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Sorafenib (SR) is one of the most potent UGT (1A1, 1A9) inhibitors (in in vitro tests). The inhibition of UGT1A1 may cause hyperbilirubinaemia, whereas the inhibition of UGT1A9 and 1A1 may result in drug-drug interactions (DDIs). Tapentadol (TAP) is a synthetic μ-opioid agonist and is used to treat moderate to severe acute pain. Tapentadol is highly glucuronidated by the UGT1A9 and UGT2B7 isoenzymes. The aim of the study was to assess the DDI between SR and TAP. Wistar rats were divided into three groups, with eight animals in each. The rats were orally treated with SR (100 mg/kg) or TAP (4.64 mg/kg) or in combination with 100 mg/kg SOR and 4.64 TAP mg/kg. The concentrations of SR and sorafenib N-oxide, TAP and tapentadol glucuronide were respectively measured by means of high-performance liquid chromatography (HPLC) with ultraviolet detection and by means of ultra-performance liquid chromatography-tandem mass spectrometry. The co-administration of TAP with SR caused TAP maximum plasma concentration (Cmax) to increase 5.3-fold whereas its area under the plasma concentration-time curve (AUC0-∞) increased 1.5-fold. The tapentadol glucuronide Cmax increased 5.3-fold and whereas its AUC0-∞ increased 2.0-fold. The tapentadol glucuronide/TAP AUC0-∞ ratio increased 1.4-fold (p = 0.0118). TAP also increased SR Cmax 1.9-fold, whereas its AUC0-∞ increased 1.3-fold. The sorafenib N-oxide Cmax increased 1.9-fold whereas its AUC0-∞ increased 1.3-fold. The sorafenib N-oxide/SR AUC0-t ratio increased 1.4-fold (p = 0.0127). The results show that the co-administration of sorafenib and tapentadol increases the exposure to both drugs and changes their metabolism. In consequence, the pharmacological effect may be intensified, but the toxicity may increases, too.The multidrug resistance (MDR) which widely observed in multiple cancer types is responsible for the poor chemotherapy benefits of doxorubicin (Dox). Here in our study, Dox was firstly loaded into a scramble siRNA and then condensed by polyethyleneimine (PEI) 25k together with anti-autophagy siRNA, the obtained PEI/Si-D containing mirror RNAs was further coated with hyaluronic acid (HA) to shield the surface charge of PEI and offer tumor-homing property that finally developed a platform for effective cancer chemotherapy (HP/Si-D). Our results revealed that the obtained HP/Si-D was showed high stability and biocompatibility with promising transfection profile. As a result, the anti-autophagy siRNA downregulated autophagy level of target cells, which further decreased ATP supply to enhance drug retention and cell cycle arrest. These results contributed significantly to reverse the MDR of A549/Dox (Dox resistance A549 cell line) cells with promising in vitro and in vivo results, which suggested the potential of effective MDR cancer therapy using synergistic anti-autophagy and chemotherapy.To characterise the mass concentration, size-distribution, and respiratory deposition of selected trace metals (Cr, Mn, Fe, Ni, Cu, Zn, Ba, and Pb) in size-segregated PM2.5, a long-term monitoring campaign was undertaken at an urban background site in Como (Northern Italy). 96-h aerosol samples were collected weekly, from May 2015 to March 2016, using a 13-stage low pressure impactor and analysed via laser ablation-inductively coupled plasma-mass spectrometry. Irinotecan chemical structure Significantly higher levels of trace metals were generally found during the heating season (two to more than four times) compared to the non-heating period at all size ranges, especially for concentrations in PM0.1-1. Distinct distribution profiles characterised the different elements, even though the corresponding heating and non-heating shapes always exhibited similar features, with negligible seasonal shifts in the average mass median aerodynamic diameters. Fe, Ba, and Cu had >70% of their mass in PM1-2.5, whereas Pb, Zn, and Ni showed higher contrib less then 1.As top-predators in marine ecosystems, seabirds are regarded as appropriate bioindicator species for a variety of contaminants. Mercury (Hg) is a global pollutant, which can biomagnify along marine and freshwater food webs. Therefore, mercury body burden in seabirds, such as gulls, will integrate information about pollution in the environment. In the Ebro Delta (NE Spain), legacy mercury pollution from a chlor-alkali industry located ca. 100 km upstream of the Ebro river mouth has been affecting the delta environment. We have analyzed a 15-year temporal series (2004-2019) of Hg in birds from a breeding colony of Audouin's gull (Ichthyaetus audouinii) in the Ebro Delta to understand how fluctuations in Hg levels are coupled to human activities in the industrial area in the upstream region of the river. Stable isotopic signatures of C and N (δ13Cbulk and δ15Nbulk) are determined to characterize the trophic ecology of the species. Since only δ13Cbulk but not δ15Nbulk was associated with THg levels, we used compound-specific stable nitrogen isotope analysis of amino acids (AA-CSIA) to evaluate the causes of variation in δ15Nbulk to further investigate the idea of a decoupling of δ15Nbulk and THg over time. We found Audouin's gull to be sensitive to Hg variations in the environment due to anthropogenic changes and to be a good indicator species for this contaminant in the Ebro Delta.

Osteoporosis is associated with the risk of fractures near the hip. Age and comorbidities increase the perioperative risk. Due to the ageing population, fracture of the proximal femur also proves to be a socio-economic problem. Preventive surgical measures have hardly been used so far.

10 pairs of human femora from fresh cadavers were divided into control and low-volume femoroplasty groups and subjected to a Hayes fall-loading fracture test. The results of the respective localization and classification of the fracture site, the Singh index determined by computed tomography (CT) examination and the parameters in terms of fracture force, work to fracture and stiffness were evaluated statistically and with the finite element method. In addition, a finite element parametric study with different position angles and variants of the tubular geometry of the femoroplasty was performed.

Compared to the control group, the work to fracture could be increased by 33.2%. The fracture force increased by 19.9%. The used technique and instrumentation proved to be standardized and reproducible with an average poly(methyl methacrylate) volume of 10.