• Journal of Pharmaceutical Investigation
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• v.27 no.3
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• pp.225-231
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• 1997

For the effective administration of naloxone, we attempted to investigate the naloxone sustained-release implants. Using the biodegradable polymer, poly[(diethyl glutamate)-co-(ethyl glycinate)phosphazenes](PGGP), the implantable devices containing naloxone hydrochloride(NLX HCl) and naloxone base(NLX) were prepared. The release rates of NLX and NLX HCl were compared. Influences of NLX contents on release rates were examined. For pharmacokinetic studies, NLX and NLX HCl loaded devices were implanted subcutaneously in rabbits and then the plasma concentrations of NLX were determined by HPLC(ECD). NLX-containing devices were implanted with various doses and pharmacokinetic parameters according to dose were calculated. The relative bioavailabilities were evaluated and compared. Incorporation of NLX in the polymer leaded to a slow release. There were no differences of release rates based on drug contents. In pharmacokinetic parameters determined in 216 hours, NLX loaded devices resulted in enhanced bioavailability with the higher AUC (p<0.01) than NLX HCl loaded devices and MRT was significantly (p<0.05) increased. This result demonstrates that NLX is more suitable for sustained release devices than NLX HCl. Therefore it is anticipated that the effective concentrations of naloxone could be maintained for longer periods and bioavailabilities could be improved by naloxone sustained-release implants, with varying drug base/hydrochloride.

• Korean Journal of Biological Psychiatry
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• v.8 no.1
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• pp.79-84
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• 2001

Objectives : To investigate the effects of (-)-3-PPP(0.5, 2, and 10mg/kg, s.c.) and haloperidol(0.1, 0.5, and 2mg/kg, s.c.) on the extracellular dopamine concentrations, and the effect of pretreatment with (-)-3-PPP(2mg/kg) on the haloperidol(2mg/kg)-induced extracellular dopamine concentrations in the nucleus accumbens(NAS) of free moving rats. Methods : Dopamine levels in dialysate were determined with high pressure liquid chromatography(HPLC) with electrochemical detection(ECD). Results : (1)(-)-3-PPP had dual actions depending on the doses: at 2mg/kg, it decreased and at 10mg/kg, increased extracellular dopamine concentrations ; (2) haloperidol at all doses increased dopamine levels with higher dose having a greater increase; and (3) pretreatment of (-)-3-PPP reduced the increase in dopamine levels elicited by acute treatment with haloperidol. Conclusions : These findings suggest that pretreatment of (-)-3-PPP in low dose could accelerate the onset of therapeutic effect of haloperidol by diminishing the haloperidol-induced dopamine release in the limbic system.

• Journal of Preventive Medicine and Public Health
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• v.26 no.4 s.44
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• pp.565-573
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• 1993

Noise is not only affecting the ear and the auditory cortex locally, but its influence is widely spread throughout the brain structures, e. g., the reticular formation, the brain stem nuclei or the subcortical forebrain area. Hence, any of the organism's activities can be hindered or stimulated by noise. High noise is a stressor and the catecholamine level can be used both as a stress marker and as an indicator of modified sympathetic nervous system activity. Several recent studies have found that the urinary excretion of catecholamines is increased due to high noise intensity, especially unexpectedly high and long lasting noise. The present study was conducted in order to examine the effects of noise stress on urinary excretion of ctecholamines in rats and humans. Rats were exposed to 90 dB noise for 10, 30, and 60 minutes, 3 and 12 hours. 24 hour . urinary samples were collected and the catecholamones were extracted by alumina and analyzed by HPLC-ECD. Catecholamine levels increased with time of exposure up to 60 minutes : norepinephrine concentration at 60 min of noise=1.038 ng/ml, epinephrine=0.636 ng/ml. Urine catecholamines of blue collar workers exposed to 90 dB of noise at the work place were collected between 2 and 4 p.m. and compared to that of white collar workers exposed to 70 dB. Mean norepinephrine level of the blue collar workers was 0.89 ng/ml (${\pm}0.25$), epinephrine 0.24ng/m1 (${\pm}0.09$), and that of the white collar workers 0.48 ng/ml (${\pm}0.12$), epinephrine 0.19 ng/ml(${\pm}0.05$). It was concluded that noise acts as a stressor and increases the catecholamine levels in both rats and humans.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.210-210
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• 1996

Changs in the glutamatergic nervous system following AF64A injection into lateral ventricle were studied in rats. Rats were treated with the infusion of AF64A (3mM) into lateral ventricle At a week after the infusion of AF64A into lateral ventricle, rats were sacrified and each brain resions was dissected ; striatum, hippocampus and frontal cortex. At these resions, total glutamate and other amino acids levels. [$^3$H]Mk801 binding sites and glutamine synthetase activity were measured using HPLC-ECD, ligand binding assay and enzyme activity assay, respectively. The levels of total glutamate were decreased in striatum, hippocampus and frontal cortex Also, the levels of total glycine and taurine were decreased in all examined regions. Furthermore, the levels of total aspartate and GABA were decreased in both hippocampus and frontal cortex but these didn't alter in striatum. Additionally, the levels of total glutamine were decreased in both striatum and frontal cortex. The u\numbers of [$^3$H]MK801 binding sites were differently dffected in each brain resions ; the decrease in striatum, the increase in frontal cortex and no change in hippocampus Glutamine synthetase activity in striatum was significantly decreased. But, that in both hippocampus and frontal cortex didn't alter These results suggest that changes in the glutamatergic nervous system in three regions are induced by following AF64A injection into lateral ventricle in rats.

• Korean Journal of Environmental Agriculture
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• v.32 no.2
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• pp.136-141
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• 2013

BACKGROUND: This study was performed to establishment the PHRLs of peach during cultivation period, and also to estimate biological half-lives for residues of fenarimol and flufenoxuron. METHODS AND RESULTS: The extracted samples of fenarimol were analyzed by GC-ECD and the flufenoxuron extracted samples were analyzed by HPLC-DAD. Recoveries of fenarimol at two fortification levels of 0.1 mg/kg, 0.5 mg/kg were $93.69{\pm}6.56$(%) and $94.45{\pm}1.60$ (%), respectively. And recoveries of flufenoxuron at two fortification levels of 0.1 mg/kg, 0.5 mg/kg were $106.73{\pm}5.90$(%) and $96.37{\pm}6.66$(%), respectively. CONCLUSION(S): The biological half-lives of fenarimol in single treatment and triple treatment were 3.5day and 3.8day. that of Flufenoxuron was also 7.1day and 4.9day, respectively. The PHRL of fenarimol were recommended as 1.5 mg/kg for 10day before harvest and the PHRL of flufenoxuron were recommended as 1.4 mg/kg for 10day before harvest.

• Korean Journal of Environmental Agriculture
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• v.31 no.3
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• pp.271-276
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• 2012

BACKGROUND: It is hard to control the agricultural products exceeding MRL (maximum residue limit) before forwarding. Therefore, NAQS (National Agricultural Products Quality Management Service, South Korea) established PHRL (pre-harvest residue limit) on agricultural products during their cultivation periods. This study was performed to set the PHRLs of peach during cultivation period, and also to estimate biological half-lives for residues of clothianidin and fluquinconazole. METHODS AND RESULTS: Two groups of peach were treated under Korean GAP (Good Agricultural Practices) with application time, single and triple treatments. Sample was collected over 14days (each after 0, 2, 4, 6, 8, 10, 12, 14 days. 8times), and clothianidin and fluquinconazole were analyzed by HPLC/DAD and GC/ECD, respectively. CONCLUSION: The biological half-life of clothianidin in single treatment and triple treatment was 5.2days and 7.0days. That of fluquinconazole was also 3.9days and 4.1days, respectively. The PHRL of peach on 10days before harvest was 1.4 mg/kg in clothianidin and 1.8 mg/kg in fluquinconazole.

• Environmental Mutagens and Carcinogens
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• v.25 no.3
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• pp.118-123
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• 2005

Nicotine has been implicated as a potential factor in the pathogenesis of human lung cancer, however its mechanism of action in the development of lung cancer remains largely unknown. To explore the role of nicotine in the development of lung cancer, we first investigated the effects of nicotine on the expression of tumor associated genes by treating Sprague-Dawley rats with nicotine (10 mg/kg) by gavage once daily for 10 days. We determined the expression of proteins and mRNAs of the ras, raf, myc, jun, fos oncogenes and p53, Rb tumor suppressor genes by Western and Northern blotting, respectively. We did not detect any changes on the levels of proteins and mRNAs of these tumor associated genes in the lung of Sprague-Dawley rats from 3 days to 12 weeks after the last treatment of nicotine, indicating that nicotine appears to have no effect on expression of these oncogenes and tumor suppressor genes at an early stage in multistage chemical carcinogenesis. In a second experiment, we investigated the possibility that 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) could be formed endogenously by treating with nicotine and sodium nitrite. We treated groups of Fischer 344 rats with nicotine ($60{\mu}mol/kg$) and sodium nitrite ($180{\mu}mol/kg$), nicotine, sodium nitrite and NNK (120 nmol/kg) alone by gavage once daily for 7 days, respectively and determined the 8-hydroxydeoxyguanosine (8-OHdG), as an indicator of NNK formation, in the lungs of rats 24 hours and 48 hours after the last treatment by HPLC/ECD method. We detect increased level of 8-OHdG in the lungs of rats treated with NNK, but in the case of nicotine plus sodium nitrite, nicotine and sodium nitrite alone we could not detected any changes of 8-OHdG, respectively.

• Preventive Nutrition and Food Science
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• v.18 no.2
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• pp.145-149
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• 2013

We tested for residual pesticide levels in dried vegetables in Seoul, Korea. A total of 100 samples of 13 different types of agricultural products were analyzed by a gas chromatography-nitrogen phosphate detector (GC-NPD), an electron capture detector (GC-${\mu}ECD$), a mass spectrometry detector (GC-MSD), and a high performance liquid chromatography- ultraviolet detector (HPLC-UV). We used multi-analysis methods to analyze for 253 different pesticide types. Among the selected agricultural products, residual pesticides were detected in 11 samples, of which 2 samples (2.0%) exceeded the Korea Maximum Residue limits (MRLs). We detected pesticide residue in 6 of 9 analyzed dried pepper leaves and 1 sample exceeded the Korea MRLs. Data obtained were then used for estimating the potential health risks associated with the exposures to these pesticides. The estimated daily intakes (EDIs) range from 0.1% of the acceptable daily intake (ADI) for bifenthrin to 8.4% of the ADI for cadusafos. The most critical commodity is cadusafos in chwinamul, contributing 8.4% to the hazard index (HI). This results show that the detected pesticides could not be considered a serious public health problem. Nevertheless, an investigation into continuous monitoring is recommended.

• Environmental Mutagens and Carcinogens
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• v.25 no.1
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• pp.13-18
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• 2005

In the present study, we have measured 8-hydroxy-2'-deoxyguanosine in DNA of stomach cancers, adjacent stomach cancer tissues, normal stomach tissues and peripheral blood leukocytes of the same stomach cancer patients (n = 48) to investigate their etiological association with gastric cancer and possibility whether peripheral blood leukocytes can use surrogate marker for early stomach cancer diagnosis by HPLC/ECD system. In normal stomach tissues, we found that 8-hydroxy-2'-deoxyguanosine levels in tissues infected with Helicobacter pylori were 1.4 fold higher than those in tissues without infected with Helicobacter pylori. However, in adjacent stomach cancer tissues, we found that 8-hydroxy-2'-deoxyguanosine levels in tissues infected with Helicobacter pylori were 1.5 fold lower than those in tissues without infected with Helicobacter pylori. In stomach cancer tissues, 8-hydroxy-2'-deoxyguanosine levels in tissues infected with Helicobacter pylori were not significantly different from those in tissues without infected with Helicobacter pylori. In Helicobacter pylori-negative specimens, 8­hydroxy-2'-deoxyguanosine levels of adjacent stomach cancer tissues were found to be significantly higher than those of normal stomach and cancer tissues. The 8-hydroxy-2'-deoxyguanosine levels of female were 1.7 fold higher than those of male in peripheral blood leukocytes of the same stomach cancer patients. The 8-hydroxy-2'­deoxyguanosine levels in Helicobacter pylori-negative specimens among adjacent stomach cancer tissues were found to be reversely correlated with those in peripheral blood leukocytes, suggesting that 8-hydroxy-2'-deox­yguanosine in peripheral blood leukocytes may not use as surrogate marker for the early diagnosis of human stomach cancer.

• Journal of Ginseng Research
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• v.46 no.3
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• pp.357-366
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• 2022

Background: Withania somnifera (Solanaceae), generally known as Indian ginseng, is a medicinal plant that is used in Ayurvedic practice for promoting health and longevity. This study aims to identify the bioactive metabolites from Indian ginseng and elucidate their structures. Methods: Withanolides were purified by chromatographic techniques, including HPLC coupled with LC/MS. Chemical structures of isolated withanolides were clarified by analyzing the spectroscopic data from 1D and 2D NMR, and HR-ESIMS experiment. Absolute configurations of the withanolides were established by the application of NMR chemical shifts and ECD calculations. Anti-adipogenic activities of isolates were evaluated using 3T3-L1 preadipocytes with Oil Red O staining and quantitative real-time PCR (qPCR). Results: Phytochemical examination of the roots of Indian ginseng afforded to the isolation of six withanolides (1-6), including three novel withanolides, withasilolides GeI (1-3). All the six compounds inhibited adipogenesis and suppressed the enlargement of lipid droplets, compared to those of the control. Additionally, the mRNA expression levels of Fabp4 and Adipsin, the adipocyte markers decreased noticeably following treatment with 25 µM of 1-6. The active compounds (1-6) also promoted lipid metabolism by upregulating the expression of the lipolytic genes HSL and ATGL and downregulating the expression of the lipogenic gene SREBP1. Conclusion: The results of our experimental studies suggest that the withasilolides identified herein have anti-adipogenic potential and can be considered for the development of therapeutic strategies against adipogenesis in obesity. Our study also provides a mechanistic rationale for using Indian ginseng as a potential therapeutic agent against obesity and related metabolic diseases.