• Journal of Chest Surgery
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• 제30권5호
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• pp.471-478
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• 1997

Introduction: The use of rabbits as a cardiopulmonary bypass(CPB) animal model is extremely dif%cult mainly due to technical problems. On the other hand, deep hypothermic circulatory arrest(CA) is used to facilitate surgical repair in a variety of cardiac diseases. Although steroids are generally known to be effective in the treatment of cerebral edema, the protective effects of steroids on the brain during CA are not conclusively established. Objectives of this study are twofold: the establishment of CPB technique in rabbits and the evaluation of preventive effect of steroid on the development of brain edema during CA. Material '||'&'||' Methods: Fifteen New Zealan white rabbits(average body weight 3.5kg) were divided into three experimental groups; control CA group(n=5), CA with Trendelenberg position group(n=5), and CA with Trendelenberg position + steroid(methylprednisolone 30 mglkg) administration group(n=5). After anesthetic induction and tracheostomy, a median sternotomy was performed. An aortic cannula(3.3mm) and a venous ncannula(14 Fr) were inserted, respectively in the ascending aorta and the right atrium. The CPB circuit consisted of a roller pump and a bubble oxygenator. Priming volume of the circuit was approximately 450m1 with 120" 150ml of blood. CPB was initiated at a flow rate of 80~85ml/kg/min, Ten min after the start of CPB, CA was established with duration of 40min at $20^{\circ}C$ of rectal temperature. After CA, CPB was restarted with 20min period of rewarming. Ten min after weaning, the animal was sacrif;cod. One-to-2g portions of the following tissues were rapidly d:ssected and water contents were examined and compared among gr ups: brain, cervical spinal cord, kidney, duodenum, lung, heart, liver, spleen, pancreas. stomach. Statistical significances were analyzed by Kruskal-Wallis nonparametric test. Results: CPB with CA was successfully performed in all cases. Flow rate of 60-100 mlfkgfmin was able to be maintained throughout CPB. During CPB, no significant metabolic acidosis was detected and aortic pressure ranged between 35-55 mmHg. After weaning from CPB, all hearts resumed normal beating spontaneously. There were no statistically significant differences in the water contents of tissues including brain among the three experimental groups. Conclusion: These results indicate (1) CPB can be reliably administered in rabbits if proper technique is used, (2) the effect of steroid on the protection of brain edema related to Trendelenburg position during CA is not established within the scope of this experiment.

• The Korea Journal of Herbology
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• 제29권6호
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• pp.165-173
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• 2014

Objectives : Platycodon Root is frequently used in traditional medicine to treat inflammatory diseases of the throat. The purpose of this study was to characterize the effect of the EtOH extract of fermented Platycodon grandiflorum on the ameliorative effects on the Antipruritic Effect of atopic dermatitis mouse model induced by compound 48/80 and ovalbumin (OVA)-induced allergic responses in mice. Methods : In the present study, we examined the anti allergic effect of Platycodon grandiflorum (PR) and its fermented production (FPR) in several mouse model. We measured acute ear edema in a mouse model caused by TPA and consecutively histological change of Ear tissue was observed by hematoxylin and eosin (H&E) staining. and also Scratching behaviors by compound 48/80 was investigated. The levels of allergic mediators such as immunoglobulin (Ig) E, and anti-oxidant markers such as SOD and MDA in the sera of OVA induced allergic mice were measured by enzyme-linked immunosorbent assay. Results : FPR inhibited compoud 48/80-induced scratching behavior in mice, as well as acetic acid-induced writhing in mice. The anti-scratching behavioral effect of FPR was more potent than PR. FPR extract significantly decreased the serum levels of IgE and MDA compared with those of OVA control group. Conclusions : These results indicate that Anti allergic effect of Platycodon grandiflorum is enhanced by fermentation with Saccharomyces cerevisae and FPR may be useful for protection from the itching reactions, which are IgE-mediated representative skin allergic diseases.

• Journal of Pharmacopuncture
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• 제19권4호
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• pp.319-328
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• 2016

Objectives: Advancements in nanotechnology have led to nanoparticle (NP) use in various fields of medicine. Although the potential of NPs is promising, the lack of documented evidence on the toxicological effects of NPs is concerning. A few studies have documented that homeopathy uses NPs. Unfortunately, very few sound scientific studies have explored the toxic effects of homeopathic drugs. Citing this lack of high-quality scientific evidence, regulatory agencies have been reluctant to endorse homeopathic treatment as an alternative or adjunct treatment. This study aimed to enhance our insight into the impact of commercially-available homeopathic drugs, to study the presence of NPs in those drugs and any deleterious effects they might have, and to determine the distribution pattern of NPs in zebrafish embryos (Danio rerio). Methods: Homeopathic dilutions were studied using high-resolution transmission electron microscopy with selected area electron diffraction (SAED). For the toxicity assessment on Zebrafish, embryos were exposed to a test solution from 4 - 6 hours post-fertilization, and embryos/larvae were assessed up to 5 days post-fertilization (dpf ) for viability and morphology. Toxicity was recorded in terms of mortality, hatching delay, phenotypic defects and metal accumulation. Around 5 dpf was found to be the optimum developmental stage for evaluation. Results: The present study aimed to conclusively prove the presence of NPs in all high dilutions of homeopathic drugs. Embryonic zebrafish were exposed to three homeopathic drugs with two potencies (30CH, 200CH) during early embryogenesis. The resulting morphological and cellular responses were observed. Exposure to these potencies produced no visibly significant malformations, pericardial edema, and mortality and no necrotic and apoptotic cellular death. Conclusion: Our findings clearly demonstrate that no toxic effects were observed for these three homeopathic drugs at the potencies and exposure times used in this study. The embryonic zebrafish model is recommended as a well-established method for rapidly assessing the toxicity of homeopathic drugs.

• BMB Reports
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• 제44권12호
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• pp.787-792
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• 2011

We investigated whether silk fibroin peptide derived from the silkworm, Bombyx mori, could inhibit inflammation and enhance the anti-inflammatory activity of Tat-superoxide dismutase (Tat-SOD), which was previously reported to effectively penetrate various cells and tissues and exert anti-oxidative activity in a mouse model of inflammation. Inflammation was induced by topical treatment of mouse ears with 12-O-tetradecanoylphorbol-13-acetate (TPA). Histological, Western blot, and reverse transcription-polymerase chain reaction data demonstrated that silk fibroin peptide or Tat-SOD alone could suppress elevated levels of cyclooxygenase-2, interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha induced by TPA. Moreover, silk fibroin peptide significantly enhanced the anti-inflammatory activity of Tat-SOD, although it had no influence on in vitro and in vivo transduction of Tat-SOD. Silk fibroin peptide exhibited anti-inflammatory activity in a mice model of inflammation. Therefore, silk fibroin peptide alone or in combination with Tat-SOD might be used as a therapeutic agent for various inflammatory diseases.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• 제16권3호
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• pp.116-128
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• 2003

Objectives : The incidence of allergic rhinitis has increased but treatment in most cases has only dealt with the symptoms. Medicine has been developed that shows fewer side effects. However, some side effects and the psychological stress over taking medicine has remained. There have been no studies so far performed on the effect of this Jeulminmilmae-tang's use, only. The purpose of this study was find out the therapeutic effects of its exclusive use on an Animal Model with Allergic Rhinitis. Methods : Thirty Sprague-Dawley rats were divided into three group : normal group, control group and sample group. To induce the allergic rhinitis in control group and sample group, rats were sensitized intraperitoneally with 0.1$\%$ ovalumin solution 3 times at intervals of 1 week. Then intranasal sensitization was performed by diffusing 0.1$\%$ ovalumin solution 3 times at intervals of 2 days. After that time, rats in the sample group were oral administration treated by Jeulminmilmae-tang for 28 days. Compared with the sample group, rats in the control group were oral administration treated by normal saline for 28 days. We observed changes in nasal mucosa and submucosa; also changes in the segment of neutrophil, eosinophil, Iympocyte and monocyte in blood. We used the statistical methods of student t-test(p 〈0.05). And we observed the changes of AST, ALT of three groups and used anova test statistically. Results : The segment of eosinophil was significantly decreased in treated group when compared with the control group(p 〈0.05). The segment of neutrophil. in blood were decreased in the treated group when compared with the control group but. that was not significant statistically(p 〈0.05). There were some regrowth of the cilium in the treated group. Histologic changes showed edema congestion and expantion of grandular cells in nasal submucosa and hypertrophy of epithelium ill nasal mucosa were decreased in treated group when compared with control group. Effects of Jeulminmilmae-tang on the liver function were also studies in rats. Treatment of Jeulminmilmae-tang did not affected on AST and ALT. Conclusions : The results may suggest that oral administration treatment using Jeulminmilmae-tang decreases the inflammatory response on an Animal Model with Allergic Rhinitis.

• The Journal of Pediatrics of Korean Medicine
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• 제29권4호
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• pp.97-107
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• 2015

Objectives Hataedock is the treatment that dispels toxic heat and meconium gathered at the fetus for the new born baby by orally administered herbal extracts. The purpose of this study was to evaluate whether Hataedock alleviate inflammatory skin damages in AD-induced NC/Nga mice through regulating of skin barrier maintain and Th2 differentiation. Methods We established an AD model in the 3-week-old NC/Nga mice through the repeated application of DNFB (dinitrochlorobenzene) on days 28, 35, 42 after Hataedock treatment which was orally administered. We identified the changes of skin barrier and Th2 differentiation through the histological and immunohistochemical changes of protein kinase C (PKC), interleukin (IL)-4, degranulated mast cell, Substance P and MMP-9. Results Our results suggested that Hataedock treatment significantly down-regulated levels of PKC by 82% (p < 0.001), as well as IL-4 by 56% (p < 0.001). Hataedock also suppressed mast cell infiltration, ear edema formation. and Substance P in the tissue of NC/Nga mice were decreased by 57% (p < 0.001), and MMP-9 by 55% (p < 0.001). Conclusions These results suggest that Hataedock alleviates AD through the down-regulation of PKC and Th2 cytokines, which are involved in the initial steps of AD development. Hataedock have potential application for the treatment of AD.

• Environmental Mutagens and Carcinogens
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• 제21권2호
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• pp.99-105
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• 2001

Sophoricoside was isolated as the inhibitor of IL-5 bioactivity from Sophora japonica (Leguminosae). It has been reported to has an anti-inflammatory effect on rat paw edema model. To develope as an anti-allergic drug, genotoxicity of sophoricoside was investigated in bacterial and mammalian cell system such as Ames bacterial reversion test, chromosomal aberration assay and single cell gel electrophoresis (Comet) assay. As results, in the range of 1,250~40 $\mu\textrm{g}$/plate sophoricoside concentrations was not shown significant mutagenic effects in Salmonella typhimurium TA 98, TA 100, TA 1535 and TA 1537 strains in Ames test. The 80% cell growth inhibition concentration (IC/SUB 80/) of sophoricoside was determined as above 5,000 $\mu\textrm{g}$/$m\ell$ in Chinese hamster lung (CHL) fibroblast cell and L5178Y mouse lymphoma cell line for the chromosomal aberration and comet assay, respectively. Sophoricoside was not induced chromosomal aberration in CHL fibroblast cell at concentrations of 700, 350 and 175 $\mu\textrm{g}$/$m\ell$ or 600, 300 and 150 $\mu\textrm{g}$/$m\ell$ in the absence or presence of S-9 metabolic activation system, respectively. Also, in the comet assay, the induction of DNA damage was not observed in L5178Y mouse lymphoma cell line both in the absence or presence of S-9 metabolic activation system. From these results, no genotoxic effects of sophoricoside were observed in bacterial and mammalian cell systems used in these experiments.

• Journal of Chest Surgery
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• 제32권11호
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• pp.978-983
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• 1999

Background: Complement activation with transpulmonary leukocyte sequestration is considered a main mediator leading to ischemia-reperfusion lung(I-R) injury. We studied the role of leukocytes in the formation of I-R injury in ovine cardiopulmonary bypass(CPB) model with a membrane oxygenator. Material and Method: Five sheep were used. CPB circuitry consisted of a roller pump(American Optical Corp., Greenwich, CT, USA) and a membrane oxygenator(UNIVOX-IC, Bentley, Baxter Health Corp, Irvine, CA, USA). The CPB time was fixed at 120 min. Ten minutes after the start of CPB, total CPB was established. Thereafter a total CPB of 100 min was performed, followed by another 10 min of partial CPB. The CPB was discontinued and the animals were fully recovered. For measuring left and right atrial leukocyte counts, blood samples were taken before thoracotomy, 5 min and 109 in after the start of CPB, and 30 min and 120 min after weaning. C3a was measured before thoracotomy, 109 min after the start of CPB, and 30 min and 120 min after weaning. Plasma malondialdehyde(MDA) was checked before thoracotomy, 109 min after the start of CPB, and 30 min after weaning. One to two grams of lung tissue were taken for water content measurement before thoracotomy, 109 min after the start of CPB, and 30 min after weaning. Lung biopsy specimens were examined by light and electron microscopy. Result: Of 5 animals, 4 survived the experimental procedures. Of these, 3 animals survived on a long-term basis. No significant differences in transpulmonary gradients of leukocyte were found and no significant complement activation was expressed by C3a levels. MDA level did not show significant changes related to lung reperfusion despite an increase after the start of CPB. On both light and electron microscopic examinations, mild to moderate acute lung change was observed. Interstitial edema, leakage of erythrocytes into the alveolar space and endothelial cell swelling were the main findings. Water content of the lung showed a slight increase after the start of CPB, but there was no statistical significance. Conclusion: These findings indicate that ischemia-repersusion lung injury may not be from complement activation-leukocyte sequestration but from another source of oxygen free radicals related to CPB.

• Journal of Physiology & Pathology in Korean Medicine
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• 제16권4호
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• pp.810-817
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• 2002

This study was carried out to know the effects of sopunghwalhyeoltang-gamibang(hereinafter referred to SPHHT) on the inhibition of arthritis induced by collagen on the mouse. Various experimental were performed in vivo (in DBA/1 J mice which are experimental model of arthritis induced by collagen) to analyse the immunomodulatory effects of SPHHT. The results were obtained as follows: 1. The cytotoxicity against mLFC was not measured in all concentration. 2. The arthritis index, incidence, hind paw edema, delayed-type hypersensitivity reaction, spleen weight were reduced in SPHHT treated group. 3. The expression of CD3 ε +/CD4+, CD3 ε +/CD8+ and CD19+ in peripheral blood mononuclear were reduced in SPHHT treated group. 4. The production of pro-inflammatory cytokines such as IL-6 and TNF-α were significantly reduced in SPHHT treated group. 5. The formation of new bones and synivium were stimulated in SPHHT treated group. Comparison of the results for this study showed that Sopung-hwalhyeoltang-gamibang had immunomodulatory effects. So we expect that Sopunghwalhyeoltang-gamibang should be used as a effective drugs for not only rheumatoid arthritis but also another auto-immune disease. Therefore we have to survey continuously in looking for the effective substance and mechanism in the future.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 한국환경독성학회 2003년도 춘계학술대회
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• pp.183-184
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• 2003

Sophoricoside was isolated as the inhibitor of IL-5 bioactivity from Sophora japonica (Leguminosae). It has been reported to have an anti-inflammatory effect on rat paw edema model. To develop as an anti-allergic drug, genotoxicity of sophoricoside was investigated in bacterial and mammalian cell system such as Ames bacterial test, chromosomal aberration assay, Comet assay and MOLY assay. In Ames test, sophoricoside of 5000 ∼ 313 $\mu\textrm{g}$/plate concentrations was not shown significant mutagenic effect in Salmonella typhimurium TA98, TA100, TA1535 and TA1537 strains. The cytotoxicity (IC$\_$50/ and IC$\_$20/) of sophoricoside was determined above the concentration of 5000 $\mu\textrm{g}$/ml in Chinese hamster lung (CHL) fibroblast cell and L5178Y mouse lymphoma cell line. At concentrations of 5000, 2500 and 1250 $\mu\textrm{g}$/ml, this compound was not induced chromosomal aberration in CHL fibroblast cell in the absence and presence of S-9 metabolic activation system. Also in comet assay, DNA damage was not observed in L5178Y cell line. Also in MOLY assay, sophoricoside of 5000 ∼ 313 $\mu\textrm{g}$/ml concentrations was not shown significant mutagenic effect in absence of S-9 metabolic activation system. However, the higher concentration of 5000 and 2500 $\mu\textrm{g}$/ml of sophoricoside induced the increased mutation frequency (MF) in the presence of S-9 metabolic activation system. From these results, no genotoxic effects of sophoricoside observed in bacterial systems whereas, genotoxic effects observed in mammalian cell systems in the presence of metabolic activation system. These results suggested that the metabolite(s) of sophoricoside can cause some genotoxic effects in mammalian cells.