Reproducible measurement of macular light flash recovery time using a novel device can indicate the presence and worsening of macular diseases.

PURPOSE: To determine the safety, sensitivity, and specificity of a novel flash photorecovery timing instrument with response verification in differentiating normal from abnormal maculae, and in detecting worsening macular disease. METHODS: Right and left eye photorecovery times were determined at baseline and after 5 min using a xenon arc, flash filtered for infrared, ultraviolet, and visible short wavelengths, delivered through an aperture in a hand-held tube. A push-button actuated timer and flash and stopped timer when lighted numbers became visible post-flash. A numeric keypad verified responses. Normal subjects (two eyes tested, n = 144; one eye tested, n = 108) ranged in age from 15 to 84. Photorecovery times were measured in one eye of subjects with small drusen and 20/20 acuity (53-55 correct ETDRS letters; n = 57); in both eyes of subjects with dry age-related macular degeneration (AMD; n = 118); wet AMD with (n = 19) or without (n = 17) macular fluid; and eyes of diabetics with background retinopathy with (n = 19) or without (n = 17) macular retinal thickening. Once-weekly photorecovery measurements for 6 months in each eye of 10 dry AMD subjects and 10 dry diabetic maculopathy subjects provided longitudinal data. RESULTS: Normal subjects' mean right eye recovery time was 9.6 sec (+/- 1.9 SD); left 10.8 sec (+/- 1.0 SD). Photorecovery lengthened after age 55, nearly doubling that of young subjects by age 80. Macular edema, serous macular detachment, or worsened dry AMD were accompanied by prolonged photorecovery (p < .01). When abnormal new vessels or retinal thickening appeared in three serially followed patients, photorecovery at least doubled (p < .01). In all three, photorecovery prolongation occurred without clinical symptoms. None of the 499 tested subjects reported adverse events due to the flash testing. CONCLUSIONS: These findings support the usefulness of a reproducible light flash macular vision recovery measurement as an indicator of macular pathology and worsening disease.

A randomized, prospective, placebo-controlled clinical trial of a novel zinc-monocysteine compound in age-related macular degeneration.

PURPOSE: To test the hypothesis that daily use of zinc-monocysteine (ZMC) supplement will be well tolerated and result in improved macular function in persons with dry age-related macular degeneration (AMD). METHODS: Eligible, consenting subjects were randomized to either ZMC 25 mg or placebo twice daily for 6 months. Both ZMC and placebo groups enrolled 40 participants, with best corrected visual acuity 20/25 to 20/70, macular drusen, and pigment changes. Masked personnel determined baseline, 3- and 6-month best-corrected visual acuity, contrast sensitivity, and light flash recovery time. Differences between ZMC and placebo were analyzed by a one-sided unpaired t-test of the paired differences between baseline and 3- and 6-month timepoints for right and left eyes separately. RESULTS: By 6 months the ZMC group showed improved visual acuity (p < 0.0001) and contrast sensitivity (p < 0.0001). Macular light flash recovery time shortened in the ZMC group at 3 months by 2.1 sec (left eye, p = 0.0001) to 3.6 sec (right eye, p < 0.0001), and at 6 months by 7.2 sec (left eye, p < 0.0001) to 7.4 sec (right eye, p < 0.0001). This variable had no improvement in the placebo group. ZMC had a gastrointestinal irritation rate of under 2%. CONCLUSION: ZMC 25 mg twice daily was well tolerated and was associated with improved macular function in comparison to a placebo in persons with dry AMD.

Molecular dynamics simulations of mass transfer resistance in grain boundaries of twinned zeolite membranes.

The net mass transfer resistance for gas molecules permeating through zeolite membranes includes contributions from intracrystalline diffusion and contributions from interfacial effects. These interfacial effects can arise either from gas-zeolite interfaces or from interfaces that exist within zeolite crystals due to grain boundaries. We present the first atomically detailed simulations that examine interfacial mass transfer resistance due to internal grain boundaries in zeolites that are relevant for membrane applications. Our calculations examine twinned silicalite crystals in crystallographic configurations that have been identified in previous experiments. We used the dual control volume grand canonical molecular dynamics method to simulate the permeance of CH(4) and CF(4) through thin twinned silicalite crystals. The magnitudes of the grain boundary resistances are quite substantial, at least for the thin crystals that are accessible in our simulations.

Influences of interfacial resistances on gas transport through carbon nanotube membranes.

Carbon nanotubes have significant promise as gas separation membranes. Gas permeation through nanopores involves mass transfer resistances from molecules entering and leaving pores (so-called surface resistances) and diffusion within the pores. We use molecular simulations to give the first estimates of surface resistances for gas transport through nanotubes. For CH4 transport through (20,0) carbon nanotubes at 300 K, surface resistances are small for nanotubes 5-10 mum in length but can be significant for shorter nanotubes.

A novel zinc compound (zinc monocysteine) enhances the antioxidant capacity of human retinal pigment epithelial cells.

PURPOSE: The aim of this study was to document the effect of a novel zinc amino acid combination on the concentrations of important antioxidants in cultured human retinal pigment epithelial (hRPE) cells. METHODS: Primary confluent hRPE cells were treated with 30 microM of zinc acetate, zinc chloride, zinc cysteine, and zinc sulfate. The antioxidants catalase, glutathione, glutathione peroxidase, and metallothionein were measured. MTT assays were performed to determine the relative protection of the zinc compounds from the cytotoxic effects of H202 and t-butyl hydroperoxide. RESULTS: Catalase and glutathione peroxidase activities were increased by the zinc formulations compared with the untreated control. Glutathione and metallothionein content were also increased. The greatest increases occurred with zinc conjugated to the amino acid cysteine. The MTT assays showed that zinc monocysteine protected cultured RPE cells from the toxicity of H2O2 and t-butyl hydroperoxide. CONCLUSIONS: Our results demonstrate that zinc treatment of RPE cells increases antioxidants and protects cultured RPE cells from the cytotoxic effects of H2O2 and t-butyl hydroperoxide. The results show that zinc conjugated to cysteine offers greater benefits than either zinc salts or cysteine alone.

Predictive assessment of surface resistances in zeolite membranes using atomically detailed models.

The diffusive transport of molecules through nanoporous membranes is determined by both intracrystalline diffusion and mass transport resistances associated with entering and leaving the membrane material. We compare two methods for assessing the relative importance of these resistances based on atomically detailed descriptions of the membrane material. For extremely thin membranes, net transport can be assessed using dual control volume grand canonical molecular dynamics (DCV-GCMD). We show that previous implementations of this technique may have been influenced by nonisothermal effects in interfacial regions and suggest a simple remedy to this situation. We also introduce an approximate method that uses information only from equilibrium MD simulations, which avoids the significant computational expense associated with DCV-GCMD. This approximate method can be used to rapidly assess the importance of interface-related resistances to mass transport over broad ranges of membrane operating conditions. This method will be useful in allowing a rapid determination of whether these interface resistances are significant in practical experimental situations. These two methods are compared by considering the transport of CH(4) and CF(4) through defect-free silicalite membranes.

Expression of metallothionein isoforms in human chorioretinal complex.

PURPOSE: To determine the relative expression of metallothionein isoforms and their differential induction by oxidative stress in cultured RPE cells and to localize the isoforms in the human chorioretinal complex. METHODS: Total RNA was isolated from cultured human retinal pigment epithelial cells using TRI-Reagent. An "anchor-oligo-dT primer" was used for the synthesis of cDNA, reverse transcribed using avian reverse transcriptase and subsequently subjected to PCR analysis using oligonucleotides specific for metallothionein (MT) I, MT II, and MT III. The selected transcripts were then used to assess the expression of the above elements in fixed tissue sections by in situ hybridization. Cultured RPE cells were allowed to phagocytose bovine photoreceptor outer segments (ROS) or were treated with H(2)O(2) for 6 hours and then analyzed by RT-PCR or in situ hybridization to ascertain the effect of oxidative stress on metallothionein mRNA isoform expression. RESULTS: Relative density analysis of amplified products demonstrate the presence of MT I, MT II and MT III in RPE cells, with an apparent relative expression MT II > MT I > MT III [corrected]. Expression of MT I and MT II mRNA was increased by both phagocytosis and hydrogen peroxide, however MT III was not induced by either stress. In situ hybridization corroborated the findings of the RT-PCR analysis and showed that MTs were mainly localized in the RPE and the photoreceptor layer of the retina. CONCLUSIONS: The localization of MT and the response of MT to oxidative stress are consistent with a role for MT as an antioxidant in the RPE and retina. Studies are ongoing to determine the specific mechanisms of action of these antioxidants in RPE cells.