Chronic stress causes protein kinase C epsilon-aldehyde dehydrogenase 2 signaling pathway perturbation in the rat hippocampus and prefrontal cortex, but not in the myocardium.

Chronic stress is strongly associated with the occurrence and development of depression and cardiovascular disease. Stress can induce altered mitochondrial function and activation of apoptosis in the cardio-cerebral system. However, it is unknown whether the protein kinase C ε (PKCε)-aldehyde dehydrogenase 2 (ALDH2) pathway is altered under chronic stress, and this study sought to address this question. A rat model of depression was established using a chronic unpredictable mild stress (CUMS) protocol. After experiencing CUMS for 4 weeks, the sucrose preference test and the forced swim test verified depressive-like behaviors. Enzyme linked immunosorbent assays showed that ALDH2 activity was decreased in the rat hippocampus and prefrontal cortex, but was not altered in the myocardium. Western blot assays demonstrated reduced levels of ALDH2 and PKCε, but increased levels of 4-hydroxy-2-nonenal (4HNE) adducts. Caspase-3 expression did not obviously alter, but active forms of caspase-3 were increased in the hippocampus and prefrontal cortex. In the myocardium, expression of ALDH2, PKCε and 4HNE adducts did not remarkably alter; while caspase-3 expression was reduced and the active forms of caspase-3 were upregulated. Pearson's correlation test demonstrated that expression of 4HNE adducts was positively correlated with levels of the active forms of caspase-3 in the hippocampus and prefrontal cortex, but not in the myocardium. In conclusion, chronic stress can damage the PKCε-ALDH2 signaling pathway in the hippocampus and prefrontal cortex, but not in the myocardium. Moreover, 4HNE is associated with active forms of caspase-3 in the hippocampus and prefrontal cortex.

A cross-sectional analysis of prescription and stakeholder surveys following essential medicine reform in Guangdong Province, China.

BACKGROUND: An essential medicine (EM) system has been implemented in China to reduce patients' financial burden and to make the use of drugs more rational. This study aims to evaluate the current state of the EM system in Guangdong Province. METHODS: We conducted surveys in 21 cities in 2012, covering 98 medical institutions, 1,509 doctors, 17 medicine manufacturers, and 17 distribution companies. We also reviewed outpatient prescriptions (n = 9,941) for treating hypertension, diabetes, bacterial infections and gout to measure the rational use of drugs in secondary and tertiary (upper-level) hospitals. RESULTS: The percentage of non-priority EM use ranged from 8.1% to 10.7% in upper-level hospitals, and this non-priority use significantly increased prescription drug costs. Other types of inappropriate medicine use were found more frequently in treating bacterial infections (7.4%) than in treating hypertension (1.6%), diabetes (1.3%) and gout (1.7%). Tertiary hospitals prescribed fewer EMs than secondary hospitals; moreover, tertiary hospitals had higher prescription drug costs. The zero mark-up policy decreased prescription drug costs in secondary hospitals. The survey revealed that forced full-prescription EM use might lead to fewer patient visits to primary hospitals. Manufacturers had halted the production of four (1, 23) types of EMs at the time of the survey. CONCLUSIONS: Encouraging the priority use of EMs and implementation of the zero mark-up policy were effective in curtailing prescription medicine costs in upper-level hospitals. Further work should focus on the following: creating guidelines to enhance rational prescription behavior, establishing policies to support EM use in upper-level hospitals and improving the bidding system to ensure a steady supply of the lowest-priced generic drugs.