Background: A major ingredient of green tea is epigallocatechin-3-gallate (EGCG), and this is known to have many beneficial effects for cancer prevention and also on the cardiovascular system and neurodegenerative diseases through its anti-oxidant, anti-angiogenic, anti-inflammatory, lipid-lowering and neuroprotective properties. Its actions on nociception and the spinal nervous system have been examined in only a few studies, and in these studies EGCG showed an antinociceptive effect on inflammatory and neuropathic pain, and a neuroprotective effect in motor neuron disease. This study was performed to investigate the effect of EGCG on acute thermal pain and the development of morphine tolerance at the spinal level. Methods: The experimental subjects were male Sprague-Dawley rats and the Hot-Box test was employed. A single or double-lumen intrathecal catheter was implanted at the lumbar enlargement for drug administration. An osmotic pump was used to infuse morphine for 7 days for induction of morphine tolerance. EGCG was injected repeatedly for 7 days at twice a day through the intrathecal catheter. Results: Intrathecal EGCG increased the paw withdrawal latency (PWL) after repeated administration for 7 days at twice a day, but this did not happen with administering on single bolus injection of EGCG. In addition, the antinociceptive effect of intrathecal morphine was not affected by co-administration with EGCG. A continuous 7-day infusion of morphine caused a significant decrease of the PWL in the control group (M + S, morphine plus saline). In contrast, intrathecal EGCG injection over 7 days blocked the decrease of the PWL in the experiment group (M + E, morphine plus EGCG). Conclusions: Intrathecal ECGC produced a weak antinociceptive effect for acute thermal pain, but it did not change the morphine's analgesic effect. However, the development of antinociceptive tolerance to morphine was attenuated by administering intrathecal EGCG.
In accordance with requirements of the ICH S7B safety pharmacology guidelines, numerous next-generation cardiotoxicity studies using human stem cell-derived cardiomyocytes (CMs) are being conducted globally. Although several stem cell-derived CMs are being developed for commercialization, there is insufficient research to verify if these CMs can replace animal experiments. In this study, in vitro high-efficiency CMs derived from human embryonic stem cells (hESC-CMs) were compared with Sprague-Dawley rats as in vivo experimental animals, and primary cultured in vitro rat-CMs for cardiotoxicity tests. In vivo rats were administrated with two consecutive injections of 100 mg/kg isoproterenol, 15 mg/kg doxorubicin, or 100 mg/kg nifedipine, while in vitro rat-CMs and hESC-CMs were treated with 5 μM isoproterenol, 5 μM doxorubicin, and 50 μM nifedipine. We have verified the equivalence of hESC-CMs assessments over various molecular biological markers, morphological analysis. Also, we have identified the advantages of hESC-CMs, which can distinguish between species variability, over electrophysiological analysis of ion channels against cardiac damage. Our findings demonstrate the possibility and advantage of high-efficiency hESC-CMs as next-generation cardiotoxicity assessment.
Bethanechol, a cholinergic agonist, has been recommended for the management of peripheral anticholinergic side effects during the treatment of antipsychotic medications. But there have been few studies which have evaluated the drug interactions of antipsychotics and bethanechol, even the treatment effects of bethanechol on anticholinergic side effects. So the authors have evaluated whether psychopathology and plasma haloperidol and reduced haloperidol concentrations are significantly changed or not when bethanechol was administrated with maintained doses of haloperidol and other coadministrated drugs(such a benztropine). Also we have evaluated the abating effects of bethanechol on anticholinergic side effects during the treatment with haloperidol. Fifteen schizophrenics with higher than 5 of total score of anticholinergic side effects of 'Rating scale for side effect' were assigned to two groups, and bethanechol 30mg/day and 60mg/day were applied on each group for 4 weeks. The daily haloperidol dosages were fixed before 2 weeks of study. We assessed anticholinergic side effects by 'Rating scale for side effect' and psychopathology by BPRS, and plasma haloperidol and reduced haloperidol concentrations by HPLC at baseline, 2nd week and 4th week. The results were as followed, 1) there was no significant change of plasma haloperidol and reduced haloperidol concentration, 2) at baseline, the dosage of haloperidol showed significant correlation with the total score of anticholinergic side effect, but not at 2nd week and 4th week, 3) in 60mg/day group, dry mouth and the total score of anticholinergic side effects were significantly improved, but not in 30mg/day group, 4) there was no significant change of BPRS except withdrawal at 2nd week. These results suggest that coadministration of bethanechol influenced neither on psychopathology nor on plasma haloperidol and reduced haloperidol concentrations and that improved dry mouth and total score of anticholinergic side effects at 60mg/day.
Narcotic drugs generally refer to serious and habitual hidden rash such as opium, heroin, methyphetamin, nabinol, cocaine, and so forth. At present, narcotic drugs are spread unchecked and are causing a big social problem. So many countries and narcotists are making every effort to set up a barricade against narcotic drugs. And there is a limit suitable treatment for them. Thus Tuo Yin Tang Jiang is developed. As indicated by Chinese letters, Tuo Yin Tang Jiang(TYTJ) is a crude drug. It is a traditional chinese medicine developed by the study done from June in 1998 to June in 1999 that Hubeisheng was entrusted with by People's Republic of China. This study is a treatise on etiology and syntomatology of narcotism. TYTJ is a medicine which is in accord with Pharmacopeia of the People's Republic of Chinal) in order to remove from the body the toxic materials resulting from narcotic drugs such as opium and heroin. According to the standard diagnosis on narcotism, 105 cases are studied and treated at the Rehabilitation Center attached to Enshi Autonomous Region Hospital in Hubeisheng. 105 cases are divided into 2 groups by double-blind method. One is the experimental group which has 56 cases. The other is the control group which has 49 ones.13 cases among 105 cases are addicted by intravenously injections. 9 cases are by oral takings. It took 10 days for this experiment to be performed. Two groups didn't show a striking individual variation based on the age, gender, period of taking drugs, withdrawal symptoms, complication, and state of health. The experimental group had a higher effect of treatment than the control group had. TYTJ treats diseases effectively and has no side effect, irrespective of the serious or slight addiction to opium and morphine.
한국생물정보시스템생물학회 2000년도 International Symposium on Bioinformatics
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pp.74-82
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2000
Prostate cancer initially responds and regresses in response to androgen depletion therapy, but most human prostate cancers will eventually recur, and re-grow as an androgen independent tumor. Once these tumors become hormone refractory, they usually are incurable leading to death for the patient. Little is known about the molecular details of how prostate cancer cells regress following androgen ablation and which genes are involved in the androgen independent growth following the development of resistance to therapy. Such knowledge would reveal putative drug targets useful in the rational therapeutic design to prevent therapy resistance and control androgen independent growth. The application of genome scale technologies have permitted new insights into the molecular mechanisms associated with these processes. Specifically, we have applied functional genomics using high density cDNA microarray analysis for parallel gene expression analysis of prostate cancer in an experimental xenograft system during androgen withdrawal therapy, and following therapy resistance, The large amount of expression data generated posed a formidable bioinformatics challenge. A novel template based gene clustering algorithm was developed and applied to the data to discover the genes that respond to androgen ablation. The data show restoration of expression of androgen dependent genes in the recurrent tumors and other signaling genes. Together, the discovered genes appear to be involved in prostate cancer cell growth and therapy resistance in this system. We have also developed and applied tissue microarray (TMA) technology for high throughput molecular analysis of hundreds to thousands of clinical specimens simultaneously. TMA analysis was used for rapid clinical translation of candidate genes discovered by cDNA microarray analysis to determine their clinical utility as diagnostic, prognostic, and therapeutic targets. Finally, we have developed a bioinformatic approach to combine pharmacogenomic data on the efficacy and specificity of various drugs to target the discovered prostate cancer growth associated candidate genes in an attempt to improve current therapeutics.
Studies have shown that both the psychomotor stimulant effects and rewarding properties of addictive drugs, including morphine, are sensitized by repeated drug administration and it is suggested that both of these effects are mediated by the same or closely overlapping dopamine systems. Specifically, the mesolimbic dopamine system has been implicated in the reinforcing and sensitizing properties of morphine. In oriental medicine, Shenmen (HT7) point on the heart channel has been used to treat mental and psychosomatic disorders. This study was designed to investigate the effect of acupuncture on acute and repeated morphine-induced changes in extracellular dopamine levels using in vivo microdialysis and morphine-induced behavioral changes. In the morphine sensitization experiment, male Sprague-Dawley rats were treated twice a day for three days with increasing doses of morphine (10, 20 and 40 mg/kg, s.c.) or with saline. After 15 days of withdrawal, rats were challenged with morphine hydrochloride (5 mg/kg, s.c.). Acupuncture was applied at bilateral Shenmen (HT7) points for 1 min after the morphine challenge. In the acute experiment, rats also received acupuncture for 1 min after an injection of morphine hydrochloride (5 mg/kg, s.c.). Results showed that acupuncture at the specific acupoint HT7, but not at control points (tail) significantly decreased both dopamine release and behavior induced by a systemic morphine challenge or a single sc morphine injection in the acute animals. These results suggest that reduction in sensitization may be one mechanism whereby acupuncture alleviates morphine craving in addicts.
Objective : This study was designed to test the anti-craving effect of Gigaltang(extracts of Oriental medicinal herbs ; Hovenia dulcis and Puerariae flos) in C57BL/6 mice. Anti-craving effect was substituted by alcohol intake amount of C57BL/6 mice. Method : 60 C57BL/6 mice was randomized into vehicle(water) group and Gigaltang group. Only 39(vehicle group(21) and Gigaltang group(18)) was eligible for this study, and 21 C57BL/6 mice was dropped out. The procedure was composed of 5 days of adjustment period and 32 days of alcohol exposure and withdrawal period with limited access paradigm and 10 days of treatment period. Alcohol was offered only for 2 hours a day from 2 to 4PM and water was offered for 22 hours left. Food was offered for 24 hours a day. 1140mg/Kg/day of Gigaltang was administrated to 18 mice of Gigaltang group for 10 days whereas water to 21 mice of vehicle group. The amount of alcohol intake, water intake, food intake, body weight were measured every other day. Result : There weren't significant differences in 2 hours of alcohol intake, 22 hours of water intake, 24 hours of food intake and body weight for ten days between Gigaltang and vehicle group. Conclusion : Anti-craving effect of Gigaltang on C57BL/6 mice wasn't verified. To verify the anti-craving effect, further study with advanced animal model, various dose of Gigaltang and diverse period of drug administration should be taken.
Chung, Hee Sik;Kim, Suk;Chun, Myung Sun;Jung, Won Chul;Kim, Dong Hyeok;Shon, Ho Yeong;Lim, Jeong Ju;Lee, Hu-Jang
대한수의학회지
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제47권2호
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pp.241-245
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2007
Parallux (IDEXX Laboratories, USA), a solid-phase fluorescence immunoassay (SPFIA) developed for antibiotics residue detection in milk, was applied for analysis of antibiotics in muscle tissue of olive flounder (Paralichthys olivaceus), rockfish (Sebastes schlegeli), and red sea bream (Pagrus major). Fishes were dipped in streptomycin 20 g/ton water, the recommended therapeutic dose, for 3 consecutive days. Muscle was sampled after 1st, 2nd, 3rd, 4th and 5th day drug treatment. The concentration of streptomycin in muscle, determined by SPFIA, was compared with that of internal standard (200 ppb as streptomycin). The absorbance ratio of sample to internal standard (S/C) was employed as an index to determine the muscle residues in fishes. The standard solutions were added to muscle samples to give final concentrations in muscle of 0.2 and 0.5 mg/ml to investigate the recovery rate. The recovery rates of all spiked samples were > 84% of the spiked value. Streptomycin was detected in muscles of fishes treated after the 1st day of withdrawal period. The present study showed that the SPFIA can be easily adopted in predicting muscle tissue residues for streptomycin in farmed fishes.
Park, Eun-Kee;Ryu, Yong-Jae;Cha, Chun-Nam;Yoo, Chang-Yeul;Kim, Suk;Lee, Hu-Jang
대한수의학회지
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제56권4호
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pp.233-239
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2016
This study was conducted to analyze penicillin G (PEG), streptomycin (STR) and neomycin (NEO) residues in milk of healthy lactating cows. Milk samples were collected from all four quarters of 12 dairy cows 2−7 days after intramammary infusions of an ointment containing PEG, STR and NEO once (n = 4; group I) or twice (n = 4, group II) daily. Ultra-performance liquid chromatography coupled with electrospray tandem mass spectrometry was used to determine the antibiotic residues in the samples. The correlation coefficient ($r^2$) of the calibration curves for all antibiotics was > 0.999 and the limits of detection and quantification were $0.002-0.005{\mu}g/mL$ and $0.007-0.02{\mu}g/mL$, respectively. Recovery rates were ranged from 75.5 to 92.3%. In group I, PEG, STR and NEO residues were detected in milk at 2, 3 and 2 days post-treatment, respectively, which were below the maximum residue limit (MRL). In group II, PEG, STR and NEO residues were detected in milk at 2, 3 and 3 days post-treatment, respectively, which were bellow the MRL. These results suggest that a 3-day for milk withdrawal period after the ointment treatment might be sufficient for reduction of the antibiotic residues below the MRL.
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