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1.
Nanotechnology ; 35(35)2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38838661

ABSTRACT

This study investigates the effect of an oxidized Ta capping layer on the boosting of field-effect mobility (µFE) of amorphous In-Ga-Zn-O (a-IGZO) Thin-film transistors (TFTs). The oxidation of Ta creates additional oxygen vacancies on the a-IGZO channel surface, leading to increased carrier density. We investigate the effect of increasing Ta coverage on threshold voltage (Vth), on-state current,µFEand gate bias stress stability of a-IGZO TFTs. A significant increase inµFEof over 8 fold, from 16 cm2Vs-1to 140 cm2Vs-1, was demonstrated with the Ta capping layer covering 90% of the channel surface. By partial leaving the a-IGZO uncovered at the contact region, a potential barrier region was created, maintaining the low off-state current and keeping the threshold voltage near 0 V, while the capped region operated as a carrier-boosted region, enhancing channel conduction. The results reported in this study present a novel methodology for realizing high-performance oxide semiconductor devices. The demonstrated approach holds promise for a wide range of next-generation device applications, offering new avenues for advancement in metal oxide semiconductor TFTs.

2.
Nanotechnology ; 35(34)2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38806010

ABSTRACT

We report on improved high voltage operation of amorphous-In-Ga-Zn-O (a-IGZO) thin film transistors (TFTs) by increasing carrier density and distributing the high bias field over the length of the device which utilizes an off-set drain structure. By decreasing the O2partial pressure during sputter deposition of IGZO, the channel carrier density of the high voltage a-IGZO TFT (HiVIT) was increased to ∼1018cm-3. Which reduced channel resistance and therefore the voltage drop in the ungated offset region during the on-state. To further decrease the electric field in the offset region, we applied Ta capping and subsequent oxidation to locally increase the oxygen vacancy levels in the offset region thereby increasing local carrier density. The reduction of the drain field in the offset region from 1.90 Vµm-1to 1.46 Vµm-1at 200 V drain voltage, significantly improved the operational stability of the device by reducing high field degradation. At an extreme drain voltage of 500 V, the device showed an off-state current of ∼10-11A and on-state current of ∼1.59 mA demonstrating that with further enhancements the HiVIT may be applicable to thin-film form, low leakage, high voltage control applications.

3.
Clin Hypertens ; 28(1): 7, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35227313

ABSTRACT

BACKGROUND: This study evaluated the circadian efficacy of a telmisartan 40 mg/S-amlodipine 2.5 mg fixed-dose combination (Telmisartan40/S-Amlodipine2.5) compared to telmisartan 80 mg (Telmisartan80) in patients with essential hypertension who did not respond to 2-4 weeks' treatment with telmisartan 40 mg. METHODS: Eligible patients with essential hypertension (clinic mean sitting systolic blood pressure [MSSBP] ≥140 mmHg, or ≥ 130 mmHg in those with diabetes mellitus or chronic kidney disease) were randomly assigned to Telmisartan40/S-Amlodipine2.5 or Telmisartan80 for 8 weeks. All patients underwent ambulatory BP monitoring (ABPM) at baseline and 8 weeks later. Primary endpoints were changes in mean 24-h SBP and DBP on 24-h ABPM from baseline after 8 weeks. Secondary endpoints were changes in daytime, nighttime, and morning SBP and DBP, and clinic MSSBP and MSDBP. RESULTS: A total of 316 Korean patients were enrolled, 217 patients were randomized to treatment, and 192 patients completed the study. Compared to Telmisartan80, Telmisartan40/S-Amlodipine2.5 showed significantly better reductions in 24-h mean SBP and DBP after 8 weeks. Telmisartan40/S-Amlodipine2.5 also significantly reduced secondary endpoints compared to Telmisartan80. Among 15 adverse events (7 [Telmisartan40/S-Amlodipine2.5] and 8 [Telmisartan80]), there were five adverse drug reactions; 14 events were mild, and none were identified with significant between-group differences. CONCLUSIONS: Telmisartan40/S-Amlodipine2.5 was tolerable and more effective than Telmisartan80 in lowering 24-h mean ambulatory BP in patients with essential hypertension not responding adequately to Telmisartan40. Our findings support the fact that the combination of S-amlodipine with telmisartan is more appropriate than increasing the dose of telmisartan monotherapy. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02231788 . Registered 4 September 2014.

4.
J Am Chem Soc ; 143(3): 1641-1650, 2021 01 27.
Article in English | MEDLINE | ID: mdl-33427458

ABSTRACT

Catalytic reactions involving 1,n-metal migration represent a powerful method for the synthesis of complex molecules from simple precursors through the activation of C-H bonds. By utilizing this attractive feature, herein we devised a palladium-catalyzed synthesis of new members of 5H-dibenzo[b,f]silepins, a class of underexplored but potentially useful silicon-bridged π-conjugated compounds. The reaction sequence is composed of 1,n-palladium migrations and unusual anti-carbopalladation of alkynes, which was realized by the proper choice of ligand for palladium. A series of deuterium-labeling experiments were conducted toward an understanding of the reaction mechanism to propose plausible catalytic cycles. The newly obtained 5H-dibenzo[b,f]silepins exhibited tunable optical and electronic properties, demonstrating the power and importance of developing a new synthetic method based on 1,n-metal migration processes.

6.
Sci Rep ; 10(1): 11833, 2020 07 16.
Article in English | MEDLINE | ID: mdl-32678265

ABSTRACT

The magnetic particle imaging (MPI) is a technology that can image the concentrations of the superparamagnetic iron oxide nanoparticles (SPIONs) which can be used in biomedical diagnostics and therapeutics as non-radioactive tracers. We proposed a point-of-care testing MPI system (PoCT-MPI) that can be used for preclinical use for imaging small rodents (mice) injected with SPIONs not only in laboratories, but also at emergency sites far from laboratories. In particular, we applied a frequency mixing magnetic detection method to the PoCT-MPI, and proposed a hybrid field free line generator to reduce the power consumption, size and weight of the system. The PoCT-MPI is [Formula: see text] in size and weighs less than 100 kg. It can image a three-dimensional distribution of SPIONs injected into a biosample with less than 120 Wh of power consumption. Its detection limit is [Formula: see text], 10 mg/mL, [Formula: see text] (Fe).


Subject(s)
Brain/diagnostic imaging , Image Processing, Computer-Assisted/statistics & numerical data , Imaging, Three-Dimensional/methods , Magnetic Iron Oxide Nanoparticles/administration & dosage , Point-of-Care Testing , Animals , Humans , Imaging, Three-Dimensional/instrumentation , Limit of Detection , Magnetic Iron Oxide Nanoparticles/chemistry , Magnetic Phenomena , Male , Mice , Mice, Inbred C57BL , Rats , Rats, Sprague-Dawley
7.
Angew Chem Int Ed Engl ; 59(21): 8057-8061, 2020 05 18.
Article in English | MEDLINE | ID: mdl-31997528

ABSTRACT

A new and efficient synthesis of 8H-benzo[e]phenanthro[1,10-bc]silines from 2-((2-(arylethynyl)aryl)silyl)aryl triflates under palladium catalysis has been developed. The reaction mechanism was experimentally investigated and a catalytic cycle involving C-H/C-H coupling through a new mode of 1,4-palladium migration with concomitant alkene stereoisomerization is proposed.

8.
Can J Physiol Pharmacol ; 98(6): 373-382, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31999472

ABSTRACT

Acute myocarditis is an unpredictable heart disease that is caused by inflammation-associated cell death. Although viral infection and drug exposure are known to induce acute myocarditis, the molecular basis for its development remains undefined. Using proteomics and molecular analyses in myosin-induced rat experimental autoimmune myocarditis (EAM), we identified that elevated expression of aldolase 1A, retrogene 1 (Aldoart1) is critical to induce mitochondrial dysfunction and acute myocarditis development. Here, we demonstrate that cardiac cell death is associated with increased expressions of proapoptotic genes in addition to high levels of glucose, lactate, and triglyceride in metabolite profiling. The functional protein association network analysis also suggests that Aldoart1 upregulation correlates with high levels of dihydroxyacetone kinase and triglyceride. In H9c2 cardiac cells, lipopolysaccharides (LPS) or high glucose exposure significantly increases the cytochrome c release and the conversion of pro-caspase 3 into the cleaved form of caspase 3. We also found that LPS- or glucose-induced toxicities are almost completely reversed by siRNA-mediated knockdown of Aldoartl, which consequently increases cell viability. Together, our study strongly suggests that Aldoart1 may be involved in inducing mitochondrial apoptotic processes and can be a novel therapeutic target to prevent the onset of acute myocarditis or cardiac apoptosis.


Subject(s)
Apoptosis/genetics , Autoimmune Diseases/genetics , Autoimmune Diseases/pathology , Fructose-Bisphosphate Aldolase/genetics , Myocarditis/genetics , Myocarditis/pathology , Myocytes, Cardiac/pathology , Animals , Disease Models, Animal , Gene Expression , Male , Rats
9.
Sci Rep ; 9(1): 19050, 2019 12 13.
Article in English | MEDLINE | ID: mdl-31836804

ABSTRACT

Occlusion of the major cerebral artery usually results in brain hypoxic-ischemic injury, which evokes neuroinflammation and microglial activation. Activated microglia are considered a source of multiple neurotoxic factors, such as reactive oxygen species (ROS), in the central nervous system (CNS). We herein present a 3D-rendering brain imaging technique in an experimental rodent model of cerebral ischemia based on 2D magnetic images of superparamagnetic iron oxide nanoparticles (SPIONs) using the planar frequency mixing magnetic detection (p-FMMD) technique. A rat model of cerebral ischemia was established by unilateral middle cerebral artery occlusion with reperfusion (MCAO/R) injury. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was performed to demonstrate the irreversibly damaged ischemic brain tissues, and double immunofluorescent labeling of OX6 (activated microglial marker) and ethidium (ROS marker) was conducted to confirm ROS generation in the activated microglia in the infarcted brain region. The ischemic brain sections treated with OX6-conjugated SPIONs were scanned using our p-FMMD system, yielding 2D images on the basis of the nonlinear magnetic characteristics inherent in SPIONs. The p-FMMD signal images representing microglia activation show an infarct ratio of 44.6 ± 7.1% compared to the contralateral counterpart, which is smaller than observed by TTC (60.9 ± 4.9%) or magnetic resonance imaging (MRI, 65.7 ± 2.7%). Furthermore, we developed a 3D-rendering brain imaging process based on the 2D p-FMMD signal images. The 3D reconstructed model showed a decreased ratio of coincidence of the ischemic regions compared with MRI models. In this study, we successfully conducted a feasibility test on whether our p-FMMD technology, a technique for signaling and imaging based on the nonlinearity of SPIONs, can be used to visualize the ischemic brain region in real time by detecting activated microglia in an MCAO/R animal model. Therefore, our method might allow for a different approach to analyze the pathophysiology of ischemic stroke through molecular imaging. Furthermore, we propose that this magnetic particle imaging (MPI) technique that detects the nonlinear magnetization properties of SPIONs could be applied not only to a stroke model but also to various types of pathophysiological studies as a new bioimaging tool.


Subject(s)
Brain Ischemia/diagnostic imaging , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Animals , Disease Models, Animal , Infarction, Middle Cerebral Artery/complications , Male , Rats, Sprague-Dawley , Signal Processing, Computer-Assisted
10.
BMC Musculoskelet Disord ; 18(1): 40, 2017 01 25.
Article in English | MEDLINE | ID: mdl-28122599

ABSTRACT

BACKGROUND: The purpose of this study was to determine whether additional tension band wiring in the plate for traumatic disruption of symphysis pubis has clinical benefits. Therefore, outcomes and complications were compared between a plate fixation group and a plate with tension band wiring group. METHODS: We retrospectively evaluated 64 consecutive patients who underwent open reduction and internal fixation of the symphysis pubis by using a plate alone (n = 39) or a plate with tension band wiring (n = 25). All the patients were followed up for a minimum of 24 months (mean, 34.4 months; range, 26-39 months). Demographic characteristics, outcomes, movement of the metal works, complications, revision surgery, and Majeed functional score were compared. RESULTS: Significant screw pullout was relatively significantly more frequently found in the plate fixation group than in the plate with tension band wiring group (P = 0.009). In terms of the overall rate of all-cause revision surgery, including significant loosening, symptomatic hardware, and patient-requested hardware removal during follow-up period, the plate with tension band wiring group showed a significantly lower rate. CONCLUSION: Tension band wiring in combination with a symphyseal plate showed better radiological outcomes, a lower incidence of hardware loosening, and a lower rate of revision surgery than plate fixation alone. This technique would have some potential advantages in terms of avoiding significant movement of plate, symptomatic hardware failure, and revision surgery.


Subject(s)
Bone Plates , Bone Wires , Pubic Symphysis Diastasis/diagnostic imaging , Pubic Symphysis Diastasis/surgery , Adolescent , Adult , Aged , Bone Plates/statistics & numerical data , Bone Wires/statistics & numerical data , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pubic Symphysis/diagnostic imaging , Pubic Symphysis/surgery , Retrospective Studies , Treatment Outcome , Young Adult
11.
Anal Chim Acta ; 892: 77-84, 2015 Sep 10.
Article in English | MEDLINE | ID: mdl-26388477

ABSTRACT

The rapid simultaneous determination of cadmium, lead, copper, and mercury ions is performed by employing a disposable sensor modified with graphene oxide (GO) doped diaminoterthiophene (GO/DTT) for chronocoulometry (CC). The performances of CC with and without pre-deposition in two opposite potential step directions were compared with square wave anodic stripping voltammetry (SWASV) under various conditions. The surface of the GO/DTT modified screen print carbon electrode (SPCE) was characterized by SEM, EDXS, and electrochemical impedance spectroscopy (EIS). Experimental variables that affect the response signal such as the pH, deposition time, type of supporting electrolyte, concentration of DTT, content ratio of GO to DTT, and Nafion content were optimized. Interference effects due to other heavy metal ions were also investigated. The dynamic ranges of SWASV and CC were between 1 ng mL(-1) and 2.5 µg mL(-1) and between 1 ng mL(-1) and 10 µg mL(-1), respectively. The detection limits for Cd(2+), Pb(2+), Cu(2+), Hg(2+) ions were 1.9 ± 0.4 ng mL(-1), 2.8 ± 0.6 ng mL(-1), 0.8 ± 0.2 ng mL(-1), and 2.6 ± 0.9 ng mL(-1) for the CC stripping method; 2.6 ± 0.2 ng mL(-1), 0.5 ± 0.1 ng mL(-1), 1.8 ± 0.3 ng mL(-1), and 3.2 ± 0.3 ng mL(-1) for the CC deposition method; and 7.1 ± 0.9, 1.9 ± 0.3, 0.4 ± 0.1, and 0.7 ± 0.1 ng mL(-1) for SWASV. The reliability of the method for point-of-analysis was evaluated by analyzing a urine standard reference material and some water samples.


Subject(s)
Dielectric Spectroscopy , Graphite/chemistry , Metals, Heavy/analysis , Thiophenes/chemistry , Carbon/chemistry , Electrodes , Humans , Hydrogen-Ion Concentration , Ions/chemistry , Metals, Heavy/urine , Oxides/chemistry
12.
J Orthop Trauma ; 28(7): e164-8, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24343253

ABSTRACT

Displaced femoral head fractures often require open reduction and internal fixation. This article describes 3 cases of displaced large-fragment femoral head fractures (OTA 31-C1.3) that were treated by arthroscopic reduction and internal fixation, which was accomplished using an anterolateral viewing portal, an anterior portal, and an accessory distal anterior working portal. By 3 months postoperatively, all 3 patients had returned to full function. Therefore, we conclude that an arthroscopic approach results in stable fixation and early joint motion, thereby effectively treating displaced femoral head fractures in a minimally invasive manner.


Subject(s)
Femur Head/surgery , Fracture Fixation, Internal/methods , Hip Fractures/surgery , Accidents, Traffic , Adult , Arthroscopy , Female , Femur Head/injuries , Humans , Male , Middle Aged , Recovery of Function
13.
Arthrosc Tech ; 2(3): e221-5, 2013.
Article in English | MEDLINE | ID: mdl-24265988

ABSTRACT

Femoral head fractures associated with acetabular fractures are usually treated by an open method. After a closed reduction of a hip dislocation, open reduction and internal fixation of acetabular fractures usually depend on the type of acetabular fracture. Acetabular fractures associated with femoral head fractures, torn labrums, or osteochondral fractures are often managed simultaneously by a posterior approach. The patient in this study was referred to us because of pain and limited motion after open reduction and internal fixation of an acetabular fracture. Postoperative computed tomography showed remnant osteochondral fragments located in the cotyloid fossa. Using hip arthroscopy, we found a torn labrum and multiple osteochondral fragments in the cotyloid fossa. The avulsed torn labrum was reattached with 2 anchors through the midanterior portal. Osteochondral fragments were curetted and removed. This article reviews the treatment of the torn labrum and multiple fragments after acetabular fracture reduction. The patient recovered immediately and had a satisfactory outcome. We conclude that hip arthroscopy is a valuable option for treating femoral head fracture dislocations associated with acetabular fractures.

14.
Hip Int ; 23(3): 323-9, 2013.
Article in English | MEDLINE | ID: mdl-23559194

ABSTRACT

Reduction for displaced quadrilateral plates in complicated acetabular fractures is difficult and requires wide exposure. The purpose of this study is to assess the usefulness of the additional cable in this complicated fracture and to evaluate the potential danger of compressing the superior gluteal artery and nerve with cable application. We evaluated 31 hips (these included 25 hips with fractures of both columns, two posterior wall and column fractures, three anterior column and posterior hemitransverse fractures, and one high T-shaped fracture) with an average six-year follow-up. Clinical outcomes were evaluated using a modification of the Matta grading system and radiographic arthritic grades. We assessed the postoperative clinical outcomes in relation with other variables such as anatomical reduction, delayed operation, seagull sign, and femoral head injuries. We determined whether the superior gluteal artery and nerve were compressed by cerclage with the help of femoral angiography and EMG. Clinical outcomes were graded as very good to excellent for 18 patients, good for five, fair for three and poor for five. Preoperative femoral head injury (P = 0.011), a seagull sign (P = 0.001), poor reduction (P = 0.015), and delayed reduction (P = 0.05) were found to statistically influence clinical results. We found that there were no injuries to the superior gluteal artery and nerve in spite of using a cable. Cerclage methods can be useful for initial reduction of displaced medial plates in acetabular fractures. These methods reduce operation time and blood loss as compared with other methods.


Subject(s)
Acetabulum/injuries , Bone Plates , Bone Wires , Fracture Fixation, Internal/instrumentation , Hip Fractures/surgery , Acetabulum/diagnostic imaging , Acetabulum/surgery , Adult , Aged , Female , Follow-Up Studies , Hip Fractures/diagnostic imaging , Humans , Male , Middle Aged , Radiography , Retrospective Studies , Treatment Outcome , Young Adult
15.
Biomol Ther (Seoul) ; 20(4): 413-7, 2012 Jul.
Article in English | MEDLINE | ID: mdl-24009829

ABSTRACT

Chrysanthemum indicum Linne is an ancient herbal medicine used to treat bone and muscle deterioration, ocular infl ammation, headache, and anxiety in Korea, China, and Japan. Furthermore, tea derived from Chrysanthemum indicum Linne has been used to treat anxiety by facilitating relaxation and curing insomnia. However, no reports exist on the anxiolytic-like effects of Chrysanthemum indicum Linne water extract (CWE) in mice. In the present study, we investigated the anxiolytic-like effects of CWE using the elevated plus-maze (EPM) test in mice. CWE, at a dose of 500 mg/kg (p.o.), signifi cantly increased the time spent in the open arms of the EPM compared to a vehicle-injected control group. Moreover, the effect of CWE (500 mg/kg) was blocked by bicuculline (a selective GABAA receptor antagonist) and WAY 100635 (a selective 5-HT1A receptor antagonist). Taken together, these fi ndings suggest that the anxiolytic-like effects of CWE might be mediated by the GABAA receptor and the 5-HT1A receptor.

16.
Arch Pharm Res ; 34(2): 269-80, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21380811

ABSTRACT

We have evaluated the possible underlying mechanisms of immobilization stress-induced analgesia (SIA) by behavioral cross-tolerance studies and molecular studies. In the behavioral studies, the cross-tolerance between single or repeated immobilization SIA and the antinociceptive effects of ß-endorphin, morphine, 5-hydroxytryptamine (5-HT), or WIN55,212-2 were assessed. Both single and repeated (×7) immobilization stress significantly attenuated the ß-endorphin and 5-hydroxytryptamine-induced antinociception in the 2nd phase of formalin response, respectively. However, these cross-tolerances disappeared in prolonged repetition of the stress (×14). Neither single nor repeated (×7 and ×14) immobilization stress affected the antinociceptive effect of morphine or WIN55,212-2 at all. We also found that immobilization stress activated hypothalamic proopiomelanocortin (POMC) gene and ß-endorphin expression. Since, it has potent inhibitory activity on the noxious stimuli-induced POMC expression, immobilization stress seemed to dissipate the POMC gene expression process. Meanwhile, we did not find any changes in the opioid receptors' (mu-, delta- and kappa-receptor) and the cannabinoid receptors' (CB1 and CB2) expressions in the midbrain regions elicited by single or repeated stress. These results suggested that a single immobilization stress activates the descending pain modulatory system, which is mainly mediated through endorphinergic and serotonergic activation. Moreover, the tolerance of SIA induced by repeated stresses may be due to the prolonged activation of these systems induced by repeated immobilization.


Subject(s)
Analgesics/pharmacology , Benzoxazines/pharmacology , Morphine/pharmacology , Morpholines/pharmacology , Naphthalenes/pharmacology , Pain/physiopathology , Serotonin/pharmacology , Stress, Physiological , Stress, Psychological , beta-Endorphin/pharmacology , Animals , Disease Models, Animal , Inflammation/physiopathology , Infusions, Intraventricular , Male , Mice , Mice, Inbred ICR , Receptors, Cannabinoid/metabolism , Receptors, Opioid, delta/metabolism , Receptors, Opioid, kappa/metabolism , Receptors, Opioid, mu/metabolism , Restraint, Physical
17.
Arch Pharm Res ; 33(7): 1103-10, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20661721

ABSTRACT

It has been reported that hypobaric hypoxia exposure by high altitude is responsible for neuropsychological impairment. In the present study, we examined an effect of hypobaric hypoxia on the writhing test. The ICR mice were exposed in hypobaric chamber with several altitudes (5000, 10,000 or 20,000 ft) for 1 or 2 h, and then immediately injected intraperitoneally (i.p.) with 1% acetic acid for writhing test. Our results show that both 10,000 ft and 20,000 ft exposure induce antinociceptive effect in writhing test, but 5,000 ft does not. In addition, this antinociceptive effect was abolished by L-NAME (nitric oxide synthase inhibitor) pre-treated intraperitoneally, but not naloxone (non-specific opioid receptor antagonist). Furthermore, we examined that neuronal NOS immunoreactivities in the hypothalamus (paraventricular nucleus and arcuate nucleus) were increased by hypobaric hypoxic exposure (10,000ft). These results suggest that hypobaric hypoxic-induced antinociception may be associated with neuronal NOS IR in the hypothalamus.


Subject(s)
Arcuate Nucleus of Hypothalamus/enzymology , Hypoxia/enzymology , Nitric Oxide Synthase Type I/physiology , Pain Measurement/methods , Paraventricular Hypothalamic Nucleus/enzymology , Animals , Hypoxia/metabolism , Hypoxia/physiopathology , Male , Mice , Mice, Inbred ICR , Random Allocation
18.
Brain Res Bull ; 80(6): 359-70, 2009 Dec 16.
Article in English | MEDLINE | ID: mdl-19723567

ABSTRACT

We studied the effects of supraspinally administered morphine on the expression of the hypothalamic pro-opiomelanocortin (POMC) gene and beta-endorphin. Mice were administered morphine intracerebroventricularly (i.c.v.) either once or 5 times for 5 days (once/day). A single morphine administration significantly increased the hypothalamic POMC gene and beta-endorphin expression at 2h after application in dose-dependent fashion; however, repeated morphine administration had no effect on the hypothalamic POMC gene and beta-endorphin expression. In the immunoblot and immunohistochemical study, the increase of beta-endorphin was observed in the arcuate nucleus of the hypothalamus. Moreover, the expressions of c-Fos, phosphorylated calcium/calmodulin-dependent protein kinase-IIalpha (pCaMK-IIalpha), and phosphorylated cAMP response element-binding protein (pCREB) were increased by a single i.c.v. morphine injection at various time points, but the expressions of phosphorylated extracellular signal-regulated protein kinase1/2 (pERK1/2) and phosphorylated IkappaB (pIkappaB) were not. We also found that the expressions of c-Fos, pCaMKIIalpha, and pCREB were co-localized with the POMC expression. Meanwhile, naloxone as well as muscimol and baclofen significantly attenuated the increases of the POMC gene expression induced by a single morphine administration. Furthermore, the pretreatment of muscimol and baclofen 10 min before morphine injection robustly attenuated the withdrawal behavior induced by a single morphine administration. These results imply that the hypothalamic POMC gene and beta-endorphin expression may play an important role in the development of an acute physical dependency of morphine. In that, GABAergic neurotransmission appear to be involved in the regulation of the hypothalamic POMC gene expression induced by supraspinal morphine administration.


Subject(s)
Hypothalamus/drug effects , Morphine/pharmacology , Narcotics/pharmacology , Pro-Opiomelanocortin/metabolism , Substance Withdrawal Syndrome/metabolism , beta-Endorphin/metabolism , Animals , Arcuate Nucleus of Hypothalamus/drug effects , Arcuate Nucleus of Hypothalamus/metabolism , Baclofen/pharmacology , Dose-Response Relationship, Drug , GABA Agonists/pharmacology , Gene Expression/drug effects , Hypothalamus/metabolism , Male , Mice , Mice, Inbred ICR , Morphine/administration & dosage , Muscimol/pharmacology , Naltrexone/administration & dosage , Naltrexone/pharmacology , Narcotic Antagonists/pharmacology , Narcotics/administration & dosage , Pro-Opiomelanocortin/genetics , Substance Withdrawal Syndrome/genetics , beta-Endorphin/genetics
19.
Arch Pharm Res ; 32(6): 937-43, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19557373

ABSTRACT

Although decursinol, which is one of the coumarins purified from the dried roots of Angelica gigas Nakai, was previously demonstrated to have antinociceptive effects on various mouse pain models such as tail-flick, hot-plate, formalin, writhing, and several cytokine-induced pain tests, the possible involvement of its analgesic effects and non-steroidal anti-inflammatory drugs (NSAIDs) has not been clearly elucidated yet. In this study, we characterized the possible interaction between decursinol and aspirin or acetaminophen in the writhing test. The antinociceptive effects of decursinol were observed at an orally-administered dose of 50 mg/kg but not at 25 or 10 mg/kg. In addition, the analgesic effects of aspirin (ASA) and acetaminophen (APAP) were shown at an orally-administered dose of 200 mg/kg but not at 50 or 100 mg/kg. We examined the effects of decursinol on the ASA or APAP at sub-analgesic doses. Although the co-administration of decursinol and ASA did not show any differences at doses of 10 or 25 mg/kg and 50 or 100 mg/kg, respectively, synergistic effects between decursinol and APAP were observed in the group of decursinol (25 mg/kg) and APAP (100 mg/kg) co-administration. These results indicated that the analgesic effect of decursinol might be involved in supraspinal cyclooxygenase regulation that might be overlapped with APAP-induced analgesic mechanisms rather than systemic or peripheral prostaglandin modulation.


Subject(s)
Analgesics/pharmacology , Benzopyrans/isolation & purification , Benzopyrans/pharmacology , Butyrates/isolation & purification , Butyrates/pharmacology , Pain/drug therapy , Acetaminophen/administration & dosage , Acetaminophen/pharmacology , Acetic Acid , Analgesics/administration & dosage , Angelica , Animals , Aspirin/administration & dosage , Aspirin/pharmacology , Benzopyrans/administration & dosage , Butyrates/administration & dosage , Disease Models, Animal , Drug Synergism , Drug Therapy, Combination , Male , Mice , Mice, Inbred ICR , Pain/chemically induced , Plant Extracts/pharmacology
20.
Arch Pharm Res ; 32(11): 1643-9, 2009 Nov.
Article in English | MEDLINE | ID: mdl-20091280

ABSTRACT

In the present study, the antinociceptive profiles of vanillin were examined in ICR mice. Vanillin administered orally (from 1 to 10 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Duration of antinociceptive action of vanillin maintained at least for 30 min. But, the cumulative response time of nociceptive behaviors induced by a subcutaneous (s.c.) formalin injection, intrathecal (i.t.) substance P (0.7 microg) or glutamate (20 microg) injection was not affected by vanillin. Intraperitoneal (i.p.) pretreatment with yohimbine (alpha2-adrenergic receptor antagonist) or naloxone (opioid receptor antagonist) attenuated antinociceptive effect induced by vanillin in the writhing test. However, phentolamine (alpha1-adrenergic receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by vanillin in the writhing test. Our results suggest that vanillin exerts a selective antinociceptive property in the acetic acid-induced visceral inflammatory pain model. Furthermore, this antinociceptive effect of vanillin may be mediated by alpha2-adrenergic and opioid receptors, but not alpha1-adrenergic and serotonergic receptors.


Subject(s)
Analgesics/pharmacology , Benzaldehydes/pharmacology , Pain/drug therapy , Administration, Oral , Analgesics/administration & dosage , Animals , Benzaldehydes/administration & dosage , Disease Models, Animal , Dose-Response Relationship, Drug , Inflammation/drug therapy , Inflammation/physiopathology , Male , Mice , Mice, Inbred ICR , Pain/physiopathology , Receptors, Adrenergic, alpha-2/metabolism , Receptors, Opioid/metabolism
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