Canavanine increases glucose uptake in C2C12 cells through the activation of imidazoline I‐2B receptors

Canavanine is a guanidinium derivative that contains the basic structure of the ligand(s) of imidazoline receptor (I‐R). Canavanine has been reported to activate the imidazoline I‐3 receptor (I‐3R) both in vivo and in vitro. Additionally, the activation of the imidazoline I‐2B receptor (I‐2BR) by guanidinium derivatives may increase glucose uptake. Therefore, the effect of canavanine on the I‐2BR was investigated in the present study. Glucose uptake into cultured C₂C₁₂ cells was determined using the radio‐ligated tracer 2‐[¹⁴C]‐deoxy‐glucose. The changes in 5′ AMP‐activated protein kinase (AMPK) expression were also identified using Western blotting analysis. The canavanine‐induced glucose uptake was inhibited in a dose‐dependent manner by BU224 (0.01–1 μmol/L), which is a specific I‐2BR antagonist, in the C₂C₁₂ cells. Additionally, the canavanine‐stimulated AMPK phosphorylation and glucose transporter (GLUT4) expression were also sensitive to BU224 inhibition in the C₂C₁₂ cells. Moreover, both canavanine‐stimulated glucose uptake and AMPK phosphorylation were attenuated by high concentrations of amiloride (1–2 μmol/L), which is another established I‐2BR inhibitor, in a dose‐dependent manner in C₂C₁₂ cells. Additionally, compound C abolished the canavanine‐induced glucose uptake and AMPK phosphorylation at a concentration (0.1 μmol/L) sufficient to inhibit AMPK. In conclusion, these data demonstrated that canavanine has an ability to activate I‐2BR through the AMPK pathway to increase glucose uptake, which indicates I‐2BR as a new target for diabetic therapy.     

Enhanced vasorelaxation effect of endogenous anandamide on thoracic aorta in renal vascular hypertension rats

Emerging evidence has indicated that anandamide (AEA) is able to stimulate vasorelaxation in both spontaneously hypertensive rats (SHRs) and L‐NAME‐induced hypertensive rats. Yet it remains unknown whether AEA modulates vasomotion of the aorta in renovascular hypertensive (RVH) rats. The aim of present study is to explore the effect of AEA on the relaxation of thoracic aortas in two‐kidney one‐clip (2K1C)‐induced RVH rats. It is demonstrated that AEA stimulates a pronounced relaxation in the aortas of 2K1C rats compared with sham rats. The enhanced relaxation caused by AEA in aortas from 2K1C rats was diminished in the presence of the cannabinoid receptor‐1 (CB₁) antagonist AM251 and the CB₂ receptor antagonist AM630. Likewise, the vasodilation action of AEA was blocked in L‐NAME‐treated or endothelium‐denuded aortas. The Western blot results revealed that the expression of CB₁ and CB₂ receptors was increased in the 2K1C rat aortas compared with sham rats. The phosphorylation of endothelial nitric oxide synthase (p‐eNOS) at the activation site Ser1177 was enhanced in AEA‐treated rings from 2K1C rats in both time‐dependent and dose‐dependent manners. The augmented p‐eNOS expression was inhibited by the co‐treatment with AM251 or AM630. Taken together, the present study demonstrated that AEA enhanced endothelium‐dependent aortic relaxation through activation of both CB₁ and CB₂ receptors and P‐eNOS/NO pathway in 2K1C rats.     

HSP60 overexpression increases the protein levels of the p110α subunit of phosphoinositide 3‐kinase and c‐Myc

Heat shock protein 60 (HSP60) is a chaperone protein which plays an essential role in facilitating the folding of many newly synthesized proteins to reach their native forms. Increased HSP60 expression is observed in various types of human cancers. However, proteins induced by HSP60 to mediate transformation remain largely unknown. Here we show that HSP60 overexpression increases the protein levels of the p110α subunit of phosphoinositide 3‐kinase (PI3K). The amino acid domain 288‐383 of HSP60 is used to increase the protein levels. Overexpression of HSP60 also induces the levels of phosphorylated Akt. In addition, the amino acid domain 288‐383 of HSP60 is used to induce c‐Myc expression. Finally, a mono‐ubiquitinated form of β‐catenin has a higher activity to activate β‐catenin downstream targets compared to wild‐type β‐catenin. These results indicate that HSP60 overexpression induces the levels or activity of multiple oncogenic proteins to mediate transformation.     

Correlation between osteocalcin‐positive endothelial progenitor cells and spotty calcification in patients with coronary artery disease

Immature endothelial progenitor cells (EPC) carrying osteocalcin (OCN) might mediate vascUlar calcification in coronary artery disease (CAD). Spotty calcification within atherosclerotic plaque is associated with cardiovascular events. The aim of the present study was to assess the correlation between immature EPC levels and spotty calcification in CAD patients. In the 224 CAD patients studied, 76 had acute myocardial infarction (AMI), 102 had unstable angina pectoris (UAP), and 46 had stable angina pectoris (SAP). The levels of OCN‐positive (OCN+) EPC were analysed by flow cytometry. The status of spotty calcification was determined by cardiac computed tomography angiography. OCN+ EPC and calcium deposits were significantly increased in acute coronary artery syndrome (ACS) when compared with those in SAP patients. Positive correlation was also revealed between the number of OCN+ EPC and the frequency of spotty calcification and levels of serum high‐sensitivity C‐reactive protein (hs‐CRP) and serum alkaline phosphatase in AMI and UAP patients. In summary, the number of OCN+ EPC is positively related to the frequency of spotty calcification in ACS patients. Serum hs‐CRP and serum alkaline levels are thought to contribute to the elevation of OCN+ EPC.     

Do Diagnosis‐Related Group‐Based Payments Incentivise Hospitals to Adjust Output Mix?

This study investigates whether the diagnosis‐related group (DRG)‐based payment method motivates hospitals to adjust output mix in order to maximise profits. The hypothesis is that when there is an increase in profitability of a DRG, hospitals will increase the proportion of that DRG (own‐price effects) and decrease those of other DRGs (cross‐price effects), except in cases where there are scope economies in producing two different DRGs. This conjecture is tested in the context of the case payment scheme (CPS) under Taiwan's National Health Insurance programme over the period of July 1999 to December 2004. To tackle endogeneity of DRG profitability and treatment policy, a fixed‐effects three‐stage least squares method is applied. The results support the hypothesised own‐price and cross‐price effects, showing that DRGs which share similar resources appear to be complements rather substitutes. For‐profit hospitals do not appear to be more responsive to DRG profitability, possibly because of their institutional characteristics and bonds with local communities. The key conclusion is that DRG‐based payments will encourage a type of ‘product‐range’ specialisation, which may improve hospital efficiency in the long run. However, further research is needed on how changes in output mix impact patient access and pay‐outs of health insurance. Copyright © 2014 John Wiley & Sons, Ltd.     

Empowerment in healthcare policy making: three domains of substantive controversy

This paper distinguishes between the uses of empowerment across different contexts in healthcare policy and health promotion, providing a model for the ethical and political scrutiny of those uses. We argue that the controversies currently engendered by empowerment are better understood by means of a historical distinction between two concepts of empowerment, namely, what we call the radical empowerment approach and the new wave of empowerment. Building on this distinction, we present a research agenda for ethicists and policy makers, highlighting three domains of controversy raised by the new wave of empowerment, namely: (1) the relationship between empowerment and paternalistic interferences on the part of professionals; (2) the evaluative commitment of empowerment strategies to the achievement of health‐related goals; and (3) the problems arising from the emphasis on responsibility for health in recent uses of empowerment. Finally, we encourage the explicit theorisation of these moral controversies as a necessary step for the development and implementation of ethically legitimate empowerment processes.     

Realigning Demand and Supply Side Incentives to Improve Primary Health Care Seeking in Rural China

China's recent and ambitious health care reform involves a shift from the reliance on markets to the reaffirmation of the central role of the state in the financing and provision of services. In collaboration with the Government of the Ningxia province, we examined the impact of two key features of the reform on health care utilisation using panel household data. The first policy change was a redesign of the rural insurance benefit package, with an emphasis on reorientating incentives away from inpatient towards outpatient care. The second policy change involved a shift from a fee‐for‐service payment method to a capitation budget with pay‐for‐performance amongst primary care providers. We find that the insurance intervention, in isolation, led to a 47% increase in the use of outpatient care at village clinics and greater intensity of treatment (e.g. injections). By contrast, the two interventions in combination showed no effect on health care use over and above that generated by the redesign of the insurance benefit package. Copyright © 2014 John Wiley & Sons, Ltd.