Arctigenin Efficiently Enhanced Sedentary Mice Treadmill Endurance

Physical inactivity is considered as one of the potential risk factors for the development of type 2 diabetes and other metabolic diseases, while endurance exercise training could enhance fat oxidation that is associated with insulin sensitivity improvement in obesity. AMP-activated protein kinase (AMPK) as an energy sensor plays pivotal roles in the regulation of energy homeostasis, and its activation could improve glucose uptake, promote mitochondrial biogenesis and increase glycolysis. Recent research has even suggested that AMPK activation contributed to endurance enhancement without exercise. Here we report that the natural product arctigenin from the traditional herb Arctium lappa L. (Compositae) strongly increased AMPK phosphorylation and subsequently up-regulated its downstream pathway in both H9C2 and C2C12 cells. It was discovered that arctigenin phosphorylated AMPK via calmodulin-dependent protein kinase kinase (CaMKK) and serine/threonine kinase 11(LKB1)-dependent pathways. Mice treadmill based in vivo assay further indicated that administration of arctigenin improved efficiently mice endurance as reflected by the increased fatigue time and distance, and potently enhanced mitochondrial biogenesis and fatty acid oxidation (FAO) related genes expression in muscle tissues. Our results thus suggested that arctigenin might be used as a potential lead compound for the discovery of the agents with mimic exercise training effects to treat metabolic diseases

Prospects, achievements, challenges and opportunities for scaling-up malaria chemoprevention in pregnancy in Tanzania: the perspective of national level officers

OBJECTIVES: To describe the prospects, achievements, challenges and opportunities for implementing intermittent preventive treatment for malaria in pregnancy (IPTp) in Tanzania in light of national antenatal care (ANC) guidelines and ability of service providers to comply with them. METHODS: In-depth interviews were made with national level malaria control officers in 2006 and 2007. Data was analysed manually using a qualitative content analysis approach. RESULTS: IPTp has been under implementation countrywide since 2001 and the 2005 evaluation report showed increased coverage of women taking two doses of IPTp from 29% to 65% between 2001 and 2007. This achievement was acknowledged, however, several challenges were noted including (i) the national antenatal care (ANC) guidelines emphasizing two IPTp doses during a woman's pregnancy, while other agencies operating at district level were recommending three doses, this confuses frontline health workers (HWs); (ii) focused ANC guidelines have been revised, but printing and distribution to districts has often been delayed; (iii) reports from district management teams demonstrate constraints related to women's late booking, understaffing, inadequate skills of most HWs and their poor motivation. Other problems were unreliable supply of free SP at private clinics, clean and safe water shortage at many government ANC clinics limiting direct observation treatment and occasionally pregnant women asked to pay for ANC services. Finally, supervision of peripheral health facilities has been inadequate and national guidelines on district budgeting for health services have been inflexible. IPTp coverage is generally low partly because IPTp is not systematically enforced like programmes on immunization, tuberculosis, leprosy and other infectious diseases. Necessary concerted efforts towards fostering uptake and coverage of two IPTp doses were emphasized by the national level officers, who called for further action including operational health systems research to understand challenges and suggest ways forward for effective implementation and high coverage of IPTp. CONCLUSION: The benefit of IPTp is appreciated by national level officers who are encouraged by trends in the coverage of IPTp doses. However, their appeal for concerted efforts towards IPTp scaling-up through rectifying the systemic constraints and operational research is important and supported by suggestions by other authors

Molecular dynamics simulations of non-equilibrium systems

Peer reviewe