To determine whether an antihypertrophic effect is class specific, we tested if doxercalciferol (a pro-hormone vitamin D2 analog) could also attenuate the development of cardiac hypertrophy in DSS rats.
Methods and Results: Male DSS rats were fed a high salt (HS) diet for 6 weeks beginning at 6 weeks of age. Doxercalciferol was administered intraperitoneally at 150 ng, 3 times
per week (Monday, Wednesday, Friday) for 6 weeks. Pathological and echocardiographic findings demonstrated that rats on HS diet with doxercalciferol administration had significant decrease in cardiac hypertrophy and improved cardiac function compared to the HS + vehicle. In addition, there was a significant decrease in plasma brain natriuretic peptide (BNP) level and tissue atrial natriuretic factor (ANF) mRNA level with doxercalciferol treatment. Doxercalciferol also significantly reduced the level of protein kinase C-alpha (PKC alpha) suggesting that PKC-mediated JNJ-26481585 clinical trial cardiac hypertrophy may be associated with vitamin D deficiency.
Conclusions: Administration of doxercalciferol attenuated the development of HS diet induced cardiac hypertrophy and cardiac dysfunction in DSS rats. (J Cardiac Fail 2011;17:1051-1058)”
“We propose the design for a switchable mirror with high efficiency and a 30 nm bandwidth. The device is based
on a liquid STA-9090 in vitro crystal filled etalon. Broad bandwidth is achieved through the use of integrated half-wave layers into the dielectric stack design, while high efficiency is achieved using a polarization independent liquid crystal effect. Potential applications in the area of displays are also presented.”
“The serotonin receptor agonist triptan drugs (5-HT1B/1D receptor Cell Cycle inhibitor agonists) have been in use for over 20 years in the abortive management of migraine. Although clearly effective, their ability to produce vasoconstriction
in cerebral and coronary arteries, thought to be mediated by their high affinity for the 5-HT1B receptor, has been a limitation to their use in certain patient populations. Variable potency triptan binding at the 5-HT1F receptor occurs in addition to binding at the 5-HT1B and 5-HT1D receptors. A more selective serotonin agonist without 5-HT1B-mediated vasoconstriction might prove efficacious yet safer. The 5-HT1F receptor has been targeted as a site of action for such a drug. In experimental models, 5-HT1F receptor agonists have been shown to block neurogenic inflammation and c-Fos expression in neural tissue and, as well, show no evidence of vasoconstriction in vascular tissue models in vitro. In clinical trials, efficacy in the abortive management of migraine has been established. Lasmiditan (LY573144), a selective 5-HT1F receptor agonist (K1 = 2.21 mu M), showed efficacy in its primary endpoint, with a 2-hour placebo-subtracted headache response of 28.8%, though with frequent reports of dizziness, paresthesias, and vertigo. Study results support an emerging central neuronal mechanism of migraine pathophysiology.