Tagitinin F has anti-inflammatory, anti-nociceptive and anti-matrix metalloproteinase properties: An in silico, in vitro and in vivo study.

Sesquiterpene lactones (SL) are natural bioactive molecules indicated as potential scaffolds for anti-inflammatory and analgesic drug design. However, their anti-inflammatory applicability remains underestimated since the impact of SL on inflammatory nociception and tissue repair are overlooked. Thus, we used an integrated in silico, in vitro and in vivo framework to investigate the impact of tagitinin F (TAG-F) on lipopolysaccharide (LPS)-challenged macrophages, excisional skin wounds, and carrageenan-induced paw edema and mechanical hyperalgesia in mice. RAW 264.7 macrophages in culture were challenged with LPS and treated with TAG-F (5, 10, 50 and 100 µM). The paw of BALB/c mice was injected with carrageenan and treated with 0.5% and 1% TAG-F. Excisional wounds were also produced in BALB/c mice and treated with 0.5% and 1% TAG-F. Our results indicated a consistent concentration-dependent downregulation in 5-lipoxygenase, cyclooxygenase 1 and 2 (COX-1 and COX-2), matrix metalloproteinase 1 and 2 (MMP-1 and MMP-2) activities; as well as attenuation in prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and tumor necrosis factor-α (TNF-α) production in both in vitro and in vivo models. In vivo, TAG-F also attenuated carrageenan-induced paw edema and mechanical hyperalgesia in mice. From the excisional skin wound, TAG-F was still effective in reducing neutrophils and macrophages infiltration and stimulating collagen deposition in the scar tissue, accelerating tissue maturation. Together, our findings indicate that the anti-inflammatory effect of TAG-F is more comprehensive than previously suggested, exerting a significant impact on the control of edema, inflammatory pain and modulating central metabolic processes linked to skin wound healing.

Evaluation of methotrexate-loaded surfactants, ceramides and cholesterol-based lamellar phases as a topical treatment for psoriasis.

OBJECTIVE: Psoriasis is a chronic inflammatory skin disorder. Oral or subcutaneous methotrexate (MTX) is a first-line antipsoriatic treatment, whose adverse effects can be observed even at low doses. To minimize systemic side effects, antipsoriatic drugs should be administered topically, since they could permeate the stratum corneum. As liquid crystals with lamellar phase (LP) can be helpful in promoting skin permeation, this work evaluated two MTX-loaded LPs (C1CH and C1CHCE), based on stearic acid, cholesterol and ceramides, like topical treatments for mice with imiquimod-induced psoriasis. METHODS: C1CH and C1CHCE were topically administered to mice with imiquimod-induced psoriasis. Dexamethasone cream was used as positive treatment control. Skin histology and inflammation biomarkers were assessed. KEY FINDINGS: C1CH and C1CHCE exhibited marked immunomodulatory effects and induced extensive microstructural skin remodelling on the epidermis and dermis. These formulations increased keratinization score, epidermis thickness, inflammatory infiltrate, hair follicle hypertrophy and vascular congestion in the dermis. C1CH and C1CHCE also attenuated IL-10 upregulation and upregulated IL-1, IFN-γ, TNF-α and prostaglandin E2 levels, as well as myeloperoxidase, N-acetyl-ß-d-glucosaminidase and cyclooxygenase 2 activity compared with untreated psoriatic animals. CONCLUSION: Although liquid crystals have been reported as good options for carrying topical drugs, they need to be carefully assessed on a case-by-case basis.

Impact of sesquiterpene lactones on the skin and skin-related cells? A systematic review of in vitro and in vivo evidence.

Although anti-inflammatory properties are attributed to sesquiterpene lactones (SL), cutaneous hypersensitivity reactions are proposed as limitations for SL-based therapies. Thus, the impact of SL on the skin and skin-related cells was systematically reviewed. Studies indexed in electronic databases were screened from the PRISMA strategy. The risk of bias in all studies was verified from the SYRCLE's tool. Thirty original studies were recovered and analyzed. Mice and guinea pig, keratinocytes and fibroblasts were predominantly investigated from in vivo and in vitro studies, respectively. In vivo studies indicated that most SL induced contact dermatitis associated with edema, erythema, and inflammatory infiltrate. Conversely, in vitro evidence was consistent with a dose-dependent anti-inflammatory effect of SL in response to reduced cytokines, 5-LOX, and COX-2 levels or activity in keratinocytes, fibroblasts, macrophages and dendritic cells; which are events potentially triggered by downregulation of gene expression and/or inhibition of the NF-κB signaling pathway. In vivo studies presented uncertain to high-risk of bias mainly associated with underreporting of randomization and experimental blinding. The current evidence supports potent cutaneous immunomodulatory properties of SL. Although in vitro and in vivo studies indicate opposite anti- or proinflammatory effects, this contradiction exhibits a dose-dependent component. In addition, the anti-inflammatory pathways activated by SL are better understood from in vitro evidence. However, additional studies are required to elucidating specific anti-inflammatory and proinflammatory mechanisms triggered by SL in vivo. Thus, controlling the sources of bias described in this review can contribute to improving the quality of the evidence in further investigations.

Preclinical study of methotrexate-based hydrogels versus surfactant based liquid crystal systems on psoriasis treatment.

Psoriasis is an autoimmune, inflammatory and chronic skin disease in which cell growth and proliferation are increased, causing erythema, lesions and skin's peeling. Oral methotrexate (MTX) is the first-choice drug when phototherapy or retinoid treatment are not effective. Topical administration can be advantageous to better orientate the drug's delivery; however, the stratum corneum performs as a barrier for hydrofilic drugs penetration. This study sought to evaluate two different types of vehicles for MTX on the psoriasis treatment - hydrogel and liquid crystal systems (LCs). Lamellar and hexagonal liquid crystalline phases were selected from a ternary phase diagram based on polysorbate 80, isopropyl miristate and water. The hydrogel was based on alkylated carbomer (ACH). Rheological analysis showed ACH was more elastic than lamellar and hexagonal phases. ACH interacted better with pig skin than LCs in bioadhesion assay. Preclinical study revealed the ACH decreased inflammation in mice with induced psoriasis, being as effective as dexamethasone to regulate epidermis thickness, COX-2 and myeloperoxidase activity and TNF-α level, while LCs demonstrated inflammatory effect. Therefore, MTX-loaded hydrogel based platforms are indicated for local treatment of psoriasis and present great potential for further studies.

Performance funcional, composição corporal e medo de cair em idosas com desmineralização óssea caidoras e não caidoras. Existem diferenças? / Functional performance, body composition and fear of falling in fallers and non-fallers elderly women with bone demineralization. Are there differences?

Objetivou-se comparar performance funcional, composição corporal e medo de cair em idosas com desmineralização óssea caidoras e não caidoras. Estudo transversal, analítico com 19 idosas com baixa da densidade mineral óssea (DMO), sete apresentaram osteoporose e 12 tinham osteopenia. IMC=28,9 ± 4,3kg.m-2 , idade média de 70 ± 5 anos. As idosas foram alocadas em grupos quanto à queda: Caidoras (n=9) e Não Caidoras (n=10). A avaliação da performance funcional englobou: 1) Capacidade Funcional com a bateria Senior Fitness Test (SFT); 2) Variáveis da marcha captadas com o sensor inercial Wivar® Science durante o Teste de Caminhada de 10 metros (TC10M). Composição corporal: DMO, gordura e massa magra foram analisadas através da Absortometria Radiológica de Dupla Energia (DEXA). Verificou-se o medo de cair com a Falls Efficacy Scale - Internacional ­ Brasil. Testou-se a comparação entre médias com teste t de Student e U de Mann Whitney. Quanto ao medo de cair, o escore total atingiu 28±11 pontos. Não houve diferença estatística entre as médias dos testes de capacidade funcional e marcha, exceto a simetria da marcha (p=0,017). Os grupos alcançaram resultados semelhantes de performance funcional, marcha e medo de cair. O estímulo e manutenção da função devem ser feitos como caráter preventivo no público em questão independente do evento queda ter ocorrido. A simetria da marcha pode ser uma variável complementar na avaliação de quedas em idosas com osteopenia e osteoporose.(AU)

The aim of this study was to compare functional performance, body composition and fear of falling in fallers and non-fallers elderly women with bone demineralization. This is a cross-sectional, analytical study with 19 elderly women with low bone mineral density (BMD), seven had osteoporosis and 12 had osteopenia. BMI = 28.9 ± 4.3 kg.m-2 , mean age 70 ± 5 years. The elderly were allocated by fall reported event in groups: Fallers (n = 9) and Non-fallers (n = 10). Functional performance included: 1) Functional Capacity mesuared by Senior Fitness Test (SFT) battery; 2) Walking variables captured by the inertial sensor Wivar® Science during the 10-meter Walk Test (TC10M). Body composition: BMD, fat and lean mass were mesuared by Dual Energy Radiological Absortometry (DEXA). There fear of falling was acessed by Falls Efficacy Scale - International - Brazil. The comparison between means was made with Student's t test and Mann Whitney U test. As results, the total score for fear of falling reached 28 ± 11 points. There was no statistically significant difference between the means of functional capacity and gait tests. Only gait symmetry differed between groups (p = 0.017). Both groups achieved similar results of functional performance, gait and fear of falling. The stimulus and maintenance of the function must be done as a preventive character in the public in question regardless of the event that occurred. The gait symmetry may be a complementary variable to evaluate falls in elderly women with osteopenia and osteoporosis.(AU)

Inertial sensor and Timed Up and Go test in elderly women with bone demineralization: a reliability and agreement study / Sensor inercial e Timed Up and Go em idosas com desmineralização óssea: estudo de confiabilidade e concordância

The study aims to assess: 1) reliability test-retest and error measures of quantitative variables of Timed Up and Go (TUG) testing collected with the inertial sensor wireless Wiva® Science (TUGis), and 2) the agreement of TUGis and the timed method (TUGs) and between the two methods applied to elderly women with osteoporosis and osteopenia. Eighteen elderly women with bone demineralization were enrolled in this study. The time (s) for two executions of the TUG (T1 and T2) was measured with a manual stopwatch by an evaluator and with the inertial sensor at-tached to the body at the level of the L5 vertebra with remote collection. T1 and T2 were performed with an interval of 1 min. TUG's subtasks were also captured by the inertial sensor. The reliability test-retest and error variables were assessed by the intraclass correlation coefficient (ICC), standard error of measurement (SEm) and minimal detectable change (MDC). The agreement between the averages from the total time of the TUGs and TUGis and between T1 and T2 measured with the sensor and stopwatch were evaluated by the Bland-Altman method. The consistency inside of the subtasks TUGis ranged from substantial to almost complete. The SEm and MDC for TUGis were 1.27s and 2.48s, respectively. The agreement between sensor and stopwatch measurements showed low systematic error. The inertial sensor was reliable in verifying the performance of the TUG and can be a complement for assessing the risk of falls and functional mobility of elderly women with bone demineralization. However, it does not represent an improvement in the exclusive investigation of the total test time

O estudo visa avaliar: 1) confiabilidade teste-reteste e medidas de erro das variáveis quantitativas do teste Timed Up and Go (TUG) coletadas com o sensor inercial wireless Wiva® Science (TUGsi) e, 2) a concordância do TUGsi e o método cronometrado (TUGc) e entre os dois métodos aplicados em idosas com osteoporose e osteopenia. Foram recrutadas 18 idosas com desmineralização óssea. O tempo (s) de duas execuções do TUG (T1 e T2) foi mensurado com cronômetro manual por um avaliador e com o sensor inercial acoplado ao corpo em nível da vértebra L5 com coleta remota. T1 e T2 foram executadas com intervalo de 1 min. As subtarefas do TUG também foram captadas pelo sensor inercial. A confiabilidade teste-reteste e erro das variáveis foram avaliados pelo coeficiente de correlação intraclasse (CCI), erro padrão de medida (EPM) e mínima mudança detectável (MMD). A concordância entre as médias do tempo total do TUGc e TUCsi e entre T1 e T2 mensuradas com o sensor e cronômetro foram avaliadas pelo método Bland-Altman. A consistência interna das subtarefas do TUGsi variaram entre substancial a quase completa. O EPM e a MMD para o TUGsi foram de 1,27s e 2,48s, respectivamente. A concordância entre medidas do sensor e cronômetro apresentaram baixo erro sistemático. O sensor inercial foi confiável na verificação do desempenho do TUG e pode ser um complemento para avaliação de risco de quedas e mobilidade funcional de idosas com desmineralização óssea. Porém, não representa melhoria na investigação exclusiva do tempo total do teste

[Factors associated with difficulty of access of the elderly with disabilities to the health services]. / Fatores associados com a dificuldade no acesso de idosos com deficiência aos serviços de saúde.

This study seeks to analyze which are the variables associated with the difficulty of elderly people with disabilities gaining access to the health services. This is an observational study of an analytical cross-sectional nature, with a sample of 244 elderly people with disabilities. Data relating to socio-economic profile, the nature of the disability, and the conditions of access to health services were gathered. Version 11.0 of the Statistical Package for the Social Sciences software was used for descriptive, statistical and analytical assessment of the data. The protection variables for difficulties in being treated in the health services were: the lack of drains, culverts, trash, bags of refuse, or irregular floor surfaces; the absence of ramps on sidewalks and pavements; the availability of transport; ease in scheduling appointments; and the length of the waiting period to be attended. The number of factors listed shows that the architectonic barriers and the current situation of healthcare need to be adequate in order to ensure full access and use by the elderly with disabilities to the health services.

Fatores associados com a dificuldade no acesso de idosos com deficiência aos serviços de saúde / Factors associated with difficulty of access of the elderly with disabilities to the health services

Este estudo propõe analisar quais variáveis se associam com a dificuldade no acesso de idosos com deficiência aos serviços de saúde. Trata-se de um estudo observacional analítico de caráter transversal, com uma amostra de 244 idosos com deficiência. Foram agrupados dados pertinentes ao perfil socioeconômico, à caracterização da deficiência e às condições de acessibilidade aos serviços de saúde. Para análise estatística descritiva e analítica dos dados, foi utilizado o software Statistical Package for the Social Science, versão 11.0. As variáveis de proteção para a dificuldade em ser atendido nos serviços de saúde foram: ausência de esgotos, bueiros, dejetos, sacos de lixos, ou pisos quebrados; ausência de degraus nas calçadas e existência de calçamento; presença de transporte; facilidade na marcação de consultas; e o baixo tempo de espera para ser atendido. O somatório dos fatores expostos mostra que as barreiras arquitetônicas e situação atual de atenção à saúde precisam ser adequadas, visando o ingresso e utilização plena dos idosos com deficiência aos serviços de saúde.

This study seeks to analyze which are the variables associated with the difficulty of elderly people with disabilities gaining access to the health services. This is an observational study of an analytical cross-sectional nature, with a sample of 244 elderly people with disabilities. Data relating to socio-economic profile, the nature of the disability, and the conditions of access to health services were gathered. Version 11.0 of the Statistical Package for the Social Sciences software was used for descriptive, statistical and analytical assessment of the data. The protection variables for difficulties in being treated in the health services were: the lack of drains, culverts, trash, bags of refuse, or irregular floor surfaces; the absence of ramps on sidewalks and pavements; the availability of transport; ease in scheduling appointments; and the length of the waiting period to be attended. The number of factors listed shows that the architectonic barriers and the current situation of healthcare need to be adequate in order to ensure full access and use by the elderly with disabilities to the health services.