Short-Term Pulmonary Toxicity Assessment of Pre- and Post-incinerated Organomodified Nanoclay in Mice.

Organomodified nanoclays (ONCs) are increasingly used as filler materials to improve nanocomposite strength, wettability, flammability, and durability. However, pulmonary risks associated with exposure along their chemical lifecycle are unknown. This study's objective was to compare pre- and post-incinerated forms of uncoated and organomodified nanoclays for potential pulmonary inflammation, toxicity, and systemic blood response.

Effect of surface functionalizations of multi-walled carbon nanotubes on neoplastic transformation potential in primary human lung epithelial cells.

Functionalized multi-walled carbon nanotube (fMWCNT) development has been intensified to improve their surface activity for numerous applications, and potentially reduce toxic effects. Although MWCNT exposures are associated with lung tumorigenesis in vivo, adverse responses associated with exposure to different fMWCNTs in human lung epithelium are presently unknown. This study hypothesized that different plasma-coating functional groups determine MWCNT neoplastic transformation potential.

Evaluation of tumorigenic potential of CeO and FeO engineered nanoparticles by a human cell screening model.

With rapid development of novel nanotechnologies that incorporate engineered nanomaterials (ENMs) into manufactured products, long-term, low dose ENM exposures in occupational settings is forecasted to occur with potential adverse outcomes to human health. Few ENM human health risk assessment efforts have evaluated tumorigenic potential of ENMs. Two widely used nano-scaled metal oxides (NMOs), cerium oxide (nCeO) and ferric oxide (nFeO) were screened in the current study using a sub-chronic exposure to human primary small airway epithelial cells (pSAECs).

Carcinogenic Potential of High Aspect Ratio Carbon Nanomaterials.

Engineered nanomaterials, including high aspect ratio carbon nanomaterials, are often commercialized without a complete human risk assessment and safety evaluation. A health concern has been raised that high aspect ratio nanomaterials such as carbon nanotubes may cause unintended health consequences, such as asbestos-like lung cancer and mesothelioma, when chronically inhaled. Considering the widespread industrial and clinical applications and the increasing incidence of human exposure to nanomaterials, it is important to address the issue of nanomaterial carcinogenicity in a timely manner.

Direct stimulation of human fibroblasts by nCeO2 in vitro is attenuated with an amorphous silica coating.

Background: Nano-scaled cerium oxide (nCeO2) is used in a variety of applications, including use as a fuel additive, catalyst, and polishing agent, yet potential adverse health effects associated with nCeO2 exposure remain incompletely understood. Given the increasing utility and demand for engineered nanomaterials (ENMs) such as nCeO2, "safety-by-design" approaches are currently being sought, meaning that the physicochemical properties (e.g.

Potential model for testing the effect of exposure to nanoparticles on the lung alveolar epithelial barrier.

Pulmonary barrier function plays a pivotal role in protection from inhaled particles. However, some nano-scaled particles, such as carbon nanotubes (CNT), have demonstrated the ability to penetrate this barrier in animal models, resulting in an unusual, rapid interstitial fibrosis. To delineate the underlying mechanism and specific bio-effect of inhaled nanoparticles in respiratory toxicity, models of lung epithelial barriers are required that allow accurate representation of systems; however, there is currently a lack of consistent methods to do so.

Targeting platelet-derived soluble CD40 ligand: a new treatment strategy for HIV-associated neuroinflammation?

Human immunodeficiency virus type 1 (HIV) continues to be one of the most prevalent global health afflictions to date. The advent and introduction of combined antiretroviral therapy (cART) has made a significant impact on the course of infection. However, as patients are living longer, many HIV-associated illnesses are becoming prevalent among the infected population, especially those associated with chronic inflammation.

Valproic acid inhibits the release of soluble CD40L induced by non-nucleoside reverse transcriptase inhibitors in human immunodeficiency virus infected individuals.

Despite the use of highly active antiretroviral therapies (HAART), a majority of Human Immunodeficiency Virus Type 1 (HIV) infected individuals continually develop HIV - Associated Neurocognitive Disorders (HAND), indicating that host inflammatory mediators, in addition to viral proteins, may be contributing to these disorders. Consistent with this notion, we have previously shown that levels of the inflammatory mediator soluble CD40 ligand (sCD40L) are elevated in the plasma and cerebrospinal fluid (CSF) of HIV infected, cognitively impaired individuals, and that excess sCD40L can contribute to blood brain barrier (BBB) permeability in vivo, thereby signifying the importance of this inflammatory mediator in the pathogenesis of HAND. Here we demonstrate that the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV) induces the release of circulating sCD40L in both HIV infected individuals and in an in vitro suspension of washed human platelets, which are the main source of circulating sCD40L.

Excess soluble CD40L contributes to blood brain barrier permeability in vivo: implications for HIV-associated neurocognitive disorders.

Despite the use of anti-retroviral therapies, a majority of HIV-infected individuals still develop HIV-Associated Neurocognitive Disorders (HAND), indicating that host inflammatory mediators, in addition to viral proteins, may be contributing to these disorders. Consistently, we have previously shown that levels of the inflammatory mediator soluble CD40L (sCD40L) are elevated in the circulation of HIV-infected, cognitively impaired individuals as compared to their infected, non-impaired counterparts. Recent studies from our group suggest a role for the CD40/CD40L dyad in blood brain barrier (BBB) permeability and interestingly, sCD40L is thought to regulate BBB permeability in other inflammatory disorders of the CNS.

Alterations of platelet function and clot formation kinetics after in vitro exposure to anti-A and -B.

Background: ABO-mismatched platelets (PLTs) are commonly transfused despite reported complications. We hypothesized that because PLTs possess A and B antigens on their surface, ABO-mismatched transfused or recipient PLTs could become activated and/or dysfunctional after exposure to anti-A or -B in the transfused or recipient plasma. We present here in vitro modeling data on the functional effects of exposure of PLTs to ABO antibodies.

Detection of circulating platelet-monocyte complexes in persons infected with human immunodeficiency virus type-1.

Activated platelets form transient aggregates with monocytes in circulation and have a half-life of approximately 30-60 min. These complexes are increased in various inflammatory conditions and are an early marker of myocardial infarction. HIV-1 infection is associated with chronic inflammation, and increased CD16⁺ inflammatory monocytes have been observed in these individuals, probably as a result of increased interaction with platelets.

Antiplatelet activity of valproic acid contributes to decreased soluble CD40 ligand production in HIV type 1-infected individuals.

CD40L is a type II membrane glycoprotein of the TNF family that is found on activated T cells, B cells, and platelets. We previously reported that the soluble form of this inflammatory mediator (sCD40L) is elevated in the plasma and cerebrospinal fluid of HIV-1-infected, cognitively impaired individuals. In this study, we demonstrate that the mood-stabilizing drug valproic acid (VPA) reduces sCD40L levels in plasma samples of HIV-1-infected patients (n = 23) and in washed human platelets, which are the main source of circulating sCD40L.