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ABSTRACT: Presently, few treatments for spinal cord injury (SCI) are available and none have facilitated neural regeneration and/or significant functional improvement. Agmatine (Agm), a guanidinium compound formed from decarboxylation of L-arginine by arginine decarboxylase, is a neurotransmitter/neuromodulator and been reported to exert neuroprotective effects in central nervous system injury models including SCI. The purpose of this study was to demonstrate the multifaceted effects of Agm on functional recovery and remyelinating events following SCI. Compression SCI in mice was produced by placing a 15 g/mm(2) weight for 1 min at thoracic vertebra (Th) 9 segment. Mice that received an intraperitoneal (i.p.) injection of Agm (100 mg/kg/day) within 1 hour after SCI until 35 days showed improvement in locomotor recovery and bladder function. Emphasis was made on the analysis of remyelination events, neuronal cell preservation and ablation of glial scar area following SCI. Agm treatment significantly inhibited the demyelination events, neuronal loss and glial scar around the lesion site. In light of recent findings that expressions of bone morphogenetic proteins (BMPs) are modulated in the neuronal and glial cell population after SCI, we hypothesized whether Agm could modulate BMP- 2/4/7 expressions in neurons, astrocytes, oligodendrocytes and play key role in promoting the neuronal and glial cell survival in the injured spinal cord. The results from computer assisted stereological toolbox analysis (CAST) demonstrate that Agm treatment dramatically increased BMP- 2/7 expressions in neurons and oligodendrocytes. On the other hand, BMP- 4 expressions were significantly decreased in astrocytes and oligodendrocytes around the lesion site. Together, our results reveal that Agm treatment improved neurological and histological outcomes, induced oligodendrogenesis, protected neurons, and decreased glial scar formation through modulating the BMP- 2/4/7 expressions following SCI.
PLoS ONE 01/2013; 8(1):e53911. · 4.09 Impact Factor
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ABSTRACT: ABSTRACT In recent years, laser toning has gained popularity for the treatment of melasma, and tyrosinase inhibitors are conventionally used to prevent recurrence after this treatment. The effectiveness of this treatment modality, however, is still questionable, and additional in vivo studies are needed to validate the method. In this study, we used adult zebrafish skin as an adult melanocyte regenerative system and examined the simulated human skin response to laser toning. Melanosomes regenerated after selective photothermolysis, and these organelles showed a bi-directional translocation pattern in accordance with the changes of intact melanosome patterns. Furthermore, a tyrosinase inhibitor, 1-phenyl-2-thiourea (PTU), completely blocked melanosome regeneration after laser irradiation, but this inhibitor failed to prevent melanosome regeneration after the medication was discontinued. Finally, arbutin and kojic acid, the commercially available tyrosinase inhibitors, slowed down but did not completely block melanosome regeneration. Based on these findings, we describe the limitations of laser toning treatment of melasma and the combined use of tyrosinase inhibitors. We suggest that melanosomes in adult zebrafish skin can be utilized for studying melanosome regeneration response to laser irradiation and for developing a system to assess the comparative efficacy of melanogenic regulatory compounds.
Journal of Cosmetic and Laser Therapy 10/2012; · 0.98 Impact Factor
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ABSTRACT: Emergence agitation (EA) frequently occurs after desflurane anesthesia in children. Ketamine, because of its sedative and analgesic properties, might be useful for the management of separation anxiety and EA. We investigated the preventive effect of ketamine on separation anxiety and EA after desflurane anesthesia in children for brief ophthalmic surgery.
Sixty children, ranging in age from 2-8 years old, undergoing brief ophthalmic surgery were randomly allocated to one of the 3 groups: group C received normal saline, group K1.0 received ketamine 1.0 mg/kg intravenously before entering the operating room, or group K0.5 received ketamine 0.5 mg/kg 10 min before the end of the surgery. Before induction, the separation anxiety score was evaluated. Extubation time, post-anesthesia care unit stay time, postoperative nausea and vomiting, emergence agitation, and pain were assessed.
The group K1.0 had a lower separation anxiety score compared with groups K0.5 and C. Extubation time in group K0.5 was significantly prolonged compared with groups K1.0 and C. The incidence of EA and the modified Children's Hospital of Eastern Ontario Pain Scale were significantly lower in group K1.0 and group K0.5 compared to group C, but there was no significant difference between groups K1.0 and K0.5.
In children undergoing brief ophthalmic surgery with desflurane anesthesia, ketamine 1.0 mg/kg administered before entering the operating room reduced separation anxiety, postoperative pain, and incidence of EA without delay in recovery.
Korean journal of anesthesiology 09/2012; 63(3):203-8.
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ABSTRACT: The aim of this prospective, double-blind, randomized study was to investigate the analgesic effects of low-dose ketamine on intravenous patient-controlled analgesia (IV-PCA) with fentanyl for pain control in pediatric patients following the Nuss procedure for pectus excavatum.
Sixty pediatric patients undergoing the Nuss procedure were randomly assigned to receive fentanyl (Group F, n=30) or fentanyl plus ketamine (Group FK, n=30). Ten minutes before the end of surgery, following the loading dose of each solution, 0.5 μg/kg/hr of fentanyl or 0.5 μg/kg/hr of fentanyl plus 0.15 mg/kg/hr of ketamine was infused via an IV-PCA pump (basal rate, 1 mL/hr; bolus, 0.5 mL; lock out interval, 30 min). Fentanyl consumption, pain score, ketorolac use, nausea/vomiting, ondansetron use, pruritus, respiratory depression, hallucination, dreaming, and parent satisfaction with pain control were measured throughout the 48 hours following surgery.
The pain scores, ketorolac use, and fentanyl consumption of Group FK were significantly lower than in Group F (p<0.05). The incidence of nausea/vomiting and ondansetron use in Group FK was significantly lower than in Group F (p<0.05). There were no reports of respiratory depression, hallucination or dreaming. Parent satisfaction with pain control was similar between the two groups.
We concluded that low-dose ketamine added to IV-PCA with fentanyl after the Nuss procedure in pediatric patients can reduce pain scores, consumption of fentanyl, and incidence of nausea/vomiting without increasing side effects.
Yonsei medical journal 03/2012; 53(2):427-32. · 0.77 Impact Factor
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Dermatologic Surgery 02/2012; 38(6):960-3. · 1.80 Impact Factor
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Korean journal of anesthesiology 02/2012; 62(2):194-5.
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ABSTRACT: Nuss surgery is preferred in pectus excavatum repair because this procedure produces excellent cosmetic results and prevents postoperative distressed pulmonary function. However, the procedure causes severe pain due to thoracic expansion. This study was designed to investigate the analgesic effect of small doses of ketamine on an intravenous patient-controlled analgesia (IV-PCA) using hydromorphone and ketorolac for pain control after Nuss surgery.
Forty-four patients undergoing elective Nuss surgery were randomly assigned to receive hydromorphone 3 µg/kg/hr, ketorolac 0.05 mg/kg/hr and ondansetron 0.1 mg/kg/day (Group HO, n = 22) or hydromorphone 3 µg/kg/hr, ketorolac 0.05 mg/kg/hr, ondansetron 0.1 mg/kg/day and ketamine 0.15 mg/kg/hr (Group HK, n = 22) via an IV-PCA pump after surgery. A blind observer evaluated each patient using the Modified Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) for the assessment of pain control. The total administered PCA volume, side effects and parents satisfaction with pain control were assessed at postoperative 1, 4, 8, 12, 24, and 48 hours.
There were no significant differences in Modified CHEOPS between the groups during postoperative 48 hours. The total PCA volume in group HK was significantly lower than that in group HO (P < 0.05). The side effects in both groups did not significantly differ except for pruritus. The levels of satisfaction from the parents were not significantly different between the groups.
A small dose of ketamine on IV-PCA reduced the total administered dose of IV-PCA with hydromorphone and ketorolac and reduced the incidence of pruritus after the Nuss procedure in pediatric patients.
Korean journal of anesthesiology 02/2012; 62(2):142-7.
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Annals of Dermatology 02/2012; 24(1):107-8. · 0.53 Impact Factor
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International journal of dermatology 12/2011; 50(12):1467-9. · 1.18 Impact Factor
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International journal of dermatology 09/2011; · 1.18 Impact Factor
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ABSTRACT: A large reservoir of bacterial lipopolysaccharide (LPS) is available in the colon and this could promote colon cancer metastasis by enhancing tumor cell adhesion, intravasation, and extravasation. Furthermore, adhesion molecules like ICAM-1, VCAM-1, and E-selectin play important roles in the adhesion of tumor cells to endothelium. This study was designed to determine whether morphine can attenuate the expressions of adhesion molecules up-regulated by the supernatant of LPS-stimulated HCT 116 colon cancer cells (LPS-Sup). In this study, we divided to three groups by cell-growth medium of human umbilical vascular endothelial cells (HUVECs): the control group was incubated in growth factor-free endothelial medium, the Sup group was incubated in the supernatant of HCT 116 cells (Sup), and the LPS-Sup group was incubated in LPS-Sup. To observe effect of morphine to the adhesion molecules expressions in the LPS-Sup group, we co-treated morphine with LPS or added it to LPS-Sup. Adhesion molecule expressions on HUVECs in all three groups were measured during incubation period. Consquentially, ICAM-1, VCAM-1, and E-selectin expressions on HUVECs were significantly lower when morphine was co-treated with LPS than not co-treated. Thus, we suggest that morphine affects the expressions of adhesion molecules primarily by attenuating LPS stimuli on tumor cells.
Journal of Korean medical science 06/2011; 26(6):747-52. · 0.84 Impact Factor
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Dermatologic Surgery 06/2011; 37(6):851-4. · 1.80 Impact Factor
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ABSTRACT: Adding opioid to spinal anaesthetic provides additional analgesia during the postoperative period. The purpose of this study was to determine the dose of intrathecal hydromorphone necessary to achieve postoperative pain relief after arthroscopic knee surgery.
In a prospective, double-blinded parallel, placebo-controlled manner, 60 patients who were undergoing unilateral knee arthroscopy randomly received unilateral spinal anaesthesia with 0.5% hyperbaric bupivacaine 6 mg combined with 0.0, 2.5, 5.0 or 10.0 μg per 0.05 ml hydromorphone. Fifteen patients were assigned to receive each dose. The visual analogue pain scores (VAPSs) were measured at 30 min and 2, 4, 6, 12 and 24 h postoperatively, and the side-effects of hydromorphone were recorded.
The postoperative VAPSs at 4, 6 and 12 h for the 5 and 10 μg hydromorphone groups were significantly decreased, compared to the control group. The 2.5 μg hydromorphone group had lower VAPS only at 4 and 6 h postoperatively. Nausea was significantly increased in the 10 μg hydromorphone group (46.6%).
The analgesic effects of 5 and 10 μg intrathecal hydromorphone provided satisfactory pain relief for 12 h postoperatively and nausea increased significantly in a dose-dependent manner.
European Journal of Anaesthesiology 05/2011; 29(1):17-21. · 2.23 Impact Factor
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Dermatologic Surgery 04/2011; · 1.80 Impact Factor
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ABSTRACT: The purpose of this study is to determine 1) whether morphine post condition (MPostC) can attenuate the intercellular adhesion molecules-1 (ICAM-1) expression after reoxygenation injury and 2) the subtype(s) of the opioid receptors (ORs) that are involved with MPostC. Human umbilical vein endothelial cells (HUVECs) were subjected to 6 hr anoxia followed by 12 hr reoxygenation. Three morphine concentrations (0.3, 3, 30 µM) were used to evaluate the protective effect of MPostC. We also investigated blockading the OR subtypes' effects on MPostC by using three antagonists (a µ-OR antagonist naloxone, a κ-OR antagonist nor-binaltorphimine, and a δ-OR antagonist naltrindole) and the inhibitor of protein kinase C (PKC) chelerythrine. As results, the ICAM-1 expression was significantly reduced in the MPostC (3, 30 µM) groups compared to the control group at 1, 6, 9, and 12 hours reoxygenation time. As a consequence, neutrophil adhesion was also decreased after MPostC. These effects were abolished by co administering chelerythrine, nor-binaltorphimine or naltrindole, but not with naloxone. In conclusion, it is assumed that MPostC could attenuate the expression of ICAM-1 on endothelial cells during reoxygenation via the κ and δ-OR (opioid receptor)-specific pathway, and this also involves a PKC-dependent pathway.
Journal of Korean medical science 02/2011; 26(2):290-6. · 0.84 Impact Factor
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Jae Hwan Kim
Korean journal of anesthesiology 02/2011; 60(2):73-4.
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ABSTRACT: We present here the case of a 33-month-old male patient with Wolf-Hirschhorn syndrome (WHS) and who underwent tympanoplasty and myringotomy. WHS is caused by a rare chromosomal abnormality, which is the deletion of the short arm of chromosome number 4. The typical craniofacial features of WHS patients such as micrognathia, microcephaly and the muscular weakness can make using neuromuscular blocking agents and performing intubation difficult. Moreover, there are a few previous case reports showing that malignant hyperthermia occurred during and after an operation in which the anesthesia was done with inhalation agents, so special anesthetic care is needed when operating on a WHS patient. By carefully intubating the patient and using total intravenous anesthesia, we performed successful anesthesia without any complications. We describe here the anesthetic management of a WHS patient and we review the relevant literature.
Korean journal of anesthesiology 02/2011; 60(2):119-23.
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ABSTRACT: Intended to investigate whether agmatine treatment reduces collagen scar area in mice subjected to spinal cord injury (SCI).
The purpose of the present study is to demonstrate the protective effect of agmatine on complete transection SCI mice. SUMMARY OF BACK GROUND DATA: The deposition of collagen that occurs at the lesion site, during the SCI, was well known. Agmatine has been reported to exert neuroprotective effect in various stress models including central nervous system injuries. In the present investigation, we hypothesized that agmatine treatment could rescue the mice subjected to SCI.
Complete SCI was made at the T9 level. Agmatine was dissolved in normal saline (100 mg/kg, Sigma, St. Louis, MO) and given intraperitoneally 5 minutes after complete transection daily for 4 weeks (agmatine-treated mice, n = 30). Controls received normal saline in the same manner (experimental control, n = 30). Surface righting reflex test, expression of bone morphogenetic protein-7 (BMP-7), TGFβ-2 (transforming growth factor β-2), and collagen scar area were measured and the results were compared with Mann-Whitney U test using SAS.
Agmatine treatment improved the surface righting reflex of mice at 4 weeks after SCI (P = 0.030). The collagen scar, physical barrier to axon regeneration, was noticeably diminished by agmatine treatment at 4 weeks after SCI (P = 0.001). The expression of BMP-7, which is considered both neuroprotective and neuroregenerative, was increased in agmatine treatment group compared with experimental control group in the early stages after SCI (P = 0.015 at 1 day after SCI; P = 0.010 at 3 days; P = 0.035 at 1 week; P = 0.826 at 2 weeks). The expression of TGFβ-2 correlated with the deposition of the collagen matrix at the lesion site was decreased with agmatine treatment at 1 and 2 weeks after SCI (P = 0.001 at 1 week; P = 0.002 at 2 weeks). Survival rate was found to be higher in agmatine treatment group than in the experimental control group for 4 weeks after SCI (P = 0.076).
These results suggest that agmatine treatment could support neuroregeneration by reducing the collagen scar area through decreasing the expression of TGFβ-2 and increasing the expression of BMP-7 after SCI. Especially, the improved surface righting reflex of agmatine-treated group proposes that agmatine treatment have the potency to facilitate functional recovery after SCI. However, the drug (agmatine) warrants further investigation in higher mammals.
Spine 02/2011; 36(25):2130-8. · 2.08 Impact Factor
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ABSTRACT: The arginine decarboxylase (ADC) is a significant functional enzyme, synthesizes agmatine through arginine metabolism, and agmatine was reported to posses protective properties in various tissues. This study first optimized the conditions for efficient hexahistidine tagged human ADC (hisADC) gene delivery into mouse fibroblast cell line (NIH3T3) using retroviral vector (pLXSN). Later, the functionality of the delivered hisADC gene in synthesizing agmatine during H(2)O(2) injury in NIH3T3 was also elucidated. Amplification of hisADC gene was performed using hisADC specific primers under specified conditions. The hisADC PCR product (1.4 kb) was ligated with pLXSN considering the restriction enzyme sites. The complete hisADC pLXSN clone was transfected into PT67 cell line following CalPhos Mammalian transfection method. RT-PCR and western blot results showed the specific and strong detection of hisADC genes in hisADC PT67 transfected cells compared with normal control and pLXSN transfected PT67 cells. The retrovirus containing hisADC gene (vhisADC) was infected into NIH3T3 (vhisADC NIH) using polybrene reagent. Immunocytochemical results showed hisADC expression in the cytoplasm of vhisADC NIH. HPLC analysis revealed high agmatine concentration in the vhisADC NIH, and the induced agmatine synthesized from the retroviral gene delivery prevented vhisADC NIH from H(2)O(2) injury which is evident by the decrease in lactate dehydrogenase (P < 0.05) leakage into the medium and less number of propidium iodide positive cells during injury compared to control group. The obtained results provide compelling evidence that higher level of hisADC transgene expression completely triggered the endogenous agmatine synthesis during H(2)O(2) injury thus protecting NIH3T3 cells against cytotoxicity.
Molecular and Cellular Biochemistry 12/2010; 345(1-2):53-60. · 2.06 Impact Factor
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ABSTRACT: We experienced a case of malignant hyperthermia (MH) in 6-year-old boy during anesthesia induction for strabismus surgery. It has been generally reported that sevoflurane can induce the delayed onset of MH in the absence of succinylcholine. Our case of MH was elicited after about 2-3 min of sevoflurane administration with N(2)O, O(2) and rocuronium. However, we successfully treated the patient by early recognition of his condition and administering symptomatic treatment and dantrolene.
Korean journal of anesthesiology 12/2010; 59 Suppl:S6-8.