• Clinical Psychopharmacology and Neuroscience
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• 제16권4호
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• pp.376-382
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• 2018

We reviewed clinical studies investigating the pharmacological treatment of major depressive episodes (MDEs) with mixed features diagnosed according to the dimensional criteria (more than two or three [hypo]manic symptoms+principle depressive symptoms). We systematically reviewed published randomized controlled trials on the pharmacological treatment of MDEs with mixed features associated with mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD). We searched the PubMed, Cochrane Library, and ClinicalTrials.gov databases through December 2017 with the following key word combinations linked with the word OR: (a) mixed or mixed state, mixed features, DMX, mixed depression; (b) depressive, major depressive, MDE, MDD, bipolar, bipolar depression; and (c) antidepressant, antipsychotic, mood stabilizer, anticonvulsant, treatment, medication, algorithm, guideline, pharmacological. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We found few randomized trials on pharmacological treatments for MDEs with mixed features. Of the 36 articles assessed for eligibility, 11 investigated MDEs with mixed features in mood disorders: six assessed the efficacy of antipsychotic drugs (lurasidone and ziprasidone) in the acute phase of MDD with mixed features, although four of these were post hoc analyses based on large randomized controlled trials. Four studies compared antipsychotic drugs (olanzapine, lurasidone, and ziprasidone) with placebo, and one study assessed the efficacy of combination therapy (olanzapine+fluoxetine) in the acute phase of BD with mixed features. Pharmacological treatments for MDEs with mixed features have focused on antipsychotics, although evidence of their efficacy is lacking. Additional well-designed clinical trials are needed.

• 약학회지
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• 제58권4호
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• pp.255-261
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• 2014

Poly-pharmacy has been on the rise because of aging of population and chronic disease. Most of drug metabolism happens in the liver by CYP isozymes and the metabolism by CYP450 enzymes. The Cytochrome P450 (CYP) is a superfamily of enzymes that catalyzes the oxidations of many endogenous and exogenous compounds. Primary human Hepatocytes (HH) are considered as the gold standard model for In vitro drug interaction studies. However, there are several limitations (cost, limited life span) for using HH cells. HepaRG cells are being used as a possible alternative. HepaRG cells were cultured in William E medium containing the positive control inducers (1A2: 10, 25, 50 ${\mu}M$ omeprazole, 2C9 and 2C19: 10 ${\mu}M$ rifampin, 3A4: 10, 25, 50 ${\mu}M$ rifampin) at $37^{\circ}C$, 5 % $CO_2$ in a humidified atmosphere. This study was to evaluate the induction of CYP isozymes (1A2, 2C9, 2C19 and 3A4) using LC-MS/MS. We evaluated the potential induction ability of Bosentan, as a drug of pulmonary artery hypertension, in HepaRG cells. For reference, dose of the Bosentan is determined to the basis of the $C_{max}$ (835 mg/ml) value. The enzyme activity demonstrated that CYP2C9 and 3A4 were induced up to 20 times by Bosentan. Like as In vivo, the enzyme activity of CYP2C9 and CYP3A4 is significantly induced in a dose-dependent by Bosentan.

• Biomolecules & Therapeutics
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• 제23권6호
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• pp.597-603
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• 2015

Synthetic cannabinoids JWH-018 and JWH-250 in 'herbal incense' also called 'spice' were first introduced in many countries. Numerous synthetic cannabinoids with similar chemical structures emerged simultaneously and suddenly. Currently there are not sufficient data on their adverse effects including neurotoxicity. There are only anecdotal reports that suggest their toxicity. In the present study, we evaluated the neurotoxicity of two synthetic cannabinoids (JWH-081 and JWH-210) through observation of various behavioral changes and analysis of histopathological changes using experimental mice with various doses (0.1, 1, 5 mg/kg). In functional observation battery (FOB) test, animals treated with 5 mg/kg of JWH-081 or JWH-210 showed traction and tremor. Their locomotor activities and rotarod retention time were significantly (p<0.05) decreased. However, no significant change was observed in learning or memory function. In histopathological analysis, neural cells of the animals treated with the high dose (5 mg/kg) of JWH-081 or JWH-210 showed distorted nuclei and nucleus membranes in the core shell of nucleus accumbens, suggesting neurotoxicity. Our results suggest that JWH-081 and JWH-210 may be neurotoxic substances through changing neuronal cell damages, especially in the core shell part of nucleus accumbens. To confirm our findings, further studies are needed in the future.

• Biomolecules & Therapeutics
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• 제25권3호
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• pp.288-295
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• 2017

The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK293 cells and primary human hepatocytes overexpressing the target genes were treated with bosentan and various concentrations of rifampin, which decreased the uptake activities of OATP transporters in a dose-dependent manner. In primary human hepatocytes, CYP2C9 and CYP3A4 gene expression and activities decreased upon treatment with $20{\mu}M$ $bosentan+200{\mu}M$ rifampin. Rifampin also reduced gene expression of OATP1B1, OATP1B3, and OATP2B1 transporter, and inhibited bosentan influx in human hepatocytes at increasing concentrations. These results confirm rifampin- and bosentan-induced interactions between OATP transporters and CYP450.

• 생물정신의학
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• 제19권4호
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• pp.179-186
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• 2012

Depression and executive dysfunction are common neuropsychiatric sequelae of stroke. Patients with stroke are more predisposed to depression and executive dysfunction compared to patients with similar degree of physical disability. Both depression and executive dysfunction are also associated with poor prognosis such as high mortality and delayed recovery after stroke. Complex neurobiological and anatomical mechanisms are associated with the development of depression and executive dysfunction after stroke. Activation of pro-inflammatory cytokines is thought to be associated with onset of depression, whereas injuries in frontal-subcortical circuit are thought to be a link between depression and executive dysfunction. Early detection of depressive symptoms and both pharmacological and non-pharmacological treatment would be helpful. In this review paper, the authors investigated 1) biological and neuroanatomical substrate for poststroke depression and executive dysfunction, 2) the relationship and common etiopathology for poststroke depression and executive dysfunction, and 3) pharmacological and non-pharmacological treatment for poststroke depression. The contents of the paper are as follows : the prevalence, clinical manifestation, and biological etiology for poststroke depression, neuroanatomical abnormalities as a common etiological factor for depression and executive dysfunction, pharmacotherapy and non-pharmacological approach.

• 한국한의학연구원논문집
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• 제14권1호
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• pp.123-128
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• 2008

Glehnia littoralis (Umbelliferae), a perennial herb distributed along the coastline of northern Pacific countries, is the medicinal plant used traditionally for treatment of various diseases. This review focuses on the various pharmacological activities of Glehnia littoralis for understanding about its traditional medicinal applications, medicinal uses in the modern society, and potentials for drug development Glehnia littoralis was reported to have anti-oxidant, anti-tumor, anti-amnesic, blood circulation-promoting, immunomodulatory, anti-microbial, and allelopathic activities. However, their mechanisms remain to be clarified. Because Glehnia littoralis has been prescribed in traditional Oriental medicine as a tonic herb, Glehnia littoralis can be better than other chemical drugs and medicines which exert the equal pharmacological activities. Although the activities of Glehnia littoralis are not specifically high-potent with unique mode of action, it may turn out that it can be beneficial to exert multiple pharmacological activities. In view of low toxicity, relative cheapness, presence in the diet, and occurrence in various herbal remedies of Glehnia littoralis, it needs to be prudent to evaluate its properties and applications further.

• 생약학회지
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• 제26권2호
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• pp.139-147
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• 1995

Crinum asiaticum var. japonicum is a wild plant growing only in Jeju-island, Korea, and in Japan. The whole part of this plant has been known to have the pharmacological actions such as analgesic, anti-inflammatory, platelet-aggregation inhibitory, antitussive, and expectorant. With these assumed actions, the leaves (Crinum folium) of this plant has been used in the folk remedies for arthritis and arthralgia. There is, however, no scientific evidences for the pharmacological actions of Crinum asiaticum var. japonicum. In the present study, the analgesic, anti-inflammatory, and platelet-aggregation inhibitory actions of Crinium folium were evaluated using writhing test, tail-flick test, carrageenin antiedema test, in vitro thromboxane $B_2$ quantitation assay and in vitro platelet aggregation test. In order to obtain the partially purified fraction whose pharmacological action is excellent, the methanol extract of Crinium folium was fractionated consecutively into four biological fractions such as ether, ethyl acetate, butanol, and water fractions and their pharmacological actions of the fractions were investigated. Putting our results together, Crinium folium, especially ethyl acetate fraction was proven to have significant analgesic, anti-inflammatory and platelet-aggregation inhibitory actions by inhibition of prostanoids biosynthesis as one of its mechanism of action.

• Genomics & Informatics
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• 제7권2호
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• pp.85-96
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• 2009

The differentiation of neural precursor cells (NPCs) into neurons and astrocytes is a process that is tightly controlled by complicated and ill-defined gene networks. To extend our knowledge to gene networks, we performed a temporal analysis of gene expression during the differentiation (2, 4, and 8 days) of spinal cord-derived NPCs using oligonucleotide microarray technology. Out of 32,996 genes analyzed, 1878 exhibited significant changes in expression level (fold change>2, p<0.05) at least once throughout the differentiation process. These 1878 genes were classified into 12 groups by k-means clustering, based on their expression patterns. K-means clustering analysis revealed that the genes involved in astrogenesis were categorized into the clusters containing constantly upregulated genes, whereas the genes involved in neurogenesis were grouped to the cluster showing a sudden decrease in gene expression on Day 8. Functional analysis of the differentially expressed genes indicated the enrichment of genes for Pax6- NeuroD signaling.TGFb-SMAD and BMP-SMAD.which suggest the implication of these genes in the differentiation of NPCs and, in particular, key roles for Nova1 and TGFBR1 in the neurogenesis/astrogenesis of mouse spinal cord.

• 대한본초학회지
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• 제31권5호
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• pp.25-39
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• 2016

Objectives : Atractylodes rhizomes, which have been widely used to treat gastrointestinal disorders, consist of numerous chemical compounds. Polyacetylenes are the parts of characteristic compounds of importance required to understand the therapeutic properties of Atractylodes rhizomes. It is necessary to understand the physicochemical and pharmacological properties of polyacetylenes in the Atractylodes rhizomes.Methods : The literatures from 1970 to January 2016 were searched using Korean and international electronic databases. The chemical structures of polyacetylenes were drawn by structure-drawing software.Results : The reported polyacetylenes were classified by their chemical skeletons and original resources, and their physicochemical and pharmacological features were discussed. Polyacetylenes with skeletal moieties were reported, such as diene-diyne types (two double and two triple carbon-bonds), triene-diyne types (three double carbon bonds and two triple carbon bonds), and monoene-diyne types (one double carbon bonds and two double carbon bonds), with various functional groups. Atractylodin was most frequently reported from many Atractylodes species. Atractylodin-related polyacetylenes showed chemical instability in both high and freezing temperatures. Processing of the Atractylodes rhizomes by stir-frying with bran could affect the contents of polyacetylenes and their bioavailability in vivo. Several polyacetylenes showed structure-related anti-inflammatory activities and gastrointestinal activities.Conclusion : Polyacetylene compounds in Atractylodes rhizomes were based on three chemical backbones and showed diverse physicochemical and pharmacological features. The present study provides structural, physicochemical, and pharmacological information of polyacetylene from Atractylodes rhizomes. This information provides fundamental data for further research.

• 보건교육건강증진학회지
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• 제35권5호
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• pp.35-45
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• 2018

Objectives: Despite the importance of Non-pharmacological interventions for Eating Disorders, no meta-analysis providing definite conclusions in this field has been reported. The purpose of the this study was to conduct meta-analysis of Non-pharmacological interventions for the improvement of eating disorders. Methods: We searched the Koreamed, KISTI, KMBASE, RISS and KISS and so on up to October 2017 using search terms such as ((Eating disorders OR anorexia OR binge) AND (Mediation OR program OR treatment OR therapy OR technique)) in Korean. Results: Initial searches yielded 602 citations. Of these results, seven met selection criteria. Interventions reduced the risk of binge eating disorder (standardised mean difference [SMD] -2.133, 95% CI -3.107~-1.159). Interventions reduced drive for leanness (-1.857, -3.143~-0.571), body dissatisfaction (-1.357, -2.238~-0.477), depression (-0.745, -1.298~-0.192), but not physical function (0.191, -0.089~0.471). Conclusions: The results from this study indicate that Non-pharmacological Interventions may help Eating disorders' binge eating, drive for thinness, body dissatisfaction, depression. However, larger-scale studies are needed to confirm this conclusion.