Percorrer por autor "Ramos, Acácio"
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- Amentadione from the Alga Cystoseira usneoides as a Novel Osteoarthritis Protective Agent in an Ex Vivo Co-Culture OA ModelPublication . Araujo, Nuna C. P.; Viegas, Carla; Zubía, Eva; Magalhães, Joana; Ramos, Acácio; Carvalho, Maria M.; Cruz, Henrique; Sousa, João Paulo; Blanco, Francisco J.; Vermeer, Cees; Simes, DinaOsteoarthritis (OA) remains a prevalent chronic disease without effective prevention and treatment. Amentadione (YP), a meroditerpenoid purified from the alga Cystoseira usneoides, has demonstrated anti-inflammatory activity. Here, we investigated the YP anti-osteoarthritic potential, by using a novel OA preclinical drug development pipeline designed to evaluate the anti-inflammatory and anti-mineralizing activities of potential OA-protective compounds. The workflow was based on in vitro primary cell cultures followed by human cartilage explants assays and a new OA co-culture model, combining cartilage explants with synoviocytes under interleukin-1β (IL-1β) or hydroxyapatite (HAP) stimulation. A combination of gene expression analysis and measurement of inflammatory mediators showed that the proposed model mimicked early disease stages, while YP counteracted inflammatory responses by downregulation of COX-2 and IL-6, improved cartilage homeostasis by downregulation of MMP3 and the chondrocytes hypertrophic differentiation factors Col10 and Runx2. Importantly, YP downregulated NF-κB gene expression and decreased phosphorylated IkBα/total IkBα ratio in chondrocytes. These results indicate the co-culture as a relevant pre-clinical OA model, and strongly suggest YP as a cartilage protective factor by inhibiting inflammatory, mineralizing, catabolic and differentiation processes during OA development, through inhibition of NF-κB signaling pathways, with high therapeutic potential.
- Amentadione from the alga Cystoseira usneoides as a novel osteoarthritis trotective agent in an ex vivo co-culture OA ModelPublication . Araujo, Nuna C. P.; Viegas, Carla; Zubía, Eva; Magalhães, Joana; Ramos, Acácio; Carvalho, Maria M.; Cruz, Henrique; Sousa, João Paulo; Blanco, Francisco J.; Vermeer, Cees; Simes, DinaOsteoarthritis (OA) remains a prevalent chronic disease without effective prevention and treatment. Amentadione (YP), a meroditerpenoid purified from the alga Cystoseira usneoides, has demonstrated anti-inflammatory activity. Here, we investigated the YP anti-osteoarthritic potential, by using a novel OA preclinical drug development pipeline designed to evaluate the anti-inflammatory and anti-mineralizing activities of potential OA-protective compounds. The workflow was based on in vitro primary cell cultures followed by human cartilage explants assays and a new OA co-culture model, combining cartilage explants with synoviocytes under interleukin-1β (IL-1β) or hydroxyapatite (HAP) stimulation. A combination of gene expression analysis and measurement of inflammatory mediators showed that the proposed model mimicked early disease stages, while YP counteracted inflammatory responses by downregulation of COX-2 and IL-6, improved cartilage homeostasis by downregulation of MMP3 and the chondrocytes hypertrophic differentiation factors Col10 and Runx2. Importantly, YP downregulated NF-κB gene expression and decreased phosphorylated IkBα/total IkBα ratio in chondrocytes. These results indicate the co-culture as a relevant pre-clinical OA model, and strongly suggest YP as a cartilage protective factor by inhibiting inflammatory, mineralizing, catabolic and differentiation processes during OA development, through inhibition of NF-κB signaling pathways, with high therapeutic potential.
- Amentadione is a new modulating agent for osteoarthritis in an ex-vivo co-culture preclinical assayPublication . Araujo, Nuna C. P.; Viegas, Carla; Perrolas, Inês; Costa, Rúben; Magalhães, Joana; Blanco, Francisco; Ramos, Acácio; Miguel, Maria; Vermeer, Cees; Zubía, Eva; Simes, DinaOsteoarthritis (OA) is a whole-joint disease where inflammation interplays with extracellular matrix mineralization in a cycle that leads to its degradation. The lack of effective preventing treatments and disease modifying agents, demands new therapeutic targets and development of effective drugs.
- O uso do ácido tranexâmico na artroplastia total do joelho com instrumentação específica para o doente: um estudo prospetivo controlado e randomizadoPublication . Carvalho, Maria Miguel; Couto, André; Vide, João; Ramos, Acácio; Alonso, Thabata R.; Santos, Cássio F.; Fontes, Ana PaulaNos últimos anos, cada vez se tem utilizado mais o ácido tranexâmico (Atx) na artroplastia total do joelho (ATJ) para reduzir as perdas de sangue. O objectivo deste estudo é analisar o potencial benefício do uso do Atx na redução do risco de hemorragia em doentes submetidos a ATJ pelo sistema de instrumentação específica para o doente (PSI). Métodos: 55 pacientes randomizados em dois grupos, de forma sequencial, com osteoartrose do joelho em estadio avançado, submetidos a ATJ PSI. O grupo experimental recebeu uma primeira dose de 1000mg de Atx via intravenosa (iv) em bolus durante 10 minutos, 15 minutos antes de se desinsuflar o garrote. A segunda dose 1000mg diluídos em 100mL de soro fisiológico iniciada no final da cirurgia e em perfusão durante 8 horas (12,5mL/h). No grupo de controlo, os pacientes receberam 1000mL de soro fisiológico em tempos semelhantes aos do grupo do Atx. Resultados: Com a aplicação deste protocolo do Atx a queda de hemoglobina (Hb) diminui de 2,9 para 2,2g/dl às 24h (p<0,001) e de 4 para 3g/dl às 72h (p=0,002). Esta redução permitiu uma taxa de 0% de transfusões nos 55 pacientes apresentados neste estudo. Não foram descritas complicações para os dois grupos. O uso do Atx na ATJ PSI tem um efeito benéfico na redução da Hb, evitando as complicações e custos de uma maior perda de sangue e número de transfusões, respetivamente, sem o risco acrescido de efeitos tromboembólicos.
