Ameliorative Effects of Ombuoside on Dopamine Biosynthesis in PC12 Cells

This study investigated the effects of ombuoside, a flavonol glycoside, on dopamine biosynthesis in PC12 cells. Ombuoside at concentrations of 1, 5, and 10 µM increased intracellular dopamine levels at 1 – 24 h. Ombuoside (1, 5, and 10 µM) also significantly increased the phosphorylation of tyrosine hydroxylase (TH) (Ser40) and cyclic AMP-response element binding protein (CREB) (Ser133) at 0.5 – 6 h. In addition, ombuoside (1, 5, and 10 µM) combined with L-DOPA (20, 100, and 200 µM) further increased intracellular dopamine levels for 24 h compared to L-DOPA alone. These results suggest that ombuoside regulates dopamine biosynthesis by modulating TH and CREB activation in PC12 cells.

Risk Factors for Cognitive Impairment in Patient with Parkinson's Disease Treated with Levodopa

BACKGROUND: Long-term levodopa therapy relieves the motor dysfunction associated with Parkinson's disease (PD), but has various effects on non-motor symptoms, including cognitive dysfunction, hallucinations, and affective disorders, and can exacerbate certain aspects of dementia-like cognitive dysfunction. Here, we investigated the relationship between levodopa treatment and development of dementia in patients with PD. METHODS: This retrospective study analyzed 76 consecutive patients with PD who had taken levodopa between 2011 and 2015. The participants were initially free of dementia and had initial daily levodopa doses of below 600 mg. Patients who did and did not develop comorbid dementia were compared in terms of potential predictor variables, including PD onset age, sex, levodopa doses, and non-dementia comorbidities. RESULTS: Of the 76 patients, 21 (27.6%) developed dementia, which was followed by hallucinations and insomnia. The independent predictors of incident dementia were PD onset age and second-year and third-year average levodopa doses that were higher than the first-year average levodopa dose. Patients who developed dementia had significantly higher average daily levodopa doses and levodopa dose increases over the 6-year treatment period than those who did not develop dementia. In addition, patients with higher levodopa doses were more likely to experience hallucinations. CONCLUSION: These results suggest that increases in levodopa doses may be associated with a greater risk of cognitive impairment in patients with PD. Therefore, motor and cognitive functions and levodopa dose increases should be evaluated regularly during long-term levodopa therapy in patients with PD.

Effects of (−)-Sesamin on Memory Deficits in MPTP-lesioned Mouse Model of Parkinson's Disease

This study investigated the effects of (−)-sesamin on memory deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD). MPTP lesion (30 mg/kg/day, 5 days) in mice showed memory deficits including habit learning memory and spatial memory. However, treatment with (−)-sesamin (25 and 50 mg/kg) for 21 days ameliorated memory deficits in MPTP-lesioned mouse model of PD: (−)-sesamin at both doses improved decreases in the retention latency time of the passive avoidance test and the levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid, improved the decreased transfer latency time of the elevated plus-maze test, reduced the increased expression of N-methyl-D-aspartate (NMDA) receptor, and increased the reduced phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB). These results suggest that (−)-sesamin has protective effects on both habit learning memory and spatial memory deficits via the dopaminergic neurons and NMDA receptor-ERK1/2-CREB system in MPTP-lesioned mouse model of PD, respectively. Therefore, (−)-sesamin may serve as an adjuvant phytonutrient for memory deficits in PD patients.

Effects of Gypenosides on Dopaminergic Neuronal Cell Death in 6-Hydroxydopamine-lesioned Rat Model of Parkinson's Disease with Long-term L-DOPA Treatment

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.

Epigallocatechin gallate attenuates L-DOPA-induced apoptosis in rat PC12 cells

In this study, the protective effects of EGCG on L-3,4-dihydroxyphenylalanine (L-DOPA)-induced oxidative cell death in catecholaminergic PC12 cells, the in vitro model of Parkinson's disease, were investigated. Treatment with L-DOPA at concentrations higher than 150 microM caused cytotoxicity in PC12 cells, as determined using the 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry detection. The apoptotic ratio was similar in cells treated with 100 microM EGCG plus 150 microM L-DOPA (5.02%) and the control (0.96%) (P > 0.05), and was lower than that of cells treated with L-DOPA only (32.24%, P < 0.05). The generation level of ROS (% of control) in cells treated with EGCG plus L-DOPA was lower than that in cells treated with L-DOPA only (123.90% vs 272.32%, P < 0.05). The optical density in production of TBARS in cells treated with L-DOPA only was higher than that in the control (0.27 +/- 0.05 vs 0.08 +/- 0.04, P < 0.05), and in cells treated with EGCG only (0.14 +/- 0.02, P < 0.05), and EGCG plus L-DOPA (0.13 +/- 0.02, P < 0.05). The intracellular level of GSH in cells treated with EGCG plus L-DOPA was higher than that in cells treated with L-DOPA only (233.25 +/- 16.44 vs 119.23 +/- 10.25, P < 0.05). These results suggest that EGCG protects against L-DOPA-induced oxidative apoptosis in PC12 cells, and might be a potent neuroprotective agent.

Analysis of Factors Affecting Nontherapeutic INRs in Korean Outpatients with Mechanical Heart Valves / 대한흉부외과학회지

BACKGROUND: Following the implantation of heart valve prostheses, it is important to maintain therapeutic INR to reduce the risk of thromboembolism. The objectives of this study were to determine the causes of nontherapeutic INRs, and to identify the factors associated with nonadherences to warfarin therapy in Korean outpatients with prosthetic heart valves managed by a pharmacist-run anticoagulation service (ACS). MATERIAL AND METHOD: A retrospective chart review was completed for all patients enrolled in the ACS at Seoul National University Hospital from March, 1997 to September, 2000. The data on 868 patients (5,304 visits) who were at least 6 months post-valve replacement were included. All possible causes of nontherapeutic INRs were documented for each patient visit. The association of covariates to noncompliance was investigated by univariate analysis. RESULT: The reasons for nontherapeutic INRs were identified as follows: inadequate dosage adjustment (21%), nonadherences to dosing regimen (13%), drug/herbal interactions (12%), changes in diet (7%), and indeterminate cause (42%). Younger age, shorter duration of ACS and longer duration of warfarin therapy were associated with nonadherence. CONCLUSION: In this study, nonadherence and interactions between diet and medications were found to be important factors influencing nontherapeutic INRs. Longer duration of enrollment in the ACS affected the adherence to warfarin therapy positively whereas younger age and longer duration of warfarin therapy affected negatively.

Determination of Practical Dosing of Warfarin in Korean Outpatients with Mechanical Heart Valves / 대한흉부외과학회지

BACKGROUND: Following the implantation of heart valve prostheses, it is important to maintain therapeutic INR to reduce the risk of thromboembolism. The objective of this study was to suggest a practical dosing guideline for Korean outpatients with prosthetic heart valves managed by a pharmacist-run anticoagulation service (ACS). MATERIAL AND METHOD: A retrospective chart review was completed for all patients enrolled in the ACS at Seoul National University Hospital from March, 1997 to September, 2000. Patients who were at least 6 months post-valve replacement and had nontherapeutic INR value (less than 2.0 or greater than 3.0) were included. The data on 688 patients (1,782 visits) requiring dosing adjustment without any known drug or food interaction with warfarin were analyzed. The amount of adjusted dose and INR changes based on the INR at the time of the event were calculated. Aortic valve replacements (AVR) patients and mitral or double valve replacement (MVR/DVR) patients were evaluated separately. RESULT: Two methods for the warfarin dosage adjustment were suggested: Guideline I (mg-based total weekly dose (TWD) adjustment), Guideline II (percentage-based TWD adjustment). The effectiveness of Guideline I was superior to Guideline II overall in patients with both AVR and MVR/DVR. CONCLUSION: The guideline suggested in this study could be useful when the dosage adjustment of warfarin is necessary in outpatients with mechanical heart valves.

The Association of Subjective Stress, Urinary Catecholamine Concentrations and PC Game Room Use and Musculoskeletal Disorders of the Upper Limbs in Young Male Koreans

The use of PCs can cause health problems, including musculoskeletal disorders (MSDs) of the upper limbs. This study was performed to investigate whether using PCs in PC game rooms may induce MSDs of the upper limbs. 284 young male Koreans were included. A self-administered, structured questionnaire was used to gather information about game room use, perceived subjective stress, and the symptoms related to MSDs. Urinary concentrations of epinephrine, norepinephrine, and dopamine were measured in spot urine. The symptom prevalence of MSDs of the upper limbs increased according to the increase of the duration of game room use. The intensity of perceived subjective stress showed a significant dose-response relationship with the frequency of MSDs symptoms in neck and shoulder areas. However, the urinary level of catecholamines was not significantly correlated with the symptom prevalence of MSDs in the upper limbs. These findings suggest that using PCs in game rooms produce physical stress on the upper limbs, strong enough to induce MSDs.

The Effect of Corticosteroid on the Treatment of Endobronchial Tuberculosis / 결핵

OBJECTIVE: Appropriate antituberculosis chemotherapy may not prevent occurrence or progression of tracheobronchial stenosis and obstruction in the patients with endobronchial tuberculosis. The effect of corticosteroid treatment combined with antituberculosis chemotherapy was inconclusive. We evaluated prospectively the effect of corticosteroid treatment. METHODS: We diagnosed endobronchial tuberculosis by bronchoscopic examination and bronchial biopsy in the patients of tuberculosis within one month of antituberculosis chemotherapy. After randomization, we prescribed isoniazid, rifampin, ethambutol, and pyrazinamide with or without prednisolone 40 mg for 4 weeks. We carried out bronchoscopy in second month and ninth month of treatment. RESULTS: Edematous endobronchial tuberculosis showed significant improvement of bronchial stenosis after corticosteroid treatment(p<0.05). Corticosteroid treatment did not have advantage of improvement of bronchial stenosis in the patients with infiltrative endobronchial tuberculosis. CONCLUSION: Corticosteroid is effective in the treatment of bronchial stenosis when endobronchial tuberculosis is edematous type, in the early period of antituberculosis chemotherapy.

A case of pulmonary hypersensitivity reaction associated with etodolac / 대한내과학회지

No abstract available.

A case of juvenile form Pompe's disease manifested as chronic alveolar hypoventilation

We describe a case of the juvenile form of Pompe's disease that presented as primary alveolar hypoventilation due to respiratory muscle involvement. This 17-year-old girl had been asymptomatic until this admission, although she had a delayed puberty. Arterial blood gas analysis, pulmonary function test as well as physical findings were compatible with chronic alveolar hypoventilation syndrome. Since she had lower extremity muscle weakness and pseudomyotonic discharge on electromyography a muscle biopsy was done, which revealed glycogen storage disease. The patient was managed successfully with nasal intermittent positive pressure ventilation.