• Journal of Pharmacopuncture
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• v.23 no.1
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• pp.30-36
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• 2020

Objectives: The objective of the study was to prepare Bauhinia variegata loaded nanoemulsion(formulation and determine the efficacy of herbal drug formulation against diabetic peripheral neuropathic pain through acupuncture technique. Methods: Nine different ba tches of nanoemulsion (NE1 NE9) of BVN was prepared by varying the S_mix ratio and the concentration of oil. BVN was characterized to determine particle size, shape, zeta potential, polydispersity index, optical transmittance, drug release profile and stora ge stability. The optimized formulation was subjected to plantar test, behavioral tests of neuropathic pain and Von Frey filament stimulation test. Diabetes was induced by intraperitoneal injection of freshly prepared solution of Streptozotocin (60 mg/kg) to the experimental rats. Animals were made diabetic divided into four groups, Group I was untreated normal control group, Group II was diabetic control group, Group III was Bauhinia variegata extract ( treated group (100 mg/kg/day, p.o) and Group IV was BVN treated groups (100 mg/kg/day, p.o) acute and chronically. Results: The prepared B. variegata loaded nanoemulsion was nanosized (124 nm), spherical, uniform and stable over the period of 180 days with no change in physiochemical properties. The bl ood glucose and body weight of animals was normalizing after four weeks of treatment that was significant with BVN in comparison to diabetic control group. The chronic administration of BVN significantly (P<0.001) decreased hind paw withdrawal latency an d attenuated mechanical allodynia as compared with diabetic rats. Conclusion: Thus, BVN may be an effective drug formulation against diabetic peripheral neuropathic pain.

• Journal of Yeungnam Medical Science
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• v.40 no.1
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• pp.78-85
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• 2023

Background: Poor sleep quality is associated with psychoactive substance abuse/addiction/withdrawal. Auricular acupuncture (AA) is a nonpharmacological method used for the treatment of sleep disturbances. This study aimed to examine the quality of sleep before and after AA in participants with mental and behavioral disorders due to prior multiple drug use in the therapeutic community. Methods: This was a consecutive case series of 27 participants (25 male [92.6%]). The median age was 35.0 years (interquartile range [IQR], 29.0-37.2 years), methadone/buprenorphine were not used, and the participants were treated with AA (median number of treatments, 15.0 [IQR, 12.0-18.0]) during a median period of 51.0 days (IQR, 49.0-51.0 days) according to the National Acupuncture Detoxification Association (NADA)-Acudetox protocol. Sleep quality was determined using the Pittsburgh Sleep Quality Index (PSQI), a self-rated questionnaire that assesses sleep quality and disturbances over a 1-month interval. Results: The global PSQI score dropped (indicating better sleep quality) by a median of 3.0 points (IQR, 0.0-8.0 points) after treatment. In the multivariate logistic regression analysis, with an increase in global PSQI score during AA by 1 point, there was a 0.73-fold reduction in the risk of poor sleep quality post-AA (adjusted odds ratio, 0.73; 95% confidence interval, 0.52-1.01; p<0.055; Nagelkerke's R² =0.66). Conclusion: The results revealed a positive effect of AA (by the NADA-Acudetox protocol) on sleep quality (as measured by PSQI) among participants in a treatment center with mental and behavioral disorders due to multiple drug use.

• The Korean Journal of Pain
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• v.19 no.2
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• pp.131-136
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• 2006

Background: The aim of this study was to clarify the role of spinal groups II and III metabotropic glutamate receptors (mGluRs) with respect to postoperative pain at the spinal level. In addition, the nature of the pharmacological interaction between groups II and III mGluRs agonists and morphine was determined. Methods: Catheters were inserted into the intrathecal space of male SD rats. To induce postoperative pain, an incision was made in the plantar surface of the hind paw. A pharmacological characteristic for the interaction between groups II and III mGluRs agonists and morphine was evaluated using a fixed-dose analysis. Results: None of intrathecal group II and III mGluRs agonists modified the withdrawal threshold of the incisional pain. The administration of intrathecal morphine resulted in an increase of a dose dependent withdrawal threshold. A fixed-dose analysis revealed that the group III mGluRs agonist, ACPT-III, increased the antinociceptive action of morphine, while the group II mGluRs agonist, APDC, had no effect the antinociception of morphine. Conclusions: These results suggest that group II and III mGluRs may not play a direct modulatory role in the processing of postoperative pain at the spinal level. However, agonizing group III mGluRs may indirectly contributable to the potentiation of morphines antinociception in the spinal cord. Thus, the combination of morphine and a group III mGluRs agonist may be useful in the management of spinal postoperative pain.

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.45-51
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• 2011

These experiments were designed to use typical makers from behaviors and molecular basis in addicted animals of morphine and cocaine. Morphine has been widely abused with a high physical dependence liability. Morphine withdrawal activates the intracellular cAMP signaling pathway and further leads to changes in the expression of the cAMP response element binding protein (CREB), which may be important to the development and expression of morphine dependence. From these experiments, repeated morphine (10 mg/kg, twice per day for 7 days) developed physical dependence. Withdrawal signs were precipitated by naloxone and also increased the expression of the CREB. In addition, repeated exposure of cocaine (15 mg/kg) to mice develops locomotor sensitization and produced lasting behavioral sensitivity. Cocaine- and amphetamine-regulated transcript peptide (CART) peptide was up-regulated by repeated administration of cocaine in the striatum. Therefore, repeated morphine induced the development of physical dependence and increased pCREB. In addition, repeated cocaine induced locomotor sensitization and over-expressed CART peptide. In conclusion, the development of physical dependence and pCREB for morphine, and locomotor sensitization and CART peptide over-expression for cocaine would be useful markers to predict the abuse potential of opioid analgesics and pychostimulant drugs in animals, respectively.

• Clinical and Experimental Pediatrics
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• v.45 no.12
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• pp.1559-1570
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• 2002

Purpose : There has been no exact answer to the question of when to discontinue antiepileptic drugs(AEDs) in children with well-controlled epilepsy for a long period. This study is about the risk factors of relapse after withdrawal of AEDs in seizure(Sz)-free patients to show a guideline for discontinuation of AEDs. Methods : One hundred and sixty-nine children were diagnosed as epileptic at the Pediatric Dept. of Kyung-Hee Univ. between 1993 to 1998, in whom AEDs had been withdrawn after at least two years of Sz-free period. Univariate analysis using Kaplan-Meier survival analysis and multivariate analysis using Cox-proportional hazard model were performed for sixteen risk factors. Results : Forty-nine of the 169 patients(28.9%) had recurrence of Szs. The mean follow-up after withdrawal of AEDs was 4.1 years, mean treatment period was 4.1 years, and the mean Sz-free period was 3.3 years. Factors associated with an increased risk of relapse were young age at onset, symptomatic Sz, Sz type in West and Lennox-Gastaut syndrome, neurologic deficit, longer Sz-controlling period, shorter total treatment period, number of AEDs used(more than one drug), age at withdrawal of AEDs, and Sz-free period less than two years in univariate analysis using Kaplan-Meier mothod. From multivariate analysis, the factors indicating a significantly higher relapse risk were pre-treatment period after first Sz attack, Sz-controlling period, Sz-free period, number of AEDs used, neurologic abnormalities. Conclusion : For epileptic children who were Sz-free for more than two years, and were more than six-years-old, the discontinuation of AEDs should be considered positively, according to age of onset, Sz type, age at withdrawal of AEDs, total treatment period, Sz-controlling period, number of AEDs used, etiology, neurologic deficit, and the wishes of the patients and the their parents.

• The Korean Journal of Pain
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• v.18 no.2
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• pp.107-112
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• 2005

Background: Nerve ligation injury may produce mechanical allodynia, but this can be reversed after an intrathecal administration of adenosine analogues. In many animal and human studies, ATP-sensitive potassium channel blockers have been known to reverse the antinociceptive effect of various drugs. This study was performed to evaluate the mechanical antiallodynic effects of spinal R-PIA (Adenosine A1 receptor agonist) and the reversal of these effects due to pretreatment with glibenclamide (ATP-sensitive potassium channel blocker). Thus, the relationship between the antiallodynic effects of R-PIA and ATP-sensitive potassium channel were investigated in a neuropathic model. Methods: Male Sprague Dawley rats were prepared by tightly ligating the left lumbar 5th and 6th spinal nerves and implantation of a chronic lumbar intrathecal catheter for drug administration. The mechanical allodynia was measured by applying von Frey filaments ipsilateral to the lesioned hind paw. And the thresholds for paw withdrawal assessed. In study 1, either R-PIA (0.5, 1 and $2{\mu}g$) or saline were administered intrathecally for the examination of the antiallodynic effect of R-PIA. In study 2, glibenclamide (2, 5, 10 and 20 nM) was administered intrathecally 5 min prior to an R-PIA injection for investigation of the reversal of the antiallodynic effects of R-PIA. Results: The antiallodynic effect of R-PIA was produced in a dose dependent manner. In study 1, the paw withdrawal threshold was significantly increased with $2{\mu}g$ R-PIA (P < 0.05). In study 2, the paw withdrawal threshold with $2{\mu}g$ R-PIA was significantly decreased almost dose dependently by intrathecal pretreatment of 5, 10 and 20 nM glibenclamide (P < 0.05). Conclusions: These results demonstrated that an intrathecal injection of ATP-sensitive potassium channel blockers prior to an intrathecal injection of adenosine A1 receptors agonist had an antagonistic effect on R-PIA induced antiallodynia. The results suggest that the mechanism of mechanical antiallodynia, as induced by an intrathecal injection of R-PIA, may involve the ATP-sensitive potassium channel at both the spinal and supraspinal level in a rat nerve ligation injury model.

• Journal of Food Hygiene and Safety
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• v.28 no.3
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• pp.213-216
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• 2013

Antibiotic Detection Kit (Combination I), a lateral flow immunoassay (LFIA) developed for the detection of antibiotic residues in milk, was utilized for the analysis of antibiotic residues in the muscle tissue of olive flounder. After 60-min treatment by dipping in water dosed with ampicillin (200-g/ton water), the residue depletion of ampicillin was investigated in 25 cultured olive flounder (Paralichthys olivaceus). Muscles of fish were sampled on the 1st, 2nd, 3rd, 4th and 5th day after drug treatment. The concentration of ampicillin in the muscle was determined by LFIA. The absorbance ratio of the sample to the control blank (Bs/Bo) was employed as an index to determine the muscle residues in olive flounder. To investigate the recovery rate, standard solutions were added to muscle samples to give final concentrations in the muscle of 4 and 8 ng/ml. The recovery rates of all spiked samples were > 96% of the spiked value. Ampicillin was detected in the muscle of fish treated with the drug until the 2nd day of the withdrawal period. The present study showed that the LFIA can be easily adopted to predict ampicillin residues in tissue of farmed fishes.

• The Journal of Korean Medicine
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• v.29 no.4
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• pp.55-67
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• 2008

Objectives: The purpose of this study was to investigate the effect of Hwangryunhaedok-tang, its major component Coptidis Rhizoma, and the major component of Coptidis Rhizoma, berberine, on the expression of behavioral sensitization induced by the repeated administration of nicotine. Methods: Experimental ratswere divided into 3 groups and each group treated with saline, nicotine, and Hwangryunhaedok-tang. Experiments were performed on 4 further groups, each group treated with saline, nicotine, Coptidis Rhizoma, and berberine. To obtain rats addicted todrugs, nicotine was injected repeatedly. After 3 days of withdrawal phase, on the 11th day, rats were re-exposed to nicotine and thus able to induce the expression of the activity sensitization phenomenon successfully. To examine the change of c-Fos in the brain of experimental rats with the nicotine-induced activity sensitization, their neurological activation rate was assessed by c-Fos staining with Fos-like immunihistochemistry of the dopamine releasing area, the striatum and the nucleus accumbens. Results: The result demonstrate that Hwangryunhaedok-tang, its major component Coptidis Rhizoma and berberine,the major component of Coptidis Rhizoma, significantly reduced the walking activity rate in the drug addict models induced by nicotine administration, and Coptidis Rhizoma and its major component berberine reduce the marker of the neurological activation c-Fos, and thus revealed an effect of suppressing drug addiction. Conclusions: These results suggest the possibility of Hwangryunhaedok-tang, its major component Coptidis Rhizoma and the major component of Coptidis Rhizoma, berberine,as therapeutic for nicotine addiction.

• Journal of Pharmacopuncture
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• v.17 no.1
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• pp.74-79
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• 2014

Objectives: This study was conducted to clarify the analgesic effect of toad cake and toad-cake-containing herbal drugs. Methods: We counted the writhing response of mice after the intraperitoneal administration of acetic acid as a nociceptive pain model and the withdrawal response after the plantar surface stimulation of the hind paw induced by partial sciatic nerve ligation of the mice as a neuropathic pain model to investigate the analgesic effect of toad cake and toad-cake-containing herbal drugs. A co-treatment study with serotonin biosynthesis inhibitory drug 4-chloro-DL-phenylalanine methyl ester hydrochloride (PCPA), the catecholamine biosynthesis inhibitory drug ${\alpha}$-methyl-DL-tyrosine methyl ester hydrochloride (AMPT) or the opioid receptor antagonist naloxone hydrochloride was also conducted. Results: Analgesic effects in a mouse model of nociceptive pain and neuropathic pain were shown by oral administration of toad cake and toad-cake-containing herbal drugs. The effects of toad cake and toad-cake-containing herbal drugs disappeared upon co-treatment with PCPA, but not with AMPT or naloxone in the nociceptive pain model; the analgesic effect of toad-cake-containing herbal drugs also disappeared upon co-treatment with PCPA in the neuropathic pain model. Conclusion: Toad cake and toad-cake-containing herbal drugs have potential for the treatments of nociceptive pain and of neuropathic pain, such as post-herpetic neuralgia, trigeminal neuralgia, diabetic neuralgia, and postoperative or posttraumatic pain, by activation of the central serotonin nervous system.

• Journal of Pharmaceutical Investigation
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• v.39 no.4
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• pp.233-242
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• 2009

Bioequivalence (BE) studies provide important information in the overall set of data that ensure the availability of safe and effective medicines to patients and practitioners. Thus its determination of proper criterion for assessing BE is very important. BE is frequently expressed or measured by estimating area under the plasma concentration-time curve (AUC) and maximum concentration ($C_{max}$) that are reflective of systemic exposure. In all countries except Canada, the acceptance criteria of BE is that the 90% confidence interval of difference in the average values of logarithmic AUC and $C_{max}$ between test and reference products is within the acceptable range of log(0.8) ${\sim}$ log(1.25). In Canada, unlike other countries, point estimation instead of applying 90% confidence interval is applied to assess $C_{max}$ which is, in essence, more variable than AUC. We also compared other parts of BE guidelines which include a fed study, average BE (ABE), scaled-ABE, population BE (PBE), individual BE (IBE), dropout & withdrawal, sampling frequency & time and number of subjects. This article reviews the most recent BE guidelines of Korea, USA, Europe, Canada and Japan, highlighting the differences focused on Korean BE guidelines compared to other countries. It will help us to revise BE guideline of Korea reflecting international trends. Finally, it is strongly recommended that the extended acceptance criterion for the highly variable drug among all the considering aspects for the revision of current BE guideline has to be adopted into Korea BE guideline in the nearest future.