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Management of diabetic dyslipidemia: An update

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World Journal of Diabetes 2019年第5期10卷 280-290页

作者： Ishwarlal Jialal Gurdeep Singh California North-state University College of Medicine VA Medical Center Lady of Lourdes Memorial Hospital

Diabetic dyslipidemia is a cluster of lipoprotein abnormalities characterized by increased triglyceride level, decreased high-density lipoprotein-cholesterol levels and increase in small dense low-density lipoprotein(LDL) particles. It is extremely common in type 2 diabetes(T2DM) affecting around 70 % of *** is a significant risk factor for atherosclerotic cardiovascular disease(ASCVD) which is the most common cause of death in the United States and LDL-cholesterol is the number 1 predictor of ASCVD events in T2DM. The purpose of this review is to discuss the pathophysiology and treatment of diabetic dyslipidemia. In this review, we have discussed both nonpharmacological and pharmacological treatment modalities including major treatment trials which have impacted the cardiovascular outcomes in patients with diabetes. Statin therapy is the mainstay of treatment to reduce ASCVD by decreasing LDL-C by 30%-49% or at least 50% depending on risk level. Attractive adjunctive therapies include ezetimibe which is more cost effective and PCSK9 inhibitors which display potent LDL-cholesterol lowering and ASCVD event reduction. For severe hypertriglyceridemia, to avert the risk of pancreatitis, both fish oil and fenofibrate in concert with diet is the best strategy.

关键词： Diabetes Dyslipidemia Statins Atherosclerosis ezetimibe PCSK9

Combination drug treatment in patients with non-alcoholic fatty liver disease

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World Journal of Hepatology 2010年第4期2卷 139-142页

作者： Theodosios D Filippatos Moses S Elisaf Department of Internal Medicine University of Ioannina Ioannina 45110 Greece

Non-alcoholic fatty liver disease (NAFLD) includes simple steatosis, a benign condition, and non-alcoholic steatohepatitis, a condition that beyond TG accumulation also includes necroinflammation and fibrosis. An association between NAFLD and cardiovascular disease (CVD) has been recently suggested. NAFLD patients usually have an increased CVD risk profile. NAFLD is also associated with metabolic syndrome (MetS) and is considered as the hepatic component of MetS by some authors. Currently, the only established treatment of NAFLD is gradual weight loss. However, multifactorial treatment of NAFLD risk factors may be needed to reduce the increased CVD risk of NALFD patients. Drug combinations that include antiobesity drugs (such as orlistat and sibutramine) and target CVD risk factors may be a good approach to NAFLD patients. Our group has investigated the orlistat-fenofibrate combination treatment in obese patients with MetS and the orlistatezetimibe and sibutramine-antihypertensive combination treatment in obese patients with hyperlipidaemia with promising results in CVD risk factor reduction and improvement of liver function tests. Small studies give promising results but double-blind, randomized trials examining the effects of such multifactorial treatment in hard CVD endpoints in NAFLD patients are missing.

关键词： Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Treatment Orlistat Sibutramine Fenofibrate ezetimibe Weight loss

Intensive lipid-lowering therapy,time to think beyond low-density lipoprotein cholesterol

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World Journal of Cardiology 2021年第9期13卷 472-482页

作者： Ahmed Abdalwahab Ayman Al-atta Azfar Zaman Mohammad Alkhalil Cardiothoracic Centre Freeman HospitalNewcastle upon Tyne NE77DNUnited Kingdom Department of Cardiovascular Medicine Faculty of MedicineTanta UniversityTanta 35127Egypt Vascular Biology Newcastle UniversityNewcastle upon Tyne NE77DNUnited Kingdom

Statins have been shown to be effective in reducing cardiovascular *** magnitude of benefits has been proportionate to the reduction in low-density lipoprotein cholesterol(LDL-c).Intensive lipid-lowering therapies using ezetimibe and more recently proprotein convertase subtilisin kexin 9 inhibitors have further improved clinical *** application of these treatments is undesirable and unaffordable and,therefore,has been guided by LDL-c ***,the residual risk in the post-statin era is markedly heterogeneous,including thrombosis and inflammation ***,the lipoprotein related risk is increasingly recognised to be related to other non-LDL-c markers such as Lp(a).Emerging data show that intensive lipid-lowering therapy produce larger absolute risk reduction in patients with polyvascular disease,post coronary artery bypass graft and ***,these clinical entities share similar phenotype of large burden of atherosclerotic *** plaque imaging may aid decision making by identifying patients with propensity to develop lipid rich plagues at multi-vascular *** patients may be suitable candidates for intensive lipid lowering treatment.

关键词： Intensive lipid-lowering Proprotein convertase subtilisin kexin 9 inhibitors ezetimibe Plaque imaging Low-density lipoprotein cholesterol

Lowering low-density lipoprotein cholesterol: from mechanisms to therapies

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Life Metabolism 2022年第1期1卷 25-38页

作者： Jie Luo Jin-Kai Wang Bao-Liang Song College of Life Sciences Hubei Key Laboratory of Cell HomeostasisTaiKang Center for Life and Medical SciencesTaiKang Medical SchoolWuhan UniversityWuhanChina

Low-density lipoprotein(LDL)is the main carrier of cholesterol and cholesteryl ester in *** plasma levels of LDL cholesterol(LDL-C)are a major risk factor of atherosclerotic cardiovascular disease(ASCVD).LDL-C lowering is recommended by many guidelines for the prevention and treatment of ***,ezetimibe,and proprotein convertase subtilisin/kexin type 9 inhibitors are the mainstay of LDL-C-lowering *** therapies are also emerging for patients who are intolerant to statins or respond poorly to standard ***,we review the most recent advances on LDL-C-lowering drugs,focusing on the mechanisms by which they act to reduce LDL-C *** article starts with the cornerstone therapies applicable to most patients at risk for *** treatments for those with little or no LDL receptor function then *** inhibitors of ATP-citrate lyase and cholesteryl ester transfer protein,which are recently approved and still under investigation for LDL-C lowering,respectively,are also *** targeting the stability of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and cholesterol catabolism can be novel regimens to reduce LDL-C levels and cardiovascular risk.

关键词： cholesterol low-density lipoprotein statin ezetimibe proprotein convertase subtilisin/kexin type 9 atherosclerotic cardiovascular disease

Two spectrophotometric methods for simultaneous determination of some antihyperlipidemic drugs

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Journal of Pharmaceutical Analysis 2012年第4期2卷 279-284页

作者： Nada S.Abdelwahab Badr A.El-Zeiny Salwa I.Tohamy Beni-suif University Faculty of PharmacyDepartment of Analytical Chemistry Cairo University Faculty of PharmacyDepartment of Analytical Chemistry

Two simple, accurate, precise and economic spectrophotometric methods have been developed for simultaneous determination of Atorvastatin calcium (ATR) and ezetimibe (EZ) in their bulk powder and pharmaceutical dosage form. Method (I) is based on dual wavelength analysis while method (II) is the mean centering of ratio spectra spectrophotometric (MCR) method. In method (I), two wavelengths were selected for each drug in such a way that the difference in absorbance was zero for the second drug. At wavelengths 226.6 and 244 nm EZ had equal absorbance values; therefore, these two wavelengths have been used to determine ATR; on a similar basis 228.6 and 262.8 nm were selected to determine EZ in their binary mixtures. In method II, the absorption spectra of both ATR and EZ with different concentrations were recorded over the range 200-350, divided by the spectrum of suitable divisor of both ATR and EZ and then the obtained ratio spectra were mean centered. The concentrations of active components were then determined from the calibration graphs obtained by measuring the amplitudes at 215-260 nm (peak to peak) for both ATR and EZ. Accuracy and precision of the developed methods have been tested; in addition recovery studies have been carried out in order to confirm their accuracy. On the other hand, selectivities of the methods were tested by application for determination of different synthetic mixtures containing different ratios of the studied drugs. The developed methods have been successfully used for determination of ATR and EZ in their combined dosage form and statistical comparison of the developed methods with the reported spectrophotometric one using F and Student’s t-tests showed no significant difference regarding both accuracy and precision.

关键词： Atorvastatin ezetimibe Dual wavelength method Mean centering of ratio spectra Spectrophotometry

Is there a role of lipid-lowering therapies in the management of fatty liver disease?

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World Journal of Hepatology 2022年第1期14卷 119-139页

作者： Ismini Tzanaki Aris P Agouridis Michael S Kostapanos School of Medicine European University CyprusNicosiaCyprusNicosia 2404Cyprus School of Medicine European University CyprusNicosia 2404Cyprus General Medicine Addenbrooke's HospitalCambridge University HospitalsCambridge CB20QQUnited Kingdom

Atherogenic dyslipidemia is characterized by increased triglyceride-rich lipoproteins and low high-density lipoprotein cholesterol *** is highly prevalent in non-alcoholic fatty liver disease(NAFLD)and contributes to the increased cardiovascular risk associated with this *** insulin resistance it plays an important pathogenetic role in NAFLD/non-alcoholic steatohepatitis(NASH)development and *** has been shown that cholesterol-lowering reduces cardiovascular risk more in NAFLD vs non-NAFLD high-risk *** evidence highlights the importance of effective lipid modulation in *** this narrative review the effects of the most commonly used lipid-lowering therapies on liver outcomes alongside their therapeutic implications in NAFLD/NASH are critically *** and clinical evidence suggests that statins reduce hepatic steatosis,inflammation and fibrosis in patients with NAFLD/*** data are derived from observational and small prospective clinical studies using changes in liver enzyme activities,steatosis/fibrosis scores,and imaging evidence of steatosis as ***,relevant histologic benefits were noted in small biopsy *** and rosuvastatin showed greater benefits,whereas data for other statins are scarce and sometimes *** studies to those of statins showed efficacy of ezetimibe against hepatic ***,no significant anti-inflammatory and anti-fibrotic actions of ezetimibe have been *** studies showed that fibrates through peroxisome proliferator-activated receptor(PPAR)αactivation may have a role in NAFLD prevention and ***,no relevant benefits have been noted in human ***-related differences in PPARαexpression and its activation responsiveness may help explain this ***-3 fatty acids reduced hepatic steatosis in numerous heterogeneous studies,but their benefits on hepatic inflammation and

关键词： Non-alcoholic fatty liver Non-alcoholic steatohepatitis Statin ezetimibe Fibrates ω-3 fatty acids Bile acid resins

Lipid lowering in patients 75 years and older

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World Journal of Cardiology 2021年第10期13卷 526-532页

作者： Umidakhon Makhmudova P Christian Schulze Harry R Davis Oliver Weingartner Klinik fur Innere Medizin I Universitatsklinikum JenaJena 07747Germany Synergy Partners RD Solutions Synergy Partners RD SolutionsGaithersburgMD 20850United States

More than twenty years ago,knowledge about the importance of cholesterol absorption and the potential therapeutic effect of its inhibition led to the discovery and clinical application of the first and only cholesterol absorption inhibitor to date–*** then,ezetimibe has become a well-recognized player in lipid-lowering *** findings of IMPROVE-IT and EWTOPIA 75 imply that elderly patients over the age of 75 years in particular benefit from *** review summarizes the evidence,discusses the possible underlying pathophysiological mechanisms and calls for a change in future dyslipidemia guidelines.

关键词： Cholesterol Cholesterol absorption Cholesterol synthesis ezetimibe Elderly

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EZETROL

中国新药杂志 2003年第11期12卷 956-957页

作者：刘萍边强武警重庆市总队医院药剂科重庆400061 重庆华邦制药有限公司重庆400041

[通用名称]ezetimibe[化学名称]1-(4-氟苯基)-3(R)-[3-(4-氟苯基)-3(S)-羟丙基]4(S)-(4-羟苯基)-2-氮杂环丁烷酮[理化性状]本品为白色结晶性粉末,极易溶于乙醇、甲醇和丙酮,不溶于水,溶液点约为163℃,在常温下稳定.

关键词： ezetimibe 降血脂药物胆固醇吸收抑制剂药理作用药动学

Therapy of gallstone disease:What it was,what it is,what it will be

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2012年第2期3卷 7-20页

作者： Piero Portincasa Agostino Di Ciaula Leonilde Bonfrate David QH Wang Department of Biomedical Sciences and Human Oncology Clinica Medica "A.Murri"University of Bari Medical SchoolPiazza Giulio Cesare 11Policlinico70124 BariItaly Division of Internal Medicine Hospital of Bisceglievia Bovio 27970052 Bisceglie (Bari)Italy Division of Gastroenterology and Hepatology Department of Internal MedicineEdward Doisy Research CenterSaint Louis University School of MedicineSt.LouisMO 63104United States

Cholesterol gallstone disease is a common clinical condition influenced by genetic factors,increasing age,female gender,and metabolic *** laparoscopic cholecystectomy is currently considered the gold standard in treating patients with symptomatic gallstones,new perspectives regarding medical therapy of cholelithiasis are currently under discussion,also taking into account the pathogenesis of gallstones,the natural history of the disease and the analysis of the overall costs of therapy.A careful selection of patients may lead to successful nonsurgical therapy in symptomatic subjects with a functioning gallbladder harboring small radiolucent *** classical oral litholysis by ursodeoxycholic acid has been recently paralleled by new experimental observations,suggesting that cholesterol-lowering agents which inhibit cholesterol synthesis (statins) or intestinal cholesterol absorption (ezetimibe),or drugs acting on specific nuclear receptors involved in cholesterol and bile acid homeostasis,might be proposed as additional approaches for treating cholesterol *** this review we discuss old,recent and future perspectives on medical treatment of cholesterol cholelithiasis.

关键词： Gallstones Dissolution therapy Cholecystectomy Bile acids ezetimibe Statins Gallbladder Bile Nuclear receptors