Novel Non-equilibrium Phase Transition Caused by Non-linear Hadronic-quark Phase Structure

We consider how the occurrence of first-order phase transitions in non-constant pressure differs from those at constant pressure. The former has shown the non-linear phase structure of mixed matter, which implies a particle number dependence of the binding energies of the two species. If the mixed matter is mixed hadron-quark phase, nucleon outgoing from hadronic phase and ingoing to quark phase probably reduces the system to a non-equilibrium state, in other words, there exists the imbalance of the two phases when deconfinement takes place. This novel non-equilibrium process is very analogous to the nuclear reactions that nuclei emit neutrons and absorb them under appropriate conditions. We present self-consistent thermodynamics in description for the processes and identify the microphysics responsible for the processes. The microphysics is an inevitable consequence of non-linear phase structure instead of the effect of an additional dissipation force. When applying our findings to the neutron star containing mixed hadron-quark matter, it is found that the newly discovered energy release might strongly change the thermal evolution behavior of the star.Comment: 18pages,3figures;to be accepted for publication in Physics Letters

The New Anthelmintic Tribendimidine is an L-type (Levamisole and Pyrantel) Nicotinic Acetylcholine Receptor Agonist

Intestinal parasitic nematodes or roundworms infect over 1 billion people in tropical countries. Overall, they are a huge source of morbidity in infected people, including children and pregnant women, and are increasingly being recognized as key poverty-promoting parasites. Despite their importance, few drugs for dealing with them exist. Furthermore, none has optimal efficacy, all can be resisted by the parasites, and, for practical reasons, only one is used for single-dose Mass Drug Administrations (MDAs). There is a dire need for better roundworm drugs (anthelmintics). In the past 30 years, only one anthelmintic, tribendimidine, developed by the Chinese CDC, has entered human clinical trials. Tribendimidine has good single-dose efficacy against some roundworm parasites. However, how tribendimidine works was unknown. Here, using the roundworm Caenorhabditis elegans to evolve resistance to tribendimidine in the lab, followed by genetic and molecular testing and cross-resistance drug studies, we demonstrate that tribendimidine is unequivocally in the same drug family as two known anthelmintics, levamisole and pyrantel. These results have important implications for how tribendimidine might be used in MDAs where resistance to current drugs is known or suspected and for how tribendimidine might be combined with other drugs to maximize therapy while minimizing resistance threats

Artesunate and artemether are effective fasciolicides in the rat model and in vitro

Objectives: To study the fasciocidal properties of artesunate and artemether in the rat model and in vitro. Methods: Adult Fasciola hepatica were exposed in vitro to 1, 10 and 100 µg/mL of artesunate, artemether and dihydroartemisinin for 72 h. Female Wistar rats were administered a single oral dose of artesunate and artemether (100-400 mg/kg) commencing 3 or 10-14 weeks post-infection and worm burden reductions were assessed against infected but untreated control rats. F. hepatica were also observed by scanning electron microscopy (SEM) after recovery from bile ducts of rats given a single oral dose of 200 mg/kg artesunate 24 and 72 h post-treatment. Results: F. hepatica exposed for 72 h to10 µg/mL of artesunate, artemether and dihydroartemisinin in vitro showed poor mobility, swelling of the worm body, roughness, damage of the tegument and blebbing. Exposure to drug concentrations of 100 µg/mL resulted in the death of all F. hepatica by 72 h. One hundred per cent worm burden reductions were achieved in rats infected with adult F. hepatica after treatment with artesunate and artemether at 400 and 200 mg/kg, respectively. Administration of artesunate and artemether at a dose of 200 mg/kg to rats harbouring juvenile F. hepatica resulted in worm burden reductions of 46% and 82%, respectively. F. hepatica recovered from rats' bile ducts 24 h after administration of 200 mg/kg artesunate showed normal activity and SEM observations revealed that there was no visible damage. Seventy-two hours post-treatment F. hepatica displayed very poor mobility and there was focal swelling of the tegument and spines. Conclusions: Artesunate and artemether exhibit promising fasciocidal activities, with the latter showing better tolerability by the host