RESUMO
Vitamin D takes part in the functioning of many processes that ensure the homeostasis of the body. In orthopedics, it is indicated as an inseparable element ensuring proper bone growth and functioning, and its deficiencies are indicated in various diseases, mainly in the proper structure and function of the skeleton. In this review, we focus on the most important components of the vitamin D metabolic pathway, in correlation with selected orthopedic conditions. Records were obtained from the PubMed database in a timeline of 2010-2022. The keywords were as follows: vitamin D/cholesterol/vitamin D binding protein/ VDBP/Cytochrome/CYP24A1/CYP 27B1/Vitamin D receptor/VDR/ + diseases (ACL reconstruction, rotator cuff, arthroplasty knee/hip/shoulder). The recent original studies were analyzed, discussed, and the most important data were shown. The vast majority of articles concern the metabolite of vitamin D (25(OH)D), which is measured as a standard in diagnostic laboratories. Even though there is a lot of valuable information in the literature, we believe that the other elements of the vitamin D pathway also deserve attention and suggest their research in correlation with orthopedic disorders to supplement the missing knowledge on this topic.
Assuntos
Ortopedia , Vitamina D , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Redes e Vias Metabólicas , Receptores de Calcitriol/metabolismo , Vitamina D/metabolismo , Vitamina D3 24-Hidroxilase/metabolismo , VitaminasRESUMO
INTRODUCTION: Osteogenesis imperfecta (OI) is a disorder of the connective tissue that mainly causes the bones to become excessively brittle. The vast majority of OI cases are associated with mutations in the genes encoding the I alpha. PATIENT CONCERNS: A 57-year-old woman office worker was admitted because of severe, long-lasting pain in the thoracic spine while bending down. She and her daughter have a history of multiple atraumatic fractures form early childhood. DIAGNOSIS: Both women were pre-diagnosed with OI based on their phenotype. The genetic testing has shown single nucleotide polymorphism (rs193922155) in the gene encoding the collagen type I alpha 1 which until now was only likely pathogenic. INTERVENTIONS: Bone mineral density measurement revealed osteoporosis. The mother was prescribed with Vitamin D3 and calcium supplementation, but the daughter does not take any medication. The mother had vertebroplasty performed because of Th 9-12 vertebral body compression fractures. The cardiovascular diseases, spontaneous hematomas, joint dislocations were excluded. OUTCOMES: For mother postoperative pain reduction was achieved. CONCLUSION: To the best of our knowledge, this is the first publication that confirms the pathogenic effect of this mutation and describes the phenotype.
Assuntos
Colágeno Tipo I/genética , Osteogênese Imperfeita/genética , Densidade Óssea , Cálcio/uso terapêutico , Colecalciferol/uso terapêutico , Cadeia alfa 1 do Colágeno Tipo I , Feminino , Fraturas por Compressão/etiologia , Fraturas por Compressão/cirurgia , Humanos , Pessoa de Meia-Idade , Osteogênese Imperfeita/complicações , Osteogênese Imperfeita/tratamento farmacológico , Fenótipo , Polimorfismo de Nucleotídeo Único , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/patologiaRESUMO
Lipopolysaccharydes (LPS) are responsible for the intestinal inflammatory reaction, as they may disrupt tight junctions and induce cytokines (CKs) secretion. Osthole has a wide spectrum of pharmacological effects, thus its anti-inflammatory potential in the LPS-treated Caco-2 cell line as well as in Caco-2/THP-1 and Caco-2/macrophages co-cultures was investigated. In brief, Caco-2 cells and co-cultures were incubated with LPS to induce an inflammatory reaction, after which osthole (150-450 ng/mL) was applied to reduce this effect. After 24 h, the level of secreted CKs and changes in gene expression were examined. LPS significantly increased the levels of IL-1ß, -6, -8, and TNF-α, while osthole reduced this effect in a concentration-dependent manner, with the most significant decrease when a 450 ng/mL dose was applied (p < 0.0001). A similar trend was observed in changes in gene expression, with the significant osthole efficiency at a concentration of 450 ng/µL for IL1R1 and COX-2 (p < 0.01) and 300 ng/µL for NF-κB (p < 0.001). Osthole increased Caco-2 monolayer permeability, thus if it would ever be considered as a potential drug for minimizing intestinal inflammatory symptoms, its safety should be confirmed in extended in vitro and in vivo studies.
Assuntos
Anti-Inflamatórios/farmacologia , Colite/tratamento farmacológico , Cumarínicos/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Anti-Inflamatórios/uso terapêutico , Células CACO-2 , Técnicas de Cocultura , Colite/imunologia , Colite/patologia , Cumarínicos/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Lipopolissacarídeos/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Permeabilidade/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Células THP-1 , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Junções Íntimas/patologiaRESUMO
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by Diagnosis and Statistic Manual 5 (DSM-5) as persistent social interaction and communication deficient across multiple contexts. Various immunological findings have been reported in children with ASD, and co-existing allergic problems have been recorded in children diagnosed with ASD. Osthole, the effective component of Chinese traditional medicine, is reported to have anti-inflammatory effects. This study assessed the anti-inflammatory effect of osthole on the histamine-induced inflammatory responses in PBMC cells. METHODS: Peripheral blood mononuclear cells (PBMC's) from children with: (1) ASD group with co-existing allergies/asthma (nâ¯=â¯29); (2) ASD group without allergy/asthma (nâ¯=â¯29); (3) Allergy group (nâ¯=â¯30) and from typically developing age-matched control subjects (nâ¯=â¯28) were stimulated with either histamine, FXF, osthole or mixture of this substances. mRNA COX-2 gene expression, COX-2 production and inhibitory effect of tested substances on COX-2 were assessed after stimulation. RESULTS: Children with ASD may show either an innate proinflammatory response or increased activity of COX-2 which could display more impaired behavioral profile than children with non-inflamed. This study indicated that COX-2 may be involved in pathogenesis of ASD and/or allergy, and osthole could be used to decrease the effects of COX-2 in inflammation and ASD development. High incidence of allergy in ASD patients may indicate immune dysregulation that could be of relevance to the pathophysiology, symptomatology or neuroimmunology of ASD. CONCLUSIONS: This study shows that fexofenadine (FXF - antihistamine drug) and osthole exhibit selective COX-2 enzyme inhibitory activity. The selective COX-2 activity of osthole may explain further the anti-inflammatory properties of osthole in relieving congestion in allergic rhinitis, and as distinctive effects between FXF and osthole were observed, individual antihistamines may have different modes of action via the COX enzyme system.
Assuntos
Anti-Inflamatórios/farmacologia , Transtorno do Espectro Autista/imunologia , Cumarínicos/farmacologia , Hipersensibilidade/imunologia , Leucócitos Mononucleares/efeitos dos fármacos , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/metabolismo , Criança , Pré-Escolar , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Feminino , Histamina/imunologia , Antagonistas dos Receptores Histamínicos/farmacologia , Humanos , Hipersensibilidade/genética , Hipersensibilidade/metabolismo , Lactente , Leucócitos Mononucleares/imunologia , Masculino , Terfenadina/análogos & derivados , Terfenadina/farmacologiaRESUMO
BACKGROUND: Osthole (7-methoxy-8-isopentenylcoumarin) is natural coumarin isolated from the fruit of Cnidium monnieri (L.) Cusson, which is commonly used in medical practice of traditional Chinese medicine (TCM) in various diseases including allergies and asthma disorders. PURPOSE: Osthole was tested for the anti-histamine, anti-allergic, and inhibitory effects of COX-2 (cyclooxygenase-2) in children with diagnosed allergies. Additionally, we hypothesize that stated alterations in children with diagnosed allergies including increased expression of interleukin 1-ß receptor type 1 (IL-1 type I) and E-prostanoid (EP) 2 receptors, as well as raised expression, production, and activity of COX-2 and IL-1ß in incubated medium are approximately connected. Furthermore, we establish the mechanisms included in the changed regulation of the COX-2 pathway and determine whether osthole may be COX-2 inhibitor in peripheral blood mononuclear cells (PBMCs). METHOD: PBMCs were obtained from peripheral blood of healthy children (control, n = 28) and patients with diagnosed allergies (allergy, n = 30). Expression of the autocrine loop components regulating PGE2 production and signaling namely IL-1 type I receptor (IL-1RI), cyclooksygenaze-2 (COX-2), E-prostanoid (EP) 2, and also histamine receptor-1 (HRH-1) was assessed at baseline and after stimulation with histamine, osthole, and a mixture of histamine/osthole 1:2 (v/v). This comprised the expression of histamine receptor 1 (HRH-1), IL-1RI, COX-2, EP2 receptor, and the secretion of IL-1ß and COX-2 in cultured media and sera. RESULTS: Compared with control group, basal mRNA expression levels of HRH-1, IL-1RI, COX-2, and EP2 were higher in the allergy group. Histamine-induced EP2 and COX-2 expression mRNA levels were also increased. CONCLUSIONS: Osthole successively inhibits PGE2 and COX-2 mRNA expression. Furthermore, osthole reduces the secretion of COX-2 protein in signaling cellular mechanisms. Changed EP2 expression in children with allergies provides higher IL-1RI induction, increasing IL-1ß capacity to increase COX-2 expression. This effects in higher PGE2 production, which in turn increases its capability to induce IL-1RI.