Synthesis of 2-substituted-pyrrolidinethiourea derivatives and their antagonist effect on vanilloid receptor

Four pyrrolidine derivatives were prepared by the formation of a 5-membered ring based on capsazepine. Among them, the two carbon extended derivatives, 4a (IC(50)=55 microM) and 4b (IC(50)=3 microM), both showed different levels of antagonist activity against the vanilloid receptor in a (45)Ca(2+)-influx assay.     

Endurance training alters outward K+ current characteristics in rat cardiocytes.

The effect of endurance run training on outward K+ currents with rapidly inactivating (I(to)) and sustained or slowly inactivating (I(sus)) characteristics was examined in left ventricular (LV) cardiocytes isolated from sedentary (Sed) and treadmill-trained (Tr) female Sprague-Dawley rats. Isolated LV cardiocytes were used in whole cell patch-clamp studies to characterize whole cell I(to) and I(sus). Peak I(to) was greatest in cells isolated from the Tr group. When I(to) was corrected for cell capacitance to yield a current density, most, but not all, of the Sed vs. Tr differences in I(to) magnitude were eliminated. Regardless of how I(to) was expressed (e.g., I(to) or I(to) density), the time required to achieve a peak value was markedly shortened in the cardiocytes isolated from the Tr group. Training elicited a reduction in I(sus) density. Action potential characteristics were determined in Sed and Tr cardiocytes in primary culture. Training did not affect resting membrane potential, whereas peak membrane potential was reduced and time to peak membrane potential was prolonged in the Tr group. In addition, time to 50% repolarization was significantly increased in cells from the Tr group. Collectively, these data indicate that I(to) and I(sus) characteristics are altered by training in isolated LV cardiocytes. These alterations in I(to) and I(sus) may be responsible, at least in part, for the training-induced alterations in action potential configuration in cardiocytes in primary culture.     

Asiaticoside mimetics as wound healing agent

Novel asiaticoside mimetics simplified the sugar moiety by alkoxyalkyl groups were synthesized, and tested their wound healing effects by tensile strength measurement.     

Microbially enhanced dissolution of HgS in an acid mine drainage system in the California Coast Range

Mercury sulfides (cinnabar and metacinnabar) are the main ores of Hg and are relatively stable under oxic conditions (K_sp = 10^?54 and 10^?52, respectively). However, until now their stability in the presence of micro‐organisms inhabiting acid mine drainage (AMD) systems was unknown. We tested the effects of the AMD microbial community from the inoperative Hg mine at New Idria, CA, present in sediments of an AMD settling pond adjacent to the main waste pile and in a microbial biofilm on the surface of this pond, on the solubility of crystalline HgS. A 16S rRNA gene clone library revealed that the AMD microbial community was dominated by Fe‐oxidizing (orders Ferritrophicales and Gallionellas) and S‐oxidizing bacteria (Thiomonas sp.), with smaller amounts (≤6%) being comprised of the orders Xanthomondales and Rhodospirillales. Though the order Ferritrophicales dominate the 16S rRNA clones (>60%), qPCR results of the microbial community indicate that the Thiomonas sp. represents ~55% of the total micro‐organisms in the top 1 cm of the AMD microbial community. Although supersaturated with respect to cinnabar and metacinnabar, microcosms inoculated with the AMD microbial community were capable of releasing significantly more Hg into solution compared to inactivated or abiotic controls. Four different Hg‐containing materials were tested for bacterially enhanced HgS dissolution: pure cinnabar, pure metacinnabar, mine tailings, and calcine material (processed ore). In the microcosm with metacinnabar, the presence of the AMD microbial community resulted in an increase of dissolved Hg concentrations up to 500 μg L^‐1 during the first 30 days of incubation. In abiotic control microcosms, dissolved Hg concentrations did not increase above 100 ng L^?1. When Hg concentrations were below 50 μg L^‐1, the Fe‐oxidizing bacteria in the AMD microbial community were still capable of oxidizing Fe(II) to Fe(III) in the AMD solution, whereas concentrations above 50 μg L^?1 resulted in inhibition of microbial iron oxidation. Our experiments show that the AMD microbial community contributes to the dissolution of mercury sulfide minerals. These findings have major implications for risk assessment and future management of inoperative Hg mines worldwide.     

Exercise training alters an anoxia-induced, glibenclamide-sensitive current in rat ventricular cardiocytes.

The effect of training on properties of a sarcolemmal ATP-sensitive K+ current (I(K(ATP))) was examined in left ventricular cardiocytes isolated from sedentary (Sed) and trained (Tr) female Sprague-Dawley rats. Whole cell patch-clamp techniques were used to characterize I(K(ATP)), an anoxia-inducible, glibencamide-sensitive current. An anoxic condition was induced by superfusing cells with a buffer that was equilibrated with 100% N(2), maintained under a layer of argon, and that contained 2-deoxy-D-glucose. Over a 1-h period of anoxia, 59% of Tr cells and 85% Sed cells expressed I(K(ATP)). In those cells that did express I(K(ATP)), the time to expression of the current during the anoxic period occurred significantly later in cells from the Tr group compared with the Sed. Peak I(K(ATP)) density was significantly lower in the Tr cells compared with the Sed cells. These results indicate that the onset and magnitude of I(K(ATP)) were altered by training. These alterations in I(K(ATP)) may be reflective of processes that contribute to training-induced cardioprotection against ischemia-reperfusion damage.