• The Korean Journal of Pharmacology
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• v.9 no.1
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• pp.39-46
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• 1973

It has been reported previously that 2,2-methylene bis(3,4,6-trichlorophenoxy acetic acid) (MTPA) is effective treating for clonorchiasis and less toxic to the hosts. In this studies the absorption, distribution and excretion of MTPA were observed. For this purpose $^{14}C-MTPA$ was synthesised from bis(2-hydroxy-3,5,6-trichlorophenoxyl) methan $^{14}C$ and administerd to the normal rabbit in a single dose of 10mg/kg IV or 20 mg/kg P.O. or to the Clonorchis infected rabbit in dose of 20 mg/kg/day for 6 days. Radioactivity in blood, tissue, bile, urine, feces and tissue of the fluke was measured after the drug was given. The concentration of MTPA in these samples were calcurated from the radioactivity. The result obtained as followes. 1. The increase in concentration of MTPA in blood and urine after oral administration of MTPA was so slow that the absorption of MTPA from the gastrointestinal tract appears very slow. 2. It is presumed that the excretion of MTPA also is slow because the reduction of MTPA concentration in blood after IV injection was very slow. 3. Large amount of MTPA was excreted from the bile. 4. During repeat dose of 20mg/kg/day for 6 days the concentration of MTPA in blood and tissue gradually increased. 5. The highest concentration of MTPA in the kidney and liver, heart, lung, spleen and muscle in decreasing order and the lowest concentration in the brain was noted. 6. During daily dose of 20 mg/kg of MTPA for 6 days of administration the concentration of MTPA gradually increased in urine and feces and the concentration of MTPA in feces was higher than of in urine. It appeares that MTPA take place enterophepatic circulation. 7. It is assumed that accumulation in large amount of MTPA in the liver and tissue of clonorchis, excretion of large amount from the bile is a favorable property of MTPA as a chemotherapeutic agent for clonorchiasis.

• Journal of Chest Surgery
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• v.35 no.4
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• pp.255-260
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• 2002

Paraplegia remains unresolved as the most dreaded operative complication with surgical treatment of descending thoracic and thoracoabdominal aortic diseases. In this study, the neuroprotective effect of trimetazidine that has been used clinically for ischemic heart disease was investigated in a rabbit spinal cord ischemia model. Material and Method: Thirty-three New Zealand white rabbits were randomized as follows: control group undergoing abdominal aortic occlusion but receiving no pharmacologic intervention(Group 1, n= 17); TMZ group(Group 2, n= 16) receiving 3 mg/kg trimetazidine intravenously before the occlusion of the aorta. Ischemia was induced by clamping the abdominal aorta just distal to the left renal artery for 30 minutes. Neurologic status was assessed at 2, 24, and 48 hours after the operation according to the modified Tarlov scale, then the lumbosacral spinal cord was processed for histopathologic examinations 48 hours after the final assessment. Result: The average motor function score was significantly higher in the TMZ group(3.20 $\pm$ 0.77 vs 1.13 $\pm$ 1.25 at 2 hours, 3.50 $\pm$ 0.76 vs 1.45 $\pm$ 1.57 at 24 hours, and 3.91 $\pm$ 0.30 vs 1.86 $\pm$ 1.86 at 48 hours after operation; p value$\leq$0.05). Histologic observations were correlated with the motor scores. Conclusion: The results suggested that trimetazidine reduced spinal cord injury during aortic clamping and that it may have clinical utility for the thoracoabdominal aortic surgery:

• Journal of Chest Surgery
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• v.33 no.5
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• pp.398-406
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• 2000

Background: Cardiac atrium is an endocrine gland secreting a family of natriuretic peptides. The secretion of atrial natriuretic peptide(ANP) had been shown to be controlled by variable factors. The change in atrial dynamics have been considered as one of the most prominent stimuli for the stimulation of ANP secretion. Hypoxic stress has been shown to increase cardiac ANP secretion. However, the mechanism by which hypoxia increases ANP secretion cardiac ANP secretions. However, the mechanism by which hypoxia increases ANP secretion has not to be defined. Therefore, the purpose of the present study was tow-fold: to develop a protocol to defined the effect of hypoxia on ANP secretion in perfused beating rabbit atria and to clarify the mechanism responsible for the accentuation by hypoxia of ANP secretion. Material and Method: Experiments have been done in perfused beating rabbit atria. ANP was measured by radioimmunoassay. Result: Hypoxic stimulus with nitrogen decreased atrial stroke volume. The decrease in atrial stroke volume recovered basal level during the period of recovery with oxygen. ANP secretion and the concentration of perfusate ANP in terms of extracellular fluid(ECF) translocation which reflects the rate of myocytic release of ANP were increased by hypoxia and returned to basal levels during the recovery. Changes in ECF translocation paralleled by hypoxia and returned to basal levels during the recovery. Changes in ECF translocation paralleled to that of atrial stroke volume. At the start of recovery in atrial storke volume, ECF tranalocation incrased for several minutes. The above responses were stable and reproducible. Glibenclamide treatment prevented the recovery in atrial stroke volume. Increments by hypoxia of ANP secretion and ANP concentration were suppressed by glibenclamide. Conclusion: These results indicate that hypoxia incrased atrial myocytic ANP release and that the mechanism responsible for the accentuation is partially related to the change in K+ATP channel activity.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.5
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• pp.640-648
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• 2010

Insulin-responsive glucose transporter 4 (GLUT4) is a member of the glucose transporter family and mainly presents in skeletal muscle and adipose tissue. To clarify the molecular structure of porcine GLUT4, RACE was used to clone its cDNA. Several cDNA clones corresponding to different regions of GLUT4 were obtained by amplifying reverse-transcriptase products of total RNA extracted from Landrace porcine skeletal muscles. Nucleotide sequence analysis of the cDNA clones revealed that porcine GLUT4 cDNA was composed of 2,491 base pairs with a coding region of 509 amino acids. The deduced amino acid sequence was over 90% identical to human, rabbit and cattle GLUT4. The tissue distribution of GLUT4 was also examined by Real-time RT-PCR. The mRNA expression abundance of GLUT4 was heart>liver, skeletal muscle and brain>lung, kidney and intestine. The developmental expression of GLUT4 and insulin receptor (IR) was also examined by Real-time RT-PCR using total RNA extracted from longissimus dorsi (LM), semimembranosus (SM), and semitendinosus (SD) muscle of Landrace at the age of 1, 7, 30, 60 and 90 d. It was shown that there was significant difference in the mRNA expression level of GLUT4 in skeletal muscles of Landrace at different ages (p<0.05). The mRNA expression level of IR also showed significant difference at different ages (p<0.05). The developmental change in the mRNA expression abundance of GLUT4 was similar to that in IR, and both showed a higher level at birth and 30 d than at other ages. However, there was no significant tissue difference in the mRNA expression of GLUT4 or IR (p>0.05). These results showed that the nucleotide sequence of the cDNA clones was highly identical with human, rabbit and cattle GLUT4 and the developmental change of GLUT4 mRNA in skeletal muscles was similar to that of IR, suggesting that porcine GLUT4 might be an insulin-responsive glucose transporter. Moreover, the tissue distribution of GLUT4 mRNA showed that GLUT4 might be an important nutritional transporter in porcine skeletal muscles.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.9-14
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• 2016

Adenosine 3',5'-cyclic monophosphate (cAMP) participates in the regulation of numerous cellular functions, including the $Na^+-K^+$-ATPase (sodium pump). Ouabain, used in the treatment of several heart diseases, is known to increase cAMP levels but its effects on the atrium are not understood. The aim of the present study was to examine the effect of ouabain on the regulation of atrial cAMP production and its roles in atrial endothelin-1 (ET-1) secretion in isolated perfused beating rabbit atria. Our results showed that ouabain ($3.0{\mu}mol/L$) significantly increased atrial dynamics and cAMP levels during recovery period. The ouabain-increased atrial dynamics was blocked by KB-R7943 ($3.0{\mu}mol/L$), an inhibitor for reverse mode of $Na^+-Ca^{2+}$ exchangers (NCX), but did not by L-type $Ca^{2+}$ channel blocker nifedipine ($1.0{\mu}mol/L$) or protein kinase A (PKA) selective inhibitor H-89 ($3.0{\mu}mol/L$). Ouabain also enhanced atrial intracellular cAMP production in response to forskolin and theophyline ($100.0{\mu}mol/L$), an inhibitor of phosphodiesterase, potentiated the ouabain-induced increase in cAMP. Ouabain and 8-Bromo-cAMP ($0.5{\mu}mol/L$) markedly increased atrial ET-1 secretion, which was blocked by H-89 and by PD98059 ($30{\mu}mol/L$), an inhibitor of extracellular-signal-regulated kinase (ERK) without changing ouabain-induced atrial dynamics. Our results demonstrated that ouabain increases atrial cAMP levels and promotes atrial ET-1 secretion via the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. These findings may explain the development of cardiac hypertrophy in response to digitalis-like compounds.

• Journal of Chest Surgery
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• v.16 no.2
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• pp.199-212
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• 1983

The inhibition/influences of adenine compounds on the heart have been described repeatedly by many investigators, since the first report by Druny and Szent-Gyorgyi [1929]. These studies have shown that adenosine and adenine nucleotides have an over-all effect similar to that of acetylcholine [ACh] by slowing and weakening the heartbeat. The basic cellular and membrane events underlying the inhibitory action of adenosine on sinus rate, however, are not well understood. Furthermore, the physiological role of adenosine in regulation of the heartbeat remains still to be elucidated. Therefore, this study was undertaken in order to examine the response of rabbit SA node to adenosine and to compare the response to that of ACh. Isolated SA node preparation, whole atrial pair, or left atrlal strip was used in each experiment. Action potentials of SA node were recorded through the intracellular glass microelectrodes, which were filled with 3M KCI and had resistance of 30-50 M. All experiments were performed in a bicarbonate-buffered Tyrode solution which was aerated with 3% $CO_2-97%$ $O_2$ gas mixture and kept at $35^{\circ}C$. Spontaneous firing rate of SA node at 35C [Mean + SEM, n=16] was 154 + 3.3 beats/min. The parameters of action potentials were: maximum astolic potential [MDP], -731.7mV: overshoot [OS], 9 + 1.4mV; slope of pacemaker potential [SPP], 94 3.0mV/sec.Adenosine suppressed the firing rate of SA node in a dose dependent manner. This inhibitory effect appeared at the concentration of $10^{-6}M$ and was potentiated in parallel with the increase in adenosine concentration. Changes in action potential by adenosine were dose-dependent increase of MDP and decrease of SPP until $10^{-4}$. Above this concentration, however, the amplitude of action potential decreased markedly due to the simultaneous decrease of both MDP and OS. All these effects of adenosine were not affected by pretreatment of atropine [2mg/l] and propranolol [$5{\times}10^{-6}M$]. ACh [$10^{-6}M$] responses on action potential were similar to those of adenosine by increasing MDP and decreasing SPP. These effects of ACh disappeared by pretreatment of atropine [2mg/1]. Inhibition/effects of adenosine and ACh on sinus rate were enhanced synergistically with the simultaneous administration of adenosine and ACh. Marked decrease of overshoot potential was the most prominent feature on action potential. Dipyridamole [DPM], which is known to block the adenosine transport across cell membrane, definitely potentiated the action of adenosine . Adenosine suppressed the sinus rate and atrial contractility in the same dosage range, even in the reserpinized preparation. Above` results suggest that adenosine suppresses pacemaker activity, like ACh, by acting directly on the membrane of SA node, increasing MDP and decreasing SPP.

• Journal of the Korean Society of Radiology
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• v.6 no.2
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• pp.93-98
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• 2012

Micro-computed tomography (microCT) is an important tool for preclinical vascular imaging, with micron-level resolution. This non-destructive means of imaging allows for rapid collection of 2D and 3D reconstructions to visualize specimens prior to destructive analysis such as pathological analysis. Objectives. The aim of this study was to suggest a method for ex vivo, postmortem examination of stented arterial segments with microCT. And ex vivo evaluation of stents such as bare metal or drug eluting stents on in-stent restenosis (ISR) in rabbit model was performed. The bare metal stent (BMS) and drug eluting stent (DES, paclitaxel) were implanted in the left or right iliac arteries alternatively in eight New Zealand white rabbits. After 4 weeks of post-implantation, the part of iliac arteries surrounding the stent were removed carefully and processed for microCT. Prior to microCT analysis, a contrast medium was loaded to lumen of stents. All samples were subjected to an X-ray source operating at 50 kV and 200 ${\mu}A$ by using a 3D isotropic resolution. The region of interest was traced and measured by CTAN analytical software. Objects being exposed to radiation had different Hounsfield unit each other with values of approximately 1.2 at stent area, 0.12 ~ 0.17 at a contrast medium and 0 ~ 0.06 at outer area of stent. Based on above, further analyses were performed. As a result, the difference of lengths and volumes between expanded stents, which may relate to injury score in pathological analysis, was not different significantly. Moreover, ISR area of BMS was 1.6 times higher than that of DES, indicating that paclitaxel has inhibitory effect on cell proliferation and prevent infiltration of restenosis into lumen of stent. And ISR area of BMS was higher ($1.52{\pm}0.48mm^2$) than that of DES ($0.94{\pm}0.42mm^2$), indicating that paclitaxel has inhibitory effect on cell proliferation and prevent infiltration of restenosis into lumen of stent. Though it was not statistically significant, it showed that the extent of neointema of mid-region of stents was relatively higher than that of anterior and posterior region in parts of BMS as showing cross-sectional 2-D image. suggest that microCT can be utilized as an accessorial tool for pathological analysis.

• The Korean Journal of Nuclear Medicine
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• v.27 no.2
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• pp.223-232
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• 1993

Technetium labeled isonitrile analogues are widely used as myocardial perfusion imaging agents. We synthesized and characterized a new isonitrile compound, ethyl 3-isocyanobutyrate(EIB). Proton and $^{13}C$ NMR spectroscopy and thin layer chromatography with a $C_{18}$ coat was performed. EIB was easily labeled with $^{99m}TcO_4^-$- with sodium dithionite. The labeling efficiency measured by RP-HPLC was over 95%. The labeled product was stable with dilution in normal saline and with prolonged incubation at room temperature. There was no formation of secondary products or free $^{99m}TcO_4^-$. In vivo kinetics study of $^{99m}Tc$ (I) labeled EIB in rabbits showed adequate myocardial uptake, good contrast against lung background, and relatively rapid liver clearance. The heart to lung ratio was over 2.5 and the heart to liver ratio was approximately from 0.4 to 5 at 60 minutes post injection. Hepatic clearance of $^{99m}Tc-MIBI$ was faster ($t_{1/2}$=6 minutes) than that of $^{99m}Tc-MIBI$. In vivo kinetics observed in dog was similar to that in rabbit but there was faster gallbladder filling, and thus lower liver background. SPECT imaging of the canine myocardium showed favorable imaging characteristics. However, biodistribution in mice demonstrated a myocardial % injected dose/organ of less than 0.1%. This was thought to be due to interspecies difference in plasma esterase activity. In human plasma, $^{99m}Tc$ ( I ) labeled EIB was stable for at least 2 hours, without production of secondary products by HPLC. We conclude that ethyl 3-isocyanobutyrate may be a potential new myocardial perfusion imaging agent and deserves further investigation as to its usefulness for clinical use.

• The Korean Journal of Physiology
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• v.15 no.1
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• pp.53-59
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• 1981

In the present study, an effort was directed to elucidate the effect of osmolality on the absorption of ethanol in rabbits. A single dose of 13.67 ml(2. 16 gm ethanol/kg BW) of hypo-, iso-hyphen and hypertonic ethanol per kg BW was administered into the stomach to albino rabbits and the experiment was performed at 30 th, 60 th and 120 th minute. The blood ethanol level was determined by the method of Williams et al, and hematocrit(Hct) was determined by the conventional Hct centrifuge and reader. The results are summarized as follow. The blood ethanol level showed the highest value at 60 min after the ethanol ingestion in the hypo- and isotonic groups, $171.3{\pm}13.3\;mg%$ and $204.5{\pm}23.0\;mg%$, respectively, but in the hypertonic group, the highest value was observed at 120min after the ingestion. The absorption rate of ethanol between 0 to 30 min after the ingestion of hypo- and isotonic ethanol was $88.54{\pm}12.04$ and $94.73{\pm}8.33\;mg/min$, respectively, but a decreased value of $44.72{\pm}6.69\;mg/min$ was noted after hypertonic ethanol ingestion comparing with hypo- and isotonic groups, The Hct value after hypo- and isotonic ethanol ingestion was decreased at 30 min but returned to the control level at 120 min. In contrast with hypo- and isotonic ethanol ingestion, hypertonic ethanol ingestion produced an increase of the Hct value at 30 min and returned to the control level at 120 min. The heart rate was increased but the respiratory rate was decreased after ethanol ingestion regardless of the osmolality.

• The Korean Journal of Pharmacology
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• v.30 no.2
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• pp.227-242
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• 1994

The general pharmacological effects of a new anthracycline anticancer agent, DA-125 $[7-0-(2,\;6-dideoxy-2-fluoro-{\alpha}-L-talopyranosyl)-adriamycinone-14-{\beta}-alaninate{\cdot}HCI]$ were investigated in mice, rats, guinea pigs, rabbits and dogs. Intravenous administration of DA-125 presented no significant effects on the central and peripheral nervous systems of ICR mice except a decrease in the numbers of acetic acid-induced writhing response at a dose of 10 mg/kg. In anesthetized rats and dogs, DA-125 produced a transient depression of blood pressure and an increase in heart rate, but did not affect the peripheral blood flow in the isolated ear vessels of rabbits and the mechanical functions of the isolated hearts of guinea pigs. No significant effects were observed on the gastrointestinal functions and the contractilities of smooth muscle preparations obtained from guinea pig trachea, rabbit ileum, pregnant and non-pregnant uterus and vas deferens of rats. DA-125 Increased the contractility of the isolated ileum of guinea pigs in a dose range of $10^{-6}{\sim}10^{-9}g/ml$, and also increased, but weaker than adriamycin, the vascular permeability in rat skin. DA-125 had no effect on the kallikrein-induced increase in permeability and the permeability of the visceral organs. DA-125 did not adversely affect the liver function and the blood coagulation system, and did not induce hemolysis in vitro. It is concluded from the results that the general pharmachological effects of DA-125 are similar to or weaker than those of adriamycin, and that little adverse effects are anticipated with a therapeutic dose range.