Synthesis and evaluation of N⁶-substituted apioadenosines as potential adenosine A₃ receptor modulators

Adenosine receptors (ARs) trigger signal transduction pathways inside the cell when activated by extracellular adenosine. Selective modulation of the A(3)AR subtype may be beneficial in controlling diseases such as colorectal cancer and rheumatoid arthritis. Here, we report the synthesis and evaluation of beta-D-apio-D-furano- and alpha-D-apio-L-furanoadenosines and derivatives thereof. Introduction of a 2-methoxy-5-chlorobenzyl group at N-6 of beta-D-apio-D-furanoadenosine afforded an A(3)AR antagonist (10c, K = 0.98 mu M), while a similar modification of an alpha-D-apio-L-furanoadenosine gave rise to a partial agonist (11c, K-i = 3.07 mu M). The structural basis for this difference was examined by docking to an A(3)AR model; the antagonist lacked a crucial interaction with Thr94

High-intensity exercise training induces morphological and biochemical changes in skeletal muscle

Skeletal muscle shows an elevated plasticity and can adapt its metabolic and contractile properties in response to a variety of stimuli such as physical exercise. This implies a series of biochemical and morphological changes in the recruited muscle, in order to produce the more appropriate functional response dependent on the specific stimulation. To determine the effective role of physical exercise in the muscle plasticity, in the present study we investigated the effect of two different exercise protocols on fiber composition and metabolism of two specific muscles of mice: the quadriceps -a fast-twitch muscle- and the gastrocnemius -a typical slow-twitch muscle. Mice were run daily on a motorized treadmill for 8 weeks, at a velocity corresponding to 60% (low-intensity exercise) or 90% (high-intensity exercise) of the maximal running velocity previously determined by an incremental exercise test. We found that at the end of training the body weight was significantly increased in highintensity exercise mice (18.2 ± 1.4 %) compared to low-intensity exercise (8.7 ± 0.6 %) and control (12.7 ± 0.5 %) groups, and it was lesser in low-intensity exercise mice compared to controls. In contrast, the food intake of both exercise training mice was greater compared to control group. Whereas low-intensity exercise mice, despite consumed significantly more food compared to control mice, increased the weight lesser, the weight increase of high-intensity exercise mice, that consumed significantly more food compared to other experimental groups, was significantly greater. These effects were accompanied by a progressive reduction in blood lactate levels at the end of training in both the exercised mice compared with controls; in particular, blood lactate levels after highintensity exercise were significantly lower than those measured in low-intensity exercise mice. Moreover, in the present study we demonstrated that high-intensity exercise training produced a significant increase in the expression of mitochondrial complex enzymes (significant for the enzymes corresponding to the Complex IV, II and I of mitochondrial chain) both in gastrocnemius and quadriceps muscle, compared with controls. These changes were associated with an increase in the amount of slow fibers in both these muscle of high-intensity exercise mice. No changing in the expression of mitochondrial enzymes and in the percentage of slow fibers were found in low-intensity exercise mice

Analysis of Labor Women at Star Hotels in the City of Pekanbaru

The research was conducted in the city of Pekanbaru in 2013. This study aims to determine how the image of women in the labor-star hotel in the city of Pekanbaru is viewed from the aspect of education, past work, income, region of origin, and the factors driving women working in five-star hotel in the city Pekanbaru. This study uses primary data collected directly from the respondents on the female labor-star hotel in the city of Pekanbaru. The population in this study were all women in labor-star hotel in the city of Pekanbaru is classified at 3.4 and 5 star hotel that is numbered 511 people. While the sample used in this study amounted to 100 people. Secondary data were obtained from the Department of Culture and Tourism of Pekanbaru, Central Bureau of Statistics (BPS) of Pekanbaru. Engineering data was collected directly by visiting the employment of women in the five-star hotel in the city of Pekanbaru. This study analyzed using descriptive analysis method. Based on the survey results revealed that female employees who worked at the five-star hotel in the city of Pekanbaru seen from the aspect of education, which is dominated workforce education level diploma. Then views of the work, where workers who work at five-star hotel in the city of Pekanbaru has over 5 years experience. Viewed from the aspect of labor income, where the amount of earned income workers who worked at the hotel in Pekanbaru City Star above the minimum wage and depend on the position occupied. From the aspect of the origin, generally derived from the city of Pekanbaru. Then the drivers of women working in five-star hotel in the city of Pekanbaru is the salary offered as expected