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1.
Article in English | WPRIM | ID: wpr-728095

ABSTRACT

We studied the effects of acetylcholinesterase inhibitors, donepezil and galantamine, and an N-methyl-D-aspartate (NMDA) receptor blocker, memantine, on sleep-wake architecture in rats. Screw electrodes were chronically implanted into the frontal and parietal cortex for the electroencephalography (EEG). EEG was recorded with a bio-potential amplifier for 8 h from 09:30 to 17:30. Vibration was recorded to monitor animal activity with a vibration measuring device. Sleep-wake states such as wake (W), slow-wave sleep (S) and paradoxical or rapid eye movement sleep (P), were scored every 10 sec by an experimenter. We measured mean episode duration and number of episode to determine which factor sleep disturbance was attributed to. Donepezil and memantine showed a significant increase in total W duration and decreases in total S and P duration and delta activity. Memantine showed increases in sleep latency and motor activity. Changes of S and P duration in memantine were attributed from changes of mean episode duration. Galantamine had little effect on sleep architecture. From these results, it is showed that galantamine may be an anti-dementia drug that does not cause sleep disturbances and memantine may be a drug that causes severe sleep disturbance.


Subject(s)
Animals , Cholinesterase Inhibitors , Electrodes , Electroencephalography , Galantamine , Indans , Memantine , Motor Activity , N-Methylaspartate , Organothiophosphorus Compounds , Piperidines , Rats , Sleep, REM , Vibration
2.
Article in Korean | WPRIM | ID: wpr-88569

ABSTRACT

OBJECTIVE : Modafinil, methylphenidate, and caffeine are wakefulness-promoting substances. Previously, it was reported that caffeine-induced wakefulness differs from natural wakefulness in terms of the EEG spectral profiles. In order to evaluate whether wakefulness induced by other psychostimulants differs from both caffeine-induced and natural wakefulness, we examined the effects of the psychostimulants on sleep-wake architecture and EEG spectral profiles. METHODS : Eighteen Sprague-Dawley male rats underwent an EEG/EMG recording session from 10 : 30 to 17 : 30. They received caffeine (7.5, 15, 30 mg/kg i.p.), methylphenidate (1, 2, 5, 10 mg/kg i.p.) or modafinil (5, 10, 25, 50, 100 mg/kg i.p.) at 13 : 30. The number, total duration, and average duration of sleepwake states were obtained. EEG band powers were calculated by spectral analysis. Frequency bands were divided into the following ranges : D1, 1-2.5 Hz ; D2, 2.5-4.5 Hz ; T1, 4.5-7 Hz ; T2, 7-10 Hz ; SI, 10-14 Hz ; B1, 14-22 Hz ; B2, 22-34 Hz ; GA, 34-50 Hz. RESULTS : All three psychostimulants significantly and dose-dependently increased active wake duration and decreased slow-wave sleep. Equipotent doses of caffeine, methylphenidate, and modafinil for increasing active wake and decreasing slow-wave sleep were 7.5 mg/kg, 10 mg/kg, and 100 mg/kg, respectively. In equipotent doses, an increase of active wake duration by caffeine and methylphenidate was attributed to increases of both frequency and average duration of active wake state, whereas increase of active wake duration by modafinil was attributed to increase of average duration of active wake state only. In equipotent doses, caffeine and methylphenidate decreased the power of lower frequency bands (1-22 Hz), whereas modafinil did not. During slow-wave sleep, modafinil and methylphenidate increased the power of lower frequency bands, but caffeine did not. All the psychostimulants increased the power of the GA band, which was more prominent in the frontal cortex than the parietal cortex. CONCLUSION : These results suggest that moda-nil-induced wakefulness differs from caffeine- or methylphenidate-induced wakefulness in terms of EEG spectral profiles and sleep-wake architecture.


Subject(s)
Animals , Benzhydryl Compounds , Caffeine , Electroencephalography , Humans , Male , Methylphenidate , Rats , Wakefulness
3.
Article in Korean | WPRIM | ID: wpr-182287

ABSTRACT

PURPOSE: 99mTc-sestamibi (MIBI) and 99mTc-tetrofosmin have been used as substrates for P-glycoprotein (Pgp) and multidrug resistance associated protein (MRP), which are closely associated with multidrug resistance of the tumors. To understand different handling of radiotracers in cancer cell lines expressing Pgp and MRP, we compared cellular uptakes of 99mTc-MIBI and 99mTc-tetrofosmin. The effects of cyclosporin A (CsA), well-known multidrug resistant reversing agent, on the uptake of both tracers were also compared. MATERIALS AND METHODS: HCT15/CL02 human colorectal cancer cells for Pgp expressing cells, and human non-small cell lung cancer A549 cells for MRP expressing cells, were used for in vitro and in vivo studies. RT-PCR, western blot analysis and immunohistochemistry were used for detection of Pgp and MRP. MDR-reversal effect with CsA was evaluated at different drug concentrations after incubation with MIBI or tetrofosmin. Radioactivities of supernatant and pellet were measured with gamma well counter. Tumoral uptake of the tracers were measured from tumor bearing nude mice treated with or without CsA. RESULTS: RT-PCR, western blot analysis of the cells and immunochemical staining revealed selective expression of Pgp and MRP for HCT15/CL02 and A549 cells, respectively. There were no significant difference in cellular uptakes of both tracers in HCT15/CL02 cells, but MIBI uptake was slightly higher than that of tetrofosmin in A549 cells. Co-incubation with CsA resulted in a increase in cellular uptakes of MIBI and tetrofosmin. Uptake of MIBI or tetrofosmin in HCT15/CL02 cells was increased by 10- and 2.4-fold, and by 7.5 and 6.3-fold in A549 cells, respectively. Percentage increase of MIBI was higher than that of tetrofosmin with CsA for both cells (p< 0.05). In vivo biodistribution study showed that MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively increased by the time, up to 240 min with CsA. But increases in tumoral uptake were not significantly different between MIBI and tetrofosmin for both tumors. CONCLUSION: MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators in vitro, but these differences were not evident in vivo tumoral uptake. Both MIBI and tetrofosmin seem to be suitable tracers for imaging Pgp- and MRP-mediated drug resistance in tumors.


Subject(s)
Animals , Blotting, Western , Carcinoma, Non-Small-Cell Lung , Cell Line , Colorectal Neoplasms , Cyclosporine , Drug Resistance , Drug Resistance, Multiple , Humans , Immunohistochemistry , Mice , Mice, Nude , Multidrug Resistance-Associated Proteins , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Radioactivity , Technetium Tc 99m Sestamibi
4.
Article in Korean | WPRIM | ID: wpr-200012

ABSTRACT

PURPOSE: Adenosine myocardial perfusion SPECT has proven to be useful in the detection of coronary artery disease, in the follow up the success of various therapeutic regimens and in assessing the prognosis of coronary artery disease. The purpose of this study is to define the reproducibility of myocardial perfusion SPECT using adenosine stress testing between two consecutive Tc-99m sestaMIBI (MIBI) SPECT studies in the same subjects. METHODS: Thirty patients suspected of coronary artery disease in stable condition underwent sequential Tc-99m MIBI SPECT studies using intravenous adenosine. Gamma camera, acquisition and processing protocols used for the two tests were identical and no invasive procedures were performed between two tests. Mean interval between two tests were 4.1 days (range: 2-11 days). The left ventricular wall was divided into 18 segments and the degree of myocardial tracer uptake was graded with four-point scoring system by visual analysis. Images were interpretated by two independent nuclear medicine physicians and consensus was taken for final decision, if segmental score was not agreeable. RESULTS: Hemodynamic responses to adenosine were not different between two consecutive studies. There were no serious side effects to stop infusion of adenosine and side effects profile was not different. When myocardial uptake was divided into normal and abnormal uptake, 481 of 540 segments were concordant (agreement rate 89%, Kappa index 0.74). With four-grade scoring system, exact agreement was 81.3% (439 of 540 segments, tau b=0.73). One and two-grade differences were observed in 97 segments (18%) and 4 segments (0.7%) respectively, but three-grade difference was not observed in any segment. Extent and severity scores were not different between two studies. The extent and severity scores of the perfusion defect revealed excellent positive correlation between two test (r value for percentage extent and severity score is 0.982 and 0.965, p< 0.001) CONCLUSION: Hemodynamic responses and side effects profile were not different between two consecutive adenosine stress tests in the same subjects. Adenosine Tc-99m sestaMIBI SPECT is highly reproducible, and could be used to assess temporal changes in myocardial perfusion in individual patients.


Subject(s)
Adenosine , Consensus , Coronary Artery Disease , Coronary Vessels , Diagnosis , Exercise Test , Follow-Up Studies , Gamma Cameras , Hemodynamics , Humans , Nuclear Medicine , Perfusion , Prognosis , Tomography, Emission-Computed, Single-Photon
5.
Article in Korean | WPRIM | ID: wpr-48604

ABSTRACT

PURPOSE: iNOS expression in vascular smooth muscle cells (VSMC) causes the development of septic shock, and multiple organ dysfunction syndrome (MODS). For the inhibition of iNOS expression, glucocorticoids are known to inhibit iNOS expression but immunosuppression decreases its clinical availability. Recently, aspirin was reported to inhibit iNOS expression, but the mechanism and effectiveness are still unclear. In this investigation, on aspirin, several non steroidal antiinflammatory drugs (NSAIDs) were applied to clarify the inhibitory mechanism of iNOS expression and NO production in lipopolysaccharide (LPS) treated VSMCs. METHOD: VSMCs were primarily cultured from rat aorta and confirmed by immunocytochemistry of anti-smooth muscle myosin antibody. LPS, an inducer of iNOS, and NSAIDs, such as aspirin, indomethacin, ketoprofen sodium salicylate and acetaminophen were used. The concentrations of nitrite in culture media following the addition of LPS with a 1-hour pretreatment of NSAIDs were measured by spectrophotometry with griess reaction. Western blot and RT-PCR for iNOS protein and iNOS mRNA, respectively, were performed. RESULT: Acetaminophen had no effect on the inhibition of nitrite production. NSAIDs, especially ketoprofen and sodium salicylate, showed a significant inhibitory effect on nitrite production. In their mechanism, all the NSAIDs in present study inhibited iNOS mRNA and protein expression. CONCLUSION: These results suggest that the inhibitory mechanism on iNOS expression of NSAIDs is due to the inhibition of iNOS mRNA expression and subsequent inhibition of iNOS protein expression.


Subject(s)
Acetaminophen , Animals , Anti-Inflammatory Agents, Non-Steroidal , Aorta , Aspirin , Blotting, Western , Culture Media , Glucocorticoids , Immunohistochemistry , Immunosuppression , Indomethacin , Ketoprofen , Multiple Organ Failure , Muscle, Smooth, Vascular , Myosins , Rats , RNA, Messenger , Shock, Septic , Sodium Salicylate , Spectrophotometry
6.
Article in English | WPRIM | ID: wpr-225225

ABSTRACT

PURPOSE: To evaluate the use of monoclonal antibody (MoAb) as a carrier of the receptor-binding ligand, the receptor mediated uptake into liver and subsequent metabolism of (111) In-labeled galactosylated MoAb-chelator conjugates were investigated and compared with those of (111) In labeled MoAb. MATERIALS AND METHODS: T101 MoAb, IgG2 against human lymphocytic leukemic cell, conjugated with cyclic DTPA dianhydride (DTPA) or 2-p-isothiocyanatobenzyl-6-methyl-DTPA (1B4M) was galactosylated with 2-imino-2-methoxyethyl-1-thio-beta-D-galactose and then radiolabeled with (111) In. Biodistribution and metabolism study was performed with two (111) In-conjugates in mice and rats. RESULTS: (111) In-labeled T101 and its galactosylated conjugates were taken to the liver by the time, mostly within 10 min. However DTPA conjugate was retained longer in the liver than the 1B4M conjugate (55% vs 20% of injected dose at 44 hr). During this time, the radiometabolite of DTPA conjugate was excreted similarly into urine (24%) and feces (17%). The radiometabolite of 1B4M was excreted primarily into feces (68%) rather than urine (8%). Size exclusion HPLC analysis of the bile and supernatant of liver homogenate showed two peaks, the first (35%) with the retention time (Rt) identical to IgG and the second (65%) with Rt similar to free 111In at 3 hr post-injection for the 1B4M conjugate, indicating that the metabolite is rapidly excreted through the biliary system. In contrast to DTPA conjugate, the small (111) In-DTPA-like metabolite was the major radioindium component (90%) in the liver homogenate as early as 3 hour post-injection, but the cumulative radioindium activity in feces was only 17% at 44 hour, indicating that the metabolite from DTPA conjugate does not clear readily through the biliary tract. CONCLUSION: The galactosylation of the MoAb conjugates resulted in higher hepatocyte uptake and enhanced metabolism, compared to those without galactosylation. Metabolism of the MoAb-conjugates is different between compounds radiolabled with different chelators due to different characteristics of radiometabolites generated in the liver.


Subject(s)
Animals , Bile , Biliary Tract , Chelating Agents , Chromatography, High Pressure Liquid , Feces , Hepatocytes , Humans , Immunoglobulin G , Liver , Metabolism , Mice , Pentetic Acid , Rats
7.
Article in English | WPRIM | ID: wpr-103639

ABSTRACT

The Pogo mouse is an autosomal recessive ataxic mutant that arose spontaneously in the inbred KJR/MsKist strain derived originally from Korean wild mice. The ataxic phenotype is characterized by difficulty in maintaining posture and side to side stability, faulty coordination between limbs and trunk, and the consequent inability to walk straight. In the present study, the cerebellar concentrations of glutamate and GABA were analyzed, since glutamate is a most prevalent excitatory neurotransmitter whereas gammar-aminobutyric acid (GABA) is one of the most abundant inhibitory neurotransmitters, which may be the main neurotransmitters related with the ataxia and epilepsy. The concentration of glutamate of cerebellum decreased significantly in ataxic mutant Pogo mouse compared to those of control mouse. However, GABA concentration was not decrease. These results suggested that the decrease in glutamate concentration may contribute to ataxia in mutant Pogo mouse.


Subject(s)
Animals , S100 Calcium Binding Protein G/metabolism , Cerebellum/metabolism , Gait Ataxia/metabolism , Glutamic Acid/metabolism , Immunohistochemistry , Mice , Mice, Mutant Strains , gamma-Aminobutyric Acid/metabolism
9.
Article in Korean | WPRIM | ID: wpr-41071

ABSTRACT

PURPOSE: This study was conducted to evaluate the expressions of the mdr1 gene and the MRP gene in tumor and adjacent normal gastric tissues. MATERIALS AND METHODS: The specimens were obtained from 53 patients who had gastric cancer. None of these patients had received any kind of preoperative chemotherapy. The reverse transcription polymerase chain reaction and immunohistochemical stain were used to check the level of expressions of mRNAs and their associated proteins. RESULTS: Highly positive expressions of mdr1 mRNA, MRP mRNA, p-glycoprotein, and MRP (multidrug resistance associated protein) were observed in the tumor and the adjacent normal tissues. Most tumor tissues coexpressed mdr1 mRNA and MRP mRNA significantly (p<0.001). The expression of these genes in the tumor was much stronger than in the normal counterpart tissues. The expression of the p-glycoprotein was correlated only with the pathological stage (p<0.05). MRP expression was correlated with lymph node metastasis (p<0.05). CONCLUSION: Normal gastric tissue showed strong physiologic expressions of the mdr1 and MRP genes. Overexpressions of these genes were observed in gastric cancer tissue. The presence of multidrug resistance should be considered when planning anticancer chemotherapy for treating gastric cancer.


Subject(s)
Drug Resistance, Multiple , Drug Therapy , Humans , Lymph Nodes , Mucous Membrane , Multidrug Resistance-Associated Proteins , Neoplasm Metastasis , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Polymerase Chain Reaction , Reverse Transcription , RNA, Messenger , Stomach Neoplasms
10.
Article in English | WPRIM | ID: wpr-727418

ABSTRACT

This study was undertaken to investigate the mechanism of lipopolysaccharide (LPS) and nitric oxide (NO) as a regulator of vascular smooth muscle cell (VSMC) proliferation. VSMC was primarily cultured from rat aorta and confirmed by the immunocytochemistry with anti-smooth muscle myosin antibody. The number of viable VSMCs were counted, and lactate dehydrogenase (LDH) activity was measured to assess the degree of cell death. Concentrations of nitrite in the culture medium were measured as an indicator of NO production. LPS was introduced into the medium to induce the inducible nitric oxide synthase (iNOS) in VSMC, and Western blot for iNOS protein and RT-PCR for iNOS mRNA were performed to confirm the presence of iNOS. Inhibitors of iNOS and soluble guanylate cyclase (sGC), sodium nitroprusside (SNP) and L-arginine were employed to observe the action of LPS on the iNOS-NO-cGMP signalling pathway. LPS and SNP decreased number of VSMCs and increased the nitrite concentration in the culture medium, but there was no significant change in LDH activity. A cell permeable cGMP derivative, 8-Bromo-cGMP, decreased the number of VSMCs with no significant change in LDH activity. L-arginine, an NO substrate, alone tended to reduce cell count without affecting nitrite concentration or LDH level. Aminoguanidine, an iNOS specific inhibitor, inhibited LPS-induced reduction of cell numbers and reduced the nitrite concentration in the culture medium. LY 83583, a guanylate cyclase inhibitor, suppressed the inhibitory actions of LPS and SNP on VSMC proliferation. LPS increased amounts of iNOS protein and iNOS mRNA in a concentration-dependent manner. These results suggest that LPS inhibits the VSMC proliferation via production of NO by inducing iNOS gene expression. The cGMP which is produced by subsequent activation of guanylate cyclase would be a major mediator in the inhibitory action of iNOS-NO signalling on VSMC proliferation.


Subject(s)
Animals , Aorta , Arginine , Blotting, Western , Cell Count , Cell Death , Gene Expression , Guanylate Cyclase , Immunohistochemistry , L-Lactate Dehydrogenase , Muscle, Smooth, Vascular , Myosins , Nitric Oxide , Nitric Oxide Synthase Type II , Nitroprusside , Rats , RNA, Messenger
11.
Article in Korean | WPRIM | ID: wpr-84488

ABSTRACT

PURPOSE: Thallium behaves similarly to potassium in vivo. Potassium channel opener (K-opener) opens ATP-sensitive K+/-channel located at cell membrane, resulting in potassium efflux from cytosol. We have previously reported that K-opener can alter biokinetics of Tl-201 in cultured cells and in vivo. Malignant tumor cells have high Na-K ATPase activity due to increased metabolic activities and dedifferentiation, and differential delineation of malignant tumor can be possible with Tl-201 imaging. K-opener may affect tumoral uptake of Tl-201 in vivo. To investigate the effects of pinacidil (one of the potent K-openers) on the localization of the tumor with Tl-201 chloride, we evaluated the changes in biodistribution of Tl-201 with pinacidil treatment in tumor-bearing mice. MATERAL AND METHODS: Balb/c mice received subcutaneous implantation of murine breast cancer cells in the thigh and were used for biodistribution study 3 weeks later. 100 microgram of pinacidil dissolved in 200 microliter DMSO/PBS solution was injected intravenously via tail vein at 10 min after 185 KBq (5 microcurie) Tl-201 injection. Percentage organ uptake and whole body retention ratio of Tl-201 were measured at various periods after injection, and values were compared between control and pinacidil-treated mice. RESULTS: Pinacidil treatment resulted in mild decrease in blood levels of Tl-201, but renal uptakes were markedly decreased at 30-min, 1- and 2-hour, compared to control group. Hepatic, intestinal and muscular uptake were not different. Absolute percentage uptake and tumor to blood ratios of Tl-201 were lower in pinacidil treated mice than in the control group at all time points measured. Whole body retention ratio of Tl-201 was lower in pinacidil treated mice (58+/-4%), than in the control group (67+/-3%) at 24 hours after with injection of 100 microgram pinacidil. CONCLUSION: K-opener did not enhance, but rather decreased absolute tumoral uptake and tumor-to-blood ratios of Tl-201. Decreased whole body retention ratio and renal uptake were observed with pinacidil treatment in tumor-bearing mice.


Subject(s)
Adenosine Triphosphatases , Animals , Breast Neoplasms , Cell Membrane , Cells, Cultured , Cytosol , Mice , Pinacidil , Potassium , Potassium Channels , Thallium , Thigh , Veins
12.
Article in Korean | WPRIM | ID: wpr-8978

ABSTRACT

Renin-Angiotensin system (RAS) has been suggested as one of important factors in stress-related responses, and also suggested to be a pro-oxidant in mammals. Studies about antioxidant activity changes in brain by systemic administration of angiotensin II (Ang II) may be valuable data in the clarification of pathogenesis and development of treatment modalities for the psychologic stress-induced somatic disease, such as stress-induced hypertension. We examined, therefore, antioxidant defense changes in the brain induced by Ang II. Antioxidant enzyme activities including superoxide dismutase (SOD), contents of glutathione (GSH), and lipoperoxidation (LPO) were measured in the dissected specimens of the brain regions after subcutaneous injection of human Ang II. In this study, peripheral administration of Ang II decreased LPO in the cerebral cortex, hippocampus, striatum, hypothalamus of Sprague-Dawley rats. Ang II increased activities of SOD, glutathione peroxidase, and glutathione reductase in the hippocampus and striatum. Borderline-hypertensive rats (BHR), a well-known animal model for stress-induced hypertension, showed some differences in the Ang II-induced antioxidant activity changes, comparing with SD rats. In the BHR, peripheral administration of Ang II significantly decreased the activities of antioxidant enzymes and contents of GSH, increased LPO contents in the various regions of brain. These results suggested that oxidative stress on the brain due to Ang II may be greater in the BHR than SDs, and RAS may be one of important pathophysiologic factors for stress-induced hypertension in BHR.


Subject(s)
Angiotensin II , Animals , Brain , Cerebral Cortex , Glutathione , Glutathione Peroxidase , Glutathione Reductase , Hippocampus , Humans , Hypertension , Hypothalamus , Injections, Subcutaneous , Mammals , Models, Animal , Oxidative Stress , Rats , Rats, Sprague-Dawley , Renin-Angiotensin System , Superoxide Dismutase
13.
Article in English | WPRIM | ID: wpr-728140

ABSTRACT

This study was undertaken to investigate an involvement of nitroxergic innervation in gastric smooth muscle of rat. Isometric tension study, the measurement of single cell length, NADPH diaphorase stain of smooth muscle layers and neuronal nitric oxide synthase (nNOS) western blotting were performed. Sodium nitroprusside (SNP), a nitric oxide donor, relaxed the muscle strips precontracted by acetylcholine (ACh) in a concentration-dependent manner. Pretreatment of L-arginine decreased the contraction induced by electric field stimulation (EFS). Pretreatment of NG-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, increased the EFS-induced contractions. LY 83583, a guanylate cyclase (GC) inhibitor, reversed the inhibitory actions of L-arginine on the muscle contractions. The effects of L-Arginine, L-NAME and LY 83583 on ACh-induced contractions were not significant. L-arginine reduced the EFS-induced contraction in circular muscle, whereas L-NAME enhanced the EFS-induced contraction in longitudinal strips. By EFS, the phasic contractions appeared approximately 20~25 seconds later. L-NAME significantly shortened the delay time to about 2~3 seconds. In single cell study, ACh contracted gastric smooth muscle cells, SNP relaxed the cells, and the latter also inhibited the ACh-induced contraction. LY 83583 enhanced the ACh-induced contraction and antagonized SNP-induced relaxation. NADPH diaphorase activity was assessed by a histochemistry, nitroblue tetrazolium (NTB) staining. Positive staining was observed in both circular and longitudinal muscle layers. L-arginine increased the staining, while L-NAME decreased the staining. Western blotting for nNOS proved the presence of nNOS in rat gastric smooth muscle. EFS and additional Ca2+ increased nNOS protein expression. These results suggest that in rat stomach, both circular and longitudinal muscle layers are innervated with nitroxergic nerves which relax the gastric smooth muscle via NO-cGMP pathway.


Subject(s)
Acetylcholine , Animals , Arginine , Blotting, Western , Guanylate Cyclase , Humans , Muscle Contraction , Muscle, Smooth , Myocytes, Smooth Muscle , NADPH Dehydrogenase , NG-Nitroarginine Methyl Ester , Nitric Oxide , Nitric Oxide Synthase Type I , Nitroblue Tetrazolium , Nitroprusside , Rats , Relaxation , Stomach , Tissue Donors
14.
Article in Korean | WPRIM | ID: wpr-198832

ABSTRACT

OBJECTIVES: Behavioral stress has been suggested as one of important factors which destruct the physiologic antioxidant system. Studies about antioxidant activity changes in brain by repeated stress may be valuable data in the clarification of pathogenesis and development of treatment modalities for the psychologic stress-induced somatic disease. METHODS: We examined, therefore, immobilization stress -induced antioxidant defense chages in the rat brain. Superoxide dismutase, glutathione peroxidase and, glutathione reductase activities were measured in the dissected specimens of the cerebral cortex, hippocampus, striatum, brain stem, cerebellum and hypothalamus of adult male Sprague-Dawley rats subjected to 2 hour immobilization stress for 14 consecutive days. RESULTS: In this study, immobilization inhibited glutathione peroxidase and glutathione reductase activities in striatum and hypothalamus than any other brain regions. CONCLUSION: These results suggest that striatum and hypothalmus are subject to strong pro-oxidant impacts arising at the repeated immobilization stress.


Subject(s)
Adult , Animals , Brain Stem , Brain , Cerebellum , Cerebral Cortex , Glutathione Peroxidase , Glutathione Reductase , Hippocampus , Humans , Hypothalamus , Immobilization , Male , Rats , Rats, Sprague-Dawley , Superoxide Dismutase
15.
Article in English | WPRIM | ID: wpr-727851

ABSTRACT

This study is to investigate the mechanism of inhibitory effect of imipramine on the calcium utilization in single cells isolated from canine detrusor. 2 mm thick smooth muscle chops were incubated in 0.12% collagenase solution at 36degreeC, and aerated with 95% O2/5% CO2, and then cell suspension was examined Acetylcholine (ACh) evoked a concentration-dependent contraction of the isolated detrusor cells in normal physiologic salt solution (PSS), and the ACh-induced contraction was significantly inhibited by imipramine. In Ca2+-free PSS, ACh-induced contraction was less than those in normal PSS and it was not affected by the pretreatment with imipramine. Ca2+-induced contraction in Ca2+-free PSS was supressed by imipramine, but addition of A 23187, a calcium ionophore, overcomed the inhibitory effect of imipramine. High potassium-depolarization (40 mM KCl) evoked cell contraction, which was inhibited by imipramine. Caffeine, a releasing agent of the stored Ca2+ from sarcoplasmic reticulum, evoked a contraction of the cells that was not blocked by the pretreatment with imipramine. These results suggest that imipramine inhibits the influx of calcium in the detrusor cells through both the receptor-operated- and voltage-gated-calcium channels, but does not affect the release of calcium from intracellular storage site.


Subject(s)
Acetylcholine , Caffeine , Calcimycin , Calcium , Collagenases , Imipramine , Muscle, Smooth , Sarcoplasmic Reticulum
16.
Article in Korean | WPRIM | ID: wpr-68427

ABSTRACT

Primary small cell carcinoma of the salivary gland is a rare neoplasm that accounts for approximately 1.8% of all primary major salivary gland malignancies. Because of its rarity, it is difficult to diagnose small cell carcinoma of the parotid gland by fine needle aspiration cytology(FNAC). We experienced a case of primary small cell carcinoma of the parotid gland in a 72-year-old woman who presented with two palpable masses of the left infraauricular and ocular regions of two to three month's duration, respectively. Aspirate smears from the left infraauricular area were highly cellular on necrotic and lymphocytic background and showed individually dispersed cells or three-dimensional clusters of small cells. The tumor cells were round to oval with a very high nucleocytoplasmic ratio. Nuclei were about two times the size of lymphocytes and had uniformly dispersed but hyperchromatic to pyknotic chromatin. Nucleoli were occasionally visible but were generally inconspicuous. Numerous mitotic figures were detected. The clusters of these small tumor cells exhibited angular nuclear molding, irregular nuclear outlines, and occasionally rosette like arrangement. The tumor was confirmed by histology and immunohistochemistry.


Subject(s)
Aged , Animals , Benzodiazepines , Biopsy, Fine-Needle , Carcinoma, Small Cell , Chromatin , Female , Fungi , Humans , Immobilization , Immunohistochemistry , Lymphocytes , Parotid Gland , Rats , Receptors, GABA-A , Salivary Glands , Thyroid Gland
17.
Article in Korean | WPRIM | ID: wpr-197100

ABSTRACT

BACKGROUND: Anticholinesterase drug inhibits acetylcholinesterase(AChE), induce accumulation of acetylcholine(ACh) near cholinergic receptors and cholinergic stimulation. This experiment was performed to study the effects of anticholinesterase drugs on gastric motility and the effect of ethanal on anticholinesterase drug-induced motility change. MATERIALS AND METHODS: After excision of stomach, 2x10mm circular musele strips were made, which were then fixed to the isolated muscle chamber. An isometric tension transducer was used to measure the contraction change of the gastric smooth muscle strips after drug addition. RESULTS: Fenthion, and irreversible anticholinesterase drug, increased ACh induced contraction of gastric smooth muscle strips and PAM, a cholinesterase activator, antagnized this action. Physostigmine, a reversible anticholinesterase drug, also increased the ACh induced contraction. The gastric motility was decreased by PAM. Ethanol, which is known to induce smooth muscle relaxation, inhibited the increase of contraction by fenthion. CONCLUSION: These results indicate that irreversible and reversible anticholinesterase drugs increase gastric motility and antagonized by cholinesterase activating drugs. And when exposed to both ethanol and anticholinesterase drug, gastric motility was decreased by the smooth muscle relaxation effect by ethanal.


Subject(s)
Acetaldehyde , Cholinesterase Inhibitors , Cholinesterases , Ethanol , Fenthion , Muscle, Smooth , Physostigmine , Receptors, Cholinergic , Relaxation , Stomach , Transducers
18.
Article in Korean | WPRIM | ID: wpr-197099

ABSTRACT

BACKGROUND: In korea the agricultural community widely uses organophosphorous, and organophosphorous poisonings are increasing every year. We compared change in activity of acetylcholinesterase and pseudocholinesterase by organophosphorous and by the interaction of ethanol and organophosphorous. We also compared the effect of reversible anticholinesterase drugs, physostigmine and neostigmine. The object of this study is to investigate the effects of several anticholinesterase drugs and on how ethanol influences the activity of cholinesterase. MATERIALS AND METHODS: Fifteen male university students were randomly selected, and blood samples were taken from the antecubital vein. The acetylcholinesterase in the RBC and the pseudocholinesterase in the serum were extracted and separated. The enzyme activity change was measured by the electrometric method. After adding acetylcholine, the pH change was measured with a pH meter. RESULTS AND CONCLUSION: Our results indicated that reversible anticholinesterase drugs decreased the cholinesterase activity more efficiently than organophosphorous. The acetyl cholinesterase and pseudocholinosterase activity were decreased by ethanol. When ethanol was added, oxime a cholinesterase activator, increased acetylcholinesterase activity but dose not increased pseudocholinesterase activity.


Subject(s)
Acetylcholine , Acetylcholinesterase , Cholinesterase Inhibitors , Cholinesterases , Ethanol , Humans , Hydrogen-Ion Concentration , Korea , Male , Neostigmine , Physostigmine , Poisoning , Butyrylcholinesterase , Veins
19.
Article in Korean | WPRIM | ID: wpr-150888

ABSTRACT

Benzodiazepines(BZDs) are among the widely prescribed drugs in the world. They are potent anxiolytic, antiepileptic, hypnotic, and muscle relaxing agents. There is an emerging model of the role of several neural systems in anxiety and their relation to the mechanism of action of BZDs. It has been postulated that BZD drugs exert their anxiolytic action by regulating GABAergic transmission in limbic areas such as the amygdala, in the posterior hypothalamus, and in the raphe nuclei. The involvement of the amygdala in the behaviors triggered by fear and stress has been suggested by many previous studies. In this review, reports about regulatory effects of endogenous BZD receptor ligands on the perception of anxiety and memory consolidation were summerized. These findings further support the contention that BZD receptor ligands modulate memory consolidation of averse learning tasks by influencing the level of stress and/or anxiety that accompanies a learning experience. The findings suggest that the decrease in the limbic levels of BZD-like molecules seen after the various behavioral procedures represent a general response to stress and/or anxiety, since it occurs in proportion to the level of stress and/or anxiety that accompany these tasks. In addition, these findings further support the hypothesis that the GABAA/BZD receptor complex in limbic structures plays a pivotal role in the stress and anxiety.


Subject(s)
Amygdala , Anxiety , Brain , Hypothalamus, Posterior , Learning , Ligands , Memory , Raphe Nuclei , Receptors, GABA-A
20.
Article in Korean | WPRIM | ID: wpr-16810

ABSTRACT

PURPOSE: This study was aimed to investigate the modulatory effect of ammonium carbonate on the GABAA receptor. METHODS: The effects of ammonium carbonate on the binding of radioligands to components of the GABAA receptor complex were observed. RESULTS: [3H]Flunitrazepam binding to the benzodiazepine receptor was enhanced by ammonium (1mM) ammonia concentrations. This increase in GABAergic neurotransmission is consistent with the clinical picture of lethargy, ataxia and cognitive deficits associated with liver failure and congenital hyperammonemia.


Subject(s)
Ammonia , Ammonium Compounds , Ataxia , Carbon , gamma-Aminobutyric Acid , Hyperammonemia , Lethargy , Liver Failure , Muscimol , Neurons , Receptors, GABA , Receptors, GABA-A , Synaptic Transmission
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