Toxic Indoor Air Is a Potential Risk of Causing Immuno Suppression and Morbidity-A Pilot Study

We aimed to establish an etiology-based connection between the symptoms experienced by the occupants of a workplace and the presence in the building of toxic dampness microbiota. The occupants (5/6) underwent a medical examination and urine samples (2/6) were analyzed by LC-MS/MS for mycotoxins at two time-points. The magnitude of inhaled water was estimated. Building-derived bacteria and fungi were identified and assessed for toxicity. Separate cytotoxicity tests using human THP-1 macrophages were performed from the office's indoor air water condensates. Office-derived indoor water samples (n = 4/4) were toxic to human THP-1 macrophages. Penicillium, Acremonium sensu lato, Aspergillus ochraceus group and Aspergillus section Aspergillus grew from the building material samples. These colonies were toxic in boar sperm tests (n = 11/32); four were toxic to BHK-21 cells. Mycophenolic acid, which is a potential immunosuppressant, was detected in the initial and follow-up urine samples of (2/2) office workers who did not take immunosuppressive drugs. Their urinary mycotoxin profiles differed from household and unrelated controls. Our study suggests that the presence of mycotoxins in indoor air is linked to the morbidity of the occupants. The cytotoxicity test of the indoor air condensate is a promising tool for risk assessment in moisture-damaged buildings.Peer reviewe

Intra-Laboratory Pre-Validation of a Human Cell Based in vitro Angiogenesis Assay for Testing Angiogenesis Modulators

The developed standardized human cell based in vitro angiogenesis assay was intra-laboratory pre-validated to verify that the method is reliable and relevant for routine testing of modulators of angiogenesis, e.g., pharmaceuticals and industrial chemicals. This assay is based on the earlier published method but it was improved and shown to be more sensitive and rapid than the previous assay. The performance of the assay was assessed by using six reference chemicals, which are widely used pharmaceuticals that inhibit angiogenesis: acetyl salicylic acid, erlotinib, 2-methoxyestradiol, levamisole, thalidomide, and anti-vascular endothelial growth factor. In the intra-laboratory pre-validation, the sensitivity of the assay (upper and lower limits of detection and linearity of response in tubule formation), batch to batch variation in tubule formation between different Master cell bank batches, and precision as well as the reliability of the assay (reproducibility and repeatability) were tested. The pre-set acceptance criteria for the intra-laboratory pre-validation study were met. The relevance of the assay in man was investigated by comparing the effects of reference chemicals and their concentrations to the published human data. The comparison showed a good concordance, which indicates that this human cell based angiogenesis model predicts well the effects in man and has the potential to be used to supplement and/or replace of animal tests

Cytotoxicity of Water Samples Condensed from Indoor Air : An Indicator of Poor Indoor Air Quality

Introduction: The impurities of the air inside the buildings and the resulting adverse health effects have become an increasing problem. Typically indoor air impurities are mixtures of many chemical substances at relative low concentrations. The toxicity of individual substances may be negligible, the mixture effect being the primary cause for toxicity and the potential adverse health effects. Standardized screening methods for identifying the health hazard are lacking. The aim of this study was, by using conventional cytotoxicity/cell viability assays, to investigate whether indoor air cytotoxicity can be detected from water samples condensed from indoor air. Materials and Methods: The cytotoxicity of 712 water samples condensed from indoor air was investigated. First, 24 samples were tested in four different cell types (human bronchial epithelial cells, BJ fibroblasts, Tohoku Hospital Pediatric-1 [THP-1] monocytes, and THP-1 macrophages) using neutral red uptake and water-soluble tetrazolium salt 1 (WST-1) assays. Thereafter, 688 samples were tested using THP-1 macrophage/WST-1 assay. All samples were tested at 10% sample concentration, 56 samples were also tested at 25% concentration to see dose-response effects. Results: THP-1 macrophage/WST-1 assay was the most reproducible method for assessing indoor air cytotoxicity. The adverse effects of indoor air samples on THP-1 cells ranged from ca. 33% loss in cell viability to ca. 17% increase in mitochondrial activity ("cell stress"). Indoor air samples from 75% sampling sites where people reported health symptoms caused adverse effects in THP-1 macrophage/WST-1 assay. Conclusions: The assessment of indoor air cytotoxicity using water samples condensed from the indoor air and THP-1 macrophage/WST-1 assay provides a novel and practical biological approach for investigating indoor air quality. This method does not replace existing methods, but supplements them and provides a fast and cheap alternative for the first-stage screening for recognizing poor indoor air regardless of its source.publishedVersionPeer reviewe

NANOCI-Nanotechnology Based Cochlear Implant With Gapless Interface to Auditory Neurons

Cochlear implants (CI) restore functional hearing in the majority of deaf patients. Despite the tremendous success of these devices, some limitations remain. The bottleneck for optimal electrical stimulation with CI is caused by the anatomical gap between the electrode array and the auditory neurons in the inner ear. As a consequence, current devices are limited through 1) low frequency resolution, hence suboptimal sound quality and 2), large stimulation currents, hence high energy consumption (responsible for significant battery costs and for impeding the development of fully implantable systems). A recently completed, multinational and interdisciplinary project called NANOCI aimed at overcoming current limitations by creating a gapless interface between auditory nerve fibers and the cochlear implant electrode array. This ambitious goal was achieved in vivo by neurotrophin-induced attraction of neurites through an intra-cochlear gel-nanomatrix onto a modified nanoCI electrode array located in the scala tympani of deafened guinea pigs. Functionally, the gapless interface led to lower stimulation thresholds and a larger dynamic range in vivo, and to reduced stimulation energy requirement (up to fivefold) in an in vitro model using auditory neurons cultured on multi-electrode arrays. In conclusion, the NANOCI project yielded proof of concept that a gapless interface between auditory neurons and cochlear implant electrode arrays is feasible. These findings may be of relevance for the development of future CI systems with better sound quality and performance and lower energy consumption. The present overview/review paper summarizes the NANOCI project history and highlights achievements of the individual work packages