RESUMEN
Articular cartilage possesses a remarkable, mechanically-robust extracellular matrix (ECM) that is organized and distributed throughout the tissue to resist physiologic strains and provide low friction during articulation. The ability to characterize the make-up and distribution of the cartilage ECM is critical to both understand the process by which articular cartilage undergoes disease-related degeneration and to develop novel tissue repair strategies to restore tissue functionality. However, the ability to quantitatively measure the spatial distribution of cartilage ECM constituents throughout the tissue has remained a major challenge. In this experimental investigation, we assessed the analytical ability of Raman micro-spectroscopic imaging to semi-quantitatively measure the distribution of the major ECM constituents in cartilage tissues. Raman spectroscopic images were acquired of two distinct cartilage tissue types that possess large spatial ECM gradients throughout their depth: native articular cartilage explants and large engineered cartilage tissue constructs. Spectral acquisitions were processed via multivariate curve resolution to decompose the "fingerprint" range spectra (800-1800 cm-1) to the component spectra of GAG, collagen, and water, giving rise to the depth dependent concentration profile of each constituent throughout the tissues. These Raman spectroscopic acquired-profiles exhibited strong agreement with profiles independently acquired via direct biochemical assaying of spatial tissue sections. Further, we harness this spectroscopic technique to evaluate local heterogeneities through the depth of cartilage. This work represents a powerful analytical validation of the accuracy of Raman spectroscopic imaging measurements of the spatial distribution of biochemical components in a biological tissue and shows that it can be used as a valuable tool for quantitatively measuring the distribution and organization of ECM constituents in native and engineered cartilage tissue specimens.
RESUMEN
Eleven patients with primary acquired cold-induced urticaria were treated with ketotifen (1 mg b.i.d.) or placebo in a double-blind, crossover design trial. After seven days of ketotifen treatment, reaction times to a cold stimulus were significantly delayed in ten of the 11 subjects. No effect was seen after placebo treatment. It is concluded that ketotifen may have a place in the treatment of primary acquired cold urticaria.
Asunto(s)
Cetotifen/uso terapéutico , Urticaria/prevención & control , Adolescente , Adulto , Niño , Ensayos Clínicos como Asunto , Frío/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placebos , Factores de Tiempo , Urticaria/etiologíaRESUMEN
Eight subjects with primary-acquired cold urticaria were treated with chlorpheniramine maleate, cyproheptadine hydrochloride, and placebo in a double-blind clinical trial. During three separate seven-day treatment periods, each patient took 4 mg of either active drug or lactose placebo three times a day. Objective measurements were made at the beginning and end of each treatment period by establishing the minimum time (MT) of cold stimulus application required to provoke urtication. In addition, the spontaneous appearance of cold urticaria lesions was recorded during each treatment period. The MT required for induction of urtication with a cold stimulus was significantly greater for eight patients receiving cyproheptadine as compared to chlorpheniramine or placebo (P less than .01). The study demonstrated that cyproheptadine had a significant suppressive action on experimental cold-induced urticaria, while placebo and chlorpheniramine proved ineffective.