1.Influence of Mining Pollution on Metal Bioaccumulation and Biomarker Responses in Cave Dwelling Fish, Clarias gariepinus.
du Preez G1, Wepener V2. Bull Environ Contam Toxicol. 2016 Apr 16. [Epub ahead of print]
Cave ecosystems remain largely unstudied and risk being severely degraded as a result of anthropogenic activities. The Wonderfontein Cave, situated in the extensive gold mining region of the Witwatersrand Basin, is one such system that hosts a population of Clarias gariepinus, which is exposed to the influx of polluted mine water from the Wonderfontein Spruit River. The aim of this study was to investigate the bioaccumulation of metals, as well as relevant biomarkers, in C. gariepinus specimens sampled from the Wonderfontein Cave during high (April 2013) and low (September 2013) flow surveys. Results were also compared to a surface population associated with the Wonderfontein Spruit River. There were temporal differences in metal bioaccumulation patterns and this was attributed to the lack of dilution during the low flow period. Metals associated with acid mine drainage, i.e. Co, Mn and Zn were significantly higher in the Wonderfontein Cave population and were reflected in an increase in oxidative stress biomarkers (catalase, protein carbonyls and superoxide dismutase) and the induction of metallothionein, a biomarker of metal exposure.
2.Crosstalk between liver antioxidant and the endocannabinoid systems after chronic administration of the FAAH inhibitor, URB597, to hypertensive rats.
Biernacki M1, Łuczaj W1, Gęgotek A1, Toczek M2, Bielawska K1, Skrzydlewska E3. Toxicol Appl Pharmacol. 2016 Apr 13. pii: S0041-008X(16)30076-X. doi: 10.1016/j.taap.2016.04.006. [Epub ahead of print]
Hypertension is accompanied by perturbations to the endocannabinoid and antioxidant systems. Thus, potential pharmacological treatments for hypertension should be examined as modulators of these two metabolic systems. The aim of this study was to evaluate the effects of chronic administration of the fatty acid amide hydrolase (FAAH) inhibitor [3-(3-carbamoylphenyl)phenyl]N-cyclohexylcarbamate (URB597) on the endocannabinoid system and on the redox balance in the livers of DOCA-salt hypertensive rats. Hypertension caused an increase in the levels of endocannabinoids [anandamide (AEA), 2-arachidonoyl-glycerol (2-AG) and N-arachidonoyl-dopamine (NADA)] and CB1 receptor and the activities of FAAH and monoacylglycerol lipase (MAGL). These effects were accompanied by an increase in the level of reactive oxygen species (ROS), a decrease in antioxidant activity/level, enhanced expression of transcription factor Nrf2 and changes to Nrf2 activators and inhibitors.
3.Clinical Drug-Drug Pharmacokinetic Interaction Potential of Sucralfate with Other Drugs: Review and Perspectives.
Sulochana SP1, Syed M2, Chandrasekar DV1, Mullangi R1, Srinivas NR3. Eur J Drug Metab Pharmacokinet. 2016 Apr 16. [Epub ahead of print]
Sucralfate, a complex of aluminium hydroxide with sulfated sucrose, forms a strong gastrointestinal tract (GIT) mucosal barrier with excellent anti-ulcer property. Because sucralfate does not undergo any significant oral absorption, sucralfate resides in the GIT for a considerable length of time. The unabsorbed sucralfate may alter the pharmacokinetics of the oral drugs by impeding its absorption and reducing the oral bioavailability. Because of the increased use of sucralfate, it was important to provide a reappraisal of the published clinical drug-drug interaction studies of sucralfate with scores of drugs. This review covers several category of drugs such as non-steroidal anti-inflammatory drugs, fluoroquinolones, histamine H2-receptor blockers, macrolides, anti-fungals, anti-diabetics, salicylic acid derivatives, steroidal anti-inflammatory drugs and provides pharmacokinetic data summary along with study design, objectives and key remarks.
4.Multivalent hyaluronic acid bioconjugates improve sFlt-1 activity in vitro.
Altiok EI1, Santiago-Ortiz JL2, Svedlund FL3, Zbinden A1, Jha AK1, Bhatnagar D1, Loskill P4, Jackson WM1, Schaffer DV5, Healy KE6. Biomaterials. 2016 Mar 12;93:95-105. doi: 10.1016/j.biomaterials.2016.03.017. [Epub ahead of print]
Anti-VEGF drugs that are used in conjunction with laser ablation to treat patients with diabetic retinopathy suffer from short half-lives in the vitreous of the eye resulting in the need for frequent intravitreal injections. To improve the intravitreal half-life of anti-VEGF drugs, such as the VEGF decoy receptor sFlt-1, we developed multivalent bioconjugates of sFlt-1 grafted to linear hyaluronic acid (HyA) chains termed mvsFlt. Using size exclusion chromatography with multiangle light scattering (SEC-MALS), SDS-PAGE, and dynamic light scattering (DLS), we characterized the mvsFlt with a focus on the molecular weight contribution of protein and HyA components to the overall bioconjugate size. We found that mvsFlt activity was independent of HyA conjugation using a sandwich ELISA and in vitro angiogenesis assays including cell survival, migration and tube formation. Using an in vitro model of the vitreous with crosslinked HyA gels, we demonstrated that larger mvsFlt bioconjugates showed slowed release and mobility in these hydrogels compared to low molecular weight mvsFlt and unconjugated sFlt-1.