Simvastatin Reduces Protection and Intestinal T cell Responses Induced by a Norovirus P Particle Vaccine in Gnotobiotic Pigs
Lijuan Yuan in Vaccine Efficacy Evaluation, 2022
Simvastatin is a cholesterol-reducing drug that inhibits HMG-CoA reductase, an enzyme in the cholesterol biosynthesis pathway, resulting in the reduction of low-density lipoprotein (LDL) cholesterol levels (Goldstein and Brown, 2009). Forty mg of simvastatin decreases LDL cholesterol and the risk of cardiovascular events by 23% over five years (Heart Protection Study Collaborative et al., 2011) with similar effects witnessed in low-risk populations (Cholesterol Treatment Trialists et al., 2012). Based on the report by the National Center for Health Statistics, 50% of men and 36% of women who are 65–74 years old took statin-type drugs in 2010. In 2013, the American Heart Association and American College of Cardiology released new guidelines which expand the recommendation for the use of simvastatin in the prevention of heart diseases even to people without high LDL levels.
Cardiovascular disease in rheumatoid arthritis
Rajan Madhok, Hilary Capell in The Year in Rheumatic Disorders Volume 4, 2004
Fig. 4.2 Effects of simvastatin on developing (prophylactic) and clinically evident (therapeutic) CIA. DBA/1 mice were immunized with CM and an i.p. challenge injection was given at day 21. (a) and (b) Prophylactic protocol: mice were treated daily from days 21 to 40 with increasing doses of simvastatin starting from 10 mg/kg (?n = 10), 20 mg/kg ( n = 8), 40 mg/kg (O n= 10), or PBS (? n = 10). The appearance of arthritis was monitored daily and presented as disease incidence or mean articular index (calculated only from arthritic mice). Simvastatin administered at 40 mg/kg significantly lowered incidence and severity of arthritis (*P<0.05 by Mann-Whitney U test). There was no statistically significant difference between the 10 mg/kg, 20 mg/kg and PBS groups, (c) and (d) Therapeutic protocol: mice were treated 1 day postonset of clinically evident articular disease for a total of 14 days either with simvastatin 40 mg/kg (On = 13) or PBS (? n = 14). Significant suppression of disease activity (*P<0.05) was observed in simvastatin-treated mice as indicated by mean articular index and mean number of arthritic paws. Data are expressed as mean SEM. Source: Leung et al. (2003).
Identification and Management of Children with Dyslipidemia
James M. Rippe in Lifestyle Medicine, 2019
It is important to have routine monitoring of patients while on statin therapy (Figure 79.4). Short- and long-term safety concerning liver and muscle toxicity is the most common concern for patients and their families when starting a statin, and adequate counseling should be performed. Before starting a statin, the physician should assess for contraindications to use, such as liver disease or the potential for pregnancy. Once menses have started, girls should be counseled that statins may be teratogenic; physicians should document that female patients are not pregnant before starting medication and, if the female patient is sexually active, that she is using adequate birth control. The patient’s current medications should also be reviewed to assess for potential drug interactions, notably with cyclosporine, niacin, fibrates, erythromycin, azole antifungals, nefazodone, and many HIV protease inhibitors. Patients should limit their grapefruit juice consumption if they are taking atorvastatin, simvastatin, or lovastatin due to inactivation of the intestinal CYP3A4, thereby inhibiting the pre-systemic degradation and increasing the blood levels of these statins.33
Promoting vascularization for tissue engineering constructs: current strategies focusing on HIF-regulating scaffolds
Published in Expert Opinion on Biological Therapy, 2019
Tilman U. Esser, Kaveh Roshanbinfar, Felix B. Engel
Simvastatin is a widely used lipid-lowering drug, which inhibits cholesterol biosynthesis. Interestingly, simvastatin was also found to upregulate HIF-1α and accordingly, induce angiogenic signaling [135,136]. Highly porous scaffolds, made from hydroxyapatite, TiO2 or titanium alloys have been used as carriers for simvastatin, allowing for slow, continuous drug release [137–139]. Simvastatin release from alginate/TiO2 scaffolds promoted VEGF secretion and osteogenic differentiation of osteoblasts [137]. Deposited onto hydroxyapatite microspheres, simvastatin was also shown to induce HIF-1α and VEGF expression from BMSCs in vitro [138]. Further, simvastatin-hydroxyapatite microspheres embedded in a collagen matrix, were used in a rat calvarial defect model, and found to increase the formation of new bone (bone volume/tissue volume: 20.7% vs. 10.4% at 8 weeks post-implantation) and neovascularization (Vessel area: 19.6% vs. 10.5% at 8 weeks), compared to simvastatin-free microspheres [138]. Simvastatin has also been incorporated into a poloxamer hydrogel, which was embedded in a highly porous titanium alloy scaffold for use in a rabbit tibia defect model [139]. This simvastatin-loaded scaffold, too, was found to increase bone formation (Bone volume/tissue volume: 37.9% vs. 28.9% at 8 weeks) and vascularization (volume of neovascularization: 10.0 mm3vs. 5.1 mm3 at 8 weeks) over simvastatin-free controls.
Promising treatment strategies to combat Staphylococcus aureus biofilm infections: an updated review
Published in Biofouling, 2020
P. S. Seethalakshmi, Riya Rajeev, George Seghal Kiran, Joseph Selvin
Simvastatin is an antihyperlipidemic drug which decreases cholesterol levels by inhibiting the enzyme HMG-CoA reductase (Todd and Goa 1990). Thangamani, Mohammad, et al. (2015) reported that simvastatin reduced the planktonic growth and biomass of mature MRSA biofilms by 40%. In addition to this, simvastatin acted synergistically with the antibiotics daptomycin, retapamulin, fusidic acid, and mupirocin against clinical isolates of S. aureus. Proteomic analysis of simvastatin treated S. aureus cells disclosed massive degradation of bacterial proteins. At the same time, the ELISA test of J774A.1 mammalian cells treated with simvastatin at 40 μg ml−1 concentration did not suggest any interference with mitochondrial protein synthesis, which indicates that the inhibitory activity of simvastatin is directed only towards prokaryotic cells. Another important outcome of this study was that, topical administration of 1% simvastatin in mice with MRSA skin infection showed reduced the levels of pro-inflammatory cytokines.
Co-amorphous systems for the delivery of poorly water-soluble drugs: recent advances and an update
Published in Expert Opinion on Drug Delivery, 2020
Jiawei Han, Yuanfeng Wei, Yan Lu, Runze Wang, Jianjun Zhang, Yuan Gao, Shuai Qian
For drug-drug CAMs, a drug could be designed by co-amorphization with another drug (with same or different pharmacological effects) for combination therapy. At the same time, the drug-drug CAMs could also exhibit significantly improved in vitro solubility/dissolution behaviors for each drug. For instance, indomethacin with low solubility is a nonsteroidal anti-inflammatory drug. Löbmann et al. selected another nonsteroidal anti-inflammatory drug naproxen as the co-former to develop indomethacin-naproxen CAM in order to obtain pharmacological complementarity in pain relief [84]. The CAM exhibited a synchronized release with 7.6-fold and 1.4-fold increase in IDR for indomethacin and naproxen, respectively. Simvastatin, as a cholesterol-lowering agent belonging to statins, is widely used to treat hypercholesterolemia [105]. Nifedipine acts as a calcium channel antagonist to treat high blood pressure [106]. Cecilia et al. developed these two BCS II drugs into simvastatin-nifedipine CAM as a promising formulation with enhanced solubility for simultaneously targeting hypertension and hypercholesterolemia [91]. The CAM showed 3.7 and 1.7 times increase in solubility for simvastatin and nifedipine, respectively. In addition, it exhibited excellent stability for at least 1 year.
Related Knowledge Centers
- Chronic Kidney Disease
- Statin
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- Dyslipidemia
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- Hyperlipidemia
- Lipid-Lowering Agent
- Breastfeeding
- Generic Drug