Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts.

The photosensitizing properties of m-tetrahydroxyphenylchlorin (mTHPC) and polyethylene glycol-derivatized mTHPC (pegylated mTHPC) were compared in nude mice bearing human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts. Laser light (20 J/cm2) at 652 nm was delivered to the tumour (surface irradiance) and to an equal-sized area of the hind leg of the animals after i.p. administration of 0.1 mg/kg body weight mTHPC and an equimolar dose of pegylated mTHPC, respectively. The extent of tumour necrosis and normal tissue injury was assessed by histology. Both mTHPC and pegylated mTHPC catalyse photosensitized necrosis in mesothelioma xenografts at drug-light intervals of 1-4 days. The onset of action of pegylated mTHPC seemed slower but significantly exceeds that of mTHPC by days 3 and 4 with the greatest difference being noted at day 4. Pegylated mTHPC also induced significantly larger photonecrosis than mTHPC in squamous cell xenografts but not in adenocarcinoma at day 4, where mTHPC showed greatest activity. The degree of necrosis induced by pegylated mTHPC was the same for all three xenografts. mTHPC led to necrosis of skin and underlying muscle at a drug-light interval of 1 day but minor histological changes only at drug-light intervals from 2-4 days. In contrast, pegylated mTHPC did not result in histologically detectable changes in normal tissues under the same treatment conditions at any drug-light interval assessed. In this study, pegylated mTHPC had advantages as a photosensitizer compared to mTHPC. Tissue concentrations of mTHPC and pegylated mTHPC were measured by high-performance liquid chromatography in non-irradiated animals 4 days after administration. There was no significant difference in tumour uptake between the two sensitizers in mesothelioma, adenocarcinoma and squamous cell carcinoma xenografts. Tissue concentration measurements were of limited use for predicting photosensitization in this model.

Molecular detection and identification of zygomycetes species from paraffin-embedded tissues in a murine model of disseminated zygomycosis: a collaborative European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) evaluation.

The present study was performed to assess the interlaboratory reproducibility of the molecular detection and identification of species of Zygomycetes from formalin-fixed paraffin-embedded kidney and brain tissues obtained from experimentally infected mice. Animals were infected with one of five species (Rhizopus oryzae, Rhizopus microsporus, Lichtheimia corymbifera, Rhizomucor pusillus, and Mucor circinelloides). Samples with 1, 10, or 30 slide cuts of the tissues were prepared from each paraffin block, the sample identities were blinded for analysis, and the samples were mailed to each of seven laboratories for the assessment of sensitivity. A protocol describing the extraction method and the PCR amplification procedure was provided. The internal transcribed spacer 1 (ITS1) region was amplified by PCR with the fungal universal primers ITS1 and ITS2 and sequenced. As negative results were obtained for 93% of the tissue specimens infected by M. circinelloides, the data for this species were excluded from the analysis. Positive PCR results were obtained for 93% (52/56), 89% (50/56), and 27% (15/56) of the samples with 30, 10, and 1 slide cuts, respectively. There were minor differences, depending on the organ tissue, fungal species, and laboratory. Correct species identification was possible for 100% (30 cuts), 98% (10 cuts), and 93% (1 cut) of the cases. With the protocol used in the present study, the interlaboratory reproducibility of ITS sequencing for the identification of major Zygomycetes species from formalin-fixed paraffin-embedded tissues can reach 100%, when enough material is available.

Hazardous substances in frequently used professional cleaning products.

A growing number of studies have identified cleaners as a group at risk for adverse health effects of the skin and the respiratory tract. Chemical substances present in cleaning products could be responsible for these effects. Currently, only limited information is available about irritant and health hazardous chemical substances found in cleaning products. We hypothesized that chemical substances present in cleaning products are known health hazardous substances that might be involved in adverse health effects of the skin and the respiratory tract. We performed a systematic review of cleaning products used in the Swiss cleaning sector. We surveyed Swiss professional cleaning companies (n = 1476) to identify the most used products (n = 105) for inclusion. Safety data sheets (SDSs) were reviewed and hazardous substances present in cleaning products were tabulated with current European and global harmonized system hazard labels. Professional cleaning products are mixtures of substances (arithmetic mean 3.5 +/- 2.8), and more than 132 different chemical substances were identified in 105 products. The main groups of chemicals were fragrances, glycol ethers, surfactants, solvents; and to a lesser extent, phosphates, salts, detergents, pH-stabilizers, acids, and bases. Up to 75% of products contained irritant (Xi), 64% harmful (Xn) and 28% corrosive (C) labeled substances. Hazards for eyes (59%) and skin (50%), and hazards by ingestion (60%) were the most reported. Cleaning products potentially give rise to simultaneous exposures to different chemical substances. As professional cleaners represent a large workforce, and cleaning products are widely used, it is a major public health issue to better understand these exposures. The list of substances provided in this study contains important information for future occupational exposure assessment studies.

Toxicity assessment of refill liquids for electronic cigarettes.

We analyzed 42 models from 14 brands of refill liquids for e-cigarettes for the presence of micro-organisms, diethylene glycol, ethylene glycol, hydrocarbons, ethanol, aldehydes, tobacco-specific nitrosamines, and solvents. All the liquids under scrutiny complied with norms for the absence of yeast, mold, aerobic microbes, Staphylococcus aureus, and Pseudomonas aeruginosa. Diethylene glycol, ethylene glycol and ethanol were detected, but remained within limits authorized for food and pharmaceutical products. Terpenic compounds and aldehydes were found in the products, in particular formaldehyde and acrolein. No sample contained nitrosamines at levels above the limit of detection (1 μg/g). Residual solvents such as 1,3-butadiene, cyclohexane and acetone, to name a few, were found in some products. None of the products under scrutiny were totally exempt of potentially toxic compounds. However, for products other than nicotine, the oral acute toxicity of the e-liquids tested seems to be of minor concern. However, a minority of liquids, especially those with flavorings, showed particularly high ranges of chemicals, causing concerns about their potential toxicity in case of chronic oral exposure.