• 제목/요약/키워드: Biological assessment

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Manganese and Iron Interaction: a Mechanism of Manganese-Induced Parkinsonism

  • Zheng, Wei
    • Proceedings of the Korea Environmental Mutagen Society Conference
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    • 2003.10a
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    • pp.34-63
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    • 2003
  • Occupational and environmental exposure to manganese continue to represent a realistic public health problem in both developed and developing countries. Increased utility of MMT as a replacement for lead in gasoline creates a new source of environmental exposure to manganese. It is, therefore, imperative that further attention be directed at molecular neurotoxicology of manganese. A Need for a more complete understanding of manganese functions both in health and disease, and for a better defined role of manganese in iron metabolism is well substantiated. The in-depth studies in this area should provide novel information on the potential public health risk associated with manganese exposure. It will also explore novel mechanism(s) of manganese-induced neurotoxicity from the angle of Mn-Fe interaction at both systemic and cellular levels. More importantly, the result of these studies will offer clues to the etiology of IPD and its associated abnormal iron and energy metabolism. To achieve these goals, however, a number of outstanding questions remain to be resolved. First, one must understand what species of manganese in the biological matrices plays critical role in the induction of neurotoxicity, Mn(II) or Mn(III)? In our own studies with aconitase, Cpx-I, and Cpx-II, manganese was added to the buffers as the divalent salt, i.e., $MnCl_2$. While it is quite reasonable to suggest that the effect on aconitase and/or Cpx-I activites was associated with the divalent species of manganese, the experimental design does not preclude the possibility that a manganese species of higher oxidation state, such as Mn(III), is required for the induction of these effects. The ionic radius of Mn(III) is 65 ppm, which is similar to the ionic size to Fe(III) (65 ppm at the high spin state) in aconitase (Nieboer and Fletcher, 1996; Sneed et al., 1953). Thus it is plausible that the higher oxidation state of manganese optimally fits into the geometric space of aconitase, serving as the active species in this enzymatic reaction. In the current literature, most of the studies on manganese toxicity have used Mn(II) as $MnCl_2$ rather than Mn(III). The obvious advantage of Mn(II) is its good water solubility, which allows effortless preparation in either in vivo or in vitro investigation, whereas almost all of the Mn(III) salt products on the comparison between two valent manganese species nearly infeasible. Thus a more intimate collaboration with physiochemists to develop a better way to study Mn(III) species in biological matrices is pressingly needed. Second, In spite of the special affinity of manganese for mitochondria and its similar chemical properties to iron, there is a sound reason to postulate that manganese may act as an iron surrogate in certain iron-requiring enzymes. It is, therefore, imperative to design the physiochemical studies to determine whether manganese can indeed exchange with iron in proteins, and to understand how manganese interacts with tertiary structure of proteins. The studies on binding properties (such as affinity constant, dissociation parameter, etc.) of manganese and iron to key enzymes associated with iron and energy regulation would add additional information to our knowledge of Mn-Fe neurotoxicity. Third, manganese exposure, either in vivo or in vitro, promotes cellular overload of iron. It is still unclear, however, how exactly manganese interacts with cellular iron regulatory processes and what is the mechanism underlying this cellular iron overload. As discussed above, the binding of IRP-I to TfR mRNA leads to the expression of TfR, thereby increasing cellular iron uptake. The sequence encoding TfR mRNA, in particular IRE fragments, has been well-documented in literature. It is therefore possible to use molecular technique to elaborate whether manganese cytotoxicity influences the mRNA expression of iron regulatory proteins and how manganese exposure alters the binding activity of IPRs to TfR mRNA. Finally, the current manganese investigation has largely focused on the issues ranging from disposition/toxicity study to the characterization of clinical symptoms. Much less has been done regarding the risk assessment of environmenta/occupational exposure. One of the unsolved, pressing puzzles is the lack of reliable biomarker(s) for manganese-induced neurologic lesions in long-term, low-level exposure situation. Lack of such a diagnostic means renders it impossible to assess the human health risk and long-term social impact associated with potentially elevated manganese in environment. The biochemical interaction between manganese and iron, particularly the ensuing subtle changes of certain relevant proteins, provides the opportunity to identify and develop such a specific biomarker for manganese-induced neuronal damage. By learning the molecular mechanism of cytotoxicity, one will be able to find a better way for prediction and treatment of manganese-initiated neurodegenerative diseases.

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Relationships between Nailfold Plexus Visibility, and Clinical Variables and Neuropsychological Functions in Schizophrenic Patients (정신분열병 환자에서 손톱 주름 총 시도(叢 視度) (Nailfold Plexus Visibility)와 임상양상, 신경심리 기능과의 관계)

  • Kang, Dae-Yeob;Jang, Hye-Ryeon
    • Korean Journal of Biological Psychiatry
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    • v.9 no.1
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    • pp.50-61
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    • 2002
  • Objectives:High nailfold plexus visibility can reflect central nervous system defects as an etiologic factor of schizophrenia indirectly. Previous studies suggest that this visibility is particularly related to the negative symptoms of schizophrenia and frontal lobe deficiency. In this study, we examined the relationships between nailfold plexus visibility, and various clinical variables and neuropsychological functions in schizo-phrenic patients. Methods:Forty patients(21males, 19 females) satisfying the DSM-IV criteria for schizophrenia and thirty eight normal controls(20 males, 18 females) were measured for Plexus Visualization Score(PVS) by using the capillary microscopic examination. For the assessment of psychopathology, process-reactivity, premorbid adjustment, and neuropsychological functions, we used Positive and Negative Syndrome Scale(PANSS), Ullmann-Giovannoni Process-Reactive Questionnaire(PRQ), Phillips Premorbid Adjustment Scale(PAS), Korean Wechsler Adult Intelligence Scale(KWIS), Continuous Performance Test(CPT), Wisconsin Card Sort Test (WCST), and Word Fluency Test. We also collected data about clinical variables. Results:PVS was correlated with PANSS positive symptom score and composite score negatively. There were no correlations between PVS and PRQ score, PAS score and neuropsychological variables respectively. Conclusions:This study showed that nailfold plexus visibility was a characteristic feature in some schizophrenic patients, and that higher plexus visibility was associated with the negative symptoms of schizophrenia. There was no association between plexus visibility and neuropsychological functions.

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A Double-Blind Comparison of Paroxetine and Amitriptyline in the Treatment of Depression Accompanied by Alcoholism : Behavioral Side Effects during the First 2 Weeks of Treatment (주정중독에 동반된 우울증의 치료에서 Paroxetine과 Amitriptyline의 이중맹 비교 : 치료초기 2주 동안의 행동학적 부작용)

  • Yoon, Jin-Sang;Yoon, Bo-Hyun;Choi, Tae-Seok;Kim, Yong-Bum;Lee, Hyung-Yung
    • Korean Journal of Biological Psychiatry
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    • v.3 no.2
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    • pp.277-287
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    • 1996
  • Objective : It has been proposed that cognition and related aspects of mental functioning are decreased in depression as well as in alcoholism. The objective of the study was to compare behavioral side effects of paroxetine and amitriptyline in depressed patients accompanied by alcoholism. The focused comparisons were drug effects concerning psychomotor performance, cognitive function, sleep and daytime sleepiness during the first 2 weeks of treatment. Methods : After an alcohol detoxification period(3 weeks) and a washout period(1 week), a total of 20 male inpatients with alcohol use disorder (DSM-IV), who also had a major depressive episode(DSM-IV), were treated double-blind with paroxetine 20mg/day(n=10) or amitriptyline 25mg/day(n=10) for 2 weeks. All patients were required to have a scare of at least 18 respectively on bath the Hamilton Rating Scale far Depression(HAM-D) and Beck Depression Inventory(BDI) at pre-drug baseline. Patients randomized to paroxetine received active medication in the morning and placebo in the evening whereas those randomized to amitriptyline received active medication in the evening and placebo in the morning. All patients performed the various tasks in a test battery at baseline and at days 3, 7 and 14. The test battery included : critical flicker fusion threshold for sensory information processing capacity : choice reaction time for gross psychomotor performance : tracking accuracy and latency of response to peripheral stimulus as a measure of line sensorimotor co-ordination and divided attention : digit symbol substitution as a measure of sustained attention and concentration. To rate perceived sleep and daytime sleepiness, 10cm line Visual analogue scales were employed at baseline and at days 3, 7 and 14. The subjective rating scales were adapted far this study from Leeds sleep Evaluation Questionnaire and Epworth Sleepiness Scale. In addition a comprehensive side effect assessment, using the UKU side effect rating scale, was carried out at baseline and at days 7 and 14. The efficacy of treatment was evaluated using HAM-D, BDI and clinical global impression far severity and improvement at days 7 and 14. Results : The pattern of results indicated thai paroxetine improved performance an mast of the lest variables and also improved sleep with no effect on daytime sleepiness aver the study period. In contrast, amitriptyline produced disruption of performance on same tests and improved sleep with increased daytime sleepiness in particular at day 3. On the UKU side effect rating scale, mare side effects were registered an amitriptyline. The therapeutic efficacy was observed in favor of paroxetine early in day 7. Conclusion : These results demonstrated thai paroxetine in much better than amitriptyline for the treatment of depressed patients accompained by alcoholism at least in terms of behavioral safety and tolerability, furthermore the results may assist in explaining the therapeutic outcome of paroxetine. For example, and earlier onset of antidepressant action of paroxetine may be caused by early improved cognitive function or by contributing to good compliance with treatment.

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An Open-label, Randomized, Comparative Assessment of the Efficacy and Safety between Tofisopam and Lorazepam in Anxiety Disorder (Tofisopam과 lorazepam의 항불안효과와 안전성에 대한 비교 연구)

  • Lee, Min Soo;Kim, Yong-Ku;Kwak, Dong-Il
    • Korean Journal of Biological Psychiatry
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    • v.4 no.2
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    • pp.265-271
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    • 1997
  • Objective : A 4-week, single-blind, parallel group study was conducted to evaluate the efficacy and safety of tofisopam and lorazepam in 32 outpatients with anxiety disorder. Methods : Patients were randomized to receive either tofisopam(N=17) or lorazepam(N=15). The starting dose of tofisopam was 50mg t.i.d. daily, which could be increased to a maximum of 100mg t.i.d. according to the patient's clinical response and side effect. The starting dose of lorazepam was 0.75mg b.i.d. daily, which could be increased to a maximum of 1.5mg b.i.d. depending on the patient's clinical response and side effect. Efficacy evaluations at baseline, week 1, 2, and 4 used the 14-item Hamilton Rating Scale for Anxiety(HAM-A) and Clinical Global Impression(CGI). Tolerability was assessed by response to a nonleading question concerning adverse events. Laboratory parameters including vital sign, EKG, hematological, and biochemical values were measured during trial. Results : No significant differences between HAM-A total scores, two HAM-A factors(psychic, somatic) and CGI severity scores were recorded at any point during tofisopam and lorazepam treatments. However, in each group there was a significant decrease in HAM-A total scores, two HAM-A factor s(psychic, somatic), CGI severity scores over time. The pecentages of patients with tofisopam who at least minimally improved increased from 64.7% at week 1 to 94.1% at week 4. The pecentages of patients with lorazepam who at least minimally improved increased from 40.0% at week 1 to 66.7% at week 4. The pecentages of patients with tofisopam who had not any adverse event increased from 58.8% at week 1 to 87.9% at week 4. The pecentages of patients with lorazepam who had not any adverse event were not changed from 46.7% at week 1 to 46.7% at week 4. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial in both groups. Conclusion : These data suggest that tofisopam may be effective in reducing anxiety and is a anti-anxiety drug of identical potency with lorazepam. Tolerability of tofisopam was superior to lorazepam. These findings should be confirmed by using double-blind crossover study with a large member of patients.

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Ttrosine Hydroxylase in Japanese Medaka (Oryzias latipes): cDNA Cloning and Molecular Monitoring of TH Gene Expression As a Biomarker (송사리 Tyrosine Hydroxylase: cDNA 클로닝 및 생물지표로서의 TH 유전자 발현의 분자생물학적 추적)

  • Shin, Sung-Woo;Kim, Jung-Sang;Chon, Tae-Soo;Lee, Sung-Kyu;Koh, Sung-Cheol
    • Environmental Analysis Health and Toxicology
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    • v.15 no.4
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    • pp.131-137
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    • 2000
  • The release of hazardous waste materials into the environment poses serious risks in humans and ecosystems. The risk assessment of environmental pollutants including hazardous chemicals requires a comprehensive measurement of hazard and exposure of the chemicals that can be achieved by toxicity evaluation using a biological system such as biomarkers. In this report we have tried to develop a biomarker used to elucidate a molecular basis of, and to monitor abnormal behaviors caused by diazinon in Japanese medaka (Oryzias latipes) as a model organism. First, an attempt was made to clone tyrosine hydroxylase gene from Japanese medaka that would be a candidate for a biomarker for neuronal modulations and behaviors. For monitoring experiments at behavioral and molecular biological levels, the fish were treated under different sublethal conditions of diazinon and their behavioral responses were observed . In this study we have successfully cloned a partial TH gene from the medaka fish through PCR screening of an ovary cDNA library. DNA sequencing analysis revealed that the amplified fragment was 327 bp encoding 109 amino acids. Comparing the DNA sequence of medaka TH with other species, TH gene revealed the DNA sequence was completely identical to that of rat TH. In the RT-PCR, 330 Up of mRNA was consistently amplified in all the treated samples including control There were no significant differences in the TH expression level regardless of treating concentrations (1∼5,000 ppb) and time (0∼48 hr) The reason appeared to be that RT-PCR was not performed using through a quantitative analysis normalized against an actin gene expression. Organ or tissue - specific detection of TH activity and mRNA as biomarkers will be a useful monitoring tool for neurobehavioral changes in fish influenced by toxic chemicals. Furthermore, quantitative analysis of locomotive patterns and its correlation with the neurochemical and molecular data would be highly useful in measuring toxicity and hazard ofvarious environmental pollutants.

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A Clinical Study of Child Abuse (아동학대로 진단된 환아의 임상적 고찰)

  • Choi, Yoon Jin;Kim, Shin Mi;Sim, Eun Jung;Cho, Do Jun;Kim, Dug Ha;Min, Ki Sik;Yoo, Ki Yang
    • Clinical and Experimental Pediatrics
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    • v.50 no.5
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    • pp.436-442
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    • 2007
  • Purpose : To promote awareness and efforts by pediatricians to identity and prevent child abuse by investigation of characteristics of victim and types of injury caused by abuse. Methods : A retrospective study was performed with 20 patients who had been diagnosed or suspected as child abuse at Hallym University Hospital from January 1999 to December 2005. The medical records, radiologic documents, and social worker's notes were reviewed to investigate age, sex, visiting time, form of abuse, perpetrator, risk factor, and type of injury. Results : The mean age of the subjects was 2.8 years. Fourteen patients were between 0-1 years old, 2 patients between 1-6 years old, 3 patients between 7-12 years old, and 1 case over 13 years old. The ratio of male to female was 1:1. The majority of these patients (70%) visited via emergency department. Eight five percent of these patients reported with physical abuse, 5% psychological abuse, 5% sexual abuse, and 5% neglect respectively. The suspected perpetrator was the biological father in six cases, the biological mother in three cases, the stepmother in two cases, caregiver in one case, relatives in one case and "unknown" in six cases. Bruise and hematoma (80%) were the most common physical findings. Skull fractures were diagnosed in six cases, long bone fractures in two cases, hemoperitoneum in two cases, subdural hemorrhage in 10 cases, epidural hemorrhages in two cases, subarachnoidal hemorrhages in two cases, and retinal hemorrhages in five cases respectively. Seventeen cases required hospitalization and surgical operations performed were in nine cases. Four patients died and three patients had sequalae such as developmental delay and quadriplegia. Conclusion : Child abuse results in high mortality and morbidity in victims. Therefore early recognition and prevention is very important. Pediatricians should always suspect the possibilities of abuse in cases of fracture, intracranial hemorrhage, abdominal injury, or even any injury to the body. We recommend that the clinical investigation of suspicious children should include a full multidisciplinary social assessment, a skeletal survey and CT or MRI.

Management of plant genetic resources at RDA in line with Nagoya Protocol

  • Yoon, Moon-Sup;Na, Young-Wang;Ko, Ho-Cheol;Lee, Sun-Young;Ma, Kyung-Ho;Baek, Hyung-Jin;Lee, Su-Kyeung;Lee, Sok-Young
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2017.06a
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    • pp.51-52
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    • 2017
  • "Plant genetic resources for food and agriculture" means any genetic material of plant origin of actual or potential value for food and agriculture. "Genetic material" means any material of plant origin, including reproductive and vegetative propagating material, containing functional units of heredity. (Internal Treaty on Plant Genetic Resources for Food and Agriculture, ITPGRFA). The "Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization (ABS) to the Convention on Biological Diversity (shortly Nagoya Protocol)" is a supplementary agreement to the Convention on Biological Diversity. It provides a transparent legal framework for the effective implementation of one of the three objectives of the CBD: the fair and equitable sharing of benefits arising out of the utilization of genetic resources. The Nagoya Protocol on ABS was adopted on 29 October 2010 in Nagoya, Japan and entered into force on 12 October 2014, 90 days after the deposit of the fiftieth instrument of ratification. Its objective is the fair and equitable sharing of benefits arising from the utilization of genetic resources, thereby contributing to the conservation and sustainable use of biodiversity. The Nagoya Protocol will create greater legal certainty and transparency for both providers and users of genetic resources by; (a) Establishing more predictable conditions for access to genetic resources and (b) Helping to ensure benefit-sharing when genetic resources leave the country providing the genetic resources. By helping to ensure benefit-sharing, the Nagoya Protocol creates incentives to conserve and sustainably use genetic resources, and therefore enhances the contribution of biodiversity to development and human well-being. The Nagoya Protocol's success will require effective implementation at the domestic level. A range of tools and mechanisms provided by the Nagoya Protocol will assist contracting Parties including; (a) Establishing national focal points (NFPs) and competent national authorities (CNAs) to serve as contact points for information, grant access or cooperate on issues of compliance, (b) An Access and Benefit-sharing Clearing-House to share information, such as domestic regulatory ABS requirements or information on NFPs and CNAs, (c) Capacity-building to support key aspects of implementation. Based on a country's self-assessment of national needs and priorities, this can include capacity to develop domestic ABS legislation to implement the Nagoya Protocol, to negotiate MAT and to develop in-country research capability and institutions, (d) Awareness-raising, (e) Technology Transfer, (f) Targeted financial support for capacity-building and development initiatives through the Nagoya Protocol's financial mechanism, the Global Environment Facility (GEF) (Nagoya Protocol). The Rural Development Administration (RDA) leading to conduct management agricultural genetic resources following the 'ACT ON THE PRESERVATION, MANAGEMENT AND USE OF AGRO-FISHERY BIO-RESOURCES' established on 2007. According to $2^{nd}$ clause of Article 14 (Designation, Operation, etc. of Agencies Responsible for Agro-Fishery Bioresources) of the act, the duties endowed are, (a) Matters concerning securing, preservation, management, and use of agro-fishery bioresources; (b) Establishment of an integrated information system for agro-fishery bioresources; (c) Matters concerning medium and long-term preservation of, and research on, agro-fishery bioresources; (d) Matters concerning international cooperation for agro-fishery bioresources and other relevant matters. As the result the RDA manage about 246,000 accessions of plant genetic resources under the national management system at the end of 2016.

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Assessment of Adsorption Capacity of Mushroom Compost in AMD Treatment Systems (광산배수 자연정화시설 내 버섯퇴비의 중금속 흡착능력 평가)

  • Yong, Bo-Young;Cho, Dong-Wan;Jeong, Jin-Woong;Lim, Gil-Jae;Ji, Sang-Woo;Ahn, Joo-Sung;Song, Ho-Cheol
    • Economic and Environmental Geology
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    • v.43 no.1
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    • pp.13-20
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    • 2010
  • Acid mine drainage (AMD) from abandoned mine sites typically has low pH and contains high level of various heavy metals, aggravating ground- and surface water qualities and neighboring environments. This study investigated removal of heavy metals in a biological treatment system, mainly focusing on the removal by adsorption on a substrate material. Bench-scale batch experiments were performed with a mushroom compost to evaluate the adsorption characteristics of heavy metals leached out from a mine tailing sample and the role of SRB in the overall removal process. In addition, adsorption experiments were perform using an artificial AMD sample containing $Cd^{2+}$, $Cu^{2+}$, $Pb^{2+}$ and $Zn^{2+}$ to assess adsorption capacity of the mushroom compost. The results indicated Mn leached out from mine tailing was not subject to microbial stabilization or adsorption onto mushroom compost while microbially mediated stabilization played an important role in the removal of Zn. Fe leaching significantly increased in the presence of microbes as compared to autoclaved samples, and this was attributed to dissolution of Fe minerals in the mine tailing in a response to the depletion of $Fe^{3+}$ by iron reduction bacteria. Measurement of oxidation reduction potential (ORP) and pH indicated the reactive mixture maintained reducing condition and moderate pH during the reaction. The results of the adsorption experiments involving artificial AMD sample indicated adsorption removal efficiency was greater than 90% at pH 6 condition, but it decreased at pH 3 condition.

Overwintering and Succession of the Phytoplankton in Pilot Culture System (현장규모 대형 배양장치에서 식물플랑크톤의 월동 및 천이)

  • Noh, Seongyu;Lee, Kyung-Lak;Shin, Yuna;Lee, Jaeyoon;Song, Mi-Ae;Lee, Jaean;Rhew, Doughee;Lee, Jaekwan
    • Korean Journal of Ecology and Environment
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    • v.50 no.1
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    • pp.57-69
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    • 2017
  • Overwintering and succession of phytoplankton community with physicochemical and biological characteristics were investigated in pilot culture system. Water and phytoplankton samples were collected twice a week from February 23 to June 28, 2016. A total of 17 overwintering taxa including cyanophyceae, chlorophyceae, bacillariophyceae were identified in the experimental group in winter (February), and these overwintering species showed a marked succession pattern along with environment changes. In the process of phytoplankton succession, a total of 56 species in 28 genera were identified in two (experimental, control) pilot culture system. In the experimental group, 52 phytoplankton species in 24 genera were identified, and the number of taxa was highest in chlorophyceae (35 species), followed by Bacillariophyceae (9 species), Cyanophyceae (5 species) and others (3 species). In the control group, 25 phytoplankton species in 14 genera were classified and these taxa consisted of 17 chlorophyceae, 3 cyanophyceae, 2 Bacillariophyceae and 3 others. The standing crops ranged from 40 to $325,450cells\;mL^{-1}$ in the experimental group, and from 900 to $37,100cells\;mL^{-1}$ in the control group, respectively. The dominant species were represented by Monoraphidium minutum, Microcystis aeruginosa, Rhodomonas lacustris, Ankyra judai and Chlorella vulgaris in the experimental group; and M. minutum and Coenochloris cf. pyrenoidosa in the control group. In conclusion, overwintering and succession of predominant phytoplankton species developed due to interactions of internal environmental factors(physicochemical and biological factors) in the pilot culture system.

Treatment Strategies for Depression during Pregnancy and Lactation (임신과 수유기 우울증의 치료 전략)

  • Lee, Soyoung Irene;Jung, Han-Yong
    • Korean Journal of Biological Psychiatry
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    • v.14 no.2
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    • pp.91-98
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    • 2007
  • Objectives : Considering the impact of depressive illness on physical and mental health of both mother and fetus, specification of a treatment algorithm for depressive disorder during pregnancy is legitimated. This article provides a systemic review of treatments for depressive disorder during pregnancy and lactation. Methods : According to the search strategy of the Clinical Research Center for Depression of Korean Health 21 R & D Project, PubMed and EMBASE were searched using terms with regard to the treatment of depressive disorders during pregnancy and lactation. Reference lists of related reviews and studies were searched. In addition, relevant practice guidelines were searched using the PubMed. All identified clinical literatures were reviewed and summarized in a narrative manner. Results : Pharmacotherapy during pregnancy and lactation requires a comprehensive assessment of the risks and benefits of treatment for both mother and fetus or neonate. Recently, there is growing evidence that the use of tricyclic and selective serotonin reuptake inhibitors during pregnancy and lactation does not result in increased risks of teratogenicity. Treatment strategies are described according to the point of time of pregnancy or lactation. FDA categories for antidepressants during pregnancy and lactation are described. In addition, issues regarding to the electroconvulsive therapy and psychosocial treatment are discussed. Conclusion : The treatment option for depressive disorders during pregnancy and lactation depends on the severity of depressive illnesses of the individual patient. For mild to moderate depression, the non-pharmacological treatment should be considered first. For moderate to severe depression, pharmacotherapy should be administered in addition to the psychosocial treatment. ECT is recommended for depressive disorder of severe intensity. As the research knowledge is limited, the recommendations should based on the best judgement of psychiatrists.

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