Evaluation of Adverse Effects of Resorbable Hyaluronic Acid Fillers: Determination of Macrophage Responses.

Resorbable tissue fillers for aesthetic purposes can induce severe complications including product migration, late swelling, and inflammatory reactions. The relation between product characteristics and adverse effects is not well understood. We hypothesized that the degree of cross-linking hyaluronic acid (HA) fillers was associated with the occurrence of adverse effects. Five experimental HA preparations similar to HA fillers were synthesized with an increasing degree of cross-linking. Furthermore, a series of commercial fillers (Perfectha®) was obtained that differ in degradation time based on the size of their particulate HA components. Cytotoxic responses and cytokine production by human THP-1-derived macrophages exposed to extracts of the evaluated resorbable HA fillers were absent to minimal. Gene expression analysis of the HA-exposed macrophages revealed the responses related to cell cycle control and immune reactivity. Our results could not confirm the hypothesis that the level of cross-linking in our experimental HA fillers or the particulate size of commercial HA fillers is related to the induced biological responses. However, the evaluation of cytokine induction and gene expression in macrophages after biomaterial exposure presents promising opportunities for the development of methods to identify cellular processes that may be predictive for biomaterial-induced responses in patients.

The Health Risks of Electronic Cigarette Use to Bystanders.

This works aimed to assess the health risks of e-cigarette use to bystanders. The exhaled breath of 17 volunteers was collected while they were vaping, and the levels of nicotine, propylene glycol, glycerol, formaldehyde, acetaldehyde, acrolein, tobacco-specific nitrosamines (TSNAs), and heavy metals were analyzed. Increased levels of nicotine, propylene glycol, TSNAs and copper were found in the exhaled breath of the volunteers. From these measurements, bystander exposure was estimated for two different scenarios: (1) A non-ventilated car with two e-cigarette users and (2) a ventilated office with one e-cigarette user. Our results show that bystanders may experience irritation of the respiratory tract as a result of exposure to propylene glycol and glycerol. Systemic effects of nicotine should also be expected if nicotine-containing e-liquid is used, including palpitations, and an increase of the systolic blood pressure. Furthermore, due to the presence of TSNAs in some e-liquids, an increased risk of tumors could not be excluded for the 'car' scenario. While e-cigarette use can clearly have effects on the health of bystanders, the risks depend on the rate of ventilation, dimensions of the room, and vaping behavior of the e-cigarette user. The presence of TSNAs in e-liquids can be avoided, which will prevent the most serious effect identified (increased risk of tumors).

Can the Direct Peptide Reactivity Assay Be Used for the Identification of Respiratory Sensitization Potential of Chemicals?

Prospective identification of low molecular weight respiratory sensitizers is difficult due to the current lack of adequate test methods. The direct peptide reactivity assay (DPRA) seems to be a promising method to determine the sensitization potential of chemicals because it determines the intrinsic characteristic of sensitizers to bind to proteins. It is already applied in the field of skin sensitization, and adaptation to respiratory sensitization has started recently. This article further evaluates the ability of the DPRA to predict the respiratory sensitization potential of chemicals. In addition, the added value of applying High Performance Liquid Chromatography (HPLC)-MS and measurements after 20 minutes and 24 hours of incubation was evaluated. Eighteen respiratory sensitizers (10 haptens, 3 prehaptens, and 5 prohaptens) and 14 nonsensitizers were tested with 2-model peptides. Based on peptide depletion, a prediction model was proposed for the identification of (respiratory) sensitizers. Application of mass spectrometry and measurements at 2 time-points increased prediction accuracy of the assay by resolving discordant results. The prediction model correctly identified all haptens and prehaptens as sensitizers. The 5 prohaptens were not identified as sensitizers, most likely due to lack of metabolic activity in the DPRA. All but 1 nonsensitizer was correctly predicted. The model, therefore, shows an accuracy of 78% for the tested dataset. Unfortunately, this assay cannot be used to distinguish respiratory from skin sensitizers. To make this distinction, the DPRA needs to be combined with other test methods that are able to identify respiratory sensitizers.