• Journal of Pharmaceutical Investigation
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• v.32 no.1
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• pp.47-54
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• 2002

Cimetropium bromide, a quaternary ammonium compound which is chemically related to scopolamine, exhibits its antispasmodic activity by competing with acetylcholine for the muscarinic receptors of the smooth muscle of gastrointestinal tract. The drug has been used for the treatment of various disorders involving spasms of the musculature of the gastrointestinal, biliary and genitourinary tracts. The purpose of the present study was to evaluate the bioequivalence of two cimetropium bromide tablets, $Algiron^{TM}$ (Boehringer Ingelheim Korea Ltd.) and $Alpit^{TM}$ (Hana Pharmaceutical Co., Ltd.), according to the prior and revised guidelines of Korea Food and Drug Administration (KFDA). The cimetropium bromide release from the two cimetropium bromide tablets in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty normal male volunteers, $25.25{\pm}2.10$ years in age and $65.76{\pm}6.39$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After three tablets containing 50 mg of cimetropium bromide per tablet were orally administered, blood was taken at predetermined time intervals and the concentrations of cimetropium bromide in serum were determined using HPLC method with UV detector. The dissolution profiles of two cimetropium bromide tablets were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using non-transformed and logarithmically transformed $AUC_t\;and\;C_{max}$. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets based on the $Algiron^{TM}$ were 2.19%, -5.97% and 3.49%, respectively. Minimum detectable differences $({\Delta})\;at \;{\alpha}=0.05\;and\;1-{\beta}=0.8$ were less than 20% (e.g., 13.71 %, 19.05% and 15.11% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively). The powers $(1-{\beta})\;at\;{\alpha}=0.05,\;{\Delta}=0.2\;for\;AUC_t$, $C_{max}\;and\;T_{max}$ were 97.79%, 83.22% and 95.60%, respectively. The 90% confidence intervals were within ${\pm}20%$ (e.g., $-5.84{\sim}10.21,\;-17.11{\sim}5.18\;and\;-5.35{\sim}12.33\;for\;AUC_t,\;C_{max}\;and\;T_{max}$, respectively). There were no sequence effect between two tablets in logarithmically transformed $AUC_t\;and\;C_{max}$. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) (e.g., $0.94{\sim}1.10\;and\;0.85{\sim}1.05\;for\;AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of prior and revised KFDA guideline for bioequivalence, indicating that $Alpit^{TM}$ tablet is bioequivalent to $Algiron^{TM}$ tablet.

• Applied Microscopy
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• v.15 no.2
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• pp.111-129
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• 1985

The morphology and histology of the gastrointestinal mucosa of the mole, Talpa micrura coreana (Thomas), were studied using light and scanning electron microscopes. Tissue specimens were taken from body and pyloric portions of the stomach, and from the initial, proximal, middle, distal and terminal portions of the intestine. For light microscopy, tissue blocks were fixed in 10% buffered neutral formalin, embedded in paraffin wax, and sectioned at a thickness of $5{\mu}m$. These sections were stained with hematoxylin-eosin. For scanning electron microscopy, tissue blocks were fixed in 1% glutaraldehyde-1.5% paraformaldehyde, and postfixed in 1% osmium tetroxide, dehydrated in graded alcohol, transferred to isoamylacetate and dried by the critical point drier(Polaron E 3000). Subsequently, specimens were coated with gold and observed with a JSM-35C scanning electron microscope. The results were as follows: The mucous membrane of the body portion of the stomach had numerous irregular folds and the pyloric mucosa formed the strawberry-shaped folds, and general histological structures of each portion were similar to those of man. The intestine could not be differentiated macroscopically and microscopically into small and large intestines. There was no cecum, appendix, taenia coli, haustra coli or appendices epiploicae. In the initial portion (4 mm long), conical or tongue-shaped villi with the height of $143.3{\pm}10.7{\mu}m$ were present, and large mucous glands were seen in the submucosa. In the proximal, middle and distal portions, wavy folds composed of the epithelium and lamina propria were densely and transversely arranged, and their heights were $440.4{\pm}45.5{\mu}m,\;454.4{\pm}19.9{\mu}m\;and\;205.2{\pm}33.5{\mu}m$, respectively. The mucosa of the terminal portion (3 cm long) formed several longitudinal folds, and the intestinal glands were directly opened on the smooth surface of the folds. Aggregated lymphoid follicles were observed in the major portions of the intestine except the initial and terminal portions. There was no circular or semilunar fold throughout the intestine.

• Applied Microscopy
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• v.23 no.2
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• pp.53-77
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• 1993

In this study, an attempt was made to investigate the probable organelles participating in the secretion of biligrafin. The animals (ICR male mice, 25-30gm) were divided into normal control and 6 biligrafin injected groups to which 30% biligrafin (0.006ml/gm b.w.) were injected at 10, 20, 40, 80, 160 and 320 min prior to the sampling. The mice of each group were perfused through the heart with ice-cold 2.5% glutaraldehyde buffered with 0.1M Na-cacodylate (pH. 7.4) under the Na-pentobarbital (Nembtal 0.0015mg/gm b.w.) anesthesia and liver tissues were taken from each group. Some specimens were immersed 1 hr in the same solution used in the perfusion. After an overnight rinse in 0.1M Na-cacodylate buffer containing 10% DMSO and 7.6% sucrose, $75{\mu}m$ fronzen sections were made for cytochemical study. The sections were incubated in thiamin pyrophosphatase (TPPase) and inosine diphosphatase (ID Pase) media for 70 min at $37^{\circ}C$ respectively and acid phosphatase (AcPase) medium for 40 min at $37^{\circ}C$. They were postfixed in 1 % $OsO_4$ for 1 hr. The other specimens were immersed for 8 hrs in the fixative consisting of 2.5% glutaraldehyde and 3.0% paraformaldehyde buffered with Na-cacodylate (pH. 7.4). All of the osmificated specimens were processed for electron microscopy. In both normal and biligrafin injected groups, endoplasmic reticulum (ER), vacuoles, Golgi apparatus and lysosomes were seen in the vicinity of bile canaliculus. In the biligrafin injected groups, however, the Golgi apparatus appeared to be decreased and ER and vacuoles were dilated and increased. The rough endoplasmic reticulum (RER) having a few attached ribosomes appeared to be the round saccule, especially at 20 min after biligrafin injection. Smooth endoplasmic reticulum (SER) seemed to be formed by the detachment of ribosomes at the cisternal end of RER. The cistern of SER showed saccules which probably budded off to form the vacuole. The vacuoles were devoid of visible centents. This finding seemed to be in agreement with the biochemical property of the bile constituents. The fusion between the vacuoles and bile canaliculus were frequently seen in the groups injected with biligrafin. The lysosome did not show any changes in the biligrafin injected groups. Accumulation of some material and lipid droplets were seen at the 40 and 80 min after biligrafin injection, especially at the latter. At 160 and 320 min after biligrafin injections, however, they were decreased successively while the RER stack, free ribosomes and polysomes were increased. Although the reactive products of TPPase and IDPase were observed in the ER saccules and vesicles of the normal control and biligrafin injected groups, the fusion between the bile canaliculus and saccules or vesicles could easily be seen in the latter. The AcPase activity, however, was observed in the cistern at the maturing face of Golgi apparatus and lysosomes in both normal and biligrafin groups. The results suggest that the biligrafin is excreted via the vesicles, vacuoles or sacoules probably derived from the SER without the participation of Golgi apparatus and lysosomes, and the excess amount of material is stored as inclusions during the repairing of the organelles being overactive.

• Applied Microscopy
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• v.39 no.3
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• pp.267-276
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• 2009

A SEM study on morphology of lingual papillae of Korean long-fingered bat (Miniopterus schreibersi fuliginosus) and Savi's Pipistrelle (Pipistrellus savii) was conducted. Three kinds of lingual papillae were observed: filiform, fungiform, circumvallate papillae. Filiform papillae were divided into two types; the type 1 had a group of needle-like projections, and was distributed throughout the front half of the tongue; the type 2 had a smooth and thick body, and was found in rear half of the tongue. 35 to 45 fungiform papillae were found on the dorsal surface of the tongue in both species. They were observed along the lateral margins and were also found on front and rear end part of the tongue. There were two to three noticeably large fungiform papillae arranged in a straight line on the region between lingual prominence and circumvallate papillae. There were two circumvallate papillae close to the rear end of the tongue. They were large and round, each having two layers of pads. The overall morphology of lingual papillae of M. schreibersi fuliginosus and P. savii was found to be similar with other Chiroptera. However, few but noticeable differences were found among the filiform papillae and fungiform papillae. Type 2 filiform papillae differed in that bifid and trifid configuration were found in M. schreibersi fulginosus unlike in P. savii. In addition, numbers of large fungiform papillae located in the center of posterior region of the tongue were different with M. schreibersi have three while P. savii having only two.

• The Korean Journal of Cytopathology
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• v.4 no.1
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• pp.45-51
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• 1993

A 30-year-old woman who was diagnosed as peripheral neuroblastoma by fine needle aspiration of a soft mass of the right upper arm is described. She presented a slowly growing, soft mass of the right upper arm for 1 month. The right humerus revealed no abnormal finding on X-ray. Ultrasonogram of the right upper arm revealed a well demarcated, smooth marginated solid mass without invasion of adjacent structures. Fine needle aspiration was done under the impression of soft tissue tumor with undetermined biologic behavior. The aspirates were highly cellular and the tumor cells were dispersed both singly and in clusters of varying size. The clusters occasionally showed a central capillary core and rosette-like structures. The tumor cells were small in size and had a small to medium amount of cytoplasm. Some of them revealed slender cytoplasmic processes. The nuclei showed distinct nuclear membranes, finely clumped chromatin and small conspicuous nucleoli. Cellular pleomorphism or mitotic figure was not definite. These cytologic findings were interpreted as a malignant, non-lymphomatous small round cell tumor, most likely representing peripheral neuroblastoma or Ewing's sarcoma. Final diagnosis was confirmed by simple excision as peripheral neuroblastoma.

• Microbiology and Biotechnology Letters
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• v.43 no.4
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• pp.314-321
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• 2015

Agar-hydrolyzing bacteria were isolated from the coastal sea water of Jeju Island. One isolate, designated as S4, was selected for further study. The S4 cells were Gram-negative and rod-shaped with smooth beige surfaces and single polar flagellum. Cells were grown at $15-42^{\circ}C$, 0.5-5% (w/v) NaCl, between pH 6.0 and 9.0, and in media containing 0.5-5% (w/v) NaCl. The G+C content was 49.93 mol%. The major fatty acids (>15%) were $C_{18:1}{\omega}7c$, $C_{16:0}$ and Summed feature 3 (comprising $C_{16:1}{\omega}7c/iso-C_{15:0}$ 2-OH). Based on 16S rRNA sequencing and biochemical and chemotaxonomic characteristics, the strain was designated as Vibrio sp. S4. In liquid culture supplemented with 0.1% agar the cell density and agarase activity reached a maximum level in 72 h, while agarase activity in the culture without agar was negligible, implying agarose expression is induced by agar. The optimum pH and temperature for the extracellular crude agarase of S4 were 7.0 and $45^{\circ}C$, respectively. However, it also exhibited 98.6% and 87.6% at $40^{\circ}C$ and $50^{\circ}C$, respectively, of the maximum activity seen at $45^{\circ}C$. The crude agarase hydrolyzed agarose into (neo)agarotetraose and (neo)agarohexaose.

• Journal of Korean society of Dental Hygiene
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• v.5 no.2
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• pp.279-296
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• 2005

The purpose of this study was to examine what types of experiences dental hygienists underwent with patients who were unapproachable in an effort to find out the latter group's needs and expectations, explore how to treat them of different personality type, and provide better dental services in response to their needs. To attain the purpose, Q-methodology was employed, which made a subjective and systematic assessment of human subjectivity. There were three types of subjectivity among dental hygienists in conjunction with their experiences with patients who were hard to please. Each group whose subjectivity was different also had a different preference for patients, which was not exclusive to one another but unique. Type 1 was "avoiding patients who showed off". Dental hygienists of this type found it unpleasant to treat patients who boasted of their background, position or relations with the head of hospital and wanted to be given special treatment. They avoided those patients, since giving special treatment to specific patients was likely to do damage to others. They believed that better medical services could be provided through mutual concern and good manners between medical personnels and patients. Dental hygienists of type 2 considered it hard to treat patients who were picky and looked at treatment or its outcome negatively. Those who had to be separated from others on account of possible cross-infection or who called for special decontamination methods of dental instruments were also difficult to deal with. Dental hygienists of this type could be said to "avoid picky patients", as they preferred to fare with patients by offering good, faithful treatment rather than by giving special treatment. Dental hygienists of type 3 believed that smooth and successful treatment hinged on mutual trust, confidence and collaboration between medical personnels and patients. According to them, patients who choose a specific hospital or a particular medical team at their own option have to cooperate if necessary, listen carefully to medical personnels and treat them without any hostility or bias. Therefore, they could be said to "avoid patients who were not cooperative".

• Journal of Bio-Environment Control
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• v.10 no.1
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• pp.42-49
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• 2001

This study was carried out to develop a fuzzy control technique of ventilation window for controlling a temperature in a greenhouse. To reduce the fuzzy variables, the inside air temperature shop was taken as one of fuzzy variables, because the inside air temperature variation of a greenhouse by ventilation at the same window aperture is affected by difference between inside and outside air temperature, outside wind speed and the wind direction. Therefore, the antecedent variables for fuzzy algorithm were used the control error and its slop, which was same value as the inside air temperature slop during the control period, and the conclusion variable was used the window aperture opening rate. Through the basic and applicative control experiment with the control period of 3 minutes the optimum ranges of fuzzy variables were decided. The control error and its slop were taken as 3 and 1.5 times compared with target error in steady state, and the window opening rate were taken as 30% of full size of the window aperture. To evaluate the developed fuzzy algorithm in which the optimized 19 rules of fuzzy production were used, the performances of fuzzy control and PID control were compared. The temperature control errors by the fuzzy control and PID control were lower than 1.3$^{\circ}C$ and 2.2$^{\circ}C$ respectively. The accumulated operating size of the window, the number of operating and the number of inverse operating for the fuzzy control were 0.4 times, 0.5 times and 0.3 times of those compared with the PID control. Therefore, the fuzzy control can operating the window more smooth and reduce the operating energy by 1/2 times of PID control.

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.195-206
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• 1995

The study was undertaken to examine the possibility of the involvement of $K^+$ channels in the mechanism of relaxant-action of imipramine on the isolated canine detrusor muscle strips. Canine urinary bladder were isolated, and smooth muscle strips of 15 mm long and 2 mm wide from the mid-portion of anterior wall were made in the Tyrode solution of $0{\sim}4^{\circ}C$. The strips were prepared for isometric myography in Biancani's isolated muscle chamber containing 1 ml of Tyrode solution, which was maintained with pH 7.4 by aeration with $95%\;O_2/5%CO_2\;at\;37^{\circ}C$. RP 52891, a non-specific $K^+$ channel opener, concentration-dependently suppressed the spontaneous phasic contractions of the detrusor strips. Imipramine, a tricyclic antidepressant, also reduced the spontaneous contractions in a concentration-dependent manner. RP 52891 was more potent than imipramine(p<0.05), and Imipramine was more efficient than RP 52891(p<0.05).Procaine, a voltage-dependent $K^+$ channel blocker, glibenclamide, an ATP-dependent $K^+$ channel blocker, and apamin, a calcium-dependent $K^+$ channel blocker antagonized the relaxant effect of RP 52891, but not of imipramine. Imipramine reduced the electric field stimulation (EFS) -induced contractions concentration-dependently. None of the $K^+$ channel blockers employed for this study, procaine, glibenclamide or apamin antagonized the inhibitory action of imipramine on the EFS-induced contraction. These results suggest that in canine detrusor, the $K^+$ channels of the characteristics of voltage-dependent, ATP-dependent and/or calcium-dependent are exist, and the inhibitory action of imipramine on the contractility of the detrusor is independent from the $K^+$ channels.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.547-556
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• 2016

Myometrial relaxation of mouse via expression of two-pore domain acid sensitive (TASK) channels was studied. In our previous report, we suggested that two-pore domain acid-sensing $K^+$ channels (TASK-2) might be one of the candidates for the regulation of uterine circular smooth muscles in mice. In this study, we tried to show the mechanisms of relaxation via TASK-2 channels in marine myometrium. Isometric contraction measurements and patch clamp technique were used to verify TASK conductance in murine myometrium. Western blot and immunehistochemical study under confocal microscopy were used to investigate molecular identity of TASK channel. In this study, we showed that TEA and 4-AP insensitive non-inactivating outward $K^+$ current (NIOK) may be responsible for the quiescence of murine pregnant longitudinal myometrium. The characteristics of NIOK coincided with two-pore domain acid-sensing $K^+$ channels (TASK-2). NIOK in the presence of $K^+$ channel blockers was inhibited further by TASK inhibitors such as quinidine, bupivacaine, lidocaine, and extracellular acidosis. Furthermore, oxytocin and estrogen inhibited NIOK in pregnant myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed stronger inhibition of NIOK by quinidine and increased immunohistochemical expression of TASK-2. Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretch-activated channels in the longitudinal myometrium of mouse. Activation of TASK-2 channels seems to play an essential role for relaxing uterus during pregnancy and it might be one of the alternatives for preventing preterm delivery.