Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.1 (ACS)
 78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The process of acquiring new surgical skills beyond the period of residency training should include selection of a complete educational experience founded on a disease-based approach rather than an isolated intervention. Deliberate practice and avoidance of automaticity through the establishment of learning goals that exceed the current level of performance should help in developing expertise. The Division of Education of the American College of Surgeons (Chicago, Ill) has undertaken steps to support surgeons' efforts in acquiring skills in new procedures and technologies. A major area of focus is verifying the knowledge and skills of surgeons at the completion of experiential courses. The division is developing a model to establish a network of ACS-Accredited Education (Skills) Centers. A comprehensive and well-designed approach is essential to support surgeons' efforts to acquire new skills to provide the best care to patients.
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PMID:Acquiring skills in new procedures and technology: the challenge and the opportunity. 1583 89

Atherogenic dyslipidemia is characterised by high levels of triglycerides, low levels of high-density lipoprotein-cholesterol (HDL-C), and moderate to marked elevations in low-density lipoprotein-cholesterol (LDL-C) concentrations; such dyslipidemia is further characterised by high apolipoprotein B (apoB): apolipoprotein A1 (apoA1) ratios. Numerous clinical trials have demonstrated that statins are effective in lowering LDL-C and reducing cardiovascular (CV) risk in people with dyslipidemia. However, the most effective treatments should target all of the key atherogenic features, rather than LDL-C alone. Pitavastatin is a new member of the statin class whose distinct pharmacological features translate into a broad spectrum of action on both apoB-containing and apoA1-containing lipoprotein components of the atherogenic lipid profile. The efficacy and safety of this statin has been demonstrated by a large clinical development programme conducted both in Japanese and Caucasian populations. Phase III and IV studies in a wide range of patients with primary hypercholesterolemia or combined dyslipidemia showed that 12 weeks' treatment with pitavastatin l-4 mg was well tolerated, significantly improved lipid profiles (including LDL-C, TG, and HDL-C levels) and increased the EAS-/NCEP ATP Ill-recommended LDL-C target attainment rate to a similar or greater degree as comparable doses of atorvastatin, simvastatin, or pravastatin. Results were similar across all patient groups and were generally sustained after 52 weeks of treatment. However, whereas the effects of atorvastatin and simvastatin on HDL-C levels remained constant over the long term, pitavastatin-treated patients experienced progressive and maintained elevations in HDL-C, ultimately increasing by up to 14.3% vs. initial baseline. In this context, it is significant that the in vitro studies of Yamashita et al. [J Atheroscler Thromb 2010;17:436-51] have shown pitavastatin to be distinguished by its potent stimulation of apoA1 production in hepatocyte-like cells. These findings suggest that pitavastatin may be highly efficacious in raising levels of lipid-poor apoA1 particles, which are known to be highly active in ABCA1-mediated cellular cholesterol efflux, an observation which is pertinent to the excessive accumulation of cholesterol in macrophage foam cells of the atherosclerotic plaque. Indeed, the intravascular remodelling and maturation of lipid-poor apoA1 particles is known to drive flux of apoA1, cholesterol and phospholipid through the HDL pathway. It is equally relevant that pitavastatin therapy has been shown to be efficacious in markedly reducing coronary atheroma volume in acute coronary syndrome patients in the JAPAN-ACS trial, a therapeutic effect which may be linked to its impact on apoA1/HDL metabolism and function. Overall, Phase III and IV studies demonstrate that pitavastatin 1-4 mg is well tolerated, attenuates the atherogenic lipid profile and increases LDL-C target attainment rates with a similar or greater efficacy to comparable doses of atorvastatin, simvastatin and pravastatin. Furthermore, pitavastatin may be particularly beneficial in high-risk patients with elevated concentrations of TG-rich lipoproteins and low levels of HDL-C, and in whom the atheroprotective function of HDL particles is typically defective; significantly, such patients typically exhibit persistent, residual cardiometabolic risk even when LDL-C is at goal. In this context, it is relevant that such patient groups cover a wide spectrum of metabolic diseases, including metabolic syndrome, type 2 diabetes, coronary disease, familial and non-familial forms of hypercholesterolemia, auto-immune diseases such as rheumatoid arthritis and lupus, renal disease and some forms of hepatic insufficiency.
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PMID:Pitavastatin: novel effects on lipid parameters. 2215 82

Lorcaserin (LOR) is a selective 5-HT2C receptor agonist that has been FDA approved as a treatment for obesity. The most frequently reported side-effects of LOR include nausea and headache, which can be dose limiting. We have previously reported that in the rat, while LOR produced unconditioned signs characteristic of nausea/malaise, the highly selective 5-HT2C agonist CP-809101 (CP) produced fewer equivalent signs. Because this may indicate a subclass of 5-HT2C agonists having better tolerability, the present studies were designed to further investigate this apparent difference. In a conditioned gaping model, a rodent test of nausea, LOR produced significantly higher gapes compared to CP consistent with it having higher emetogenic properties. Subsequent studies were designed to identify features of each drug that may account for such differences. In rats trained to discriminate CP-809101 from saline, both CP and LOR produced full generalization suggesting a similar interoceptive cue. In vitro tests of functional selectivity designed to examine signaling pathways activated by both drugs in CHO (Chinese hamster ovary) cells expressing h5-HT2C receptors failed to identify evidence for biased signaling differences between LOR and CP. Thus, both drugs showed similar profiles across PLC, PLA2, and ERK signaling pathways. In studies designed to examine pharmacokinetic differences between LOR and CP, while drug plasma levels correlated with increasing dose, CSF levels did not. CSF levels of LOR increased proportionally with dose; however CSF levels of CP plateaued from 6 to 12 mg/kg. Thus, the apparently improved tolerability of CP likely reflects a limit to CNS levels attained at relatively high doses.
ACS Chem Neurosci 2017 05 17
PMID:Studies To Examine Potential Tolerability Differences between the 5-HT2C Receptor Selective Agonists Lorcaserin and CP-809101. 2833 24