The chrondoprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1β

BACKGROUND: Cartilage loss is a hallmark of arthritis and follows activation of catabolic processes concomitant with a disruption of anabolic pathways like insulin-like growth factor 1 (IGF-1). We hypothesized that two natural products of South American origin, would limit cartilage degradation by respectively suppressing catabolism and activating local IGF-1 anabolic pathways. One extract, derived from cat's claw (Uncaria guianensis, vincaria(®)), is a well-described inhibitor of NF-κB. The other extract, derived from the vegetable Lepidium meyenii (RNI 249), possessed an uncertain mechanism of action but with defined ethnomedical applications for fertility and vitality. METHODS: Human cartilage samples were procured from surgical specimens with consent, and were evaluated either as explants or as primary chondrocytes prepared after enzymatic digestion of cartilage matrix. Assessments included IGF-1 gene expression, IGF-1 production (ELISA), cartilage matrix degradation and nitric oxide (NO) production, under basal conditions and in the presence of IL-1β. RESULTS: RNI 249 enhanced basal IGF-1 mRNA levels in human chondrocytes by 2.7 fold, an effect that was further enhanced to 3.8 fold by co-administration with vincaria. Enhanced basal IGF-1 production by RNI 249 alone and together with vincaria, was confirmed in both explants and in primary chondrocytes (P <0.05). As expected, IL-1β exposure completely silenced IGF-1 production by chondrocytes. However, in the presence of IL-1β both RNI 249 and vincaria protected IGF-1 production in an additive manner (P <0.01) with the combination restoring chondrocyte IGF-1 production to normal levels. Cartilage NO production was dramatically enhanced by IL-1β. Both vincaria and RNI 249 partially attenuated NO production in an additive manner (p < 0.05). IL-1β – induced degradation of cartilage matrix was quantified as glycosaminoglycan release. Individually RNI 249 or vincaria, prevented this catabolic action of IL-1β. CONCLUSION: The identification of agents that activate the autocrine production of IGF-1 in cartilage, even in the face of suppressive pro-inflammatory, catabolic cytokines like IL-1β, represents a novel therapeutic approach to cartilage biology. Chondroprotection associated with prevention of the catabolic events and the potential for sustained anabolic activity with this natural product suggests that it holds significant promise in the treatment of debilitating joint diseases

Bromfenac 0.09% bioavailability in aqueous humor, prophylactic effect on cystoid macular edema, and clinical signs of ocular inflammation after phacoemulsification in a Mexican population

Claudia Palacio,1 Lourdes Fern&aacute;ndez De&nbsp;Ortega,2 Francisco R Bustos,3 Eduardo Ch&aacute;vez,4 Aldo A Oregon-Miranda,5 Arieh R Mercado-Sesma5 1Anterior Segment Department, Fundaci&oacute;n Hospital Nuestra Se&ntilde;ora de la Luz, M&eacute;xico City, M&eacute;xico; 2Anterior Segment Department, Asociaci&oacute;n Para Evitar la Ceguera en&nbsp;M&eacute;xico, Hospital Dr Luis S&aacute;nchez Bulnes, M&eacute;xico; 3Anterior Segment Department, Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, M&eacute;xico; 4Anterior&nbsp;Segment Department, Instituto de Oftalmolog&iacute;a, Fundaci&oacute;n de Asistencia Privada Conde de Valenciana, IAP, M&eacute;xico; 5Clinical Research Department, Laboratorios Sophia, SA de CV, Zapopan, Jalisco, M&eacute;xico Purpose: The purpose of this study was to evaluate the aqueous humor bioavailability and clinical efficacy of bromfenac 0.09% vs nepafenac on the presence of cystoid macular edema (CME) after phacoemulsification.Material and methods: A Phase II, double-blind, masked, active-controlled, multicenter, clinical trial of 139 subjects, randomized to either a bromfenac 0.09% ophthalmic solution (n=69) or nepafenac 0.1% (n=70). Subjects instilled a drop three times a day for a period of 30 days. Follow-up visits were on days 2, 7, 15, 30, and 60. Biomicroscopy, clinical ocular signs, and assessment of posterior segment were performed. The primary efficacy endpoints included the presence of CME evaluated by optical coherence tomography. Safety evaluation included intraocular pressure, transaminase enzymes, lissamine green, and fluorescein stain.Results: The demographic and efficacy variables were similar between groups at baseline. The presence of pain, photophobia, conjunctival hyperemia, chemosis, cellularity, and corneal edema disappeared by day 30 in both groups. The central retinal thickness did not show significant changes after treatment when compared to baseline as follows: in the bromfenac group (247.2&plusmn;32.9 vs 252.0&plusmn;24.9 &micro;m; P=0.958) and in nepafenac group (250.8&plusmn;34 vs 264.0&plusmn;34.1 &micro;m; P=0.137), respectively. A statistically significant difference was observed between bromfenac and nepafenac group: (252.0&plusmn;24.9 vs 264.0&plusmn;34.1 &micro;m; P=0.022), at day 30, respectively; even though there was no clinical relevance in the presentation of CME. There were no significant alterations in intraocular pressure, either lissamine green or fluorescein stains. The adverse events were not related to the interventions. Conclusion: Bromfenac 0.09% ophthalmic solution showed similar clinical efficacy to reduce the presentation of CME after phacoemulsification compared to nepafenac 0.01%. Keywords: bromfenac, ocular NSAID, cystoid macular edema, OC