• Journal of Apiculture
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• v.34 no.3
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• pp.245-254
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• 2019

We investigated the anti-tumor effects and molecular mechanism of Brazil, China and Korean regional propolis on HeLa ovarian cancer cell line. Each propolis extracts was prepared by ethanol extraction method. Cytotoxicity of propolis extracts was determinated by EZ-cytox cell viability assay. To necessity of anti-tumor effect and molecular mechanism of propolis, we must be adjusting propolis concentration. Due to 100 ㎍/mL of propolis extract were reduced cell viability to less than 50%, we adjusted all of propolis concentration to 100 ㎍/mL. By Western blotting analysis, we confirmed that anti-tumor mechanism of Brazil, China and Korea regional propolis has significantly difference. All of propolis was activated apoptosis related molecules such as PARP, caspase-3. However, cell proliferation signaling molecules including Akt1, ERK and Bcl-2 were reduced the protein expression level. Especially, the expression of tumor suppressor protein p53 was significantly increased in propolis-treated group such as Gyeonggi, Chungbuk, Chungnam, Jeonbuk, Gyeongnam and China. The phosphorylation of Bax which as apoptosis indicator was appeared in propolis-treated group such as Gyeonggi, Gangwon, Chungnam, Gyeongbuk, China. In this results showed that the regional propolis has completely different mechanism in anti-tumor. Thus, propolis extracts may be useful source of functional materials on anti-cancer and it will be able to choose the suitable propolis for cancer therapy by analyzing individual characteristics.

• The Korean Journal of Pharmacology
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• v.16 no.1 s.26
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• pp.25-34
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• 1980

The in vitro guinea pig ureter responded to 5 sec trains of electrical stimuli with two contractions; the first an 'on response' (ON) occurred with $0.1{\sim}0.3$ sec after the onset o the stimulus train, the second an 'off response'(OFF) occurred $0.2{\sim}1.0$ sec after the termination of the stimulus train. Relaxation occurred between the two responses during a time when the stimulus was still being delivered. Longer duration and/or higher frequencies of stimuli within the train were required to elicit the OFF than the ON. Decreasing temperature from $37^{\circ}$ to $22^{\circ}$ decreased ON amplitude and increased OFF amplitude. $Ca^{++}$-free solution, 2 mM EDTA, 1 mM $Mn^{++}$ or $1{\mu}M$ verapamil rapidly abolished ON. OFF persisted when ON had disappeared by repeated stimulation at 0.12 train per sec. Conversely, caffeine, $50{\mu}M$ and theophylline, $10{\mu}M$ abolished OFF with only slight reduction of ON, and sodium nitroprusside decreased preferentially ON amplitude rather than OFF. Relaxation between ON and OFF was incomplete in low $Na^+$ solution. ON and OFF were not affected by the neural blockers tetrodotoxin, atropine or phentolamine, also pyrilamine and methysergide, and relaxation between ON and OFF was $Na^+$ dependent. Furthermore, ON depends on free $Ca^{++}$ and OFF is more dependent on bound or stored $Ca^{++}$.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.479-492
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• 1997

Background : Isoniazid(INH) and rifampicin(RFP) are potent antituberculous drugs which have made tuberculous disease become decreasing. In Korea, prescribed doses of INH and RFP have been different from those recommended by American Thoracic Society. In fact they were determined by clinical experience rather than by scientific basis. Even there has been. few reports about pharmacokintic parameters of INH and RFP in healthy Koreans. Method : Oral pharmacokinetics of INH were studied in 22 healthy native Koreans after administration of 300 mg and 400mg of INH to each same person successively at least 2 weeks apart. After an overnight fast, subjects received medication and blood samples were drawn at scheduled times over a 24-hour period. Urine collection was also done for 24 hours. Pharmacokinetics of RFP were studied in 20 subjects in a same fashion with 450mg and 600mg of RFP. Plasma and urinary concentrations of INH and RFP were determined by high-performance liquid chromatography(HPLC). Results : Time to reach peak serum concentration (Tmax) of INH was $1.05{\pm}0.34\;hrs$ at 300mg dose and $0.98{\pm}0.59\;hrs$ at 400mg dose. Half-life was $2.49{\pm}0.88\;hrs$ and $2.80{\pm}0.75\;hrs$, respectively. They were not different significantly(p > 0.05). Peak serum concentration(Cmax) after administration of 400mg of INH was $7.14{\pm}1.95mcg/mL$ which was significantly higher than Cmax ($4.37{\pm}1.28mcg/mL$) by 300mg of INH(p < 0.01). Total clearance(CLtot) of INH at 300mg dose was $26.76{\pm}11.80mL/hr$. At 400mg dose it was $21.09{\pm}8.31mL/hr$ which was significantly lower(p < 0.01) than by 300mg dose. While renal clearance(CLr) was not different among two groups, nonrenal clearance(CLnr) at 400mg dose ($18.18{\pm}8.36mL/hr$) was significantly lower than CLnr ($23.71{\pm}11.52mL/hr$) by 300mg dose(p < 0.01). Tmax of RFP was $1.11{\pm}0.41\;hrs$ at 450mg dose and $1.15{\pm}0.43\;hrs$ at 600mg dose. Half-life was $4.20{\pm}0.73\;hrs$ and $4.95{\pm}2.25\;hrs$, respectively. They were not different significantly(p > 0.05). Cmax after administration of 600mg of RFP was $13.61{\pm}3.43mcg/mL$ which was significantly higher than Cmax($10.12{\pm}2.25mcg/mL$) by 450mg of RFP(p < 0.01). CLtot of RFP at 450mg dose was $7.60{\pm}1.34mL/hr$. At 600mg dose it was $7.05{\pm}1.20mL/hr$ which was significantly lower(p < 0.05) than by 450mg dose. While CLr was not different among two groups, CLnr at 600 mg dose($5.36{\pm}1.20mL/hr$) was significantly lower than CLnr($6.19{\pm}1.56mL/hr$) by 450mg dose(p < 0.01). Conclusion : Considering Cmax and CLnr, 300mg, of INH and 450mg RFP might be sufficient doses for the treatment of tuberculosis in Koreans. But it remains to be clarified in the patients with tuberculosis.

• Korean Journal of Psychosomatic Medicine
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• v.12 no.2
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• pp.165-173
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• 2004

Objectives: Diabetes mellitus is a heterogeneous, chronic, progressive disease characterized by hyperglycemia and abnormality in protein, carbohydrate, fat metabolism. Recent studies have reorted two times prevalence of depression in individuals with diabetes compared to individuals without diabetics. This study was designed to investigate glycemic controls, anxiety, alexithymia, stress responses between depressed diabetic patients and non-depressed diabetic patients. Methods The subjects were 60 diabetic patients(mean age : $50.3{\pm}9.7$ years, 31 men and 29 women) who were confirmed to have diabetes depending on the laboratory findings as welt as clinical symptoms at the St. Vincent Hospital Diabetes Clinic, from Mar. 2004 to Sep. 2004. Laboratory test including, blood chemistry. glycated hemoglobin, urinalysis for proteinuria and Korean version of Beck Depression Inventory(BDI), State and Trait Anxiety Inventory(STAI), Toronto Alexithymia Scale(TAS) and Stress Response Inventory(SRI) were used for assessment. Based on BDI scores, all diabetics were divided into 13 depressed-diabetics group(above 20 point) and 47 non-depressed group(below 20 point). We compared demographic data. glycemic controls, STAI, TAS and SRI scores between two groups by independent t-test. Results : 1) Depressed diabetic groups were 13(mean age : $55.4{\pm}7.2$ years, 7 men and 6 women) and non depressed groups were 47(mean age $48.9{\pm}9.8$ years, 24 men and 23 women). In depressed diabetics, compared with non-depressed group, manifested aged(p=0.031), but other demographic data showed no difference between two groups. 2) No significant differences were noted in FBS, PP2h, Hb A1C, total cholesterol, HDL-cholesterol, SGOT/SGPT, BUN levels between depressed and non-depressed groups. But, blood creatine levels of depressed group were significantly increased than non-depressed group(p=0.026). 3) No significant differences were found in the score of STAI, STAI-S, STAI-T, TAS between depressed and non-depressed groups. 4) The SRI scores of depressed groups were significantly higher than non-depressed groups$(59.7{\pm}24.9\;vs.\;31.5{\pm}22.0)(p=0.000)$. Conclusion : The above results suggest that depressed diabetic patients are have more stress responses and higher blood creatine levels. However, there were no differences in laboratory data related to glycemic controls, and anxiety. alexithymia levels between two groups. We suggest that physicians should consider integrated approaches for psychiatric problems in the management of diabetes.

• Journal of Chest Surgery
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• v.30 no.2
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• pp.131-136
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• 1997

The hemodynamic effects of thyroid hormones which is well established, affect myocardial contractility, heart rate, and myocardial oxygen consumption. The alterations in thyroid function test are frequently seen in patients with nonthyroidal illness and often correlate with the severity of the illness and the prosnosis. In this study, thyroid hormone changes were investigated in 20 patients who received cardiopulmonary bypass(CPB). All patients showed a state of biochemical euthyroidism preoperatively: The results were as follows : 1. Serum triiodothyronine(73) reached to its nadir(30.05 $\pm$ 17.5ng/dl, p(0.001) at 10 minutes after the start of CPB and remained low(p(0.05) throughout the study period. 2. Serum thyroxine(74) concentr tion slightly decreased after CPB, but maintained within normal range. 3. Serum free thyroxine(W4) concentration slightly increased after CPB, but maintained within normal range. 4. Serum thyroid stimulating hormone(TSH) concentration increased 10 minute after CPB, reached to its nadir(3.37 $\pm$ 0.81u1U/m1, p(0.001) at 2 hours after CPB. After then, serum TSH concentration decreased and reached its normal levels at 24 hours after CPB. 5. The patients whose postoperative recovery was uneventful(Group 1) had higher serum 73 levels than those who had postoperative complications(Group 2)(p<0.05). Group 1 showed elevating patterns of serum 73 in the fourth day after operation, whereas group 2 did not show such an elevating pattern. These findings are similar to the euthyroid sick syndrome seen in severely ill patients and indicate that patients undergoing open heart surgery have suppression of the pituitary-thyroid axis.

• The Korean Journal of Pharmacology
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• v.29 no.2
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• pp.175-182
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• 1993

As it has been reported that the depolarization-induced ACh release is modulated by activation of presynaptic $A_1-adenosine$ heteroreceptor in hippocampus and various lines of evidence indicate the adenosine effect is magnesium dependent, the present study was undertaken to delineate the role of endogenus adenosine as a modulator of hippocampal acetylcholine release in this study. Slices from the rat hippocampus were equilibrated with $[^3H]-choline$ and the release of the labelled product, $[^3H]-ACh$, was evoked by electrical stimulation(3Hz, $5\;V\;cm^{-1},$ 2ms, rectangular pulses), and the influence of various agents on the evoked tritium outflow was investigated. Adenosine, in concentrations ranging from $0.3\;to\;100\;{\mu}M$, decreased the $[^3H]-ACh$ release in a dose-dependent manner without changing the basal rate of release. $DPCPX(1{\sim}10{\mu}M)$, a selective $A_1-receptor$ antagonist, increased the $[^3H]-ACh$ release in a dose-related fashion with slight increase of basal tritium release. And the effects of adenosine were significantly inhibited by $DPCPX(2{\mu}M)$ treatment. CPCA, a specific $A_2-agonist$, in concentration ranging from $0.3\;to\;30\;{\mu}M$ decreased evoked tritium outflow with increase of basal rate of tritium release, and these effects were also abolished by $DPCPX(2{\mu}M)$ pretreatment. But, $CGS(0.1{\sim}10{\mu}M)$, a recently introduced potent $A_2-agonist$, did not alter the evoked tritium outflow. When the magnesium concentration of the medium was reduced to 0 mM, there was no change in evoked ACh release by adenosine. In contrast, increasing the magnesium concentration to 4 mM, the inhibitory effects of adenosine were significantly potentiated. These results indicate that $A_1-adenosine$ heteroreceptor is involved in ACh-release in the rat hippocampus and the inhibitory effects of adenosine mediated by $A_1-receptor$ is magnesium-dependent.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.5
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• pp.561-570
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• 2008

This study aimed to determine the effects of freeze-dried onion powder (OP) which contains rich in quercetin (22 mg/10 g) on hyperlipidemic participants. Fourteen participants (total cholesterol level in plasma $270.8{\pm}21.4mg/dL$) $40{\sim}59$ years of age who were diagnosed as hyperlipidemia by a physician at Fatima Hospital in Changwon took part in this study for 12 weeks. We investigated the anthropometric data and dietary habit by using questionnaires. Also, blood samples were collected from the patients in fasting before and after this 12 weeks intervention study. 78.6% of the patients showed interest in health diet management and weight control; however, they also showed some problems in their dietary habit (meal irregularity, food choice, calorie nutrient balance, high fat and cholesterol etc.) and life style (smoking, eating out, alcohol intake) that could have adverse effect on hyperlipidemic therapy. Most participants (85.7%) thought that OP was good for their health. The total cholesterol and LDL-cholesterol significantly decreased with OP intake. The HDL-cholesterol increased and the Atherogenic index (AI) significantly decreased. Regarding the correlations of dietary habit and life style with anthropometric and biochemical factors, the alcohol intake level was significantly correlated with the frequency of eating out and body mass index (BMI). Exercise level showed positive correlation with HDL-cholesterol and negative correlation with atherogenic index (AI). These results suggest that the intake of polyphenol rich onion may decrease the risk of hyperlipidemia by reducing cholesterol level. We consider these hypolipidemic effects of OP as a possible functional food. However, further research such as a well designed longterm clinical study with experimental and placebo groups is needed.

• Journal of the korean academy of Pediatric Dentistry
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• v.47 no.1
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• pp.53-61
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• 2020

Midazolam is a short-acting benzodiazepine that is widely used in pediatric dental sedation. However, its clinical effectiveness as an intravenous sedative agent in children has not been widely documented. A retrospective study was conducted to evaluate the efficacy and safety of intravenous midazolam and nitrous oxide inhalation sedation in pediatric dental treatment. The subjects were 115 patients (118 cases) who received dental treatment under intravenous midazolam and nitrous oxide inhalation sedation. Demographic factors, general health status, sedation time, midazolam and nitrous oxide dosage, and success rate of sedation were evaluated from electronic medical records. Behavioral management was the main reason of choosing sedation. Mean duration of sedation was 56.7 minutes for surgical treatment, and 74.4 minutes for restorative treatment. The initial dosage of intravenous midazolam was 0.051 ± 0.019 mg/kg. In 34 cases (28.8%), additional midazolam of 0.036 ± 0.057 mg/kg was delivered during the treatment. The concentration of nitrous oxide was maintained between 40% and 50%. The success rate of sedation was 99% (n = 117). In 1 case, laryngospasm occurred and the patient was reversed with benzodiazepine antagonist, flumazenil. Intravenous midazolam sedation with nitrous oxide was shown to be clinically effective for the dental treatment in children, if administered by trained personnel and patients are carefully selected in accordance with guidelines.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.12 no.2
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• pp.165-178
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• 2001

In order to elucidate the biological etiology and the relationship between the ontogenesis of serotonin system and psychopathology in ADHD, plasma serotonin(5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid(5-HIAA) were measured and the correlation between the plasma levels of 5-HT and 5-HIAA and age were evaluated in 46 ADHD patients and 18 control subjects. The ADHD patients were composed of 16 combined type, 10 inattentive type, and 20 hyperactive-impulsive type and the control subjects were communication disorders. The results are summarized as follows：1) There was significant difference in plasma 5-HT levels among combined, inattentive and hyperactive-impulsive and control subjects(ANOVA F=4.33, df 3, 60, p<0.05), and post-hoc test using Scheffe method showed significant difference between the combined type and control group. But, post-hoc tests showed no significant differences between combined and inattentive, combined and hyperactive-impulsive, hyperactive-impulsive and inattentive, hyperactive-impulsive and control and inattentive and control groups. 2) There was no significant differences in plasma 5-HIAA levels among the combined, hyperactive- impulsive, inattentive and control groups(ANOVA F=2.08, df 3, 60, p>0.05). 3) Significant difference in 5-HT level was found between the whole ADHD group(N=46) and the control group(N=18)(T=3.10, df 62, p<0.05). But no significant difference in 5-HIAA level was found between the whole ADHD group and the control group(T=1.90, df 62, p>0.05). 4) Plasma 5-HT and 5-HIAA levels showed no significant correlation with TOVA findings(5-HT：omission pearson correlation 0.10, commision 0.23, reaction time 0.01, variability in attention 0.11, all p>0.05, 5-HIAA：omission 0.21, commision 0.15, reaction time 0.09, variability in attention 0.15, all p>0.05). 5) Plasma 5-HT and 5-HIAA levels showed no significant correlation with attention, hyperactivity and impulsivity based on DSM-IV criteria. 6) Plasma 5-HT and 5-HIAA levels showed no significant correlation with age both in ADHD and control group. These findings show that decreased plasma 5-HT level may play a role in the genesis of ADHD, but this finding has no significant correlation with the psychopathology of ADHD. And we could not find any significant differences in ontogenetic processes in 5-HT. Future studies should be focused on the drug effects, family history and prognosis based on the biochemical subtypes(high and low 5-HT group).

• Childhood Kidney Diseases
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• v.2 no.2
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• pp.138-144
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• 1998

Purpose : The use of cyclosporine and mitomycin in various immunologic or neoplastic disorders has been known to cause wide-ranged nephrotoxic effects including thrombotic microangiopathy. However, the mechanism of nephrotoxicity of these drugs has not been studied adequately, so that present experimental study has been undertaken to find out whether these drugs can cause direct damage to the kidney and to clarify the pathogenetic mechanism of nephrotoxic effect of these drugs. Materials and methods : Sprague-Dawley rats weighing 250-300 gm were used for experimental animals and unilateral renal perfusion technique, modified from the method described by Hoyer et al was used. Isolation of left kidney from systemic circulation was made by clamping aorta and left renal vein and a hole was punctured in the anterior wall of the left renal vein. Cyclosporine (2.5 mg in 4 ml solution) and mitomycin (1.6 mg in 4ml solution) were infused through left renal artery and normal saline was used in control rats. Forty-eight hours after infusion of the drugs, animals were sacrificed and left kidney removed and processed for histologic examination. Total ischemic time of left kidney was less than 15 minutes: Results : Cyclosporine-perfused group showed severe swelling of glomerular endothelial ceil along with swelling of glomerular epithelial cell and interstitial vascular endothelial cell. Mitomycin-perfused group also showed severe swelling of glomerular endothelial and epithelial cells. And in addition to these findings, they demonstrated platelets aggregation, swelling and degranulation of platelets and fibrin accumulation in some of the capillaries, indicating occurrance of thrombotic microangiopathy. Conclusion : present experiment indicates that cyclosporine and mitomycin can cause direct toxic injury to renal endothelial cell. And this direct toxic damage to endothelial cell seems to be an important initiating event for the development of thrombotic microangiopathy.