Simvastatin

Co-amorphous systems consisting of a drug and an amino acid have been investigated extensively for the enhancement of drug solubility and amorphous stability. The purpose of this study is to investigate which molecular descriptors are important for predicting the likelihood of a successful co-amorphisation between amino acid and drug. The predictions are thought to be used in an early screening phase to identify potential drug-amino acid combinations for further studies. A large variety of molecular descriptors was calculated for six drugs (carvedilol, mebendazole, carbamazepine, furosemide, indomethacin and simvastatin) and the twenty naturally occurring amino acids...

Professional antigen presenting cells (APC: myeloid dendritic cells (DC) and macrophages (MΦ); B lymphocytes) mediate highly efficient HIV-1 infection of CD4+ T cells, termed trans infection, that could contribute to HIV-1 pathogenesis. We have previously shown that lower cholesterol content in DC and B lymphocytes is associated with a lack of HIV-1 trans infection in HIV-1 infected nonprogressors (NP). Here we assessed whether HIV-1 trans infection mediated by another major APC, MΦ, is deficient in NP due to altered cholesterol metabolism...

PURPOSE OF REVIEW: Multiple sclerosis (MS) is an immune-mediated disorder that affects the central nervous system (CNS), often first affecting people in early adulthood. Although most MS patients have a relapsing-remitting course (RRMS) at disease onset, a substantial proportion later develop chronic progression, termed secondary progressive MS (SPMS). Approximately 10% of MS patients experience chronic progression from disease onset, termed primary progressive multiple sclerosis (PPMS)...

Pancreatic ductal adenocarcinoma (PDA) has poor therapeutic options. Recent patient studies indicate that cholesterol-lowering statins have anti-tumor capacities. We examined several established and primary PDA and normal cell lines as well as PDA patient tissues (n = 68). We found that simvastatin inhibited viability, stemness, tumor growth and metastasis and that it enhanced the efficacy of gemcitabine. These changes were associated with modulation of Shh-related gene expression. Overexpression of Shh prevented the anti-cancer effect of simvastatin, and inhibition of Shh mimicked the simvastatin effect...

The presence of cancer stem-like cells (CSC) within canine mammary tumors, may explain partly local recurrence and spreading, since their ability to resist conventional antitumor treatments as chemo and radiotherapy. It has been recently described that simvastatin - a drug that inhibits synthesis of cholesterol - attenuates the proliferation of canine mammary CSC derived from CF41.Mg canine mammary carcinoma cells, promoting their chemosensitizing and apoptosis. The canonical Wnt/β-catenin pathway is usually activated at CSC and up-regulates multidrug resistance protein 1 (MDR1), triggering chemoresistance...

Prostate cancer (PCa) is one of the most commonly diagnosed cancers in the western world, and the mortality rate from PCa in Asia has been increasing recently. Statins are potent inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase and are commonly used for treating hyperlipidemia, with beneficial effects for cardiovascular disease and they also exhibit anti-cancer activity. However, the protective effects of statins against PCa are controversial. In this study, we investigated the effect of two types of statins (simvastatin and lovastatin) and the mortality rate of PCa patients by using the Taiwan National Health Insurance Research Database (NHIRD)...

BACKGROUND: Crocin (CRO), chlorogenic acid (CGA), geniposide (GEN), and quercetin (QUE) are all natural compounds with anti-obesity properties, in particular, hypolipidemic effects, which have been widely used for the treatment of obesity-related metabolic diseases. However, it is not yet known whether these compounds interact synergistically. Here, we investigated the effects and molecular mechanisms of CRO, CGA, GEN, QUE, and a combination of all four compounds (CCGQ), on lipid accumulation in human hepatoma (HepG2 cells)...

BACKGROUND/AIMS: Isoflurane inhibited neurogenesis and induced subsequent neurocognitive deficits in developing brain. Simvastatin exerts neuroprotection in a wide range of brain injury models. In the present study, we investigated whether simvastatin could attenuate neurogenetic inhibition and cognitive deficits induced by isoflurane exposure in neonatal rats. METHODS: Sprague-Dawley rats at postnatal day (PND) 7 and neural stem cells (NSCs) were treated with either gas mixture, isoflurane, or simvastatin 60 min prior to isoflurane exposure, respectively...

Simvastatin is a drug commonly used to reduce the cholesterol level. 32 clinically healthy female pigs with a bodyweight of 35-40 kg, kept in standard laboratory conditions were chosen for the experiment and divided into 2 groups (control and experimental) consisting of 16 animals. The experimental group received simvastatin orally at a dose of 40 mg (one tablet once a day) for 56 days, and at the same time the control group received placebo (empty gelatin capsules). Bone marrow smears and peripheral blood samples were evaluated...

Nephrogenic diabetes insipidus (NDI) is a rare disorder characterized by resistance of the kidney to the action of antidiuretic hormone (ADH), resulting in a decrease in the capacity of the kidney to concentrate the urine. NDI can be inherited or acquired due to, for example, chronic lithium therapy. Current treatment options are limited to attempts to lower urine output by a low-solute diet and the use of diuretics or anti-inflammatory drugs. These measures are only partially effective. Recent reports suggested that sildenafil, metformin, and simvastatin might improve ADH-independent urine concentration...

Background: Traumatic brain injury (TBI) is a significant public health concern for older adults. Small-scale human studies have suggested pre-TBI statin use is associated with decreased in-hospital mortality following TBI, highlighting the need for large-scale translational research. Objective: To investigate the relationship between pre-TBI statin use and in-hospital mortality following TBI. Methods: A retrospective study of Medicare beneficiaries 65 and older hospitalized with a TBI during 2006 to 2010 was conducted to assess the impact of pre-TBI statin use on in-hospital mortality following TBI...

Chronic mild stress (CMS) has been demonstrated to contribute to atherosclerosis. 6-gingerol (6-Gin), a phenolic component of ginger (Zingiber officinale), has been shown to exert numerous pharmacological properties, such as anti-inflammatory and cardioprotective effects. Here we investigated the role of CMS in the development of atherosclerosis in high-fat diet (HFD)-fed ApoE-/- mice and evaluated the potential therapeutic effects of 6-Gin. Mice were exposed to CMS for 20 weeks, at week 5, they were fed with a high-fat diet (HFD), then received 6-Gin (20 mg/kg/day, intragastrically) treatment...

Hybrid nanocapsules constituted of phospholipids and polysaccharides have been proposed as colloidal systems for the delivery of drugs via non-parenteral administration routes, due their capacity of high drug loading, controlled drug release and targeted delivery to the specific organ. Moreover, nanoparticles systems offer the possibility of co-encapsulation of drugs in the same drug delivery system and, consequently, the simultaneous administration of compounds. Characterization of nanoparticles properties, specifically involves quantification of the active pharmaceutical ingredients and is pivotal in the development of innovative nanomedicines...

Neutrophil adhesion to the vasculature in response to potent inflammatory stimuli, such as TNF-α (TNF), can contribute to atheroprogression amongst other pathophysiological mechanisms. Previous studies have shown that simvastatin, a statin with known pleiotropic anti-inflammatory properties, can partially abrogate the effects of TNF-induced neutrophil adhesion, in association with the modulation of β2 -integrin expression. We aimed to further characterize the effects of this statin on neutrophil and leukocyte adhesive mechanisms in vitro and in vivo...

BACKGROUND AND AIMS: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with cardiovascular disease. Statins lower both low-density lipoprotein (LDL)-cholesterol and C-reactive protein (CRP), resulting in improved outcomes. However, whether lipid-lowering therapy also lowers suPAR levels is unknown. METHODS: We investigated whether treatment with Simvastatin 40 mg and Ezetimibe 10 mg lowered plasma suPAR levels in 1838 patients with mild-moderate, asymptomatic aortic stenosis, included in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, using a pattern mixture model...

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The aim of the present study was to examine the combined efficacy of simvastatin and kallistatin treatment for pediatric burn sepsis. A total of 72 pediatric patients with burn sepsis were recruited and randomly divided into 3 groups, receiving simvastatin (40 mg/day), kallistatin (20 mg/day) or combined treatment. ELISA, reverse transcription-quantitative polymerase chain reaction, western blotting and flow cytometry were used to analyze the therapeutic effects of simvastatin and kallistatin. The results revealed that combined treatment in pediatric burn sepsis patients decreased the inflammatory cytokine tumor necrosis factor α and interleukin (IL)-1β serum levels, whereas it increased IL-10 and human leukocyte antigen-D related levels...

Background: The shrinkage of the alveolar ridge might be minimized by the ridge preservation stages and applied alloplasts, after tooth extraction. According to studies on statins, angiogenesis and osteogenesis are observed as a topical application of these drugs. Objectives: The aim of this study is to the application of simvastatin in terms of bone regeneration of the alveolar ridge after tooth extraction. Materials and Methods: This study assessed this issue through the split-mouth method which assessed 10 dental sockets filled with simvastatin and collagen and 10 others filled just by collagen postextraction...

Graphene oxide (GO), nanosized Fe3 O4 and zeolite imidazolate framework-8 (ZIF-8) were hybridized as a multifunctional sorbent for use in microextraction. The sorbent was characterized by SEM, TEM, XRD and FTIR. The composite is porous, has a high specific surface (> 600 m2 ·g-1 ) and is paramagnetic. The GO sheets are shown to act as carriers for the Fe3 O4 nanoparticles and ZIF-8. The composite is a viable material for the preconcentration of atorvastatin and simvastatin from urine prior to their determination by HPLC with PDA detection...

Rhabdomyolysis is a well-documented side effect of statin therapy. This risk is increased with concurrent use of medications that inhibit cytochrome p450-3A4 (CYP3A4), such as macrolide antibiotics. We present the case of a 67-year-old patient who was commenced on clarithromycin on a background of simvastatin therapy, resulting in rhabdomyolysis. This case highlights the need for awareness of common drug interactions associated with statins. It also emphasizes the significance of commencing statins at a lower dose in new patients, and lastly, the importance of early recognition and management of rhabdomyolysis to prevent the development of complications...