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.

The effect of the geomagnetic field on cosmic ray energy estimates and large scale anisotropy searches on data from the Pierre Auger Observatory

We present a comprehensive study of the influence of the geomagnetic field on the energy estimation of extensive air showers with a zenith angle smaller than 60 degrees, detected at the Pierre Auger Observatory. the geomagnetic field induces an azimuthal modulation of the estimated energy of cosmic rays up to the similar to 2% level at large zenith angles. We present a method to account for this modulation of the reconstructed energy. We analyse the effect of the modulation on large scale anisotropy searches in the arrival direction distributions of cosmic rays. At a given energy, the geomagnetic effect is shown to induce a pseudo-dipolar pattern at the percent level in the declination distribution that needs to be accounted for.

First detection of the Sunyaev Zel'dovich effect increment at λ < 650 μm

The Sunyaev-Zel'dovich (SZ) effect is a spectral distortion of the cosmic microwave background as observed through the hot plasma in galaxy clusters. This distortion is a decrement in the CMB intensity for λ > 1.3 mm, an increment at shorter wavelengths, and small again by λ ~ 250 μm. As part of the Herschel Lensing Survey (HLS) we have mapped 1E0657–56 (the Bullet cluster) with SPIRE with bands centered at 250, 350 and 500 μm and have detected the SZ effect at the two longest wavelengths. The measured SZ effect increment central intensities are ΔI_0 = 0.097 ± 0.019 MJy sr^-1 at 350 μm and ΔI_0 = 0.268 ± 0.031 MJy sr^-1 at 500 μm, consistent with the SZ effect spectrum derived from previous measurements at 2 mm. No other diffuse emission is detected. The presence of the finite temperature SZ effect correction is preferred by the SPIRE data at a significance of 2.1σ, opening the possibility that the relativistic SZ effect correction can be constrained by SPIRE in a sample of clusters. The results presented here have important ramifications for both sub-mm measurements of galaxy clusters and blank field surveys with SPIRE.