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https://www.readbyqxmd.com/read/29243172/therapeutic-delivery-of-simvastatin-loaded-in-pla-peg-polymersomes-resulted-in-amplification-of-anti-inflammatory-effects-in-activated-microglia
#1
Dharani Manickavasagam, Kimberly Novak, Moses O Oyewumi
Simvastatin (Sim), a lipid-lowering drug has been studied in chronic neuroinflammation associated with degenerative brain disorders due to its potential protective properties against inflammatory reaction, oxidative damage, neuronal dysfunction, and death. Meanwhile, potential application of Sim in neuroinflammation will require a suitable delivery system that can overcome notable challenges pertaining to poor blood-brain barrier (BBB) permeability and side/off-target effects. Herein, we engineered and characterized nano-sized polymersomes loaded with Sim (Sim-Ps) using PEG-PdLLA (methoxy polyethylene glycol-poly(D,L) lactic acid) diblock co-polymers...
December 14, 2017: AAPS Journal
https://www.readbyqxmd.com/read/29242847/simvastatin-intolerance-genetic-determinants-some-features-in-ethnic-uzbek-patients-with-coronary-artery-disease
#2
Aleksandr B Shek, Ravshanbek D Kurbanov, Guzal J Abdullaeva, Aleksandr V Nagay, Shavkat U Hoshimov, Ulugbek I Nizamov, Adolat V Ziyaeva, Rano B Alieva
Introduction: The objective is to study the influence of CYP3A5 (6986A>G), CYP2C9 (430C>T), CYP2C9 (1075A>C), SLCO1B1 (521T>C) and BCRP (ABCG2, 421C>A) gene polymorphisms on the development of simvastatin intolerance in ethnic Uzbek patients with coronary artery disease (CAD). Material and methods: The case group contained 50 patients with clinical simvastatin-induced intolerance symptoms; the control group contained 50 patients without side-effects...
2017: Archives of Medical Sciences. Atherosclerotic Diseases
https://www.readbyqxmd.com/read/29236027/simvastatin-inhibits-cell-proliferation-and-migration-in-human-anaplastic-thyroid-cancer
#3
Mei-Chieh Chen, Yuan-Chin Tsai, Jen-Ho Tseng, Jr-Jiun Liou, Steve Horng, Heng-Ching Wen, Yu-Ching Fan, Wen-Bin Zhong, Sung-Po Hsu
Malignant human anaplastic thyroid cancer (ATC) is pertinacious to conventional therapies. The present study investigated the anti-cancer activity of simvastatin and its underlying regulatory mechanism in cultured ATC cells. Simvastatin (0-20 μM) concentration-dependently reduced cell viability and relative colony formation. Depletions of mevalonate (MEV) and geranylgeranyl pyrophosphate (GGpp) by simvastatin induced G1 arrest and increased apoptotic cell populations at the sub-G1 phase. Adding MEV and GGpp prevented the simvastatin-inhibited cell proliferation...
December 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29233637/compound-heterozygous-familial-hypercholesterolemia-in-a-chinese-boy-with-a-de%C3%A2-novo-and-transmitted-low-density-lipoprotein-receptor-mutation
#4
Yizhe Ma, Yingyun Gong, Abhimanyu Garg, Hongwen Zhou
BACKGROUND: Homozygous familial hypercholesterolemia is characterized by extremely elevated serum low-density lipoprotein cholesterol (LDL-C) levels and increased risk of cardiovascular complications due to biallelic mutations in LDL receptor (LDLR). OBJECTIVE: We present a 10-year-old Chinese homozygous familial hypercholesterolemia boy with biallelic LDLR mutations including an extremely rare de novo mutation. METHODS: Detailed family history and clinical and biochemical data were gathered from the pedigree...
October 26, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29232287/the-effects-of-known-cardioprotective-drugs-on-proinflammatory-cytokine-secretion-from-human-coronary-artery-endothelial-cells
#5
Michael J Haas, Marilu Jurado-Flores, Ramadan Hammoud, Victoria Feng, Krista Gonzales, Luisa Onstead-Haas, Arshag D Mooradian
BACKGROUND: Endothelial cell dysfunction in diabetes is involved in the pathogenesis and progression of premature atherosclerosis. High-dextrose has been shown to induce both oxidative stress and endoplasmic reticulum stress in cultured human coronary artery endothelial cells (HCAEC). STUDY QUESTION: To determine whether or not several classes of cardioprotective drugs inhibit proinflammatory cytokine expression by HCAEC. MEASURES AND OUTCOMES: To determine the effects of high dextrose on expression of proinflammatory cytokines by HCAEC, cells were treated with either 5...
November 27, 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/29228833/in-vitro-in-silico-approach-in-the-development-of-simvastatin-loaded-self-microemulsifying-drug-delivery-systems
#6
Zora Ćetković, Sandra Cvijić, Dragana Vasiljević
OBJECTIVE: The aims of this study were to formulate simvastatin (SV)-loaded self-microemulsifying drug delivery systems (SMEDDS), and explore the potential of these drug delivery systems to improve SV solubility, and also to identify the optimal place in the gastrointestinal (GI) tract for the release of SV using coupled in vitro/in silico approach. SIGNIFICANCE: In comparison to other published results, this study considered the extensive presystemic clearance of SV, which could significantly decrease its systemic and hepatic bioavailability if SV is delivered into the small intestine...
December 12, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29224179/antidiabetic-polypill-improves-central-pathology-and-cognitive-impairment-in-a-mixed-model-of-alzheimer-s-disease-and-type-2-diabetes
#7
Carmen Infante-Garcia, Juan Jose Ramos-Rodriguez, Carmen Hierro-Bujalance, Esperanza Ortegon, Eleanor Pickett, Rosemary Jackson, Fernando Hernandez-Pacho, Tara Spires-Jones, Monica Garcia-Alloza
Type 2 diabetes (T2D) is an important risk factor to suffer dementia, being Alzheimer's disease (AD) as the most common form. Both AD and T2D are closely related to aging and with a growing elderly population it might be of relevance to explore new therapeutic approaches that may slow or prevent central complications associated with metabolic disorders. Therefore, we propose the use of the antidiabetic polypill (PP), a pharmacological cocktail, commonly used by T2D patients that include metformin, aspirin, simvastatin, and an angiotensin-converting enzyme inhibitor...
December 9, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29223273/a-79-year-old-woman-with-dyspnea-and-hypoxemia-that-worsened-in-an-upright-position
#8
Tjeerd van der Veer, Johannes C C M In 't Veen, Wijnand K den Dekker, Jelle Miedema
A 79-year-old woman presented to the ED with complaints of gradually worsening exertional dyspnea, dizziness, and chest discomfort. For several weeks she had not been able to perform light household work. The patient's medical history mentioned pulmonary embolism following immobilization (2012), several fractures after trauma, an ischemic cerebral vascular accident (2014), and curative treatment for breast cancer (1995). Her current medication included esomeprazole, clopidogrel, simvastatin, calcium/vitamin D, amitriptyline, and acetaminophen...
December 2017: Chest
https://www.readbyqxmd.com/read/29217967/tuning-properties-of-poly-ethylene-glycol-block-poly-simvastatin-copolymers-synthesized-via-triazabicyclodecene
#9
Theodora A Asafo-Adjei, Thomas D Dziubla, David A Puleo
Simvastatin was polymerized into copolymers to better control drug loading and release for therapeutic delivery. When using the conventional stannous octoate catalyst in ring-opening polymerization (ROP), reaction temperatures ≥200 °C were required, which promoted uncontrollable and undesirable side reactions. Triazabicyclodecene (TBD), a highly reactive guanidine base organocatalyst, was used as an alternative to polymerize simvastatin. Polymerization was achieved at 150 °C using 5 kDa methyl-terminated poly(ethylene glycol) (mPEG) as the initiator...
October 2017: Reactive & Functional Polymers
https://www.readbyqxmd.com/read/29211309/statins-in-nonsurgical-and-surgical-periodontal-therapy-a-systematic-review-and-meta-analysis-of-preclinical-in-vivo-trials
#10
REVIEW
K Bertl, I Steiner, N Pandis, K Buhlin, B Klinge, A Stavropoulos
The cholesterol-lowering drugs, statins, possess anti-inflammatory, antimicrobial and pro-osteogenic properties, and thus have been tested as an adjunct to periodontal treatment. The present systematic review aimed to answer the following focused research question: What is the effect of local and/or systemic statin use on periodontal tissues in preclinical in vivo studies of experimentally induced periodontitis (EIP) and/or acute/chronified periodontal defect (ACP) models? A literature search (of Medline/PubMed, Embase/Ovid, CENTRAL/Ovid) using the following main eligibility criteria was performed: (i) English or German language; (ii) controlled preclinical in vivo trials; (iii) local and/or systemic statin use in EIP and/or ACP models; and (iv) quantitative evaluation of periodontal tissues (i...
December 6, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/29210030/pharmacologic-prevention-of-variceal-bleeding-and-rebleeding
#11
REVIEW
Anna Baiges, Virginia Hernández-Gea, Jaime Bosch
BACKGROUND: Variceal bleeding is a major complication of portal hypertension, which is associated with significant mortality. Moreover, patients surviving a variceal bleeding episode have very high risk of rebleeding, which is associated with mortality as high as that of the first bleed. Because of this, prevention of bleeding from gastroesophageal varices has been one of the main therapeutic goals since the advent of the first effective therapies for portal hypertension. AIM: This review deals with the present day state-of-the-art pharmacological prevention of variceal bleeding in primary and secondary prophylaxis...
December 5, 2017: Hepatology International
https://www.readbyqxmd.com/read/29209217/arylacetamide-deacetylase-is-involved-in-vicagrel-bioactivation-in-humans
#12
Jinfang Jiang, Xiaoyan Chen, Dafang Zhong
Vicagrel, a structural analog of clopidogrel, is now being developed as a thienopyridine antiplatelet agent in a phase II clinical trial in China. Some studies have shown that vicagrel undergoes complete first-pass metabolism in human intestine, generating the hydrolytic metabolite 2-oxo-clopidogrel via carboxylesterase-2 (CES2) and subsequently the active metabolite H4 via CYP450s. This study aimed to identify hydrolases other than CES2 that are involved in the bioactivation of vicagrel in human intestine...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29208461/simvastatin-inhibits-the-development-of-radioresistant-esophageal-cancer-cells-by-increasing-the-radiosensitivity-and-reversing-emt-process-via-the-pten-pi3k-akt-pathway
#13
Yingying Jin, Kun Xu, Qingjuan Chen, Baofeng Wang, Jiyuan Pan, Shan Huang, Yang Wei, Hongbing Ma
Acquired radioresistance compromises the efficacy of radiotherapy for carcinomas including esophageal cancer (EC), thus resulting in recurrence and poor survival. Recent research corroborated radiosensitive function of simvastatin in stem-like breast cancer cells. However, its role in EC radioresistance remains poorly elucidated. Here, we developed a radioresistant EC cell line Ec9706-R with higher resistance to irradiation relative to control Ec9706 cells. Intriguingly, Ec9706-R cells exhibited epithelial-mesenchymal transition (EMT) characteristics with high invasion and migration ability...
December 2, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29207644/protection-by-simvastatin-on-hyperglycemia-induced-endothelial-dysfunction-through-inhibiting-nlrp3-inflammasomes
#14
Zhen-Huan Lv, Trinh Anh Phuong, Shi-Jie Jin, Xiao-Xue Li, Ming Xu
Recent studies have demonstrated that NLRP3 inflammasome complex acts as pivotal elements to initiate inflammatory responses and plays an important role in the dysfunction of cardiovascular complications. Meanwhile, simvastatin prevents vascular endothelial dysfunction from inflammasome invasion contributing to reduce cardiovascular risk. However, Whether or not the simvastatin improves vascular endothelial barrier function through inhibiting the activation of NLRP3 inflammasome pathway remains unknown. Here, we explored the role and mechanisms of simvastatin in the activation of NLRP3 inflammasome which are involved in vascular endothelial hyperpermeability causing by the disruption of tight junction protein ZO-1 and adherens junction protein VE-Cadherin, an early initiation of cardiovascular complication...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29204687/a-physiologically-based-pharmacokinetic-pbpk-parent-metabolite-model-of-the-chemotherapeutic-zoptarelin-doxorubicin-integration-of-in-vitro-results-phase-i-and-phase-ii-data-and-model-application-for-drug-drug-interaction-potential-analysis
#15
Nina Hanke, Michael Teifel, Daniel Moj, Jan-Georg Wojtyniak, Hannah Britz, Babette Aicher, Herbert Sindermann, Nicola Ammer, Thorsten Lehr
PURPOSE: Zoptarelin doxorubicin is a fusion molecule of the chemotherapeutic doxorubicin and a luteinizing hormone-releasing hormone receptor (LHRHR) agonist, designed for drug targeting to LHRHR positive tumors. The aim of this study was to establish a physiologically based pharmacokinetic (PBPK) parent-metabolite model of zoptarelin doxorubicin and to apply it for drug-drug interaction (DDI) potential analysis. METHODS: The PBPK model was built in a two-step procedure...
December 4, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29203418/electronic-medical-records-can-be-used-to-emulate-target-trials-of-sustained-treatment-strategies
#16
Goodarz Danaei, Luis Alberto García Rodríguez, Oscar Fernández Cantero, Roger W Logan, Miguel A Hernán
OBJECTIVE: To emulate three target trials: single treatment versus no treatment, joint treatment versus no treatment, and head-to-head comparison of two treatments. We explain how to estimate the observational analogs of intention-to-treat and per-protocol effects, using hazard ratios and survival curves. For per-protocol effects, we describe two methods for adherence adjustment via inverse-probability weighting. STUDY DESIGN AND SETTING: Prospective observational study using electronic medical records of individuals aged 55-84 with coronary heart disease from >500 practices in the United Kingdom between 2000-2010...
December 1, 2017: Journal of Clinical Epidemiology
https://www.readbyqxmd.com/read/29202630/concurrent-new-drug-prescriptions-and-prognosis-of-early-breast-cancer-studies-using-the-danish-breast-cancer-group-clinical-database
#17
Deirdre Cronin-Fenton, Timothy L Lash, Thomas P Ahern, Per Damkier, Peer Christiansen, Bent Ejlertsen, Henrik T Sørensen
BACKGROUND: Myriad reports suggest that frequently used prescription drugs alter the viability of breast cancer cells in pre-clinical studies. Routine use of these drugs, therefore, may impact breast cancer prognosis, and could have important implications for public health. METHODS: The Danish Breast Cancer Group (DBCG) clinical database provides high-quality prospectively collected data on breast cancer diagnosis, treatment, and routine follow-up for breast cancer recurrence...
December 5, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29201188/simvastatin-augments-activation-of-liver-regeneration-through-attenuating-transforming-growth-factor-%C3%AE-1-induced-apoptosis-in-obstructive-jaundice-rats
#18
Dazheng Fang, Ying He, Zhou Luan
Obstructive jaundice, owing to biliary obstruction, has been illustrated to trigger various biochemical, histological and immunological changes, leading to liver damage or even failure. The detailed molecular mechanism of simvastatin (Sim) involvement in liver regeneration during obstructive jaundice progression remains poorly elucidated. In the present study, an acute obstructive jaundice rat model was established by ligation and division of common bile duct, which was used to investigate the effects of Sim as a hepatoprotective treatment...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29200765/simvastatin-ezetimibe-therapy-for-recalcitrant-alopecia-areata-an-open-prospective-study-of-14-patients
#19
Joong-Woon Choi, Dong-Woo Suh, Bark-Lynn Lew, Woo-Young Sim
Background: Simvastatin belongs to the statin family, whose members have immunomodulatory activities. Ezetimibe have synergetic effects when co-administered with simvastatin. In several case reports, alopecia totalis and alopecia universalis were successfully treated with simvastatin/ezetimibe, suggesting that this combination could be a new efficient therapy for recalcitrant alopecia areata (AA). Objective: To verify the efficacy of the simvastatin/ezetimibe combination therapy for recalcitrant AA and investigate the relationship between various treatment responses and prognostic factors...
December 2017: Annals of Dermatology
https://www.readbyqxmd.com/read/29197789/nanostructured-lipid-carriers-for-improved-oral-delivery-and-prolonged-antihyperlipidemic-effect-of-simvastatin
#20
Heba A Fathi, Ayat Allam, Mahmoud Elsabahy, Gihan Fetih, Mahmoud El-Badry
The purpose of the current study is to develop nanostructured lipid carriers (NLCs) for the delivery of the antihyperlipidemic drug simvastatin (SIM) to increase its extremely low oral bioavailability (<5%) and prolong its antihyperlipidemic effect. NLCs were prepared via emulsification-solvent evaporation technique followed by ultrasonication, and the effect of composition of the nanocarriers on the particle size, size distribution, surface charge, entrapment efficiency, drug release kinetics and physical stability was extensively studied...
November 28, 2017: Colloids and Surfaces. B, Biointerfaces
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