Role of metalloproteinases in platelet function

Platelets contain and release matrix metalloproteinases (MMPs), their inhibitors (TIMPs) and disintegrin metalloproteinases (ADAMs) including MMP-1, MMP-2, MMP-3, MMP-9, MT1-MMP (MMP-14), ADAM-10, ADAM-17, ADAMTS-13, TIMP-1, TIMP-2 and TIMP-4. These proteins exert several effects regulating platelet functions such as agonist-stimulated platelet adhesion and aggregation, tumour cell-induced platelet aggregation and platelet-leukocyte aggregation. In this review, mechanisms of MMPs, TIMPs and ADAMs on platelets are discussed.     

Current and emerging paradigms in the therapeutic management of atherosclerosis

Background: The pathogenesis of atherosclerosis lies in abnormalities in lipoprotein metabolism leading to pathological interactions with vessel walls and the release of inflammatory components, which further aggravate the disease condition. Objective: To elucidate current and emerging trends in drug discovery towards the development of new entities regulating lipoprotein metabolism and inflammatory components to combat the progression of atherosclerosis. Methods: Research/review articles in the public domain and press releases were employed. Results/conclusion: With the recent failure of torcetrapib and succinobucol, drug discovery and development efforts towards the treatment of atherosclerosis have received a big jolt and have been slowed down to certain extent. But this could be a starting point for several new mechanisms that are emerging to discover new drugs to combat the disease.     

Particle Characteristics and Biodistribution of Camptothecin-Loaded PLA/(PEG-PPG-PEG) Nanoparticles

Poly(DL-lactic acid) (PLA)/poly(ethylene glycol)-block-poly (propylene glycol)-block-poly(ethylene glycol) copolymer (PEG-PPG-PEG) nanoparticles loaded with camptothecin (CPT), called CPT-NP, were prepared and examined for particle size change and drug release in phosphate-buffered saline, pH 7.4, (PBS), and drug biodistribution profiles in mice bearing sarcoma 180 solid tumor. CPT-NP kept an almost constant mean size and exhibited an initial rapid release of approximately 20%, following by very slow release. As compared with CPT solution, CPT-NP showed higher tissue accumulation and better tumor localization, which were considered essentially associated with the better efficacy of CPT-NP reported in the previous study.     

Techniques for efficient entrapment of pharmaceuticals in biodegradable solid micro/nanoparticles

Importance of the field: Biodegradable solid particles are potential carriers for both hydrophobic and hydrophilic drugs and have been marketed for prolongation of pharmaceutical activity. In developing such particles, it is important to achieve stable encapsulation of the drugs in the particles and a controlled rate of drug release.

Areas covered in this review: In this paper, the principles and techniques for preparing such particles are reviewed.

What the reader will gain: Overall, it remains difficult to identify a general approach for achieving effective entrapment and controlled release, because these qualities are determined by multiple complex factors. The encapsulation efficiency of drugs in particles can be improved through various techniques, including hydrophobic interaction, covalent bonding, ionic interaction and physical isolation. In addition, the release behaviors of drugs are strongly influenced by environmental conditions as well as the physicochemical properties of the polymers and drugs.

Take home message: Solid particles with targeting ability in addition to prolongation of biological activity may have potential for development of a new type of pharmaceutical in the clinical field.     

Copolymers of poly(lactic acid) and d-α-tocopheryl polyethylene glycol 1000 succinate-based nanomedicines: versatile multifunctional platforms for cancer diagnosis and therapy

Introduction: The major drawbacks associated with most of the anti-cancer drugs are their potential adverse effects. Distribution of these drugs throughout the body causes untoward adverse effects and less accumulation of drug at the site of tumors also causes decrease in therapeutic efficacy. Targeted nanomedicines are the emerging systems to improve the targetability of drug to the tumor site and to reduce the toxicity with maximum efficacy. Copolymers of poly-lactic acid (PLA) and d-α-tocopheryl polyethylene glycol 1000 succinate (Vitamin-E TPGS or TPGS) are innovative materials being actively investigated for the fabrication of non-targeted and targeted nanomedicines for diagnosis and therapy of cancer.

Areas covered: In this review, different nanomedicines of copolymers such as poly-lactic acid – polyoxyethylene sorbitan monooleate (PLA – Tween® 80), poly-lactic acid – poly-ethyleneglycol (PLA-PEG), poly-lactic acid-d-α-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS) and TPGS-based nanomedicines (i.e., TPGS emulsified polymeric nanoparticles, TPGS prodrugs, TPGS liposomes, and TPGS micelles) for the diagnosis and therapy of cancer have been discussed.

Expert opinion: PLA, PLA-Tween® 80, PLA-PEG, PLA-TPGS, and TPGS are the promising polymeric biomaterials well studied as cancer nanomedicines. These biomaterials have proved that they could be applied in the fabrication of multifunctional nanomedicines for the future needs in simultaneous diagnosis of cancer as well as targeted chemotherapy.     

The cyclooxygenase-2/thromboxane A2 pathway: a bridge from rheumatoid arthritis to lung cancer?

Patients with rheumatoid arthritis (RA) appear to be at a higher risk of lung cancer (LC). Although the connection between RA and LC has been an active area of research for many years, the molecular pathogenesis of the disease process remains unclear. The cyclooxygenase (COX)-2/thromboxane A2 (TxA2) pathway has been shown to play a potential role in LC development through an auto-regulatory feedback loop. An increased level of TxA2 has been found in RA patients, and intriguingly, the positive feedback loop for the COX-2/TxA2 pathway was shown to have a potential function in RA fibroblast-like synoviocytes (RA-FLS). Thus, the molecular basis of LC development in patients with RA has been at least in partly described. It is possible that COX-2-derived TxA2 could be monitored for the early detection of LC in RA patients, and targeting this molecular pathway may decrease the risk of LC in patients with RA.     

Microencapsulation of thyme oil by coacervation

The objective of this work is to develop a novel coacervation process to produce microcapsules of polylactide (PLA) to encapsulate thyme oil that will be used in cosmetics. The novelty of this approach consists of dissolving PLA in dimethylformamide (DMF) which is a good solvent for PLA but in addition has high solubility in water. Upon contact with water, the homogeneous solution of PLA in DMF promotes the precipitation of PLA around the thyme oil core. The produced microcapsules have bimodal particle size distributions in volume with a mean particle size of 40 µm. Microcapsules analysis by microscopy have confirmed the spherical shape, the rough surface and allowed the estimation of the wall thickness around 5 µm. Quantification of the encapsulated thyme oil was performed by gas chromatography and allowed to evaluate the quality of the encapsulated oil and pointed out for a preferential encapsulation of thyme oil apolar compounds.     

Ivermectin-loaded microparticles for parenteral sustained release: in vitro characterization and effect of some formulation variables

Ivermectin (IVM) is a BCS II drug with potent antiparasitic activity in veterinary applications. In this study, poly(lactide-co-glycolide) (PLGA) and poly(DL-lactide) (PLA) Ivermectin-loaded microparticles were prepared by the simple emulsion (O/W) solvent evaporation method in order to obtain sustained release formulations for parenteral applications. The effects of polymer end-groups (ester or free acid) and the addition of the hydrophilic polyvinylpyrrolidone polymer (PVP) in in vitro drug release profiles were also studied. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analysis showed that IVM was present in an amorphous state or as a molecular dispersion within the polymers or theirs mixtures with PVP and that a PVP-drug complex was formed. Drug entrapment efficiency in the microparticles (>90%) was independent of the polymer composition, the end groups and the presence of PVP. However, microscopic (SEM) observations showed that the addition of PVP led to more porous microparticles accompanied by the increased rates of drug release.     

老年急性阑尾炎病情严重程度的超声评估及其临床应用

目的 探讨高龄急性阑尾炎患者的超声声像图特征与炎症病变严重程度的关系,为临床治疗提供影像学参考.方法 回顾性分析2011年1月至2021年1月中国人民解放军空军特色医学中心经临床及辅助检查诊断为急性阑尾炎、年龄>70岁的患者78例.剔除仅行保守、抗炎治疗患者21例,最终入组患者57例.按超声表现初步分为炎症反应轻、重2...     

老年男性人群高血压合并糖耐量减低与全因死亡风险的相关性

目的 探讨高血压合并糖耐量减低(IGT)对老年男性人群全因死亡风险的影响。方法 纳入2005年5月至2007年5月在解放军总医院第二医学中心行口服葡萄糖耐量试验检出的老年男性IGT患者和正常糖耐量(NGT)人群,根据基线时是否存在高血压病史和IGT分为4组:非高血压(NH)+正常糖耐量(NGT)组、高血压(H)+NGT组、NH+IGT组、H+IGT组,每年至少随访1次。采用SPSS 13.0统计软件进行数据分析。采用Cox回归模型分析不同组别全因死亡风险的差异。结果 与NH+NGT组比较,H+IGT组(HR=2.55,95%CI 1.56-4.16; P<0.001)和NH+IGT组(HR=2.40,95%CI 1.35-4.25; P=0.003)2型糖尿病发病风险显著升高。单因素Cox比例风险回归分析提示,与NH+NGT组比较,H+IGT组(HR=2.59,95%CI 1.34-5.01; P=0.005)全因死亡风险明显升高,而H+NGT组和NH+IGT组无统计学差异(P>0.05)。在调整相关危险因素后多因素Cox比例风险回归分析显示,H+IGT组(HR=1.83,95%CI 0.90-3.70; P=0.095)全因死亡风险较NH+NGT组虽无统计学差异(P>0.05),但有升高的趋势。结论 老年男性人群高血压合并IGT与全因死亡风险密切相关,高血压与IGT并存可导致全因死亡风险增加。