During the past 20 years, improvements in nanoscale materials synthesis and characterization have given scientists great control over the fabrication of materials with features between 1 and 100 nm, unlocking many unique size-dependent properties and, thus, promising many new and/or improved technologies. Recent years have found the integration of such materials into commercial goods; a current estimate suggests there are over 800 nanoparticle-containing consumer products (The Project on Emerging Nanotechnologies Consumer Products Inventory, , accessed Oct. 2008), accounting for 147 billion USD in products in 2007 (Nanomaterials state of the market Q3 2008: stealth success, broad impact, Lux Research Inc., New York, NY, 2008). Despite this increase in the prevalence of engineered nanomaterials, there is little known about their potential impacts on environmental health and safety. The field of nanotoxicology has formed in response to this lack of information and resulted in a flurry of research studies. Nanotoxicology relies on many analytical methods for the characterization of nanomaterials as well as their impacts on in vitro and in vivo function. This review provides a critical overview of these techniques from the perspective of an analytical chemist, and is intended to be used as a reference for scientists interested in conducting nanotoxicological research as well as those interested in nanotoxicological assay development.
Nanoparticle toxicology, an emergent field, works toward establishing the hazard of nanoparticles, and therefore their potential risk, in light of the increased use and likelihood of exposure. Analytical chemists can provide an essential tool kit for the advancement of this field by exploiting expertise in sample complexity and preparation as well as method and technology development. Herein, we discuss experimental considerations for performing in vitro nanoparticle toxicity studies, with a focus on nanoparticle characterization, relevant model cell systems, and toxicity assay choices. Additionally, we present three case studies (of silver, titanium dioxide, and carbon nanotube toxicity) to highlight the important toxicological considerations of these commonly used nanoparticles.
cTnI increases are encountered in approximately a third of patients, the majority due to nonatherothrombotic conditions. Compared with patients without myonecrosis, type 2 myocardial infarction and myocardial injury have worse short-term outcomes, with mortality rates >20% at 2 years. hs-cTnI assay does not lead to more myocardial injury or infarction.
Background
How to select healthy reference subjects in deriving 99th percentiles for cardiac troponin assays still needs to be clarified. To assist with global implementation of high sensitivity (hs)-cardiac troponin (cTn) I and hs-cTnT assays in clinical practice, we determined overall and sex-specific 99th percentiles in 9 hs-cTnI and 3 hs-cTnT assays using a universal sample bank (USB).
Methods
The Universal Sample Bank (USB) comprised healthy subjects, 426 men and 417 women, screened using a health questionnaire. Hemoglobin A1c (>URL 6.5%), NT-proBNP (>URL 125 ng/L) and eGFR (<60 mL/min), were used as surrogate biomarker exclusion criteria along with statin use. 99th percentiles were determined by nonparametric, Harrell--Davis bootstrap, and robust methods.
Results
Subjects were ages 19 to 91 years, Caucasian 58%, African American 27%, Pacific Islander/Asian 11%, other 4%, Hispanic 8%, and non-Hispanic 92%. The overall and sex-specific 99th percentiles for all assays, before and after exclusions (n = 694), were influenced by the statistical method used, with substantial differences noted between and within both hs-cTnI and hs-cTnT assays. Men had higher 99th percentiles (ng/L) than women. The Roche cTnT and Beckman and Abbott cTnI assays (after exclusions) did not measure cTn values at ≥ the limit of detection in ≥50% women.
Conclusions
Our findings have important clinical implications in that sex-specific 99th percentiles varied according to the statistical method and hs-cTn assay used, not all assays provided a high enough percentage of measurable concentrations in women to qualify as a hs-assay, and the surrogate exclusion criteria used to define normality tended to lower the 99th percentiles.
A total of six nanotherapeutic formulations are already approved for medical use and more are in the approval pipeline currently. Despite the massive research effort in nanotherapeutic materials, there is relatively little information about the toxicity of these materials or the tools needed to assess this toxicity. Recently, the scientific community has begun to respond to the paucity of information by investing in the field of nanoparticle toxicology. This review is intended to provide an overview of the techniques needed to assess toxicity of these therapeutic nanoparticles and to summarize the current state of the field. We begin with background on the toxicological assessment techniques used currently as well as considerations in nanoparticle dosing. The toxicological research overview is divided into the most common applications of therapeutic nanoparticles: drug delivery, photodynamic therapy and bioimaging. We end with a perspective section discussing the current technological gaps and promising research aimed at addressing those gaps.
Strategies using a single hs-cTnI alone or in combination with a normal ECG allow the immediate identification of patients unlikely to have acute myocardial infarction and who are at very low risk for adverse events at 30 days.
Using two of the most commonly synthesized noble metal nanoparticle preparations, citrate-reduced Au and Ag, the impacts of short-term accidental nanoparticle exposure are examined in primary culture murine adrenal medullary chromaffin cells. Transmission electron microscopy (TEM), inductively coupled plasma atomic emission spectroscopy (ICP-AES) and Alamar Blue viability studies revealed that nanoparticles are taken up by cells but do not decrease cell viability within 48 hours of exposure. Carbon-fiber microelectrode amperometry (CFMA) examination of exocytosis in nanoparticle-exposed cells revealed that nanoparticle exposure does lead to decreased secretion of chemical messenger molecules, of up to 32.5% at 48 hours of Au exposure. The kinetics of intravesicular species liberation also slows after nanoparticle exposure, between 30 and 50% for Au and Ag, respectively. Repeated stimulation of exocytosis demonstrated that these effects persisted during subsequent stimulations, meaning that nanoparticles do not interfere directly with the vesicle recycling machinery but also that cellular function is unable to recover following vesicle content expulsion. By comparing these trends with parallel studies done using mast cells, it is clear that similar exocytosis perturbations occur across cell types following noble metal nanoparticle exposure, supporting a generalizable effect of nanoparticle-vesicle interactions.
BACKGROUND:The frequency and characteristics of myocardial infarction (MI) subtypes per the Third Universal Definition of MI (TUDMI) classification system using high-sensitivity (hs) cardiac troponin assays with sexspecific cutoffs is not well known. We sought to describe the diagnostic characteristics of type 1 (T1MI) and type 2 (T2MI) MI using an hs-cardiac troponin I (hs-cTnI) assay with sex-specific cutoffs.
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