Discovery of N-(3,5-bis(1-pyrrolidylmethyl)-4-hydroxybenzyl)-4-methoxybenzenesulfamide (sulcardine) as a novel anti-arrhythmic agent.

AIM: To investigate the anti-arrhythmic effects of sulfamide analogues of changrolin and to characterize the sulfate of compound 6f (sulcardine sulfate, Sul) as a novel anti-arrhythmic agent. METHODS: The anti-arrhythmic effects of compounds were studied against aconitine-induced arrhythmias in rats and ouabain-induced arrhythmias in guinea pigs. The effects of Sul on transmembrane action potentials were investigated in isolated rabbit sinoatrial nodes and guinea-pig papillary muscles using intracellular recording. With a whole-cell recording technique, the effects of Sul on sodium current, calcium current, and potassium currents were examined in isolated single guinea-pig ventricular myocytes. RESULTS: In aconitine-induced arrhythmias of rats, sulfamide analogues of changrolin (4, 5, and 6a-6p) exhibited various anti-arrhythmic activities. The sulfate of compound 6f (Sul) increased the amount of aconitine required to induce arrhythmias in each treated animal. The ED50 value of Sul in rats was 196 mg/kg. In ouabain-induced arrhythmias of guinea pigs, 25, 50, and 100 mg/kg doses of Sul increased the dose of ouabain required to induce VP, VT, and VF in a dose-dependent manner. In papillary preparations, Sul produced a concentration-dependent decrease in APA and V(max), prolonged APD(90) and ERP, whereas RP was unaffected. In the spontaneously beating sinus nodes, Sul reduced APA and V(max) in a concentration-dependent manner. The whole-cell recording studies revealed that Sul produced a reversible reduction in I(Na) (IC50=26.9 µmol/L) and I(Ca,L)(IC50=69.2 µmol/L), whereas the inward rectifier (I(K1)) and the delayed rectifier potassium currents (I(K)) were unaffected. CONCLUSION: As a multi-ion channel blocker, Sul may have potent efficacy in anti-atrial and ventricular arrhythmias.

Legacies of past exploitation and climate affect mammalian sexes differently on the roof of the world - the case of wild yaks.

In polar environments, a lack of empirical knowledge about biodiversity prompts reliance on species distribution models to predict future change, yet these ignore the role of biotic interactions including the role of long past human exploitation. To explore how mammals of extreme elevation respond to glacial recession and past harvest, we combined our fieldwork with remote sensing and used analyses of ~60 expeditions from 1850-1925 to represent baseline conditions for wildlife before heavy exploitation on the Tibetan Plateau. Focusing on endangered wild yaks (Bos mutus), we document female changes in habitat use across time whereupon they increasingly relied on steeper post-glacial terrain, and currently have a 20x greater dependence on winter snow patches than males. Our twin findings­that the sexes of a cold-adapted species respond differently to modern climate forcing and long-past exploitation­indicate that effective conservation planning will require knowledge of the interplay between past and future if we will assure persistence of the region's biodiversity.

Human-carnivore conflict in China: a review of current approaches with recommendations for improved management.

Human-wildlife conflict (HWC) is a conservation concern that increasingly threatens the continued existence of some of the world's most endangered species. With an increase in human population, urban sprawl and subsequent encroachment on wild land, human and wildlife interaction has become inevitable. In the majority of cases, this interaction results in a negative outcome for humans, wildlife or both. In China, these key elements, along with a decrease in wild prey species, have resulted in the expansion of HWC encounters, and the need for alleviating this conflict has become a conservation priority. Loss of human life, livestock and/or crops is most often the catalysts that fuel HWC. Techniques to alleviate conflict around the world have included preventative measures and mitigation techniques, such as financial compensation and other incentive programs. Both types of measures have had variable success. We review the current status of human-carnivore conflict management in China, and, drawing lessons from around the globe, we make recommendations for improving conservation management in China. For example, an increase in law enforcement in nature reserves is vital to reducing human disturbance in prime carnivore habitat, thereby reducing conflict encounters. Also, modifications to current wildlife compensation programs, so that they are linked with preventative measures, will ensure that moral hazards are avoided. Furthermore, investigating the potential for a community self-financed insurance scheme to fund compensation and increasing efforts to restore wild prey populations will improve the outcome for wildlife conservation. Ultimately, HWC management in China will greatly benefit from an integrative approach.

Historic distribution and recent loss of tigers in China.

Historical records can provide important evidence of changes in distributions of wildlife species. Here we discuss the distribution of the tiger (Panthera tigris Linnaeus, 1758) over the past 2000 years in China based on 2635 historical records. We also compare tiger distributions outlined in these records with ecosystem type maps. Throughout this time period, tigers maintained a broad distribution across 7 biomes (from forests to deserts). However, in recent decades the range has been significantly condensed. Today, only 2 populations remain, neither of which is independently viable. Tigers have completely disappeared from the temperate broadleaf and mixed forests of central China, a region that was traditionally their most important biome in China. The continued presence of wild tigers in China is highly dependent on significant conservation measures.