The Role of CO2-EOR for the Development of a CCTS Infrastructure in the North Sea Region: A Techno-Economic Model and Application

Scenarios of future energy systems attribute an important role to Carbon Capture, Transport, and Storage (CCTS) in achieving emission reductions. Using captured CO2 for enhanced oil recovery (CO2-EOR) can improve the economics of the technology. This paper examines the potential for CO2-EOR in the North Sea region. UK oil fields are found to account for 47% of the estimated additional recovery potential of 3739 Mbbl (1234 MtCO2 of storage potential). Danish and Norwegian fields add 28% and 25%, respectively. Based on a comprehensive dataset, the paper develops a unique techno-economic market equilibrium model of CO2 supply from emission sources and CO2 demand from CO2-EOR to assess implications for a future CCTS infrastructure. A detailed representation of decreasing demand for fresh CO2 for CO2-EOR operation is accomplished via an exponential storage cost function. In all scenarios of varying CO2 and crude oil price paths the assumed CO2-EOR potential is fully exploited. CO2-EOR does add value to CCTS operations but the potential is very limited and does not automatically induce long term CCTS activity. If CO2 prices stay low, little further use of CCTS can be expected after 2035

Heterogeneous transport of digitalis-like compounds by P-glycoprotein in vesicular and cellular assays

Digitalis-like compounds (DLCs), the ancient medication of heart failure and Na,K-ATPase inhibitors, are characterized by their toxicity. Drug-drug interactions (DDIs) at absorption and excretion levels play a key role in their toxicity, hence, knowledge about the transporters involved might prevent these unwanted interactions. In the present study, the transport of fourteen DLCs with human P-glycoprotein (P-gp; ABCB1) was studied using a liquid chromatography-mass spectrometry (LC-MS) quantification method. DLC transport by P-gp overexpressing Madin-Darby canine kidney (MDCK) and immortalized human renal cells (ciPTEC) was compared to vesicular DLC transport. Previously, we identified convallatoxin as a substrate using membrane vesicles overexpressing P-gp; however, we could not measure transport of other DLCs in this assay (Gozalpour et al., 2014a). Here, we showed that lipophilic digitoxin, digoxigenin, strophanthidin and proscillaridin A are P-gp substrates in cellular accumulation assays, whereas the less lipophilic convallatoxin was not. P-gp function in the cellular accumulation assays depends on the entrance of lipophilic compounds by passive diffusion, whereas the vesicular transport assay is more appropriate for hydrophilic substrates. In conclusion, we identified digitoxin, digoxigenin, strophanthidin and proscillaridin A as P-gp substrates using cellular accumulation assays and recognized lipophilicity as an important factor in selecting a suitable transport assay

Interaction of digitalis-like compounds with p-glycoprotein

Contains fulltext : 111359.pdf (publisher's version ) (Closed access)Digitalis-like compounds (DLCs), or cardiac glycosides, are produced and sequestered by certain plants and animals as a protective mechanism against herbivores or predators. Currently, the DLCs digoxin and digitoxin are used in the treatment of cardiac congestion and some types of cardiac arrhythmia, despite a very narrow therapeutic index. P-glycoprotein (P-gp; ABCB1) is the only known ATP-dependent efflux transporter that handles digoxin as a substrate. Ten alanine mutants of human P-gp drug-binding amino acids-Leu(65), Ile(306), Phe(336), Ile(340), Phe(343), Phe(728), Phe(942), Thr(945), Leu(975), and Val(982)-were generated and expressed in HEK293 cells with a mammalian baculovirus system. The uptake of [(3)H]-N-methyl-quinidine (NMQ), the P-gp substrate in vesicular transport assays, was determined. The mutations I306A, F343A, F728A, T945A, and L975A abolished NMQ transport activity of P-gp. For the other mutants, the apparent affinities for six DLCs (cymarin, digitoxin, digoxin, peruvoside, proscillaridin A, and strophanthidol) were determined. The affinities of digoxin, proscillaridin A, peruvoside, and cymarin for mutants F336A and I340A were decreased two- to fourfold compared with wild type, whereas that of digitoxin and strophanthidol did not change. In addition, the presence of a hydroxyl group at position 12beta seems to reduce the apparent affinity when the side chain of Phe(336) and Phe(942) is absent. Our results showed that a delta-lactone ring and a sugar moiety at 3beta of the steroid body are favorable for DLC binding to P-gp. Moreover, DLC inhibition is increased by hydroxyl groups at positions 5beta and 19, whereas inhibition is decreased by those at positions 1beta, 11alpha, 12beta, and 16beta. The understanding of the P-gp-DLC interaction improves our insight into DLCs toxicity and might enhance the replacement of digoxin with other DLCs that have less adverse drug effects

Interaction of Digitalis-Like Compounds with Liver Uptake Transporters NTCP, OATP1B1, and OATP1B3

Contains fulltext : 138326.pdf (publisher's version ) (Closed access)Digitalis-like compounds (DLCs) such as digoxin, digitoxin, and ouabain, also known as cardiac glycosides, are among the oldest pharmacological treatments for heart failure. The compounds have a narrow therapeutic window, while at the same time, DLC pharmacokinetics is prone to drug-drug interactions at the transport level. Hepatic transporters organic anion transporting polypeptide (OATP) 1B1, OATP1B3, and Na(+)-dependent taurocholate co-transporting polypeptide (NTCP) influence the disposition of a variety of drugs by mediating their uptake from blood into hepatocytes. The interaction of digoxin, digitoxin, and ouabain with hepatic uptake transporters has been studied before. However, here, we systematically investigated a much wider range of structurally related DLCs for their capability to inhibit or to be transported by these transporters in order to better understand the relation between the activity and chemical structure of this compound type. We studied the uptake and inhibitory potency of a series of 14 structurally related DLCs in Chinese hamster ovary cells expressing NTCP (CHO-NTCP) and human embryonic kidney cells expressing OATP1B1 and OATP1B3 (HEK-OATP1B1 and HEK-OATP1B3). The inhibitory effect of the DLCs was measured against taurocholic acid (TCA) uptake in CHO-NTCP cells and against uptake of beta-estradiol 17-beta-d-glucuronide (E217betaG) in HEK-OATP1B1 and HEK-OATP1B3 cells. Proscillaridin A was the most effective inhibitor of NTCP-mediated TCA transport (IC50 = 22 muM), whereas digitoxin and digitoxigenin were the most potent inhibitors of OATP1B1 and OAPTP1B3, with IC50 values of 14.2 and 36 muM, respectively. Additionally, we found that the sugar moiety and hydroxyl groups of the DLCs play different roles in their interaction with NTCP, OATP1B1, and OATP1B3. The sugar moiety decreases the inhibition of NTCP and OATP1B3 transport activity, whereas it enhances the inhibitory potency against OATP1B1. Moreover, the hydroxyl group at position 12 reinforces the inhibition of NTCP but decreases the inhibition of OATP1B1 and OATP1B3. To investigate whether DLCs can be translocated, we quantified their uptake in transporter-expressing cells by LC-MS. We demonstrated that convallatoxin, ouabain, dihydroouabain, and ouabagenin are substrates of OATP1B3. No transport was observed for the other compounds in any of the studied transporters. In summary, this work provides a step toward an improved understanding of the interaction of DLCs with three major hepatic uptake transporters. Ultimately, this can be of use in the development of DLCs that are less prone to transporter-mediated drug-drug interactions

Apolipoprotein E polymorphisms status in Iranian patients with multiple sclerosis.

Item does not contain fulltextBACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system. Evidences linking apolipoprotein E (APOE) to myelin repair, neuronal plasticity, and cerebral inflammatory processes suggest that it may be relevant in MS. The main goal of this study was to determine whether the APOE genotypes and alleles are associated with MS patients. MATERIALS AND METHODS: In total, 147 MS cases and 168 control subjects from Iranian population were genotyped for APOE gene using PCR-RFLP method. RESULTS: The frequency of APOE-epsilon2epsilon3 genotype was significantly higher in controls than cases (14.3% vs. 6.1%, P=0.009, OR=0.39) whereas APOE-epsilon3epsilon4 genotype frequency was significantly higher in cases compared with controls (8.2% vs. 3.6%, P=0.03, OR=2.4). APOE-epsilon2 allele frequency in cases was significantly lower than that of controls (4.4% vs. 8.0%, P=0.03, OR=0.52). Also male controls were significantly more likely to have APOE-epsilon2 allele (7.8% vs. 1%, P=0.01, OR=0.11). APOE-epsilon4 allele frequency in cases was significantly higher than control group (4.8% versus 2.1%, P=0.03, OR=2.35). CONCLUSION: It seems that individuals carrying APOE-epsilon4 allele and/or APOE-epsilon3epsilon4 genotype develop MS two times more than non-carriers. Also APOE-epsilon2epsilon3 genotype or APOE-epsilon2 allele may have a protective role against MS development in Iranian population. Further investigation would be warranted to understand the role of APOE alleles and genotypes and risk of MS