The influence of size and abiotic factors on cutaneous water loss.

The greatest physiological threat to terrestrial life is dehydration; however, examining the factors that influence water balance in a teaching setting can be problematic. The proposed exercise examines cutaneous water loss using gelatin frogs. The use of models provides a unique approach to learning about water loss without the need of Institutional Animal Care and Use Committee approval or specialized equipment to measure dehydration from relatively small invertebrates. The first described hands-on experiment examines gelatin frogs of different sizes to understand how surface area-to-volume ratio impacts water loss. The second experiment exposes gelatin models to various conditions, such as convective air currents (wind) or extreme temperature, to understand how abiotic factors influence the vapor pressure deficit between the animal and environment and thus water loss. These easily adaptable activities use everyday household items and can be scaled accordingly to classes of different sizes and academic levels. Thus these flexible exercises can be approached through facilitated, guided, or open inquiry, as students formulate hypotheses, design the experiments, create graphs, and interpret the data through answering questions or a write up.

The efficacy and cardiac evaluation of aminomethyl tetrahydronaphthalene ketopiperazines: a novel class of potent MCH-R1 antagonists.

The design, synthesis, and biological studies of a novel class of MCH-R1 antagonists based on an aminotetrahydronaphthalene ketopiperazine scaffold is described. Compounds within this class promoted significant body weight reduction in mouse diet induced obesity studies. The potential for hERG blockage activity and QT interval studies in anesthetized dogs are discussed.

Aminomethyl tetrahydronaphthalene ketopiperazine MCH-R1 antagonists--Increasing selectivity over hERG.

A direct correlation between hERG binding and QTc prolongation was established for a series of aminomethyl tetrahydronaphthalene ketopiperazine MCH-R1 antagonists. Compounds within this class with greater selectivity over hERG were developed. Compound 4h proved to have the best profile, with MCH-R1 Ki = 16 nm and hERG IC50 = 25 microM.

Profiling of drugs for membrane activity using liposomes as an in vitro model system.

The increasing size of chemical libraries being analyzed by high-throughput screening results in a growing number of active compounds that need to be assessed before moving forward in the drug development process. As a consequence, more rapid and highly sensitive strategies are required to accelerate the process of drug discovery without increasing the cost. Due to the fact that significant numbers of compounds from combinatorial libraries are hydrophobic in nature, approaches are needed to evaluate the potentialfor these compounds to interfere with the functions of biological membranes. The liposome system was used to detect agents that act as follows: (i) ionophores able to induce specific ion permeability, e.g., valinomycin for K+ and protonophoric uncouplers for H+; (ii) ion antiporters which exchange H+ for other ions, e.g., nigericin; (iii) agents that form low specificity ion channels in the membrane, e.g., gramicidin; and (iv) detergents and other membrane-disrupting agents. We propose using this liposome assay during the drug development process to identify compounds that have membrane activity and, as a consequence, produce a biological effect by altering the physico-chemical properties of the cell membrane rather than interacting with a protein target. Screening of a representative set of biologically-active compounds (198) indicated that the majority of systemic antimicrobial drugs, but not topical drugs, lack membrane activity in this model system.