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https://www.readbyqxmd.com/read/28629155/repositioning-fda-drugs-as-potential-cruzain-inhibitors-from-trypanosoma-cruzi-virtual-screening-in-vitro-and-in-vivo-studies
#1
Isidro Palos, Edgar E Lara-Ramirez, Julio Cesar Lopez-Cedillo, Carlos Garcia-Perez, Muhammad Kashif, Virgilio Bocanegra-Garcia, Benjamin Nogueda-Torres, Gildardo Rivera
Chagas disease (CD) is a neglected disease caused by the parasite Trypanosoma cruzi, which affects underdeveloped countries. The current drugs of choice are nifurtimox and benznidazole, but both have severe adverse effects and less effectivity in chronic infections; therefore, the need to discover new drugs is essential. A computer-guided drug repositioning method was applied to identify potential FDA drugs (approved and withdrawn) as cruzain (Cz) inhibitors and trypanocidal effects were confirmed by in vitro and in vivo studies...
June 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28618994/role-of-anti-pcsk9-antibodies-in-the-treatment-of-patients-with-statin-intolerance
#2
Julia Schreml, Ioanna Gouni-Berthold
Statin intolerance is usually defined as the inability of a patient to tolerate statin-treatment due to muscle-related complaints. While randomised trials show that these complaints occure with similar frequency in patients receiving placebo, namely in up to ~5% of the subjects, data from registries as well as clinical experience indicate a much higher frequency of up to ~30%. The lack of standard definition or of a diagnostic marker of statin intolerance confounds the problem. The diagnosis remains subjective based on the symptoms the patient reports...
June 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28595549/apoc-iii-antisense-oligonucleotides-a-new-option-for-the-treatment-of-hypertriglyceridemia
#3
Joel Schmitz, Ioanna Gouni-Berthold
Elevated triglyceride levels (higher than ~1000 mg/dL) are associated with an increased risk for pancreatitis. Apolipoprotein-CIII (apoC-III) plays a key role in the metabolism of triglycerides and triglyceride-rich lipoproteins. Loss of function mutations in the gene encoding apoC-III (APOC3) are associated with low triglyceride levels and a decreased risk for cardiovascular disease (CVD) while overexpression of APOC3 is associated with hypertriglyceridemia. Although many drugs such as fibrates, statins and omega-3 fatty acids modestly decrease triglyceride levels (and apoC-III concentrations), there are many patients who still have severe hypertriglyceridemia and are at increased risk for pancreatitis and potentially for CVD...
June 8, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28581332/ppars-regulators-of-metabolism-and-as-therapeutic-targets-in-cardiovascular-disease-part-i-ppar-%C3%AE
#4
Lu Han, Wen-Jun Shen, Stefanie Bittner, Fredric B Kraemer, Salman Azhar
This article provides a comprehensive review about the molecular and metabolic actions of PPAR-α. It describes its structural features, ligand specificity, gene transcription mechanisms, functional characteristics and target genes. In addition, recent progress with the use of loss of function and gain of function mouse models in the discovery of diverse biological functions of PPAR-α, particularly in the vascular system and the status of the development of new single, dual, pan and partial PPAR agonists (PPAR modulators) in the clinical management of metabolic diseases are presented...
June 5, 2017: Future Cardiology
https://www.readbyqxmd.com/read/28535810/fibrates-for-the-treatment-of-cholestatic-itch-fitch-study-protocol-for-a-randomized-controlled-trial
#5
Ruth Bolier, Elsemieke S de Vries, Albert Parés, Jeltje Helder, E Marleen Kemper, Koos Zwinderman, Ronald P Oude Elferink, Ulrich Beuers
BACKGROUND: Pruritus (itch) is a frequent, burdensome and difficult-to-treat symptom in patients with cholestasis. Fibrates are currently under investigation for the treatment of primary biliary cholangitis in patients with a suboptimal response to ursodeoxycholic acid. Moreover, there is empirical evidence for a possible antipruritic effect. We aim to prove this in a randomized controlled trial, including patients with cholestatic liver diseases other than primary biliary cholangitis that are accompanied by pruritus...
May 23, 2017: Trials
https://www.readbyqxmd.com/read/28528456/pharmacologic-treatment-of-dyslipidemia-in-diabetes-a-case-for-therapies-in-addition-to-statins
#6
REVIEW
Abeer Anabtawi, Patrick M Moriarty, John M Miles
PURPOSE OF REVIEW: The purpose of the study is to review the use of statins and the role of both non-statin lipid-lowering agents and diabetes-specific medications in the treatment of diabetic dyslipidemia. RECENT FINDINGS: Statins have a primary role in the treatment of dyslipidemia in people with type 2 diabetes, defined as triglyceride levels >200 mg/dl and HDL cholesterol levels <40 mg/dL. A number of clinical trials suggest that treatment with a fibrate may reduce cardiovascular events...
July 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28517369/treatment-of-primary-biliary-cholangitis-non-responders-a-systematic-review
#7
Duminda Suraweera, Harman Rahal, Melissa Jimenez, Matthew Viramontes, Gina Choi, Sammy Saab
BACKGROUND: Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is a chronic cholestatic liver disease characterized by an immune mediated destruction of intrahepatic bile ducts. Ursodeoxycholic acid (UDCA) has been the primary medication for the treatment of PBC, resulting in improved liver tests, resolution of symptoms and increased transplant free survival. However, not all patients respond to UDCA. The aim of this systematic review is to provide an evidence based assessment of the medications that have been studied in patients who are refractory to UDCA...
May 18, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28516251/-severe-hypertriglyceridemia-diagnostics-and-new-treatment-principles
#8
U Kassner, M Dippel, E Steinhagen-Thiessen
Severe hypertriglyceridemia is defined at a plasma triglyceride (TG) concentration of >885 mg/dl and may result - in particular when clinical symptoms appear before the age of 40 - from "large variant" mutations in genes which influence the function of the lipoprotein lipase (LPL). For diagnosis, secondary factors have to be excluded and treated before further genetic tests are considered. Typical symptoms in almost all patients are recurrent, sometimes severe abdominal pain attacks, which can result in acute pancreatitis, the most important, sometimes life-threatening complication...
May 17, 2017: Der Internist
https://www.readbyqxmd.com/read/28495810/management-of-lipid-lowering-therapy-in-patients-with-cardiovascular-events-in-the-uk-a-retrospective-cohort-study
#9
Mark D Danese, Michelle Gleeson, Lucie Kutikova, Robert I Griffiths, Kamlesh Khunti, Sreenivasa Rao Kondapally Seshasai, Kausik K Ray
OBJECTIVES: To describe low-density lipoprotein (LDL) cholesterol management and lipid-lowering treatment patterns in patients with a cardiovascular (CV) event. DESIGN: Retrospective cohort study using Clinical Practice Research Datalink records linked with Hospital Episode Statistics data. SETTING: Routine clinical practice in the UK from 2006 to 2012. PARTICIPANTS: Individuals ≥18 years were selected at their first CV-related hospitalisation (first event cohort) if they had received ≥2 lipid-lowering therapy prescriptions within 180 days beforehand...
May 10, 2017: BMJ Open
https://www.readbyqxmd.com/read/28476288/adverse-events-associated-with-unblinded-but-not-with-blinded-statin-therapy-in-the-anglo-scandinavian-cardiac-outcomes-trial-lipid-lowering-arm-ascot-lla-a-randomised-double-blind-placebo-controlled-trial-and-its-non-randomised-non-blind-extension-phase
#10
Ajay Gupta, David Thompson, Andrew Whitehouse, Tim Collier, Bjorn Dahlof, Neil Poulter, Rory Collins, Peter Sever
BACKGROUND: In blinded randomised controlled trials, statin therapy has been associated with few adverse events (AEs). By contrast, in observational studies, larger increases in many different AEs have been reported than in blinded trials. METHODS: In the Lipid-Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes Trial, patients aged 40-79 years with hypertension, at least three other cardiovascular risk factors, and fasting total cholesterol concentrations of 6·5 mmol/L or lower, and who were not taking a statin or fibrate, had no history of myocardial infarction, and were not being treated for angina were randomly assigned to atorvastatin 10 mg daily or matching placebo in a randomised double-blind placebo-controlled phase...
May 2, 2017: Lancet
https://www.readbyqxmd.com/read/28474570/targeting-pparalpha-in-alzheimer-s-disease
#11
Barbara D Orio, Anna Fracassi, Maria Paola Cerù, Sandra Moreno
Alzheimer's disease (AD) is the result of a combination of genetic and environmental risk factors and the molecular mechanisms underlying cognitive decline are yet to be fully elucidated. The so-called "amyloid cascade hypothesis" has long been the prevailing paradigm for causation of disease, and today being revisited in relation to other pathogenic pathways, such as oxidative stress, neuroinflammation and lipid and glucose dysmetabolism. The peroxisome proliferator-activated receptors (PPARs) are expressed in the CNS and regulate many physiological processes, such as energy metabolism, neurotransmission, redox homeostasis, autophagy and cell cycle...
May 4, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28468009/what-comes-after-ursodeoxycholic-acid-in-primary-biliary-cholangitis
#12
Lin Lee Wong, Vinod S Hegade, David E J Jones
Primary biliary cholangitis (PBC) is a rare autoimmune liver disease characterized by chronic cholestasis. Treatment with the accepted primary therapy ursodeoxycholic acid (UDCA) has been shown to be associated with delayed disease progression probably through reduced impact of cholestatic injury on the target biliary epithelial cells. Patients with inadequate response to UDCA (which can be identified through validated biochemical criteria) are at increased risk of disease progression, need for liver transplantation, and death...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28443263/a-1-month-old-infant-with-chylomicronemia-due-to-gpihbp1-gene-mutation-treated-by-plasmapheresis
#13
Mo Kyung Jung, Juhyun Jin, Hyun Ok Kim, Ahreum Kwon, Hyun Wook Chae, Seok Jin Kang, Duk Hee Kim, Ho-Seong Kim
Chylomicronemia is a severe type of hypertriglyceridemia characterized by chylomicron accumulation that arises from a genetic defect in intravascular lipolysis. It requires urgent and proper management, because serious cases can be accompanied by pancreatic necrosis or persistent multiple organ failure. We present the case of a 1-month-old infant with chylomicronemia treated by plasmapheresis. His chylomicronemia was discovered incidentally when lactescent plasma was noticed during routine blood sampling during a hospital admission for fever and irritability...
March 2017: Annals of Pediatric Endocrinology & Metabolism
https://www.readbyqxmd.com/read/28441507/new-metrics-for-economic-evaluation-in-the-presence-of-heterogeneity-focusing-on-evaluating-policy-alternatives-rather-than-treatment-alternatives
#14
David D Kim, Anirban Basu
BACKGROUND: Cost-effectiveness analysis (CEA) methods fail to acknowledge that where cost-effectiveness differs across subgroups, there may be differential adoption of technology. Also, current CEA methods are not amenable to incorporating the impact of policy alternatives that potentially influence the adoption behavior. Unless CEA methods are extended to allow for a comparison of policies rather than simply treatments, their usefulness to decision makers may be limited. METHODS: We conceptualize new metrics, which estimate the realized value of technology from policy alternatives, through introducing subgroup-specific adoption parameters into existing metrics, incremental cost-effectiveness ratios (ICERs) and Incremental Net Monetary Benefits (NMBs)...
April 1, 2017: Medical Decision Making: An International Journal of the Society for Medical Decision Making
https://www.readbyqxmd.com/read/28441155/do-triglyceride-lowering-drugs-decrease-risk-of-cardiovascular-disease
#15
Kevin C Maki, Mary R Dicklin
PURPOSE OF REVIEW: This review summarizes the evidence supporting a relationship between lowering triglycerides (TGs) and TG-rich lipoprotein cholesterol (TGRL-C) levels and reduced atherosclerotic cardiovascular disease (ASCVD) event risk. RECENT FINDINGS: Data from observational investigations, including studies of genetic variants, provide evidence consistent with a causal relationship between elevations in TG and TGRL-C and greater risk for ASCVD. Randomized controlled trial evidence of ASCVD risk reduction with therapies that substantially lower TG and TGRL-C is limited by the fact that no large-scale trial results have been published from a study that enrolled subjects selected specifically on the basis of TG or TGRL-C elevation, although three such trials are underway or in the planning stages...
April 22, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28413978/advances-and-challenges-in-drug-design-of-ppar%C3%AE-ligands
#16
Vinicius Gonçalves Maltarollo, Thales Kronenberger, Björn Windshügel, Carsten Wrenger, Gustavo Henrique Goulart Trossini, Kathia Maria Honorio
Peroxisome proliferator-activated receptors (PPAR) are nuclear receptors activated by endogenous fatty acids and prostaglandins that are classified into three types: α, γ and δ, which have different functions and tissue distribution. PPAR modulators have been exploited to the treatment of important metabolic diseases, such as type 2 diabetes mellitus and metabolic syndrome, which are considered relevant epidemic diseases currently. Along the last decades, several studies have reported structural differences between the three PPAR subtypes associated with the discovery of selective ligands, dual and pan-agonists...
April 14, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28401920/occurrence-of-fibrates-and-their-metabolites-in-source-and-drinking-water-in-shanghai-and-zhejiang-china
#17
Akiko Ido, Youhei Hiromori, Liping Meng, Haruki Usuda, Hisamitsu Nagase, Min Yang, Jianying Hu, Tsuyoshi Nakanishi
Fibrates, which are widely used lipidaemic-modulating drugs, are emerging environmental pollutants. However, fibrate concentrations in the environment have not been thoroughly surveyed. Here, we determined concentrations of the most commonly used fibrates and their metabolites in source water and drinking water samples from ten drinking water treatment plants in Shanghai and Zhejiang, China, using solid-phase extraction and liquid chromatography-tandem mass spectrometry. All the target compounds were detected in at least some of the source water samples, at concentrations ranging from 0...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28394011/how-has-the-treatment-of-hypercholesterolemia-in-poland-changed-over-the-last-6-years
#18
Agnieszka Kapłon-Cieślicka, Marcin Michalak, Łukasz Kołtowski, Krzysztof J Filipiak
BACKGROUND: To assess changes in the treatment of hypercholesterolemia in Polish ambulatory care over the last 6 years. METHODS: Data were obtained from two separate questionnaire-based studies, conducted in 2009 and 2015. The analysis included only those patient visits, which were associated with modifications of previous hypercholesterolemia treatment (1924 visits from the year 2009 and 1888 visits from the year 2015). RESULTS: In the present registry, there was a 19 mg/dL reduction in the level of total cholesterol and a 17 mg/dL reduction in the level of low-density lipoprotein compared to year 2009...
April 10, 2017: Cardiology Journal
https://www.readbyqxmd.com/read/28391900/estrogen-associated-severe-hypertriglyceridemia-with-pancreatitis
#19
Sumayah Aljenedil, Robert A Hegele, Jacques Genest, Zuhier Awan
BACKGROUND: Estrogen, whether therapeutic or physiologic, can cause hypertriglyceridemia. Hypertriglyceridemia-induced pancreatitis is a rare complication. CASES: We report 2 women who developed estrogen-associated severe hypertriglyceridemia with pancreatitis. The first patient developed pancreatitis secondary to hypertriglyceridemia associated with in vitro fertilization cycles. Marked reduction in her triglyceride was achieved with dietary restrictions and fibrate...
January 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28391898/severe-decrease-in-high-density-lipoprotein-cholesterol-with-the-combination-of-fibrates-and-ezetimibe-a-case-series
#20
Estelle Nobecourt, Bertrand Cariou, Gilles Lambert, Michel Krempf
A sudden and severe drug-induced decrease in plasma high-density lipoprotein cholesterol (HDL-C) is a rare condition. We report 2 patients with familial hypercholesterolemia treated with statins and fibrates and 2 others with mixed dyslipidemia treated with fibrates, who presented with a sudden and severe decrease in HDL-C (from -44% to -95%, compared with baseline). Three of the patients were treated with fibrates and had a sudden decrease in HDL-C after the adjunction of ezetimibe. HDL-C returned to normal levels after discontinuation of the offending therapies...
January 2017: Journal of Clinical Lipidology
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