Consequences of exposure to peri-articular injections of micro- and nano-particulate cobalt–chromium alloy

Metal hip replacements generate both metal particles and ions. The biological effects of peri-articular exposure to nanometre and micron sized cobalt chrome (CoCr) wear particles were investigated in a mouse model. Mice received injections of two clinically relevant doses of nanoparticles (32 nm), one of micron sized (2.9 μm) CoCr particles or vehicle alone into the right knee joint at 0, 6, 12 and 18 weeks. Mice were analysed for genotoxic and immunological effects 1, 4 and 40 weeks post exposure. Nanoparticles but not micron particles progressively corroded at the injection site. Micron sized particles were physically removed. No increase of Co or Cr was seen in peripheral blood between 1 and 40 weeks post exposure to particles. No significant inflammatory changes were observed in the knee tissues including ALVAL or necrosis. DNA damage was increased in bone marrow at one and forty weeks and in cells isolated from frontal cortex at 40 weeks after injection with nanoparticles. Mice exposed to the micron sized, but not nanoparticles became immunologically sensitized to Cr(III), Cr (VI) and Ni(II) over the 40 week period as determined by lymphocyte transformation and ELISpot (IFN-γ and IL-2) assays. The data indicated that the response to the micron sized particles was Th1 driven, indicative of type IV hypersensitivity. This study adds to understanding of the potential adverse biological reactions to metal wear products.     

Substance P enhanced titanium particles-induced RANKL expression in fibroblasts from periprosthetic membrane

Abstract

Aseptic loosening remains the primary cause of failure in total joint arthroplasty. Implant-derived particles are thought to be a main cause of osteolysis that leads to the failure. Substance P (SP) immunoreactive nerve fibers have been detected in the periprosthetic membrane of aseptic loose hip prostheses. We isolated fibroblasts from periprosthetic membrane. Fibroblasts were examined by real-time RT-PCR and enzyme-linked immunosorbent assay for expression of the receptor activator of nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), cyclooxygenase (COX)-1, and COX-2. Experiments were performed in the presence and absence of titanium particles, SP and NS-398 (a selective COX-2 inhibitor). Titanium particles or SP stimulated RANKL and COX-2 expression in fibroblasts, whereas NS-398 inhibited RANKL production, suggesting a COX-2-mediated event. Moreover, SP enhanced COX-2 and RANKL expression by titanium particles-stimulated fibroblasts. Thus, SP and titanium particles acted synergistically to increase RANKL expression.     

Effects of concentrated ambient ultrafine particulate matter on hallmarks of Alzheimer’s disease in the 3xTgAD mouse model

BackgroundExposure to air pollution has been identified as a possible environmental contributor to Alzheimer’s Disease (AD) risk. As the number of people with AD worldwide continues to rise, it becomes vital to understand the nature of this potential gene-environment interaction. This study assessed the effects of short-term exposures to concentrated ambient ultrafine particulates (UFP, <100 nm) on measurements of amyloid-β, tau, and microglial morphology.MethodsTwo cohorts of aged (12.5–14 months) 3xTgAD and NTg mice were exposed to concentrated ambient UFP or filtered air for 2 weeks (4-h/day, 4 days/week). Bronchoalveolar lavage fluid and brain tissue were collected twenty-four hours following the last exposure to evaluate lung inflammation, tau pathology, amyloid-β pathology, and glial cell morphology.ResultsNo exposure- or genotype-related changes were found with any of the measures of lung inflammation or in the hippocampal staining density of astrocyte marker glial fibrillary acidic protein. The microglia marker, ionized calcium binding adaptor molecule 1, and amyloid-β marker, 6E10, exhibited significant genotype by exposure interactions such that levels were lower in the UFP-exposed as compared to filtered air-exposed 3xTgAD mice. When microglia morphology was assessed by Sholl analysis, microglia from both NTg mouse groups were ramified. The 3xTgAD air-exposed mice had the most ameboid microglia, while the 3xTgAD UFP-exposed mice had microglia that were comparatively more ramified. The 3xTgAD air-exposed mice had more plaques per region of interest as measured by Congo red staining as well as more plaque-associated microglia than the 3xTgAD UFP-exposed mice. The number of non-plaque-associated microglia was not affected by genotype or exposure. Levels of soluble and insoluble human amyloid-β₄₂ protein were measured in both 3xTgAD groups and no exposure effect was found. In contrast, UFP-exposure led to significant elevations in phosphorylated tau in 3xTgAD mice as compared to those that were exposed to air, as measured by pT205 staining.ConclusionsExposure to environmentally relevant levels of ultrafine particulates led to changes in tau phosphorylation and microglial morphology in the absence of overt lung inflammation. Such changes highlight the need to develop greater mechanistic understanding of the link between air pollution exposure and Alzheimer’s disease.     

Forces acting on particle-enhanced immunoassays

The aim of the present work is to study the role of the different forces involved in the agglutination of immune γ-globulin (IgG) covered latex particles due to antigen-antibody reaction. An experimental investigation on the adsorption of IgG molecules on three latexes with different surface charge densities is described. Photon correlation spectroscopy was used to determine the hydrodynamic layer thickness of the IgG molecules adsorbed on the latexes. In order to get an insight into the forces acting between two antibody-covered particles approaching each other, the colloidal stability and immunoreactivity of these biocomplexes were studied. They can be stabilized by electrostatic or hydration forces. The immunological agglutination of IgGimmobilized latex particles due to the addition of the antigen was quantified through scattered light intensity measurements. The immunoresponse increases with ionic strength of the medium until a maximum value is achieved. Above this maximum, the immunoreactivity decreases.     

A pandemic H1N1 influenza virus-like particle vaccine induces cross-protection in mice

Influenza virus-like particles (VLPs) represent promising alternative vaccines. However, it is necessary to demonstrate that influenza VLPs confer cross-protection against antigenically distinct viruses. In this study, a VLP vaccine comprising hemagglutinin (HA) and M1 from the A/California/04/2009 (H1N1) were used and its ability to induce cross-protective efficacy against heterologous viruses A/PR/8/34 (H1N1) and A/New Caledonia/20/99 (H1N1) in mice was assessed. Vaccination with 2009 H1 VLPs induced significantly higher levels of IgG cross-reactive with these heterologous viruses after the second boost compared to after the prime or first boost. Lung virus titers also decreased significantly and the lung cross-reactive IgG response after lethal virus challenge was significantly greater in immunized mice compared to naïve mice. Vaccinated mice showed 100% protection against A/PR/8/34 and A/Caledonia/20/99 viruses with only moderate body weight loss and induction of cross-reactive recall, IgG antibody-secreting cell responses. The variations in HA amino acid sequences and antigenic sites were determined and correlated with induction of cross-protective immunity. These results indicate that VLPs can be used as an effective vaccine that confers cross-protection against antigenically distinct viruses.     

Retroviral Sequences in Rheumatoid Arthritis Synovium

There are several relationships between retroviruses and cellular transformation, as well as retroviruses being involved in the development of autoimmune diseases. Retroviruses have been discussed as etiologic agents modulating or triggering certain pathways in the pathogenesis of rheumatoid arthritis (RA). However, none of the currently known retroviruses has been identified as specific for RA. Due to the unique properties of retroviruses, distinct experimental approaches can be used to detect retroviral activity in cells and tissues. Current research in RA using state-of-the-art molecular biology techniques includes both the search for exogenous and endogenous retroviral gene sequences in synovium of patients with RA.     

硅纳米颗粒诱导小鼠间充质干细胞成骨分化和迁移的体外研究*

目的 通过溶胶-凝胶法合成纳米尺径的硅基生物活性颗粒（SBPs）,检测其对间充质干细胞（MSCs）成骨分化和迁移的作用。方法 通过溶胶-凝胶法合成SBPs,通过扫描电镜和ZATA电位分析仪检测颗粒的物理特征。在培养基中添加SBPs配置成系列浓度的条件培养基,检测不同浓度的SBPs对小鼠MSCs增殖、成骨分化和迁移的影响。结果 SBPs的平均直径为134.3 nm,并且呈均匀分散球形颗粒。不同浓度的SBPs对MSCs增殖无影响;但4 µg/mL的SBPs对细胞成骨分化有明显的促进作用;高浓度（>16 µg/mL）的SBPs抑制MSCs的成骨分化;4 µg/mL的SBPs对MSCs有明显的促进迁移的作用。结论 在适宜浓度范围内（1 ～ 4 μg/mL）,SBPs具有促成骨作用和诱导MSCs迁移,未来可能被用来与其他生物材料复合制备新型的骨移植材料。     

Polystyrene Brushes on Fully Deuterated Organic Nanoparticles by Surface‐Initiated Nitroxide‐Mediated Radical Polymerization

The synthesis of polystyrene (PS) brushes on fully deuterated PS nanoparticles by surface‐initiated nitroxide‐mediated radical polymerization (SI‐NMRP) is reported. Due to the high demand of deuterated monomers, an efficient deuteration procedure of suitable and readily available precursors is developed. SI‐NMRP of styrene is improved regarding reaction control, grafting density, and conversion. Insights into the scaling behavior and conformational features of surface‐attached PS chains on deuterated particles are investigated by using dynamic light scattering measurements, proving that polymer brushes are formed. The particles with surface‐attached initiator are shown to be uniform spherical core‐shell particles by small‐angle neutron scattering measurements.

     

Uterine artery embolisation for uterine fibroids: Our experience at a tertiary care service hospital

Background

Uterine artery embolisation (UAE) has evolved as a minimally invasive and effective alternative, treatment modality for women with symptomatic fibroids. We discuss our initial experience of UAE in the management of symptomatic fibroids.

Methods

Twenty five symptomatic patients of uterine fibroids were treated with UAE by selectively cannulating and injecting poly vinyl alcohol particles into the uterine arteries. Post treatment follow up was done at 2 and 6 months respectively.

Results

Pre-treatment, the sizes of fibroids were between 3.9 and 10.9 cm (mean 7.4) on ultrasonography. Of the total 25 patients, 49 uterine arteries were embolised with a technical success rate of 98%. Menorrhagia persisted in 7 patients, dysmenorrhea in 4 patients and pressure symptoms in 2 patients respectively in follow up study of six months which corresponds to a reduction in symptoms by 68% for menorrhagia, 71% for dysmenorhoea and 75% for those with pressure symptoms respectively. At 2 months follow-up post embolisation, the mean diameter of the fibroid was 4.03 cm (range 2–5.2 cm) and at 6 months 3.2 cm (range 1.3–4.1 cm), corresponding to size reduction of 45.5% and 57%, respectively. Follow up with ultrasonography at 2 and 6 months period showed successful fibroid reduction in 24 patients with corresponding reduction in the symptomatology. One patient remained symptomatic with increase in fibroid size and had to undergo hysterectomy.

Conclusion

Uterine artery embolisation can be considered as an alternative to hysterectomy in appropriately selected symptomatic patients of uterine fibroids.     

桑杏颗粒治疗小儿风热挟痰证型咳嗽的疗效研究

目的：比较中药复方桑杏颗粒与急支糖浆治疗小儿咳嗽（风热挟痰证）的疗效,探讨复方桑杏颗粒治疗小儿咳嗽的临床应用前景。方法选择某市医院就诊的符合条件的患儿60例,随机分为两组,治疗组（30例）口服桑杏颗粒剂,对照组（30例）口服急支糖浆口服液,两组均以7天为一疗程,观察比较两组的疗效。结果治疗组咳嗽、咯痰症状、肺部听诊体征及胸片改善上均优于对照组。桑杏颗粒治疗小儿咳嗽的效果优于对照组,与急支糖浆相比,其需要治疗人数（NNT）为5人。结论桑杏颗粒剂治疗小儿急性支气管炎疗效显著,临床上值得推广应用。