Kwon, Jung Hyun;Kim, Kwan Chang;Cho, Min-Sun;Kim, Hae Soon;Sohn, Sejung;Hong, Young Mi
Clinical and Experimental Pediatrics
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v.56
no.3
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pp.116-124
/
2013
Purpose: Tumor necrosis factor (TNF)-${\alpha}$ is thought to contribute to pulmonary hypertension. We aimed to investigate the effect of infliximab (TNF-${\alpha}$ antagonist) treatment on pathologic findings and gene expression in a monocrotaline-induced pulmonary hypertension rat model. Methods: Six-week-old male Sprague-Dawley rats were allocated to 3 groups: control (C), single subcutaneous injection of normal saline (0.1 mL/kg); monocrotaline (M), single subcutaneous injection of monocrotaline (60 mg/kg); and monocrotaline + infliximab (M+I), single subcutaneous injection of monocrotaline plus single subcutaneous injection of infliximab (5 mg/kg). The rats were sacrificed after 1, 5, 7, 14, or 28 days. We examined changes in pathology and gene expression levels of TNF-${\alpha}$, endothelin-1 (ET-1), endothelin receptor A (ERA), endothelial nitric oxide synthase (eNOS), matrix metalloproteinase (MMP) 2, and tissue inhibitor of matrix metalloproteinase (TIMP). Results: The increase in medial wall thickness of the pulmonary arteriole in the M+I group was significantly lower than that in the M group on day 7 after infliximab treatment (P<0.05). The number of intraacinar muscular arteries in the M+I group was lower than that in the M group on days 14 and 28 (P<0.05). Expression levels of TNF-${\alpha}$, ET-1, ERA, and MMP2 were significantly lower in the M+I group than in the M group on day 5, whereas eNOS and TIMP expressions were late in the M group (day 28). Conclusion: Infliximab administration induced early changes in pathological findings and expression levels of TNF-${\alpha}$, and MMP2 in a monocrotaline-induced pulmonary hypertension rat model.
Objective : The purpose of this study was to verify the appropriateness of ovariectomized rats as the osteoporosis animal model. Methods : Twelve female Sprague-Dawley rats underwent a sham operation (the sham group) or bilateral ovariectomy [the ovariectomy (OVX) group]. Eight weeks after operations, serum biochemical markers of bone turnover were analyzed; osteocalcin and alkaline phosphatase, which are sensitive biochemical markers of bone formation, and C-terminal telopeptide fragment of type I collagen C-terminus (CTX), which is a sensitive biochemical marker of bone resorption. Bone histomorphometric parameters and microarchitectural properties of 4th lumbar vertebrae were determined by micro-computed tomographic (CT) scan. Results : The OVX group showed on average 75.4% higher osteocalcin and 72.5% higher CTX levels than the sham group, indicating increased bone turnover. Micro-CT analysis showed significantly lower bone mineral density (BMD) (p=0.005) and cortical BMD (p=0.021) in the OVX group. Furthermore, the OVX group was found to have a significantly lower trabecular bone volume fraction (p=0.002). Conclusion : Our results showed that bone turnover was significantly increased and bone mass was significantly decreased 8 weeks after ovariectomy in rats. Thus, we propose that the ovariectomized rat model be considered a reproducible and reliable model of osteoporosis.
Objective : The authors developed a stereotactic device for irradiation of small animals with Leksell Gamma Knife Model C. Development and verification procedures were described in this article. Methods : The device was designed to satisfy three requirements. The mechanical accuracy in positioning was to be managed within 0.5 mm. The strength of the device and structure were to be compromised to provide enough strength to hold a small animal during irradiation and to interfere the gamma ray beam as little as possible. The device was to be used in combination with the Leksell G-$frame^{(R)}$ and $KOPF^{(R)}$ rat adaptor. The irradiation point was determined by separate imaging sequences such as plain X-ray images. Results : The absolute dose rate with the device in a Leksell Gamma Knife was 3.7% less than the value calculated from Leksell Gamma $Plan^{(R)}$. The dose distributions measured with $GAFCHROMIC^{(R)}$ MD-55 film corresponded to those of Leksell Gamma $Plan^{(R)}$ within acceptable range. The device was used in a series of rat experiments with a 4 mm helmet of Leksell Gamma Knife. Conclusion : A stereotactic device for irradiation of small animals with Leksell Gamma Knife Model C has been developed so that it fulfilled above requirements. Absorbed dose and dose distribution at the center of a Gamma Knife helmet are in acceptable ranges. The device provides enough accuracy for stereotactic irradiation with acceptable practicality.
Journal of the Korean Institute of Intelligent Systems
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v.14
no.5
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pp.545-550
/
2004
The study of available genotypes (biodiversity analysis) in bacterial communities is of growing importance in several fields such as ecology, environmental technology, clinical diagnostics, etc. These culture-independent genotyping techniques, especially amplifying 16S rRNA genes, attempt to overcome some shortcomings of conventional cultivation method. Biodiversity analysis based on molecular technique were laborious for base-calling chromatogram, trimming primer sites, correcting strand directions, electing representative operation taxonomic units (OTU), etc. Also, biologists wanted intuitively to confirm results of the above processes. For making up these demands, we developed the web application based on Folder-Process-Filter (FPF) modeling with correspondence to classical Model-View-Controller model. The model of web application leads to keep virtues of simplicity and directness for development and management of the stepwise web interfaces. The web application was developed in Perl and CGI on Linux workstation. It can be freely accessed from http://home.pusan.ac.kr/~genome/tools/rat.htm.
We recently described a novel animal model of trigeminal neuropathic pain following compression of the trigeminal ganglion (Ahn et al., 2009). In our present study, we adapted this model using male Sprague-Dawley rats weighing between 250-260 g and then analyzed the behavioral responses of these animals following modified chronic compression of the trigeminal ganglion. Under anesthesia, the rats were mounted onto a stereotaxic frame and a 4% agar solution ($10{\mu}L$) was injected in each case on the dorsal surface of the trigeminal ganglion to achieve compression without causing injury. In the control group, the rats received a sham operation without agar injection. Air-puff, acetone, and heat tests were performed at 3 days before and at 3, 7, 10, 14, 17, 21, 24, 30, 40, 55, and 70 days after surgery. Compression of the trigeminal ganglion produced nociceptive behavior in the trigeminal territory. Mechanical allodynia was established within 3 days and recovered to preoperative levels at approximately 60 days following compression. Mechanical hyperalgesia was also observed at 7 days after compression and persisted until the postoperative day 40. Cold hypersensitivity was established within 3 days after compression and lasted beyond postoperative day 55. In contrast, compression of the trigeminal ganglion did not produce any significant thermal hypersensitivity when compared with the sham operated group. These findings suggest that compression of the trigeminal ganglion without any injury produces prolonged nociceptive behavior and that our rat model is a useful system for further analysis of trigeminal neuralgia.
Kim Jong-Woo;Whang Wei-Wan;Kwak So-Young;Kim Min-Jung;Park Eun-Hye;Lee Jeong-A
Journal of Oriental Neuropsychiatry
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v.12
no.1
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pp.123-135
/
2001
Objective: This study was designed to assess antidepressant effects of Quibitang on an Animal Model of Depression induced by Chronic Mild Stress. Method: The consumption of 1% sucrose solution and active avoidance learning test were used to evaluate antidepressant effect of Quibitang. The consumption of 1% sucrose solution was measured every week for 8 weeks, and active avoidance learning test was executed after 4 weeks treatment of saline or Quibitang. Result: 1. The consumption of 1% sucrose solution was significantly reversed in test group (Quibitang-treated group) at 5th, 7th, 8th weeks, but there was no significant change in control group. 2. Chronic Mild Stress was found to suppress the increase of body weight at 5th, 6th, 7th, 8th weeks. Treatment of Quibitang did not enhanced the body weigt, but it enhanced the consumption of sucrose solution. 3. In order to measure the learning ability of rat which drived to be depressed, we executed active avoidance test. The result revealed that depressed rat showed impaired acquisition than control group, and the treatment of Quibitang restored the learning activity. Conclusion: These results suggest that Quibitang may have antidepressant effects on depression induced by chronic mild stress.
Sindhuri, Vishnumolakala;Lee, Ji Eun;Park, Hye-Ji;Kim, So-Hee;Koo, Sungtae
Korean Journal of Acupuncture
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v.36
no.4
/
pp.264-273
/
2019
Objectives : Microglia play a crucial role in electroacupuncture (EA) analgesia on neuropathic pain. The role of chemokines in producing analgesic effects of EA, however, is largely unknown. In the present study, we investigated the role of chemokines in producing analgesic effects of EA in the neuropathic pain model. Methods : Sprague-Dawley rats were randomly assigned into three groups (anesthetized group (ANE), non-acupoint EA group (NAP), and ST36 - GB34 EA group (ACU)). Neuropathic pain was induced by tight ligation of L5 spinal nerve. Mechanical and thermal hypersensitivity of hind paw was tested. Western blot tests and immunofluorescence assay for C-C motif chemokine ligand 2 (CCL2) levels and microglia activation were performed on spinal cord L5/6. EA was treated once daily from the 3rd day after surgery for 5 days. Results : EA treatments applied to ST36 and GB34 significantly reduced both mechanical and thermal hypersensitivity after two and three times of treatment, respectively. While CCL2 expression significantly increased in neuropathic rats, it was significantly reduced in the ACU. In addition, co-localization of CCL2 and activated microglia significantly decreased in the ACU compared to those of ANE and NAP in the spinal cord L5/L6 dorsal horn. Conclusions : The present results suggest that EA applied to ST36 and GB34 modulates the reduction of CCL2 release from the injured neurons and consequently decreases microglia activation in the spinal cord. Regulation of chemokine induced spinal activation of microglia plays a key role in analgesic effects of EA in the rat model of neuropathic pain.
A purified histone Hl protein, p961, which plays a role in mediating the condensation of DNA into chromatin, was recently proved as an arthritis-suppressing agent in the mouse CIA model. The pharmacokinetics of p961 was carried out in rats and rabbits. The rat's blood, bile and urine samples were serially collected from the femoral vein, common bile duct, and bladder respectively, after bolus i.v. injection at low (10 mg/kg) and high (30 mg/mg) doses. The rabbit's blood samples were also collected from the marginal ear vein after bolus i.v. injection at a dose 10 mg/kg. p961 and its major metabolite in the physiological samples were analyzed by reverse-phase HPLC using a Yydac C4 protein column and a multistep water-acetonitrile gradient containing 0.24% trifluoroacetic acid. The major pharmacokinetic parameters (AUC, $C_{max}$, MRT, $t_{1}$2/, $V_{ss}$ and Cl) were estimated from the time course of plasma p961 and metabolite concentrations using WinNonlin. A two-compartment model was chosen for p961 as the most appropriate pharmacokinetic model. After i.v. injection of p961 at doses of 10 mg/kg and 30 mg/kg, more than 80% of p961 was removed rapidly from the plasma within 15 min. The plasma half-life of p961 in rats and rabbits was found not to exceed 12 min. p961 (22448.9 mol wt) was rapidly cleaved to 21612 mot wt fragment and the breakdown product appeared rapidly in the circulation with no lag phase. p961 and metabolite were not detected in rat urine and bile....
Objectives : In order to find a possible non-invasive manipulation tool for maintenance of the cardiovascular functions in hemorrhagic shock, this study was aimed at evaluating effects of acupoints acupressure on the changes in blood pressure and heart rate from an animal model of hemorrhagic shock. Methods : In adult Sprague-Dawley rats, hemorrhagic shock was induced by a withdrawal of arterial blood from the femoral artery with volume of 0.8 ml per 100 g of body weight using peristaltic syringe pump. We applied the acupressure with a pressure oscillator to tail as a control and 2 different acupoints of sobu(HT8), youngchun(KI1) under 3 different conditions : 1) normal arterial blood pressure without bleeding, 2) at the beginning of bleeding, and finally 3) hemorrhagic shock. Results : Under normal arterial blood pressure without hemorrhage, there was a significant increase in systolic and diastolic blood pressures by the acupressure to the tail, HT8 and especially KI1 for 30 sec compared with before acupressure. Under hemorrhagic shock condition, the tail acupressure had minimal changes in cardiovascular parameters. Either the HT8 or KI1 acupressure resulted in a significant increase in arterial pressure but did not heart rate. At the beginning of bleeding, tail acupressure failed to change the reduction of arterial pressure and heart rate. However, there was a significant increase in blood pressure and heart rate following either the HT8 or especially KI1 acupressure. Conclusions : HT8 and KI1 acupressure affected cardiovascular signs but tail acupressure did not in rat model of hemorrhagic shock. These experimental data suggest that a acupressure with a pressure oscillator to HT8 or KI1 can be one of alternative emergency manipulations to ameliorate compromised cardiovascular functions under hemorrhagic shock condition.
Background: This study was conducted to quantitatively analyze proteins associated with the calcitonin gene-related peptide (CGRP) in cerebrospinal fluid (CSF) that was obtained from a rat model of chronic neuropathic pain following administration of intrathecal $CGRP_{8-37}$. Methods: Male Sprague-Dawley rats (100-150 g, 5-6 wks) were divided into two groups, sham controls and neuropathic pain models. At the time of operation for neuropathic pain model, an intrathecal catheter was threaded through the intrathecal space. At 1 or 2 wks after the operation (maximum pain state), a test dose of 1, 5, 10, or 50 nM of $CGRP_{8-37}$ was injected into the intrathecal catheter and the CSF was then aspirated. Conventional proteomics to evaluate the CSF were then performed using high resolution 2-D, gel electrophoresis followed by computational image analysis and protein identification by mass spectrometry. Results: Treatment with $CGRP_{8-37}$ effectively alleviated mechanical allodynia in a dose dependent manner. The most effective response was obtained when a dose of 50 nM was administered, but significant differences were obtained following administration of only 5 nM $CGRP_{8-37}$. Furthermore, the results of the proteomic analysis were consistent with the experimental results. Specially we detected 30 differentially expressed spots in 7 images when 2-D gel electrophoresis was conducted. The intensity of 6 of these spots (spot number: 20 and 26-30) was found decrease the $CGRP_{8-37}$ dose increased; therefore, these spots were evaluated by mass spectrometry. This analysis identified 2 different proteins, CGRP (spot numbers: 26-30) and neurotensin-related peptide (spot number: 20). Conclusions: The results of this study suggest that CGRP plays a role in chronic central neuropathic pain and is a major target of chronic neuropathic pain management.
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