Five-Year Follow-Up of Parapapillary Atrophy: The Beijing Eye Study

Purpose: To assess longitudinal changes in parapapillary atrophy in the adult population of Greater Beijing. Methods: The population-based Beijing Eye Study 2006 included 3251 subjects who had participated in the Beijing Eye Study 2001 and returned for re-examination. The mean age was 60.4610.1 years. Using optic disc photographs, we measured parapapillary atrophy which was divided into alpha zone and beta zone. Results: Overall progression rate of alpha zone was seen in 0.660.1 % (95 % confidence interval (CI):0.3,0.9) of the subjects and of beta zone in 8.260.5 % (95%CI:7.2,9.1) of the subjects. In binary regression analysis, rate of progression of alpha zone was significantly associated higher age (P = 0.04) and the co-progression of zone Beta (P,0.001). Rate of progression of beta zone was significantly associated with higher age (P,0.001; odds ratio (OR):1.11;95%CI:1.10,1.14), higher intraocular pressure (P,0.001;OR:1.10;95%CI:1.05,1.14), higher myopic refractive error (P,0.001;OR:0.71; 95%CI:0.67,0.75), rural region of habitation (P = 0.002;OR: 0.58; 95%CI:0.41,0.82), presence of glaucomatous optic nerve damage (P,0.001;OR:2.89; 95%CI:1.62,5.14), co-progression of alpha zone (P,0.001;OR:7.13;95%CI:2.43,20.9), absence of arterial hypertension (P = 0.03;OR: 0.70; 95%CI:0.51,0.96), and thicker central corneal thickness (P = 0.02;OR:1.01;95%CI:1.00,1.01). Subjects with a non-glaucomatous optic nerve damage (n = 22) as compared to the remaining subjects did not vary in the progression rate of alpha zone (0.0 % versus 0.660.1%; P = 1.0) and beta zone (8.260.5 % versus 6.360.6%;P = 1.0)

Rapid Sampling of Molecules via Skin for Diagnostic and Forensic Applications

Skin provides an excellent portal for diagnostic monitoring of a variety of entities; however, there is a dearth of reliable methods for patient-friendly sampling of skin constituents. This study describes the use of low-frequency ultrasound as a one-step methodology for rapid sampling of molecules from the skin. Sampling was performed using a brief exposure of 20 kHz ultrasound to skin in the presence of a sampling fluid. In vitro sampling from porcine skin was performed to assess the effectiveness of the method and its ability to sample drugs and endogenous epidermal biomolecules from the skin. Dermal presence of an antifungal drug—fluconazole and an abused substance, cocaine—was assessed in rats. Ultrasonic sampling captured the native profile of various naturally occurring moisturizing factors in skin. A high sampling efficiency (79 ± 13%) of topically delivered drug was achieved. Ultrasound consistently sampled greater amounts of drug from the skin compared to tape stripping. Ultrasonic sampling also detected sustained presence of cocaine in rat skin for up to 7 days as compared to its rapid disappearance from the urine. Ultrasonic sampling provides significant advantages including enhanced sampling from deeper layers of skin and high temporal sampling sensitivity

Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis

Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al

The two sides of cytokine signaling and glaucomatous optic neuropathy

The mechanistic study of glaucoma pathogenesis has shifted to seeking to understand the effects of immune responses on retinal ganglion cell damage and protection. Cytokines are the hormonal factors that mediate most of the biological effects in both the immune and nonimmune systems. CD4-expressing T helper cells are a major source of cytokine production and regulation. Type 1 helper T (Th1) cells are characterized by the production of proinflammatory cytokines such as interferon-gamma, interleukin (IL)-2, IL-12, IL-23, and tumor necrosis factor-alpha while type 2 helper T (Th2) cells are characterized by the production of IL-4, IL-5, IL-6, and IL-10. The balance of Th1/Th2 cytokine production influences many pathological processes and plays both causative and protective roles in neuron damages. Growing evidence indicates that imbalances of Th1/Th2 cytokine production are involved in neural damage or protection in many neurological diseases. In this review, we discuss the possible roles of Th1/Th2 cytokine production and imbalance of Th1/Th2 cytokines in retina, especially glaucomatous optic neuropathy

Ultrasound-Enhanced Drug Transport and Distribution in the Brain

Drug delivery in the brain is limited by slow drug diffusion in the brain tissue. This study tested the hypothesis that ultrasound can safely enhance the permeation of drugs in the brain. In vitro exposure to ultrasound at various frequencies (85 kHz, 174 kHz, and 1 MHz) enhanced the permeation of tritium-labeled molecules with molecular weight up to 70 kDa across porcine brain tissue. A maximum enhancement of 24-fold was observed at 85 kHz and 1,200 J/cm2. In vivo exposure to 1-MHz ultrasound further demonstrated the ability of ultrasound to facilitate molecule distribution in the brain of a non-human primate. Finally, ultrasound under conditions similar to those used in vivo was shown to cause no damage to plasmid DNA, siRNA, adeno-associated virus, and fetal rat cortical neurons over a range of conditions. Altogether, these studies demonstrate that ultrasound can increase drug permeation in the brain in vitro and in vivo under conditions that did not cause detectable damage

Expression and Functional Studies of Ubiquitin C-Terminal Hydrolase L1 Regulated Genes

Deubiquitinating enzymes (DUBs) have been increasingly implicated in regulation of cellular processes, but a functional role for Ubiquitin C-terminal Hydrolases (UCHs), which has been largely relegated to processing of small ubiquitinated peptides, remains unexplored. One member of the UCH family, UCH L1, is expressed in a number of malignancies suggesting that this DUB might be involved in oncogenic processes, and increased expression and activity of UCH L1 have been detected in EBV-immortalized cell lines. Here we present an analysis of genes regulated by UCH L1 shown by microarray profiles obtained from cells in which expression of the gene was inhibited by RNAi. Microarray data were verified with subsequent real-time PCR analysis. We found that inhibition of UCH L1 activates genes that control apoptosis, cell cycle arrest and at the same time suppresses expression of genes involved in proliferation and migration pathways. These findings are complemented by biological assays for apoptosis, cell cycle progression and migration that support the data obtained from microarray analysis, and suggest that the multi-functional molecule UCH L1 plays a role in regulating principal pathways involved in oncogenesis