Crystallization at Inorganic-organic Interfaces: Biominerals and Biomimetic Synthesis.

Crystallization is an important process in a wide range of scientific disciplines including chemistry, physics, biology, geology, and materials science. Recent investigations of biomineralization indicate that specific molecular interactions at inorganic-organic interfaces can result in the controlled nucleation and growth of inorganic crystals. Synthetic systems have highlighted the importance of electrostatic binding or association, geometric matching (epitaxis), and stereochemical correspondence in these recognition processes. Similarly, organic molecules in solution can influence the morphology of inorganic crystals if there is molecular complementarity at the crystal-additive interface. A biomimetic approach based on these principles could lead to the development of new strategies in the controlled synthesis of inorganic nanophases, the crystal engineering of bulk solids, and the assembly of organized composite and ceramic materials.

Pharmacokinetics, metabolism and distribution of 1,2-dihydro-8-(4-methylpiperazinyl)-4-phenylimidazo [1,2-A] pyrido [3,2-E] pyrazine-5-oxide in C3H mice.

PURPOSE: 1,2-Dihydro-8-(4-methylpiperazinyl)-4-phenylimidazo [1,2-a] pyrido [3,2-e] pyrazine-5-oxide (RB90740) is a bioreductive drug with an oxic to hypoxic toxicity ratio of 16 in cultured V79 cells in vitro. The aim of this study was to examine the pharmacokinetics, metabolism and distribution of the drug in tumor bearing C3H mice. METHODS AND MATERIALS: A high pressure liquid chromatography assay for the quantitative determination of concentrations of the drug and its metabolites has been developed and used to examine their distribution in blood, RIF-1 and KHT tumors, brain, muscle, and liver tissue. Urine and feces collected for 24 h after drug administration have been examined for the drug and its metabolism products. RESULTS: Three metabolites, two of which have been identified, have been observed in mouse tissue. 1,2-Dihydro-8-(4-methylpiperazinyl)-4-phenylimidazo [1,2-a]pyrido[3,2-e]pyrazine (RB92815) is the two-electron reduced species, which is observed in liver, urine and occassionally in tumor samples. 1,2-dihydro-8-(4-piperazinyl)-4-phenylimidazo [1,2-a]pyrido[3,2-e]pyrazine-5-oxide (RB1739), the N-demethylated compound, is observed in urine and liver. Elimination of the drug after an intraperitoneal dose of 50 mg/kg is biphasic with t(1)2 alpha = 3 min and t(1)2 beta = 219 min. The area under the curve for blood concentration vs. time is 1.4 mg ml min-1. The drug is preferentially taken up into tumor tissue as is apparent from the area under the curve values for RIF-1 (28.3 mg ml min-1) and KHT (18.4 mg ml min-1) tumors. CONCLUSION: From these values of the area under the curve it is suggested that the drug is present in tumor tissue at concentrations sufficient to eliminate the hypoxic fraction provided reduction to a toxic species occurs. Bioreduction by the addition of two electrons to form RB92815 occurs in some tumors, but it is not known if this is due to an obligate two-electron detoxifying step or if reduction occurs by single electron additions via a toxic free radical species.

Influence of simulated microgravity on human skeletal muscle architecture and function.

Ten male volunteers underwent a period of prolonged bed rest. Four subjects performed exercise countermeasures 2-3 times per week, while 6 subjects received no countermeasures. After bed rest plantarflexor force declined significantly (P < 0.001) in both exercise (-42%) and control (-55%) groups. The internal architecture of the gastrocnemius medialis (GM) muscle was significantly altered. This was associated with a reduction in fascicle shortening during isometric contraction. Exercise countermeasures partially mitigated the loss of muscle force and function following 90 days of bed rest.