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1.
J Nat Med ; 73(1): 163-172, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30374696

ABSTRACT

Oxidative stress due to the overproduction of reactive oxygen species plays an important role in the pathogenesis of various diseases. In the present study, we comprehensively evaluated the antioxidant activities of 147 oral formulations of Japanese traditional herbal medicines (Kampo medicines), representing the entire panel of oral Kampo medicines listed in the Japanese National Health Insurance Drug List, using in vitro radical scavenging assays, including the 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity assay, the superoxide anion scavenging activity assay, and the oxygen radical absorption capacity assay. Three of the formulations tested, namely, Tsudosan, Daisaikoto, and Masiningan, showed the most potent in vitro antioxidant activities and were selected for further investigation of their intracellular and in vivo antioxidant effects. The results of the 2',7'-dichlorodihydrofluorescin diacetate assay demonstrated that all three Kampo medicines significantly inhibited hydrogen peroxide-induced oxidative stress in human hepatocellular liver carcinoma HepG2 cells. In addition, Tsudosan significantly increased the serum biological antioxidant potential values when orally administrated to mice, indicating that it also had in vivo antioxidant activity. The potent antioxidant activity of Tsudosan may be one of the mechanisms closely correlated to its clinical usage against blood stasis.


Subject(s)
Antioxidants/therapeutic use , Medicine, Kampo/methods , Plants, Medicinal/drug effects , Animals , Antioxidants/pharmacology , Humans , Japan , Reactive Oxygen Species
2.
Pediatrics ; 122(2): e341-9, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18625664

ABSTRACT

OBJECTIVE: The objective of this study was to characterize the clinical features of patients with Niemann-Pick disease type B and to identify efficacy end points for future clinical trials of enzyme-replacement therapy. METHODS: Fifty-nine patients who had Niemann-Pick disease type B, were at least 6 years of age, and manifested at least 2 disease symptoms participated in this multicenter, multinational, cross-sectional survey study. Medical histories; physical examinations; assessments of cardiorespiratory function, clinical laboratory data, and liver and spleen volumes; radiographic evaluation of the lungs and bone age; and quality-of-life assessments were obtained during a 2- to 3-day period. RESULTS: Fifty-three percent of the patients were male, 92% were white, and the median age was 17.6 years. The R608del mutation accounted for 25% of all disease alleles. Most patients initially presented with splenomegaly (78%) or hepatomegaly (73%). Frequent symptoms included bleeding (49%), pulmonary infections and shortness of breath (42% each), and joint/limb pain (39%). Growth was markedly delayed during adolescence. Patients commonly had low levels of platelets and high-density lipoprotein, elevated levels of low-density lipoprotein, very-low-density lipoprotein, triglycerides, leukocyte sphingomyelin, and serum chitotriosidase, and abnormal liver function test results. Nearly all patients had documented splenomegaly and hepatomegaly and interstitial lung disease. Patients commonly showed restrictive lung disease physiology with impaired pulmonary gas exchange and decreased maximal exercise tolerance. Quality of life was only mildly decreased by standardized questionnaires. The degree of splenomegaly correlated with most aspects of disease, including hepatomegaly, growth, lipid profile, hematologic parameters, and pulmonary function. CONCLUSIONS: This study documents the multisystem involvement and clinical variability of Niemann-Pick B disease. Several efficacy end points were identified for future clinical treatment studies. Because of its correlation with disease severity, spleen volume may be a useful surrogate end point in treatment trials, whereas biomarkers such as chitotriosidase also may play a role in monitoring patient treatment responses.


Subject(s)
Genetic Predisposition to Disease , Niemann-Pick Disease, Type B/complications , Niemann-Pick Disease, Type B/genetics , Quality of Life , Adolescent , Adult , Aged , Cardiovascular Diseases/etiology , Cardiovascular Diseases/physiopathology , Child , Cross-Sectional Studies , DNA Mutational Analysis , Disease Progression , Female , Growth Disorders/etiology , Growth Disorders/physiopathology , Hepatomegaly/etiology , Hepatomegaly/physiopathology , Humans , Linear Models , Male , Middle Aged , Multicenter Studies as Topic , Mutation, Missense , Niemann-Pick Disease, Type B/diagnosis , Niemann-Pick Disease, Type B/mortality , Probability , Prognosis , Prospective Studies , Risk Assessment , Severity of Illness Index , Splenomegaly/etiology , Splenomegaly/physiopathology , Survival Analysis
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