To evaluate the ultrastructural changes and the mechanism causing liver injury by lead, light and electron microscopic(LM and EM) examination using Timm sulphide silver method(TSM) was done. Sprague-Dawley rats were divided into a control and 3 experimental groups. The experimental groups were orally administered 0.5% lead acetate(LA). Group 1 received a one time dose of 10 ml of LA by gastric intubation. Groups 2 and 3 continuously received LA instead of drinking water. The control group was composed of 3 rats in each group which did not receive any treatment. Rats of group 1, 2 and 3 and control were sacrificed at 1/2, 1, 1 1/2 hours, 2 days, and at 1, 2, 4, 6 and 8 weeks later, except group 3. Before sacrifice, they were perfused with 0.1% sodium sulphide and 2.5% glutaraldehyde through the abdominal aorta for TSM. The liver was taken for LM and EM examinations. Blood lead concentration began to increase from the 2nd day up to 3.29 microgram/ml at 2nd week, and the urinary delta-ALA level showed a steady increase from the 2nd day. LM and EM examination of liver revealed that absorbed lead granules in group 1 were transported into sinusoidal spaces, Kupffer cells, and the hepatocytes within 1 hour and then disappeared 1/2 hour thereafter. In group 2 deposited lead was found in the hepatocytic cytosol bound to mitochondria. That in turn inhibited mitochondrial respiration with resultant mitochondrial swelling at the 1st week and thereafter at 6th week myelin figure formation and condensation of mitochondria, and peroxisomes were increased at 8th week. Based on these results it can be concluded that a transient intake of subletal dose of LA is biotransformed completely by periportal hepatocytes within 1 1/2 hours, but excessively accumulated lead can induce liver cell injury due to lipid peroxidation of membrane by direct toxic effect of lead and by products of lipid peroxidation. We postulate that lead acetate triggers presumably primarily mitochondrial membrane injury and then other organellar changes may play a role in disturbance of a network of interacting of key events capable of causing cell death.
Rats ; Animals

No abstract available.
Heart* ; Lymphoma* ; Pericardial Effusion*

OBJECTIVES: The aims of this study were to evaluate changes in plasma superoxide dismutase(SOD) activities in alcohol depedence, to fine out variables to influence on the SOD activities, and finally to identify the correlation of SOD activities with the alcohol-associated cognitive disorders. METHODS: For 24 male alcoholics and 21 healthy male controls, plasma SOD activities were measured by spectrophotometry on 1-2 wks after alcohol withdrawal. Structured interviews and laboratory tests were also performed. RESULTS: 1) Upon comparing SOD activities between controls and alcoholics, the SOD activities were significantly(p<0.01) lower in alcoholics(0.308+/-0.140 units/mL) than in healthy controls(0.313+/-0.086 units/mL). 2) Upon comparing SOD activities according to the presence of alcohol-related cognitive disorders, the SOD activities were significantly(p<0.05) lower in alcoholics with cognitive disorders(0.247+/-0.049 units/mL) than in alcoholics without cognitive disorders(0.317+/-0.148 units/mL). 3) Upon comparing SOD activities according to the presence of alcoholic polyneuropathy or alcohol withdrawal seizure, the SOD activities showed no significant differences between alcoholics with polyneuropathy or epilepsy and those without. 4) Upon analyzing variables influencing on the SOD activities in alcoholics, the SOD activities had the negative correlation with hemoglobin(gamma=-0.433) and severity of alcohol withdrawal symptoms(gamma=-0.375). 5) Upon comparing variables according to the presence of alcohol-related cognitive disorders, the occurrence of alcoholic polyneuropathy(p<0.05) and blood phosphorus concentrations(p<0.01) were significantly higher in alcoholics with cognitive disorders than those without. 6) Upon analyzing an association between SOD activities and variables in alcoholics with cognitive disorders, the SOD activities were positively correlated with the onset age(gamma=0.995), and negatively correlated with the severity of alcohol withdrawal symptoms(gamma=-0.996). CONCLUSIONS: Lower SOD activities in alcohol dependence suggested alcohol-associated cognitive disorders and alcohol withdrawal symptoms might be caused by oxidative stress.
Alcohol Withdrawal Seizures ; Alcoholic Neuropathy ; Alcoholics ; Alcoholism ; Epilepsy ; Humans ; Male ; Oxidative Stress ; Phosphorus ; Plasma ; Polyneuropathies ; Spectrophotometry ; Substance Withdrawal Syndrome ; Superoxide Dismutase* ; Superoxides*

OBJECTIVES: The aims of this study were to discriminate the clinical differences, to measure the estrogen and homovanillic acid levels. to evaluate a correlation between estrogen and homovanillic acid. and to identify an association of cognitive deficit with estrogen and homovanilli acid among male and female schizophrenics. METHODS: In addition to the structured interviews, the plasma estrogen levels by radioimmunoassay and the homovanillic acid levels by HPLC were measured in 20 male and 21 female schizophrenics as well as 10 healthy male and 9 female controls. RESULTS: 1) The plasma estrogen levels were higher in females than males, and significantly higher in female schizophenics than female controls. The homovanillic acid levels were higher in female schizophrenics than female controls, and were lower in male schizophrenics than male controls. 2) The onset age seemed to be earlier in male schizophrenics, and the frequency of admission, duration of antipsychotic drug administration. dosage of antipsychotics and duration of illnesses were more in males. The estrogen and homovanillic acid levels were significantly higher in female schizophrenics. 3) The estrogen levels had a significant positive correlation with sex, age and onset age, while the homovanillic acid levels did with sex. However, estrogen wee not correlated with homovanillic acid levels. 4) The estrogen and homovanillic acid levels were not significantly different between male and female schizophrenics with cognitive deficits. In the schizophrenic patients without cognitive deficits, the estrogen levels were significantly higher in females, while here were no significant sex differences in homovanillic acid. 5) In the male and female schizophrenics predominantly with negative symptoms, there were no significant differences in estrogen and homocanillic acid levels. In those predominantly with positive symptoms, the estrogen levels wee significantly higher in females, while there were no sex differences in homovanillic acid levels. 6) In schizophrenics with undifferentiated subtype, the estrogen and homovanillic acid levels were significantly higher in females. In those with paranoid or disorganized subtypes. the estrogen levels were significantly higher females, while there were no sex differences in the homovanillic acid levels. 7) The mean values of PANSS-negative. PANSS-total, PANSS-CF, MMSE-K and estrogen levels were significantly higher in male schizophrenics with cognitive deficits. The mean values of illness duration, CGI PANSS-positive, PANSS-negative, PANSS-total, PANSS-CF and MMSE-K were significantly higher in female schizophrenics with cognitive deficits. 8) The variables which showed significant correlation with cognitive deficits were PANSS-nagative, PANSS-total, PANSS-CF, MMSE-K and estrogen levels in male schizophrenics. The variables which showed significant correlation with cognitive deficits were subtypes, onset age, illness duration, CGI, PANSS-positive, PANSS-negative, PANSS-total, PANMSS-CF and MMSE-K in female schizophrenics. The estrogen levels were significantly correlated with admission frequencies, history of antipsychotic administration, duration of antipsychotic administration and cognitive deficits in male schizophrenics. while age were not correlated with in females. The homovanillic acid levels had a significant correlation with subtypes and onset age in male schizophrenics, while there were no correlation among variables in females. CONCLUSIONS: Although the plasma concentrations of estrogen and homovaillic acid in female schizophrenics were significantly higher than males, we could not find an association between them. Furthermore, the various factors affecting on the cognitive deficits, estrogen and homovanillic acid levels seemed to be somewhat different according to sex.
Age of Onset ; Antipsychotic Agents ; Chromatography, High Pressure Liquid ; Dopamine* ; Estrogens* ; Female ; Homovanillic Acid ; Humans ; Male ; Plasma ; Radioimmunoassay ; Schizophrenia* ; Sex Characteristics

OBJECTIVES: Phencyclidine(PCP) or PCP-like substances such as ketamine have been know to rekindle the cognitive dysfunction in schizophrenia. The aims of this study were to identify whether PCP-like substances can produce cognitive deficit in schizophrenia, to discuss relation with aging process, and finally to speculate underlying neurochemical mecha-nisms by various drug responses. METHODS: In experiment I, radial maze tests were done in 24 Sprague-Dawley rats for 3 days to get baseline data. Being divided into 4 groups(6 rats respectively) of normal aged, normal adult controls, atropine-treated and ketamine-treated, the radial maze tests were repeated on every week for 6 weeks, and then the rats were sacrificed by intracardiac perfusion with phosphate-buffered 10% formaldehyde solution for histology. The brain specimen was stained with hematoxylin-eosin to count cells in the prefrontal cortex and hippocampus. In experiment II, radial maze tests were done for 48 rats before any drug treatment and only after ketamine administration. Thereafter, haloperidol, bromocriptine, clonidine, nimodipine, tacrine, valproic acid, naloxone and fluoxetine were intramuscularly injected on every other day in addition to ketamine. Radial maze tests were repeated on every week for 6 weeks, and then rats were prepared by the same procedure for histology. RESULTS: 1) Reaction times of radial maze tests of atropine-treated rats were significantly prolonged than those of normal aged(p<0.05) or normal adult controls(p<0.05). Cell numbers of prefrontal cortex & hippocampus in ketamine-treated rats were significantly reduced than those in normal aged(p<0.05) or normal adult controls(p<0.005). 2) Reduced cell numbers by ketamine became significantly raised by tacrine administration in prefrontal cortex $ hippocampus(p<0.05), while there were no significant changes on radial maze test. Cell numbers also tended to be raised by nimodipine, fluoxetine and haloperidol administration. CONCLUSIONS: In conclusion, the visuospatial memory disorders in ketamine-induced psychotic rats might be partly associated with aging process. Furthermore, the responses to the various drugs suggested cholinergic system might have an important role in the neurochemical mechanism of the cognitive dysfunction in ketamine-induced psychosis. Otherwise, calcium metabolism as well as serotonergic and dopaminergic systems seemed to be possibly related.
Acetylcholine ; Adult ; Aging* ; Animals* ; Brain ; Bromocriptine ; Calcium ; Cell Count ; Clonidine ; Fluoxetine ; Formaldehyde ; Haloperidol ; Hippocampus ; Humans ; Ketamine ; Memory Disorders ; Metabolism ; Models, Animal* ; Naloxone ; Nimodipine ; Perfusion ; Prefrontal Cortex ; Psychotic Disorders ; Rats ; Rats, Sprague-Dawley ; Reaction Time ; Schizophrenia* ; Tacrine ; Valproic Acid

OBJECTIVE: There are four possible explanations for the sexual dysfunction of schizophrenics. The first is the possibility or a real structural aspect. The second possibility is that sexual function changes secondary to the illness. The third possibility is that there are medical and sociocultural barriers to sexual expression for chronic schizophrenics. The fourth possibility is that sexual dysfunction due to antipsychotic medication. However, we didn't know the precise cause of sexual dysfunction in schizophrenics. Therefore, the purpose of this study was to explore the mechanism of illness itself and antipsychotics on sexual dysfunction in male schizophrenics. METHODS: The serum prolactin(PRL), testosterone(TST), and the plasma serotonin(5-HT) concentrations were measured by radioimmunoassay and high performance liquid chromatography method for 100 healthy male schizophrenics according to the DSM-IV. Concomitantly, the severity of psychotic symptoms using Clinical Global Impression(CGI), Brief Psychiatric Rating Scale(BPRS), Positive and Negative Syndrome Scale(PANSS), and the severity of side effects for antipsychotics using Extrapyramidal Side Effects Scale(EPSE), Anticholinergic Side Effects Scale(ACSE), the cognitive function using PANSS-Cognitive Function(PANSS-CF), Mini Mental State Exam-Korean(MMSE-K), and sexual dysfunction using Sexual Functioning Questionnaire(SFQ), Questionnaire for Sexual Dysfunction in Men were assessed. The PRL, TST and 5-HT levels of 50 healthy male controls who had no medical, neurological, and psychiatric illnesses were evaluated The sexual function using SFQ(items FGa, FNa) were also assessed. Furthermore, the correlation with age, education, religion economic status, age at onset, duration of illnesses, duration of admission. levels of PRL, TST, 5-HT, antipsychotic dosages, potency, benztropine total duration of medication, EPSE, ACSE, CGI BPRS, PANSS, PANSS-CF MMSE-K and sexual dysfunctions were identified in male schizophrenics. RESULTS: 1) The frequencies of sexual dysfunctions for schizophrenics(80%) were significantly(p<0.001) higher than those for controls(42%). The sexual dysfunctions according to sexual response cycle were low sexual desire '76% 'impairment of achieving erection '75%, 'impairment of maintaining erection'75%, 'impairment of obtaining orgasm'32%, 'impairment in the quality of orgasm'61%, 'impairment of quantity of ejaculate'44%, premature ejaculation'15%, and 'delayed ejaculation'50%. 2) The PRL, 5-HT levels of schizophrenics(28.5+/-20.6ng/ml, 298.5+/-89.1ng/ml) were significantly(p<0.001) higher than those of controls(10+/-5.6ng/ml, 169.2+/-37.8ng/ml), while the TST levels of schizophrenics(4.3+/-1.5ng/ml) and controls(4.5+/-1.2ng/ml) were not significantly different. The sexual dysfunctions of schizophrenics who had abnormal 5-HT levels(4.7+/-1.3 scores) were significantly(p<0.05) higher than those of who had normal 5-HT levels(3.8+/-1.6 scores) on item D7. 3) The sexual dysfunctions of unmarried schizophrenics were significantly(p<0.01 : p<0.05) higher than those of married schizophrenics(6.1+/-2.8 scores, 4.7+/-1.3 scores on item FGa : beta=-0.211 on item FNa). The sexual dysfunctions we positively correlated with the rise of 5-HT levels (r=0.209, p<0.05 on item D4 and r=0.241, p<0.05 on item D7), the higher age at onset(r=0.275, p<0.01 on item FNa : r=-0.202, p<0.05 on item FDa), the longer duration of illesses(r=0.237, p<0.05 on item D6), the longer duration of admission(r=0.234, p<0.05 on item D4 : r=0.328, p<0.05 on item D6), the longer total duration of medication(r=0.237, p<0.05 in item D6). However, age, education, religion, economic status, PRL, TST levels, antipsychotics dosage, potency, benztropine, ACSE, CGI, BPRS, PANSS, PANSS-CF, MMSE-K scores were not correlated with increased sexual dysfunctions. CONCLUSIONS: Male schizophrenics have significantly more sexual dysfunction to compare with controls. The high frequencies of sexual dysfunctions were low sexual desire and erectile disorder. The unmarried, higher age at onset, are longer duration of diseases were positively correlated with increased sexual dysfunctions. Also high 5-HT levels were positively correlated with increased sexual dysfunctions. This means that studies of plasma 5-HT levels, albeit questionable indicators of central 5-HT function, offer some additional support for the association of sexual dysfunction with excess 5-HT activity as primary pathology of schizophrenia. Our findings suggest that excess 5-HT activity seems to affect the patient's sexual function.
Antipsychotic Agents ; Benztropine ; Chromatography, Liquid ; Diagnostic and Statistical Manual of Mental Disorders ; Education ; Humans ; Male* ; Pathology ; Plasma ; Prolactin ; Surveys and Questionnaires ; Radioimmunoassay ; Schizophrenia ; Serotonin ; Single Person ; Testosterone

OBJECTIVES: The alcohol dependence in elderly people has been prevalent because of increase in geriatric population. However, it is difficult to find out alcohol dependence in the aged, because they have less specific clinical features as compared with adult alcoholics. The aims of this study were to screen alcohol dependence among elderly Koreans and to know the clinical characteristics of Korean delerly alcoholics. METHODS: The questionnaires translated into Korean such as Michigan Alcoholism Screening Test(MAST-K), the Brief MAST and the MAST-Geriatirc Version(MAST-KG) were used to screen alcohol dependence in the elderly alcoholic inpatients aged over 60(N=43), adult alcoholic inpatients within 20-59 Yrs of age(N=60), which were compared with age matched normal healthy aged(N=18) or adult controls(N=45). The demographic data such as sex, age, education, occupation, socioeconomic status, marital status, numbers of children, dwelling and religion as well as alcohol history such as duration of alcohol drinking, onset age, family history, impulsivity, somatic illness and motivation were also obtained to identify characteristic features of Korean aged alcoholics by structured interviews. RESULTS: 1) The aged alcoholics had the charateristic features of more in males, lower age, low education levels, more in blue-collar workers, lower socioeconomic class, more in single few babies, more living alone, having no religion without statistical significance. 2) The onset age of alcohol dependence was significantly higher in the aged alcoholics(45.3+/-13.6Yrs) than in the adult alcoholics(27.7+/-8.7Yrs)(p<0.0001). The duration of problematic alcohol drinking was significantly longer in the aged alcoholics(22.0+/-15.1Yrs) than in adult alcoholics(14.2+/-8.4Yrs)(p<0.01). Otherwise, there were no significant difference between aged and adult alcoholics in the family history, imulsivity, somatic illness and motivation. 3) The mean score of the MAST-K was significantly higher in the aged alcoholics(20.6 +/-5.4) than in the normal aged(6.7+/-4.4)(p<0.0001), which was significantly lower than in the adult alcoholics(26.2+/-8.0)and in normal adult controls(9.5+/-3.2)(p<0.05). The mean score of the Brief MAST was significantly lower in the aged alcoholics(9.3+/-3.5) than in the adult alcoholics(14.5+/-6.6)(p<0.0001). The mean score of the MAST-KG was significantly higher in the aged alcoholics(10.6+/-3.5) than in the normal aged(4.8+/-4.3)(9<0.0001). The former was significantly lower than in adult alcoholics(12.9+/-4.3)(p<0.005), and the mean score was 4.5+/-2.8 in normal adult controls. 4) The items which showed statistically significant differences between aged alcoholics and normal aged controls could be found in 10 items of the MAST-K(item 2, 3, 4, 5, 11, 14, 17, 21, 22 and 23). 2 items of the Brief MAST(items 2 and 9), and 7 items of the MAST-KG(items 6, 13, 18, 19, 22, 23 and 24)(p<0.01). CONCLUSIONS: The scores of the MAST-K, the Brief MAST and the MAST-KG were significantly lower in the aged alcoholics than those in the adult alcoholics(p<0.05). The statistically significant differences between aged alcoholics and normal aged controls could be found in 10 items of the MAST-K, 2 items of the Brief MAST and 7 items of the MAST-KG. Therefore, a briefer rating scales around 10 items are needed to screen alcohol dependence among Korean elderly people.
Adult ; Age of Onset ; Aged ; Alcohol Drinking ; Alcoholics ; Alcoholism* ; Child ; Education ; Humans ; Impulsive Behavior ; Inpatients ; Korea* ; Male ; Marital Status ; Mass Screening* ; Michigan* ; Motivation ; Occupations ; Surveys and Questionnaires ; Social Class ; Weights and Measures

To understand a mechanism of underlying cognitive deficit in schizophrenia, the risk factors, cognitive function, blood dopamine concentrations and glutamate dehydrogenase activities of male schizophrenics with tardive dyskinesia(N=30) were compared with those of schizophrenics without tardive dyskinesia(N=30). The result were as following ; 1) The age, duration of illness and duration of medication were significantly more in schizophrenics with tardive dyskinesia than schizophrenics without tardive dyskinesia(respectively p<0.005, p<0.0001, p<0.0001). 2)The scores of MMSE, TIQ, VIQ and PIQ were significantly lower in schizophrenics with tradive dyskinesia than schizophrenics without tardive dyskinesia(respectively p<0.0001). 3) plasma dopamine concentrations were tended to be higher, and serum glutamate dehydrogenase activities were tended to be lower in schizophrenics with tardive dyskinesia than schizophrenics without tardive dyskinesia. 4) The cognitive deficit seemed to be negatively correlated with duration of illness and duration of illness and duration of medication(respectively gamma=-0.496, gamma=-0.615).
Dopamine ; Dyskinesias ; Glutamate Dehydrogenase ; Humans ; Male ; Movement Disorders* ; Plasma ; Risk Factors ; Schizophrenia*

OBJECTIVES: Risperidone, an atypical antipsychitics which blocks both dopaminergic and serotonergic receptors, have a good response to the negative symptoms as well as positive symptoms, and improve cognitive dysfunction of schizophrenic patients. Furthermore, it has few extrapyramidal side effects and tardive dyskinesia. Although it had been reported that the atypical antipsychotics have less effect on prolactin(PRL) than the classical antipsychotics, we could experience PRL-associated symptoms such as amenorrhea, galactorrhea and hyperprolactinemia in practice. Therefore we tried to identify the sex differences of risperidone-induced hyperprolactinemia, to evaluate factors affecting PRL levels, and to know the association between cognitive disorders and PRL. METHODS: The baseline levels of PRL and TSH prior th risperidone administration were measured by enzyme immunoassay method for 50 patients (25 males and 25 females) admitted with schizophrenia, schizoaffective disorder or schizophreniform disorder according to the DSM-IV classification, and the measurements of PRL were repeated on the 2nd and the 4th wks of risperidone administration. Concomitantly, the severity of psychotic symptoms using CGI, BPRS and PANSS, and the cognitive dysfunction using PANSS-CF were assessed prior to, on the 2nd and the 4th wks of risperidone administration. The PRL and TSH levels of 54 healthy controls(29 males and 25 females) who had no medical, neurological and psychiatric illnesses were also evaluated. Furthermore, the correlation with the psychiatric diagnosis, education, age, sex, duration of illnesses, risperidone dosage, duration of risperdone administration, TSH concentration, cognitive function, severity of psychotic symptoms were also identified. RESULTS: 1) The baseline PRL levels of female schizophrenics(74.3+/-49.6ng/ml) were significantly(p<0.005) higher than those of males(36.3+/-24.6ng/ml), which wee significantly(p<0.0001 respectively) higher than those of controls(females 16.9+/-6.1ng/ml, males 13.3+/-4.9ng/ml). The PRL levels measured on the 2nd wks(females 133.7+/-47.8ng/ml, males 56.9+/-23.6ng/ml) and on the 4th wks(females 146.1+/-45.9ng/ml, males 70.0+/-31.5ng/ml) after risperidone administration were significantly(p<0.0001 respectively) higher in females. The mean dosages of risperidone on the 2nd wks were 3.8+/-1.7mg(2-6mg) for the females and 4.0+/-1.6mg(2-6mg) fore the males, and on the 4th wks were 4.5+/-2.1mg(2-8mg) fore the females and 5.4+/-2.2mg(2-8mg) for the males. 2) The rise of PRL levels were positively correlated with increased risperidone dosage in males(y=0.307 on the 2nd wks and y=0.280 on the 4th wks), while they were not correlated with dosages in females. For the females, the PRL levels were negatively correlated(y=-0.320) with decrease of TSH concentration. The baseline PRL levels were not correlated with age, education, duration of illnesses, psychopathology, cognitive disorders in both males and females, while it was negatively correlated with TSH levels only in females(y=-0.320). 3) The cognitive dysfunction was correlated with PRL levels in males, while PANSS-CF scores were negatively correlated with PRL levels(y=-0.220 on the 2nd wks and y=-0.366 on the 4th wks) in females. The psychopathology was positively correlated with cognitive dysfunction in both males and females. Therefore, the risperdone-induced cognitive improvement seemed to be correlated with improvement of psychopathology in both males and females, and with increase in PRL levels only in females. CONCLUSIONS: The fact that the serum PRL levels of schizophrenics were higher than those of controls, especially in females suggested that it could be related with risperidone dosage in males and with primary pathological process in females. The risperidone-associated cognitive improvement seemed to be related with general improvement of psychopathology as well as the rise of PRL levels especially in females. The facts that the effect of risperidone-induced hyperprolactinemia and the cognitive function were more in females suggested that somewhat different mechanisms could be exerted on them.
Amenorrhea ; Antipsychotic Agents ; Classification ; Diagnostic and Statistical Manual of Mental Disorders ; Education ; Female ; Galactorrhea ; Humans ; Hyperprolactinemia ; Immunoenzyme Techniques ; Male ; Mental Disorders ; Movement Disorders ; Pregnancy ; Prolactin* ; Psychopathology ; Psychotic Disorders ; Risperidone* ; Schizophrenia ; Sex Characteristics

No abstract available.
Cytogenetics*