Posterior uveal malignant melanoma: temporal stability and ethnic variation in rates in Israel.

In a population-based study of posterior uveal malignant melanoma (755 incidence cases), the authors found a stabilized incidence in Israel from 1961-1996. Overall, Jewish immigrants to Israel had a relative rate (RR) of 2.2 [95% confidence interval [1.5-2.6] as compared to the reference population (Israeli-born Jews with Israel-born parents, i.e. third generation). Whereas individuals born in Eastern Europe or the Americas experienced the highest age adjusted incidence rates per million [for example; from 1972-1996, 8.3 for those from Poland, 8.2 from Romania, 6.4 from the former Union of Soviet Socialist Republics, 7.6 from the Americas], the lowest incidence rates were observed among immigrants from Algeria-Morocco-Tunisia (rate of 2.8), Iraq (1.7), Iran (3.2). Jews born in Israel exhibited incidence patterns similar to those individuals from the place of their parent's birth; high rates were observed among individuals born of American- or European-born parents (rate of 7.2), and low rates among offspring of parents who migrated from Africa or Asia (2.6). A low incidence was found among Israeli-born Arabs (2.6 in men, and 2.0 in women). The stable differences in incidence rates, according to populations of Jews, and the persistence of these variations within the descendants of these populations suggest that underlying susceptibility states are related to an individual's origin.

Influence of emulsion droplet surface charge on indomethacin ocular tissue distribution.

The aim of this study was to compare the corneal penetration of indomethacin from Indocollyre [a marketed hydro-poly(ethylene glycol) (PEG) ocular solution] to that of a negatively and a positively charged submicron emulsion. Male albino rabbits were separated randomly into three groups and each group (N = 15) was treated with either one drop of radiolabeled 0.1% Indocollyre, or 0.1% indomethacin positively or negatively charged submicron emulsion, respectively. The rabbits were sacrificed at selected time points and the eyes were enucleated. The eyes were dissected into the different tissues: cornea, conjunctiva, aqueous humor, iris, lens, vitreous, sclera, and retina. The samples were weighed before radioactivity counting. Regardless of the preparation instilled, the highest concentration of indomethacin was achieved in the cornea followed by conjunctiva, sclera retina, and aqueous humor. However, the positively charged emulsion provided significantly higher drug levels than the control solution and negatively charged emulsion only in the aqueous humor and sclera-retina. Furthermore, the spreading coefficient of the positively charged emulsion on cornea is four times higher than that of the negatively charged emulsion. It was therefore deduced that the positively charged submicron emulsions have better wettability properties on the cornea compared to either saline or the negatively charged emulsion. The positive charge may prolong the residence time of the drop on the epithelial layer of the cornea and thus enable better drug penetration through the cornea to the internal tissues of the eye, as confirmed by the animal studies.

Efficacy of sustained-release radioprotective drugs in vivo.

In previous publications from this laboratory we suggested the use of radioprotective drugs in a sustained-release form as a practical way to cope with their high toxicity and quick metabolism and excretion. Cysteine and cysteamine, well-established radioprotectants, were used as model drugs and compressed at various concentrations (0-65%) into an insoluble tablet matrix, composed of ethylcellulose and stearic acid at various ratios and compression pressures. We demonstrated in vitro that when the release rate of the radioprotectants was measured under nitrogen, the kinetic data conformed with the Higuchi square root of time equation, indicating that the release of both drugs correlates with Higuchi's diffusional mechanism. In the present in vivo study, tablets containing cysteine or cysteamine in a slow-release matrix were implanted, into the stomachs of female rats. The rats were irradiated at various time intervals up to 12 h after implantation and their survival recorded daily. Utilizing a 1:3 ratio of ethylcellulose:stearic acid as a matrix, the protective effect of the drugs was remarkable eight hours after tablet implantation. The results reported indicate that slow-release tablet formulation is a possible method for delivering of radioprotective drugs over an extended period of time.

Controlled release of radioprotective agents from matrix tablets--effect of preparative conditions on release rates.

Release rates of radioprotective agents from insoluble matrix tablets were measured as a function of ethylcellulose/stearic acid ratio and active ingredient concentration in the matrix. The influence of the compacting pressure applied during tablet formation on the release of these aminothiol compounds was also examined. The kinetic data conformed with the Higuchi square root equation and first order release. As both plots were linearly acceptable, a statistical method for release mechanism identification using the kinetic experimental results obtained without any further transformation was used. This non-linear regression search procedure accompanied by the chi 2-square test has shown that that aminothiol release from the matrix tablets definitely follows the Higuchi square root equation. Increasing the ethylcellulose amount in the matrix consequently improves the degree of wettability and leads to a faster rate of solvent penetration. This tends to release the aminothiols more rapidly from the matrix tablets. Solvent penetration, which also follows a square root of time relationship, is probably the rate-limiting factor in the release process. The linear increase in release rates of the aminothiols observed with ethylcellulose concentration is explained by a parallel increase in the porosity of the matrix tablets. Increase in the drug concentration in the tablet increases the cysteine hydrochloride release rate and decreases the cysteamine hydrochloride release rate. A similar effect was also observed by applying increasing compacting pressure during matrix tablet formation. It was suggested that these two experimental factors differently affect the internal structure of the matrix during the preparation process.(ABSTRACT TRUNCATED AT 250 WORDS)