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  • 1
    In: Epilepsia, July 2013, Vol.54(7), pp.1154-1160
    Description: Byline: Chunbo Zhang, Hugues Chanteux, Zhong Zuo, Patrick Kwan, Larry Baum Keywords: Lacosamide; P-glycoprotein; Transport Summary Purpose Antiepileptic drugs (AEDs) do not effectively treat 30-40% of patients with epilepsy. Export of AEDs by P-glycoprotein (Pgp, ABCB1, or MDR1), which is overexpressed in the blood-brain barrier in drug-resistant patients, may be a mechanism for resistance to AEDs. For most recently approved AEDs, whether they are transported by Pgp is unknown. We investigated whether a new AED, lacosamide (LCM), is a substrate of human Pgp. Methods LLC-PK1 and MDCKII cells transfected with the human MDR1 gene were used to determine the substrate status of LCM in concentration equilibrium transport assays (CETAs). An equal concentration of drug was initially loaded in both the apical and basal chambers, and the concentration in both chambers was measured up to 4 h. The experiments were repeated in the presence of the Pgp inhibitors verapamil and tariquidar. Caco-2 assays were used to determine the intrinsic permeability and efflux ratio of LCM as well as its potential to inhibit digoxin, a Pgp substrate. Key Findings Lacosamide was transported by MDR1-transfected cells from basolateral to apical sides. The efflux of LCM could be completely blocked by verapamil or tariquidar. In Caco-2 assays, LCM showed high permeability without a significant efflux ratio; it did not inhibit digoxin, a Pgp substrate. Significance Although LCM is a substrate of Pgp in CETA, Caco-2 data demonstrated that passive diffusion should play a major role in the overall disposition of LCM. The critical role of Pgp should be addressed in vivo. Author Affiliation:
    Subject(s): Acosamide ; ‐Glycoprotein ; Ransport
    ISSN: 0013-9580
    E-ISSN: 1528-1167
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  • 2
    In: Epilepsia, October 2011, Vol.52(10), pp.1894-1904
    Description: Antiepileptic drugs (AEDs) are widely used not only in the treatment of epilepsy but also as treatments for psychiatric disorders. Pharmacoresistance of AEDs in the treatment of epilepsy and psychiatric disorders is a serious problem. Transport of antiepileptic drugs by P‐glycoprotein (Pgp, ABCB1, or MDR1), which is overexpressed in the blood–brain barrier, may be a mechanism for resistance of AEDs. For most AEDs, conflicting evidence precludes consensus on whether they are substrates of Pgp. The objective of this study was to evaluate whether analogs and metabolites of the AED carbamazepine are substrates of human Pgp. Polarized cell lines MDCKII and LLC transfected with the human gene were used in the bidirectional transport assay and concentration equilibrium transport assay. The expression of Pgp was detected by real‐time polymerase chain reaction (PCR) and immunofluorescent staining. Rhodamine‐123 uptake was also determined. Pgp did not transport carbamazepine, but it did transport its active metabolite carbamazepine‐10,11‐epoxide. Pgp also pumped eslicarbazepine acetate and oxcarbazepine, as well as their active metabolite (S)‐licarbazepine. Transport of the drugs was in the order of ESL〉OXC〉S‐LC〉CBZ‐E in concentration equilibrium conditions. The transport of these drugs was blocked by Pgp inhibitors tariquidar and verapamil. All carbamazepine analogs or metabolites tested are Pgp substrates, except for carbamazepine. These data suggest that resistance to carbamazepine, oxcarbazepine, or eslicarbazepine acetate may be attributed to increased efflux function of Pgp because they or their active metabolites are Pgp substrates.
    Subject(s): Antiepileptic Drugs Aeds ; P‐Glycoprotein Pgp ; Blood–Brain Barrier ; Carbamazepine Analog ; Metabolites
    ISSN: 0013-9580
    E-ISSN: 1528-1167
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  • 3
    Language: English
    In: Life sciences (1973), 2010, Vol.86(23), pp.899-905
    Description: One possible mechanism for epilepsy drug resistance is overexpression of P-glycoprotein in the blood–brain barrier, but whether (or which) antiepileptic drugs (AEDs) are transported by P-gp remains unclear. We evaluated AEDs as P-gp substrates using cell monolayers. Bi-directional transport assays and concentration equilibrium transport assays (CETAs) were performed for phenytoin (PHT), phenobarbital (PB), and ethosuximide (ESM) using wildtype Madin–Darby Canine Kidney II cell line MDCKII and porcine renal endothelial cell line LLC–PK1 cells and these cells transfected with human MDR1 cDNA to express P-gp. Wildtype cells demonstrated no efflux transport of PHT, PB, or ESM. In CETAs, both MDR1-transfected cell lines transported PHT from basolateral to apical when PHT loading concentrations were 5 or 10, but not 20 µg/ml. MDCK–MDR1 cells transported PB when initial concentrations were 10 or 20, but not 5 µg/ml. LLC–MDR1 did not transport...
    Subject(s): P-Glycoprotein ; Blood–Brain Barrier ; Drug Transport ; Phenytoin ; Phenobarbital ; Ethosuximide ; Antiepileptic Drugs ; P-Glycoprotein ; Blood–Brain Barrier ; Drug Transport ; Phenytoin ; Phenobarbital ; Ethosuximide ; Antiepileptic Drugs ; Sciences (General) ; Biology
    ISSN: 0024-3205
    E-ISSN: 1879-0631
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  • 4
    Language: English
    In: PloS one, 01 January 2018, Vol.13(12), p.e0207687
    Description: Governments in high income countries allocate funding for Official Development Assistance (ODA), and population-based surveys tend to show support for the concept of affluent nations assisting the development of poorer regions. A public opinion survey was conducted in Hong Kong to: (1) assess public support for foreign aid for social development and Hong Kong's current Disaster Relief Fund (DRF); and (2) assess how much respondents thought should be contributed to foreign aid for social development and/or DRF. Interviewers conducted a random telephone survey of Cantonese-speaking Hong Kong citizens aged 18 or above during 2017. Of the 1004 individuals surveyed, 55% (552) agreed that a portion of the government budget should be allocated to the DRF and 37% (372) disagreed. The mean and the median amount of the government budget suggested to be allocated were 5.1% and 2.4% respectively. However only 16% (164) supported the government giving foreign aid for social development, with...
    Subject(s): Sciences (General)
    E-ISSN: 1932-6203
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  • 5
    Language: English
    In: Alzheimer's & dementia, July 2013, Vol.9(4), pp.P8-P8
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jalz.2013.04.027 Byline: Kwok Kin Cheng, Larry Baum Author Affiliation: The Chinese University of Hong Kong, Hong Kong, Hong Kong Article Note: (miscellaneous) IC-O3-02
    Subject(s): Alzheimer'S Disease – Diagnosis;
    ISSN: 1552-5260
    E-ISSN: 1552-5279
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  • 6
    In: Epilepsia, September 2010, Vol.51(9), pp.1878-1881
    Description: A recent study in Caucasians found an association between the single nucleotide polymorphism (SNP) of , IVS5N +5 G〉A (rs3812718), and febrile seizures (FS). We examined whether this and other tagging SNPs of were associated with an increased risk of FS in Han Chinese. A total of 728 Han Chinese patients with focal epilepsy were recruited: 97 had a history of FS (58% male, mean age 35 ± 12 years) and 631 did not (50% male, mean age 40 ± 15 years). Genotyping was performed for IVS5N +5 G〉A and seven other tagging SNPs selected from the HapMap database. Genotyping was also performed in 848 ethnically matched population controls (50% male, mean age 37 ± 17 years). There was no statistically significant difference in either allele or genotype frequency of any of the SNPs studied between epilepsy patients with and without FS, and between epilepsy patients with FS and controls. The results do not suggest that SNPs are susceptibility factors for FS in Han Chinese.
    Subject(s): Febrile Seizures ; Scn1a ; Epilepsy ; Chinese
    ISSN: 0013-9580
    E-ISSN: 1528-1167
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  • 7
    In: Journal of Gastroenterology and Hepatology, October 2011, Vol.26(10), pp.1475-1484
    Description: Recent genome‐wide association studies of colorectal cancer (CRC) have identified rs6983267 and trs10505477 polymorphisms as key loci in the 8q24 region to be associated with CRC. In the present study, we performed a meta‐analysis to determine whether these loci are risk factors for susceptibility to CRC. We meta‐analyzed the 22 included studies (47 003 cases and 45 754 controls) that evaluated the association of rs6983267 and trs10505477 with CRC under alternative genetic models. A meta‐analysis of the pooled data showed allelic and genotypic association of the rs6983267 polymorphism with CRC risk in Asians, Europeans, and European‐Americans. A subanalysis of the US studies showed negative results in the studies with non‐identified ethnicity of the patients. A meta‐analysis of included studies of rs10505477 polymorphisms identified allelic and genotypic associations with CRC risk in the US patients. A further meta‐analysis of the US studies demonstrated positive results in the studies with non‐identified ethnicity of the samples. Our data suggested that the rs6983267 G 〉 T polymorphism is a risk factor for CRC in Asians, Europeans, and Americans with European ancestry.
    Subject(s): 8q24 ; Colorectal Cancer ; Meta‐Analysis ; Polymorphism ; Susceptibility
    ISSN: 0815-9319
    E-ISSN: 1440-1746
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  • 8
    Article
    Article
    2005
    ISSN: 1079-5006 
    Language: English
    In: The journals of gerontology. Series A, Biological sciences and medical sciences, June 2005, Vol.60(6), pp.736-43
    Description: More women than men have Alzheimer's disease (AD). Retrospective studies suggested that hormone replacement therapy (HRT) might counteract this disparity by reducing the risk of developing dementia. However, a recent, large, prospective study revealed the puzzling result that HRT increased dementia risk. A review of the literature was conducted to generate hypotheses that might explain why more women than men have AD, and how HRT may increase dementia risk. Longer life span of women than men may be the largest factor in the preponderance of women with AD. Longer duration of disease, less vascular dementia, and less testosterone in women than men may also contribute somewhat. HRT might increase dementia risk by several mechanisms: greater risk of strokes, leading to dementia; use of medroxyprogesterone acetate and estrone, which might have somewhat different possible effects on neuronal and cerebrovascular function than may progesterone and estradiol; decrease of free testosterone which...
    Subject(s): Alzheimer Disease -- Etiology ; Gonadal Steroid Hormones -- Physiology ; Hormone Replacement Therapy -- Adverse Effects
    ISSN: 1079-5006
    E-ISSN: 1758535X
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  • 9
    Language: English
    In: PloS one, 01 January 2016, Vol.11(12), p.e0165474
    Description: To evaluate visual outcomes and complications after phacoemulsification in eyes with cataract and previous radial keratotomy (RK) cuts using different sizes of clear corneal incisions.The study was a retrospective study. Thirty eyes with cataract and previous RK underwent phacoemulsification and intraocular lens (IOL) implantation. Among them 7 eyes had 8 RK cuts, 13 eyes had 12 RK cuts, and 10 eyes had 16 RK cuts. Phacoemulsification and IOL implantation were performed through a 2.0-3.2 mm clear corneal incision by a single surgeon. In the 8 RK cuts group, 3.2 mm clear corneal incisions were used in 4 eyes, and 3.0 mm clear corneal incisions were used in 3 eyes. In the 12 RK cuts group, 3.2 mm clear corneal incisions were used in 6 eyes, and 2.2 mm clear corneal incisions were used in 7 eyes. In the 16 RK cuts group, 3.2 mm clear corneal incisions were used in 5 eyes, and 2.0 mm clear corneal incisions were used in 5 eyes. Patients were followed up 1 day, 1 week, 1 month, 3 months,...
    Subject(s): Sciences (General)
    E-ISSN: 1932-6203
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  • 10
    Language: English
    In: Pharmacogenomics, March 2011, Vol.12(3), pp.319-25
    Description: To determine the association between polymorphisms of the multidrug transporter genes ABCC2, ABCC5 and ABCG2, and drug resistance in epilepsy by genotyping comprehensive sets of tagging SNPs. A total of 25 tagging SNPs from ABCC2, ABCC5 and ABCG2 genes were genotyped in a total of 590 Han Chinese epilepsy patients (262 drug resistant and 328 drug responsive). Genotype and allele distributions in drug-responsive and drug-resistant patients were compared. Genotype distributions of all the selected SNPs were consistent with Hardy-Weinberg equilibrium. None of the polymorphisms, either genotype or allele distributions, were significantly associated with drug resistance. For each gene, no haplotypes of over 1% frequency, and that included all SNPs of the gene, were associated with drug resistance. This gene-wide tagging study revealed no association between ABCC2, ABCC5 and ABCG2 genetic polymorphisms and multidrug resistance in epilepsy.
    Subject(s): ATP-Binding Cassette Transporters -- Genetics ; Drug Resistance, Multiple -- Genetics ; Epilepsy -- Drug Therapy ; Multidrug Resistance-Associated Proteins -- Genetics ; Neoplasm Proteins -- Genetics
    ISSN: 14622416
    E-ISSN: 1744-8042
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