treatment, on the fifth day an MRI was requested: findings suggestive of a probable inflammatory-infectious process of soft tissues with bone involvement. Completed 14 days of clindamycin and 7 days of intravenous gentamicin, blood culture negative. It persists with edema, irritability and pain. After 21 days, the clinical-imaging presentation was reassessed and Caffey's disease was considered. Anti-inflammatory begins with good evolution. Conclusions: Caffey's disease is a rare collagenopathy, that affects infants. The diagnosis is clinical - radiological (irritability, soft tissue swelling and radiological alterations). The long-term prognosis is usually favorable. It is important to consider the diagnosis in infants who present with these symptoms to avoid diagnostic delays and initiation of unnecessary treatments.

Introdução: A doença de Caffey é uma patologia óssea inflamatória rara, autolimitada, quase exclusiva de lactentes. Objetivos: Priorizar a abordagem diagnóstica de uma patologia rara. Caso clínico: 4 meses 22 dias, sexo masculino, consulta por irritabilidade e edema do membro inferior esquerdo de 4 dias de evolução. Sem trauma ou febre. Exame físico: edema endurecido em terço médio e inferior da perna esquerda, sem vermelhidão ou calor local. Dor à palpação das faces anterior e lateral da tíbia e fíbula. Limitação funcional, sem saliências ósseas. Radiografia: espessamento do periósteo na tíbia e fíbula ao nível diafisário. Hemograma: Glóbulos brancos 15.380 KU/L, Hemoglobina 10,8 g/dL, Plaquetas 816.400 10/ul, Proteína C reativa 13,90 mg/dl. Com sugestão de provável infecção osteoarticular, foi iniciada clindamicina + gentamicina e internado em cuidados moderados. Dada a persistência do edema e da irritabilidade, no quinto dia foi solicitada ressonância magnética: achados sugestivos de provável processo inflamatório-infeccioso de partes moles com envolvimento ósseo. Completou 14 dias de clindamicina e 7 dias de gentamicina intravenosa, hemocultura negativa. Persiste com edema, irritabilidade e dor. Após 21 dias, o quadro clínico-imagem foi reavaliado e considerada doença de Caffey. O antiinflamatório começa com uma boa evolução. Conclusões: A doença de Caffey é uma colagenopatia rara que afeta lactentes. O diagnóstico é clínico-radiológico (irritabilidade, edema de partes moles e alterações radiológicas). O prognóstico a longo prazo é geralmente favorável. É importante considerar o diagnóstico em lactentes que apresentam esses sintomas para evitar atrasos no diagnóstico e início de tratamentos desnecessários.

Manejo das irregularidades menstruais secundárias ao uso de contraceptivos ­ análise das recomendações atuais / Management of menstrual irregularities secondary to contraceptive use ­ analysis of current recommendations

As irregularidades menstruais representam uma série de desordens na quantida- de, duração, frequência ou regularidade do sangramento uterino. Entre suas cau- sas destaca-se o sangramento secundário ao uso de anticoncepcionais, uma razão frequente de descontinuidade dos contraceptivos, podendo aumentar as taxas de gestações não planejadas. Boa parte dos contraceptivos pode levar a mudanças no padrão de sangramento uterino, e a abordagem inicial do sangramentos irregula- res inclui a avaliação de outras possíveis causas, o reforço do uso correto da medi- cação, a tranquilização da paciente quanto à benignidade do quadro e à tendência a melhora com a continuidade do uso. Os anti-inflamatórios podem ser usados como estratégia inicial, e, não havendo resposta satisfatória, há alternativas espe- cíficas para cada método. Este trabalho visa identificar as recomendações atuais sobre o manejo do sangramento anormal decorrente de contraceptivos, por meio de revisão narrativa de estudos publicados sobre o tema nos últimos vinte anos.

Abnormal uterine bleeding represents a series of disorders in the amount, du- ration, frequency and or regularity of uterine bleeding. Among its causes, uterine bleeding secondary to the use of contraceptives stands out as a frequent reason for contraceptive discontinuity, which could lead to unplanned pregnancies. Most contraceptives can cause changes in the pattern of uterine bleeding, and the ini- tial approach of the abnormal bleeding includes assessing other possible cau- ses, reinforcing the correct use of medication, and reassuring the patient about the benignity of the condition and the tendency to improve with the continuity of the treatment. Anti-inflammatory drugs can be used as an initial strategy, and, if there is no satisfactory answer, there are specific alternatives for each contracep- tive method. This work aims to identify them current recommendations on the management of abnormal bleeding resulting from contraceptives use, through a narrative review of studies published on the subject in the last twenty years.

Compromiso cardíaco en el síndrome inflamatorio multisistémico post SARS-CoV-2 en niños / Cardiac involvement in post-SARS-CoV-2 multisystem inflammatory syndrome in children / Envolvimento cardíaco na síndrome inflamatória multissistêmica pós-SARS-CoV-2 em crianças

Objetivo: describir las características de ocho pacientes pediátricos que se presentaron con síndrome inflamatorio multisistémico (MIS-C) asociado a SARS-CoV-2 y compromiso cardíaco. Material y métodos: estudio descriptivo, retrospectivo de ocho pacientes con edades entre 1 y 13 años, con diagnóstico de MIS-C y compromiso cardíaco, asistidos en el CHPR. Se analiza su historia clínica, evolución y tratamiento. Resultados: los pacientes presentaron fiebre en el 100%, exantema e hiperemia conjuntival en el 88%, síntomas digestivos en el 50%, insuficiencia respiratoria en el 25% y shock en el 50%. Todos requirieron ingreso a cuidados intensivos. La alteración de la contractilidad cardíaca estuvo presente en el 63% de los pacientes, fue leve y segmentaria en el 80%, el 60% requirió soporte inotrópico por 3 días, recuperando una función normal en 7 días. La insuficiencia mitral se presentó en el 25% y el derrame pericárdico en el 38%, ambos de grado leve. Un paciente presentó dilatación de arterias coronarias con Z score < 2. El 85% de los pacientes presentó alteraciones del ECG, en el 29% se trató de alteración en la repolarización, en el 29% intervalo QTc prolongado, en el 15% bloqueo atrioventricular de 1er grado y bloqueo incompleto de rama derecha. Un paciente tuvo fibrilación auricular por 3 días con remisión espontánea a ritmo sinusal. Las troponinas estuvieron altas en el 57% de los pacientes y el ProBNP elevado en el 100%. Todos recibieron inmunoglobulinas, metilprednisolona y aspirina. Conclusiones: se presentaron ocho pacientes pediátricos con MIS-C y compromiso cardíaco, el 50% se presentó en shock, todos requirieron ingreso a cuidados intensivos. El 85% presento alteraciones en el ECG. El 63% presentó compromiso de la contractilidad sectorial y leve, se normalizó en 7 días. El 60% requirió soporte inotrópico por una media de 3 días.

Objective: describe the characteristics of 8 children who presented Multisystem Inflammatory Syndrome associated with SARS-CoV2 infections (MIS-C) and cardiac involvement. Material and methods: descriptive, retrospective study of 8 patients of between 1 and 13 years of age, diagnosed with MIS-C and cardiac involvement, assisted at the Pereira Rossell Children Hospital, analysis of their medical records, evolution and treatment. Results: the patients showed: fever in 100% of the cases, rash and conjunctival hyperemia in 88%, digestive symptoms in 50%, respiratory failure in 25% and shock in 50%. All required admission to Intensive Care. Cardiac contractility alteration was present in 63% of patients, the affectation was mild and segmental in 80%, 60% required inotropic support for 3 days and recovered normal functions in 7 days. Mitral regurgitation was present in 25% of the cases and pericardial effusion in 38%, mild in both cases. One patient had dilated coronary arteries with a Z score <2. 85% of the patients presented ECG abnormalities, 29% present alteration of repolarization, 29% prolonged QTc, 15% 1st degree atrioventricular block and incomplete right bundle branch block. One patient had atrial fibrillation for 3 days with spontaneous remission to sinus rhythm. Troponins were increased in 57% of the patients and ProBNP elevated in 100%. All patients received Immunoglobulins, Methylprednisolone and Aspirin. Conclusions: we present eight pediatric patients with MIS-C and cardiac involvement, 50% suffered shock, all required admission to Intensive Care. ECG abnormalities were found in 85% of the patients. Mild and segmental contractility compromise was found in 63% of the patients and normalized in 7 days. 60% required inotropic support for a mean of 3 days.

Objetivo: descrever as características de 8 pacientes pediátricos que apresentaram Síndrome Inflamatória Multissistêmica (MIS-C) associada ao SARS-CoV-2 e comprometimento cardíaco. Material e métodos: estudo descritivo, retrospectivo, de oito pacientes com idade entre 1 e 13 anos, com diagnóstico de MIS-C e comprometimento cardíaco, assistidos pelo CHPR. Seu prontuário médico, evolução e tratamento são analisados. Resultados: os pacientes apresentaram febre em 100%, erupção cutânea e hiperemia conjuntival em 88%, sintomas digestivos em 50%, insuficiência respiratória em 25% e choque em 50%. Todos necessitaram de internação nos cuidados intensivos. A alteração da contratilidade cardíaca esteve presente em 63% dos pacientes, foi leve e segmentar em 80%, 60% necessitaram de suporte inotrópico por 3 dias, recuperando a função normal em 7 dias. A regurgitação mitral ocorreu em 25% dos pacientes e o derrame pericárdico em 38%, ambos de grau leve. Um paciente apresentou dilatação da artéria coronária com escore Z < 2. 85% dos pacientes apresentaram anormalidades no ECG, 29% foram alterações de repolarização, 29% intervalo QTc prolongado em bloqueio atrioventricular de 1º grau a 15% e bloqueio incompleto do ramo direito. Um paciente apresentou fibrilação atrial por 3 dias com remissão espontânea ao ritmo sinusal. As troponinas foram elevadas em 57% dos doentes e ProBNP elevado em 100%. Todos receberam imunoglobulinas, Metilprednisolona e aspirina. Conclusões: houve oito pacientes pediátricos com SMIM-C e comprometimento cardíaco, 50% em choque, todos necessitaram de internação em terapia intensiva. 85% apresentaram elevações no ECG. 63% apresentaram comprometimento setorial e de contratilidade leve, normalizados em 7 dias. 60% necessitaram de suporte inotrópico por uma média de 3 dias.

Histopathological evaluation of the effect of Salvadoria persica and Nigella sativa on the healing of tooth extraction socket in animal

To assess the effects of Salvadoria persica and Nigella sativa combination in tooth socket healing after extraction that can be a novel remedy for tooth extraction socket. Methods: Forty rabbits were included in this study, divided into two groups (control and experimental) with 20 rabbits. Upper right central incisors were extracted for all animals, the tooth sockets of the experimental group were dressed using an admix of Salvadoria persica and Nigella sativa immediately after irrigation with normal saline. In contrast, the extraction sockets of the control group were left without dressing. Biopsies were taken after euthanizing the animals at 1, 3, 7, and 14 days after treatment, histological examination was done for the samples at the given periods respectively. Results: On day 1 post-treatment, histological examination of the experimental group sections showed less acute inflammatory reaction than the control group. This continued to be reduced until the seventh day. The amount of granulation tissue formation was more in the experimental group along the different periods of the study, while new bone formation was observed after 1 week as woven bone, increased after 2 weeks and appeared as woven and lamellar bone in both experimental and control groups. Conclusions: A mixture of Salvadoria persica and Nigella sativa has an anti-inflammatory effect and accelerate bone healing by stimulating bone formation in the tooth extraction socket

Platycodon grandiflorus polysaccharide regulates colonic immunity through mesenteric lymphatic circulation to attenuate ulcerative colitis / 中国天然药物

Platycodon grandiflorus polysaccharide (PGP) is one of the main components of P. grandiflorus, but the mechanism of its anti-inflammatory effect has not been fully elucidated. The aim of this study was to evaluate the therapeutic effect of PGP on mice with dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) and explore the underlying mechanisms. The results showed that PGP treatment inhibited the weight loss of DSS-induced UC mice, increased colon length, and reduced DAI, spleen index, and pathological damage within the colon. PGP also reduced the levels of pro-inflammatory cytokines and inhibited the enhancement of oxidative stress and MPO activity. Meanwhile, PGP restored the levels of Th1, Th2, Th17, and Treg cell-related cytokines and transcription factors in the colon to regulate colonic immunity. Further studies revealed that PGP regulated the balance of colonic immune cells through mesenteric lymphatic circulation. Taken together, PGP exerts anti-inflammatory and anti-oxidant effect and regulates colonic immunity to attenuate DSS-induced UC through mesenteric lymphatic circulation.

Alcohol extract of root and root bark of Toddalia asiatica alleviates CIA in rats through anti-inflammatory and proapoptotic effects / 中国中药杂志

This study aims to investigate the therapeutic effect of alcohol extract of root and root bark of Toddalia asiatica(TAAE) on collagen-induced arthritis(CIA) in rats through phosphatidylinoinosidine-3 kinase/protein kinase B(PI3K/Akt) signaling pathway. To be specific, CIA was induced in rats, and then the rats were treated(oral, daily) with TAAE and Tripterygium Glycoside Tablets(TGT), respectively. The swelling degree of the hind leg joints was scored weekly. After 35 days of administration, the histopathological changes were observed based on hematoxylin and eosin(HE) staining. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the levels of cytokines [tumor necrosis factor-α(TNF-α), interleukin(IL)-6)]. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) staining was performed to detect the apoptosis of synoviocytes in rats. Western blot was used to detect the expression levels of apoptosis-related proteins B-cell lymphoma 2(Bcl-2)-associated X(Bax), Bcl-2, and caspase-3 and pathway-related proteins phosphoinositide 3-kinase(PI3K), phosphorylated(p)-PI3K, protein kinase B(Akt), and p-Akt. RT-qPCR was conducted to examine the mRNA levels of Bax, Bcl-2, caspase-3, TNF-α, IL-6, and IL-1β and pathway-related proteins PI3K, p-PI3K, Akt, and p-Akt. TAAE can alleviate the joint swelling in CIA rats, reduce serum levels of inflammatory cytokines, improve synovial histopathological changes, promote apoptosis of synoviocytes, and inhibit synovial inflammation. In addition, RT-qPCR and Western blot results showed that TAAE up-regulated the level of Bax, down-regulated the level of Bcl-2, and activated caspase-3 to promote apoptosis in synoviocytes. TAAE effectively down-regulated the protein levels of p-PI3K and p-Akt. In this study, TAAE shows therapeutic effect on CIA in rats and reduces the inflammation. The mechanism is that it suppresses PI3K/Akt signaling pathway and promotes synoviocyte apoptosis. Overall, this study provides a new clue for the research on the anti-inflammatory mechanism of TAAE and lays a theoretical basis for the better clinical application of TAAE in the treatment of inflammatory and autoimmune diseases.

Otimização de método extrativo para raízes de Arctium lappa L / Extractive method optimization for Arctium lappa l. Roots / Optimización de un método de extracción de raíces de Arctium lappa L

Arctium lappa L. é indicada no Formulário de Fitoterápicos da Farmacopeia Brasileira para o tratamento de distúrbios urinários leves. Estudos já demonstraram o potencial antioxidante, anti-inflamatório e antidiabético deste extrato, onde foram identificados fenóis, lignanas, taninos e flavonoides. O objetivo deste trabalho foi otimizar o método extrativo de raízes de A. lappa. Realizou-se o preparo de extratos por diferentes métodos: Ultrassom, Soxhlet, maceração e turbo extração. A otimização foi realizada por turbo extração seguindo um planejamento fatorial 23, empregando como fatores: teor alcoólico, concentração da matéria prima e tempo de extração. Os extratos foram avaliados quanto ao resíduo seco, teores de fenóis e flavonoides, e atividade antioxidante. Com relação ao resíduo seco, e aos teores de fenóis e flavonoides, os métodos de ultrassom e turbo extração demonstraram melhor poder extrativo. Devido ao menor tempo e custo operacional, a otimização foi realizada por turbo extração, e o extrato otimizado foi obtido utilizando álcool 60%, em proporção matéria prima solvente 1:10 e tempo de extração de 15 minutos. Estas análises poderão nortear futuros testes de transposição de método para escala industrial, diminuindo mão de obra, tempo e custos, visando obter produtos fitoterápicos mais eficientes, com valor acessível à população.

Arctium lappa L. is indicated in the Brazilian Pharmacopeia Herbal Medicines Form for the treatment of mild urinary disorders. Studies have already demonstrated the antioxidant, anti-inflammatory and antidiabetic potential of this extract, where phenols, lignans, tannins and flavonoids were identified. The objective of this work was to optimize the extractive method of A. lappa roots. Extracts were prepared by different methods: Ultrasound, Soxhlet, maceration and vortical extraction. The optimization was performed by vortical extraction following a 23 full factorial design, using as factors: alcohol content, drug concentration and extraction time. The extracts were evaluated for dry residue, phenols and flavonoids contents, and antioxidant activity. Regarding the dry residue, and the phenols and flavonoids contents, the ultrasound and vortical extraction methods showed better extractive power. Due to the lower operating time and cost, the optimization was performed by vortical extraction, and the optimized extract was obtained using 60% alcohol, in a 1:10 drug solvent ratio and extraction time of 15 minutes. These assessments guide the future tests of transposition of the method to an industrial scale, reducing manpower, time and costs, aiming to obtain more efficient phytotherapic products, with affordable value for the population.

Arctium lappa L. está indicado en la Formulacao de Fitoterápicos da Farmacopeia Brasileira para el tratamiento de trastornos urinarios leves. Los estudios han demostrado el potencial antioxidante, antiinflamatorio y antidiabético de este extracto, donde se identificaron fenoles, lignanos, taninos y flavonoides. El objetivo de este trabajo fue optimizar el método extractivo de las raíces de A. lappa. Los extractos se prepararon por diferentes métodos: Ultrasonido, Soxhlet, maceración y turboextracción. La optimización se realizó mediante turboextracción siguiendo una planificación factorial de 23, empleando como factores: tenor alcohólico, concentración de materia prima y tiempo de extracción. Se evaluaron los extractos para determinar el residuo seco, el contenido de fenoles y flavonoides y la actividad antioxidante. En cuanto al contenido de residuo seco, fenoles y flavonoides, los métodos de extracción por ultrasonidos y turbo demostraron un mejor poder de extracción. Debido al menor tiempo y coste operativo, la optimización se realizó mediante turboextracción, y el extracto optimizado se obtuvo utilizando alcohol 60%, en proporción disolvente-materia 1:10 y tiempo de extracción de 15 minutos. Estos análisis podrán orientar futuros ensayos de transposición del método para escala industrial, reduciendo mano de obra, tiempo y costes, con el objetivo de obtener productos fitoterapéuticos más eficientes, con valor accesible para la población.

Avaliação in silico da afinidade de drogas ao receptor TRPA1 como preditor para o manejo farmacológico da sensibilidade provocada pelo clareamento dentário / In silico assessment of drug affinity to the TRPA1 receptor as a predictor for the pharmacological management of sensitivity caused by tooth whitening

Introdução: Reduzir a sensibilidade do clareamento dental em consultório representa um desafio para os profissionais. Pesquisadores associaram o bloqueio do receptor de dor TRPA1 com a redução da sensibilidade ao clareamento. No entanto, a afinidade química dos analgésicos/anti-inflamatórios para o TRPA1 ainda precisa ser averiguada. Objetivo: Realizar uma triagem virtual de múltiplos medicamentos (analgésicos e antiinflamatórios) para verificar a afinidade química pelo receptor TRPA1. Metodologia: A estrutura cristalina das proteínas do receptor TRPA1 foi recuperada do Protein Data Bank. Os códigos SMILES dos ligantes foram extraídos do PubChem. A energia de ligação do complexo foi obtida em ∆G - kcal/mol pelo AutoDock Vina© e replicada nos servidores SwissDock©, Dockthor© e CbDock©. LigPlus© confirmou os sítios de ligação. Resultados: Apesar dos antagonistas dos receptores analisados apresentarem alta afinidade, codeína e dexametasona apresentaram regularidade em todos os servidores, mesmo apresentando valores de energia de ligação de -7,9 kcal/mol para codeína e -8,1 kcal/mol para dexametasona. Conclusão: A codeína e a dexametasona podem ser drogas potenciais para controlar a sensibilidade ao clareamento dental caso atinjam o receptor TRPA1 da polpa dentária (AU).

Introduction: Reducing in-office tooth bleaching sensitivity represents a challenge for professionals. Researchers have associated the block of the pain receptor TRPA1 with reducing bleaching sensitivity. However, the chemical affinity of analgesic/antiinflammatory drugs to the TRPA1 needs to be verified. Objective: To perform a virtual screening of multiple drugs (analgesic and anti-inflammatory drugs) to verify chemical affinity for the TRPA1 receptor. Methodology: The crystal structure of the TRPA1 receptor proteins was retrieved from the Protein Data Bank. The SMILES codes of the ligands were extracted from PubChem. The binding energy of the complex was obtained in ∆G - kcal/mol by AutoDock Vina© and replicated in the webservers SwissDock©, Dockthor©, and CbDock©. LigPlus© confirmed the binding sites. Results: Although the receptor antagonists analyzed showed high affinity, codeine and dexamethasone showed regularity among all servers, even showing binding energy values of -7.9 kcal/mol for codeine and -8.1 kcal/mol for dexamethasone. Conclusion: Codeine and dexamethasone may be potential drugs to manage tooth bleaching sensitivity if they reach the dental pulp TRPA1 receptor (AU).

Síndrome inflamatorio multisistémico postinfección por SARS-CoV-2: a propósito de un caso clínico / Post SARS-CoV-2 multisystem inflammatory syndrome: a clinical case / Síndrome inflamatória pós-infecção por SARS-CoV-2: relato de caso

En Uruguay, la pandemia por SARS-CoV-2 ha generado menos afectación en pacientes de la edad pediátrica, aumentando el número de casos positivos en este grupo etario de forma proporcional al aumento de la circulación del virus. La forma de presentación es generalmente asintomática o con síntomas respiratorios leves a moderados. El síndrome inflamatorio multisistémico postinfección por SARS-CoV-2 (SIM-C) ha sido descrito como una de las principales complicaciones postinfección. Se describe el primer caso de un paciente con SIM-C en la ciudad de Paysandú, Uruguay. Se trata de un escolar de 6 años que cursó una infección por SARS-CoV-2 un mes previo. Se presenta con un cuadro febril de 4 días de evolución asociado a lesiones de piel e inyección conjuntival y odinofagia, con parámetros inflamatorios elevados y afectación cardiológica. Se traslada a CTI local con buena evolución posterior. El alto índice de sospecha de SIM-C mejora el diagnóstico y en consecuencia la morbimortalidad de la enfermedad.

Summary: In Uruguay, the SARS-CoV-2 pandemic has affected the pediatric population less and the number of positive cases in this age group has increased proportionally to the rise of the virus circulation. The presentation is generally asymptomatic or with mild to moderate respiratory symptoms. Post-Infection Multisystem Inflammatory Syndrome by SARS-CoV-2 (MIS-C) has been described as one of the main post-infection complications. We describe the first case of a patient with MIS-C in the city of Paysandú, Uruguay. It is a 6-year-old schoolboy who had had a SARS-CoV-2 infection a month earlier. He showed a 4-day history of fever associated with skin lesions and conjunctival injection and odynophagia, with high inflammatory parameters and cardiac involvement. He was transferred to a local ICU and had a good subsequent evolution. The high index of suspicion of MIS-C improves the diagnosis and consequently the morbidity and mortality rates of the disease.

No Uruguai, a pandemia de SARS-CoV-2 gerou menos afetação em pacientes pediátricos, e o número de casos positivos nessa faixa etária aumentou proporcionalmente ao aumento da circulação do vírus. A forma de apresentação é geralmente assintomática ou com sintomas respiratórios leves a moderados. A Síndrome Inflamatória Multissistêmica Pós-Infecção por SARS-CoV-2 (MIS-C) tem sido descrita como uma das principais complicações pós-infecção. Descreve-se o primeiro caso de paciente com MIS-C na cidade de Paysandú, Uruguai. Ele é um estudante de 6 anos de idade que tinha tido uma infecção por SARS-CoV-2 um mês antes. Apresentou história de febre de 4 dias associada a lesões cutâneas e hiperemia conjuntival e odinofagia, com parâmetros inflamatórios elevados e envolvimento cardiológico. Foi transferido para uma UTI local com boa evolução posterior. O alto índice de suspeita de MIS-C melhora o diagnóstico e, consequentemente, a morbimortalidade da doença.

Effects of different extracts of Dendrobium officinale on rats with chronic pharyngitis induced by pepper water combined with ammonia / 中国中药杂志

Dendrobium officinale can serve as Chinese medicinal material effective in nourishing yin, clearing heat, and producing fluid, and is used to treat throat diseases, but its active substances and mechanism are not clear. To clarify the active fraction and underlying mechanism of D. officinale against chronic pharyngitis(CP), the present study induced a CP model in rats by pepper water combined with low-concentration ammonia, and crude polysaccharides of D. officinale(DOP), non-polysaccharides of D. officinale(DON), and total extract of D. officinale(DOT)(0.33 g·kg~(-1), calculated according to the crude drug) were administered by gavage for six weeks. The changes in oral secretions and pharyngeal conditions of rats with CP were observed and rated. The hematological indicators were determined by an automatic hematology analyzer. The serum levels of pro-inflammatory factors, such as tumor necrosis factor-alpha(TNF-α), interleukin 1β(IL-1β), and interleukin 6(IL-6), and T-lymphocyte cytokines, including interferon γ(IFN-γ), interleukin 4(IL-4), interleukin 17(IL-17), and transforming growth factor β1(TGF-β1) were detected by the enzyme-linked immunosorbent assay(ELISA). The proportions of CD3~+, CD4~+, and CD8~+cells in peripheral blood T lymphocyte subsets were determined by the flow cytometry. The histomorphological changes of the pharynx were observed by hematoxylin-eosin(HE) staining. The protein expression of nuclear factor-κB P65(NF-κB P65), cyclooxygenase-2(COX-2), F4/80, and monocyte chemoattractant protein-1(MCP-1) in the pharynx were detected by immunohistochemistry and Western blot. The results showed that DOP and DON could significantly relieve pharyngeal lesions, reduce white blood cells(WBC) and lymphocytes(LYMP), decrease the levels of pro-inflammatory factors TNF-α, IL-6, and IL-1β, and inhibit the protein expression of NF-κB P65, COX-2, F4/80, and MCP-1 in the pharynx. DOP was superior in reducing oral secretions and serum IL-17 level and inferior in increasing CD4~+/CD8~+ratio to DON. It is suggested that both polysaccharides and non-polysaccharides of D. officinale have anti-PC effects and the anti-inflammatory mechanism may be related to the regulation of T lymphocyte distribution and inhibition of the inflammatory signaling pathways mediated by NF-κB P65. The anti-inflammatory effect of DOP may be related to the regulation of Th17/Treg balance, while that of DON may be related to the regulation of the Th/Tc ratio.

Anti-inflammatory effects of Abelmoschus manihot (L.) Medik. on LPS-induced cystitis in mice: potential candidate for cystitis treatment based on classic use / 中国天然药物

Abelmoschus manihot (L.) Medik. (A. manihot) is a traditional Chinese herbal medicine with a variety of pharmacological properties. It was first recorded in Jiayou Materia Medica dating back to the Song dynasty to eliminate urinary tract irritation by clearing away heat and diuretic effect. However, its pharmacological action on urinary tract infections has not been investigated. The present study aims to evaluate the anti-inflammatory activity of A. manihot on a mouse model of lipopolysaccharide (LPS)-induced cystitis. The results showed that A. manihot decreased white blood cell (WBC) count in urine sediments of the cystitis mice, alleviated bladder congestion, edema, as well as histopathological damage, reduced the expression levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β simultaneously. Moreover, A. manihot administration significantly downregulated the expression levels of TLR4, MYD88, IκBα, p-IκBα, NF-κB p65, and p-NF-κB p65 in LPS-induced cystitis mice. These findings demonstrated the protective effect of A. manihot against LPS-induced cystitis, which is attributed to its anti-inflammatory profile by suppressing TLR4/MYD88/NF-κB pathways. Our results suggest that A. manihot could be a potential candidate for cystitis treatment.

Anti-inflammatory effects of aucubin in cellular and animal models of rheumatoid arthritis / 中国天然药物

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. It is known that aucubin (AU) exerts anti-inflammatory activity, but its effects and mechanisms in RA are unclear. This study investigated the anti-inflammatory effects and mechanisms of AU in vivo and in vitro. Human fibroblast-like synoviocyte cells from patients with RA (HFLS-RA), RAW264.7 cells, and MC3T3-E1 cells were used to evaluate the effects of AU on migration, invasion, apoptosis, osteoclast differentiation and production. Immunofluorescence was used to observe nuclear translocation of nuclear factor (NF)-κB, the double luciferase reporter gene method was used to observe NF-κB-p65 activity in AU-treated MC3T3-E1 cells. RT-qPCR was used to measure expression of bone metabolism and inflammation-related genes, and western blot was used to measure bone metabolism and NF-κB protein expression levels. Collagen-induced arthritis (CIA) rat model was used for pharmacodynamics study. Arthritis indexes were measured in the ankle and knee, histological staining and Micro-computed tomography were performed on the ankle joints. Also, inflammatory factor gene expression and the levels of NF-κB-related proteins were detected as in vitro. AU effectively inhibited HFLS-RA cell migration and invasion, promoted apoptosis, and inhibited RAW264.7 cell differentiation into osteoclasts, as well as inhibited NF-κB-p65 activity in MC3T3-E1 cells. Notably, AU significantly reduced the gene expression levels of three cell-related inflammatory factors and bone metabolism factors, effectively inhibited the expression of p-Iκκα β, p-IκBα, and p-p65 proteins. In vivo, AU relieved joint inflammation, reduced related inflammatory factors, and inhibited NF-κB signaling. It could be used to treat RA-related synovial inflammation and bone destruction through the NF-κB pathway.

Effects of butyphthalide on microglia polarization after intracerebral hemorrhage and the underlying mechanisms / 中南大学学报(医学版)

OBJECTIVES@#Because intracerebral hemorrhage (ICH) has high morbidity, disability and mortality, it is significant to find new and effective treatments for ICH. This study aims to explore the effect of butyphthalide (NBP) on neuroinflammation secondary to ICH and microglia polarization.@*METHODS@#A total of 48 healthy male SD rats were randomly divided into 6 groups: a sham 24 h group, a sham 72 h group, an ICH 24 h group, an ICH 72 h group, an ICH+NBP 24 h group, and an ICH+NBP 72 h group (8 rats per group). After operation, the neurological deficiencies were assessed based on improved Garcia scores and corner test. The expressions of Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), aquaporin-4 (AQP4), zonula occludens-1 (ZO-1), occludin, CD68, CD86, and CD206 were observed by Western blotting. Inflammatory cytokines were detected by ELISA. The immunofluorescence was to detect the polarization of microglia.@*RESULTS@#1) Compared with the sham groups, the expression of TLR4 (24 h: P<0.05; 72 h: P<0.01), NF-κB (both P<0.01) and Nrf2 (both P<0.01) in the perihematoma of the ICH group was increased, leading to microglia activation (P<0.01). The expressions of IL-6 (24 h: P<0.05; 72 h: P<0.01) and TNF-α (both P<0.01), the pro-inflammatory cytokines were up-regulated, and the expression of anti-inflammatory cytokine IL-4 was down-regulated (both P<0.01). Besides, the expression of AQP4 was enhanced (both P<0.01). The protein level of tightly connected proteins (including ZO-1, occludin) was decreased (all P<0.01). The neurological function of the rats in the ICH group was impaired in the 2 time points (both P<0.01). 2) Compared with the sham group at 24 h and 72 h after the intervention of NBP, the expressions of TLR4 (both P<0.05) and NF-κB (both P<0.01) were significantly declined, and the expression of Nrf2 was further enhanced (both P<0.05) in the perihematoma of the ICH+NBP group. Furthermore, the expression of M1 microglia marker was inhibited (P<0.05), and the polarization of microglia to the M2 phenotype was promoted (P<0.01). 3) In terms of inflammation after ICH, the IL-4 expression in the ICH+NBP group was increased compared with the ICH group (24 h: P<0.05; 72 h: P<0.01); the expression of IL-6 was decreased significantly in the ICH+NBP 72 h group (P<0.01); the level of AQP4 was declined significantly in the ICH+NBP 24 h group (P<0.05), there was a downward trend in the 72-hour intervention group but without significant statistical difference. 4) Compared with the ICH group, the ZO-1 protein levels were increased (24 h: P<0.05; 72 h: P<0.01), and the symptoms of nerve defect were improved eventually (both P<0.05) in the ICH+NBP groups.@*CONCLUSIONS@#After ICH, the TLR4/NF-κB pathway is activated. The M1 microglia is up-regulated along with the release of detrimental cytokines, while the anti-inflammatory cytokines are down-regulated. The expression of AQP4 is increased, the tight junction proteins from the blood-brain barrier (BBB) is damaged, and the neurological function of rats is impaired. On the contrary, NBP may regulate microglia polarization to M2 phenotype and play a role in the neuroprotective effect mediated via inhibiting TLR4/NF-κB and enhancing Nrf2 pathways, which relieves the neuroinflammation, inhibits the expression of AQP4, repairs BBB, and improves neurological functional defects.

Aspirin inhibits the growth of hypertrophic scar in rabbit ears via regulating Wnt/β-catenin signal pathway / 中南大学学报(医学版)

OBJECTIVES@#Steroidal anti-inflammatory drugs have certain side effects in the treatment of hypertrophic scar, and the scar recurrence is easy after withdrawal of steroid anti-inflammatory drugs. Finding reliable alternative drugs is an effective means to improve this defect. Aspirin, a traditional non-steroidal anti-inflammatory drug, is safe for topical use and has anti-inflammatory effects similar to those of steroidal anti-inflammatory drugs, which may have similar effects on the treatment of hypertrophic scar. This study aims to investigate the inhibitory effect of aspirin on the proliferation of hypertrophic scar in rabbit ears and the underlying mechanism.@*METHODS@#The rabbit ear hypertrophic scar models were prepared. The rabbits were randomly divided into a normal skin group (group A), a blank control group (group B), a 0.9% NaCl group (group C), a 0.2% aspirin group (group D), a 0.5% aspirin group (group E), a 2% aspirin group (group F), and a triamcinolone acetonide group (group G). Macroscopic observation of hyperplasia was performed 8 weeks after local injection of the scar, followed by collecting the scar tissue samples for HE staining, Masson staining, and immunohistochemistry, respectively to assess the proliferation of fibroblasts and collagen fibers, and calculate the hypertrophic index, microvessel density, and immunohistochemical score.@*RESULTS@#All rabbit ear hypertrophic scar models were successfully constructed. In groups B and C, the hypertrophic scar edge was irregular, with reddish protruding epidermis, significant contracture and hard touch. In group D, E, and F, with the increase of aspirin administration concentration, the scar became thinner and gradually flat, the proliferation of fibrocytes and collagen fibers was weakened, and the hypertrophic index was gradually decreased (P<0.05). Immunohistochemistry showed that the expression of β-catenin was decreased in the group D, E and F in turn, and the immunohistochemical score was gradually decreased (P<0.05). There was no significant difference in hypertrophic index, microvessel density, and immunohistochemical score (all P>0.05).@*CONCLUSIONS@#Local injection of aspirin can reduce the generation of hypertrophic scar in a dose-dependent manner within a certain concentration range; aspirin inhibits the growth of hypertrophic scar in rabbit ears by inhibiting Wnt/β-catenin signal pathway; 2% aspirin and 40 mg/mL triamcinolone acetonide have similar curative efficacy on hypertrophic scar.

Anti-inflammatory Effects of Ampelopsis Japonica Root on Contact Dermatitis in Mice / 中国结合医学杂志

OBJECTIVE@#To investigate the anti-inflammatory potential of Ampelopsis japonica on contact dermatitis (CD).@*METHODS@#A total of 38 Balb/c mice were divided into 5 groups by using a random number table: normal mice (n=6), CD model mice (n=8), CD mice treated with 3 or 30 mg/kg of the ethanol extract of A. japonica (EEAJ, n=8) and 7.5 mg/kg dexamethasone treated CD mice (DEX, n=8). CD was induced using topical application of 1-fluoro-2,4-dinitrofluorobenzene in mice. EEAJ and DEX were topically applied to the shaved skin of each mouse for 6 days, and the effects of EEAJ and DEX on skin lesions and color, histopathological abnormalities such as epidermal hyperplasia and immune cell infiltration, and tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) production were investigated. The effects on changes in body weights and spleen/body weight ratio were also investigated.@*RESULTS@#EEAJ at 30 mg/kg significantly prevented scaling, erythema and enlargement of skin weight compared to using carbon dioxide. EEAJ also prevented epithelial hyperplasia and immune cell infiltrations induced by repeated application of DNFB (P<0.01). In addition, EEAJ significantly lowered levels of TNF-α, IL-6 and MCP-1 (P<0.05 or P<0.01). The anti-inflammatory effects of EEAJ were similar to those of DEX.@*CONCLUSION@#A. japonica may be a new therapeutic agent with the potential to reduce or replace corticosteroids and its mechanisms are closely related to regulation of TNF-α production.

Exopolysaccharides from Klebsiella oxytoca: anti-inflammatory activity

Abstract Exopolysaccharides (EPS) produced by Klebsiella oxytoca are of environmental, pharmaceutical, and medicinal interest. However, studies about the anti-inflammatory activity of EPS produced by this microorganism still remain limited. The aim of this study was to produce, characterize, and evaluate the anti-inflammatory activity of EPS from K. oxytoca in a pleurisy model. Colorimetric analysis revealed that precipitated crude exopolysaccharides (KEPSC) and deproteinated exopolysaccharides (KEPS) present high levels of total carbohydrates (65.57% and 62.82%, respectively). Analyses of uronic acid (7.90% in KEPSC and 6.21% in KEPS) and pyruvic acid (3.01% in KEPSC and 1.68% in KEPS) confirm that the EPS are acidic. Gas chromatography-mass spectrometry analyses demonstrated that the EPS consisted of rhamnose (29.83%), glucose (11.21%), galactose (52.45%), and mannose (6.50%). The treatment of an experimental pleurisy model in rats through subcutaneous administration of 50, 100, 200, and 400 mg/kg of KEPS decreased both the volume of inflammatory exudate and the number of leukocytes recruited to the pleural cavity. The present data showed that EPS production by K. oxytoca using the method described is easy to perform and results in a good yield. In addition, we show that KEPS exhibit anti-inflammatory activity when administered subcutaneously in rats.

Guía de diagnóstico y tratamiento: asma bronquial en niños ≥ 6 años. Actualización 2021 / Guideline on diagnosis and treatment: bronchial asthma in children ≥ 6 years old. Update 2021

En 1995 se publicó en Archivos Argentinos de Pediatría la primera "Guía de diagnóstico y tratamiento: asma bronquial en niños". En 2007 y 2016 se realizaron actualizaciones. Luego de 5 años se presentan los nuevos contenidos. Las modificaciones más relevantes, aunque no las únicas, se observan en las estrategias terapéuticas. En esta versión se estratifica el tratamiento en "niveles" (1 a 5). El paradigma de cambio en el tratamiento crónico del asma consiste en erradicar la prescripción de broncodilatadores (salbutamol) a demanda, por un lado, y por otro, aparece la opción de tratamiento combinado intermitente con corticoides inhalados y broncodilatadores acción prolongada (LABA) para las formas más leves (niveles 1 y 2), en niños de 12 años o mayores. Aún no se dispone de suficiente evidencia que avale estas opciones en menores de 12 años, por lo que se mantienen las normativas previas vigentes en este grupo. Para más detalles, sugerimos la lectura del documento completo

In 1995, the first Guideline on Diagnosis and Treatment for Childhood Asthma was published in Archivos Argentinos de Pediatría. Updates were made in 2007 and 2016. After 5 years, the new contents are presented. The most relevant modifications, although not the only ones, are observed in therapeutic strategies. In this version, treatment is stratified into "levels" (1 to 5). The current paradigm of change in chronic asthma treatment consists in eradicating the prescription of bronchodilators (salbutamol) on demand. Besides that, the option of intermittent treatment with inhaled corticosteroids plus long-acting bronchodilators (LABA) appears for milder forms (levels 1 and 2) in children > 12 years old. There is still not enough evidence to support these options in < 12 years old maintaining the previous recommendations in this group. For more details we suggest reading the full document.