Objective: In the manuscript titled “Liquid subcutaneous Levodopa-Carbidopa ND0612 effects on motor symptoms in individuals with Parkinson’s Disease: A systematic review and meta-analysis”, the objective was to con...Objective: In the manuscript titled “Liquid subcutaneous Levodopa-Carbidopa ND0612 effects on motor symptoms in individuals with Parkinson’s Disease: A systematic review and meta-analysis”, the objective was to conduct a systematic review with meta-analysis to investigate the effects ND0612 24-hour dosing regimen has on motor symptoms in individuals with Parkinson’s Disease (PD). Introduction: ND0612 is a novel minimally invasive continuous subcutaneous delivery system of liquid Levodopa-Carbidopa being investigated for the treatment of PD in individuals experiencing motor symptoms. Methods: A systematic literature search was conducted in PubMed, Cochrane, and EBSCO databases to identify randomized controlled trials investigating the effects of ND0612 on motor symptoms in individuals with PD. Outcomes included the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II and Part III scores. Methodological quality was assessed using the Cochrane Grading of Recommendations Assessment, Development, and Evaluation approach. Meta-analysis was performed using a random effects model with the DerSimonian and Laird method to estimate the effects of the ND0612 24-hour dosing regimen on UPDRS Part II and Part III scores. Results: Three studies were included in our review. There were statistically significant reductions in UPDRS Part II scores (mean difference (MD) −3.299;95% confidence interval (CI) −3.438, −3.159) and in UPDRS Part III scores (MD −12.695;95% CI −24.428, −0.962) in the ND0612 24-hour dosing regimen. Results were based on very low certainty of evidence. Conclusion: Based on very low certainty evidence, the ND0612 24-hour dosing regimen is effective at improving motor symptoms in individuals with PD. Our findings suggest that ND0612 is more effective at improving UPDRS Part II and Part III scores in individuals with PD than other pharmacological and non-pharmacological treatments, warranting further study.展开更多
The inhibitory effect of ferulic acid on the diphenolase activity of mushroom tyrosinase and the kinetic behavior were studied with L-3,4-dihydroxyphenylalanine （L-DOPA） as substrate. The inhibitor concentration lea...The inhibitory effect of ferulic acid on the diphenolase activity of mushroom tyrosinase and the kinetic behavior were studied with L-3,4-dihydroxyphenylalanine （L-DOPA） as substrate. The inhibitor concentration leading to 50% relative activity lost （IC50） was estimated to be 0.15 mmol·L^-1. The inhibition mechanism obtained from Lineweaver-Burk plots shows that ferulic acid is a competitive inhibitor and the inhibition of tyrosinase by ferulic acid is a reversible reaction. The equilibrium constant for ferulic acid binding with the tyrosinase was determined to be 0.25 mmol·L^-1 for diphenolase. Keywords tyrosinase, ferulic acid, kinetics, inhibition, L-DOPA, diphenolase展开更多
Based on the electrocatalytic oxidation of levodopa at gold electrode and the reduction of permanganate at platinum electrode, a novel flow injection irreversible biamperometric method is developed for the determinati...Based on the electrocatalytic oxidation of levodopa at gold electrode and the reduction of permanganate at platinum electrode, a novel flow injection irreversible biamperometric method is developed for the determination of levodopa under the potential difference of 0 V imposed between two electrodes. In H2SO4 solution, the linear relationships between currents and the concentrations of levodopa are obtained in the range from 0.04 mg/L to 20 mg/L with the detection limit of 0.012 mg/L. The proposed method is applied to the determination of levodopa in pharmaceutical preparations.展开更多
Long-term application of levodopa （L-3, 4-dihydroxyphenylalanine, L-DOPA） for Parkinson＇s disease can lead to adverse effects and reduce the amount of dopamine transporter （DAT） in the corpus striatum. The presen...Long-term application of levodopa （L-3, 4-dihydroxyphenylalanine, L-DOPA） for Parkinson＇s disease can lead to adverse effects and reduce the amount of dopamine transporter （DAT） in the corpus striatum. The present study attempted to vedfy whether increasing the amount of DAT can reduce the adverse effects of L-DOPA. The specific radioactive uptake value of DAT in the corpus striatum of the lesioned hemisphere was significantly decreased, but was significantly increased following administration of compound rehmannia formula [Radix rehmanniae preparata （prepared rehmannia root）, Concha margantifera usta （nacre）, Radix paeoniae alba （white peony alba）, Radix salviae miltiotThizae （Danshen root）, Scorpio （scorpion）, green tea] for 4 weeks. The changes in DAT 1251-beta-carbomethoxy-3 beta-（4-iodophenyl） tropane autoradiography were consistent with those in radioactivity. The results revealed that the compound rehmannia formula can reduce the adverse effects of L-DOPA in treating Parkinson＇s disease, possibly by increasing the amount of DAT.展开更多
AIM: Many studies have demonstrated N-methyl-D-aspartate receptor-1-subunit (NMDAR1) is associated with amblyopia. The effectiveness of levodopa in improving the visual function of the children with amblyopia has also...AIM: Many studies have demonstrated N-methyl-D-aspartate receptor-1-subunit (NMDAR1) is associated with amblyopia. The effectiveness of levodopa in improving the visual function of the children with amblyopia has also been proved. But the mechanism is undefined. Our study was to explore the possible mechanism. METHODS: Sixty 14-day-old healthy SD rats were randomly divided into 4 groups, including normal group, monocular deprivation group, levodopa group and normal saline group, 15 rats each. We sutured all the rats' unilateral eyelids except normal group to establish the monocular deprivation animal model and raise them in normal sunlight till 45-day-old. NMDAR1 was detected in the visual cortex with immunohistochemistry methods, Western Blot and Real time PCR. LD and NS groups were gavaged with levodopa (40mg/kg) and normal saline for 28 days respectively. NMDAR1 was also detected with the methods above. RESULTS: NMDAR1 in the visual cortex of MD group was less than that of normal group. NMDAR1 in the visual cortex of LD group was more than that of NS group. CONCLUSION: NMDAR1 is associated with the plasticity of visual development. Levodopa may influence the expression of NMDAR1 and improve visual function, and its target may lie in the visual cortex.展开更多
A novel method for the simultaneous determination of benserazide and levodopa using capillary electrophoresis （CE）- chemiluminescence （CL） has been developed. Under the optimal conditions, the detection limits （S...A novel method for the simultaneous determination of benserazide and levodopa using capillary electrophoresis （CE）- chemiluminescence （CL） has been developed. Under the optimal conditions, the detection limits （S/N = 3） were 1.85 μg/mL for benserazide and 0.12 μg/mL for levodopa. This method was successfully applied to the determination of benserazide and levodopa in Medopar tablet, the results showed that the detected values are in accordance with those by official methods.展开更多
BACKGROUND： Radio-imaging has been used in neurological diagnosis, in particular for extrapyramidal disease. Moreover, it has been extensively utilized for early diagnosis of Parkinson＇s disease （PD） patients and ...BACKGROUND： Radio-imaging has been used in neurological diagnosis, in particular for extrapyramidal disease. Moreover, it has been extensively utilized for early diagnosis of Parkinson＇s disease （PD） patients and in animal studies. However, it has rarely been utilized to assess drug-induced side effects in PD. OBJECTIVE： To investigate changes in dopamine transporter expression in a rat model of PD through the use of radio-imaging taking ^99mTc-TRODAT-1 as an imaging agent, and to explore the effect of levodopa （L-dopa） on dopaminergic neurons and the possible mechanisms of dyskinesia induction. DESIGN, TIME AND SETTING： A randomized, controlled, animal study was performed at the Laboratory of Department of Nuclear Medicine, Soochow University from April 2006 to June 2007. MATERIALS： 6-hydroxydopamine was purchased from Sigma, USA and L-dopa was purchased from Shanghai Fuda Pharmaceutical, China. ^99mTcO4-fresh elutriant was provided by the Department of Nuclear Medicine, First Hospital Affiliated to Soochow University. TRODAT-1 image kit was provided by Jiangsu Atomic Energy Research Establishment, China. The SN-695B radioimmunoassay gamma counter was purchased from Shanghai Hesuo Rihuan Photoelectric Instrument, China. The AZ-CA256eZ-Scope portable y camera was purchased from Anzai Medical, Japan. METHODS： A total of 34 healthy, male, Sprague Dawley rats were selected. Thirty were used to establish a PD model by injecting 6-hydroxydopamine into the right medial forebrain bundle, and four were injected with normal saline and served as the sham-surgery group. At the end of 4 weeks, 21 successful PD models were selected and randomly assigned to the L-dopa （n = 15, 20 mg/kg per day）, model （n = 6, normal saline）, and sham-surgery （n = 4, no treatment） groups. After 1 month of treatment, involuntary movement was evaluated twice weekly in each rat. A total of 0.2 mL ^99mTc-TRODAT-1 was injected into the tail vein 2 days following drug termination, and images of dopamine transporters were acquired 2 hours later. The rats were sacrificed and the ratios of specific radioactivity uptake were calculated. MAIN OUTCOME MEASURES： Manifestations of abnormal involuntary movement （AIM） were observed and total AIM scores were calculated. Images of dopamine transporters were acquired using an eZ-Scope portable y camera, and radioactive y quantification of ^99mTC-TRODAT-1 in the rat brains was assayed. The ratios of the left and right corpora striata were determined. The number and function of dopamine transporters was evaluated according to specific radioactivity uptake ratio （R） from the left and right corpora striata. RESULTS： Of 15 PD rats, nine exhibited AIM following L-dopa treatment： five scored 〉 20, i.e., severe grade, four scored 8-16, mild grade, and the remaining exhibited normal behavior. There were no differences in specific radioactivity uptake of dopamine transporter between the left and right corpora striata in the sham-surgery rats, and the images were clear and symmetrically distributed. Specific radioactivity uptake of the normal side （left） was significantly greater than the lesioned side （right） in the model group rats （P 〈 0.01）, and the R value was significantly increased compared with the sham-surgery group （P 〈 0.01）. The radio-ligand accumulation in the right corpus striatum was sparse. In the L-dopa group, specific radioactivity uptake was significantly decreased in the lesioned （right） side of the AiM rats, and the Rvalue was increased compared with the model group （P 〈 0.05）. The amount of radio-ligand in the right corpus striatum was diminished. The Rvalue was significantly reduced in the non-AIM rats compared with the AIM rats （P 〈 0.05）, and specific radioactivity uptake was significantly increased in the lesioned （right） side compared with the normal side （P 〈 0.05）. Moreover, radio-ligand accumulation was observed in the right corpus striatum, and differences in radio-ligand accumulation between the two sides were reduced. CONCLUSION： Following L-dopa treatment, the number and function of dopamine transporter in some PD rats were reduced. L-dopa was shown to be toxic to dopaminergic neurons and induced dyskinesia.展开更多
Faba bean(Vicia faba L.)has been identified as a rich source of L-DOPA,which is used in treating Parkinson's disease.Biosynthesis and accumulation of active substances such as L-DOPA in plant tissues may interact ...Faba bean(Vicia faba L.)has been identified as a rich source of L-DOPA,which is used in treating Parkinson's disease.Biosynthesis and accumulation of active substances such as L-DOPA in plant tissues may interact with growing conditions and processing methods.Accumulation trends of L-DOPA in various faba bean organs and the effect of drought stress and N fertilization on L-DOPA content were studied in a field and two greenhouse experiments.The influence of various processing methods on L-DOPA content of faba bean tissues was evaluated.The highest L-DOPA content was detected in fresh leaves(22.4 mg g^(-1))followed by flowers,young pods,mature seeds,and roots.Regardless of processing method,L-DOPA concentration in faba bean tissues was significantly reduced when tissues were boiled or dried.Among various methods of processing,freezing had the lowest detrimental effect,reducing L-DOPA concentrations by 24.1%and 21.1%in leaves and seeds,respectively.Drought stress elevated L-DOPA concentration,and maximum L-DOPA(23.3 mg g^(-1)of biomass)was extracted from plants grown under severe drought stress.However,L-DOPA yield(L-DOPA concentration×biomass)was compromised,owing to the adverse influence of drought stress on dry matter production.No significant difference in L-DOPA concentration was detected among various N application rates.展开更多
The cis-l-substituted-6,7-dihydroxy-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid esters 3 can be obtained in a highly diastereoselective fashion through 1,3-induction Pictet- Spengler (P-S) cyclization of the L-DO...The cis-l-substituted-6,7-dihydroxy-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid esters 3 can be obtained in a highly diastereoselective fashion through 1,3-induction Pictet- Spengler (P-S) cyclization of the L-DOPA (3,4-dihydroxyphenylalanine) methyl ester with aromatic or aliphatic aldehydes under acidic conditions. Their epimers 4 are also obtained as minor products.展开更多
Cognitive impairment is a frequent non-motorsymptom of Parkinson’s disease (PD). In early disease stage, this takes the features of dysexecutive syndrome, and is mostly dependent on derangement of frontostriatal circ...Cognitive impairment is a frequent non-motorsymptom of Parkinson’s disease (PD). In early disease stage, this takes the features of dysexecutive syndrome, and is mostly dependent on derangement of frontostriatal circuitries. In advanced stages, worsening of dysexecutive symptoms is accompanied by disorientation and memory deficit leading to dementia in 30% of cases, due to multiple neurotransmitter derangement. Dysexecutive symptoms in the early stages of PD may benefit from dopamine replacement therapy (DRT). Conversely, severe cognitive symptoms in more advanced stages are frequently aggravated by DRT. In particular, pulsatile stimulation of dopaminergic receptors by orally administered levodopa (LD) plays a significant negative role on cognitive and neuropsychiatric symptoms in advanced PD. The introduction of a gel of LD-carbidopa for continuous intestinal administration (LCIG) allows marked stabilization of plasma LD concentrations and provides benefit on motor fluctuations and dyskinesia of significantly greater magnitude than conventional oral administration in advanced PD patients. The results from several preliminary studies suggest that efficacy of LCGI on motor symptoms may be accompanied by good tolerability and potential benefit on several non-motor symptoms, including cognitive impairment. Future studies with longer observation period and larger cohorts are advised to confirm these preliminary observations.展开更多
文摘Objective: In the manuscript titled “Liquid subcutaneous Levodopa-Carbidopa ND0612 effects on motor symptoms in individuals with Parkinson’s Disease: A systematic review and meta-analysis”, the objective was to conduct a systematic review with meta-analysis to investigate the effects ND0612 24-hour dosing regimen has on motor symptoms in individuals with Parkinson’s Disease (PD). Introduction: ND0612 is a novel minimally invasive continuous subcutaneous delivery system of liquid Levodopa-Carbidopa being investigated for the treatment of PD in individuals experiencing motor symptoms. Methods: A systematic literature search was conducted in PubMed, Cochrane, and EBSCO databases to identify randomized controlled trials investigating the effects of ND0612 on motor symptoms in individuals with PD. Outcomes included the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II and Part III scores. Methodological quality was assessed using the Cochrane Grading of Recommendations Assessment, Development, and Evaluation approach. Meta-analysis was performed using a random effects model with the DerSimonian and Laird method to estimate the effects of the ND0612 24-hour dosing regimen on UPDRS Part II and Part III scores. Results: Three studies were included in our review. There were statistically significant reductions in UPDRS Part II scores (mean difference (MD) −3.299;95% confidence interval (CI) −3.438, −3.159) and in UPDRS Part III scores (MD −12.695;95% CI −24.428, −0.962) in the ND0612 24-hour dosing regimen. Results were based on very low certainty of evidence. Conclusion: Based on very low certainty evidence, the ND0612 24-hour dosing regimen is effective at improving motor symptoms in individuals with PD. Our findings suggest that ND0612 is more effective at improving UPDRS Part II and Part III scores in individuals with PD than other pharmacological and non-pharmacological treatments, warranting further study.
基金Supported by the Natural Science Foundation of Guangdong Province (No. 011563, No. 04020114).
文摘The inhibitory effect of ferulic acid on the diphenolase activity of mushroom tyrosinase and the kinetic behavior were studied with L-3,4-dihydroxyphenylalanine （L-DOPA） as substrate. The inhibitor concentration leading to 50% relative activity lost （IC50） was estimated to be 0.15 mmol·L^-1. The inhibition mechanism obtained from Lineweaver-Burk plots shows that ferulic acid is a competitive inhibitor and the inhibition of tyrosinase by ferulic acid is a reversible reaction. The equilibrium constant for ferulic acid binding with the tyrosinase was determined to be 0.25 mmol·L^-1 for diphenolase. Keywords tyrosinase, ferulic acid, kinetics, inhibition, L-DOPA, diphenolase
基金Thanks for the fmancial support of National Natural Science Foundation of China （No. 20665001）；Guangxi Science Fund （No. 0640029） and Master Fund of Guangxi University of Technology.
文摘Based on the electrocatalytic oxidation of levodopa at gold electrode and the reduction of permanganate at platinum electrode, a novel flow injection irreversible biamperometric method is developed for the determination of levodopa under the potential difference of 0 V imposed between two electrodes. In H2SO4 solution, the linear relationships between currents and the concentrations of levodopa are obtained in the range from 0.04 mg/L to 20 mg/L with the detection limit of 0.012 mg/L. The proposed method is applied to the determination of levodopa in pharmaceutical preparations.
基金the National Natural Science Foundation of China,No.30672684, 30973722the Third Intention Key Disciplinary Areas of Shanghai,No.S30302
文摘Long-term application of levodopa （L-3, 4-dihydroxyphenylalanine, L-DOPA） for Parkinson＇s disease can lead to adverse effects and reduce the amount of dopamine transporter （DAT） in the corpus striatum. The present study attempted to vedfy whether increasing the amount of DAT can reduce the adverse effects of L-DOPA. The specific radioactive uptake value of DAT in the corpus striatum of the lesioned hemisphere was significantly decreased, but was significantly increased following administration of compound rehmannia formula [Radix rehmanniae preparata （prepared rehmannia root）, Concha margantifera usta （nacre）, Radix paeoniae alba （white peony alba）, Radix salviae miltiotThizae （Danshen root）, Scorpio （scorpion）, green tea] for 4 weeks. The changes in DAT 1251-beta-carbomethoxy-3 beta-（4-iodophenyl） tropane autoradiography were consistent with those in radioactivity. The results revealed that the compound rehmannia formula can reduce the adverse effects of L-DOPA in treating Parkinson＇s disease, possibly by increasing the amount of DAT.
文摘AIM: Many studies have demonstrated N-methyl-D-aspartate receptor-1-subunit (NMDAR1) is associated with amblyopia. The effectiveness of levodopa in improving the visual function of the children with amblyopia has also been proved. But the mechanism is undefined. Our study was to explore the possible mechanism. METHODS: Sixty 14-day-old healthy SD rats were randomly divided into 4 groups, including normal group, monocular deprivation group, levodopa group and normal saline group, 15 rats each. We sutured all the rats' unilateral eyelids except normal group to establish the monocular deprivation animal model and raise them in normal sunlight till 45-day-old. NMDAR1 was detected in the visual cortex with immunohistochemistry methods, Western Blot and Real time PCR. LD and NS groups were gavaged with levodopa (40mg/kg) and normal saline for 28 days respectively. NMDAR1 was also detected with the methods above. RESULTS: NMDAR1 in the visual cortex of MD group was less than that of normal group. NMDAR1 in the visual cortex of LD group was more than that of NS group. CONCLUSION: NMDAR1 is associated with the plasticity of visual development. Levodopa may influence the expression of NMDAR1 and improve visual function, and its target may lie in the visual cortex.
基金This work was supported by Science Foundation of the National Education Ministry(No.206096)Education Department of Hubei Province(No.Z200522002),
文摘A novel method for the simultaneous determination of benserazide and levodopa using capillary electrophoresis （CE）- chemiluminescence （CL） has been developed. Under the optimal conditions, the detection limits （S/N = 3） were 1.85 μg/mL for benserazide and 0.12 μg/mL for levodopa. This method was successfully applied to the determination of benserazide and levodopa in Medopar tablet, the results showed that the detected values are in accordance with those by official methods.
基金the Scientific Research Foundation Program of Ministry of Health,No.wkj.2005-2-030
文摘BACKGROUND： Radio-imaging has been used in neurological diagnosis, in particular for extrapyramidal disease. Moreover, it has been extensively utilized for early diagnosis of Parkinson＇s disease （PD） patients and in animal studies. However, it has rarely been utilized to assess drug-induced side effects in PD. OBJECTIVE： To investigate changes in dopamine transporter expression in a rat model of PD through the use of radio-imaging taking ^99mTc-TRODAT-1 as an imaging agent, and to explore the effect of levodopa （L-dopa） on dopaminergic neurons and the possible mechanisms of dyskinesia induction. DESIGN, TIME AND SETTING： A randomized, controlled, animal study was performed at the Laboratory of Department of Nuclear Medicine, Soochow University from April 2006 to June 2007. MATERIALS： 6-hydroxydopamine was purchased from Sigma, USA and L-dopa was purchased from Shanghai Fuda Pharmaceutical, China. ^99mTcO4-fresh elutriant was provided by the Department of Nuclear Medicine, First Hospital Affiliated to Soochow University. TRODAT-1 image kit was provided by Jiangsu Atomic Energy Research Establishment, China. The SN-695B radioimmunoassay gamma counter was purchased from Shanghai Hesuo Rihuan Photoelectric Instrument, China. The AZ-CA256eZ-Scope portable y camera was purchased from Anzai Medical, Japan. METHODS： A total of 34 healthy, male, Sprague Dawley rats were selected. Thirty were used to establish a PD model by injecting 6-hydroxydopamine into the right medial forebrain bundle, and four were injected with normal saline and served as the sham-surgery group. At the end of 4 weeks, 21 successful PD models were selected and randomly assigned to the L-dopa （n = 15, 20 mg/kg per day）, model （n = 6, normal saline）, and sham-surgery （n = 4, no treatment） groups. After 1 month of treatment, involuntary movement was evaluated twice weekly in each rat. A total of 0.2 mL ^99mTc-TRODAT-1 was injected into the tail vein 2 days following drug termination, and images of dopamine transporters were acquired 2 hours later. The rats were sacrificed and the ratios of specific radioactivity uptake were calculated. MAIN OUTCOME MEASURES： Manifestations of abnormal involuntary movement （AIM） were observed and total AIM scores were calculated. Images of dopamine transporters were acquired using an eZ-Scope portable y camera, and radioactive y quantification of ^99mTC-TRODAT-1 in the rat brains was assayed. The ratios of the left and right corpora striata were determined. The number and function of dopamine transporters was evaluated according to specific radioactivity uptake ratio （R） from the left and right corpora striata. RESULTS： Of 15 PD rats, nine exhibited AIM following L-dopa treatment： five scored 〉 20, i.e., severe grade, four scored 8-16, mild grade, and the remaining exhibited normal behavior. There were no differences in specific radioactivity uptake of dopamine transporter between the left and right corpora striata in the sham-surgery rats, and the images were clear and symmetrically distributed. Specific radioactivity uptake of the normal side （left） was significantly greater than the lesioned side （right） in the model group rats （P 〈 0.01）, and the R value was significantly increased compared with the sham-surgery group （P 〈 0.01）. The radio-ligand accumulation in the right corpus striatum was sparse. In the L-dopa group, specific radioactivity uptake was significantly decreased in the lesioned （right） side of the AiM rats, and the Rvalue was increased compared with the model group （P 〈 0.05）. The amount of radio-ligand in the right corpus striatum was diminished. The Rvalue was significantly reduced in the non-AIM rats compared with the AIM rats （P 〈 0.05）, and specific radioactivity uptake was significantly increased in the lesioned （right） side compared with the normal side （P 〈 0.05）. Moreover, radio-ligand accumulation was observed in the right corpus striatum, and differences in radio-ligand accumulation between the two sides were reduced. CONCLUSION： Following L-dopa treatment, the number and function of dopamine transporter in some PD rats were reduced. L-dopa was shown to be toxic to dopaminergic neurons and induced dyskinesia.
基金partially funded through a graduate student grant received from Northeast Sustainable Agriculture Research and Education(GNE14-078)
文摘Faba bean(Vicia faba L.)has been identified as a rich source of L-DOPA,which is used in treating Parkinson's disease.Biosynthesis and accumulation of active substances such as L-DOPA in plant tissues may interact with growing conditions and processing methods.Accumulation trends of L-DOPA in various faba bean organs and the effect of drought stress and N fertilization on L-DOPA content were studied in a field and two greenhouse experiments.The influence of various processing methods on L-DOPA content of faba bean tissues was evaluated.The highest L-DOPA content was detected in fresh leaves(22.4 mg g^(-1))followed by flowers,young pods,mature seeds,and roots.Regardless of processing method,L-DOPA concentration in faba bean tissues was significantly reduced when tissues were boiled or dried.Among various methods of processing,freezing had the lowest detrimental effect,reducing L-DOPA concentrations by 24.1%and 21.1%in leaves and seeds,respectively.Drought stress elevated L-DOPA concentration,and maximum L-DOPA(23.3 mg g^(-1)of biomass)was extracted from plants grown under severe drought stress.However,L-DOPA yield(L-DOPA concentration×biomass)was compromised,owing to the adverse influence of drought stress on dry matter production.No significant difference in L-DOPA concentration was detected among various N application rates.
文摘The cis-l-substituted-6,7-dihydroxy-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid esters 3 can be obtained in a highly diastereoselective fashion through 1,3-induction Pictet- Spengler (P-S) cyclization of the L-DOPA (3,4-dihydroxyphenylalanine) methyl ester with aromatic or aliphatic aldehydes under acidic conditions. Their epimers 4 are also obtained as minor products.
文摘Cognitive impairment is a frequent non-motorsymptom of Parkinson’s disease (PD). In early disease stage, this takes the features of dysexecutive syndrome, and is mostly dependent on derangement of frontostriatal circuitries. In advanced stages, worsening of dysexecutive symptoms is accompanied by disorientation and memory deficit leading to dementia in 30% of cases, due to multiple neurotransmitter derangement. Dysexecutive symptoms in the early stages of PD may benefit from dopamine replacement therapy (DRT). Conversely, severe cognitive symptoms in more advanced stages are frequently aggravated by DRT. In particular, pulsatile stimulation of dopaminergic receptors by orally administered levodopa (LD) plays a significant negative role on cognitive and neuropsychiatric symptoms in advanced PD. The introduction of a gel of LD-carbidopa for continuous intestinal administration (LCIG) allows marked stabilization of plasma LD concentrations and provides benefit on motor fluctuations and dyskinesia of significantly greater magnitude than conventional oral administration in advanced PD patients. The results from several preliminary studies suggest that efficacy of LCGI on motor symptoms may be accompanied by good tolerability and potential benefit on several non-motor symptoms, including cognitive impairment. Future studies with longer observation period and larger cohorts are advised to confirm these preliminary observations.
