Kim, Yung-Hi;Song, Dong-Keun;Wie, Myung-Bok;Song, Joon-Ho;Choi, Yeun-Sik
The Korean Journal of Pharmacology
/
v.26
no.1
/
pp.1-6
/
1990
We established an in vitro system of central serotonergic neurons by culturing dissociated rat embryonic (El4) brainstem cells to 14 days in vitro and monitored the serotonergic neuronal growth by measuring 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) contents in the cells with hish performance liquid chromatography with electrochemical detection (HPLC-EC). We studied also tile effects of various drugs on the contents of 5-HT and 5-HIAA, confirming in vivo reports. The 5-HT content (13 ng/mg protein) and 5-HT turnover rate (17 pmol/mg protein/h) at 14 days in vitro were in good agreement with those reported in the adult rat brain. The 5-HT content was more easily depleted with p-chlorophenylalanine, a tryptophan hydroxylase inhibitor than with NSD 1015 (3-hydroxybenzylhydrazine), an aromatic L-amino acid decarboxylase (AADC) inhibitor. Incubation of the cultures with tryptophan or 5-hydroxytryptophan increased the rate of serotonin formation implying that neither tryptophan hydroxylase nor AADC is saturated with its amino acid substrate in this in vitro system . The 5-HT content was depleted by reserpine. The 5-HT and 5-HIAA contents were increased and decreased, respectively, by monoamine oxidase inhibitors. All the above results indicate that the biochemical properties of the central serotonergic neurons in this culture system reflect reliably those of central serotonergic neurons in vivo. We suggest that measuring 5-HT and 5-HIAA contents in the primary cultured dissociated brainstem-cells with HPLC-EC is useful in the study of pharmacology as well as toxicolgy of the central serotonergic neurons.
Among the currently recognized pathogenic vibrios, V. vulnificus and V. cholerae non O1 are the most serious bacteria from the point of view of sea food hygiene in Korea. In this paper, the authors compared the hemolytic activities of the crude hemolysin produced by V. vulnificus and V. cholerae non O1 isolated from shellfish collected in Chungmoo, Korea. The authors also attempted to improve the purification method of V. vulnificus hemolysin(VVH) and tried to make antiserum with the purified hemolysin. VVH was produced in abundance in heart infusion broth containing $2\%$ NaCl in a shaking cultivation process(140rpm) at $37^{\circ}C$ for 15 hours. While hemolysin production patterns of V. cholerae non O1 were quite different by the strain during the culture times compared with the V. vulnificus. Hemolytic activity of the VVH on sheep erythrocytes was stronger than those of rabbit, but hemolytic activities of the hemolysin produced by V. cholerae non O1 on rabbit erythrocytes were as much as twice as strong as on those of sheep and horse. VVH was purified by two steps of hydrophobic column chromatography on Phenyl-Sepharose HP with Fast Protein Liquid Chromatography(FPLC). Purification fold and yield of VVH was much improved by changing the elution buffer's pH from 6.0 to 9.8 and adding $1\%$ CHAPS(a zwitter ionic detergent) and $50\%$ ethylene glycol to the 10mM glycine buffer during the repeated hydrophobic column chromatography. Homogeneity of the purified hemolysin was shown by polyacrylamide gel electrophoresis. According to the five times repeated purification results, the specific activity was increased 27500 times and the yield was improved by $23.4\%$ on average. About $250{\mu}g$ of purified hemolysin was harvested from the 2400ml of culture supernatant of V. vulnificus. Molecular weight of VVH was estimated to be 50KDa by the SDS-PAGE and the neutralization scores of the obtained antiserum acting against VVH were $2000{\sim}8500$.
Background: Due to the irreversible nature of chronic obstructive pulmonary disease (COPD), the treatment aim in patients with COPD is not to cure but to reduce the symptoms, increase lung function, and improve the quality of life. It has been suggested that depression is a common emotional disturbance in patients with COPD who are faced with a major physical impairment and embarrassing symptoms. This study evaluated the prevalence and risk factors of depression in patients with chronic obstructive pulmonary disease. Methods: A total of 59 patients with a registered diagnosis of chronic obstructive pulmonary disease were selected. Depression was assessed using the Centers for Epidemiologic Studies Depression (CES-D) scale. The quality of life was assessed using the Korean version of the St. George's Respiratory Questionnaire. Results: The prevalence of depression was 17.0%. In the correlation model, the interaction of the $FEV_1%$ over predicted value and SGRQ score(symptom, activity, impact, overall score) was statistically significant. The interaction of the $FEV_1%$ over predicted value and depression scale(CES-D) was also statistically significant. There was a positive correlation between the SGRQ scores(symptom, activity, impact, overall score) and the depression scale. Conclusion: The prevalence of depression in patients with chronic obstructive pulmonary disease is relatively high. The pulmonary function and the living standards were found to be significant risk factors for depression.
A microorganism capable of producing high level of poly-3-hydoxybutyrate (PHB) from xylose was isolated from soil. The isolated strain J-65 was identified as Bacillus megaterium based on the morphological, biochemical and molecular biological characteristics. The optimum temperature and pH for the growth of B. megaterium J-65 were $37^{\circ}C$ and 8.0, respectively. The optimum medium composition for the cell growth was 2% xylose, 0.25% $(NH_4)_2SO_4$, 0.3% $Na_2HPO_4{\cdot}12H_2O$, and 0.1% $KH_2PO_4$. The optimum condition for PHB accumulation was same to the optimum condition for cell growth. Copolymer of ${\beta}$-hydroxybutyric and ${\beta}$-hydroxyvaleric acid was produced when propionic acid was added to shake flasks containing 20 g/l of xylose. Fermenter culture was carried out to produce the high concentration of PHB. In batch culture, cell mass was 9.82 g/l and PHB content was 35% of dry cell weight. PHB produced by B. megaterium J-65 was identified as homopolymer of 3-hydoxybutyric acid by GC and NMR.
Purpose : The prevalence of symptoms in patients with terminal cancer varies considerably and these symptoms are very difficult to control. However, patients can spend their last days or hours of life without suffering pain with appropriate care. One of the major concerns during last days of life is to predict the time of death. We would like to investigate symptom prevalence during terminal cancer patients' last 48 hours in Korea, and therefore contribute to predict the time of death and to help to determine appropriate treatments. Methods : The data for this study was recorded from 92 of 132 patients who died with terminal cancer at the hospital between February 1 and October 31, 2000. We investigated the symptom prevalence during the last 48 hours through medical obligation record and analyzed the changes of symptom prevalence at the admission, $48{\sim}24$ hours and $24{\sim}0$ hours before death. Results : The predominant symptom prevalence was pain (57.6%), followed by confusion (55.4%), dyspnea (48.9%), voiding difficulty (42.4%) in the last 48 hours before death. From the statistical analysis for the changes of symptom prevalence in time, pain, nausea and vomiting were decreased but noisy and moist breathing, sweating, groan, restlessness and agitation, and loss of consciousness were increased (P<0.05). Conclusion : The results from this study show the tendency to increase of prevalence of noisy and moist breathing, sweating, groan, restlessness and agitation as well as loss of consciousness in 48 hours before death. Therefore the symptoms above can be used for the important indicators to predict the imminent death.
Objectives: Obstructive sleep apnea syndrome (OSAS) has drawn increasing attention as medical community has become to be aware of its co-morbidities and complications, especially cardiovascular complications and excessive daytime sleepiness with accident proneness. As of now, polysomnography is the standard tool to diagnose sleep apnea and estimate the treatment validity. However, its being rather expensive and inconvenient, alternate diagnostic tools have been proposed including wrist actigraphy. So far, actigraphies have been adopted usefully to field-survey sleep apnea prevalence. In this study, we attempted in a sleep laboratory setting to assess the supplemental value of actigraphy in diagnosing OSAS. Methods: This study was done at the Division of Sleep Studies, the Seoul National University Hospital. Thirty-seven clinically suspected cases of OSAS underwent the one-night polysomnography, simultaneously wearing an actigraphy on non-dominant wrist. We analyzed the data of 27 polysomnographically-proven OSAS patients (male:female 20: 7;age $47.6{\pm}12.9$ years old;age range 23 to 72 years) with no other sleep disorders. We calculated RDI (respiratory disturbance index) from the polysomnography data and FI (fragmentation index) from the actigraphy data. Pearson correlation was calculated in order to compare FI with RDI and to evaluate the supplemental diagnostic value of the actigraphy. Results: Mean total sleep time on polysomnography was $401.4{\pm}57.8\;min$ (range of 274.0 to 514.1 min). Mean RDI was $21.7{\pm}20.4/hour$. Mean FI was $21.9{\pm}13.0/hour$. RDI and FI showed significant correlation (r=0.55, p<0.01). Conclusions: Wrist actigraphy in OSAS patients generates a comparable outcome to polysomnography, in measuring the nocturnal sleep fragmentation. The actigraphy could be used supplementally in inpatients, outpatients, and field survey subjects, if polysomnography is unavailable or impossible. In follow-ups related with nasal CPAP (continuous positive airway pressure), upper airway surgery, and oral appliance in OSAS patients, the actigraphy might play a more dominant role in the future.
Cystic fibrosis transmembrane conductance regulator (CFTR) gene and sodium-independent $Cl^-/HCO_3^-$ anion exchanger (AE) genes are expressed in a wide variety of mammalian tissues including cholangiocytes. They play an important role in the regulation of intracellular pH (pHi) as well as in transepithelial acid/base transport necessary for biliary bicarbonate secretion. The aim of this study was to examine the expression level of CFTR gene and AE genes (AE1, AE2 and AE3) in the cholangiocytes and the hepatocytes, and also measure AE2 gene expression level after bile duct ligation (BDL). As we previously described, isolated hepatocytes and cholangiocytes from the liver of normal and BDL rats were prepared and gene expression levels were measured by using RT-PCR. We found that AE1, AE2, and AE3 genes were expressed in both hepatocytes and cholangiocytes, but CFTR was only in cholangiocytes. AE2 gene expression level was higher in the BDL hepatocytes than normal hepatocytes, which was significantly different between two groups. AE2 gene expression level was lower in the BDL cholangiocytes than normal cholangiocytes. However, AE2 gene expression level in both hepatocytes and cholangiocytes were not changed with a longer duration of BDL. These results suggest that CFTR and AE2 may play an important role in the pathogenetic mechanism of biliary cholestatic liver disease.
Objectives : This cross-sectional study was performed to examine if the serum gamma-glutamyltransferase (GGT) level that is within its normal range is associated with the risk of type 2 diabetes and if the association between the waist hip ratio (WHR) and type 2 diabetes is different depending on the serum GGT levels. Methods : The study subjects were 23,436 persons aged 40 years or older and who participated in regular health check-ups at 11 hospitals (males: 5,821, females: 17,615). The gender-specific quintiles of the serum GGT and WHR were used to examine the associations with type 2 diabetes. Results : The serum GGT levels within their normal range were positively associated with type 2 diabetes only in women. The adjusted odds ratios (ORs) were 1.0, 1.0, 1.4, 2.1, and 2.5 according to the quintiles of the serum GGT ($p_{trend}$<0.01). The WHR was more strongly associated with the prevalence of diabetes among the women with a high-normal serum GGT level as compared with those with a low-normal serum GGT level (p for interaction=0.02). For example, the adjusted ORs for women with a low normal serum GGT level were 1.0, 1.2, 1.5, 2.2, and 2.4 according to the quintiles of the WHR, while those figures were 1.0, 2.4, 3.6, 5.0, and 8.3 among the women with a high normal serum GGT level. However, in men, the serum GGT was very weakly associated with type 2 diabetes and the association between the WHR and type 2 diabetes was not different depending on the serum GGT level. Conclusions : Serum GGT within its normal range was positively associated with type 2 diabetes, and central obesity was more strongly associated with the prevalence of type 2 diabetes when the serum GGT level was highnormal. However, these associations were observed only in women, which is different from the previous findings. The stronger relation between central obesity and type 2 diabetes among women with a high-normal serum GGT level can be useful for selecting a group that is at high risk for type 2 diabetes irregardless of whatever the underlying mechanism is.
Purpose: Human Na+/I- symporter (hNIS) is known to be expressed in many tissues other than thyroid gland. The breast cancer cells are one of them and the possibility of radioiodine therapy in treatment of the breast cancer may be suggested. We investigated the expression rate of hNIS and the relationship between the expression of hNIS and the finding of 99mTc-MIBI scintimammographv in the breast cancer Materials and Methods: Surgically proved 56 patients with breast cancer were the subjects of this study The expression of hNIS were evaluated by immunohistochemistry and the results were compared to the findings of 99m7c-MIBI scintimammography. Results: Overall expression rate of hNIS was 41.1% in 56 patients. According to the pathologic diagnosis, it was 42.9% in 49 patients with invasive ductal carcinoma and 28.6% in the 7 patients with ductal carcinoma in situ. The expression rate of hNIS in the 41 cases with a focal increased uptake at he breast lesion on 99m7c-MIBI sointimammogram was 31.7%. That in the 15 cases without any abnormal uptake on the scan was significantly higher(65.7%, p<0.05). Conclusion: The expression rate of hNIS in the patients with breast cancer was not so high. The rate was higher in the patients with no increased uptake at the breast lesion on 99m7c-MIBI scintimammography.
Background: Minimal pressure support(PSmin) is a level of pressure support which offset the imposed work of breathing(WOBimp) developed by endotracheal tube and ventilator circuits in pressure support ventilation While the lower applied level of pressure support compared to PSmin could induce respiratory muscle fatigue, the higher level than PSmin could keep respiratory muscle rest resulting in prolongation of weaning period during weaning from mechanical ventilation PSmin has been usually applied in the level of 5~10 cm$H_2O$, but the accurate level of PSmin is difficult to be determinated in individual cases. PSmin is known to be calculated by using the equation of "PSmin = peak inspiratory flow rate during spontaneus ventilation$\times$total ventilatory system resistance", but correlation of calculated PSmin and measured PSmin has not been known. The objects of this study were firstly to assess whether customarily applied pressure support level of 5~10 cm$H_2O$ would be appropriate to offset the imposed work of breathing among the patients under weaning process, and secondly to estimate the correlation between the measured PSmin and calculated PSmin. Method : 1) Measurement of PSmin : Intratracheal pressure changes were measured through Hi-Lo jet tracheal tube (8mm in diameter, Mallinckroft, USA) by using pulmonary monitor(CP-100 pulmonary monitor, Bicore, USA), and then pressure support level of mechanical ventilator were increased until WOBimp was reached to 0.01 J/L or less. Measured PSmin was defined as the lowest pressure to make WOBimp 0.01 J/L or less. 2) Calculation of PSmin : Peak airway pressure(Ppeak), plateau airway pressure(Pplat) and mean inspiratory flow rate of the subjects were measured on volume control mode of mechanical ventilation after sedation. Spontaneous peak inspiratory flow rates were measured on CPAP mode(O cm$H_2O$). Thereafter PSmin was calculated by using the equation "PSmin = peak inspiratory flow rate$\times$R, R = (Ppeak-Pplat)/mean inspiratory flow rate during volume control mode on mechanical ventilation". Results: Sixteen patients who were considered as the candidate for weaning from mechanical ventilation were included in the study. Mean age was 64(${\pm}14$) years, and the mean of total ventilation times was 9(${\pm}4$) days. All patients except one were males. The measured PSmin of the subjects ranged 4.0~12.5cm$H_2O$ in 14 patients. The mean level of PSmin was 7.6(${\pm}2.5\;cmH_2O$) in measured PSmin, 8.6 (${\pm}3.25\;cmH_2O$) in calculated PSmin Correlation between the measured PSmin and the calculated PSmin is significantly high(n=9, r=0.88, p=0.002). The calculated PSmin show a tendancy to be higher than the corresponding measured PSmin in 8 out of 9 subjects(p=0.09). The ratio of measured PSmin/calculated PSmin was 0.81(${\pm}0.05$). Conclusion: Minimal pressure support levels were different in individual cases in the range from 4 to 12.5 cm$H_2O$. Because the equation-driven calculated PSmin showed a good correlation with measured PSmin, the application of equation-driven PSmin would be then appropriate compared with conventional application of 5~10 cm$H_2O$ in patients under difficult weaning process with pressure support ventilation.
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