A Statin-Loaded Reconstituted High-Density Lipoprotein Nanoparticle Inhibits Atherosclerotic Plaque Inflammation

Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show this effect is mediated through inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show they accumulate in atherosclerotic lesions where they directly affect plaque macrophages. Finally we demonstrate that a three-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a one-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation

The interrelations of radiologic findings and mechanical ventilation in community acquired pneumonia patients admitted to the intensive care unit: a multicentre retrospective study

BACKGROUND: We evaluated patients admitted to the intensive care units with the diagnosis of community acquired pneumonia (CAP) regarding initial radiographic findings. METHODS: A multicenter retrospective study was held. Chest x ray (CXR) and computerized tomography (CT) findings and also their associations with the need of ventilator support were evaluated. RESULTS: A total of 388 patients were enrolled. Consolidation was the main finding on CXR (89%) and CT (80%) examinations. Of all, 45% had multi-lobar involvement. Bilateral involvement was found in 40% and 44% on CXR and CT respectively. Abscesses and cavitations were rarely found. The highest correlation between CT and CXR findings was observed for interstitial involvement. More than 80% of patients needed ventilator support. Noninvasive mechanical ventilation (NIV) requirement was seen to be more common in those with multi-lobar involvement on CXR as 2.4-fold and consolidation on CT as 47-fold compared with those who do not have these findings. Invasive mechanical ventilation (IMV) need increased 8-fold in patients with multi-lobar involvement on CT. CONCLUSION: CXR and CT findings correlate up to a limit in terms of interstitial involvement but not in high percentages in other findings. CAP patients who are admitted to the ICU are severe cases frequently requiring ventilator support. Initial CT and CXR findings may indicate the need for ventilator support, but the assumed ongoing real practice is important and the value of radiologic evaluation beyond clinical findings to predict the mechanical ventilation need is subject for further evaluation with large patient series

Plasma modification of PMMA films: surface free energy and cell-attachment studies

The surface of a material is the most important part determining the acceptance by and compatibility with the environment. In many cases, although the bulk properties are excellent for a specific application, the surface may require to be modified and engineered in the desired direction. This is especially important for materials used in biological media, since the surface charge, hydophilicity and wettability are important for thrombosis formation, cell attachment or cell proliferation. In this study, poly(methyl methacrylate) films were prepared by solvent casting and their surfaces were modified by oxygen plasma treatment by applying powers of 20, 100 and 300 W. The effects of surface chemistry alterations on hydophilicity, work of adhesion, surface free energy and cell adhesion were examined. Cell attachment and proliferation are especially important for the materials used for tissue-engineering purposes. The results demonstrated that there is an optimum value for hydrophilicity and surface free energy which enhance cell attachment

Evaluation of surface free energy for PMMA films

Surface free energy (SFE) is a property resulted from the chemical structure and the orientation of the molecules at the surface boundary of the materials. For solids, it can be calculated from the contact angles of liquid drops with known surface tension, formed on the solid surface. There are various SFE evaluation methods based on different theoretical assumptions. In this study, SFE and the dispersive, polar, acidic and basic components of the SFE of a polymeric material, poly(methyl methacrylate) (PMMA), were calculated by using Zisman, Saito, Fowkes, Berthelot, Geometric mean, Harmonic mean, and Acid-base approaches. The results obtained from various liquid couples or triplets were compared. (C) 2007 Wiley Periodicals, Inc

Influence of oxygen plasma modification on surface free energy of PMMA films and cell attachment

For any biomaterial placed into a biological medium, the surface properties of the material, such as porosity, crystallinity, presence and distribution of electrical charge and functional groups are very critical parameters that determine the acceptance or rejection of the material. Applications, especially tissue engineering require some surface modifications at the molecular level without disturbing the bulk properties of the implants in order to enhance the cell attachment on the material. An appropriate technique is the application of glow discharge plasma which employs no solvents, takes place at ambient temperatures, and alterations take place only at the surface by changing the surface chemistry along with surface free energy (SFE) and efficiency for cell-material interaction. In this study, poly(methyl methacrylate) (PMMA) film surfaces were modified with oxygen plasma. SFE and its dispersive and polar (acidic-basic) components of the modified surfaces were calculated by means of several theoretical approaches including geometric mean, harmonic mean and acid-base equations. The relation between SFE and its dispersive and polar components and cell attachment on surfaces were studied. The highest 3T3 cell attachment was obtained for the surface with the total SFE of 61.77 mJ/m(2) and polar component of 50.91 mJ/m(2) according to Geometric mean. The total SFE of this surface was calculated to be 61.06 mJ/m(2) and the polar component as 40.96 mJ/m(2) using the Harmonic mean method

Eye injuries at a tertiary health center in the west Black Sea region, Turkey

WOS: 000303134900004PubMed: 22792817BACKGROUND We aimed to investigate the clinical aspects and visual prognosis in eye injury and to constitute data in the west Black Sea region in Turkey for national statistics. METHODS A retrospective analysis of 281 eye trauma cases admitted to the Emergency Department of Zonguldak Karaelmas University Hospital between 2005 and 2010 was performed. RESULTS A majority of eye injuries (42.7%) affected individuals aged 30 to 50 years. The most frequent cause of injury in the rural areas was wooden objects. The most frequent cause of injury in males aged 30 to 50 years was work-site injuries. Corneal-scleral lacerations were found to be the most serious injuries with regard to initial and final visual acuities. CONCLUSION Eye injuries are still the most common and preventable cause of blindness. Simple precautions and public education might prevent this health problem, which causes economic and labor force loss and psychological problems. One of the basic precautions would be raising public awareness on wearing a seat belt inside the car and protective eyeglasses at the work site and while working in rural areas

Synthesis of Polymer–Lipid Nanoparticles for Image-Guided Delivery of Dual Modality Therapy

For advanced treatment of diseases such as cancer, multicomponent, multifunctional nanoparticles hold great promise. In the current study we report the synthesis of a complex nanoparticle (NP) system with dual drug loading as well as diagnostic properties. To that aim we present a methodology where chemically modified poly(lactic-co-glycolic) acid (PLGA) polymer is formulated into a polymer-lipid NP that contains a cytotoxic drug doxorubicin (DOX) in the polymeric core and an anti-angiogenic drug sorafenib (SRF) in the lipidic corona. The NP core also contains gold nanocrystals (AuNCs) for imaging purposes and cyclodextrin molecules to maximize the DOX encapsulation in the NP core. In addition, a near-infrared (NIR) Cy7 dye was incorporated in the coating. To fabricate the NP we used a microfluidics-based technique that offers unique NP synthesis conditions, which allowed for encapsulation and fine-tuning of optimal ratios of all the NP components. NP phantoms could be visualized with computed tomography (CT) and near-infrared (NIR) fluorescence imaging. We observed timed release of the encapsulated drugs, with fast release of the corona drug SRF and delayed release of a core drug DOX. In tumor bearing mice intravenously administered NPs were found to accumulate at the tumor site by fluorescence imaging. © 2013 American Chemical Society

Synthesis of Polymer–Lipid Nanoparticles for Image-Guided Delivery of Dual Modality Therapy

For advanced treatment of diseases such as cancer, multi component, multi functional nanoparticles hold great promise. In the current study we report the synthesis of a complex nanoparticle (NP) system with dual drug loading as well as diagnostic properties. To that aim we present a methodology where chemically modified poly(lactic co glycolic) acid (PLGA) polymer is formulated into a polymer lipid NP that contains a cytotoxic drug doxorubicin (DOX) in the polymeric core and an anti angiogenic drug sorafenib (SRF) in the lipidic corona. The NP core also contains gold nanocrystals (AuNCs) for imaging purposes and cyclodextrin molecules to maximize the DOX encapsulation in the NP core. In addition, a near infrared (NIR) Cy7 dye was incorporated in the coating. To fabricate the NP we used a microfluidics based technique that offers unique NP synthesis conditions, which allowed for encapsulation and fine tuning of optimal ratios of all the NP components. NP phantoms could be visualized with computed tomography (CT) and near infrared (NIR) fluorescence imaging. We observed timed release of the encapsulated drugs, with fast release of the corona drug SRF and delayed release of a core drug DOX. In tumor bearing mice intravenously administered NPs were found to accumulate at the tumor site by fluorescence imaging