Poisoning by organophosphorus compounds (OP) is characterized by inhibition of the key enzyme acetylcholinesterase (AChE) and potentially fatal outcomes in humans. Insufficient efficacy of the standard therapy with atropine and AChE reactivators (oximes) against certain OP initiated synthesis of novel non-oxime reactivators basing on the common structure 4-amino-2-((diethylamino)methyl)phenol (ADOC). Recently, we reported of a pyrrolidine-bearing ADOC analogue (3 l) with a remarkable ability to reactivate OP-inhibited AChE. This in vitro study was undertaken to determine reactivity, affinity and overall reactivation constants of 3 l, the reference compound ADOC and two structural analogues with human AChE inhibited by paraoxon, sarin, cyclosarin and VX. The data showed a 10 to 34-fold reactivating potency of 3 l compared to ADOC mainly due to improved affinity. Additionally, various interactions between non-oximes, human or guinea pig (GP) AChE and structurally different OP were investigated: OP-inhibited guinea pig AChE was less amenable to reactivation by ADOC and 3 l than human AChE. Compound 3 l was considered as potential pretreatment to prevent AChE from irreversible inhibition by OP: In the presence of 10 μM 3 l inhibition of native human AChE was attenuated resulting in protective indices (PI) ranging from about 2.7 to 6.0. A combination of 3 l and the bispyridinium oxime HI-6 was tested to reactivate OP-inhibited AChE: The superior reactivator of the respective OP-AChE combination dominated the reactivation process and a synergistic effect could not be observed. In conclusion, novel non-oxime reactivators like 3 l may be considered as promising templates for the design of more potent therapeutics against poisoning by highly toxic OP.

Objective: To analyze the pre-hospital and in-hospital linkage effect on reducing the degree and reduce the complications of phenol burn. Methods: From January 2015 to July 2016, 51 patients with phenol burns in Shanghai Chemical Industry Park Medical Center were treated by in-hospital and in-hospital treatment. Gathering the general data, clinical situation, treatment methods and treatment results were compared with the previous literature on phenol burn treatment. Results: Among the 51 cases, 50 patients with burn area <5%, 1 patient with burn area 5%~0%, 51 patients were cured, and the cure rate was 100%, during the period under observation and all treated patients out of follow-up after under observation, there were no obvious abnormalities in blood and urine routine, did not appear damage of liver and renal function. Conclusion: Phenol can damage many important organs and tissues of the whole body, and it can affect the body and develop corresponding symptoms within a few minutes and hours. Therefore, it is very important to quickly and correctly respond to the injury caused by phenol. The treatment of pre-hospital and in-hospital linkage treatment method has obvious effect on reducing phenol injury and reducing the incidence of complications.

Objective: To explore the incidence and severity of hepatic adverse events (AEs) and identify factors associated with hepatic AEs in patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with tyrosine kinase inhibitors (TKIs). Methods: Liver biochemistry parameters [including ALT(alanine aminotransferase), AST(aspartate aminotransferase), ALP(alkaline phosphatase), and TBil(total bilirubin)] during the first 6 months on imatinib (Gleevec(®)), dasatinib (Sprycel(®)) or nilotinib (Tasigna(®)) in CML-CP patients were collected and analyzed retrospectively. Results: A total of 436 patients were enrolled in this study, including 271 with imatinib, 58 with dasatinib, and 107 with nilotinib. The incidences of any abnormality of liver injury were 21.8%(59/271), 15.5%(9/58) and 32.7%(35/107) in the imatinib, dasatinib and nilotinib groups, respectively. Most of the hepatic AEs were CTCAE grade 1 or 2 and mild or moderate liver injury except 1.9% of TBil CTCAE grade 3 in the nilotinib group. Multivariate analyses showed nilotinib [OR=2.9(1.3-6.6), P=0.012; OR=4.4(1.2-15.6), P=0.023] and male gender [OR=2.3(1.4-3.9), P=0.002; OR=3.0(1.2-7.6), P=0.018] were significantly associated with moderate liver impairment. Conclusions: TKIs including imatinib, dasatinib and nilotinib were well tolerated with mild to moderate hepatic AEs in CML-CP patients. Nilotinib and male sex were associated with occurrence of liver biochemistry abnormalities and moderate hepatic injury.

Hepatic macrophages are central players in the pathogenesis of some liver diseases, but few studies have examined the effect of triptolide (TP) on these cells. In this study, we investigated the possible role of hepatic macrophage recruitment and activation in triptolide-induced hepatotoxicity based on a non-hepatotoxic dose of lipopolysaccharides (LPS). The results showed that continuous administration of TP for two weeks and a single challenge of low-dose lipopolysaccharides increased the number of hepatic macrophages but inhibited their phagocytic function. TP induced the liver to recruit monocyte-derived macrophages (MoMFs) in response to a single challenge of low-dose LPS, resulting in acute inflammation and increased sensitivity to the endotoxin. Concurrent administration of TP with LPS resulted in obvious hepatotoxicity, but a single dose of LPS did not induce hepatotoxicity. These results indicate that TP could change the number and function of hepatic macrophages to reduce the ability of the liver to clear mild endotoxins, thus increasing blood endotoxin levels and increasing the sensitivity of the liver to low-dose LPS. By investigating the critical function of hepatic macrophages in TP-induced hepatotoxicity, this study elucidated the mechanism underlying TP-induced hepatotoxicity.

Because of their widespread use, and the mutagenicity and teratogenicity observed in in vitro studies, bisphenol-diglycidyl ethers (BDGEs) were suspected of posing health risks to humans, especially to infants. Quantifying exposure of BDGEs from breast milk is essential in assessing the potential health risks of these ubiquitous compounds to infants. However, there is no reported analytical method for the determination of BDGEs in breast milk. In this context, we developed a rapid and sensitive method based on ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to measure nine BDGEs in breast milk. The analytes were extracted with acetonitrile and fat was removed by freezing under -20 °C. The extracts were further purified by PRiME HLB solid-phase extraction (SPE) cartridge. The limits of detection (LODs) and quantification (LOQs) for the analytes were 0.033-0.500 and 0.100-1.500 μg L-1, respectively. The recoveries of BDGEs were ranged from 71.33% to 114.33%. Good method reproducibility regarding intra- and interday precision was observed, yielding relative standard deviations (RSDs) less than 11.81% and 10.83%, respectively. The proposed method was successfully applied to 20 breast milk samples. BADGE·2H2O, BADGE·HCl·H2O, BADGE·H2O, BADGE·HCl, BFDGE·2H2O, and BFDGE·2HCl were detected. BFDGE·2HCl was the dominant BDGE with detection rate of 65.0% and the concentration ranging from 0.4 to 1.0 μg L-1. This is the first report describing the occurrence of BDGEs in breast milk.

The biological properties and main phenolic compounds of the O. vulgare L. ssp. vulgare extract are described in the present paper. The polyphenolic compounds were analyzed by chromatographic and spectrophotometric techniques. The antioxidant potential was evaluated using several methods: CUPRAC (cupric ion reducing antioxidant capacity), FRAP (ferric reducing ability of plasma), inhibition of lipid peroxidation catalyzed by cytochrome c, and superoxide (SO) scavenging assays. The antimicrobial activity of the oregano extract was evaluated by means of agar-well diffusion assay. The hepatoprotective effect of the O. vulgare extract on CCl₄-induced hepatotoxicity was evaluated in rats. Liver injury was estimated by determination of alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), gamma-glutamyl transferase GGT, total protein and albumin concentrations, glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA). These values were improved by the administration of oregano extract. A specific phenolic profile was evidenced by these data, with large amounts of rosmarinic and chlorogenic acids. The oregano extract showed very strong antioxidant activity in good agreement with the phenolic content. Antimicrobial activity was good, especially against Salmonella enteritidis and Aspergillus niger strains. The high hepatoprotective, antioxidant and antimicrobial activity, along with polyphenol-rich content, can support the use of O. vulgare in therapy. We also expect our results to open new research directions for designing important new drug products, using indigenous plant material.