PubMed · 889208
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A R Nissenson. 1977. Plasticizer effect on heart.. https://doi.org/10.7326/0003-4819-87-2-245_2
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This study aims to investigate the toxicity of di(2-ethylhexyl) phthalate (DEHP) and the potential molecular mechanisms of DEHP-induced bladder cancer (BLCA) using network toxicology and molecular docking strategies. The toxicity of DEHP was assessed using Prox-II software, and potential targets for DEHP-induced BLCA were identified by integrating data from ChEMBL database, Search Tool for Interactions of Chemicals, SwissTargetPrediction, GeneCards, Therapeutic Target Database, Online Mendelian Inheritance in Man, and The Cancer Genome Atlas. STRING database and Cytoscape were employed to construct target networks and determine core targets. The expression levels of core targets were analyzed using R. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on potential and core targets. Molecular docking was carried out using CB-Dock 2 to verify the interactions between DEHP and core targets. A total of 105 potential targets related to DEHP-induced BLCA were identified, from which 7 core targets were selected: cyclin-dependent kinase 1, interleukin 6, cyclin-dependent kinase 2, cyclin B1, Erb-B2 receptor tyrosine kinase 2, cyclin B2, and B-cell lymphoma 2. IL-6 and B-cell lymphoma 2 showed downregulated expression in tumor tissues, while cyclin-dependent kinase 1, cyclin-dependent kinase 2, cyclin B1, Erb-B2 receptor tyrosine kinase 2, and cyclin B2 were upregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that these targets were enriched in cell signaling and cancer-related pathways. Molecular docking confirmed that DEHP interacts with these core targets. DEHP may promote the development of BLCA by interacting with key proteins and signaling pathways. This study provides a theoretical basis for understanding the molecular mechanisms of DEHP-induced BLCA and offers references for future prevention and treatment strategies.
The stability of morphine hydrochloride in an admixture with sodium chloride 0.9% injection in a portable pump reservoir was investigated. Duplicate samples containing morphine hydrochloride 0.5, 1.5 and 2.5 mg/ml were stored in original 100 ml plastic drug reservoirs at 32 degrees C for 60 days. An amount of 3 ml was removed immediately after preparation and at fixed intervals in the weeks after. All samples were tested for loss of vehicle, for appearance of precipitation and for change in colour or pH. Furthermore, they were analysed for drug concentration using high pressure liquid chromatography. No precipitation or change in colour was observed in any of the sample admixtures. There was no change in the pH values of any of the morphine hydrochloride concentrations from day 4 and later on. Only between day 1 and day 4 a slight, but not significant rise could be detected. There was no loss of morphine hydrochloride of any importance at any concentration in the samples over 60 days when corrected for loss of vehicle. Loss of vehicle (0.8 +/- 0.1 ml a week), on the other hand, gave a rise in morphine hydrochloride concentration.
Particle spallation and plasticiser (DEHP) release from medical grade polyvinylchloride (PVC), co-extruded PVC-polyurethane (PIVIPOL)R and an experimentally produced co-extruded PVC-ethylene vinyl acetate (EVA) has been studied when used with manually occluded and self-occluding peristaltic pumps over a six hour pumping period. The shore hardness of the tubings studied were similar but the luminal coating thickness differed (0.2 mm polyurethane, 0.99 mm EVA). The pattern of particle release was similar for all materials on the pump type used with the majority of particles released being less than 5 microns in diameter. The number of particles greater than 5 microns released was independent of the tubing material but depended on the pump type. Particle release with self-occluding pumps was significantly higher (p less than 0.001) than for the manually occluded pump. Scanning electron microscopy indicated that the particles released originate from the repeated compression and flexing of the insert during pumping which leads to material structural failure. The higher release observed in the case of self-occluding pumps is suggestive of over-occlusion by the springs utilised in the pump. DEHP release (ppm) over a six hour period while perfused at 300 ml/min was significantly reduced for co-extruded tubing (0.56 +/- 0.05 mg (PVC-polyurethane) and 0.12 +/- 0.04 mg (PVC-EVA) compared with PVC (0.74 +/- 0.05 mg).