Mangiferin: Possible uses in the prevention and treatment of mixed osteoarthritic pain.
- 作者列表："Garrido-Suárez BB","Garrido G","Piñeros O","Delgado-Hernández R
:Osteoarthritis (OA) pain has been proposed to be a mixed pain state, because in some patients, central nervous system factors are superimposed upon the more traditional peripheral factors. In addition, a considerable amount of preclinical and clinical evidence has shown that, accompanying the central neuroplasticity changes and partially driven by a peripheral nociceptive input, a real neuropathic component occurs that are particularly linked to disease severity and progression. Hence, innovative strategies targeting neuroprotection and particularly neuroinflammation to prevent and treat OA pain could be introduced. Mangiferin (MG) is a glucosylxanthone that is broadly distributed in higher plants, such as Mangifera indica L. Previous studies have documented its analgesic, anti-inflammatory, antioxidant, neuroprotective, and immunomodulatory properties. In this paper, we propose its potential utility as a multitargeted compound for mixed OA pain, even in the context of multimodal pharmacotherapy. This hypothesis is supported by three main aspects: the cumulus of preclinical evidence around this xanthone, some preliminary clinical results using formulations containing MG in clinical musculoskeletal or neuropathic pain, and by speculations regarding its possible mechanism of action according to recent advances in OA pain knowledge.
: 骨关节炎 (OA) 疼痛已被提出是一种混合性疼痛状态，因为在一些患者中，中枢神经系统因素叠加在更传统的外周因素上。此外，大量的临床前和临床证据表明，伴随着中枢神经可塑性变化，部分由外周伤害性输入驱动，真正的神经性成分发生，与疾病严重程度和进展特别相关。因此，可以引入针对神经保护，特别是神经炎症的创新策略来预防和治疗OA疼痛。芒果苷 (MG) 是一种葡萄糖基xanth酮，广泛分布于高等植物中，如芒果果。以前的研究已经记录了其镇痛，抗炎，抗氧化，神经保护和免疫调节特性。在本文中，我们提出其作为混合性OA疼痛的多靶点化合物的潜在效用，即使在多模式药物治疗的背景下。这一假设得到了三个主要方面的支持: 围绕这一黄酮的临床前证据的积云，在临床肌肉骨骼或神经性疼痛中使用含有MG的制剂的一些初步临床结果，并根据OA疼痛知识的最新进展推测其可能的作用机制。
METHODS:OBJECTIVE:Patients with immune-mediated inflammatory diseases such as rheumatoid arthritis or systemic lupus erythematosus are at increased risk of cardiovascular disease. However, the cardiovascular risk of patients with primary Sjögren's syndrome (SS) remains poorly studied. We aimed to investigate the association between primary SS and cardiovascular morbidity and mortality. METHODS:We performed a systematic review of articles in Medline and the Cochrane Library and recent abstracts from US and European meetings, searching for reports of randomized controlled studies of cardiovascular morbidity and cardiovascular mortality in primary SS. The relative risk (RR) values for cardiovascular morbidity and mortality associated with primary SS were collected and pooled in a meta-analysis with a random-effects model by using Review Manager (Cochrane collaboration). RESULTS:The literature search revealed 484 articles and abstracts of interest; 14 studies (67,124 patients with primary SS) were included in the meta-analysis. With primary SS versus control populations, the risk was significantly increased for coronary morbidity (RR 1.34 [95% confidence interval (95% CI) 1.06-1.38]; P = 0.01), cerebrovascular morbidity (RR 1.46 [95% CI 1.43-1.49]; P < 0.00001), heart failure rate (odds ratio 2.54 [95% CI 1.30-4.97]; P < 0.007), and thromboembolic morbidity (RR 1.78 [95% CI 1.41-2.25]; P < 0.00001), with no statistically significant increased risk of cardiovascular mortality (RR 1.48 [95% CI 0.77-2.85]; P = 0.24). CONCLUSION:This meta-analysis demonstrates that primary SS is associated with increased cardiovascular morbidity, which suggests that these patients should be screened for cardiovascular comorbidities and considered for preventive interventions, in a multidisciplinary approach with cardiologists.
METHODS:OBJECTIVE:We aimed to evaluate the comparative risk of hospitalized infection among patients with rheumatoid arthritis (RA) who initiated abatacept versus a tumor necrosis factor inhibitor (TNFi). METHODS:Using claims data from Truven MarketScan database (2006-2015), we identified patients with RA ages ≥18 years with ≥2 RA diagnoses who initiated treatment with abatacept or a TNFi. The primary outcome was a composite end point of any hospitalized infection. Secondary outcomes included bacterial infection, herpes zoster, and infections affecting different organ systems. We performed 1:1 propensity score (PS) matching between the groups in order to control for baseline confounders. We estimated incidence rates (IRs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) for hospitalized infection. RESULTS:We identified 11,248 PS-matched pairs of patients who initiated treatment with abatacept and TNFi with a median age of 56 years (83% were women). The IR per 1,000 person-years for any hospitalized infection was 37 among patients who initiated treatment with abatacept and 47 in those who initiated treatment with TNFi. The HR for the risk of any hospitalized infection associated with abatacept versus TNFi was 0.78 (95% CI 0.64-0.95) and remained lower when compared to infliximab (HR 0.63 [95% CI 0.47-0.85]), while no significant difference was seen when compared to adalimumab and etanercept. The risk of secondary outcomes was lower for abatacept for pulmonary infections, and similar to TNFi for the remaining outcomes. CONCLUSION:In this large cohort of patients with RA who initiated treatment with abatacept or TNFi as a first- or second-line biologic agent, we found a lower risk of hospitalized infection after initiating abatacept versus TNFi, which was driven mostly by infliximab.
METHODS:OBJECTIVE:Reducing pain is one of the main health priorities for children and young people with juvenile idiopathic arthritis (JIA); however, some studies indicate that pain is not routinely assessed in this patient group. The aim of this study was to explore health care professionals' (HCPs) beliefs about the role of pain and the prioritization of its assessment in children and young people with JIA. METHODS:Semi-structured interviews were conducted with HCPs who manage children and young people with JIA in the UK (including consultant and trainee pediatric rheumatologists, nurses, physical therapists, and occupational therapists). Data were analyzed qualitatively following a framework analysis approach. RESULTS:Twenty-one HCPs participated. Analyses of the data identified 6 themes, including lack of training and low confidence in pain assessment, reluctance to engage in pain discussions, low prioritization of pain assessment, specific beliefs about the nature of pain in JIA, treatment of pain in JIA, and undervaluing pain reports. Assessment of pain symptoms was regarded as a low priority and some HCPs actively avoided conversations about pain. CONCLUSION:These findings indicate that the assessment of pain in children and young people with JIA may be limited by knowledge, skills, and attitudinal factors. HCPs' accounts of their beliefs about pain in JIA and their low prioritization of pain in clinical practice suggest that a shift in perceptions about pain management may be helpful for professionals managing children and young people with this condition.