Synthetic Hydrogel as an Artificial Vitreous Body. A One-Year Animal Study of Its Effects on the Retina

A hydrogel with a high water content was assessed in vitro and in vivo as a possible vitreous substitute. From a large series of polymers produced by the aqueous polymerization of methyl acrylamidoglycolate methyl ether (MAGME), a gel synthesized in 80% water was selected for an animal study. The gel was injected intravitreally into rabbit eyes and followed clinically by ophthalmoscopy, tonometry, and fundus photography. The gel was clinically well tolerated, but after 6 months ophthalmoscopy revealed progressive pallor of the optic nerve head. The eyes were enucleated one year after injection of polymer. Histopathological examination by light microscopy of retinal and vitreal sections revealed significant retinal disorganization, degeneration of the optic nerve and retinal neural elements, retinal detachment, and inflammatory changes. Analysis of immunohistochemically labeled retinal sections revealed loss of ganglion cells and extensive pathological reaction of the Muller cells and astrocytes. All these findings were consistent with a toxic effect of the polymer itself or some residual contaminants. The cytotoxicity of the hydrogel was assessed in vitro using cultured mouse (Balb/c-3T3) fibroblasts. The bioassay showed both cytostatic and cytocidal effects of the polymer. Our results indicate that hydrogels produced from MAGME monomer cannot function as vitreous substitutes because of severe toxic reaction elicited to the posterior segment of the eye

Asymmetric Excitatory Synaptic Dynamics Underlie Interaural Time Difference Processing in the Auditory System

In order to localize sounds in the environment, the auditory system detects and encodes differences in signals between each ear. The exquisite sensitivity of auditory brain stem neurons to the differences in rise time of the excitation signals from the two ears allows for neuronal encoding of microsecond interaural time differences

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Effect of hydration on the ablation of poly(2-hydroxyethyl methacrylate) by the 213-nm laser radiation

Since the discovery two decades ago of the possibility to remove material from the surface of solid organic polymers in a highly controllable fashion by the use of pulsed UV laser radiation, the applications of the UV lasers have diversified significantly. The excimer lasers, which operate with molecules or halides of rare gases as the gain medium to generate UV energy, have been extensively used both in microfabrication by direct etching and in surgery. With the advent of new nonlinear optical crystals, solid-state lasers have been also developed that are able to generateUVenergy from the fourth (266 nm) or fifth (213 nm) harmonic outputs of the Nd:YAG laser, which are easy to use and maintain. Results of experimental investigations regarding their use in the refractive surgery of the cornea suggest that solid-sate lasers could successfully replace excimer lasers in such procedures. © 2003 Kluwer Academic Publisher