• Clinical and Experimental Pediatrics
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• v.60 no.11
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• pp.365-372
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• 2017

Purpose: The mechanism for the pathogenesis of adriamycin (ADR)-induced cardiomyopathy is not yet known. Different hypotheses include the production of free radicals, an interaction between ADR and nuclear components, and a disruption in cardiac-specific gene expression. Apoptosis has also been proposed as being involved in cardiac dysfunction. The purpose of this study was to determine if apoptosis might play a role in ADR-induced cardiomyopathy. Methods: Male Sprague-Dawley rats were separated into 2 groups: the control group (C group) and the experimental group (ADR 5 mg/wk for 3 weeks through intraperitoneal injections; A group). Echocardiographic images were obtained at week 3. Changes in caspase-3, B-cell leukemia/lymphoma (Bcl)-2, Bcl-2-associated X (Bax), interleukin (IL)-6, tumor necrosis $factor-{\alpha}$, brain natriuretic peptide (BNP), troponin I, collagen 1, and collagen 3 protein expression from the left ventricle tissues of C and A group rats were determined by Western blot. Results: Ascites and heart failure as well as left ventricular hypertrophy were noted in the A group. Ejection fraction and shortening fraction were significantly lower in the A group by echocardiography. The expression of caspase-3, Bax, IL-6, BNP, collagen 1, and collagen 3 were significantly higher in the A group as compared with the C group. Protein expression of Bcl-2 decreased significantly in the A group compared with the C group. Conclusion: ADR induced an upregulation of caspase-3, Bax, IL-6, and collagen, as well as a depression in Bcl-2. Thus, apoptosis and fibrosis may play an important role in ADR-induced cardiomyopathy.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.2
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• pp.103-111
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• 2019

The study is to investigate effects of andrographolide on experimental autoimmune myocarditis (EAM). Lewis rats were immunized on day 0 with porcine cardiac myosin to establish EAM. The EAM rats were treated with either andrographolide (25, 50, 100 mg/kg/day) or vehicle for 21 days. An antigen-specific splenocytes proliferation assay was performed by using the cells from control rats immunized with cardiac myosin. Survival rates, myocardial pathology and myocardial functional parameters (left ventricle end-diastolic pressure, ${\pm}dP/dt$ and left ventricular internal dimension) of EAM rats received andrographolide were significantly improved. Andrographolide treatment caused an decrease in the infiltration of $CD3^+$ and $CD14^+$ positive cells in myocardial tissue. Moreover, andrographolide treatment caused a reduction in the plasma levels of tumor necrosis factor-alpha, interleukin-17 (IL-17) and myosin-antibody, and an increase in the level of IL-10 in EAM rats. Oral administration of andrographolide resulted in the decreased expression of p-PI3K, p-Akt without any change of PI3K and Akt. Further results indicate andrographolide significantly inhibited myosin-induced proliferation in splenocytes, and this effect was inhibited by co-treatment of SC79 (Akt activator). Our data indicate andrographolide inhibits development of EAM, and this beneficial effect may be due to powerful anti-inflammatory activity and inhibitory effect on PI3K/Akt pathway.

• Journal of Korean Neurosurgical Society
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• v.66 no.4
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• pp.400-408
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• 2023

Objective : Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a crucial factor for the survival of neuron. The role of NMNAT2 in damage following traumatic brain injury (TBI) remains unknown. This study was designed to investigate the role of NMNAT2 in TBI-induced neuronal degeneration and neurological deficits in rats. Methods : The TBI model was established in Sprague-Dawley rats by a weight-dropping method. Real-time polymerase chain reaction, western blot, immunofluorescence, Fluoro-Jade C staining, and neurological score analyses were carried out. Results : NMNAT2 mRNA and protein levels were increased in the injured-side cortex at 6 hours and peaked 12 hours after TBI. Knocking down NMNAT2 with an injection of small interfering RNA in lateral ventricle significantly exacerbated neuronal degeneration and neurological deficits after TBI, which were accompanied by increased expression of BCL-2-associated X protein (Bax). Conclusion : NMNAT2 expression is increased and NMNAT2 exhibits neuroprotective activity in the early stages after TBI, and Bax signaling pathway may be involved in the process. Thus, NMNAT2 is likely to be an important target to prevent secondary damage following TBI.

• Journal of Veterinary Clinics
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• v.29 no.2
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• pp.148-153
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• 2012

Atrial natriuretic peptide (ANP) is associated with the variety of disorders of myocardial function. The effect, however, of myocardial infarction (MI) on ANP has not been fully described. Thus, this study investigated the effect of experimental MI, induced by left coronary artery ligation, on ANP secretion. Male Sprague-Dawley rats aged 60 d underwent ligation of the left anterior descending coronary artery to induce MI and were compared with a group that underwent a sham operation. Rats of sham operation had a similar procedure without having the suture tightened around the coronary artery. Animals were sacrificed at 1, 3, 6, 12, and 18 h or 1, 3, 5, 7, 14, and 30 d after the procedure. MI size was assessed by planimetry and perimetry, and plasma ANP levels were determined by radioimmunoassay. Mean infarct size was 39.6-44.5% of the left ventricle after coronary occlusion in experimental groups. No significant differences were observed in infarct size among groups. In contrast, the concentration of plasma ANP was significantly higher at 1, 3, 6, 12, 18, and 24 h after left coronary artery ligation than in sham animals. This parameter, however, did not differ significantly at 3, 5, 7, 14, and 30 d after ligation compared with sham-ligated controls. These results demonstrate that plasma ANP levels are markedly increased in the early phase of MI in the male rat and can be a useful biomarker for diagnosis in acute MI.

• Applied Microscopy
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• v.29 no.1
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• pp.11-23
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• 1999

Ultrastructure of the ependymal cells of X-irradiated rats on their head were studied. Rats weighing $200\sim250gm$ were X-irradiated on their head and neck areas. Total exposures were 3,000 rads or 6,000 rads depending on experimental groups. And irradiated rats were sacrificed on 6 hours, 2 days and 6 days following the radiation exposures. Animals were perfused through the heart with 1% glutaraldehyde-1% paraformaldehyde solution, under ether-anesthesia. The tissues from the wall of lateral ventricles were fixed in the 2% osmium tetroxide solution. The results observed with electron microscope were as follow: 1. In 6 hours group, many ependymal cells were swelled, luminal portions of cytoplasms of some cells protruded into the ventricular lumen, and many cilia were lost or irregularly altered. 2. In 2 days group, ependymal cells were swelled more severely and subependymal edema were pronounced. 3. Protruded cytoplasm contained usually basal bodies of cilia, groups of mitochondria, endoplasmic reticula , etc. 4. Following X-irradiations, some protruded masses contained neural elements including the axon terminals with dense core vesicles. Axons and axon terminals were also found in the enlarged intercellular spaces among ependymal cells. From the above results, the heavy irradiation on the head area of the rat induced alteration of the ependymal cells lining the lateral ventricle. Hence the ependymal functions of selective barrier, protective barrier, and metabolic barrier could be altered following X-irradiation on the head.

• The Korean Journal of Pharmacology
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• v.9 no.1
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• pp.1-21
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• 1973

During the last decade extensive studios on catecholamines have evolved new knowledge in the physiology and biochemistry of adrenergic mechanism. Cardiac muscle, receiving adrenergic fibres from the stellate, cervical and thoracic ganglia, has been repeatedly shown to have a specific capacity to uptake and to store catecholamines. The catecholamine stores in cardiac muscle have also been shown to be important sites for the action of numerous drugs. Under normal condition, a certain level of catecholamines is maintained in the stores and serves as the basis for studying the changes in the catecholamine content of the heart. Because myocardial catecholamines play such important role in the patho-physiology of the heart, it would be interesting to compare the normal level of myocardial catecholamines among various species of animals. An occasional study has dealt with myocardial catecholamines of several species add ages of animals but these have been insufficiently comprehensive to afford a basis for an understanding of the importance of these amines as related to species and ages. The present investigation was undertaken to determine whether or not there is any significance of myocardial catecholamines in the course of the evolution and development of animals. Seasonal changes, sex difference and regional and subcellular distribution of myocardial catecholamines were also examined. The concentration of cardiac catecholamines was determined by the spectrophotofluorometric procedure described by Shore and Olin. The results obtained were summarized as follows: 1. As animals phylogenetically progressed larger amounts of catecholamines were resent in their hearts. A negligibly small amount of catecholamine was present in the hearts of the clam, a non-vertebrate. Among the vertebrates, cold-blooded animals (snake, turtle, frog, eel and fish) had less myocardial catecholamines than warm-blooded animals, of which aves (fowl and duck) had less than mammalia (cat, dog, rabbit, rat, cow and pig). The ratio of norepinephrine to epinephrine also was greater as the animals progress phylogenetically. 2. Examination of the regional distribution of cardiac catecholamines in warm-blooded animals showed that the content of the auricle was generally higher than that of the septum and considerably than that of the ventricle, but the differences of contents among these regions were not so marked. 3. In the embryonic chick, cardiac catecholamines were firstly detected on the 4th day of incubation, the time before the cardiac innervation of sympathetic nerves. The concentrations of these catecholamines increased but not markedly on the 6th day of incubation, soon after the innervation of sympathetic nerves to the heart. The level of the cardiac catecholamines fluctuated throughout the remainder of embryonic development. 4. In newborn rat hearts, a considerable amount of catecholamines was present. With the development of the rats, the concentrations of myocardial catecholamines increased. The ratio of epinephrine and norepinephrine fluctuated within the range of 40 to 60 pervent. However, as development progressed, the percentage of norepinephrine continued to rise, attaining the adult value of $80{\sim}90%$ after $45{\sim}60$ days. In contrast, the total amount of epinephrine remained fairly constant throughout the animal's development. 5. No significant sexual differences were observed in the concentration of myocardial catecholamines in the developing rat. 6. The catecholamines in the rabbit hearts increased during the summer season (from May to August) and maintained a fairly constant level in the other seasons of the year. 7. The subcellular distribution of cardiac catecholamines was examined by differential centrifugation of homogenates of cardiac muscles in rabbits, cats and rats. The catecholamines were found to be present approximately 20% in particles of mitochondrial fraction, 45% in particles of microsomal fraction and 35% in soluble supernatant fraction. The particle containing catecholamines in cardiac muscle appears to be two different sizes.

• Journal of Chest Surgery
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• v.38 no.7 s.252
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• pp.468-475
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• 2005

Transmyocardial revascularization (TMR) in end stage ischemic heart disease results in variable clinical responses. We investigated the acute effect of early reperfusion and the angiogenesis after formation of the transmyocardial channel in a transplanted rat heart model with acute myocardial infarction. Material and Method: In the 30 transplanted hearts we induced acute myocardial infarction by ligating the proximal left coronary artery and inserted a porous 22G intravenous cannula into the left ventricle. After ten minutes of reperfusion, we removed the cannula. At every stage, we recorded the heart rate, QRS size, and left coronary arterial blood flow using the electrocardiogram and Doppler. One week later the rats were sacrificed and evaluated for the patency of intramyocardial channels and the angiogenesis. Result: The heart rates after ligation and after cannula insertion were $239.1\pm61.7,\;235.8\pm58.0bpm$ respectively, and they were statistically significantly slower than that of before ligation, $277.6\pm40.3bpm\;(p=0.017,\;p=0.007\;respectively)$. QRS sizes before ligation, after ligation, and after cannula insertion were $3.6\pm3.3mm,\;2.8\pm3.3 mm,\;and\;2.4\pm2.2mm,$respectively, and there was no significant difference in the three groups. Doppler findings after ligation showed that average peak and mean values of coronary perfusion were significantly decreased from $2.11\pm0.17kHz,\;1.25\pm0.22kHz\;to\;0.83\pm0.15kHz,\;0.38\pm0.11kHz$(p<0.05 respectively). After insertion of the porous cannula, the average peak and mean values of coronary perfusion were $0.61\pm0.05kHz\;and\;0.33\pm0.05 kHz$ respectively, but there was no statistically significant change compared to values after ligation. In all cases except one, pathologic findings showed no patent channels in the acute stage, however, one case showed the angiogenesis. Conclusion: We confirmed that TMR in a rat heart transplant model did not show blood flow through the channel in the acute stage. However, reperfusion effect in some cases had a potential for angiogenesis.

• The korean journal of orthodontics
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• v.24 no.1 s.44
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• pp.37-62
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• 1994

This study was undertaken to investigate the three dimensional vascular changes of periodontal ligament following orthodontic tooth movement. Experimental tooth movement was carried out in 96 Sprague-Dawley rats with the weight of 250g. They were divided into four experimental groups (each 24 rats). The left maxillary first molar was moved mesially with 25g force in group I, and with 75g force in group II. Each three animals were sacrificed after 1, 6, 12, 24 hours, and 3, 7, 14, 21 days. In group III, 25g mesial force was applied for 3 days, and in group IV, 75g mesial force was applied for 3 days. Then the appliances were removed, and each three animals were sacrificed after 1, 6, 12, 24 hours, and 3, 7, 14, 21 days from removal of appliance. The contralateral molars were used for control group. Casting media was injected via left ventricle and polymerized in warm water. After corrosion of surrounding soft tissue, three dimensional vascular changes were examined using scanning electron microscopy. The findings of this study were as follows: 1. Pressure side of group I and II showed degenerative vascular changes such as vascular compression, reduction of vasculature, leakage of casting media. But, regenerative changes were dominant after 7 days of tooth movement. Although the degenerative vascular changes were more severe in group II, which was exposed to heavy force, the timing of these changes was not different between two groups. 2. Periodontal vasculature was reestablished by the growth of new capillaries and their differentiation and union from the remaining periodontal vessels and vessels of alveolar bone marrow. Although vascular regeneration was more rapid in group I, which was exposed to light force, the vasculature was not fully normalized in both groups even after 21 days. 3. There was no remarkable changes in tension side of group I and II, but looping of capillary, new capillary growth, dilation of vessels, redirection of vessels in the direction of tensile force were occurred. 4. In pressure side of group III and IV, in which appliance was removed after 3 days of orthodontic force, bone resorption was continued even after removal of appliance. Regeneration of vasculature was initiated after 1-6 hours, and it was more rapid in group III than group IV. In both groups, the vasculature was not fully normalized even after 21 days. 5. After removal of appliance, tension side of group III and IV showed vascular compression and loss of vasculature.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.243-243
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• 1994

Although active systemic anaphylaxis and passive cutaneous anaphylaxis have been empolyed to study anaphylactic hypersensitivity, it is difficult and time-consuming to induce these reactions in experimental animals. In recent, Jun et al have found a simple method to induced anaphylactic hypersensitivity such as anaphylactic shock(AS) and cutaneous reaction(CR) using compound48/80. Cortex mori (Morus alba L.), the root bark of mulberry tree has been used as an antiphlogistic, diuretic, and expectorant in herbal medicine. The purpose of this study was to determine whether the methanol extract of Cortex mori could inhibit the compound 48/80-induced AS and CR. To induce AS, various doses of compound 48/80 (5, 7.5, 10, 15$\mu\textrm{g}$/gm B.W.) were injected intraperitoneally (i.p.) into ICR mice. The animals were pretreated by three injection(i.p.) of Cortex mori before compound 48/80 administration. Peripheral blood was collected from the right ventricle to estimate the level of serum histamine at 15 minutes after the injctin(i.p.) of various concentration of compound48/80. Mortility rate, mean death time and mesenteric mast cell degranulation rate were evaluated over a 72 hour period. To estimate the effect of Cortex mori on compound 48/80-induced cutaneous reaction, various doses of compound 48/80 with or without Cortex mori were injected intradermally(i.d.) into the shaved flank of Sprague-Dawley rats, and the blue cutaneous patchs induced by Evans'blue injection at the compound 48/80 alone and Cortex mori plus compound 48/80 injection sites were observed. As a Parameter of these reactions, the levels of histamine in the supernatant, calcium uptake and intracellular CAMP of RPMC were measured. supernatant, 1)compound 48/80-induced mortility rate, mean death time, mesenteric mast cell degranulation rate, and serum histamine level in ICR mice were significantly inhibited by pretreatment of Cortex mori, 2) cutaneous reaction inducd by compound48/80 was well developed in Sprague-Dawley rat, but Cortex mori inhibited the compound 48/80-induced blue patch formation remarkably, 3) the compound 48/80-induced degranulation, histamine release and calcium uptake of RPMC pretreated with Cortex mori were significantly inhibited, compared to those of control without Cortex mori pretreatment, and 4)the level of cAMP of RPMC was reduced bythe increased concentration of compound 48/80, pretreatment of Cortex mori not only inhibited the compound 48/80-induced reduction of CAMP but also significantly increased the level of cAMP naturally, from the above results, it is suggested that Cortex mori has an some substances with an ability to inhibits the compound 48/80-induced AS,CR, and mast cell activation.

• Journal of Korean Neurosurgical Society
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• v.29 no.1
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• pp.5-14
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• 2000

Objective : Somatosensory evoked potential(SSEP) has been known to be a good method for evaluating brain stem function, but it is not sufficient to check the fine changes of cortical functions. A fine change of cortical function can be expressed with somatosensory evoked cortical field potential(SSEFP) rather than general SSEP. To confirm the usefulness of SSEFP for evaluating the cortical function, the authors simultaneously measured SSEFP and the intracranial pressure-volume index(PVI) in kaolin-induced hydrocephalic rats. Method : Hydrocephalus was induced with injection of 0.1ml kaolin-suspended solution into the cisterna magna in 60 Sprague-Dawley rats. The authors measured PVI and SSEFP 1 week after injection of kaolin-suspended solution. To evaluate the severity of induced hydrocephalus, we measured the transverse diameter of the lateral ventricle on the coronal slice of the rat brain 0.40mm posterior to the bregma. Result : The typical wave form of SSEFP in control rats showed a negative-positive complex wave at early latency. In SSEFP of normal rats, N0 is 10.0 msec, N1 15.3 msec, P1 31.2 msec and N1-P1 amplitude $15.4{\mu}V$. As hydrocephalus progressed, the peak latency of N1 and P1 were delayed. In mild hydrocephalus, negative peak waves were split. The N1-P1 amplitude was decreased only in severe hydrocephalus. The changes of the characteristics of SSEFP according to the severity of hydrocephalus were well correlated with the changes of PVI. Shunting normalized the characteristics of SSEFP in relation to ventricular sizes and PVI in hydrocephalic rats. Conclusion : SSEFP may be useful for evaluating the impairment of cortical function in hydrocephalus.