The Experts below are selected from a list of 969 Experts worldwide ranked by ideXlab platform

Weien Yuan - One of the best experts on this subject based on the ideXlab platform.

  • People’s Republic of China
    2016
    Co-Authors: Yunpeng Cai, Xinxin Yang, Zhenguo Liu, Weien Yuan, Ruiyuan Zheng, Meiling Liao, Correspondence Zhenguo Liu
    Abstract:

    which permits unrestricted noncommercial use, provided the original work is properly cited. International Journal of Nanomedicine 2012:7 2077–2086 International Journal of Nanomedicine Controlled-release levodopa methyl ester/ Benserazide-loaded nanoparticles ameliorate levodopa-induced dyskinesia in rat

  • Yinghui Chen2,*
    2016
    Co-Authors: Xiaoyun Hong, Zhenguo Liu, Weien Yuan, Correspondence Zhenguo Liu, Lu Song, Department Of Neurology, Jinshan Hospital
    Abstract:

    Levodopa/Benserazide microspheres reduced levodopa-induced dyskinesia by downregulating phosphorylated GluR1 expression in 6-OHDA-lesioned rats Xinxin Yang1,

  • controlled release levodopa methyl ester Benserazide loaded nanoparticles ameliorate levodopa induced dyskinesia in rats
    International Journal of Nanomedicine, 2012
    Co-Authors: Xinxin Yang, Yunpeng Cai, Weien Yuan, Ruiyuan Zheng, Meiling Liao, Zhenguo Liu
    Abstract:

    Background Levodopa remains the most effective drug in the treatment of Parkinson's disease. However, long-term administration of levodopa induces motor complications, such as levodopa-induced dyskinesia. The mechanisms underlying levodopa-induced dyskinesia are not fully understood. Methods In this study, we prepared levodopa methyl ester (LDME)/Benserazide-loaded nanoparticles, which can release LDME and Benserazide in a sustained manner. Dyskinesia was induced in rats by repeated administration of levodopa then treated with LDME plus Benserazide or the same dose of LDME/Benserazide-loaded nanoparticles. Apomorphine- induced rotations and abnormal involuntary movements (AIMs) were measured on treatment days 1, 5, 10, 15, and 20. In addition, the levels of phosphorylated dopamine- and cyclic adenosine monophosphate- regulated phosphoprotein of 32 kDa, extracellular signal-regulated kinases 1/2, and ΔfosB were determined by Western blot. Tau levels were determined by Western blot and immunohistochemistry. Dynorphin levels in the striatum and cortex of rats were measured using enzyme-linked immunosorbent assay. Results Over the course of levodopa treatment, the rats developed abnormal AIMs, classified as locomotive, axial, orolingual, and forelimb dyskinesia. The degree of reduction of apomorphine-induced rotations was comparable in dyskinetic rats treated with LDME plus Benserazide or LDME/Benserazide-loaded nanoparticles. The axial, limb, and orolingual (ALO) AIMs of dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles were 14 ± 2.5, 9 ± 2.0, and 10 ± 2.1 on treatment days 10, 15, and 20, respectively, which were significantly reduced compared with dyskinetic rats treated with LDME plus Benserazide (25 ± 3.7, 27 ± 3.8, and 25 ± 3.5, respectively). The locomotive AIMs of dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles were 2.3 ± 0.42, 1.7 ± 0.35, and 1.6 ± 0.37 on treatment days 10, 15, and 20, respectively, which were also reduced compared with dyskinetic rats treated with LDME plus Benserazide (4.4 ± 0.85, 4.7 ± 0.95 and 4.8 ± 0.37, respectively). Western blot showed that the levels of phosphorylated dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein of 32 kDa, extracellular signal-regulated kinases 1/2, tau, and ΔfosB in dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles were 134.6 ± 14.1, 174.9 ± 15.1, 134.2 ± 19.3, and 320.5 ± 32.8, respectively, which were significantly reduced compared with those of dyskinetic rats treated with LDME plus Benserazide (210.3 ± 19.7, 320.8 ± 21.9, 340.4 ± 27.1, and 620.7 ± 48.3, respectively). Immunohistochemistry indicated that the level of phosphorylated tau was (7.2 ± 1.1) × 10(4) in dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles. However, the tau level was only (14.6 ± 2.3) × 10(4) in LDME plus Benserazide-treated dyskinetic rats. There was a significant difference between the two groups. Enzyme-linked immunosorbent assay showed that dynorphin levels in the striatum and cortex of dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles were 5.7 ± 1.2 and 4.8 ± 0.87, respectively, which were significantly reduced compared with LDME plus Benserazide-treated dyskinetic rats (13.3 ± 2.1 and 8.1 ± 1.1 for the striatum and cortex, respectively). Conclusion Results suggest that LDME/Benserazide-loaded nanoparticles can be used to reduce the expression of dyskinesia in dyskinetic rats.

  • sustained release formulation of levodopa methyl ester Benserazide for prolonged suppressing dyskinesia expression in 6 ohda leisoned rats
    Neuroscience Letters, 2011
    Co-Authors: Tiantian Ren, Xinxin Yang, Yunpeng Cai, Zhenguo Liu, Weien Yuan
    Abstract:

    Abstract Although levodopa remains the most effective drug in the treatment of Parkinson's disease (PD), chronic administration of levodopa in the treatment of PD usually caused levodopa-induced dyskinesia (LID), the pathogenesis of which is poorly understood. It has been demonstrated that continuous dopamine stimulation reduces the expression of LID in PD. In the present study, levodopa methyl ester (LDME) and Benserazide were microencapsulated into poly (lactide-co-glycolide) (PLGA) microspheres and then administrated to PD model of rats, which were induced by 6-hydroxydopamine injections. We found that both LDME/Benserazide-loaded microspheres achieved sustained-release without burst release during the first day. LDME and Benserazide had the same release slope from the second day on in vivo though Benserazide released faster than LDME during the whole process. In our pharmacodynamic study, LDME/Benserazide-loaded microspheres decreased apomorphine-induced turns and improved stepping of the lesioned forepaw in PD rats. Moreover, western blot analysis showed that the levels of ΔfosB, phosphorylated dopamine, cAMP-regulated phosphoprotein of 32 kDa at threonine 34 and extracellular signal-regulated kinases 1 and 2 were decreased by LDME/Benserazide-loaded microspheres in PD rats. These data showed that LDME/Benserazide-loaded microspheres could be used to treat PD motor symptoms and ameliorate the expression of LID in this rat model of PD.

Zhenguo Liu - One of the best experts on this subject based on the ideXlab platform.

  • People’s Republic of China
    2016
    Co-Authors: Yunpeng Cai, Xinxin Yang, Zhenguo Liu, Weien Yuan, Ruiyuan Zheng, Meiling Liao, Correspondence Zhenguo Liu
    Abstract:

    which permits unrestricted noncommercial use, provided the original work is properly cited. International Journal of Nanomedicine 2012:7 2077–2086 International Journal of Nanomedicine Controlled-release levodopa methyl ester/ Benserazide-loaded nanoparticles ameliorate levodopa-induced dyskinesia in rat

  • Yinghui Chen2,*
    2016
    Co-Authors: Xiaoyun Hong, Zhenguo Liu, Weien Yuan, Correspondence Zhenguo Liu, Lu Song, Department Of Neurology, Jinshan Hospital
    Abstract:

    Levodopa/Benserazide microspheres reduced levodopa-induced dyskinesia by downregulating phosphorylated GluR1 expression in 6-OHDA-lesioned rats Xinxin Yang1,

  • controlled release levodopa methyl ester Benserazide loaded nanoparticles ameliorate levodopa induced dyskinesia in rats
    International Journal of Nanomedicine, 2012
    Co-Authors: Xinxin Yang, Yunpeng Cai, Weien Yuan, Ruiyuan Zheng, Meiling Liao, Zhenguo Liu
    Abstract:

    Background Levodopa remains the most effective drug in the treatment of Parkinson's disease. However, long-term administration of levodopa induces motor complications, such as levodopa-induced dyskinesia. The mechanisms underlying levodopa-induced dyskinesia are not fully understood. Methods In this study, we prepared levodopa methyl ester (LDME)/Benserazide-loaded nanoparticles, which can release LDME and Benserazide in a sustained manner. Dyskinesia was induced in rats by repeated administration of levodopa then treated with LDME plus Benserazide or the same dose of LDME/Benserazide-loaded nanoparticles. Apomorphine- induced rotations and abnormal involuntary movements (AIMs) were measured on treatment days 1, 5, 10, 15, and 20. In addition, the levels of phosphorylated dopamine- and cyclic adenosine monophosphate- regulated phosphoprotein of 32 kDa, extracellular signal-regulated kinases 1/2, and ΔfosB were determined by Western blot. Tau levels were determined by Western blot and immunohistochemistry. Dynorphin levels in the striatum and cortex of rats were measured using enzyme-linked immunosorbent assay. Results Over the course of levodopa treatment, the rats developed abnormal AIMs, classified as locomotive, axial, orolingual, and forelimb dyskinesia. The degree of reduction of apomorphine-induced rotations was comparable in dyskinetic rats treated with LDME plus Benserazide or LDME/Benserazide-loaded nanoparticles. The axial, limb, and orolingual (ALO) AIMs of dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles were 14 ± 2.5, 9 ± 2.0, and 10 ± 2.1 on treatment days 10, 15, and 20, respectively, which were significantly reduced compared with dyskinetic rats treated with LDME plus Benserazide (25 ± 3.7, 27 ± 3.8, and 25 ± 3.5, respectively). The locomotive AIMs of dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles were 2.3 ± 0.42, 1.7 ± 0.35, and 1.6 ± 0.37 on treatment days 10, 15, and 20, respectively, which were also reduced compared with dyskinetic rats treated with LDME plus Benserazide (4.4 ± 0.85, 4.7 ± 0.95 and 4.8 ± 0.37, respectively). Western blot showed that the levels of phosphorylated dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein of 32 kDa, extracellular signal-regulated kinases 1/2, tau, and ΔfosB in dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles were 134.6 ± 14.1, 174.9 ± 15.1, 134.2 ± 19.3, and 320.5 ± 32.8, respectively, which were significantly reduced compared with those of dyskinetic rats treated with LDME plus Benserazide (210.3 ± 19.7, 320.8 ± 21.9, 340.4 ± 27.1, and 620.7 ± 48.3, respectively). Immunohistochemistry indicated that the level of phosphorylated tau was (7.2 ± 1.1) × 10(4) in dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles. However, the tau level was only (14.6 ± 2.3) × 10(4) in LDME plus Benserazide-treated dyskinetic rats. There was a significant difference between the two groups. Enzyme-linked immunosorbent assay showed that dynorphin levels in the striatum and cortex of dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles were 5.7 ± 1.2 and 4.8 ± 0.87, respectively, which were significantly reduced compared with LDME plus Benserazide-treated dyskinetic rats (13.3 ± 2.1 and 8.1 ± 1.1 for the striatum and cortex, respectively). Conclusion Results suggest that LDME/Benserazide-loaded nanoparticles can be used to reduce the expression of dyskinesia in dyskinetic rats.

  • sustained release formulation of levodopa methyl ester Benserazide for prolonged suppressing dyskinesia expression in 6 ohda leisoned rats
    Neuroscience Letters, 2011
    Co-Authors: Tiantian Ren, Xinxin Yang, Yunpeng Cai, Zhenguo Liu, Weien Yuan
    Abstract:

    Abstract Although levodopa remains the most effective drug in the treatment of Parkinson's disease (PD), chronic administration of levodopa in the treatment of PD usually caused levodopa-induced dyskinesia (LID), the pathogenesis of which is poorly understood. It has been demonstrated that continuous dopamine stimulation reduces the expression of LID in PD. In the present study, levodopa methyl ester (LDME) and Benserazide were microencapsulated into poly (lactide-co-glycolide) (PLGA) microspheres and then administrated to PD model of rats, which were induced by 6-hydroxydopamine injections. We found that both LDME/Benserazide-loaded microspheres achieved sustained-release without burst release during the first day. LDME and Benserazide had the same release slope from the second day on in vivo though Benserazide released faster than LDME during the whole process. In our pharmacodynamic study, LDME/Benserazide-loaded microspheres decreased apomorphine-induced turns and improved stepping of the lesioned forepaw in PD rats. Moreover, western blot analysis showed that the levels of ΔfosB, phosphorylated dopamine, cAMP-regulated phosphoprotein of 32 kDa at threonine 34 and extracellular signal-regulated kinases 1 and 2 were decreased by LDME/Benserazide-loaded microspheres in PD rats. These data showed that LDME/Benserazide-loaded microspheres could be used to treat PD motor symptoms and ameliorate the expression of LID in this rat model of PD.

Xinxin Yang - One of the best experts on this subject based on the ideXlab platform.

  • People’s Republic of China
    2016
    Co-Authors: Yunpeng Cai, Xinxin Yang, Zhenguo Liu, Weien Yuan, Ruiyuan Zheng, Meiling Liao, Correspondence Zhenguo Liu
    Abstract:

    which permits unrestricted noncommercial use, provided the original work is properly cited. International Journal of Nanomedicine 2012:7 2077–2086 International Journal of Nanomedicine Controlled-release levodopa methyl ester/ Benserazide-loaded nanoparticles ameliorate levodopa-induced dyskinesia in rat

  • controlled release levodopa methyl ester Benserazide loaded nanoparticles ameliorate levodopa induced dyskinesia in rats
    International Journal of Nanomedicine, 2012
    Co-Authors: Xinxin Yang, Yunpeng Cai, Weien Yuan, Ruiyuan Zheng, Meiling Liao, Zhenguo Liu
    Abstract:

    Background Levodopa remains the most effective drug in the treatment of Parkinson's disease. However, long-term administration of levodopa induces motor complications, such as levodopa-induced dyskinesia. The mechanisms underlying levodopa-induced dyskinesia are not fully understood. Methods In this study, we prepared levodopa methyl ester (LDME)/Benserazide-loaded nanoparticles, which can release LDME and Benserazide in a sustained manner. Dyskinesia was induced in rats by repeated administration of levodopa then treated with LDME plus Benserazide or the same dose of LDME/Benserazide-loaded nanoparticles. Apomorphine- induced rotations and abnormal involuntary movements (AIMs) were measured on treatment days 1, 5, 10, 15, and 20. In addition, the levels of phosphorylated dopamine- and cyclic adenosine monophosphate- regulated phosphoprotein of 32 kDa, extracellular signal-regulated kinases 1/2, and ΔfosB were determined by Western blot. Tau levels were determined by Western blot and immunohistochemistry. Dynorphin levels in the striatum and cortex of rats were measured using enzyme-linked immunosorbent assay. Results Over the course of levodopa treatment, the rats developed abnormal AIMs, classified as locomotive, axial, orolingual, and forelimb dyskinesia. The degree of reduction of apomorphine-induced rotations was comparable in dyskinetic rats treated with LDME plus Benserazide or LDME/Benserazide-loaded nanoparticles. The axial, limb, and orolingual (ALO) AIMs of dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles were 14 ± 2.5, 9 ± 2.0, and 10 ± 2.1 on treatment days 10, 15, and 20, respectively, which were significantly reduced compared with dyskinetic rats treated with LDME plus Benserazide (25 ± 3.7, 27 ± 3.8, and 25 ± 3.5, respectively). The locomotive AIMs of dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles were 2.3 ± 0.42, 1.7 ± 0.35, and 1.6 ± 0.37 on treatment days 10, 15, and 20, respectively, which were also reduced compared with dyskinetic rats treated with LDME plus Benserazide (4.4 ± 0.85, 4.7 ± 0.95 and 4.8 ± 0.37, respectively). Western blot showed that the levels of phosphorylated dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein of 32 kDa, extracellular signal-regulated kinases 1/2, tau, and ΔfosB in dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles were 134.6 ± 14.1, 174.9 ± 15.1, 134.2 ± 19.3, and 320.5 ± 32.8, respectively, which were significantly reduced compared with those of dyskinetic rats treated with LDME plus Benserazide (210.3 ± 19.7, 320.8 ± 21.9, 340.4 ± 27.1, and 620.7 ± 48.3, respectively). Immunohistochemistry indicated that the level of phosphorylated tau was (7.2 ± 1.1) × 10(4) in dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles. However, the tau level was only (14.6 ± 2.3) × 10(4) in LDME plus Benserazide-treated dyskinetic rats. There was a significant difference between the two groups. Enzyme-linked immunosorbent assay showed that dynorphin levels in the striatum and cortex of dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles were 5.7 ± 1.2 and 4.8 ± 0.87, respectively, which were significantly reduced compared with LDME plus Benserazide-treated dyskinetic rats (13.3 ± 2.1 and 8.1 ± 1.1 for the striatum and cortex, respectively). Conclusion Results suggest that LDME/Benserazide-loaded nanoparticles can be used to reduce the expression of dyskinesia in dyskinetic rats.

  • sustained release formulation of levodopa methyl ester Benserazide for prolonged suppressing dyskinesia expression in 6 ohda leisoned rats
    Neuroscience Letters, 2011
    Co-Authors: Tiantian Ren, Xinxin Yang, Yunpeng Cai, Zhenguo Liu, Weien Yuan
    Abstract:

    Abstract Although levodopa remains the most effective drug in the treatment of Parkinson's disease (PD), chronic administration of levodopa in the treatment of PD usually caused levodopa-induced dyskinesia (LID), the pathogenesis of which is poorly understood. It has been demonstrated that continuous dopamine stimulation reduces the expression of LID in PD. In the present study, levodopa methyl ester (LDME) and Benserazide were microencapsulated into poly (lactide-co-glycolide) (PLGA) microspheres and then administrated to PD model of rats, which were induced by 6-hydroxydopamine injections. We found that both LDME/Benserazide-loaded microspheres achieved sustained-release without burst release during the first day. LDME and Benserazide had the same release slope from the second day on in vivo though Benserazide released faster than LDME during the whole process. In our pharmacodynamic study, LDME/Benserazide-loaded microspheres decreased apomorphine-induced turns and improved stepping of the lesioned forepaw in PD rats. Moreover, western blot analysis showed that the levels of ΔfosB, phosphorylated dopamine, cAMP-regulated phosphoprotein of 32 kDa at threonine 34 and extracellular signal-regulated kinases 1 and 2 were decreased by LDME/Benserazide-loaded microspheres in PD rats. These data showed that LDME/Benserazide-loaded microspheres could be used to treat PD motor symptoms and ameliorate the expression of LID in this rat model of PD.

Yunpeng Cai - One of the best experts on this subject based on the ideXlab platform.

  • People’s Republic of China
    2016
    Co-Authors: Yunpeng Cai, Xinxin Yang, Zhenguo Liu, Weien Yuan, Ruiyuan Zheng, Meiling Liao, Correspondence Zhenguo Liu
    Abstract:

    which permits unrestricted noncommercial use, provided the original work is properly cited. International Journal of Nanomedicine 2012:7 2077–2086 International Journal of Nanomedicine Controlled-release levodopa methyl ester/ Benserazide-loaded nanoparticles ameliorate levodopa-induced dyskinesia in rat

  • controlled release levodopa methyl ester Benserazide loaded nanoparticles ameliorate levodopa induced dyskinesia in rats
    International Journal of Nanomedicine, 2012
    Co-Authors: Xinxin Yang, Yunpeng Cai, Weien Yuan, Ruiyuan Zheng, Meiling Liao, Zhenguo Liu
    Abstract:

    Background Levodopa remains the most effective drug in the treatment of Parkinson's disease. However, long-term administration of levodopa induces motor complications, such as levodopa-induced dyskinesia. The mechanisms underlying levodopa-induced dyskinesia are not fully understood. Methods In this study, we prepared levodopa methyl ester (LDME)/Benserazide-loaded nanoparticles, which can release LDME and Benserazide in a sustained manner. Dyskinesia was induced in rats by repeated administration of levodopa then treated with LDME plus Benserazide or the same dose of LDME/Benserazide-loaded nanoparticles. Apomorphine- induced rotations and abnormal involuntary movements (AIMs) were measured on treatment days 1, 5, 10, 15, and 20. In addition, the levels of phosphorylated dopamine- and cyclic adenosine monophosphate- regulated phosphoprotein of 32 kDa, extracellular signal-regulated kinases 1/2, and ΔfosB were determined by Western blot. Tau levels were determined by Western blot and immunohistochemistry. Dynorphin levels in the striatum and cortex of rats were measured using enzyme-linked immunosorbent assay. Results Over the course of levodopa treatment, the rats developed abnormal AIMs, classified as locomotive, axial, orolingual, and forelimb dyskinesia. The degree of reduction of apomorphine-induced rotations was comparable in dyskinetic rats treated with LDME plus Benserazide or LDME/Benserazide-loaded nanoparticles. The axial, limb, and orolingual (ALO) AIMs of dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles were 14 ± 2.5, 9 ± 2.0, and 10 ± 2.1 on treatment days 10, 15, and 20, respectively, which were significantly reduced compared with dyskinetic rats treated with LDME plus Benserazide (25 ± 3.7, 27 ± 3.8, and 25 ± 3.5, respectively). The locomotive AIMs of dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles were 2.3 ± 0.42, 1.7 ± 0.35, and 1.6 ± 0.37 on treatment days 10, 15, and 20, respectively, which were also reduced compared with dyskinetic rats treated with LDME plus Benserazide (4.4 ± 0.85, 4.7 ± 0.95 and 4.8 ± 0.37, respectively). Western blot showed that the levels of phosphorylated dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein of 32 kDa, extracellular signal-regulated kinases 1/2, tau, and ΔfosB in dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles were 134.6 ± 14.1, 174.9 ± 15.1, 134.2 ± 19.3, and 320.5 ± 32.8, respectively, which were significantly reduced compared with those of dyskinetic rats treated with LDME plus Benserazide (210.3 ± 19.7, 320.8 ± 21.9, 340.4 ± 27.1, and 620.7 ± 48.3, respectively). Immunohistochemistry indicated that the level of phosphorylated tau was (7.2 ± 1.1) × 10(4) in dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles. However, the tau level was only (14.6 ± 2.3) × 10(4) in LDME plus Benserazide-treated dyskinetic rats. There was a significant difference between the two groups. Enzyme-linked immunosorbent assay showed that dynorphin levels in the striatum and cortex of dyskinetic rats treated with LDME/Benserazide-loaded nanoparticles were 5.7 ± 1.2 and 4.8 ± 0.87, respectively, which were significantly reduced compared with LDME plus Benserazide-treated dyskinetic rats (13.3 ± 2.1 and 8.1 ± 1.1 for the striatum and cortex, respectively). Conclusion Results suggest that LDME/Benserazide-loaded nanoparticles can be used to reduce the expression of dyskinesia in dyskinetic rats.

  • sustained release formulation of levodopa methyl ester Benserazide for prolonged suppressing dyskinesia expression in 6 ohda leisoned rats
    Neuroscience Letters, 2011
    Co-Authors: Tiantian Ren, Xinxin Yang, Yunpeng Cai, Zhenguo Liu, Weien Yuan
    Abstract:

    Abstract Although levodopa remains the most effective drug in the treatment of Parkinson's disease (PD), chronic administration of levodopa in the treatment of PD usually caused levodopa-induced dyskinesia (LID), the pathogenesis of which is poorly understood. It has been demonstrated that continuous dopamine stimulation reduces the expression of LID in PD. In the present study, levodopa methyl ester (LDME) and Benserazide were microencapsulated into poly (lactide-co-glycolide) (PLGA) microspheres and then administrated to PD model of rats, which were induced by 6-hydroxydopamine injections. We found that both LDME/Benserazide-loaded microspheres achieved sustained-release without burst release during the first day. LDME and Benserazide had the same release slope from the second day on in vivo though Benserazide released faster than LDME during the whole process. In our pharmacodynamic study, LDME/Benserazide-loaded microspheres decreased apomorphine-induced turns and improved stepping of the lesioned forepaw in PD rats. Moreover, western blot analysis showed that the levels of ΔfosB, phosphorylated dopamine, cAMP-regulated phosphoprotein of 32 kDa at threonine 34 and extracellular signal-regulated kinases 1 and 2 were decreased by LDME/Benserazide-loaded microspheres in PD rats. These data showed that LDME/Benserazide-loaded microspheres could be used to treat PD motor symptoms and ameliorate the expression of LID in this rat model of PD.

Patricio Soaresdasilva - One of the best experts on this subject based on the ideXlab platform.

  • a double blind randomized placebo and active controlled study of nebicapone for the treatment of motor fluctuations in parkinson s disease
    CNS Neuroscience & Therapeutics, 2010
    Co-Authors: Joaquim J Ferreira, Luis Almeida, Patricio Soaresdasilva, Olivier Rascol, Werner Poewe, Cristina Sampaio
    Abstract:

    To determine the efficacy, safety and tolerability of nebicapone, a new catechol-O-methyltransferase inhibitor for the treatment of motor fluctuations in Parkinson's disease (PD), we conducted a multicenter, randomized, 8-week double-blind, placebo- and active-controlled, parallel-group study comparing nebicapone 50 mg, 100 mg, or 150 mg, entacapone 200 mg (active control) or placebo administered concomitantly with levodopa/carbidopa or levodopa/Benserazide. Two hundred and fifty-two PD patients with motor fluctuations treated with levodopa/carbidopa or levodopa/Benserazide (4-8 daily doses) were enrolled and 250 patients were eligible for intention-to-treat (ITT) analysis on the basis of having at least one efficacy assessment. The primary endpoint was 8-week change from baseline in absolute "Off" time duration noted in self-scoring diaries. At 8 weeks of treatment the mean daily "Off" time decreased significantly compared to placebo for nebicapone 150 mg (-106 min; 95%CI: -192; -21) and entacapone 200 mg (-81 min; 95%CI: -142; -19). The decrease in "Off" time with nebicapone 50 mg or 100 mg did not reach statistical significance. Treatment-emergent adverse events were reported by 32% to 49% of patients in any treatment group, with no observed dose relationship in the nebicapone groups. Clinically relevant elevations in aspartate transaminase (AST) and/or alanine transaminase (ALT) were observed in 4 of 46 patients with the nebicapone 150 mg dose. The results of this study show that nebicapone 150 mg is efficacious for the treatment of motor fluctuations in PD patients. However, the risk of increasing liver transaminases and its clinically relevance deserves further evaluation.