Effects and molecular mechanism of benserazide hydrochloride on LPS-induced inflammation in human umbilical vein endothelial cells / 中国药科大学学报

@#In this article, human umbilical vein endothelial cells(HUVECs)were induced by lipopolysaccharides(LPS)to establish an in vitro inflammation model to further verify the anti-inflammation effects of benserazide hydrochloride and to explore the molecular mechanisms involving in the anti-inflammation and anti-atherosclerosis of benserazide hydrochloride. The experiments were divided into blank groups(PBS+0. 5% FBS DMEM medium), model group ［LPS(500 μg/mL)+ 0. 5% FBS DMEM medium］ and drug group ［LPS(500 μg/mL)+benserazide hydrochloride+0. 5% FBS DMEM medium］. Western blot, ELISA and qPCR were used to detect the protein and mRNA expression levels of inflammatory cytokines SAP, TNF-α and MCP-1 in HUVECs cells. The expression levels of p65/p-p65, p38/p-p38, IκBα/p-IκBα, AKT/p-AKT and the nuclear translocations of p65, p38 and IκBα were detected by Western blot. The results showed that benserazide hydrochloride(1×10-9, 1×10-10, 1×10-11 mol/L)could significantly inhibit the protein and mRNA expression of pro-inflammatory cytokines SAP, TNF-α and MCP-1. Besides, it could down-regulate the protein expression of p65/p-p65, p38/p-p38, IκBα/p-IκBα and AKT/p-AKT in the signal pathway while inhibiting the nuclear translocation of p65, p38 and IκBα, thereby inhibiting the transcriptional activity of the related genes.

Association between serum homocysteine level and cognitive impairment in PD patients / 中华老年心脑血管病杂志

Objective To study the association between serum homocysteine (Hcy) level and cognitive impairment in PD patients.Methods Eighty-one PD patients admitted to our hospital were divided into normal cognition group (n=25),mild cognitive impairment group (n=32) and dementia group (n=24) with 19 healthy persons undergoing physical examination served as a control group.Their cognitive impairment was assessed according to their medical history,detailed physical examination data,Hoehn-Yahr scale score,MMSE score,and CDR score.Their serum levels of Hcy,folic acid and vitamin B12 were measured.The association of serum Hcy,folic acid and vitamin B12 levels with cognitive impairment was analyzed.Results The serum Hcy level was significantly higher in normal cognition group,mild cognitive impairment group and dementia group than in control group (P＜0.05,P＜0.01) and in dementia group than in normal cognition group (14.8±3.9 μmol/L vs 12.5±3.3 μmol/L,P＜0.05).The serum Hcy level was associated with oral levodopa and oral benserazide daily dose,oral levodopa and oral benserazide taking time,course of PD and age (r=0.298,P=0.000;r=0.280,P=0.000;r=0.301,P=0.000;r=0.184,P=0.019) but not associated with the severity of PD.Conclusion High serum Hcy level is one of the risk factors for cognitive impairment in PD patients,and control of oral levodopa dose contributes to the prevention and treatment of dementia in PD patients.

Clinical effect of levodopa and benserazide hydrochloride tables combined with visual occlusion for amblyopia in children / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To study the therapeutic effect of visual occlusion combined with levodopa and benserazide hydrochloride tables on children with amblyopia. <p>METHODS: Totally 90 cases(140 eyes)of children diagnosed with amblyopia in our hospital were selected from January 2016 to January 2017. They were randomly divided into the monotherapy group and the combined treatment group, and 35 healthy children(70 eyes)were selected as the normal group for comparison. Patients in the monotherapy group were treated with visual cover, while patients in the combined treatment group were treated with oral administration of levodopa and benserazide tablets on the basis of visual cover. Tears were extracted from both groups of children before and after treatment, and the protein levels of CREB and PKA in tears of 140 eyes and 70 eyes of children in the normal group were detected by enzyme-linked immunosorbent assay. The index levels of the two groups and the normal group were compared, as well as the therapeutic efficiency of different age groups and the total therapeutic efficiency of different methods. <p>RESULTS: After treatment, the levels of IL-1β, IL-6 and IL-9 in the combined treatment group were significantly lower than those in the single treatment group after treatment(<i>P</i><0.05).After treatment, the levels of CREB and PKA in the combined treatment group were significantly lower than those in the single treatment group(<i>P</i><0.05).The total effective rate of children at the age of 3-6 in the combined treatment group and the single treatment group was significantly higher than those at the age of 7-9 and 10-12 in each group(<i>P</i><0.05). The total therapeutic efficiency of the combined treatment group was significantly higher than that of the single treatment group, and the difference was statistically significant(<i>P</i><0.05). <p>CONCLUSION: Combined with the traditional masking method, levodopa and benserazide hydrochloride tables can improve the treatment of children's amblyopia. The earlier the treatment time, the better and the higher efficiency is.

Formula Optimization of Levodopa Microcapsules Floating Tablets / 中国药师

To optimize the formula of levodopa microcapsules floating tablets. Methods:The contents of levodopa and benserazide in the microcapsules floating tablets were determined by HPLC simultaneously. The release rate as the index, an orthogonal design was used to optimize the formula and preparation technology of levodopa microcapsules floating tablets. The release property of the microcapsules floating tablets was evaluated. Results:The HPLC method for the in vitro determination of levodopa and benserazide in the floating tablets met the methodological requirements. The selected formula was as following:the amount ratio of stearic acid, the drugs, acrylic resin and HPMC was 2∶5∶2∶1. The average weight of the tablets was 550 mg. The results of validated tests showed that the microcapsules floating tablets had floating and sustained release property, which could be used by divided dose. Conclusion: The optimized formula of the microcapsules floating tablets is reasonable, and the production process is stable and feasible.

Clinical effects of levodopa benserazide combine with dl-3-butylphthalide capsules on limbs function of patients after stroke / 中国综合临床

Objective To investigate the effects of levodopa benserazide hydrochloride combine with dl-3-butyl phthalide capsule on patient's limbs function after stroke. Methods Ninety patients with stroke were randomly divided into rehabilitation group,treatment group and control group,and 30 cases for each group. Patients in rehabilitation group were treated with exercise therapy,in treatment group were given exercise therapy and levodopa Benserazide and Dl-3-butylphthalide capsules,and in control group were given placebo treatment. Adult hemiplegic motor function score(FMA)and motor function assessment scale(MAS)were used to assess the motor function and lower extremity function before treatment and 8 weeks after treatment. Results Before treatment,FMA and MAS in rehabilitation group,treatment group and control group were(22. 6 ± 3. 6), (23. 1 ± 2. 5)and(20. 3 ± 2. 9),and(1. 6 ± 0. 6),(2. 1 ± 0. 5),(1. 7 ± 0. 9),respectively. There was no significant differences between the two groups( F = 1. 64,P > 0. 05;F = 1. 66,P > 0. 05). After 8 weeks of treatment,FMA and MAS in rehabilitation group and treatment group were(60. 6 ± 3. 5),(14. 6 ± 1. 1),and (75. 7 ± 4. 5),(17. 7 ± 4. 5),significant improved more than that before treatment(t = 1. 738,1,716,1. 732 respectively;P < 0. 05). Meanwhile,patients in the treatment group improved more than that in rehabilitation group(P < 0. 05),and they were superior to patients in control group((31. 0 ± 3. 6),(5. 5 ± 1. 1);P < 0. 05). Conclusion Benserazide combined with dl-3- butyl phthalide capsule can further improve the limbs function.

Comparação da bioequivalência entre duas formulações de levodopa 200 mg + benserazida 50 mg comprimidos em voluntários sadios após a administração de dose única / Comparison of the bioequivalence between two formulations of Levodopa 200 mg + Benserazide 50 mg tablets in healthy volunteers after a single dose administration

O estudo foi realizado para comparar a bioequivalência de duas formulações de levodopa 200 mg + benserazida 50 mg (equivalente a 57 mg de cloridrato de benserazida) sob a forma de comprimidos (levodopa + cloridrato de benserazida do Aché Laboratórios Farmacêuticos S/A, formulação teste e Prolopa® de Produtos Roche Químicos e Farmacêuticos S/A, formulação referência) em 36 voluntários sadios. O estudo foi realizado através de um desenho aberto, randomizado, cruzado em dois períodos com tempo de washout de quatro semanas. As amostras de plasma foram obtidas ao longo de um intervalo de 96 horas. As concentrações de levodopa e do metabólito 3-O-metildopa foram determinadas através de um equipamento HPLC/MS/MS, utilizando carbidopa como padrão interno. A partir dos dados de concentração plasmática obtidos individualmente se calcularam os seguintes parâmetros farmacocinéticos: ASC0-t, Cmáx e Tmáx...

Cost-effectiveness aralysis of pramipexole combined with levodopa/benserazide in the hospitalized Parkinson's disease patients / 中国基层医药

ObjectiveTo assess cost-effectiveness of pramipexole and levodopa/benseraside in the hospitalized Parkinson's disease (PD) patient.Methods81 PD patients were divided into group A(levodopa/benserazide group) and group B( pramipexole combined with levodopa/benserazide group) according to different pharmacotherapy.The curative effects and costs of hospitalized PD patients were evaluated.The curative effects were evaluated by unified Parkinson's disease rating scale (UPDRS).ResultsThere were 44 patients in group A and 37 patients in group B.Although B group in drug costs and treatment costs were increased more significantly than A group ( P ＜0.01),but declined markedly UPDRS after treatment ( P ＜ 0.05 ) than A group.Pramipexole can be applied in all kinds of Hoehn and Yahr states in PD.ConclusionAlthough the combination of pramipexole would increase drug costs and treatment costs,but could improve the clinical symptoms of PD,and can be applied to different stages of PD.It should be individualized recommendation in the Parkinson's patients.

Observation of the effect of pramipexole combined with levodopa/benserazide in treatment of advanced Parkinson's disease / 中国基层医药

Objective To evaluate the efficacy of pramipexole and levodopa/benserazide in treatment of advanced Parkinson's disease.Methods 50 patients with advanced Parkinson's disease were randomly divided into two groups,25 cases in the control group,others in the treatment group.The patients in the control group were treated with levodopa/benserazide and placebo,while those in the treatment group were given pramipexole and levodopa/benserazide.The treatment lasted 16 weeks.The clinical effects before and after the treatment were observed and compared. Results Compared with the control group,the treatment group experienced significant drops in the score of the Unified Parkinson's Disease Rating Scale(UPDRS)(P＜0.05).The clinical efficacy was significantly improved(84.0%vs36.0%)(χ2=10.08,P＜0.01).Conclusion The clinical effect of pramipexole and levedopa/benserazide in treatment of advanced Parkinson's disease was satisfactory,and it should be widely applied.

An experiment on controlled release levodopa/benserazide-loaded microspheres in treatment of levodopa-induced dyskinesia of rats with Parkinson' s disease / 中华神经科杂志

Objective To investigate the effects of levodopa/benserazide-loaded poly-lactide-coglycolide (PLGA) microspheres on motor deficits and levodopa-induced dyskinesia in a rat model of Parkinson' s disease (PD) and to explore the mechanisms underlying this effects.Methods The content of levodopa/benserazide released from the microspheres was determined by high-performance liquid chromatography.The rat model of PD was induced by 6-OHDA injections.Then the valid PD rats were treated with levodopa ( 12 mg/kg,s.c.)/benserazide ( 15 mg/kg,s.c.) or microspheres.Forepaw adjusting steps were measured on 1,4,7,10 and 14 days after treatment.After 2 weeks of treatment,the abnormal involuntary movements (AIM) were measured.Phosphorylated dopamine,cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) at threonine 34 levels were determined by immunohistochemistry and Western blot respectively.In addition,the levels of △FosB were measured by Western blot.Results In vivo release test showed that 76.2％ of levodopa and 83.6％ benserazide were released from the microspheres on day 7.Forepaw adjusting steps showed that the scores of forepaw adjusting steps in microspheres-treated PD rats were ( 5.8 ± 1.6 ) and ( 5.2 ± 1.5 ) respectively on 10 and 14 days of treatment,which were increased compared to levodopa-treaded PD rats (2.4 ± 1.1 and 1.2 ± 0.5 ; t =4.12,5.43,all P ＜0.01 ).The AIM scores of microspheres-treated rats ( 16.0 ±2.1 ) were decreased significantly compared to levodopa-treated rats ( 26.0 ± 3.2 ) on day 14 ( t =6.59,P ＜ 0.01 ).Immunohistochemistry indicated that the phosphorylated levels of DARPP-32 in microspheres-treated rats ( (3.7 ± 1.3 ) × 104 )were decreased significantly compared to levodopa-treated rats ( (7.9 ± 2.2) × 104 ; t =2.95,P ＜ 0.05 ).In addition,Western blot showed that the levels of phosphorylated DARPP-32 and △FosB were 119.4％ ± 11.3％ and 149.3％ ± 12.3％ respectively,which were decreased significantly compared to levodopatreated rats ( 184.8％ ± 13.7％ and 300.4％ ± 14.2％ ; t =4.12,2.91,all P ＜ 0.05 ).Conclusions Microspheres can be used to improve the motor deficits and reduce the expression of dyskinesia in PD rats.This may be due to the continuous release of levodopa/beserazide from the microspheres,which leads to continuous stimulation of PD rats and reduces the levels of phosphorylated DARPP-32 and △FosB in the striata of these rats.

Restless legs syndrome:23-cases report / 中华神经科杂志

Objective To investigate the clinical features of restless legs syndrome(RLS),its possible pathogenesis.and the effects of benserazide on the patients with RLS.Methods Twenty-three patients who met the primary diagnostic criteria of RLS were retrospectively analyzed.Results Twenty-three middle-aged or elderly patients aged 56 years in average had an average onset age of 52 years.Insomnia and daytime sleepiness were mostly common complains for these patients.Based on the diagnostic criteria of International RLS study group(IRLSSG),the average IRLSSG score was 25,and 16 cases(69%)of the patients were severe(21-30).Polysomnographic examination showed that 18 cases(78%)had periodic limb movement.in which the PLM index of 11 cases(61%)patients Was moderate(25-49).PLM-arousal index of all patients was increased.that of 16 cases(67%)patients being moderate.After treatment by levodopa/benserazide 100/25 mg at bedtime each night for 4 weeks,most of patients'subjective symptoms improved markedly.and the IRLSSG score Was obviously decreased.with an average score of 13,and 5 patients became completely normal.Among patients with periodic legs movement.the PLM index became normal in 5 patients and became mild in others.In addition.the PLM-arousal index in all patients Was markedly decreased.with that of 11 patients becoming normal.The sleep latency of 19 patients became normal.On the other hand,6 patients(26%)had transient headache,nausea,and lethargy.Conclusions Patients with discomfortable feeling of lower extremity which is mitigated after movement.and legs movement during sleep should be check up as early as possible.Benserazide may be considered as an effeetive medication for patients with RLS.