• Tuberculosis and Respiratory Diseases
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• v.50 no.1
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• pp.12-28
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• 2001

Background and Object : Immunostimulatory CpG-oligodeoxynucleotides (ISS CpG-ODN) up-regulate the $T_{H1}$-type immune response and down-regulate the $T_{H2}$-type response. This study was performed to investigate the immune response changes resulting from ISS CpG-ODN on bronchial hyperresponsiveness, eosinophilic inflammation and mucus hypersecretion in rat asthma. Materials and Methods : 10 normal controls(NC) and 26 asthmatic rats, which were generated by ovalbumin(OVA) sensitization and challenge, were studied. The asthmatic rats were randomized into 11 asthma controls(AC) and 15 in the asthma-CpG treatment group(CpG). The CpG group was administered ISS CpG-ODN intramuscularly and the AC group was administered a placebo(0.9% NaCl) on day 15 and 20. After CpG-ODN or placebo administration, we measured the IFN-${\gamma}$($T_{H1}$-type cytokine) and IL-4($T_{H2}$-type cytokine) levels in the bronchoalveolar lavage fluid(BALF), the specific airway resistance(sRaw), eosinophilic fraction in BALF, eosinophilic infiltration, goblet cell dysplasia and MUC5AC gene expression in the lung tissue. Results : In the BALF of the CpG group, the IFN-${\gamma}$ concentration was significantly high and the IL-4 concentration was significantly low when compared with the AC group. Both the sRaw and eosinophilic fraction, and infiltration into the BALF and lung tissue significantly lower in the CpG group when compared with the AC group. However, little difference in goblet cell dysplasia and MUC5AC gene expression was observed between the CpG group and the AC group. Conclusion : ISS CpG-ODN decreases bronchial hyperresponsiveness and eosinophilic inflammation in the rat asthma model through the up-regulation of the $T_{H1}$-type immune response with the down-regulation of the $T_{H2}$-type response. However, the effect of these immune response changes on mucus hypersecretion was is not remarkable in this study.

• Journal of Chest Surgery
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• v.34 no.6
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• pp.447-453
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• 2001

Background: Although pulmonary resection is the standard approach for the management of pulmonary metastases from soft tissue sarcoma, most of them are unresectable and chemotherapy remains the only option. The effectiveness of the cytotoxic drugs may be limited by the toxicities that occur before the therapeutic dose is reached. The regional administration of doxorubicin using pulmonary arterial perfusion in a rodent model can produce 10 to 25 times higher concentrations in the lung than systemic administration with minimal systemic toxicities. However, it is unclear whether a high concentration of doxorubicin has beneficial effects for killing cancer cells. Material and Method: We studied this to evaluate the dose-dependent cytotoxic and apoptotic effects of doxorubicin on methylcholanthrene-induced rat fibrosarcoma(MCA) cells. This study examined the cytotoxicity and apoptosis-related gene expressions(Fas, FasL, Bax, caspase 1, caspase 2, caspase 8, Bcl-2, Bcl-xL, Bcl-xS) in MCA cells after 24 hours exposure to various concentrations of doxorubicin such as 1, 5, 10, 50, and 100 $\mu$M. Result: Dose-dependent cytotoxicity was observed after 24 hours exposure to doxorubicin. However, peak apoptosis after 24 hours exposure was observed at 5 $\mu$M of doxorubicin. Above 5 $\mu$M, apoptotic activity was decreased with dose-increment. All mRNA levels of apoptosis-related genes after 24 hours exposure were up-regulated above the control level at 1 $\mu$M of doxorubicin and then decreased by doxorubicin dose-increment except caspase 8, which showed higher levels than the control level at 5 $\mu$M. Apoptosis-related protein levels were highest at 1 $\mu$M of doxorubicin and then decreased by doxorubicin dose-increment. However, Bax and Bcl-xL proteins steadily showed higher levels than the control throughout the different concentrations of doxorubicin. Conclusion: These results suggest that apoptosis is the main cytotoxic mechanism in low concentrations of doxorubicin in MCA cells and apoptosis-related genes, such as Bax, caspase 8, and Bcl-xL, are involved. At high concentrations, doxorubicin still can kill MCA cells, even when apoptosis is inhibited, and have its propriety for achieving much cytotoxicity against MCA cells.

• Neonatal Medicine
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• v.18 no.1
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• pp.59-69
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• 2011

Purpose: Current studies have demonstrated the neuroprotective effects of 6-cyano-7-nitroquinoxalin-2,3-dione (CNQX) in many animal models of brain injury, including hypoxic-ischemic (HI) encephlopathy, trauma and excitotoxicity, but limited data are available for those during the neonatal periods. Here we investigated whether CNQX can protect the developing rat brain from HI injury via mediation of nitric oxide synthase. Methods: In an in vivo model, left carotid artery ligation was done in 7-day-old Sprague-Dawley (SD) rat pups. The animals were divided into six groups; normoxia (N), hypoxia (H), hypoxia with sham-operation (HS), hypoxia with operation (HO), HO treated with vehicle (HV), and HO treated with CNQX at a dose of 10 mg/kg (HC). Hypoxia was made by exposure to a 2 hr period in the hypoxic chamber (92% $N_2$, 8% $O_2$). In an in vitro model, embryonic cortical neuronal cell culture of SD rats at 18-day gestation was done. The cultured cells were divided into three groups: normoxia (N), hypoxia (H), and hypoxia treated with CNQX (HC). The N group was prepared in 5% $CO_2$ incubators and the other groups were placed in 1% $O_2$) incubators (94% $N_2$, 5% $CO_2$) for 16 hr. Results: In the in vitvo and in vivo models, the expressions of iNOS and eNOS were reduced in the hypoxia group when compared to the normoxia group, whereas they were increased in the CNQX-treated group compared to the hypoxia group. In contrast, the expression of nNOS was showed reversely. Conclusion: CNQX has neuroprotective property over perinatal HI brain injury via mediation of nitric oxide synthase.

• Herbal Formula Science
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• v.20 no.1
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• pp.25-40
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• 2012

The purpose of this study explain the experimental effects of Guizhishaoyaozhimu-Tang (桂枝芍藥知母湯) that have clinical efficacy in rheumatoid Arthritis. Materials of present study were Guizhishaoyaozhimu-Tang freeze dried powder (GSZT), Sprague-dawley rats (300 g or so, male), various kinds of needing experimental studis. In order to study the therapeutic effects of GSZT, this Prescription (GSZT 500 mg/kg, 1,000 mg/kg) were administered per oral to the rats with the arthritis induced by Freund's complete adjuvant ($0.2m{\ell}/kg$), several experimental items were measured and compared each other ; that is body weight, rate of edema, analgesic effect by hot plate method, WBC, total protein, TNF-${\alpha}$, IL-10 and expression and localization of H&E, COX-2 staining in synovial tissues from rat with rheumatoid arthritis by immunohistochemical staining using polyclonal COX-2 antibodies. Rats were divided into four groups. Normal group was not treated with Freund's complete adjuvant and treated with DDW 1.0 $m{\ell}$, Control group was treated with Freund's complete adjuvant 0.2 $m{\ell}/kg$ and DDW 1.0 $m{\ell}$, Sample A group was treated with Freund's complete adjuvant 0.2 $m{\ell}/kg$ and GSZT (500 $mg/m{\ell}$) $1.0m{\ell}$, Sample B group was treated with Freund's complete adjuvant 0.2 $m{\ell}/kg$ and GSZT (1,000 $mg/m{\ell}$) 1.0 $m{\ell}$. 0 was day that did not start experiment, 14 was day that confirmed rheumatism induced by Freund's complete adjuvant, 28 was day that completed experiment. The following results were obtained in this study ; Sample A group was increased in body weight, escape time and paw licking time statistical significance compared with Control group, and were decreased in edema, WBC, total protein, TNF-${\alpha}$ with statistical significance compared with Control group. Sample B group was increased in escape time with statistical significance compared with Control group, and were decreased in edema, WBC, total protein with statistical significance compared with Control group. Sample A and Sample B groups were increased in IL-10 compared with Control group, and Sample B group was decreased in TNF-${\alpha}$ compared with Control group. And, Control, Sample A and Sample B groups were showed considerable reduction of positive expression in comparison to Normal group. Especially, Sample B group was most significantly reduction of positive expression than the other groups. From above results, I suggest that GuizhiShaoyaoZhimu-Tang can be used for curing rheumatoid arthritis.

• Journal of Ginseng Research
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• v.42 no.2
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• pp.183-191
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• 2018

Background: Ginseng saponin has long been used as a traditional Asian medicine and is known to be effective in treating various kinds of pain. Ginsenoside Rf is one of the biologically active saponins found in ginseng. We evaluated ginsenoside Rf's antinociceptive and anti-inflammatory effects, and its mechanism of action on adrenergic and serotonergic receptors, in an incisional pain model. Methods: Mechanical hyperalgesia was induced via plantar incision in rats followed by intraperitoneal administration of increasing doses of ginsenoside Rf (vehicle, 0.5 mg/kg, 1 mg/kg, 1.5 mg/kg, and 2 mg/kg). The antinociceptive effect was also compared in a Positive Control Group that received a ketorolac (30 mg/kg) injection, and the $Na{\ddot{i}}ve$ Group, which did not undergo incision. To evaluate the mechanism of action, rats were treated with prazosin (1 mg/kg), yohimbine (2 mg/kg), or ketanserin (1 mg/kg) prior to receiving ginsenoside Rf (1.5 mg/kg). The mechanical withdrawal threshold was measured using von Frey filaments at various time points before and after ginsenoside Rf administration. To evaluate the anti-inflammatory effect, serum interleukin $(IL)-1{\beta}$, IL-6, and tumor necrotizing $factor-{\alpha}$ levels were measured. Results: Ginsenoside Rf increased the mechanical withdrawal threshold significantly, with a curvilinear dose-response curve peaking at 1.5 mg/kg. $IL-1{\beta}$, IL-6, and tumor necrotizing $factor-{\alpha}$ levels significantly decreased after ginsenoside Rf treatment. Ginsenoside Rf's antinociceptive effect was reduced by yohimbine, but potentiated by prazosin and ketanserin. Conclusion: Intraperitoneal ginsenoside Rf has an antinociceptive effect peaking at a dose of 1.5 mg/kg. Anti-inflammatory effects were also detected.

• Preventive Nutrition and Food Science
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• v.3 no.4
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• pp.362-367
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• 1998

Thyroid hormone(T3) stimulates hepatic lipogenesis by increasing expression of genes, indluding acetyl-CoA carboxylase and fatty acid synthase. S14 protein, which is thougth to be involved in lipid metabolism , appears to respond in parallel . Effect of T3 on lipogenesis in white and brown adipose tissue are less clear, and may be complicated by indirect effects of the hormone. We developed an adipocytes system where the indirect effects of thyroid hormone are abolished and direct effects of T3 on lipogenesis could be tested. Fat accumulation was mesured by Oil-Red O staining. Insulin clearly enhanced fat accumulation by 2-fold . Isobutylemethylxanthie(IBMX) apeared to inhibit insulin -stimulated fat accumulation. Dexamethasone increased insulin-stimulatedfat accumulation about 1.3-fold. confluent adipocytes were cultured in serum-free medium or medium containing 10% fetal calf serum or 10% fetal calf serum stripped of thyroid hormone and lipogenesis, assessed by the incorporation of 3H2O , was measured. Medium without serum or supplemented with T3-depleted serum did not amplify the stimulatory effect of T3 on lipogenesis compared to medium containing 10% fetal calf seru. Dexamethasone alone led to a decrease inlopogenesis of about 50 % in white adipocytes and 25% in brown adipocytes. However, dexamethasone amplified the lipogenic respnse to T3 by about 30% in whit eadipocytes and 60% in brown adipocytes. T3(1$\mu$M) stimulated lipogenesis and acetyl-CoA carboxylase and fatty acid syntase mRNA levels up to 2 -fold in both types of adipocytes. It seems that these adipocytes systems are as useful model to study the effects of hormones on lipogenic gene expression as well as lipogenesis.

• International Journal of Oral Biology
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• v.37 no.3
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• pp.121-129
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• 2012

Previous clinical studies have demonstrated that gabapentin, a drug that binds to the voltage-gated calcium channel ${\alpha}2{\delta}1$ subunit proteins, is effective in the management of neuropathic pain, but there is limited evidence that addresses the participation of glial cells in the antiallodynic effects of this drug. The present study investigated the participation of glial cells in the anti-nociceptive effects of gabapentin in rats with trigeminal neuropathic pain produced by mal-positioned dental implants. Under anesthesia, the left mandibular second molar was extracted and replaced by a miniature dental implant to induce injury to the inferior alveolar nerve. Mal-positioned dental implants significantly decreased the air-puff thresholds both ipsilateral and contralateral to the injury site. Gabapentin was administered intracisternally beginning on postoperative day (POD) 1 or on POD 7 for three days. Early or late treatment with 0.3, 3, or 30 ${\mu}g$ of gabapentin produced significant anti-allodynic effect in the rats with mal-positioned dental implants. On POD 9, in the mal-positioned dental implants group, OX-42, a microglia marker, and GFAP, an astrocyte marker, were found to be up-regulated in the medullary dorsal horn, compared with the naive group. However, the intracisternal administration of gabapentin (30 ${\mu}g$) failed to reduce the number of activated microglia or astrocytes in the medullary dorsal horn. These findings suggest that gabapentin produces significant antinociceptive effects, which are not mediated by the inhibition of glial cell function in the medullary dorsal horn, in a rat model of trigeminal neuropathic pain.

• Journal of the East Asian Society of Dietary Life
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• v.8 no.2
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• pp.126-136
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• 1998

This study was designed to determine the effects of linoleic acid contents and $\omega$ 6/$\omega$3 ratios on the induction of gastric ulcer by water immersion and restraint stress. Sprague-Dawley rats were fed 5diets containing 7% fat(w/w) for 6weeks. These diet groups were Lh, Mh, Hh, Mm, Ml, : 3 different linoleic acid levels(0.3% of energy(L). 3.5(M), 10(H) and 3 different $\omega$6/$\omega$3 ratios (11(1), 33(m), 100(h) with beef tallow, sunflower or fish oil. The Lh group showed a significantly higher ulcer index (UI) than the Mh and Hh groups(p<0.05). At the same linoleic levels, the UI had no significant difference within the $\omega$6/$\omega$3 ratios. The Mh group showed significantly higher (p<0.05) PGE2 and TBX2 content than any other group. Pearson's correlation coeffcients between UI and PGE2 and TBX2 had a negatively significant correlation(p<0.05). Linoleic acid of gastric mucosal phospholipids was reflected by the diet, but was not significantly different. The most significant finding of this study is that not only the absolute amount of linoleic acid, but also the $\omega$6/$\omega$3 ratios are important factors for the prevention of gastric ulcer.

• Journal of Korean Neurosurgical Society
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• v.53 no.2
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• pp.72-76
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• 2013

Objective : Cerebral aneurysm (CA) is an important acquired cerebrovascular disease that can cause catastrophic results. MicroRNAs (miRNAs) are small non-coding RNAs, playing essential roles in modulating basic physiologic and pathological processes. Currently, evidences have been established about biologic relationship between miRNAs and abdominal aortic aneurysms. However, biologic roles of miRNAs in CA formation have not been explained yet. We employed microarray analysis to detect and compare miRNA expression profiles in late stage of CA in rat model. Methods : Twenty-six, 7-week-old male Sprague-Dawley rats underwent a CA induction procedure. The control animals (n=11) were fed a normal diet, and the experimental animals (n=26) were fed a normal diet with 1% normal saline for 3 months. Then, the rats were sacrificed, their cerebral arteries were dissected, and the five regions of aneurysmal dilation on the left posterior communicating artery were cut for miRNA microarrays analysis. Six miRNAs (miRNA-1, miRNA-223, miRNA-24-1-5p, miRNA-551b, miRNA-433, and miRNA-489) were randomly chosen for validation using real-time quantitative PCR. Results : Among a set of differentially expressed miRNAs, 14 miRNAs were over-expressed more than 200% and 6 miRNAs were down-expressed lower than 50% in the CA tissues. Conclusion : The results show that miRNAs might take part in CA formation probably by affecting multiple target genes and signaling pathways. Further investigations to identify the exact roles of these miRNAs in CA formation are required.

• Biomolecules & Therapeutics
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• v.21 no.5
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• pp.381-390
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• 2013

The purpose of this study was to examine whether ginsenoside Rg3 (GRg3) could improve learning and memory impairments and inflammatory reactions induced by injecting lipopolysaccharide (LPS) into the brains of rats. The effects of GRg3 on proinflammatory mediators in the hippocampus and the underlying mechanisms of these effects were also investigated. Injection of LPS into the lateral ventricle caused chronic inflammation and produced deficits in learning in a memory-impairment animal model. Daily administration of GRg3 (10, 20, and 50 mg/kg, i.p.) for 21 consecutive days markedly improved the LPS-induced learning and memory disabilities demonstrated on the step-through passive avoidance test and Morris water maze test. GRg3 administration significantly decreased expression of pro-inflammatory mediators such as tumor necrosis factor-${\alpha}$, interleukin-1${\beta}$, and cyclooxygenase-2 in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. Together, these findings suggest that GRg3 significantly attenuated LPS-induced cognitive impairment by inhibiting the expression of pro-inflammatory mediators in the rat brain. These results suggest that GRg3 may be effective for preventing or slowing the development of neurological disorders, including Alzheimer's disease, by improving cognitive and memory functions due to its anti-inflammatory activity in the brain.