• Journal of The Association for Neo Medicine
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• v.2 no.1
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• pp.35-54
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• 1997

We tried to observe the features of ancient medical practice by analysing the records related to medicine in the book, ${\ulcorner}$the Historical Records of the Three Kingdom${\lrcorner}$ of which content includes the features of medicine in mythology, plague, delivery of twins, drugs, medical system, shamanism, constitutional medicine, psychiatry, forensic medicine, deformity, a spa, medical phrase, health and welfare work, religion, death. physiological anatomy, Taoist medicine, acupuncture, the occult af of transformation and etc. Our initial concern was about where to draw line as of medical field and we defined medicine in more broad meaning. The book ${\ulcorner}$the Historical Records of the Three Kingdoms${\lrcorner}$ describes the world of mythology by way of medicine which is not clearly a conventional one. There appears records of birth of multiple offsprings 7 times in which cases are of triplets or more. Delivering multiple offsprings were rare phenomenon though such fertility was highly admired. This shows one aspect of ancient country having more population meant more power of the nation. Of those medical records conveyed in that book includes stories of childbirth such as giving birth to a son after praying, giving birth to Kim Yoo-shin after 20 months after mother's dream of conception, and a song longing for getting a laudable child. Plagues were prevalent throughout winter to spring season and one can observe various symptoms of plagues in the record. Of these epidemic diseases, cold type might have been more common than the heat one. Appearance of epidemic diseases frequently coincided with that of natural disasters that this suggests a linkage between plague and underlying doctrine on five elements' motion and six kinds of natural factors. There exists only a few names of diseases such as epidemic disease, wind disease, and syndrome characterized by dyspnea. Otherwise there appeared only afflictions that were not specified therefore it remains cluless to keep track of certain diseases of prevalence. Since this ${\ulcorner}$Historical Records of the Three Kingdoms'${\lrcorner}$ wasn't any sort of medical book, words and terms used were not technical kind and most were the ones used generally among lay people. Therefore any mechanisms of the diseases were hardly mentioned. Some of medicinal substances such as Calculus Bovis, Radix Ginseng, Gaboderma Luciderm, magnetitum were also in use in those days. 53 kinds of dietary supplies appears in the records and some of these might have been used as medicinal purpose. Records concerning dicipline of one's body includes activities such as hunting, archery, horseback riding etc. In Shilla dynasty there were positions such as professor of medicine, Naekongbong(內供奉), Kongbong's doctor(供奉醫師), Kongbong's diviner(供奉卜師). As an educational facility, medical school was built at the first year of King Hyoso's reign and it's curricula included various subjects as ${\ulcorner}$Shin Nong's Herbal classic${\lrcorner}$, ${\ulcorner}$Kabeul classic of acupuncture and moxbustion${\lrcorner}$, ${\ulcorner}$The Plain Questions of the Yellow Emperor's Classic of Internal Medicine${\lrcorner}$, ${\ulcorner}$Classic of Acupuncturer${\lrcorner}$, ${\ulcorner}$The Pulse Classic${\lrcorner}$, ${\ulcorner}$Classic of Channels and Acupuncture Points${\lrcorner}$ and ${\ulcorner}$Difficult Classic${\lrcorner}$. There were 2 medical professors who were in charge of education. To establish pharmacopoeia, 2 Shaji(舍知), 6 Sha(史), 2 Jongshaji(從舍知) were appointed. In Baekje dynasty, Department of Herb was maintained. Doing praying for the sake of health, doing phrenology also can be extended to medical arena. Those who survived over 100 years of age appear 3 times in the record, while 98 appears once. The earliest psychiatrist Nokjin differentiated symptoms to apply either therapies using acupuncture and drug or psychotherapy. There appears a case of rape, a case of burying alive with the dead, 8 cases of suicide that can characterize a prototype of forensic medicine. Deformity-related records include phrases as follow: 'there seems protrudent bone behind the head', 'a body which has two heads, two trunks, four arms.', 'a body equipped with two heads' In those times spa can be said to be used as a place for he리ing, convalescence, and relaxation seeing the records describing a person pretended illness and went to spa to enjoy with his friends. Priest doctors and millitary surgeons were in charge of the medical sevice in the period of the Three Kingdoms by the record written by Mookhoja(墨胡子) and Hoonkyeom(訓謙). Poor diet and regimen makes people more vulnerable to diseases. So there existed charity services for those poor people who couldn't live with one's own capacity such as single parents, orphans, the aged people no one to take care and those who are ill. The cause of affliction was frequently coined with human relation. There appeared the phenomenon of releasing prisoners and allowing people to become priests at the time of king's suffering. Besides, as a healing procedure, sutra-chanting was peformed. There appears 10 cases of death related records which varies from death by drowning, or by freezing, death from animals, death from war, death from wightloss and killing oneself at the moment of spouse's death and etc. There also exist certain records which suggest the knowledge of physiology and anatomy in those times. Since the taoist books such as ${\ulcorner}$Book of the Way and Its Power(老子道德經)${\lrcorner}$ were introduced in the period of Three Kingdoms, it can be considered that medicine was also influenced by taoism. Records of higher level of acupuncture, records which links the medicine and occult art of transformation existed. Although limited, we could figure out the medical state of ancient society.

• Tuberculosis and Respiratory Diseases
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• v.46 no.1
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• pp.53-64
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• 1999

Background : Massive and untreated hemoptysis is associated with a mortality of greater than 50 percent. Since the bleeding is from a bronchial arterial source in the vast majority of patients, embolization of the bronchial arteries(BAE) has become an accepted treatment in the management of massive hemoptysis because it achieves immediate control of bleeding in 75 to 90 percent of the patients. Methods: Between 1990 and 1996, we treated 146 patients with hemoptysis by bronchial artery embolization. Catheters(4, 5, or 7F) and gelfoam, ivalon, and/or microcoil were used for embolization. Results: Pulmonary tuberculosis and related disorders were the most common underlying disease of hemoptysis(72.6%). Immediate success rate to control bleeding within 24hours was 95%, and recurrence rate was 24.7%. The recurrence rate occured within 6 months after embolization was 63.9%. Initial angiographic findings such as bilaterality, systemic-pulmonary artery shunt, neovascularity, aneurysm were not statistically correlated with rebleeding tendency(P>0.05). Among Initial radiographic findings, only pleural lesions were significantly correlated with rebleeding tendency(P<0.05). At additional bronchial artery angiograpy done due to rebleeding, recanalization of previous embolized arteries were 63.9%, and the presence of new feeding arteries were 16.7%, and 19.4% of patients with rebleeding showed both The complications such as fever, chest pain, headache, nausea and vomiting, arrhythmia, paralylytic ileus, transient sensory loss (lower extremities), hypotension, urination difficulty were noticed at 40 patients(27.4%). Conclusion: We conclude that bronchial artery embolization is relatively safe method achieving immediate control of massive hemoptysis. At initial angiographic findings, we could not find any predictive factors for subsequent rebleeding. It may warrant further study whether patients with pleural disease have definetely increased rebleeding tendency.

• Tuberculosis and Respiratory Diseases
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• v.46 no.3
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• pp.350-362
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• 1999

Background: Acute Respiratory failure which is developed after extubation in the weaning process from mechanical ventilation is an important cause of weaning failure. Once it was developed, endotracheal reintubation has been done for respiratory support. Noninvasive Positive Pressure Ventilation (NIPPV) has been used in the management of acute or chronic respiratory failure, as an alternative to endotracheal intubation, using via nasal or facial mask. In this study, we evaluated the usefulness of NIPPV as an alternative method of reintubation in patients who developed acute respiratory failure after extubation. Method: We retrospectively analyzed thirty one patients(eighteen males and thirteen females, mean ages $63\pm13.2$ years) who were developed acute respiratory failure within forty eight hours after extubation, or were extubated unintentionally at medical intensive care unit(MICU) of Asan Medical Center. NIPPV was applied to the patients. Ventilatory mode of NIPPV, level of ventilatory support and inspiratory oxygen concentration were adjusted according to the patient condition and results of blood gas analysis by the attending doctors at MICU. NIPPV was completely weaned when the patients maintained stable clinical condition under 8 $cmH_2O$ of pressure support level. Weaning success was defined as maintenance of stable spontaneous breathing more than forty eight hours after discontinuation of NIPPV. Respiratory rate, heart rate, arterial blood gas analysis, level of pressure support, and level of PEEP were monitored just before extubation, at thirty minutes, six hours, twenty four hours after initiation of NIPPV. They were also measured at just before weaning from NIPPV in success group, and just before reintubation in failure group. Results: NIPPV was successfully applied to thirty-one patients of thirty-two trials and one patient could not tolerated NIPPV longer than thirty minutes. Endotracheal reintubation was successfully obviated in fourteen patients (45%) among them. There was no difference in age, sex, APACHE III score on admission at MICU, duration of intubation, interval from extubation to initiation of NIPPV, baseline heart rate, respiratory rate, arterial blood gas, and $PaO_2/FiO_2$ between the success and the failure group. Heart rate and respiration rate were significantly decreased with increase $SaO_2$ after thirty minutes of NIPPV in both groups(p<0.05). However, in the patients of failure group, heart rate and respiratory rate were increased again with decrease in $SaO_2$ leading to endotracheal reintubation. The success rate of NIPPV treatment was significantly higher in the patients with COPD compared to other diseases(62% vs 39%) (p=0.007). The causes of failure were deterioration of arterial blood gas without aggravation of underlying disease(n=9), aggravation of undelying disease(n=5), mask intolerance(n=2), and retained airway secretion(n=l). Conclusion: NIPPV would be a useful therapeutic alternative which can avoid reintubation in patient who developed acute respiratory failure after extubation.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.237-244
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• 2001

Purpose : To assess the tolerance, complete response rate, bladder preservation rate and survival rate in patients with muscle-invading bladder cancer treated with selective bladder preservation protocol. Method and Materials : From October 1990 to June 1998, twenty six patients with muscle-invading bladder cancer (clinical stage T2-4, N0-3, M0) were enrolled for the treatment protocol of bladder preservation. They were treated with maximal TURBT (transurethral resection of bladder tumor) and 2 cycles of MCV chemotherapy (methotrexate, crisplatin, and vinblastine) followed by $39.6\~45\;Gy$ pelvic irradiation with concomitant cisplatin. After complete urologic evaluation (biopsy or cytology), the patients who achieved complete response were planed for bladder preservation treatment and treated with consolidation cisplatin and radiotherapy (19.8 Gy). The patients who had incomplete response were planed to immediate radical cystectomy. If they refused radical cystectomy, they were treated either with TURBT followed by MCV or cisplatin chemotherapy and radiotherapy. The median follow-up duration is 49.5 months. Results : The Patients with stage T2-3a and T3b-4a underwent complete removal of tumor or gross tumor removal by TURBT, respectively. Twenty one out of 26 patients $(81\%)$ successfully completed the protocol of the planned chemo-radiotherapy. Seven patients had documented complete response. Six of them were treated with additional consolidation cisplatin and radiotherapy. One patient was treated with 2 cycles of MCV chemotherapy due to refusal of chemo-radiotherapy. Five of 7 complete responders had functioning tumor-free bladder. Fourteen patients of incomplete responders were further treated with one of the followings : radical cystectomy (1 patient), or TURBT and 2 cycles of MCV chemotherapy (3 patients), or cisplatin and radiotherapy (10 patients). Thirteen patients of them were not treated with planned radical cystectomy due to patients' refusal (9 patients) or underlying medical problems (4 patients). Among twenty one patients, 12 patients $(58\%)$ were alive with their preserved bladder, 8 patients died with the disease, 1 patient died of intercurrent disease. The 5 years actuarial survival rates according to CR and PR after MCV chemotherapy and cisplatin chemoradiotherapy were $80\%\;and\;14\%$, respectively (u=0.001). Conclusion : In selected patients with muscle-invading bladder cancer, the bladder preservation could be achieved by MCV chemotherapy and cisplatin chemo-radiotherapy. All patients tolerated well this bladder preservation protoco. The availability of complete TURBT and the responsibility of neoadjuvant chemotherapy and chemoradiotherapy were important predictors for bladder preservation and survival. The patients who had not achieved complete response after neoadjuvant chemotherapy and chemoradiotherapy should be immediate radical cystectomy. A randomized prospective trial might be essential to determine more accurate indications between cystectomy or bladder preservation.

• Clinical and Experimental Pediatrics
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• v.48 no.4
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• pp.401-405
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• 2005

Purpose : The use of mechanically-assisted ventilators at home reduces morbidity and improves the quality of life in children with chronic respiratory failure. But in Korea there is no clinical data of children with home mechanical ventilation. We investigated ventilator types, duration, the causes of failure or death, and the cost needed for care. Methods : We retrospectively analyzed the medical records of 21 children who were admitted and who applied for home mechanical ventilation at the Pediatric Intensive Care Unit in Asan Medical Center. Phone interviews took place after discharge. and interviewed by phone after discharge. Results : The median age was 31 months; the median duration with ventilator was 25 months. Underlying diseases were 16 neuromuscular diseases, one metabolic disease and four chronic respiratory diseases. The types of ventilator were pressure and volume type(16 and five patients, respectively). The frequency of ventilation failure was once per 19 months. Weaning could be performed in three cases. Frequencies of admission after receiving ventilators were 1.7 times per year; the most common cause was pneumonia. Nine patients(43%) died; four of them died because of endotracheal tube obstruction. The costs for medical care were about 1,110,000 won per month. Conclusion : There is an increment in the numbers of individuals who need mechanical ventilation support. The most common cause of death was endotracheal tube obstruction. The most important problem for the patients was medical cost. There needs to be more interest in patients with ventilator and social welfare systems to support their families need to be prepared.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.889-898
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• 1997

Pulmonary Embolism can develop in variable conditions, and presents with nonspecific symptoms and signs. If diagnosis is delayed, it can be resulted in catastrophic results. Therefore, early diagnosis and adequate treatment is crucial in Pulmonary Embolism. Lung Perfusion Scan is useful screening test. Negative result can exclude pulmonary embolism. But, perfusion defects don't always mean pulmonary embolism. To find the better methods of interpretation of lung perfusion scan and To evaluate the clinical course and outcomes of the patients, in whom pulmonary embolism was suspected by lung perfusion scan, we reviewed the clinical records of 49 cases suspected by lung perfusion scan at Seoul National University Hospital during the period of January, 1995 to July, 1996. The results are as follows. First impression of cases in which PE was present at time of admission were pulmonary embolism (63%), heart diseases (26%), and pneumonia (11%) in orders. Underlying diseases of cases in which PE developed during admission were malignancy (36.5%), ICH (22.7%), sepsis (13.7%), and SLE (9.1%) in orders. The predisposing factors were operation (20%), cancer (16%), immobility (16%), connective tissue disease (16%), heart dis. (10%), old age (10%), and preg/pelvic dis. (8%) The results, of lung perfusion scan were HPPE 40 cases(26.8 %), IPPE 21 cases(14.1%), LPPE 88 cases (59.1%), and cases(%) of treatment in these cases were HPPE 34 cases(85%), IPPE 9 cases(42.9%), LPPE 0 case(0.0%). Treatments were heparin and warfarin (69.5%), heparin alone (8.2%), warfarin alone (2.0%), embolectomy (4.1%), thrombolytics (2.0%), IVC filter (2.0%), and no treatment (12.2%) In 34 cases (69.4%), follow up could be done, and 5 cases were recurred (10.2%). The causes of recurrence was incomplete anticoagulant therapy (3 cases) and recurrence of predisposing factor (2 cases). Expired case due to pulmonary embolism was one who was expired just before trial of thrombolytic therapy. Conclusion : Efforts should be made to shorten the interval from onset of Sx to Dx, ie, high index of suspision.

• Tuberculosis and Respiratory Diseases
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• v.53 no.1
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• pp.17-26
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• 2002

Background : The detection and early elimination of the causes for acute respiratory distress syndrome(ARDS) at the initial stage can result in a more favorable prognosis. Miliary tuberculosis as a cause of the ARDS is quite rare. A diagnosis of miliary tuberculosis is difficult due to the diversity of radiological patterns and non-specific clinical finfings, and low sensitivity of sputum examinations for acid-fast bacilli(AFBs). An analysis of the clinical data is the first step in diagnosing these unusual, rare cases. Materials and Methods : In this study the clinical features, laboratory data, radiological findings and diagnostic methods were analyzed in 9 cases with an initial presentation of ARDS due to miliary tuberculosis. The ARDS was defined by the definition of the American-Europian consensus conference 1992. Results : The mean age of the patients was $67{\pm}18$ years (F:M=7:2). The chief complaints were dyspnea(5/9), coughing (3/9) and fever(5/9). On a physical examination, fine or coarse crackles were noted(6/9). The ARDS developed on average 6.7 days after the initial respiratory symptoms. The mean $PaO_2/FiO_2$ of the patients was $133.5{\pm}53.4$, the number of cases with a WBC<5000/$mm^3$ was 4 out of 9 cases. A platelet count<70,000/$mm^3$ was observed in 2 out of 9 cases, and the serum albumin level was $2.6{\pm}0.6$ g/dL. The initial simple chest PA showed ground glass appearances and consolidation in all cases, However, the miliary nodular densities were observed in only 4 out of the 9 cases. HRCT revealed alveolar densities and a consolidation in 5 out of 6 cases, and miliary nodules in 5 out of 6 cases, The diagnosis of tuberculosis was made by a liver biopsy (4/4, 100% sensitivity), a bone marrow biopsy (1/2, 50% sensitivity), and an open lung biopsy (1/1), the sputum AFB was positive in only 2 out of 9 cases. The patient was treated with INH, RFP, EMB, PZA, and steroids. The survival rate was 55.5%. Conclusion : Miliary tuberculosis should be considered as one of the causes for ARDS in areas where there is a high prevalence of tuberculosis. The chief complaints of the patients on admission are dyspnea, fever and coughing without any specific riskfactors. A liver biopsy is particularly useful in ARDS patients with mechanical ventilation to determine the causes of the ARDS if miliary tuberculosis is suspected as being the underlying disease.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.590-599
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• 1996

Background : Bronchial artery embolization has been established as an effective means to control hemoptysis, especially in patients with decreased pulmonary function and those with advanced chronic obstructive pulmonary disease. We evaluated the effect of arterial embolization in immediate control of massive hemoptysis and investigated the clinical and angiographic characteristics and the course of patients with reccurrent hemoptysis after initial succeseful embolization. Another purpose of this study was to find predictive that cause rebleeding after bronchial artery embolization. Method : We reviewed 47 cases that underwent bronchial artery embolization for the management of massive hemoptysis, retrospectively. We analyzed angiographic findings in all cases before bronchial artery embolization and also reviewed the angiographic findings of patients that underwent additional bronchial artery embolization for the control of reccurrent hemoptysis to find the clauses of rebleeding. Results : 1) Underlying causes of hemoptysis were pulmonary tuberculosis(n=35), bronchiectasis(n=5), aspergilloma(n=2), lung cancer(n=2), pulmonary A-V malformation(n=1), and unknown cases(n=2). 2) Overal immediate success rate was 94%(n=44), an6 recurrence rate was 40%(n=19). 3) The prognostic factors such as bilaterality, systemic-pulmonary artery shunt, multiple feeding arteries and degree of neovascularity were not statistically correlated with rebleeding tendency (p value>0.05). 4) At additional bronchial artery embolization, Revealed recannalization of previous embolized arteries were 14/18cases(78%) and the presence of new deeding arteries was 8/18cases(44%). 5) The complications(31cases, 66%) such as fever, chest pain, cough, voiding difficulty, paralytic ileus, motor and sensory change of lower extremity, atelectasis and splenic infarction were occured. Conclusion : Recannalization of previous embolized arteries is the major cause of recurrence after bronchial artery embolization. Despite high recurrence rate of hemoptysis, bronchial artery embolization for management of massive hemoptysis is a effective and saute procedure in immediate bleeding control.

• 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.

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.153-160
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• 1999

Animal models can provide a useful tool for the study of some aspects of psychiatric disorders and their treatment. The four criteria for the evaluation of animal models of psychiatric disorders are as following : 1) similarity of inducing conditions 2) similarity of behavioral state 3) common underlying neurobiological mechanisms 4) reversal by clinically effective treatment techniques. Several animal models have been proposed for schizophrenia : phenylethylamine model, L-dopa model, hallucinogen model, cocaine model, amphetamine model, phencyclidine model, noradrenergic reward system lesion model, reticular stimulation model, social isolation model, conditioned avoidance reaction, catalepsy test, paw test, self-stimulation paradigms, latent inhibition paradigms, blocking paradigms, prepulse inhibition of the startle reflex, rodent interaction, social behavior in monkeys, hippocampal damage, high ambient pressure, and models using selective breeding. Among them, animals with bilateral lesion of the hippocampus may provide an adequate animal model for several symptoms of schizophrenia, and ketamine model can reproduce negative symptoms and cognitive deficits as well as positive symptoms of schizophrenia. In conclusion, no model of schizophrenia is entirely representative of the disease, and findings gleaned from model systems must be cautiously interpreted. Furthermore, the process of developing and validating animal models must work in concert with the process to identify reliable measures of human phenomenology.