Plos One
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We examined whether a sugary drink limit would still be effective if larger-sized drinks were converted into bundles of smaller-sized drinks. ⋯ Our research suggests that businesses have a strong incentive to offer bundles of soda when drink size is limited. Restricting larger-sized drinks may have the unintended consequence of increasing soda consumption rather than decreasing it.
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Leptin acts via neuronal leptin receptors to control energy balance. Hypothalamic pro-opiomelanocortin (POMC) and agouti-related peptide (AgRP)/Neuropeptide Y (NPY)/GABA neurons produce anorexigenic and orexigenic neuropeptides and neurotransmitters, and express the long signaling form of the leptin receptor (LepRb). Despite progress in the understanding of LepRb signaling and function, the sub-cellular localization of LepRb in target neurons has not been determined, primarily due to lack of sensitive anti-LepRb antibodies. ⋯ In addition, we found that the leptin activates STAT3 signaling in proximity to synapses on POMC and AgRP/NPY/GABA dendritic shafts. Taken together, these data suggest that the signaling-form of the leptin receptor exhibits a somato-dendritic expression pattern in POMC and AgRP/NPY/GABA neurons. Dendritic LepRb signaling may therefore play an important role in leptin's central effects on energy balance, possibly through modulation of synaptic activity via post-synaptic mechanisms.
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Tuberculosis is one of the world's leading killers, stealing 1.4 million lives and causing 8.7 million new and relapsed infections in 2011. The only vaccine against tuberculosis is BCG which demonstrates variable efficacy in adults worldwide. Human infection with Mycobacterium tuberculosis results in the influx of inflammatory cells to the lung in an attempt to wall off bacilli by forming a granuloma. Gr1(int)CD11b(+) cells are called myeloid-derived suppressor cells (MDSC) and play a major role in regulation of inflammation in many pathological conditions. Although MDSC have been described primarily in cancer their function in tuberculosis remains unknown. During M. tuberculosis infection it is crucial to understand the function of cells involved in the regulation of inflammation during granuloma formation. Understanding their relative impact on the bacilli and other cellular phenotypes is necessary for future vaccine and drug design. ⋯ We compared the bacterial burden, lung pathology and Gr1(int)CD11b(+) myeloid-derived suppressor cell immune responses in M. tuberculosis infected NOS2-/-, RAG-/-, C3HeB/FeJ and C57/BL6 mice. Gr-1(+) cells could be found on the edges of necrotic lung lesions in NOS2-/-, RAG-/-, and C3HeB/FeJ, but were absent in wild-type mice. Both populations of Gr1(+)CD11b(+) cells expressed high levels of arginase-1, and IL-17, additional markers of myeloid derived suppressor cells. We then sorted the Gr1(hi) and Gr1(int) populations from M. tuberculosis infected NOS-/- mice and placed the sorted both Gr1(int) populations at different ratios with naïve or M. tuberculosis infected splenocytes and evaluated their ability to induce activation and proliferation of CD4+T cells. Our results showed that both Gr1(hi) and Gr1(int) cells were able to induce activation and proliferation of CD4+ T cells. However this response was reduced as the ratio of CD4(+) T to Gr1(+) cells increased. Our results illustrate a yet unrecognized interplay between Gr1(+) cells and CD4(+) T cells in tuberculosis.
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Duloxetine, a serotonin and noradrenaline reuptake inhibitor, and celecoxib, a non-steroidal anti-inflammatory drug, are commonly used analgesics for persistent pain, however with moderate gastrointestinal side effects or analgesia tolerance. One promising analgesic strategy is to give a combined prescription, allowing the maximal or equal efficacy with fewer side effects. In the current study, the efficacy and side effects of combined administration of duloxetine and celecoxib were tested in the mouse formalin pain model. ⋯ A statistical difference between the theoretical and experimental ED50 for the second phase pain responses was observed, which indicated synergistic interaction of the two drugs. Concerning the emotional pain responses revealed with USVs, we assumed that the antinociceptive effects were almost completely derived from duloxetine, since celecoxib was ineffective when administered alone or reduced the dosage of duloxetine when given in combination. Based on the above findings, acute concomitant administration of duloxetine and celecoxib showed synergism on the somatic pain behavior but not emotional pain behaviors.
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Simvastatin exerts pleiotropic effects on cardiovascular system. However, its effect on non-alcoholic fatty liver disease, especially the liver fibrosis, remains obscure. We aimed to clarify the relationship between simvastatin and liver fibrosis both in vivo and in vitro. ⋯ Simvastatin improves the prognosis of NASH-related fibrosis by increasing the expression of eNOS, decreasing the expression of iNOS, and inhibiting the activation of HSC.