• YAKHAK HOEJI
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• v.55 no.6
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• pp.510-515
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• 2011

Isoquinoline compounds including berberine enhance L-DOPA-induced cytotoxicity in PC12 cells. In this study, the effects of berberine on L-DOPA therapy in unilateral 6-hydroxydopamine (6-OHDA)-induced rat models of parkinsonism were investigated. Rats were prepared for the models of Parkinson's disease by 6-OHDA-lesioning for 14 days and then treated with L-DOPA (10 mg/kg) with or without berberine (5 and 30 mg/kg, i.p.) for 21 days. Treatment with berberine (5 and 30 mg/kg, i.p.) showed a dopaminergic cell loss in substantia nigra of 6-OHDA-lesioned rats treated with L-DOPA: 30 mg/kg berberine was more intensive neurotoxic. The levels of dopamine were also decreased by berberine (5 and 30 mg/ kg) in striatum-substantia nigra of 6-OHDA-lesioned rats treated with L-DOPA. These results suggest that berberine aggravates cell death of dopaminergic neurons in L-DOPA-treated 6-OHDA-lesioned rat models of Parkinson's disease. Therefore, the long-term L-DOPA therapeutic patients with isoquinoline compounds including berberine may need to be checked for the adverse symptoms.

• Korean Journal of Pharmacognosy
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• v.34 no.3 s.134
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• pp.242-245
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• 2003

The effects of chelidonine, a benzophenanthridine isoquinoline alkaloid, on L-DOPA-induced cytotoxicity in PC12 cells were investigated. The treatment of PC12 cells with chelidonine $(1-4\;{\mu}M)$ decreased dopamine content in a dose-dependent manner (30.2% inhibition at $4\;{\mu}M)$. Chelidonine was not cytotoxic up to $4\;{\mu}M)$. However, chelidonine at concentrations higher than $5\;{\mu}M$ caused a cytotoxicity in PC12 cells. L-DOPA at concentrations higher than $50\;{\mu}M$ led to cell damage by oxidative stress in PC12 cells. Chelidonine at non-cytotoxic concentration ranges of $1-4{\mu}M$ aggravated L- DOPA $(20-50\;{\mu}M)$-induced cytotoxicity in PC12 cells. The L-DOPA-induced cytotocxicity was synergistically stimulated by chelidonine at concentrations grader than $5\;{\mu}M$. These data demonstrate that chelidonine exacerbates L-DOPA-induced cytotoxicity. Therefore, it is proposed that the long-term L-DOPA therapeutic patients with chelidonine may need to be checked for the adverse symptoms.

• Journal of Korean Dental Science
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• v.11 no.2
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• pp.43-56
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• 2018

Purpose: The purpose of this study was to assess the adhesiveness and cytotoxicity of 3, 4-dihydroxyphenylalanine (DOPA), and to evaluate the role of collagen membrane with DOPA in the guided bone regeneration. Materials and Methods: Peel resistance and cell cytotoxicity test were performed. Four defect types in nine rabbit calvaria were randomly allocated: i) control, ii) membrane, iii) deproteinized porcine bone mineral (DPBM) covered by membrane with DOPA, and iv) DPBM covered by membrane with cyanoacrylate. Animals were sacrificed at 2 (n=4) and 8 weeks (n=5) for microcomputed tomography and histomorphometric analysis. DOPA showed low peel resistance but high cell viability. Result: Cyanoacrylate and DOPA groups showed significantly higher mineralized tissue volume (MTV) compared to control and membrane groups at 2 weeks (P<0.05). At 8 weeks, DOPA group showed the highest MTV. Significantly higher new bone area was found in DOPA group at 8 weeks (P<0.05). Bone formation increased from 2 to 8 weeks in DOPA group (P<0.05). Conclusion: DOPA showed high cell viability and in vivo study revealed predictable performance in bone regeneration.

• Archives of Pharmacal Research
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• v.29 no.8
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• pp.645-650
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• 2006

Tributyltin chloride (TBTC) at concentrations of $0.5-1.0\;{\mu}M$ inhibits dopamine biosynthesis in PC12 cells. In this study, the effects of TBTC on L-3,4-dihydroxyphenylalanine (L-DOPA)-induced cytotoxicity in PC12 cells were investigated. TBTC at concentrations up to $1.0\;{\mu}M$ neither affected cell viability, nor induced apoptosis after 24 or 48 h in PC12 cells. However, TBTC at concentrations higher than $2.0\;{\mu}M$ caused cytotoxicity through an apoptotic process. In addition, exposure of PC12 cells to non-cytotoxic (0.5 and $1.0\;{\mu}M$) or cytotoxic $(2.0\;{\mu}M)$ concentrations of TBTC in combination with L-DOPA (20, 50 and $100\;{\mu}M$) resulted in a significant increase in cell loss and the percentage of apoptotic cells after 24 or 48 h compared with TBTC or L-DOPA alone. The enhancing effects of TBTC on L-DOPA-induced cytotoxicity were concentration- and treatment time-dependent. These data demonstrate that TBTC enhances L-DOPA-induced cytotoxicity in PC 12 cells.

• Journal of the Korean Chemical Society
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• v.44 no.6
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• pp.541-546
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• 2000

Methods to determine L-dopa(L-3,4-dihydroxyphenylalanine) in aqueous solution by spectrofluorimetry based upon the ligand sensitized luminescence of Tb(III) ion L-dopa complex have been studied. Tb(III) ion and Lu(III) ion were used as ligand sensitized fluorescencer and co-fluorescence enhancer, respectively. The effects of excitation wavelength, pH, concentration of Tb(III) ion, concentration of Lu(III) ion and emission wavelength on the fluorescence intensity were investigated. The fluorescence intensity of the Tb(III) ion L-dopa complex was further increased with addition of Lu(III) ion. The calibration curve for L-dopa was linear over the range from 5.0 ${\times}$ $10^{-7}$ M to 1.0${\times}$ $10^{-4}$ M and the detection limit was 4.0 ${\times}$ $10^{-8}$ M under the optimal experimental conditions of 300 nm, 8.0, 1.0 ${\times}$ $10^{-4}$ M and 545 nm for excitation wavelength, pH, concentration of Tb(III) ion and emission wavelength, respectively. When Lu(III) ion was added to Tb(Ⅲ) ion L-dopa complex, the concentration range of linear response and detection limit were 1.0${\times}$$10^{-8}$ M to 2.0 ${\times}$ $10^{-4}$ M and 1.0 ${\times}$ $10^{-9}$ M, respectively under the optimal experimental conditions of 300 nm, 8.5, 1.0 ${\times}$ $10^{-5}$ M, 1.0 ${\times}$ $10^{-5}$ M, 545 nm for excitation wavelength, pH, concentration of Tb(III) ion, concentration of Lu(III) ion and emission wavelength, respectively.

• Microbiology and Biotechnology Letters
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• v.24 no.2
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• pp.222-226
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• 1996

The enzymatic synthesis of 3, 4-dihydroxyphenyl-L-alanine (L-DOPA) was examined for the effects of the reaction additives such as sodium borate, alcohol, and organic solvents. The enzyme used was tyrosine phenol-lyase of Citrobacter freundii KCTC 2006 produced in Escherichia coli. The amounts of tyrosine phenol-lyase and pyridoxal-5-phosphate were optimized to 2.0 units/ml and 0.1 mM, respectively, for the synthetic reaction. Sodium borate, a substance that forms a complex with pyrocatechol, reduced the enzyme deactivation by pyrocatechol although it seriously inhibited the enzyme activity. Among the organic solvents tested, dimethylsulfoxide, dimethylformamide, and alcohol increased the productivity of the L-DOPA synthesis. In a reaction system with 5% methanol, L-DOPA concentration increased up to 210 mM after 24 hours, and 77.1% of which was separated as precipitates. The L-DOPA was purified to 99.96% by solubilizing and recrystallyzing the precipitates.

• Journal of Environmental Health Sciences
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• v.22 no.1
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• pp.1-4
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• 1996

I have conducted two testings to find out which water is better for drinking water. First, I made 20 mM L-DOPA solutions by solving L-DOPA (3,4-Dihydroxyphenylalanine) in tap water, Waters' mineral water and reverse osmotic water. Then I measured activities after adding Tyrosinase (purifide enzyme, step 3), which was extracted from Salanum melongena(mad apple), in each L-DOPA solution. Second, I solved 0.1, 0.5 and 0.9% salt in each 20 mM L-DOPA distilled water to measure activity of each salt solution. The results of the testings are as follows: 1. 10 minutes after adding Salanum melongena(mad apple) tyrosinase in each L-DOPA solution, activity of Waters' mineral water was 0.867 tap water 0.777 and reverse osmotic water 0.742. 2. Activity of Waters' mineral water was higher than that of tap water by 10.4% and higher then reverse osmotic by 14.4%. 3. Activity of Waters' mineral water was much higher than that of 0.9% salt water by 41.8%. 4. The optimum pH of Salanum melongena (mad apple) tyrosinase is 9.0. Most enzymes working in the human metabolism are alkaline and body fluids' pH also alkaline. In conclusion, an alkaline water is believed better than an acidic water for drinking.

• Journal of Microbiology and Biotechnology
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• v.6 no.2
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• pp.98-102
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• 1996

A thermostable tyrosine phenol-lyase gene of a thermophilic Symbiobacterium species was cloned and overexpressed in Escherichia coli in order to produce the biocatalyst for the synthesis of 3, 4-dihy-droxyphenyl-L-alanine (L-DOPA). The substrates used for the synthetic reaction were pyrocatechol, so-dium pyruvate, and ammonium chloride. The enzyme was stable up to $60^{\circ}C$, and the optimal temperature for the synthesis of L-DOPA was $37^{\circ}C$ . The optimal pH of the reaction was about 8.3. Enzyme activity was highly dependent on the amount of ammonium chloride and the optimal concentration was estimated to be 0.6 M. In the case of pyrocatechol, an inactivation of enzyme activity was observed at con-centrations higher than 0.1 M. Enzyme activity was increased by the presence of ethanol. Under op-timized conditions, L-DOPA production was carried out adding pyrocatechol and sodium pyruvate to the reaction solution intermittently to avoid substrate depletion during the reaction. The concentration of L-DOPA reached 29.8 g/l after 6 h, but the concentration didn t increase further because of the formation of byproducts by a non-enzymatic reaction between L-DOPA and pyruvate.

• Journal of Microbiology and Biotechnology
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• v.22 no.10
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• pp.1446-1451
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• 2012

Levodopa or L-3,4-dihydroxyphenylalanine (L-DOPA) is the precursor of the neurotransmitter dopamine. L-DOPA is a famous treatment for Parkinson's disease symptoms. In this study, electroenzymatic synthesis of L-DOPA was performed in a three-electrode cell, comprising a Ag/AgCl reference electrode, a platinum wire auxiliary electrode, and a glassy carbon working electrode. L-DOPA had an oxidation peak at 376 mV and a reduction peak at -550 mV. The optimum conditions of pH, temperature, and amount of free tyrosinase enzyme were pH 7, $30^{\circ}C$, and 250 IU, respectively. The kinetic constant of the free tyrosinase enzyme was found for both cresolase and catacholase activity to be 0.25 and 0.4 mM, respectively. A cyclic voltammogram was used to investigate the electron transfer rate constant. The mean heterogeneous electron transfer rate ($k_e$) was $5.8{\times}10^{-4}$ cm/s. The results suggest that the electroenzymatic method could be an alternative way to produce L-DOPA without the use of a reducing agent such as ascorbic acid.

• The Korean Journal of Nuclear Medicine Technology
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• v.19 no.1
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• pp.67-71
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• 2015

Purpose At recently, we enter into the aging society and a age-related disease is increasing. Among that, prevalence of degenerative brain disease like Parkin's disease will be increased. So, many radiopharmaceuticals is developed to diagnosis early and to evaluate the performance of therapeutic drugs. Especially $^{18}F-DOPA$ which involved at dopamine synthesis and function of storage is widely used to the diagnosis of Parkinson's disease as well as brain tumors. in the study, we will evaluate the distribution pattern of $^{18}F-DOPA$ at the striatum by using dynamic study. Materials and Methods We used Biograph Truepoint(Siemens, Germany) as PET/CT scanner, injected a $^{18}F-DOPA$ ($600{\pm}30MBq$) to patient (4men, 6women. $67{\pm}11age$) who visited our hospital from June to September, started 95min dynamic study at same time. after finishing acquisition, we reconstructed PET data with 19 frame every 5 minutes, analysed a average counts at ROI's where set at both striatums, anterior putamen, posterior putamen Results Counts in the cerebellum as the background formed a plateau after 90 minutes from the highest out rapidly reduced to 15 minutes. Counts of anterior putamen and posterior gradually increased but formed a plateau after 60min. A count ratio of Striatum to cerebellum was continuously increased up to more than 95 minutes, A count ratios of an anterior putamen to posterior one formed a plateau after 85 minutes. Conclusion The dynamic acquisition can be possible to evaluate a distribution of the $^{18}F-DOPA$ in the striatum and the VOI analysis through a dynamic acquisition and a variety of patterns. Futhermore, to make a uniformed distribution and count ratio of striatum to cerebellum, a static acquisition will have to start 90minutes later after injection.