Toxicology letters
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GAPDH, well known for its house-keeping functions, has also been shown to be involved in cell injury, apoptosis and death under conditions of stress such as starvation, chemical injury and oxidative stress. This study examines the effect of GAPDH knockdown on cell injury in response to Rotenone. ⋯ siRNA-mediated GAPDH knockdown reduced rotenone-induced H9C2 cell death occurring via autophagy and anti-oxidative stress pathway. This study enriches the understanding of GAPDH pathophysiology role, and provides potential new therapeutic targets for cardiac disease states characterized by oxidative stress.
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Postnatal isoflurane exposure leads to neurodegeneration and deficits of spatial learning and memory in the adulthood. However, the underlying mechanisms remain unclear. Ribosomal protein S6 is demonstrated to play a pivotal role in control of cell survival, protein synthesis and synaptogenesis for brain development. ⋯ S6 activation could reverse the damages above. These results indicate that S6 inhibition, led by suppression of upstream IGF-1/MEK/ERK and IGF-1/PI3K/Akt signaling pathways, is involved in the neuroapoptosis, synaptogenesis impairment and spatial learning and memory decline caused by postnatal isoflurane exposure. S6 activation may exhibit protective potential against developmental neurotoxicity of isoflurane.
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The method of choice for reversal of opioid-toxicity is administration of naloxone. This treatment can be accompanied by complications including acute lung-injury, myocardial infarction, or withdrawal-syndrome (in dependent-patients). We aimed to evaluate the efficacy of buprenorphine in reversal of opioid-overdose syndrome in dependent-rats. ⋯ Rats in the first group showed signs/symptoms of opioid-withdrawal severely and with a higher frequency (P<0.001). In the groups 2-4, all doses recovered the intoxicated-rats without inducing signs/symptoms of withdrawal; however, the 3mg/kg dose reversed toxicity slower (P<0.001) and one rat in this group died later due to the re-development of signs of toxicity. Buprenorphine recovers opioid-overdose in morphine-dependent rats and bypasses the withdrawal-syndrome due to administration of naloxone.
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The UK Health and Safety Executive has investigated several incidents of workplace accidents involving hydrogen sulphide exposure in recent years. Biological monitoring has been used in some incidents to determine the cause of unconsciousness resulting from these incidents and as a supporting evidence in regulatory enforcement. This paper reports on three case incidents and discusses the use of biological monitoring in such cases. ⋯ For routine occupational monitoring, post-shift samples should be adequate. Due to endogenous levels of urinary thiosulphate, it is likely that exposures in excess of 12 ppm for 30 min (or 360 ppm/min equivalent) would be detectable using biological monitoring. This is within the Acute Exposure Guideline Level 2 (the level of the chemical in air at or above which there may be irreversible or other serious long-lasting effects or impaired ability to escape) for hydrogen sulphide.
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This study aimed to correlate environmental sevoflurane levels with urinary concentrations of sevoflurane (Sev-U) or its metabolite hexafluoroisopropanol (HFIP) in order to assess and discuss the main issues relating to which biomarker of sevoflurane exposure is best, and possibly suggest the corresponding biological equivalent exposure limit values. Individual sevoflurane exposure was measured in 100 healthcare operators at five hospitals in north-east Italy using the passive air sampling device Radiello(®), and assaying Sev-U and HFIP concentrations in their urine collected at the end of the operating room session. All analyses were performed by gas chromatography-mass spectrometry. ⋯ Sev-U values seem to be influenced by peaks of exposure, especially at the end of the operating-room session, whereas HFIP levels by exposure on the previous day, the data being consistent with the biomarkers' very different half-lives (2.8 and 19 h, respectively). According to our results, both Sev-U and HFIP are appropriate biomarkers for assessing sevoflurane exposure at low levels, although with some differences in times/patterns of exposure. More work is needed to identify the best biomarker of sevoflurane exposure and the corresponding biological equivalent exposure limit values.