Bone spicule pigment formation in retinitis pigmentosa: insights from a mouse model.

BACKGROUND: Bone spicule pigments (BSP) are a hallmark of retinitis pigmentosa (RP). In this study, we examined the process of BSP formation in the rhodopsin knockout (rho (-/-)) mouse, a murine model for human RP. METHODS: In rho (-/-) mice from 2 to 16 months of age, representing the range from early to late stages of degeneration, retinal sections and whole mounts were examined morphologically by light and electron microscopy. The results were compared to scanning laser ophthalmoscopy of BSP degeneration in human RP. RESULTS: After the loss of all photoreceptor cells in rho-/- mice, the outer retina successively degenerated, leading to approximation and finally a direct contact of inner retinal vessels and the retinal pigment epithelium (RPE). We could show that it was the event of proximity of retinal vessel and RPE that triggered migration of RPE cells along the contacting vessels towards the inner retina. Ultrastructurally, these mislocalized RPE cells partially sealed the vessels by tight junction linkage and deposited extracellular matrix perivascularly. Also, the vascular endothelium developed fenestrations similar to the RPE-choroid interface. In whole mounts, the pigmented cell clusters outlining retinal capillaries correlated well with BSPs in human RP. The structure of the inner retina remained well preserved, even in late stages. CONCLUSIONS: The Rho (-/-) mouse is the first animal model that depicts all major pathological changes, even in the late stages of RP. Using the rho (-/-) mouse model we were able to analyze the complete dynamic process of BSP formation. Therefore we conclude that: (1) In rho (-/-) retinas, BSPs only form in areas devoid of photoreceptors; (2) Direct contact between inner retinal vessels and RPE appears to be a major trigger for migration of RPE cells; (3) The distribution of the RPE cells in BSPs reflects the vascular network at the time of formation. The similarity of the disease process between mouse and human and the possibility to study all consecutive steps of the course of the disease makes the rho (-/-) mouse valuable for further insights in the dynamics of BSP formation in human RP.

The universal NF-kappaB inhibitor a20 protects from transplant vasculopathy by differentially affecting apoptosis in endothelial and smooth muscle cells.

Transplant vasculopathy (TV) is an accelerated form of atherosclerosis resulting in chronic rejection of vascularized allografts. The causes of TV are multifactorial and integrate at the level of the vascular wall, leading to a phenotypic switch of endothelial cells (ECs) and smooth muscle cells (SMCs). A20 is a NF-kappaB-dependent stress response gene in ECs and SMCs with potent anti-inflammatory effect in both cell types through blockade of NF-kappaB. A20 expression in ECs and SMCs correlates with the absence of TV in rat kidney allografts and long-term functioning human kidney allografts. We demonstrate that A20 protects ECs from tumor necrosis factor, Fas, and natural killer cell-mediated apoptosis by inhibiting proteolytic cleavage of caspase 8. A20 also safeguards ECs from complement-mediated necrosis. Hence, effectively shutting down cell death pathways initiated by inflammatory and immune offenders associated with TV. In contrast, A20 sensitizes SMCs to cytokine and Fas-mediated apoptosis through a novel nitric oxide (NO)-dependent mechanism. The unexpected proapoptotic effect of A20 in SMCs translates in vivo by the regression of established neointimal carotid lesions following balloon angioplasty in rats. Antedating apoptosis of SMCs, expression of the inducible NO synthase increases in A20-expressing neointimal SMCs, corroborating the involvement of NO in causing the proapoptotic effect of A20 in SMCs. Combined anti-inflammatory and anti- or proapoptotic functions of A20 in ECs and SMCs respectively qualify the positive effect of A20 upon vascular remodeling and healing. We propose that A20-based therapies may be effective in prevention and treatment of TV.

Biomechanical performance of powder-free examination gloves.

Biomechanical performance studies were undertaken for powder-free, latex and nitrile examination gloves. Using standardized tests, examination glove performance was judged by measuring glove thickness, glove puncture force, glove tape adhesion force, glove donning force, glove stiffness, and immediate unrecovered stretch. Even though the nitrile examination gloves were thinner than the latex examination gloves, they exhibited a greater puncture resistance. In addition, tape adherence to the N-Dex nitrile glove was the lowest. Moreover, measurements of the handling characteristics of the nitrile examination gloves demonstrated that they are an acceptable alternative to latex examination gloves. While these biomechanical studies demonstrate the superiority of the nitrile examination gloves, clinical glove evaluation is still needed to determine their performance in the health care setting.

Biomechanical performance of latex and non-latex double-glove systems.

The purpose of this study was to evaluate ten commercially available latex, powder-free surgical gloves and four commercially available non-latex, powder-free surgical gloves using standardized, reproducible biomechanical parameters that included glove thickness, puncture resistance, and glove donning force. For all gloves tested, with one exception (Neolontrade mark PF), puncture resistance increased for double-gloves as compared to single-gloves. In addition, single-glove thickness was not a reliable determinant of puncture resistance for either latex or non-latex gloves. For the latex gloves, the Ultrafree double and single-gloves exhibited the highest puncture resistance. The glove donning forces for the Biogeltrade mark M and Biogel Sensortrade mark single-gloves were the lowest. In contrast, the Biogel Revealtrade mark and Encoretrade mark Ultra-Thick exhibited the lowest double-glove donning forces. On the basis of these performance tests of latex gloves, the surgeon should consider the Biogel Reveal as well as the Ultrafree gloves for their latex double-glove system. For the non-latex gloves, the Pure Advantage Nitriletrade mark glove had the highest puncture resistance for one layer and two layers of glove material. The thin Pure Advantage Nitrile glove was the most resistant to glove puncture. The Pure Advantage Nitrile glove had low glove donning forces for both single-glove donning configurations and double-glove donning configurations. Consequently, we recommend the Pure Advantage Nitrile glove as the powder-free, non-latex, double-glove system.