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1.
Article in English | MEDLINE | ID: mdl-32464239

ABSTRACT

BACKGROUND: Rumination is a well-known risk factor for depression. It is also associated with negative and positive symptoms and suicidality in patients suffering from psychosis. However, no studies have addressed the effect of antipsychotics on rumination. METHODS: Using the Brooding Scale (BS), we investigated the effect of antipsychotics on rumination at the 6-month follow up in patients with first-episode psychosis (n = 257). The relationship between rumination and other clinical variables was explored by conducting a correlation analysis and structural equation modeling (SEM). The clinical characteristics and short-term outcomes were compared between high and low ruminators at 6 months. RESULTS: Significant reductions in rumination and various clinical variables were observed at the 6-month follow-up. A significant correlation was observed between rumination and the score on the positive subscale of the Positive and Negative Syndrome Scale (PANSS). A direct path between the PANSS score and rumination was identified by SEM. High ruminators had more severe psychopathology, experienced more childhood traumas, and took less exercise than low ruminators. The recovery rate at 6 months was higher in low ruminators than in high ruminators. CONCLUSIONS: Our findings suggest that antipsychotics are beneficial for reducing rumination in patients with first-episode psychosis. The outcomes at the 6-month follow-up were better in low ruminators than high ruminators.


Subject(s)
Antipsychotic Agents/therapeutic use , Psychotic Disorders/drug therapy , Psychotic Disorders/psychology , Adult , Cohort Studies , Depressive Disorder/etiology , Exercise , Female , Follow-Up Studies , Humans , Male , Models, Statistical , Neuropsychological Tests , Psychotic Disorders/complications , Republic of Korea , Treatment Outcome , Wounds and Injuries/psychology , Young Adult
2.
J Hazard Mater ; 227-228: 327-33, 2012 Aug 15.
Article in English | MEDLINE | ID: mdl-22677053

ABSTRACT

Toxicity-based regulations of industrial effluent have been adopted to complement the conventional discharge limits based on chemical analyses. In this study, multi-level toxicity including acute toxicity, feeding rate inhibition and oxidative stress of effluent from a liquid crystal display (LCD) wastewater treatment plant (WWTP) to Daphnia magna (reference species) and Moina macrocopa (native species) were periodically monitored from April 2010 to April 2011. Raw wastewater was acutely toxic to both D. magna and M. macrocopa, but the toxicity reached less than 1 TU in the final effluent (FE) as treatment proceeded. Although acute toxicity was not observed in the FE, the feeding rate of daphnids was significantly inhibited. Additionally, the antioxidant enzyme activity of catalase, superoxide dismutase and glutathione peroxidase (GPx) in D. magna increased significantly when compared to the control, while only GPx activity was increased significantly in M. macrocopa (p<0.05). A toxicity identification evaluation using D. magna showed that Cu was the key toxicant in the FE, which was not effectively removed by the coagulation/flocculation process in the LCD WWTP. In addition, Al originating from the coagulant seemed to increase toxicity of the FE.


Subject(s)
Cladocera/drug effects , Copper/toxicity , Electrical Equipment and Supplies , Industrial Waste/adverse effects , Water Pollutants, Chemical/toxicity , Animals , Catalase/metabolism , Cladocera/physiology , Copper/analysis , Feeding Behavior/drug effects , Glutathione Peroxidase/metabolism , Liquid Crystals , Superoxide Dismutase/metabolism , Waste Disposal, Fluid , Water Pollutants, Chemical/analysis
3.
Arch Dermatol Res ; 301(3): 253-8, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19123006

ABSTRACT

Melanogenesis is a physiological process that results in the synthesis of melanin pigments, which play a crucial protective role against skin photocarcinogenesis. The present study was designed to determine the effects of 6-benzylaminopurine (6-BAP) on melanogenesis and elucidate the molecular events of melanogenesis induced by 6-BAP. To elucidate the pigmenting effect of 6-BAP and its mechanism, several experiments were performed in B16 melanoma cells. Melanin content, tyrosinase activity, cAMP production, and Western blots for proteins which are involved in melanogenesis were introduced in this study. Melanin content and tyrosinase activity increased in response to treatment with 6-BAP in a concentration-dependent manner. The tyrosinase, TRP-1, TRP-2 and MITF protein levels were found to increase significantly in response to 6-BAP in a time-dependent manner. In addition, Western blot analysis revealed that 6-BAP increased the phosphorylated level of CRE-binding protein. The increased melanin synthesis that was induced by treatment with 6-BAP treatment was reduced significantly in response to co-treatment with H-89 [a protein kinase A (PKA) inhibitor], whereas co-treatment with SB203580 (a p38 MAPK inhibitor) and Ro-32-0432 (a PKC inhibitor) did not attenuate the increase in melanin content levels that was induced by 6-BAP. In a cAMP production assay, 6-BAP did not increase the intracellular cAMP level. These findings suggest that 6-BAP activates PKA via a cAMP-independent pathway and subsequently stimulates melanogenesis by up-regulating MITF and tyrosinase expression.


Subject(s)
Cyclic AMP-Dependent Protein Kinases/metabolism , Cyclic AMP/metabolism , Kinetin/pharmacology , Melanins/metabolism , Melanoma/metabolism , Plant Growth Regulators/pharmacology , Skin Neoplasms/metabolism , Animals , Benzyl Compounds , Cell Line, Tumor , Cells, Cultured , Cyclic AMP Response Element-Binding Protein/metabolism , Dose-Response Relationship, Drug , Melanoma/pathology , Mice , Microphthalmia-Associated Transcription Factor/metabolism , Monophenol Monooxygenase/metabolism , Purines , Signal Transduction/physiology , Skin Neoplasms/pathology , Time Factors
4.
Obesity (Silver Spring) ; 17(2): 226-32, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18948972

ABSTRACT

Adipocyte dysfunction is strongly associated with the development of obesity, which is a major risk factor for many disorders including diabetes, hypertension, and heart disease. It is generally accepted that the regulation of adipogenesis or adipokines expression prevents obesity. In this study, we show that isorhamnetin inhibits adipocyte differentiation, as evidenced by reduced triglyceride (TG) accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity. At the molecular level, the mRNA expression levels of peroxidase proliferator-activated receptor-gamma (PPAR-gamma) and CCAAT/enhancer-binding protein-alpha (C/EBP-alpha), which are the major adipogenic transcription factors, were markedly reduced by isorhamnetin. However, the mRNA levels of C/EBP-beta and -delta, the upstream regulators of PPAR-gamma and C/EBP-alpha, were not reduced by isorhamnetin. Moreover, the mRNA levels of PPAR-gamma target genes such as lipoprotein lipase (LPL), CD36, aP2, and liver X receptor-alpha (LXR-alpha) were downregulated by isorhamnetin. We also showed that isorhamnetin inhibits the expression and secretion of adiponectin, and the results of adiponectin promoter assays suggest the inhibition of PPAR-gamma expression as a possible mechanism underlying the isorhamnetin-mediated effects. Taken together, these results indicate that isorhamnetin inhibits adipogenesis through downregulation of PPAR-gamma and C/EBP-alpha.


Subject(s)
Adipocytes/cytology , Adipocytes/metabolism , Adipogenesis/drug effects , Adiponectin/metabolism , Cell Differentiation/drug effects , Flavonols/pharmacology , 3T3-L1 Cells , Adipocytes/drug effects , Animals , CCAAT-Enhancer-Binding Protein-alpha/metabolism , Down-Regulation/drug effects , Early Growth Response Protein 2/metabolism , Glycerolphosphate Dehydrogenase/metabolism , Mice , PPAR gamma/metabolism , Quercetin/analogs & derivatives , RNA, Messenger/metabolism , Transcription Factors/metabolism , Triglycerides/metabolism
6.
J Ethnopharmacol ; 112(1): 127-31, 2007 May 30.
Article in English | MEDLINE | ID: mdl-17386986

ABSTRACT

Type I collagen is the primary component of the skin dermis. Both the quantity and quality of extracellular collagen are primarily related to skin ageing. In this study, we investigated the possibility that Camellia japonica oil (CJ oil) may be introduced as an anit-wrinkle agent. As a first step to this end, human COL1A2 promoter luciferase assay was performed in human dermal fibroblast cells. CJ oil was determined to activate human COL1A2 promoter in a concentration-dependent manner. In consistency with this result, while matrix metalloproteinase (MMP)-1 activity was inhibited by CJ oil, human type I procollagen synthesis was also induced by CJ oil. These results suggest the possibility that CJ oil may be involved in the skin ageing. For the evaluation of CJ oil's safety and efficiency on human skin, human skin primary irritation test and trans-epidermal water loss (TEWL) were performed. Transepidermal water loss (TEWL) was measured before treatment then, 1h and 2h after treatment; the forearm site was selected to measure TEWL. Also, a human skin primary irritation test was performed on the normal skin (upper back) in 30 volunteers to see if a certain material included in CJ oil has irritation or sensitization potential. In these assays, CJ oil reduced trans-epidermal water loss (TEWL) and did not induce any adverse reactions. Therefore, based on these results, we suggest the possibility that CJ oil may be considered as possible wrinkle-reducing candidates for topical application.


Subject(s)
Camellia , Collagen Type I/biosynthesis , Collagen/biosynthesis , Plant Oils/pharmacology , Skin/drug effects , Adult , Collagen/genetics , Collagen Type I/genetics , Dose-Response Relationship, Drug , Female , Fibroblasts/drug effects , Fibroblasts/metabolism , Humans , In Vitro Techniques , Matrix Metalloproteinase 1/biosynthesis , Plant Oils/adverse effects , Promoter Regions, Genetic , Skin/metabolism , Skin Aging/drug effects , Skin Irritancy Tests , Transfection , Tumor Necrosis Factor-alpha/pharmacology , Water Loss, Insensible/drug effects
7.
J Neuroimmunol ; 159(1-2): 41-7, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15652401

ABSTRACT

The cytochrome P4507B1 (P4507B1) is responsible for the 7alpha-hydroxylation of dehydroepiandrosterone (DHEA) and other 3beta-hydroxysteroids in the brain and other organs. The cDNA of human P4507B1 was used for DNA immunization of mice. The best responding mouse led to the production of monoclonal antibodies (mAbs). The clone D16-37 produced an IgM specific for P4507B1 with no cross-reaction with other human P450s. This antibody permitted the immunohistochemical detection of P4507B1 in slices of human hippocampus. P4507B1 was expressed in neurons only. This new tool will be used for the extensive examination of the P4507B1 presence and determination of its levels in slices of human normal and diseased brain and in other human tissues.


Subject(s)
Antibodies, Monoclonal/analysis , Cytochrome P-450 Enzyme System/analysis , Cytochrome P-450 Enzyme System/immunology , DNA, Complementary/administration & dosage , Steroid Hydroxylases/analysis , Steroid Hydroxylases/immunology , Amino Acid Sequence , Animals , Antibodies, Monoclonal/biosynthesis , Antibodies, Monoclonal/metabolism , Antibody Specificity , Binding Sites, Antibody , Catalysis , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Cytochrome P450 Family 7 , DNA, Complementary/immunology , Dehydroepiandrosterone/antagonists & inhibitors , Dehydroepiandrosterone/metabolism , Hippocampus/enzymology , Hippocampus/immunology , Humans , Immunoglobulin M/metabolism , Immunohistochemistry , Injections, Intramuscular , Male , Mice , Mice, Inbred C57BL , Molecular Sequence Data , Steroid Hydroxylases/genetics , Steroid Hydroxylases/metabolism , Vaccines, DNA/administration & dosage , Vaccines, DNA/immunology
8.
J Steroid Biochem Mol Biol ; 92(5): 383-9, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15698543

ABSTRACT

The cytochrome P4507B1 (P4507B1) in the human hippocampus is responsible for the production of 7alpha-hydroxylated derivatives of dehydroepiandrosterone (DHEA) and other 3beta-hydroxylated neurosteroids. Minor quantities of the 7beta-hydroxylated derivatives are also produced. Neuroprotective action of these 7-hydroxysteroids was reported. Recombinant human P4507B1 was prepared from yeast coexpressing the human hippocampal P450 cDNA and the human P450 reductase genes. Microsomal P4507B1 activity was tested in the presence of NADPH and (14)C-labeled steroid substrates to deduce kinetic parameters and to study inhibitor responses. The K(M) values obtained for DHEA, pregnenolone, epiandrosterone, 5alpha-androstane-3beta,17beta-diol and estrone were 1.90 +/- 0.06, 1.45 +/- 0.03, 1.05 +/- 0.12, 0.8 +/- 0.04 and 1.20 +/- 0.26 microM, respectively. Production of limited amounts of 7beta-hydroxylated derivatives was also observed, but only with DHEA, 5alpha-androstane-3beta,17beta-diol and epiandrosterone. K(M) values determined for 7beta-hydroxylation were identical to those for 7alpha-hydroxylation. The DHEA 7alpha-hydroxylation was inhibited by estrone and estradiol (mixed type inhibition) and by the [25-35] beta-amyloid peptide (non-competitive inhibition). These results indicate that in human, the 7-hydroxylation catalysed by P4507B1 preferentially takes place on DHEA, 5alpha-androstane-3beta,17beta-diol and epiandrosterone with major and minor formation of 7alpha- and 7beta-hydroxylated derivatives, respectively. Both estrogens and a beta-amyloid component inhibit the P4507B1-mediated production of the 7-hydroxysteroid metabolites.


Subject(s)
Cytochrome P-450 Enzyme System/metabolism , Amyloid beta-Peptides/pharmacology , Catalysis/drug effects , Cytochrome P-450 Enzyme Inhibitors , Enzyme Inhibitors/pharmacology , Estrogens/pharmacology , Gas Chromatography-Mass Spectrometry , Humans , Hydroxylation , Kinetics , Peptide Fragments/pharmacology , Steroids/chemistry , Steroids/metabolism
9.
J Clin Endocrinol Metab ; 88(11): 5199-206, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14602750

ABSTRACT

A neurodegenerative disease such as Alzheimer's disease (AD) is associated with significantly higher dehydroepiandrosterone (DHEA) levels in cerebrospinal fluid (CSF). Because the human brain is known to transform DHEA into DHEA sulfate (DHEAS), 7 alpha-hydroxy-DHEA, 7 beta-hydroxy-DHEA, and 16 alpha-hydroxy-DHEA, it is possible that DHEA accumulation in the brain results from a decreased production of such metabolites. To test this hypothesis, we have measured and compared CSF levels of DHEA, DHEAS, 7 alpha-hydroxy-DHEA, 7 beta-hydroxy-DHEA, and 16 alpha-hydroxy-DHEA in 14 patients with AD, 12 controls, and eight patients with another common dementia, vascular dementia (VD). Results indicated that DHEAS CSF levels were significantly decreased in AD and VD (P < 0.007), whereas other metabolite levels were not significantly changed. Use of steroid level ratios, such as DHEA/(7 alpha-hydroxy-DHEA + 7 beta-hydroxy-DHEA), 7 beta-hydroxy-DHEA/DHEA, and DHEAS/DHEA ratios, resulted in significant differences between diseased and control patients (P < 0.0003, P < 0.002, and P < 0.002, respectively). In addition, the 7 alpha-hydroxy-DHEA/7 beta-hydroxy-DHEA ratio was significantly different between AD and VD (P < 0.0001) and could be used for differentiating AD from VD. These results indicate that, in AD and VD, increased DHEA levels are not neuroprotective and are neither better sulfated nor better hydroxylated at the 7 alpha, 7 beta, and 16 alpha positions than in controls. The results also suggest that, in AD and VD brains, the sulfotransferase and the cytochromes P450 responsible for the 7 alpha-, 7 beta-, and 16 alpha-hydroxylations of DHEA are either present at lower levels or transformed through natural polymorphism into less-efficient enzymes.


Subject(s)
Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/diagnosis , Dehydroepiandrosterone/cerebrospinal fluid , Dementia, Vascular/cerebrospinal fluid , Dementia, Vascular/diagnosis , Aged , Aged, 80 and over , Chromatography, High Pressure Liquid , Dehydroepiandrosterone/analysis , Dehydroepiandrosterone Sulfate/analysis , Dehydroepiandrosterone Sulfate/cerebrospinal fluid , Diagnosis, Differential , Female , Humans , Male , Middle Aged
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