Clinical Pharmacokinetics and Safety of a 10% Aminolevulinic Acid Hydrochloride Nanoemulsion Gel (BF-200 ALA) in Photodynamic Therapy of Patients Extensively Affected With Actinic Keratosis: Results of 2 Maximal Usage Pharmacokinetic Trials.

The nanoemulsion-based 10% aminolevulinic acid (ALA) hydrochloride gel BF-200 ALA optimizes epidermal penetration of its active ingredient and is approved for topical photodynamic therapy (PDT) for the treatment of actinic keratosis in the United States and Europe. To characterize systemic absorption from dermal application during PDT, ALA and its key active metabolite protoporphyrin IX (PpIX) were analyzed in 2 maximal usage pharmacokinetic trials (MUsT) in patients severely affected with actinic keratosis. The primary objective of both MUsTs was to assess baseline-adjusted plasma concentration-time curves for ALA and PpIX after a single PDT treatment applying either 2 g (1 tube) of BF-200 ALA on the face (MUsT-1) or applying 6 g (3 tubes) of BF-200 ALA on the face/scalp or body periphery (MUsT-2), to 20 or 60 cm2 , respectively. All PDTs were performed using red light at around 635 nm wavelength. Safety and tolerability were documented along with pharmacokinetics. In both MUsTs, ALA plasma concentrations were transiently increased to a maximum concentration at about 2.5 to 3.3 times above endogenous baseline with time to maximum concentration at ≈3 hours after dosing. Plasma levels subsequently returned to baseline within 10 hours after dosing. Overall baseline-adjusted mean area under the baseline-adjusted plasma concentration-time curve from time zero to the last sampling time point at which the concentration was at or above the lower limit of quantification ranged from 142.8 to 146.2, indicating that a similar, minor fraction of topical ALA is systemically absorbed under both dosing regimens. Systemic PpIX exposure after administration of either dose of BF-200 ALA was equally minimal. Application site skin reactions were treatment area size-related, albeit transient and consistent with the known safety profile of BF-200 ALA.

Distribution of total and methylmercury in different ecosystem compartments in the Everglades: implications for mercury bioaccumulation.

We analyzed Hg species distribution patterns among ecosystem compartments in the Everglades at the landscape level in order to explore the implications of Hg distribution for Hg bioaccumulation and to investigate major biogeochemical processes that are pertinent to the observed Hg distribution patterns. At an Everglade-wide scale, THg concentrations were significantly increased in the following order: periphyton

A simple procedure for the covalent grafting of triphenylphosphine ligands on silica: application in the palladium catalyzed Suzuki reaction.

An organic-inorganic hybrid material derived from covalently grafting a palladium complex of the type (L)(2)PdCl(2) (L = Si(OMe)(3) functionalized PPh(3)) on silica was synthesized, characterized and sucessfully applied as a catalyst for the Suzuki reaction.

Amphibian and reptile declines over 35 years at La Selva, Costa Rica.

Amphibians stand at the forefront of a global biodiversity crisis. More than one-third of amphibian species are globally threatened, and over 120 species have likely suffered global extinction since 1980. Most alarmingly, many rapid declines and extinctions are occurring in pristine sites lacking obvious adverse effects of human activities. The causes of these "enigmatic" declines remain highly contested. Still, lack of long-term data on amphibian populations severely limits our understanding of the distribution of amphibian declines, and therefore the ultimate causes of these declines. Here, we identify a systematic community-wide decline in populations of terrestrial amphibians at La Selva Biological Station, a protected old-growth lowland rainforest in lower Central America. We use data collected over 35 years to show that population density of all species of terrestrial amphibians has declined by approximately 75% since 1970, and we show identical trends for all species of common reptiles. The trends we identify are neither consistent with recent emergence of chytridiomycosis nor the climate-linked epidemic hypothesis, two leading putative causes of enigmatic amphibian declines. Instead, our data suggest that declines are due to climate-driven reductions in the quantity of standing leaf litter, a critical microhabitat for amphibians and reptiles in this assemblage. Our results raise further concerns about the global persistence of amphibian populations by identifying widespread declines in species and habitats that are not currently recognized as susceptible to such risks.

GENETIC VARIATION AND COVARIATION IN RESPONSES TO HOST PLANTS BY ALSOPHILA POMETARIA (LEPIDOPTERA: GEOMETRIDAE).

Progeny of uncommon parthenogenetic genotypes of the polyphagous geometric Alsophila pometaria were reared on four host plant species representing the same genus, different confamilial genera, and different families. On the supposition that uncommon asexual genotypes have arisen recently from the sympatric sexual population, they may be viewed as a representation of variation in the sexual population that has been captured by parthenogenesis. In both the laboratory and the field, significant effects of genotype, host, and their interaction were found for survival. Live weight displayed significant effects of genotype, host, and genotype x host interaction in the laboratory, and significant main effects in the field. The broad heritability of live weight within hosts was significantly greater than zero in all cases, ranging from 0.18 to 0.33. Heritability values in the field were similar to those in the laboratory. Genetic correlations between weight attained on pairs of host plants, calculated from uncorrected family means, were all positive and many were statistically significant. When the data were corrected for differences in generalized vigor by taking the deviations from genotype means on a standard host plant, one of nine genetic correlations was significant and positive, and one was significant and negative. Within their limits of precision, these data suggest that genetic factors enhancing performance on one host do not generally have strong antagonistic pleiotropic effects on performance on the other hosts in this population. The relevance of these observations to the evolution of resource specialization in general and host specialization by phytophagous insects in particular is discussed. The common assumption that trade-offs in efficiency of utilization cause the evolution of specialized resource use requires more empirical evidence than seems to exist.