Objective: A perception survey of healthcare providers and pharmaceutical industries about the current package insert (PI) was conducted to evaluate whether its layout and issues such as the contents concerning drug-drug interactions are found appropriate.
Methods: A questionnaire was sent via the Internet to physicians of various subspecialties, or via the postal service to pharmacy-employed pharmacists and pharmaceutical industries.  It consisted of questions regarding the PI layout, the information contents on drug-drug interactions and other matters about PI revision.
Results: The survey showed that the PI is a major source of drug information for physicians (82.4%) and pharmacists (98.7%).  The layout (order of appearance of headings and information about drug interactions in a tabular format) of the current PI is widely accepted by physicians, pharmacists, and pharmaceutical industries.  There was, however, some degree of disagreement within these three groups in the perceptions about the presentation/contents of the several drug interactions, as well as about the timing for its updating.  Around 24% of physicians and 35% of pharmacists view that the content of drug interactions is insufficient, and that information about adverse drug reactions and drug interactions is not enough updated in the PIs.  On the other hand, near 86% of pharmaceutical industries were prone to wait for accumulation of enough data until revising the information in PIs.
Conclusions: Differences of perception were found between healthcare providers (i.e., PI users) and industries.  Our survey revealed that the basic layout of the current PI should be preserved, but there are issues such as the contents and updating of information regarding drug interactions and adverse drug interactions that may require modifications according to the healthcare providers’ point of view.

In this study, we aimed to investigate the effects of long-term voluntary running exercise and caloric restriction during development on the skeletal muscle mass and intracellular signaling in female rats. Four-week-old female Wistar rats (n = 23) were randomly divided into the sedentary (SED) and voluntary running exercise (EX) groups, and then acclimated to a new environment. At 5 weeks of age, the rats in both groups were further divided into the ad libitum (AD+SED or AD+EX, n = 6) and calorie-restricted (CR+SED or CR+EX, n = 5-6) groups. EX group underwent 12 weeks of voluntary running exercise. CR group was only fed 70% of the food fed to the AD + SED group. After 12 weeks of intervention, soleus and plantaris muscles were removed, and the levels of intracellular signal transduction proteins involved in protein synthesis and degradation were measured by Western blotting. Significant diet × condition interactions were observed in the body, soleus muscle, and plantaris muscle weights. Specifically, plantaris muscle weight in the CR + EX group was significantly lower than that in the other groups; however, their soleus muscle weight was similar to that in the CR + SED group. In the plantaris muscles, significant diet × condition interactions were observed in the phosphorylation levels of 4E-binding protein 1, UNC-51-like autophagy-activating kinase-1, and light chain 3-II/I. Moreover, these factors were significantly altered in the CR + EX group than in the other groups. Notably, no significant interactions were observed in the soleus muscles. Our data suggest that long-term voluntary running exercise and caloric restriction exacerbate skeletal muscle loss, possibly mediated by muscle type-specific intracellular signaling mechanisms involved in protein synthesis and degradation.

This study aimed to elucidate the effects of long-term high-fat diet (HFD) consumption and cage restriction-induced physical inactivity (IN) during youth on skeletal muscle autophagy in rats. Three-week-old male Wistar rats were randomly assigned to two dietary groups: the normal diet (ND) and HFD groups. Each group was further subdivided into control (CON) and IN conditions, resulting in four experimental groups (n = 7-8). The HFD group was provided with a diet containing approximately 60% of total calories from crude fat for 16 weeks, from 4 to 20 weeks of age. The ND group received a standard diet for the same duration. The physical inactivity intervention during youth involved restricting the rats’ range of activity by housing them in smaller cages for eight weeks. After 12 weeks of age, the behavioral restrictions were lifted, and all groups of rats were housed in normal-sized cages for eight weeks. The ‘diet group’ and ‘condition’ factors exerted significant effects on the relative muscle weight of the gastrocnemius muscle. The HFD groups exhibited a notable decline in relative muscle weight compared to their ND counterparts. While no significant alterations were observed in LC3-II or p62 expression levels, the ‘diet group’ factor significantly influenced LC3-II/I levels in the white gastrocnemius muscle. These levels were markedly reduced in the HFD group. Our findings suggest that 16 weeks of HFD consumption leads to a reduction in autophagy flux, specifically within the white portion of the gastrocnemius muscle, but this effect is not influenced by cage restriction-induced physical inactivity during youth.