The Use of Mucoadhesive Polymers to Enhance the Hypotensive Effect of a Melatonin Analogue, 5-MCA-NAT, in Rabbit Eyes

Purpose.: 5-Methoxy-carbonylamino-N-acetyltryptamine (5-MCA-NAT, a melatonin receptor agonist) produces a clear intraocular pressure (IOP) reduction in New Zealand White rabbits and glaucomatous monkeys. The goal of this study was to evaluate whether the hypotensive effect of 5-MCA-NAT was enhanced by the presence of cellulose derivatives, some of them with bioadhesive properties, as well as to determine whether these formulations were well tolerated by the ocular surface. Methods.: Formulations were prepared with propylene glycol (0.275%), carboxymethyl cellulose (CMC, 0.5% and 1.0%) of low and medium viscosity and hydroxypropylmethyl cellulose (0.3%). Quantification of 5-MCA-NAT (100 μM) was assessed by HPLC. In vitro tolerance was evaluated by the MTT method in human corneal-limbal epithelial cells and normal human conjunctival cells. In vivo tolerance was analyzed by biomicroscopy and specular microscopy in rabbit eyes. The ocular hypotensive effect was evaluated measuring IOP for 8 hours in rabbit eyes. Results.: All the formulations demonstrated good in vitro and in vivo tolerance. 5-MCA-NAT in CMC medium viscosity 0.5% was the most effective at reducing IOP (maximum IOP reduction, 30.27%), and its effect lasted approximately 7 hours. Conclusions.: The hypotensive effect of 5-MCA-NAT was increased by using bioadhesive polymers in formulations that are suitable for the ocular surface and also protective of the eye in long-term therapies. The use of 5-MCA-NAT combined with bioadhesive polymers is a good strategy in the treatment of ocular hypertension and glaucoma.

Search for very high energy gamma radiation from the radio bright region DR4 of the SNR G78.2+2.1

Data from the HEGRA air shower array are used to set an upper limit on the emission of gamma-radiation above 25 (18) TeV from the direction of the radio bright region DR4 within the SNR G78.2 + 2.1 of 2.5 (7.1). 10^-13 cm^-2 sec^-1. The shock front of SNR G78.2 + 2.1 probably recently overtook the molecular cloud Gong 8 which then acts as a target for the cosmic rays produced within the SNR, thus leading to the expectation of enhanced gamma-radiation. Using a model of Drury, Aharonian and Völk which assumes that SNRs are the sources of galactic cosmic rays via first order Fermi acceleration, we calculated a theoretical prediction for the gamma-ray flux from the DR4 region and compared it with our experimental flux limit. Our 'best estimate' value for the predicted flux lies a factor of about 18 above the upper limit for gamma-ray energies above 25 TeV. Possible reasons for this discrepancy are discussed.