Evaluation of pulmonary toxicity of benzalkonium chloride and triethylene glycol mixtures using in vitro and in vivo systems

Benzalkonium chloride (BAC) is a widely used disinfectant/preservative, and respiratory exposure to this compound has been reported to be highly toxic. Spray‐form household products have been known to contain BAC together with triethylene glycol (TEG) in their solutions. The purpose of this study was to estimate the toxicity of BAC and TEG mixtures to pulmonary organs using in vitro and in vivo experiments. Human alveolar epithelial (A549) cells incubated with BAC (1‐10 μg/mL) for 24 hours showed significant cytotoxicity, while TEG (up to 1000 μg/mL) did not affect cell viability. However, TEG in combination with BAC aggravated cell damage and inhibited colony formation as compared to BAC alone. TEG also exacerbated BAC‐promoted production of reactive oxygen species (ROS) and reduction of glutathione (GSH) level in A549 cells. However, pretreatment of the cells with N‐acetylcysteine (NAC) alleviated the cytotoxicity, indicating oxidative stress could be a mechanism of the toxicity. Quantification of intracellular BAC by LC/MS/MS showed that cellular distribution/absorption of BAC was enhanced in A549 cells when it was exposed together with TEG. Intratracheal instillation of BAC (400 μg/kg) in rats was toxic to the pulmonary tissues while that of TEG (up to 1000 μg/kg) did not show any harmful effect. A combination of nontoxic doses of BAC (200 μg/kg) and TEG (1000 μg/kg) promoted significant lung injury in rats, as shown by increased protein content and lactate dehydrogenase (LDH) activity in bronchoalveolar lavage fluids (BALF). Moreover, BAC/TEG mixture recruited inflammatory cells, polymorphonuclear leukocytes (PMNs), in terminal bronchioles and elevated cytokine levels, tumor necrosis factor α (TNF‐α), and interleukin 6 (IL‐6) in BALF. These results suggest that TEG can potentiate BAC‐induced pulmonary toxicity and inflammation, and thus respiratory exposure to the air mist from spray‐form products containing this chemical combination is potentially harmful to humans.     

The prevalence of fibromyalgia in axial spondyloarthritis

Rheumatology International - Comorbid fibromyalgia, in axial spondyloarthritis (axSpA) has been shown to influence disease activity and function, and quality of life. Although several papers exist,...     

No association between the IL28B SNP and response to peginterferon plus ribavirin combination treatment in Korean chronic hepatitis C patients

Background/Aims

There are few available data regarding the association between the single nucleotide polymorphisms (SNPs) of the gene encoding interleukin 28B (IL28B) and a sustained virologic response (SVR) to peginterferon (PEG-IFN) plus ribavirin (RBV) therapy in Korean chronic hepatitis C patients.

Methods

This was a retrospective cohort study of 156 patients with chronic hepatitis C virus (HCV) infection who received combination treatment of PEG-IFN plus RBV. Blood samples from these patients were analyzed to identify the IL28B SNPs at rs12979860, rs12980275, rs8099917, and rs8103142. Association analyses were performed to evaluate the relationships between each IL28B SNP and SVRs.

Results

Seventy six patients with HCV genotype 1 and 80 with genotype non-1 were enrolled. The frequencies of rs12979860 CC and CT genotypes were 90.4% and 9.6%, respectively; those of rs12980275 AA and AG genotypes were 87.2% and 12.8%, respectively; those of rs8099917 TT and TG genotypes were 92.3% and 7.7%, respectively; and those of rs8103142 TT and CT genotypes were 90.4% and 9.6%, respectively. Among the patients with HCV genotype 1, the SVR rates were 69.7% and 80.0% for rs12979860 CC and CT, respectively (P=0.71). Among the HCV genotype non-1 patients, SVR rates were 88.0% and 100% for rs12979860 CC and CT (P=1.00), respectively.

Conclusions

Genotypes of the IL28B SNP that are known to be favorable were present in most of the Korean patients with chronic hepatitis C in this study. Moreover, the IL28B SNP did not influence the SVR rate in either the HCV genotype 1 or non-1 patients. Therefore, IL28B SNP analysis might be not useful for the initial assessment, prediction of treatment outcomes, or treatment decision-making of Korean chronic hepatitis C patients.     

CT findings of acute radiation-induced pneumonitis in breast cancer

Objectives:To evaluate the CT findings of acute radiation pneumonitis (RP) in breast cancer patients undergoing post-operative radiotherapy, and to analyze clinicodosimetric factors associated with acute RP.Methods:Between 2015 and 2017, 61 patients with breast cancer who underwent follow-up chest CT at 3 months after radiotherapy were analyzed. The degree of acute RP on CT was evaluated by the change of extent and scoring system (grade 0, no RP; Grade 1, ground-glass opacities (GGOs); Grade 2, GGOs and/or consolidations; Grade 3, clear focal consolidation; Grade 4, dense consolidation). The dosimetric parameters were calculated from the dose–volume histogram of RT.Results:The acute RP on CT was scored as follows: Grade 0, in 37.7%, Grade 1 in 13.1%, Grade 2 in 44.3%, and Grade 3 in 4.9%. The median extent of RP in patients with Grades 1 to 3 was 6.2 ml (range, 0.2–95.9). There were no clinicodosimetric factors significantly associated with the presence of RP or its severity. One patient developed symptomatic RP.Conclusion:This study showed no correlation between acute RP and clinicodosimetric factors, and acute RP based on CT findings were much more common than symptomatic RP.Advances in knowledge:CT findings of acute RP or extent of RP were not significantly related to clinicodosimetric factors in breast cancer patients.     

The substitution effects of donor and acceptor on properties of poly(1,4-phenylenevinylene) derivatives. Syntheses of poly(2-methoxy-5-methylsulfinyl-1,4-phenylenevinylene) and its copolymers

Electron donor and acceptor substituted poly(2-methoxy-5-methylsulfinyl-1,4-phenylenevinylene) (PMMSPV) and a series of copolymers containing 1,4-phenylenevinylene (PV) units were synthesized via the water-soluble precursor pathway and cast into films. The electrical conductivity of FeCl₃-doped PMMSPV was 1.5 × 10⁻⁴ S ċ cm⁻¹ and the copolymers showed conductivities in the range of 10⁻⁴ ∼ 10⁻¹ S ċ cm⁻¹ depending on the copolymer compositions. The second-order nonlinear optical coefficient of PMMSPV was obtained with second harmonic generation method. The measured d₃₃ value was 1.5 pm/V and gave no decay at 100°C over 40 d.