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Yuelong Wang, Qianwei Chen, Qiang Tan, Zhou Feng, Zhenlin He, Jun Tang, Hua Feng, Gang Zhu, Zhi Chen
To date, the neuroprotective effects of statins on intracerebral hemorrhage (ICH) are not well established. This study explored the effect and potential mechanism of simvastatin treatment on ICH. In the present study, the effects of simvastatin on hematoma absorption, neurological outcome, CD36 expression and microglia polarization were examined in rat model of ICH model. In the meantime, inhibitory effect of PPARγ inhibitor GW9662 was investigated following ICH. Additionally, the effect of simvastatin on PPARγ activation was also investigated in rat ICH model and primary microglia culture...
October 17, 2017: Neuropharmacology
Huiyu Xu, Yong Han, Jiaying Lou, Hongxian Zhang, Yue Zhao, Balázs Győrffy, Rong Li
To explore the key genes associated with both PCOS and breast cancer, we overlapped the synchronously differently expressed genes in two obese insulin-resistant GEO datasets in muscle tissue and genes exert essential roles in breast cancer prognosis together base on the following reasons: (1) Androgens excess is believed to contribute to the onset of both PCOS and breast cancer. (2) PCOS is usually complicated with metabolic symptoms, such as obesity and insulin-resistance. (3) Muscle is the main place where energy metabolism and material metabolism take place...
September 19, 2017: Oncotarget
Jaleh Varshosaz, Somayeh Taymouri, Mohsen Minaiyan, Fatemeh Rastegarnasab, Azar Baradaran
The aim of this study was to develop hydroxypropyl methyl cellulose (HPMC)/chitosan gel containing polymeric micelles loaded with simvastatin (Sim) and evaluates its wound healing properties in rats. An irregular full factorial design was employed to evaluate the effects of various formulation variables including polymer/drug ratio, hydration temperature, hydration time and organic solvent type on the physicochemical characteristics of pluronic F127-cholesterol nanomicelles prepared using the film hydration method...
October 18, 2017: Drug Development and Industrial Pharmacy
Rosarita Tatè, Enrica Zona, Rosanna De Cicco, Veronica Trotta, Maria Urciuoli, Alessandro Morelli, Salvatore Baiano, Rosa Carnuccio, Maria Pia Fuggetta, Franco Morelli
Statins are a class of drugs that inhibit the rate-limiting steps in the cholesterol biosynthesis pathway. They act by inhibiting 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate. Blocking of mevalonate synthesis leads to inhibition of the farnesylation and geranylgeranylation of several functional proteins, such as RhoA and other small guanosine triphosphate-binding proteins, that are important in maintaining the undifferentiated status of the cells...
October 13, 2017: International Journal of Oncology
Camille B Carroll, Richard K H Wyse
Many now believe the holy grail for the next stage of therapeutic advance surrounds the development of disease-modifying approaches aimed at intercepting the year-on-year neurodegenerative decline experienced by most patients with Parkinson's disease (PD). Based on recommendations of an international committee of experts who are currently bringing multiple, potentially disease-modifying, PD therapeutics into long-term neuroprotective PD trials, a clinical trial involving 198 patients is underway to determine whether Simvastatin provides protection against chronic neurodegeneration...
October 13, 2017: Journal of Parkinson's Disease
Isabela Bruna Pires Borges, Marilda Guimarães Silva, Rafael Giovane Misse, Samuel Katsuyuki Shinjo
Lipid-lowering agent-triggered dermatomyositis (DM) or polymyositis (PM) is a rare event. Therefore, the aim of the present study was to describe a series of such cases. A retrospective cohort study of 5 DM and 4 PM cases triggered by prior exposure to lipid-lowering agents between 2001 and 2017 was carried out. All patients, except for two cases, had muscle biopsy compatible with inflammatory myopathy and no serum autoantibodies positive for anti-SRP or anti-HMGCoAR. Median age of the patients at time of diagnosis was 68 years...
October 12, 2017: Rheumatology International
Yu Wang, Wenping Yang, Xin Zhao, Rong Zhang
Simvastatin, which is primarily prescribed to lower cholesterol, may also mitigate lung injury caused by sepsis, although the mechanisms remain elusive. This study aimed to evaluate the protective effect of simvastatin on acute lung injury in rats with sepsis and to investigate possible mechanisms. Male Wistar rats were pretreated with simvastatin (0.2 μg/g) for 1 week before cecal ligation and puncture. Treatment with simvastatin demonstrated significant decreases in the concentration of protein, TNF-α, IL-1β, IL-6, and lipocalin 2, and the number of polymorphonuclear neutrophils in bronchoalveolar lavage fluid in septic rats...
October 11, 2017: Inflammation
Natalia Putkaradze, Martin Litzenburger, Ammar Abdulmughni, Mohammed Milhim, Elisa Brill, Frank Hannemann, Rita Bernhardt
CYP109E1 is a cytochrome P450 monooxygenase from Bacillus megaterium with a hydroxylation activity for testosterone and vitamin D3. This study reports the screening of a focused library of statins, terpene-derived and steroidal compounds to explore the substrate spectrum of this enzyme. Catalytic activity of CYP109E1 towards the statin drug-precursor compactin and the prodrugs lovastatin and simvastatin as well as biotechnologically relevant terpene compounds including ionones, nootkatone, isolongifolen-9-one, damascones, and β-damascenone was found in vitro...
October 11, 2017: Applied Microbiology and Biotechnology
Yat Hei Leung, Jacques Turgeon, Veronique Michaud
Many drugs can cause unexpected muscle disorders, often necessitating the cessation of an effective medication. Inhibition of monocarboxylate transporters (MCTs) may potentially lead to perturbation of l-lactic acid homeostasis and muscular toxicity. Previous studies have shown that statins and loratadine have the potential to inhibit l-lactic acid efflux by MCTs (MCT1 and 4). The main objective of this study was to confirm the inhibitory potentials of atorvastatin, simvastatin (acid and lactone forms), rosuvastatin, and loratadine on l-lactic acid transport using primary human skeletal muscle cells (SkMC)...
October 10, 2017: Pharmaceutics
Ruiping Kong, Xingyi Zhu, Elizaveta S Meteleva, Yulia S Chistyachenko, Lyubov P Suntsova, Nikolay E Polyakov, Mikhail V Khvostov, Dmitry S Baev, Tatjana G Tolstikova, Jianming Yu, Alexander V Dushkin, Weike Su
In the present work, complexes of simvastatin (SIM) with polysaccharide arabinogalactan (AG) or disodium salt of glycyrrhizin acid (Na2GA) have been prepared using mechanochemical technique to improve the solubility of SIM and enhance its oral bioavailability. The interactions of SIM with AG or Na2GA were investigated by FTIR, DSC, XRD and SEM. Self-association of SIM in various solvents was investigated by UV/Vis and NMR techniques. The molecular masses of supramolecular systems-inclusion complexes and micelles, which are the "hosts" for SIM molecules were measured...
October 6, 2017: International Journal of Pharmaceutics
Leigh Anne Hylton Gravatt, Rachel W Flurie, Estela Lajthia, Dave L Dixon
PURPOSE OF REVIEW: This review discusses potential drug-drug interactions between statins and antimicrobials and provides clinician's guidance on how to manage these interactions. RECENT FINDINGS: In addition to statin utilization increasing in recent years, there is greater emphasis on using moderate to high-intensity statin doses. Statin-related adverse effects are often dose-dependent; therefore, patients may be at increased risk. Antimicrobial use has also increased in recent years, and various efforts have been implemented to ensure appropriate use of antimicrobials...
October 9, 2017: Current Atherosclerosis Reports
Ahlam Elmasry, Nabil M Aladeeb, Amro Elkaref, Nora Aboulfotouh
Previous studies on simvastatin use in experimental schistosomiasis in mice did not provide a full explanation of its mechanism as antischisome. In this study, we tried to find out the role of IL-10 in the mechanism of action of simvastatin. We used 50 clear mice. Ten were used as normal not treated while 40 were infected with shistosome mansoni then divided into 4 groups; 3 treated groups by praziquantel, simvastatin and combined (praziquantel plus simvastatin) respectively and one group non-treated. The simvastatin treated group showed shortening and loss of the tubercles and disappearance of the spines with swelling and twisted shape of the worms...
October 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Fu-Cai Tang, Hong-Yan Wang, Ming-Ming Ma, Tian-Wang Guan, Long Pan, Dun-Chen Yao, Ya-Lan Chen, Sheng-Jie Li, Hang Yang, Xiao-Qin Zhu, Yong-Sheng Tu
Reactive oxygen species‑induced cyclophilin A (CyPA) release from vascular smooth muscle cells (VSMCs) may be inhibited by simvastatin in vitro. The present study aimed to further examine the effect of simvastatin on serum CyPA levels and the basigin (CD147)‑extracellular signal‑regulated kinase (ERK) 1/2‑cyclin pathway during thoracic aorta remodeling. The mechanisms through which simvastatin may inhibit CyPA secretion from VSMCs were further investigated. Serum CyPA levels and the expression kinetics of CyPA‑associated signaling pathways were examined following simvastatin treatment in rat thoracic aortas during hypertension...
September 27, 2017: Molecular Medicine Reports
Silje Bergland Ellingsen, Elisabet Nordmo, Knut Tore Lappegård
Severe hepatotoxicity is a rare but well-known adverse reaction to statins. However, despite the widespread use of statins, only a few cases describing statin reexposure or switch to another statin after liver injury have been published. The literature on hepatotoxicity with ezetimibe alone or in combination with statins is also scarce. We report a case where a patient with a history of elevated liver enzymes while using atorvastatin, but prior and subsequent good tolerance to simvastatin and pravastatin, developed drug-induced liver injury on reexposure to a combination of atorvastatin and ezetimibe...
2017: Clinical Medicine Insights. Case Reports
Tim Both, H Jeroen van de Peppel, M Carola Zillikens, Marijke Koedam, Johannes P T M van Leeuwen, P Martin van Hagen, Paul L A van Daele, Bram C J van der Eerden
We recently showed that patients with primary Sjögren Syndrome (pSS) have significantly higher bone mineral density (BMD) compared to healthy controls. The majority of those patients (69%) was using hydroxychloroquine (HCQ), which may have favourable effects on BMD. To study the direct effects of HCQ on human MSC-derived osteoblast activity. Osteoblasts were cultured from human mesenchymal stromal cells (hMSCs). Cultures were treated with different HCQ doses (control, 1 and 5 µg/ml). Alkaline phosphatase activity and calcium measurements were performed to evaluate osteoblast differentiation and activity, respectively...
October 3, 2017: Journal of Cellular and Molecular Medicine
Alaa S Tulbah, Elvira Pisano, Santo Scalia, Paul M Young, Daniela Traini, Hui Xin Ong
AIM: Current inhaled treatments are not adequate to treat all lung diseases. In this study, a promising nanotechnology has been developed to deliver a potential anti-inflammatory and muco-inhibitory compound, simvastatin, for treatment of inflammatory lung diseases via inhalation. MATERIALS & METHODS: Simvastatin nanoparticles (SV-NPs) encapsulated with poly(lactic-co-glycolic) acid were fabricated using the solvent and anti-solvent precipitation method. RESULTS: SV-NPs were found to be stable up to 9 months at 4°C in a freeze-dried form prior to reconstitution...
October 2017: Nanomedicine
Erin A Bohula, Stephen D Wiviott, Robert P Giugliano, Michael A Blazing, Jeong-Gun Park, Sabina A Murphy, Jennifer A White, Francois Mach, Frans J Van de Werf, Anthony J Dalby, Harvey D White, Andrew M Tershakovec, Christopher P Cannon, Eugene Braunwald
Background -Patients who experience an acute coronary syndrome (ACS) are at heightened risk of recurrent ischemic events, including stroke. Ezetimibe improved cardiovascular outcomes when added to statin therapy in patients stabilized after ACS. We investigated the efficacy of the addition of ezetimibe to simvastatin for the prevention of stroke and other adverse cardiovascular events in IMPROVE-IT, with a focus on patients with a stroke prior to randomization. Methods -Post-ACS patients were randomized to placebo/simvastatin or ezetimibe/simvastatin and followed for a median of 6 years...
September 30, 2017: Circulation
Khadija G Syeda, Anjan Kowluru
BACKGROUND/AIMS: Lamins are intermediate filament proteins that constitute the main components of the lamina underlying the inner-nuclear membrane and serve to organize chromatin. Lamins (e.g., lamin B) undergo posttranslational modifications (e.g., isoprenylation) at their C-terminal cysteine residues. Such modifications are thought to render optimal association of lamins with the nuclear envelop. Using human islets, rodent islets, and INS-1 832/13 cells, we recently reported significant metabolic defects under glucotoxic and endoplasmic reticulum (ER) stress conditions, including caspase 3 activation and lamin B degradation...
October 2, 2017: Cellular Physiology and Biochemistry
Hongju Liu, Xiaoli Xu
BACKGROUND: Simvastatin might be beneficial to the patients with aneurysmal subarachnoid hemorrhage. However, the results remained controversial. We conducted a systematic review and meta-analysis to explore the efficacy of simvastatin for aneurysmal subarachnoid hemorrhage. METHODS: PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of simvastatin versus placebo on aneurysmal subarachnoid hemorrhage were included...
September 5, 2017: American Journal of Emergency Medicine
Chien-Chang Lee, Meng-Tse Gabriel Lee, Tzu-Chun Hsu, Lorenzo Porta, Shy-Shin Chang, Chia-Hung Yo, Kuang-Chau Tsai, Matthew Lee
BACKGROUND: Whether statin treatment, proved by recent experimental studies to have an antimicrobial activity, exerts a drug- or a class-specific effect in sepsis remains unknown. METHODS: Short-term mortality in patients with sepsis was analyzed using data from the National Health Insurance Research Database. Use of statins was defined as the cumulative use of a specific statin (atorvastatin, simvastatin, or rosuvastatin) for > 30 days prior to the index sepsis admission...
September 27, 2017: Chest
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