Byron H.P. Li

Prevention of organophosphate intoxication with presynaptic cholinergic blockers

In Vivo cardiovascular neuromuscular preparation of rats was used to study the prophylaxis and mechanism of diisopropyl fluorophosphate (DFP) intoxication by presynaptic cholinolytic agents (ganglionic blocking agents), including hexamethonium, trimethaphan and mecamylamine. The lethal action of DFP was partially or completely prevented by pretreatment of rats with hexamethonium (10 mg/kg), trimethaphan (80 mg/kg) and mecamylamine (30 mg/kg). Combined use of these drugs with 2-PAM (100 mg/kg) improved further the prophylaxis of DFP lethality. The mechanism of prophylaxis could be due to the reduction of acetylcholine turnover and accumulation at the synaptic cleft as hemicholinium prevented the DFP intoxication efficiently. In all cases, DFP caused cardiovascular suppression before neuromuscular blockade indicating that the cardiovascular system is much more sensitive than the neuromuscular junction to DFP intoxication.

Effects of Melatonin and Haloperidol Given via Vortex Vein on the Intraocular Pressure

Melatonin injected into the vortex vein of a rabbit eye produced an increase in intraocular pressure (IOP) which lasted for up to 5 h. Injection of haloperidol caused a decrease in IOP; this effect was totally reversed by melatonin. It is probable that these effects are caused by physiological antagonisms. Injection of the mu opiate agonist (D-ala2-n-methyl-ph2-gly5-ol) enkephalin caused a decrease in the IOP of artificially ventilated rabbits and a decrease in melatonin levels in iris, iris root-ciliary body, and retina of the rabbit eye. Melatonin levels did not decrease after anesthesia with rompunketamine. It is probable that the decrease in melatonin levels is specific to certain classes of opioids, and endogenous opioids may play a role in the regulation of ocular melatonin levels and hence IOP.

Inhibition of lens protein-, endotoxin- and interleukin-1-induced ocular inflammation with osthole and some other non-steroidal anti-Inflammatory agents

Anti-inflammatory actions of osthole and some other non-steroidal anti-inflammatory agents (NSAIA) were studied along with prednisolone on ocular inflammations induced by lens protein in rabbits and those induced by endotoxin or interleukin-1 (IL-1) in rats. It was found that ocular inflammation induced by lens protein at the anterior segment of the eyes can be inhibited by all agents tested, including osthole, mefenamic acid, indomethacin and norhydroguaiaretic acid. However, the posterior uveitis induced by endotoxin was inhibited only by osthole, mefenamic acid and prednisolone. IL-1-induced posterior uveitis was inhibited only by osthole and prednisolone. It is concluded that osthole is a unique agent for ocular inflammations, particularly for those which are difficult to treat, such as posterior uveitis.

Microvascular access to the uveal tract in the rabbit eye for ocular pharmacologic studies.

Drug delivery to the eyes is quite inefficient regardless if the drugs are administered topically or intravenously. It is known that less than 1% of topically instilled drug can be absorbed into the eyes while even less of intravenously injected drugs reach the eyes. A research model has been developed in this study which allows delivery of drugs effectively to uveal and anterior structures of the eye. This experimental model allows drugs to be delivered to the eye via cannulation of and retrograde flow through the valveless vortex veins. In addition, the superficial branch of the vortex vein (draining the ciliary body and iris) or the deep branch (draining the choroid plexus of the retina) can be selectively cannulated to suit the researchers needs. Finally, this procedure minimizes systemic drug actions which otherwise would complicate interpretation of experimental results. This model can be used for in vivo laboratory studies on (a) metabolic and physiological processes of the uveal tract in the eye, and (b) drug delivery to selective tissues of the uveal tract in the eye. Dose-response relationships of pilocarpine and timolol to lower intraocular pressure were demonstrated with this model.