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Profiles of multidrug resistance protein-1 in the peripheral blood mononuclear cells of patients with refractory epilepsy.

Ban JJ, Jung KH, Chu K, Lee ST, Jeon D, Park KI, Moon HJ, Kim H, Kim S, Lee SK, Roh JK - PLoS ONE (2012)

Bottom Line: The MDR1 conformational change level was significantly higher in the high-medication-use group than the low-use group (p = 0.028).Basal MDR1 (OR = 1.16 [95% CI: 1.060-1.268]) and conformational change level (OR = 1.11 [95% CI: 1.02-1.20]) were independent predictors for seizure frequency and number of medications, respectively.The MDR1 profile of PBMNCs is associated with seizure frequency and medication conditions in patients with epilepsy.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Seoul National University Hospital, Seoul, South Korea.

ABSTRACT

Background: About one third of patients with epilepsy become refractory to therapy despite receiving adequate medical treatment, possibly from multidrug resistance. P-glycoprotein, encoded by multidrug resistance protein-1 (MDR1) gene, at the blood brain barrier is considered as a major factor mediating drug efflux and contributing to resistance. Given that peripheral blood mononuclear cells (PBMNCs) express MDR1, we investigated a MDR1 status of PBMNCs in various subsets of epilepsy patients and demonstrated their association with clinical characteristics.

Methodology/principal findings: Clinical and MDR1 data were collected from 140 patients with epilepsy, 30 healthy volunteers, and 20 control patients taking anti-epileptic drugs. PBMNCs were isolated, and basal MDR1 levels and MDR1 conformational change levels were measured by flow cytometry. MDR1 profiles were analyzed according to various clinical parameters, including seizure frequency and number of medications used in epilepsy patients. Epilepsy patients had a higher basal MDR1 level than non-epilepsy groups (p<0.01). Among epilepsy patients, there is a tendency for higher seizure frequency group to have higher basal MDR1 level (p = 0.059). The MDR1 conformational change level was significantly higher in the high-medication-use group than the low-use group (p = 0.028). Basal MDR1 (OR = 1.16 [95% CI: 1.060-1.268]) and conformational change level (OR = 1.11 [95% CI: 1.02-1.20]) were independent predictors for seizure frequency and number of medications, respectively.

Conclusions/significance: The MDR1 profile of PBMNCs is associated with seizure frequency and medication conditions in patients with epilepsy.

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Related in: MedlinePlus

MDR1 profiles among groups and refractory epilepsy patients.Graphs represent (A) basal MDR1 level and (B) conformational change level among the groups. Graphs represent (C) basal MDR1 level between low- and high-seizure-frequency groups and (D) conformational change level between low- and high-medication-use groups in the refractory epilepsy patients. The horizontal lines represent the median level and standard error of the mean.
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pone-0036985-g002: MDR1 profiles among groups and refractory epilepsy patients.Graphs represent (A) basal MDR1 level and (B) conformational change level among the groups. Graphs represent (C) basal MDR1 level between low- and high-seizure-frequency groups and (D) conformational change level between low- and high-medication-use groups in the refractory epilepsy patients. The horizontal lines represent the median level and standard error of the mean.

Mentions: The basal MDR1 and conformational change level of MDR1 in the PBMNCs were analyzed using flow cytometry. Representative superimposed histograms of basal MDR1 level and conformational change level are presented (Fig. 1D). Kruskal-Wallis test confirmed significant differences in the basal MDR1 levels among groups (p<0.01). Patients with epilepsy had higher basal MDR1 levels than the healthy volunteers and control patients taking AEDs (p<0.01; Fig. 2A). The conformational change level was not significantly different among groups (Fig. 2B).


Profiles of multidrug resistance protein-1 in the peripheral blood mononuclear cells of patients with refractory epilepsy.

Ban JJ, Jung KH, Chu K, Lee ST, Jeon D, Park KI, Moon HJ, Kim H, Kim S, Lee SK, Roh JK - PLoS ONE (2012)

MDR1 profiles among groups and refractory epilepsy patients.Graphs represent (A) basal MDR1 level and (B) conformational change level among the groups. Graphs represent (C) basal MDR1 level between low- and high-seizure-frequency groups and (D) conformational change level between low- and high-medication-use groups in the refractory epilepsy patients. The horizontal lines represent the median level and standard error of the mean.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3351424&req=5

pone-0036985-g002: MDR1 profiles among groups and refractory epilepsy patients.Graphs represent (A) basal MDR1 level and (B) conformational change level among the groups. Graphs represent (C) basal MDR1 level between low- and high-seizure-frequency groups and (D) conformational change level between low- and high-medication-use groups in the refractory epilepsy patients. The horizontal lines represent the median level and standard error of the mean.
Mentions: The basal MDR1 and conformational change level of MDR1 in the PBMNCs were analyzed using flow cytometry. Representative superimposed histograms of basal MDR1 level and conformational change level are presented (Fig. 1D). Kruskal-Wallis test confirmed significant differences in the basal MDR1 levels among groups (p<0.01). Patients with epilepsy had higher basal MDR1 levels than the healthy volunteers and control patients taking AEDs (p<0.01; Fig. 2A). The conformational change level was not significantly different among groups (Fig. 2B).

Bottom Line: The MDR1 conformational change level was significantly higher in the high-medication-use group than the low-use group (p = 0.028).Basal MDR1 (OR = 1.16 [95% CI: 1.060-1.268]) and conformational change level (OR = 1.11 [95% CI: 1.02-1.20]) were independent predictors for seizure frequency and number of medications, respectively.The MDR1 profile of PBMNCs is associated with seizure frequency and medication conditions in patients with epilepsy.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Seoul National University Hospital, Seoul, South Korea.

ABSTRACT

Background: About one third of patients with epilepsy become refractory to therapy despite receiving adequate medical treatment, possibly from multidrug resistance. P-glycoprotein, encoded by multidrug resistance protein-1 (MDR1) gene, at the blood brain barrier is considered as a major factor mediating drug efflux and contributing to resistance. Given that peripheral blood mononuclear cells (PBMNCs) express MDR1, we investigated a MDR1 status of PBMNCs in various subsets of epilepsy patients and demonstrated their association with clinical characteristics.

Methodology/principal findings: Clinical and MDR1 data were collected from 140 patients with epilepsy, 30 healthy volunteers, and 20 control patients taking anti-epileptic drugs. PBMNCs were isolated, and basal MDR1 levels and MDR1 conformational change levels were measured by flow cytometry. MDR1 profiles were analyzed according to various clinical parameters, including seizure frequency and number of medications used in epilepsy patients. Epilepsy patients had a higher basal MDR1 level than non-epilepsy groups (p<0.01). Among epilepsy patients, there is a tendency for higher seizure frequency group to have higher basal MDR1 level (p = 0.059). The MDR1 conformational change level was significantly higher in the high-medication-use group than the low-use group (p = 0.028). Basal MDR1 (OR = 1.16 [95% CI: 1.060-1.268]) and conformational change level (OR = 1.11 [95% CI: 1.02-1.20]) were independent predictors for seizure frequency and number of medications, respectively.

Conclusions/significance: The MDR1 profile of PBMNCs is associated with seizure frequency and medication conditions in patients with epilepsy.

Show MeSH
Related in: MedlinePlus