It has been reported that the antiparkinsonian efficacy of levodopa is reduced after long-term administration However, main parkinsonian motor symptoms, since they are mainly caused by the deficiency of nigrostriatal dopamine, should be corrected if sufficient dopamine is supplied exogenously. Therefore, the functional decline in patients with long-term levodopa therapy may result either from side effects such as response fluctuation and abnormal involuntary movements or from progression of doPa -unresponsive parkinsonian symptoms, instead of reduction in levodopa efficacy itself. To adress this question, we measured residual motor disability during and at 6 hours after continuous intravenous levodopa infusion with optimal dose for at least 16 hours in 54 patients with idiopathic Parkinson's disease. While the basal motor disability is increased according to the advance of symptom duration as well as Hoehn and Yahr stage, the residual motor disability after levodpa supplement is not changed. The duration of levodopa therapy until development of motor fluctuation is significantly shorter in good responder (residual motor disability<2. 0) than in poor r-ponder(residual motor disability>2.0), and positively correlated to the residual motor disability. These findings suggest; first, the functional decline observed in parkinsonian patients with chronic levodopa therapy mainly results from motor fluctuation and/or progression of dopa-unresponsive symptoms, not from decline of levodopa efficacy itself on cardinal motor symptoms; second, the parkinsonian patients with good levodopa response may develop motor fluctuation earlier than those with poor response.
Dihydroxyphenylalanine ; Dopamine ; Dyskinesias ; Humans ; Levodopa* ; Parkinson Disease

BACKGROUND: The biosynthesis of melanin is initiated by the enzymatic oxidation of L-tyrosine to L-dopa by tyrosinase. Some precursors of melanin are cytotoxic, and melanoma cells are killed as a risk of exposare to excess tyrosine or dopa in the culture medium. However, there have been few observations of the effects of L-tyrosine on cultured normal human melanocyte. OBJECTIVE: In order to investigate whether exogenous tyrosine induces cytotoxicity in cultured normal human melanocytes as in melanoma cells, we examined the effects of L-tyrosine on proliferation and melanization in normal human melanocytes. METHODS: A melanocyte culture was produced with a modified TIC medium. L-tyrosine was added to the culture medium, 100, 200, 400, and 800uM. After 2 days of incubation, the proliferation was measured by methylthiazol tetrazolium(MTT) assay and sulforhodamine B(SRB) assay. The melanin contenis were also measured by the modified Whittaker's method. RESULTS: On MTT assay, the proliferation of melanocytes had been stirnulated significantly (p< 0.05) in all L-tyrosine added groups. On SRB assay, the proliferation of melanocytes had heen stimulated significantly (p<005) in 200, 400, 800uM of L-tyrosine added groups. The melanin contents had increased in all L-tyrosine added groups, and had increased significantly (p<0.05) in 400uM of L-tyrosine added group. CONCLUSION: L-tyrosine is not toxic to normal melanocytes, It stimulates the proliferation and melnization of cultured normal human melanocytes.
Dihydroxyphenylalanine ; Humans* ; Levodopa ; Melanins ; Melanocytes* ; Melanoma ; Monophenol Monooxygenase ; Tics ; Tyrosine*

BACKGROUND: The biosynthesis of melanin is initiated by the enzymatic oxidation of L-tyrosine to L-dopa by tyrosinase. Some precursors of melanin are cytotoxic, and melanoma cells are killed as a risk of exposare to excess tyrosine or dopa in the culture medium. However, there have been few observations of the effects of L-tyrosine on cultured normal human melanocyte. OBJECTIVE: In order to investigate whether exogenous tyrosine induces cytotoxicity in cultured normal human melanocytes as in melanoma cells, we examined the effects of L-tyrosine on proliferation and melanization in normal human melanocytes. METHODS: A melanocyte culture was produced with a modified TIC medium. L-tyrosine was added to the culture medium, 100, 200, 400, and 800uM. After 2 days of incubation, the proliferation was measured by methylthiazol tetrazolium(MTT) assay and sulforhodamine B(SRB) assay. The melanin contenis were also measured by the modified Whittaker's method. RESULTS: On MTT assay, the proliferation of melanocytes had been stirnulated significantly (p< 0.05) in all L-tyrosine added groups. On SRB assay, the proliferation of melanocytes had heen stimulated significantly (p<005) in 200, 400, 800uM of L-tyrosine added groups. The melanin contents had increased in all L-tyrosine added groups, and had increased significantly (p<0.05) in 400uM of L-tyrosine added group. CONCLUSION: L-tyrosine is not toxic to normal melanocytes, It stimulates the proliferation and melnization of cultured normal human melanocytes.
Dihydroxyphenylalanine ; Humans* ; Levodopa ; Melanins ; Melanocytes* ; Melanoma ; Monophenol Monooxygenase ; Tics ; Tyrosine*

To investigate the correlation between urinary growth hormone(GH) level and peak serum GH level, urinary GH value measured by overnight collection of urine for 10 hours and serum GH value in response to GH provocation test using insulin and L-dopa were measured in 9 cases of GH complete deficiency(GCD), 19 cases of GH partial deficiency(GPD) and 40 cases of GH normal short stature(GHN). Urinary GH values were measured by the EIA method using PICOIA HGH plate(Joo Woo Pharmaceutical Co., Japan). Urinary GH was expressed in terms of nanograms per gm creatinine(ng/gCr). Serum GH was measured by immunoradiometric assay using "Daiichi kit"(Je Il Pharmaceutical Co., Japan). Wilcoxon ranked sum test and student's t-test were used to assess the significance of differences between the groups of the patients. The correlation between urinary GH level and peak serum GH level was assessed by the parametric Pearson correlation test. The correlation between peak serum GH level in GH provocation test using insulin and urinary GH level measured by overnight 10 hours collection method showed statistically significant results in all the patients(Y=0.464072X +9.208044, r=0.48987, p=0.0001) and in the GH deficiency groups(GCD+GPD) (Y=0.924659X +9.2385509, r=0.80437, p=0.0001). In case of L-dopa stimulation test, urinary GH values were also positively correlated with peak serum GH level when all the patients were participated(Y=0.572988X +8.312993, r=0.58212, p=0.0001). In contrast, no correlation was found when patients were confined to GH deficiency group(GCD+GPD)(Y=0.127712X +8.3129939, r=0.08044, p=0.6841).
Dihydroxyphenylalanine ; Growth Hormone ; Humans ; Immunoradiometric Assay ; Insulin ; Levodopa ; Methods

The goal of this study was to determine whether gypenosides (GPS) exert protective effects against dopaminergic neuronal cell death in a 6-hydroxydopamine (OHDA)-lesioned rat model of Parkinson's disease (PD) with or without long-term 3,4-dihydroxyphenylalanine (L-DOPA) treatment. Rats were injected with 6-OHDA in the substantia nigra to induce PD-like symptoms; 14 days after injection, groups of 6-OHDA-lesioned animals were treated for 21 days with GPS (25 or 50 mg/kg) and/or L-DOPA (20 mg/kg). Dopaminergic neuronal cell death was assessed by counting tyrosine hydroxylase (TH)-immunopositive cells in the substantia nigra and measuring levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the striatum. Dopaminergic neuronal cell death induced by 6-OHDA lesions was ameliorated by GPS treatment (50 mg/kg). L-DOPA treatment exacerbated 6-OHDA-induced dopaminergic neuronal cell death; however, these effects were partially reversed by GPS treatment (25 and 50 mg/kg). These results suggest that GPS treatment is protective against dopaminergic neuronal cell death in a 6-OHDA-lesioned rat model of PD with long-term L-DOPA treatment. Therefore, GPS may be useful as a phytotherapeutic agent for the treatment of PD.
3,4-Dihydroxyphenylacetic Acid ; Animals ; Cell Death* ; Dihydroxyphenylalanine ; Dopamine ; Dopaminergic Neurons* ; Homovanillic Acid ; Levodopa* ; Models, Animal* ; Norepinephrine ; Oxidopamine ; Parkinson Disease* ; Rats* ; Substantia Nigra ; Tyrosine 3-Monooxygenase

This study was undertaken to investigate the effect of UVB radiation on epidermal melanoctes of C57BIL mouse, The results are summarized as follows : l) The numerical increase of DOPA positive melanocytes following UVB irradiation was due to both of active mitosis of epidermal melanocytes and the conversion of dormant. malanocytes to DOPA-positive melsnocytes. 2) Long term effects of UVB irradiatinn on the epidermal melanocytes suggest the persistent activation of typrosinase in UVB irradiated melanocytes.
Animals ; Dihydroxyphenylalanine ; Melanocytes* ; Mice* ; Microscopy, Electron ; Mitosis

In order to observe neuronal toxical effect of Levodopa and investigate if using Levodopa together with Ginkgo Bilobar Extract (EGb) would be an workable method to treat Parkinson disease, rat models of Parkinson disease (PD) were made by injecting 6-OHDA stereotaxically to right side of the mesencephic ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Rotational behavioral observation, TUNEL, immunocytochemistry, Nissl's body staining were performed to measure the difference between group treated by Levodopa (50 mg/kg every day for 3 days, 5 days, 7 days, L-dopa group) and group treated by Levodopa combined with EGb (100 mg/kg every day, E-D group). The results showed that in the L-dopa group, the numbers of apoptosis of substantial nigra, rings of rotational behavior were more than those in the E-D group (P < 0.05). The numbers of Nissl's cells in L-dopa group were fewer than in E-D group (P < 0.05). The results suggested that Levodopa had neur toxic effect and EGb may decrease the toxicity of levodopa. The combined use of EGb with Levodopa may be a workable method to treat PD and may be better than using Levodopa alone.
Animals ; Apoptosis ; drug effects ; Dihydroxyphenylalanine ; metabolism ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Ginkgo biloba ; Levodopa ; pharmacology ; therapeutic use ; toxicity ; Male ; Neurons ; drug effects ; Oxidopamine ; Parkinson Disease ; metabolism ; pathology ; prevention & control ; Random Allocation ; Rats ; Rats, Wistar ; Substantia Nigra ; pathology

We present a case of acquired, bilateral nevus of Ota-like macules in 50-year-old women, She had deeply brownish, confluent or solitary macules and patches distributed symmetrically on the both side of the forehead and temple, since years ago. But there was no involvement (of ocular and oral mucosa. Histopathologic findings showed flattening of the rete ridges and elongated or irregular shaped melanocytes containing many melaiiin granules, in upper-and mid-dermis. And most of melanocytes showed positive reactions on Dopa stain.
Dihydroxyphenylalanine ; Female ; Forehead ; Humans ; Melanocytes ; Middle Aged ; Mouth Mucosa ; Nevus*

We report a case of morphea occuring in vitiliginous lesions. About 5 months ago, two lesions of 4X4cm-sized depigmented patches appeared on her left thigh. The depigmented patches had begun to be hardened about 3 months ago. Histopathologic examinations showed that the reticular dermis appeared thickened, closely packed, hypocellular, and stained more deeply eosinophilic than in normal skin. The epidermis had no melanin pigments. Dopa stain was negative in white lesion, whereas Dopa stain was positive in normal lesion.
Dermis ; Dihydroxyphenylalanine ; Eosinophils ; Epidermis ; Melanins ; Scleroderma, Localized* ; Skin ; Thigh ; Vitiligo

Tatbion is a tripeptide, reduced form of Glutathione(GSH or p-glutamyl-cysteiny1 -glycine). Glutathione(SH compound)is believed to inhibit melanin formation by combining witb the copper in tyrnsinase whicb is essential in the conversion of tyrosine to DOPA (3, 4-dihydroxyphenylalanine) and DOPA to DOPA-quinone or by forming cornplex with the intermediate in the tyrosine-to-melaa.in reaction. The effect of Tathion in the treatment of melasma has not been reported in Korea. We have observed the effect of Tatbion in 150 patients with melasma. After the average duration of Gwks of treatment(50-100mg tree tirnes/daily), we were abIe to grade the results as follow. Excellent(Pigmentation almost disappeared): 17. 4 % Good (Pigmentation markedly improved): 56. 7% Fair (Pigmentation slightly improved: 7. 3% None (No effect) : 18.6% The result showed relatively good effects of Tathion in the treatment of 122pts (81.4%) with melasma in total. The brief review of literature on the treatment of melasma was undertaken.
Copper ; Dihydroxyphenylalanine ; Glutathione* ; Humans ; Korea ; Melanins ; Melanosis* ; Tyrosine