Low-density lipoprotein encapsulated thiosemicarbazone metal complexes is active targeting vehicle for breast,lung, and prostate cancers

Cancer is a leading cause of death worldwide and affects society in terms of the number of lives lost. Current cancer treatments are based on conventional chemotherapy which is nonspecific in targeting cancer. Therefore, intensive efforts are underway to better target cancer-specific cells while minimizing the side effects on healthy tissues by using LDL particles as active drug delivery vehicles. The goal is to encapsulate anticancer agents thiosemicarbazone metal-ligand complexes into LDL particles to increase the cytotoxic effect of the agent by internalization through LDL receptors into MCF7, A549, and C42 cancer cell lines as segregate models for biological evaluations targeting tubulin. Zeta potential data of LDL-particles encapsulated anticancer agents showed an acceptable diameter range between 66–91 nm and uniform particle morphology. The results showed cell proliferation reduction in all tested cell lines. The IC₅₀ values of LDL encapsulated thiosemicarbazone metal-ligand complexes treated with MCF7, A549, and C42 ranged between 1.18–6.61 µM, 1.17–9.66 µM, and 1.01–6.62 µM, respectively. Western blot analysis showed a potent decrease in tubulin expression when the cell lines were treated with LDL particles encapsulated with thiosemicarbazone metal-ligand complexes as anticancer agents. In conclusion, the data provide strong evidence that LDL particles are used as an active drug delivery strategy for cancer therapy.     

Alcance das Metas de Colesterol LDL após Infarto Agudo do Miocárdio: Dados Reais do Sistema Público de Saúde da Cidade de Curitiba

BackgroundReduction of LDL-cholesterol (LDL-c) levels is the cornerstone in risk reduction, but many high-risk patients are not achieving the recommended lipid goals, even in high-income countries.ObjectiveTo evaluate whether patients seen in the city of Curitiba public health system are reaching LDL-c goals after an acute myocardial infarction (AMI).MethodsThis retrospective cohort explored the data of patients admitted with AMI between 2008 and 2015 in public hospitals from the city of Curitiba. In order to evaluate the attainment of the LDL-c target, we have used the last value registered in the database for each patient up to 2016. For those who had at least one LDL-c registered in the year before AMI, percentage of reduction was calculated. The level of significance adopted for statistical analysis was p<0.05.ResultsOf 7,066 patients admitted for AMI, 1,451 were followed up in an out-patient setting and had at least one evaluation of LDL-c. Mean age was 60.8±11.4 years and 35.8%, 35.2%, 21.5%, and 7.4% of patients had LDL-c levels ≥100, 70–99, 50–69 and <50 mg/dL, respectively. Of these, 377 patients also had at least one LDL-c evaluation before the AMI. Mean LDL-c concentrations were 128.0 and 92.2 mg/dL before and after AMI, with a mean reduction of 24.3% (35.7 mg/dL). LDL-c levels were reduced by more than 50% in only 18.3% of the cases.ConclusionIn the city of Curitiba public health system patients, after myocardial infarction, are not achieving adequate LDL-c levels after AMI.     

同型半胱氨酸、氧化低密度脂蛋白、内皮素和尿酸与老年冠心病关系探讨

目的观察同型半胱氨酸、氧化低密度脂蛋白、内皮素和尿酸与老年冠心病的关系。方法测定84例老年冠心病患者血中同型半胱氨酸、氧化低密度脂蛋白、内皮素和尿酸水平,另选58例健康体检者为对照组。结果老年冠心病组血中同型半胱氨酸、氧化低密度脂蛋白、内皮素和尿酸水平均高于健康对照组（P〈0．01）,老年冠心病组同型半胱氨酸与内皮素、氧化低密度脂蛋白与内皮素呈明显正相关。结论同型半胱氨酸、氧化低密度脂蛋白、内皮素和尿酸与老年冠心病密切相关。     

家族性高胆固醇血症家系低密度脂蛋白受体活性及其基因突变分析

目的:对1例临床诊断为家族性高胆固醇血症(FH)纯合子患者家系进行低密度脂蛋白受体(LDL-R)活性研究及其基因突变分析,旨在探讨其分子病理机制。方法:对先证者及其父母进行血脂、颈动脉超声等检查;采用流式细胞仪检测先证者及其父母外周血淋巴细胞LDL-R表达量和功能;以先证者基因组DNA为模板,扩增载脂蛋白B100(ApoB100)基因3500区域片断,PCR产物进行核苷酸序列分析,排除由该突变导致家族性ApoB100缺陷症;用降落式PCR方法,在同一程序中分别扩增LDL-R基因的启动子和全部18个外显子片段,扩增产物进行核苷酸序列分析;发现突变后验证其父母是否存在相同基因突变。结果:先证者血清TC和LDL水平明显升高、颈动脉内中膜明显增厚;LDL-R的表达量和结合功能显著下降(分别为正常人的13.6%和21.1%);ApoB100基因3500区域未见突变,LDL-R基因第1864位碱基T取代了G发生纯合错义突变,导致第601位氨基酸天冬氨酸变成脯氨酸(D601Y)。其父母LDL-R基因发现了相同的杂合突变,经检索该突变在我国未见报道。结论:证实家系先证者存在LDL-R基因突变,分别来源于父系和母系的遗传,该突变可能是家系发病的分子基础;D601Y也可能是我国FH患者LDL-R基因一种新的突变类型。     

Immunoaffinity beads for selective removal of cholesterol from human plasma

Anti-low density lipoprotein antibody (anti-LDL antibody) attached poly(2-hydroxyethyl methacrylate-methacryloylamidophenylalanine) (poly(HEMA-MAPA)) beads were prepared for selective removal of cholesterol from hypercholesterolemic human plasma. Poly(HEMA-MAPA) beads were produced by a modified suspension polymerization and then characterized by swelling tests and SEM. Blood-compatibility tests were also investigated. The water swelling ratio of the poly(HEMA-MAPA) beads increased significantly (68%) compared with pHEMA (55%). All the clotting times increased when compared with poly(HEMA) beads. Loss of platelets and leukocytes was very low. The maximum anti-LDL antibody attachment was achieved at pH 7.0. Attachment of anti-LDL antibody was 29.6 mg/g. There was a very low non-specific cholesterol binding onto the poly(HEMA-MAPA) beads, about 0.74 mg/g. Anti-LDL antibody attached beads adsorbed in the range of 13.3-16.0 mg cholesterol/g from hypercholesterolemic human plasma. Up to 92% of the adsorbed LDL was desorbed. The binding-elution cycle was repeated 10 times using the same beads. There was no significant loss of binding capacity.     

Comparative evaluation of a heparin‐citrate anticoagulation for LDL‐apheresis in two primary apheresis systems

BACKGROUND: As COBE Spectra has been replaced in many parts of the world, we describe a new protocol for low‐density lipoprotein (LDL)‐apheresis performed on familial hypercholesterolemia patients for the Spectra Optia platform. METHODS: For all procedures, after administering a bolus of heparin of 2,500 U, 10,000 U of heparin added to a 600 ml ACD‐A bag was used as anticoagulant (AC). In a first phase (A), 16 apheresis procedures with COBE Spectra using an inlet:AC ratio of 25:1 were compared to 18 LDL‐apheresis treatments with Spectra Optia at split Inlet:AC ratios of 16:1/18:1 or 20:1/25:1. Platelet activation and coagulation markers were assessed. In a follow‐up phase (B), 20 procedures on Spectra Optia using an inlet:AC ratio of 20:1 were performed. RESULTS: Although coagulation markers and platelet activation analyzed were similar in both apheresis devices used, COBE Spectra procedures did not show any visual clumping in the sets. Visual analysis of clumping was highest in the Spectra Optia's 20:1/25:1 AC regimen (5/8 procedures). For the lowest Spectra Optia, AC regimen and during the follow‐up phase reversible clump formation in the disposable set was similar (1/10 procedures). Clumping was successfully reversed in all cases by temporarily lowering the inlet:AC ratio to 18:1. Blood cell counts (WBC, Plt, Hct) were similar for both COBE Spectra and Spectra Optia procedures. Spectra Optia had a significantly higher plasma removal efficiency versus COBE Spectra (84% vs.75%, P < .05). No serious adverse events were observed. CONCLUSION: Apheresis procedures on the Spectra Optia system with low‐dose heparin‐citrate anticoagulation are feasible and safe.     

Thyroid Hormones and Cardiovascular Function and Diseases

Thyroid hormone (TH) receptors are present in the myocardium and vascular tissue, and minor alterations in TH concentration can affect cardiovascular (CV) physiology. The potential mechanisms that link CV disease with thyroid dysfunction are endothelial dysfunction, changes in blood pressure, myocardial systolic and diastolic dysfunction, and dyslipidemia. In addition, cardiac disease itself may lead to alterations in TH concentrations (notably, low triiodothyronine syndrome) that are associated with higher morbidity and mortality. Experimental data and small clinical trials have suggested a beneficial role of TH in ameliorating CV disease. The aim of this review is to provide clinicians dealing with CV conditions with an overview of the current knowledge of TH perturbations in CV disease.     

Effect of nutritional counseling on low-density lipoprotein cholesterol among Thai HIV-infected adults receiving antiretroviral therapy

HIV-infected patients receiving antiretroviral therapy have increased risk of metabolic syndrome, including dyslipidemia. In this study, we determined whether individual nutritional counseling reduced dyslipidemia, particularly low-density lipoprotein (LDL) cholesterol, among HIV-infected patients with dyslipidemia not currently taking lipid-lowering medication. We conducted a randomized 24-week trial among HIV-infected patients with dyslipidemia who were on antiretroviral therapy and were eligible to initiate therapeutic lifestyle changes according to the Thai National Cholesterol Education Program. Participants were randomly assigned to an intervention group that received individual counseling with a nutritionist for seven sessions (baseline, weeks 2, 4, 8, 12, 18, and 24) and a control group that received standard verbal diet information at baseline and nutritional counseling only at week 24. A 24-h recall technique was used to assess dietary intake for both groups at baseline and week 24. Lipid profile (total cholesterol, LDL, high-density lipoprotein (HDL), and triglyceride) was measured at baseline and after 12 and 24 weeks of therapy. An intention-to-treat and linear mixed model were used. Seventy-two patients were randomly assigned, and 62 (86%) participants completed their lipid profile test. After 12 weeks of follow-up, there were significant reductions in the intervention group for total cholesterol (?14.4?±?4.6?mg/dL, P?=?.002), LDL cholesterol (?13.7?±?4.1?mg/dL, P?=?.001), and triglyceride (?30.4?±?13.8?mg/dL, P?=?.03). A significant reduction in LDL cholesterol was also observed in the control group (?7.7?±?3.8?mg/dL, P?=?.04), but there were no significant differences in change of mean lipid levels between the groups at 12 weeks of follow-up. After 24 weeks, participants assigned to the intervention group demonstrated significantly greater decreases in serum total cholesterol (?19.0?±?4.6?vs. 0.2?±?4.3?mg/dL, P?=?.003) and LDL cholesterol (?21.5?±?4.1?vs. ?6.8?±?3.8?mg/dL, P?=?.009). There were no significant changes in HDL cholesterol or triglyceride levels in either group.