A Correlation between Neurocognitive Function and Serum Lipid Levels among the Korean Elderly / 신경정신의학

OBJECTIVES: In this study, we evaluated the correlation between neurocognitive function and serum lipids levels among Koreans over 60 years old. Also, we investigated the sociodemographic risk factors and vascular risk factors in Alzheimer's disease. METHODS: Six hundred fifty elderly persons participated in this study. We screened for cognitive impairment via the Mini-Mental Status Examination-Korean version (MMSE-KC) and evaluated 181 participants using the Consortium to Establish a Registry for Alzheimer's disease, Korean version (CERAD-K). For further classification, we employed the Clinical Dementia Rating Scale (CDRS) and DSM-IV diagnostic criteria. Participants having a CDRS score of 1 or more were diagnosed as having Alzheimer's disease. RESULTS: We diagnosed 38 participants as having Alzheimer's disease, 67 participants as having mild cognitive impairment, and 76 participants as having no cognitive impairment. There were significant differences among the groups with regard to age, education, history of diabetes mellitus medication, history of head trauma, history of CVA, and Hachinski ischemic score (p<0.05). The mild cognitive impairment group showed inverse correlations between triglyceride serum level and both total MMSE-KC score and Orientation in MMSE-KC (rs=-0.267, p=0.029 ; rs=-0.324, p=0.007). This group also showed inverse correlations between total cholesterol serum level and both total MMSE-KC score and Orientation in MMSE-KC (rs=-0.259, p=0.034 ; rs=-0.417, p=0.000) and an inverse correlation between low density lipoprotein serum level and Orientation in MMSE-KC (rs=-0.320, p=0.008). CONCLUSION: There were inverse correlations between some lipids' serum levels and cognitive functions in the mild cognitive impairment group.

Multicenter Clinical Trials for Efficacy and Safety of Mirtazapine in Moderate-to-Severe Major Depressive Patients / 대한정신약물학회지

OBJECTIVE: The purpose of this study is to evaluate the efficacy and safety of mirtazapine treatment in multicenter population consisting of Korean patients suffering from moderate-to-severe depression. METHODS: Total 163 of in and outpatients with a diagnosis of major depressive disorder (DSM-IV) and 18 or over scores of 17-items Hamilton Rating Scale for Depression (HAMD) received treatment with mirtazapine (15-45 mg/day) for 6 weeks. Efficacy was assessed by HAMD, Montgomery and Asberg Depression Rating Scale (MADRS), Beck's Depression Inventory (BDI), and Clinical Global Impression (CGI) scales and statistical analyses were performed on the intent-to-treat sample (143 patients) using the last-observation-carried-forward method. In addition, reported adverse events, routine laboratory parameters, and vital signs were investigated to evaluate the safety of mirtazapine. RESULTS: Mean daily dose of mirtazapine was 28.4 mg. At the end of the study, the response rate (50% or more reduction from baseline in HAMD scores) was 75.5% and the remission rate (7 or less in HAMD score) was 42.7%. Mirtazapine treatment induced significant reduction in depressive symptoms at the 4(th) day and substantial reduction along the treatment period, as assessed by changes in HAMD, MADRS, BDI, and CGI scales. At the 4(th) day and first week of mirtazapine treatment, the mean HAMD-17 total score was significantly reduced compared that of the baseline and the response rates were 11.9% and 28.7%, respectively. Mirtazapine was well tolerated in general, and somnolence and sedation were the most common adverse events reported. In addition, there were no clinically relevant changes in laboratory parameters and vital signs, although body weight was increased. CONCLUSION: Although this trial had many limitations of open non-comparative study, mirtazapine was demonstrated to an effective treatment for moderate to severe major depressive disorder and was well tolerated. A potentially rapid onset of overall therapeutic efficacy of mirtazapine was suggested by significant changes in all major variables of efficacy after 4(th) day of treatment.

Kinesin Superfamily KIF1Balpha Protein Binds to the PDZ Domain of MALS-3 / 대한해부학회지

The Kinesin superfamily proteins (KIFs) make up a large superfamily of molecular motors that transport cargo such as vesicles, protein complexes, and organelles. KIF1Balpha is a monomeric motor that conveys mitochondria and plays an important role in cellular function. Here, we used the yeast two-hybrid system to identify the proteins that interacts with KIF1Balpha and found a specific interaction with the mammalian LIN-7 (MALS)-3/vertebrate homology of LIN-7 (Veri) and synaptic scaffolding molecule (S-SCAM). MALS-3 protein bound to the tail region of KIF1Balpha but not to other kinesin family members in the yeast two-hybrid assay. The "T-X-V" motif at the C-terminal end of KIF1Balpha is essential for interaction with MALS-3. In addition, this protein showed specific interactions in the Glutathione S-transferase (GST) pull-down assay. An antibody to MALS-3 specifically coimmunoprecipitated KIF1Balpha associated with MALS-3 from mouse brain extracts. These results suggest that MALS-3, as KIF1Balpha receptor, is involved in the KIF1Balpha-mediated transport.

Kinesin Superfamily KIF1A Protein Binds to Synaptotagmin XI / 대한해부학회지

The kinesin proteins (KIFs) make up a large superfamily of molecular motors that transport cargo such as vesicles, protein complexes, and organelles. KIF1A is a monomeric motor that conveys synaptic vesicle precursors and plays an important role in neuronal function. Here, we used the yeast two-hybrid system to identify the neuronal protein (s) that interacts with the tail region of KIF1A and found a specific interaction with synaptotagmin XI. The amino acid residues between 830 and 1300 of KIF1A are required for the interaction with synaptotagmin XI. KIF1A also bound to the tail region of synaptotagmin IV but not to other synaptotagmin in the yeast two-hybrid assay. KIF1A interacted with GST-synaptotagim XI fusion proteins, but not with GST alone. An antibody to synaptotagmin XI specifically co-mmunoprecipitated KIF1A associated with synaptotagimin from mouse brain extracts. These results suggest that KIF1A motor protein transports of synaptotagmin XI-containing synaptic vesicle precursors along microtubule.

Expression of Aquaporin-8 in Placenta of Preeclampsia / 대한산부인과학회잡지

OBJECTIVE: This study was to determine whether aquaporin-8, which plays a role as a transcellular water channel, is expressed in human placenta, and to compare the degree of its expression between preeclamptic women and normal pregnant women. METHODS: Placentas were obtained from severely preeclamptic women and normal pregnant women who were delivered babies by cesarean section before the onset of labor in the Chungbuk National University Hospital. In situ hybridization with aquaporin-8 cRNA probe was performed using paraffin-embedded tissue section. Signal of aquaporin-8 expression was observed with light microscope. RESULTS: In situ hybridization demonstrated strong expression of aquaporin-8 mRNA in the placentas of both preeclamptic women and normal pregnant women. The degree of expression was the same in both group. CONCLUSION: Aquaporin-8 in human placenta may not be related to the pathogenesis of preeclampsia.

Live Birth After Expectant Management of Second Trimester Placental Abruption / 대한산부인과학회잡지

Prognosis of placental abruption depends on gestational age and the status of the mother and the fetus, and perinatal mortality was almost entirely attributable to prematurity. A midtrimester women with placental abruption was successfully treated by expectant management including fetal surveillance, serial ultrasonography and maternal hematologic examination, and delivered a healthy baby 11 weeks later. We suggest that expectant management may be considered as a good treatment option until fetal lung maturation is documented in preterm pregnancy with placental abruption if there is no maternal or fetal compromise.

Tardive Dyskinesia and CAG Repeat Expansions / 신경정신의학

OBJECTIVES: Much interest has recently been focused on the possibility of the involvement of unstable DNA in the etiology of schizophrenia following several publications that reported increases in frequency of large CAG repeats in affected individuals. Tardive dyskinesia(TD), an involuntary movement disorder following pharmacological treatment of schizophrenia, shares a great deal of common clinical and biological features with Huntington's disease, a representative movement disorder with CAG repeat expansions. The authors studied for a possible CAG repeat expansions in patients with schizophrenia and TD. METHODS: TD was diagnosed by the Abnormal Involuntary Movement Scale. Using repeat expansion detection(RED), a method in which a thermostable ligase is used to detect repeat expansions directly from genomic DNA, subjects with schizophrenia with/without TD(n=79/n=75) and normal controls (n=72) were studied for the presence of the CAG repeat expansions were analyzed. RESULTS: No significant size differences were detected in the(CTG)17 ligation products between schizophrenic cases and controls using RED(X(2)=2.907, df=2, p=0.234). CONCLUSIONS: This finding does not support the hypothesis that CAG repeat expansions contributes to the susceptibility for schizophrenia and TD.

Association between Tardive Dyskinesia and Soft Neurological Signs / 대한정신약물학회지

OBJECTIVE: The goal of this study was to examine association between tardive dyskinesia and soft neurological signs in schizophrenic patients. METHODS: 35 schizophrenic inpatients who met the diagnostic criteria for tardive dyskinesia developed by Schooler and Kane and 30 schizophrenic inpatients without tardive dyskinesia were enrolled in this study. Tardive dyskinesia, soft neurological signs, and cognitive function were evaluated with Abnormal Involuntary Movement Scale (AIMS), Neurological Evaluation Scale (NES), and Mini-Mental State Examination (MMSE) independently by 2 psychiatrists, respectively. Data of the two schizophrenic groups were compared and also those of 31 normal controls. RESULTS: Total schizophrenics scored higher than normal controls in total mean scores of NES (p<0.01), and its three functional area scores, sensory integration (p<0.01), motor coordination (p<0.05), and sequencing of complex motor acts (p<0.05). Patients with tardive dyskinesia showed higher prevalence rates than those without in 5 items-left graphesthesia (p<0.05), right fist-ring test (p<0.05), right fist-edge-palm test (p<0.05), right synkinesis (p<0.05), and left synkinesis (p<0.05). The total scores of NES were not significantly related to the severity of tardive dyskinesia and cognitive dysfunction. CONCLUSION: Schizophrenics had more soft neurological signs than normal subjects. Five items of NES were more impaired in the patients with tardive dyskinesia than in those without tardive dyskinesia.

Antidepressant Effect of Ethaverine / 대한정신약물학회지

The effects of a L-type calcium channel blocker, ethaverine were investigated in the rat forced swimming test, after single and repeated administration. Ethaverine in doses of 20 mg/kg, 40 mg/kg after single and repeated administration reduced significantly the duration of immobility in the forced swimming test. Fluoxetine administered in a single dose of 40 mg/kg did not influence the duration of immobility, but fluoxetine in a dose of 40 mg/kg administered repeatedly reduced significantly the duration of immobility. Ethaverine in a dose of 10 mg/kg did not affect the immobility after single and repeated administration. Imipramine and fluoxetine in doses which were not effective by themselves, increased the immobilityreducing effect when administered concormitantly with ethaverine in a dose of 10 mg/kg. Imipramine in a dose of 20 mg/kg and fluoxetine in a dose of 80 mg/kg, administered alone reduced the immobility time. The reduction of immobility after the concormitant administration of ethaverine in a dose of 10 mg/kg and imipramine in a dose of 20 mg/kg, fluoxetine in a dose of 80 mg/kg was significantly greater than after imipramine or fluoxetine, administered alone. The anti-immobility effect of the ethaverine was significantly counteracted by haloperidol in a dose of 0.5 mg/kg. The effects of ethaverine on the levels of monoamines and their metabolites were also investigated in rat striatum, cerebral cortex, cerebellum, medulla oblongata, hypothalamus, midbrain, hippocampus. Treatment with ethaverine caused alterations on the levels of dopamine and its metabolite in rat striatum, cerebral cortex, hypothalamus, medulla oblongata, cerebellum, but not on the levels of norepinephrine and serotonin and its metabolite. The observed effects of ethaverine indicate that ethaverine may have an antidepressant activity and may interact with the brain dopaminergic system. The present results suggest that the concormitant administration of ethaverine and antidepressants may have a more potent therapeutic antidepressant effect and/or may permit reduction of the dose of antidepressant and thus diminish its side effects.

A Recent Review of Tardive Dyskinesia: Focused on Basic Experimental Results / 대한정신약물학회지

Long-term treatment with antipsychotics can lead to a sometimes irreversible motor disorder, tardive dyskinesia(TD). Although TD is a serious side effect, the pathophysiology of it remains unclear. This article reviews recent experiments designed to determine the pathophysiology of TD. The review is divided into three parts; the first part describes the existing hypotheses on the pathophysiology of TD, the second part consists of the animal models of TD, and the third part consists of the other descriptions of the exerimental researches on TD. The challenge for the future is to integrate these data into a more complete understanding of the pathophysiology of TD.

A Recent Review of Tardive Dyskinesia: Focused on Basic Experimental Results / 대한정신약물학회지

Long-term treatment with antipsychotics can lead to a sometimes irreversible motor disorder, tardive dyskinesia(TD). Although TD is a serious side effect, the pathophysiology of it remains unclear. This article reviews recent experiments designed to determine the pathophysiology of TD. The review is divided into three parts; the first part describes the existing hypotheses on the pathophysiology of TD, the second part consists of the animal models of TD, and the third part consists of the other descriptions of the exerimental researches on TD. The challenge for the future is to integrate these data into a more complete understanding of the pathophysiology of TD.

Antidepressant Effects of Ethaverine, a Calcium Channel Antagonist, in Animal Models of Depression / 신경정신의학

OBJECTIVES: This pre-clinical study was performed to assess the effects of ethaverine in the two kinds of behavioral models of depression in rats. METHODS: We observed the changes of the immobility time in the forced swimming test and the quantity of sucrose consumed in the chronic mild stress model, using ethaverine(20mg/kg) alone, imipramine(20mg/kg) alone, or ethaverine and imipramine concomitantly. RESULTS: In the forced swimming test, both single treatment and chronic treatment(for 7 days) with imipramine or ethaverine significantly reduced the immobility time, and concomitant chronic treatment with ethaverine potentiated the effect of imipramine. In the chronic mild stress model, both imipramine and ethaverine reversed the decreased sucrose consumption induced by 3-week stress and concomitantly treated ethaverine potentiated the effect of imipramine in the early phase of treatment. CONCLUSIONS: The data suggest that ethaverine can be used alone or concomitantly with other anti-depressants in the clinical situation.

Neurobiology of Depression

At the beginning, researches on the biology of depression or affective illness have focused mainly on the receptor functions and neuroendocrine activities. And the studies of the past years did not break new theoretical background, but the recent advances in the research on the molecular mechanisms underlying neural communication and signal transduction do add some insights to many established ideas. This article will overview some of the more recent advances in the clinical researches of depression. Our major concerns to be presented here include the following : (1) alterations in the post-synaptic neural transduction ; (2) changes in the neurons of hypothalamic neuropeptides ; (3) decreased peptidase enzyme activities : (4) associations of hypothalamic-pituitary-adrenal axis abnormalities with serotonin neurotransmission ; (5) role of serotonin transporter ; (6) changes in the responsiveness of intracellular calcium ion levels ; (7) the inositol deficiency theory of lithium and depression ; (8) the transcription factors including immediate early genes ; (9) recent genetic studies in some families. This brief overview will suggest that changes in DNA occur during antidepressant therapy. These changes at the DNA level initiating a cascade of events underlying antidepressant modality will give us the insight on the molecular biological basis of the pathogenesis of depression and cues for a new class of antidepressants.

Effects of Concomitant Treatment with Drugs Affecting Monoaminergic Systems on the Clozapine-induced Myoclonic Jerks in Partially Restrained Rats

This study was performed to investigate the mechanism of the clozapine-induced seizures in partially restrained rats by concomitant treatment with drugs affecting monoaminergic systems. Partially restrained rats treated with acute single doses of 10mg/kg clozapine exhibited myoclonic jerks(MJs). Drugs affecting the monoaminergic systems, including 2mg/kg haloperidol, 5mg/kg propranolol, 2mg/kg ritanserin, 20mg/kg fluoxetine, and 20mg/kg imipramine, were concomitantly treated with clozapine to observe the effects of these drugs on the MJs. The drugs were given intraperitoneally either as acute single doses(haloperidol, propranolol, ritanserin, and fluoxetine) or as chronic doses for 21 days(haloperidol, imipramine, ritanserin, and fluoxetine). The effects of the concomitant treatment of other drugs on the clozapine-induced MJs were evaluated by comparison of the total numbers of the MJs between the clozapine-treated and concomitantly treated groups. The results were as follows. 1) Concomitant treatment with acute single doses of haloperidol, propranolol, and fluoxetine reduced the total numbers of the clozapine-induced MJs, while concomitant treatment with ritanserin did not. 2) Concomitant treatment with chronic doses of imipramine and ritanserin increased the total numbers of the MJs, while concomitant treatment with fluoxetine reduced them. Concomitant chronic treatment with haloperidol did not affect the numbers of the MJs. These results suggest that dopamine and serotonin, not noradrenalin may be involved in the clozapine-induced MJs in partially restrained rats. Future research needs to study the function of each subtype of monoaminergic receptors on the mechanism of the clozapine-induced seizure.

A Comparison Study on the Psychopathology between the Patients with Dementia of Alzheimer Type and Normal Controls in an Urban Community / 신경정신의학

OBJECT: There are lots of studies on the cognitive impairments in patients with dementia of Alzheimer type in our country, but those on the psychopathology in them are very scanty. We investigated the psychopathology such as psychotic symptoms, depression, and anxiety and their correlations with the severity of cognitive impairments in our urban subjects with dementia of Alzheimer type. METHODS: Our subjects(N=34) with dementia of Alzheimer type in an area of Pusan, aged over 65, are screened with MMSE-K(below 24) and Hachinski's Ischemic Scale(below 4) and enrolled in this study when they met with the criteria of dementia of DSM-IV. They were devided into the mild(N=16) and severe dementic group(N=18) according to their scores of MMSE-K(cut-off point 20/21). The severities of psychiatric symptoms in the two groups were evaluated by using sets of clinical symptom rating scales such as BPRS, HAM-D, and HAM-A and the frequencies of aggressive behaviors and sleep disturbances in them were also rated at that time by two psychiatrists. Data of the two dementic groups were compared with those of healthy control subjects(N=40). RESULTS: The mean total score of BPRS, scores of thinking disturbance and withdrawal retardation subscale were lowest in the healthy control group and highest in the severe dementic group(p<0.05). Mean score of anxious depression subscale of mild dementic group was higher than that of other two groups(p<0.05). There were no ststistical differences in the mean score of hostile suspiciousness subscale among the three groups. The mean total scores of HAM-D and HAM-A tended to be higher in mild dementic group than in other two groups, but the differences were not reached to the statistical significance. These findings were thought to be identical with those of following. The total frequency of insomnia only tended to be higher, but the frequency of initial insomnia and that of using hypnotics were highest in mild dementic group(p<0.05). The frequency of aggressive behaviors tended to be higher in mild dementic group than in other two groups, but the differences were not reached to the statistical significance. CONCLUSION: Patients with dementia of Alzheimer type suffered from several psychiatric problems such as psychotic symptoms, depression, anxiety, insomnia, and aggressive behaviors from the initial stage of the illness. Clinicians should be more aware of those symptoms which need proper pharmacological and social interventions, especially in patients with mild cognitive impairment.

Effect of bronchial artery enbolization in the treatment of massive hemoptysis / 결핵

No abstract available.