Case Report: The Clinical Toxicity of Dimethylamine Borane

Context: Dimethylamine borane (DMAB) is a reducing agent used in nonelectric plating of semiconductors. Exposures are usually through occupational contact. We report here four cases of people who suffered from work-related exposure to DMAB. Case presentation: Three patients exposed to DMAB decontaminated immediately by drinking a lot of water; they reported dizziness, nausea, diarrhea 6–8 hr later. The other patient did not decontaminate at once, and he suffered from more severe symptoms, including dizziness, nausea, limb numbness, slurred speech, irritable mood, and ataxia 13 hr later. Magnetic resonance imaging showed symmetric lesions with hyperintensity on T2WI and FLAIR in bilateral cerebellar dantate nuclei. This patient was readmitted to the hospital due to difficulty in walking and climbing 18 days after exposure. Lower leg weakness and drop foot were found bilaterally. A nerve conduction study revealed polyneuropathy with motor-predominant axonal degeneration. This patient receives regular outpatient followups and still walks with a clumsy gait and has difficulty with hand-grasping activity. Discussion: This case study demonstrates that DMAB is highly toxic to humans through any route of exposure, and dermal absorption is the major route of neurotoxicity. DMAB induces acute cortical and cerebellar injuries and delayed peripheral neuropathy. Relevance: Further investigation of the toxic mechanism of DMAB is warranted. Early decontamination with copious water is the best current treatment for exposure to DMAB

Role of pirenoxine in the effects of catalin on in vitro ultraviolet-induced lens protein turbidity and selenite-induced cataractogenesis in vivo

Purpose: In this study, we investigated the biochemical pharmacology of pirenoxine (PRX) and catalin under in vitro selenite/calcium- and ultraviolet (UV)-induced lens protein turbidity challenges. The systemic effects of catalin were determined using a selenite-induced cataractogenesis rat model. Methods: In vitro cataractogenesis assay systems (including UVB/C photo-oxidation of lens crystallins, calpain-induced proteolysis, and selenite/calcium-induced turbidity of lens crystallin solutions) were used to screen the activity of PRX and catalin eye drop solutions. Turbidity was identified as the optical density measured using spectroscopy at 405 nm. We also determined the in vivo effects of catalin on cataract severity in a selenite-induced cataract rat model. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS–PAGE) was applied to analyze the integrity of crystallin samples. Results: PRX at 1,000 μM significantly delayed UVC-induced turbidity formation compared to controls after 4 h of UVC exposure (p<0.05), but not in groups incubated with PRX concentrations of <1,000 μM. Results were further confirmed by SDS–PAGE. The absolute γ-crystallin turbidity induced by 4 h of UVC exposure was ameliorated in the presence of catalin equivalent to 1~100 μM PRX in a concentration-dependent manner. Samples with catalin-formulated vehicle only (CataV) and those containing PRX equivalent to 100 μM had a similar protective effect after 4 h of UVC exposure compared to the controls (p<0.05). PRX at 0.03, 0.1, and 0.3 μM significantly delayed 10 mM selenite- and calcium-induced turbidity formation compared to controls on days 0~4 (p<0.05). Catalin (equivalent to 32, 80, and 100 μM PRX) had an initial protective effect against selenite-induced lens protein turbidity on day 1 (p<0.05). Subcutaneous pretreatment with catalin (5 mg/kg) also statistically decreased the mean cataract scores in selenite-induced cataract rats on post-induction day 3 compared to the controls (1.3±0.2 versus 2.4±0.4; p<0.05). However, catalin (equivalent to up to 100 μM PRX) did not inhibit calpain-induced proteolysis activated by calcium, and neither did 100 μM PRX. Conclusions: PRX at micromolar levels ameliorated selenite- and calcium-induced lens protein turbidity but required millimolar levels to protect against UVC irradiation. The observed inhibition of UVC-induced turbidity of lens crystallins by catalin at micromolar concentrations may have been a result of the catalin-formulated vehicle. Transient protection by catalin against selenite-induced turbidity of crystallin solutions in vitro was supported by the ameliorated cataract scores in the early stage of cataractogenesis in vivo by subcutaneously administered catalin. PRX could not inhibit calpain-induced proteolysis activated by calcium or catalin itself, and may be detrimental to crystallins under UVB exposure. Further studies on formulation modifications of catalin and recommended doses of PRX to optimize clinical efficacy by cataract type are warranted

Longer telomere length in peripheral white blood cells is associated with risk of lung cancer and the rs2736100 (CLPTM1L-TERT) polymorphism in a prospective cohort study among women in China.

A recent genome-wide association study of lung cancer among never-smoking females in Asia demonstrated that the rs2736100 polymorphism in the TERT-CLPTM1L locus on chromosome 5p15.33 was strongly and significantly associated with risk of adenocarcinoma of the lung. The telomerase gene TERT is a reverse transcriptase that is critical for telomere replication and stabilization by controlling telomere length. We previously found that longer telomere length measured in peripheral white blood cell DNA was associated with increased risk of lung cancer in a prospective cohort study of smoking males in Finland. To follow up on this finding, we carried out a nested case-control study of 215 female lung cancer cases and 215 female controls, 94% of whom were never-smokers, in the prospective Shanghai Women's Health Study cohort. There was a dose-response relationship between tertiles of telomere length and risk of lung cancer (odds ratio (OR), 95% confidence interval [CI]: 1.0, 1.4 [0.8-2.5], and 2.2 [1.2-4.0], respectively; P trend = 0.003). Further, the association was unchanged by the length of time from blood collection to case diagnosis. In addition, the rs2736100 G allele, which we previously have shown to be associated with risk of lung cancer in this cohort, was significantly associated with longer telomere length in these same study subjects (P trend = 0.030). Our findings suggest that individuals with longer telomere length in peripheral white blood cells may have an increased risk of lung cancer, but require replication in additional prospective cohorts and populations

A new measurement of antineutrino oscillation with the full detector configuration at Daya Bay

We report a new measurement of electron antineutrino disappearance using the fully-constructed Daya Bay Reactor Neutrino Experiment. The final two of eight antineutrino detectors were installed in the summer of 2012. Including the 404 days of data collected from October 2012 to November 2013 resulted in a total exposure of 6.9$\times$10$^5$ GW$_{\rm th}$-ton-days, a 3.6 times increase over our previous results. Improvements in energy calibration limited variations between detectors to 0.2%. Removal of six $^{241}$Am-$^{13}$C radioactive calibration sources reduced the background by a factor of two for the detectors in the experimental hall furthest from the reactors. Direct prediction of the antineutrino signal in the far detectors based on the measurements in the near detectors explicitly minimized the dependence of the measurement on models of reactor antineutrino emission. The uncertainties in our estimates of $\sin^{2}2\theta_{13}$ and $|\Delta m^2_{ee}|$ were halved as a result of these improvements. Analysis of the relative antineutrino rates and energy spectra between detectors gave $\sin^{2}2\theta_{13} = 0.084\pm0.005$ and $|\Delta m^{2}_{ee}|= (2.42\pm0.11) \times 10^{-3}$ eV$^2$ in the three-neutrino framework.Comment: Updated to match final published versio