Statins are the most widely used cholesterol-lowering drugs for cardiovascular diseases prevention.However, some patients are refractory to treatment, whereas others experience statin-related adverse events (SRAE). It has been increasingly important to identify pharmacogenetic biomarkers for predicting statin response and adverse events. This case report describes a female patient with familial hypercholesterolemia (FH) who showed late response to rosuvastatin and experienced myalgia on statin treatment. In the first visit (V1), the patient reported myalgia to rosuvastatin 40 mg, which was interrupted for a 6-week wash-out period. In V2, rosuvastatin 20 mg was reintroduced, but her lipid profile did not show any changes after 6 weeks (V3) (LDL-c: 402 vs. 407 mg/dL). Her lipid profile markedly improved after 12 weeks of treatment (V4) (LDL-c: 208 mg/dL), suggesting a late rosuvastatin response. Her adherence to treatment was similar in V1 and V3 and no drug interactions were detected. Pharmacogenetic analysis revealed that the patient carries low-activity variants in SLCO1B1*1B and*5, SLCO1B3 (rs4149117 and rs7311358), and ABCB11 rs2287622, and the non-functional variant in CYP3A5*3. The combined effect of variants in pharmacokinetics-related genes may have contributed to the late response to rosuvastatin and statin-related myalgia. Therefore, they should be considered when assessing a patient's response to statin treatment. To the best of our knowledge, this is the first report of a pharmacogenetic analysis on a case of late rosuvastatin response.
Poly (vinyl chloride) (PVC) is commonly used to manufacture biomedical devices and hospital components, but it does not present antimicrobial activity enough to prevent biofouling. With the emergence of new microorganisms and viruses, such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that was responsible for the global pandemic caused by Coronavirus Disease 2019 (COVID-19), it is evident the importance of the development of self-disinfectant PVC for hospital environments and medical clinics where infected people remain for a long time. In this contribution, PVC nanocomposites with silver nanoparticles (AgNPs) were prepared in the molten state. AgNPs are well-known as antimicrobial agents suitable for designing antimicrobial polymer nanocomposites. Adding 0.1 to 0.5 wt% AgNPs significantly reduced Young’s modulus and ultimate tensile strength of PVC due to the emergence of microstructural defects in the PVC/AgNP nanocomposites, but the impact strength did not change significantly. Furthermore, nanocomposites have a higher yellowness index (YI) and lower optical bandgap values than PVC. The PVC/AgNP nanocomposites present virucidal activity against SARS-CoV-2 (B.1.1.28 strain) within 48 h when the AgNP content is at least 0.3 wt%, suitable for manufacturing furniture and hospital equipment with self-disinfectant capacity to avoid secondary routes of COVID-19 contagion.
Statins are the first-line treatment for familial hypercholesterolemia (FH), but response is highly variable due to genetic and nongenetic factors. Here, we explored the association between response and genetic variability in 114 Brazilian adult FH patients. Specifically, a panel of 84 genes was analyzed by exon-targeted gene sequencing (ETGS), and the functional impact of variants in pharmacokinetic (PK) genes was assessed using an array of functionality prediction methods. Low-density lipoprotein cholesterol (LDL-c) response to statins (reduction ≥ 50%) and statin-related adverse event (SRAE) risk were assessed in carriers of deleterious variants in PK-related genes using multivariate linear regression analyses. Fifty-eight (50.8%) FH patients responded to statins, and 24 (21.0%) had SRAE. Results of the multivariate regression analysis revealed that ABCC1 rs45511401 significantly increased LDL-c reduction after statin treatment (p < 0.05). In silico analysis of the amino-acid change using molecular docking showed that ABCC1 rs45511401 possibly impairs statin efflux. Deleterious variants in PK genes were not associated with an increased risk of SRAE. In conclusion, the deleterious variant ABCC1 rs45511401 enhanced LDL-c response in Brazilian FH patients. As such, this variant might be a promising candidate for the individualization of statin therapy.
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