• IMMUNE NETWORK
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• v.3 no.3
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• pp.201-210
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• 2003

Objective: The role of prostaglandin $E_2$ (PGE2) in the etiopathogenesis of immune and inflammatory diseases has become the subject of recent debate. To determine the role of PGE2 in rheumatoid arthritis (RA), we tested the effect of exogenous PGE2 on the production of cyclooxygenase-2 (COX-2) by rheumatoid synoviocytes. Methods: Fibroblast-like synoviocytes (FLS) were prepared from the synovial tissues of RA patients, and cultured in the presence of PGE2. The COX-2 mRNA and protein expression levels were determined by RT-PCR and Western blot analysis, respectively. The PGE2 receptor subtypes in the FLS were analyzed by RT-PCR. Electrophoretic mobility shift assay (EMSA) was used to measure the NF-${\kappa}B$ binding activity for COX-2 transcription. The in vivoeffect of PGE2 on the development of arthritis was also tested in collagen induced arthritis (CIA) animals. Results: PGE2 ($10^{-11}$ to $10^{-5}M$) dose-dependently inhibited the expression of COX-2 mRNA and the COX-2 protein stimulated with IL-$1{\beta}$, but not COX-1 mRNA. NS-398, a selective COX-2 inhibitor, displayed an additive effect on PGE2-induced COX-2 downregulation. The FLS predominantly expressed the PGE2 receptor (EP) 2 and EP4, which mediated the COX-2 suppression by PGE2. Treatment with anti-IL-10 monoclonal antibodies partially reversed the PGE2-induced suppression of COX-2 mRNA, suggesting that IL-10 may be involved in modulating COX-2 by PGE2. Experiments using an inducer and an inhibitor of cyclic AMP (cAMP) suggest that cAMP is the major intracellular signal that mediates the regulatory effect of PGE2 on COX-2 expression. EMSA revealed that PGE2 inhibited the binding of NF-${\kappa}B$ in the COX-2 promoter via a cAMP dependent pathway. In addition, a subcutaneous injection of PGE2 twice daily for 2 weeks significantly reduced the incidence and severity of CIA as well as the production of IgG antibodies to type II collagen. Conclusion: Our data suggest that overproduced PGE2 in the RA joints may function as an autocrine regulator of its own synthesis by inhibiting COX-2 production and may, in part, play an anti-inflammatory role in the arthritic joints.

• Bulletin of the Korean Chemical Society
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• v.28 no.12
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• pp.2449-2453
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• 2007

L-[18F]FMAU ([18F]1b) was prepared from the precursor 2-O-[(trifluoromethyl)-sulfonyl]-1,3,5-tri-Obenzoyl- α-L-ribofuranose, by coupling the radioactive fluoro-sugar with the corresponding silylated thymine in 4 steps. The final products, including the α and β anomers, were purified using reverse phase HPLC with an appropriate solvent (5% CH3CN/H2O) at a flow rate of 3.0 mL/min. The total elapsed time of synthesis was about 180-200 min from EOB. The α/β anomeric ratio of the compounds was about 1:9, and the radiochemical purity of the product (β-form) was >98% with decay-corrected yields of 25-35%. All radioactive samples were confirmed using co-injection with pure non-radioactive analogues in every step. In the cellular uptake in vitro test of herpes simplex virus-thymidine kinase (HSV1-TK) gene expressed cells, the percent uptake of injected dose (%ID) of L- and D-FMAU was 37.28 and 65.86, respectively after 240 min incubation. However, the relative uptake (MCA-TK/MCA cellular uptake ratio) of L-FMAU was higher than that of D-FMAU (%ID of L-FMAU, 0.36 and D-FMAU, 0.93 after 240 min incubation in MCA cells). This means that L-FMAU will show better specific HSV1-TK gene expressed cell uptake for selective HSV1-TK gene imaging.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.4
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• pp.506-510
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• 2010

As an attempt to develop new functional health beverage by using medicinal herb, we investigated the effect of medicinal plant extract (MPE) on mean arterial blood pressure (MABP) and regional cerebral blood flow (rCBF) of rats. The changes of MABP and rCBF were determined by LDF methods. LDF allows for real time, noninvasive, continuous recordings of local CBF. MABP in MPE treated rats showed significant change of MPE 1.0 and 10.0 mg/kg. MPE i.v. administration showed significant increase of rCBF in a dose-dependent manner. Propranolol pretreated MABP showed significant change in the increase of MPE. rCBF of propranolol pretreated rats showed significant change from the i.v. injection concentration of 1.0 and 10.0 mg/kg. The ischemia/reperfusion induced oxidative stress may have contributed to cerebral damage in rats, and the present study provides clear evidence for the beneficial effect of MPE on ischemia induced brain injury. Also, the action mechanism in elevation effect of MPE on rCBF might be concerned with the role of $\beta$-adrenoceptor. The exact component and mechanism remains for the future study.

• Environmental Mutagens and Carcinogens
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• v.22 no.2
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• pp.65-69
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• 2002

To elucidate the effect of microsphere coinjection on the administration of oligodeoxynucleotides (ODN), we have investigated biodistribution of ［S-35］-labeled antisense ODN targeted to cAMP-dependent protein kinase (PKA) RI-$\alpha$ subunit in nude mice xenografted with WiDr (human colon cancer, ATCC CCL218). The strategy of using microsphere has been proposed for cancer treatment as a carrier of therapeutic ODN so that it could offer an advantage with respect to maintaining constant ODN levels in blood and obtaining higher therapeutic ODN concentration at tumor sites. Comparative biodistribution studies were performed in nude mice (female, 20 g of body weight, n = 4-6) xenografted with WiDr cancer cells, when 0.1 $\mu$Ci (specific activity, 2.94 mCi/$\mu$mole) of ［S-35］-labeled RI-$\alpha$ antisense ODN was injected alone or with microsphere (PLG-18, polylactic copolymer with cationic surfactant DDAB18). Peak tumor uptake of ［S-35］-labeled ODN was significantly increased from 17.7% (at 6 h) of injected dose per gram of tissue (ID/g) to 42.5% (at 24 h) ID/g when microsphere was coinjected with ODN. The different biodistribution in the kidney accumulation (e.g., 100.2% ID/g for ODN alone and 54.9%/ID/g for microshpere coinjection) may contribute to higher blood concentration (e.g., 21.5%ID/$m\ell$ for ODN alone and 37.5%ID/$m\ell$ for microsphere coinjection) of radiolabeled ODN. Of importance is the fact that the whole body retention of radioactivity increased with microsphere coinjection from 50.8%ID/g to 68.0%ID/g after 24-h of injection. This decreased kidney accumulation and increased whole body retention of ［S-35］-labeled ODN resulted in a significant improvement of ODN targeting to the tumor site. In conclusion, the coinjection of microsphere appears to be an important carrier system in vehiculation of antisense oligonucleotide to the tumor tissue in vivo.

• Physical Therapy Korea
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• v.10 no.2
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• pp.45-59
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• 2003

The purpose of this study was to assess the effects of ultrasound on adjuvant-induced arthritis in rats. Adjuvant arthritis was induced in 26 female Sprauge-Dawley rats by the subcutaneous injection of a single dose of .1 mL of Complete Freund's Adjuvant (CFA) (1 mg of Mycobacterium Butyricum suspended in .1 $m{\ell}$ paraffin oil) into the right hind paw. After confirming inflammatory edema and arthritis in the paw 2 weeks later, the arthritic rats were divided into 3 groups, i.e., a control group, a pulsed ultrasound group (Group A), and a continuous ultrasound group (Group B) with 8 rats placed in each group. The rats in Group A were treated with pulsed ultrasound at 1 MHz frequency with .5 $W/cm^2$ intensity in 1 : 4 mode for 3 minutes. The rats in Group B were treated with continuous ultrasound at 1 MHz frequency with 2 $W/cm^2$ intensity in the continuous mode for 3 minutes. The ultrasound treatment was done in the left and right ankles for 2 weeks. Clinical, radiographic and histopathologic findings were then evaluated before and after treatment and yielded the following results. 1. No significant difference was present in body weight between the control group and the treated groups. 2. A statistically significant decrease in the edema of the paw was seen in the rats in Group A that was treated with pulsed ultrasound by 26~29 days after the treatment started (p<.05). 3. According to radiological examination, Group A showed the lowest score in arthritis scale which means it showed a tendency to suppress arthritic inflammation of the left and right hind paws. However, no statistically significant difference was present in the score between the control group, Group A and Group B. 4. According to histopathologic findings, the degree of infiltration by inflammatory cells and hypertrophy of the synovium were less in Group A compared with the control group and Group B. The results of the study show that rats that were treated with the pulsed ultrasound effectively suppressed adjuvant arthritis. However, more effort is needed to objectively prove the effectiveness of ultrasound by developing more sensitive testing methods that could quantitatively evaluate the treatment effects of acute rheumatoid arthritis and by trying out different ultrasound treatment methods.

• Journal of fish pathology
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• v.19 no.1
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• pp.73-82
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• 2006

Streptococcal infections were considered as a serious problem because of significant economic losses in fish farm industry. We evaluated the efficacies of Streptococcus iniae vaccines in olive flounder, Paralichthys olivaceus. The vaccines were prepared from 10% neutral buffered formalin to give a final concentration of 0.3% or 3%, respectively. Fish were immunized by intraperitoneal injection of the experimental vaccines once or twice. Neither of the vaccines gave rise to any significant side effects. The antibody titers of booster immunized groups were significantly higher than those of prime immunized groups with both of the vaccines. According to formalin dosage, significantly increased antibody titers were produced by 3% formalin-killed cells (FKC) at 4weeks and 8weeks after prime and booster vaccination, respectively. Although the different levels of antibody production were showed by the vaccinated fish, the good protection obtained in challenge trials of the both vaccines. Fish immunized with 0.3% FKC once or twice had the relative percent survival (RPS) of 66.7% and 87.5%, respectively. Similarly, fish immunized with 3% FKC once or twice had the RPS of 70.0% and 77.0%, respectively. Further experiments are needed to study not only correlation between the antibody titers and RPS against S. iniae but also the side effects of high dose of formalin on antigenicity.

• Journal of Gastric Cancer
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• v.20 no.1
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• pp.60-71
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• 2020

Purpose: The utility of 18-fluordesoxyglucose positron emission tomography ([¹⁸F]-FDG-PET) combined with computer tomography or magnetic resonance imaging (MRI) in gastric cancer remains controversial and a rationale for patient selection is desired. This study aims to establish a preclinical patient-derived xenograft (PDX) based [¹⁸F]-FDG-PET/MRI protocol for gastric cancer and compare different PDX models regarding tumor growth and FDG uptake. Materials and Methods: Female BALB/c nu/nu mice were implanted orthotopically and subcutaneously with gastric cancer PDX. [¹⁸F]-FDG-PET/MRI scanning protocol evaluation included different tumor sizes, FDG doses, scanning intervals, and organ-specific uptake. FDG avidity of similar PDX cases were compared between ortho- and heterotopic tumor implantation methods. Microscopic and immunohistochemical investigations were performed to confirm tumor growth and correlate the glycolysis markers glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) with FDG uptake. Results: Organ-specific uptake analysis showed specific FDG avidity of the tumor tissue. Standard scanning protocol was determined to include 150 μCi FDG injection dose and scanning after one hour. Comparison of heterotopic and orthotopic implanted mice revealed a long growth interval for orthotopic models with a high uptake in similar PDX tissues. The H-score of GLUT1 and HK2 expression in tumor cells correlated with the measured maximal standardized uptake value values (GLUT1: Pearson r=0.743, P=0.009; HK2: Pearson r=0.605, P=0.049). Conclusions: This preclinical gastric cancer PDX based [¹⁸F]-FDG-PET/MRI protocol reveals tumor specific FDG uptake and shows correlation to glucose metabolic proteins. Our findings provide a PET/MRI PDX model that can be applicable for translational gastric cancer research.

• Asian-Australasian Journal of Animal Sciences
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• v.15 no.12
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• pp.1760-1764
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• 2002

In order to elucidate the physiological function of circulating IGF-I on muscle protein synthesis in the chicken under malnutritional conditions, we administrated recombinant chicken IGF-I using a osmotic mini pump to fasted young chickens and measured the rate of muscle protein synthesis and plasma metabolite. The pumps delivered IGF-I at the rate of $22{\mu}g/d\{300{\mu}g{\cdot}(kg\;body\;weight{\cdot}d)^{-1}\}$. Fractional rate of protein synthesis in the muscle was measured using a large dose injection of L-[$2,6-^3H$]phenylalanine. Constant infusion of chicken IGF-I did not affect plasma glucose level. Significant interaction between dietary treatment and IGF-I infusion was observed in plasma NEFA and total cholesterol concentrations. When chicks were fasted, IGF-I infusion decreased plasma NEFA and total cholesterol concentrations. On the other hand, IGF-I administration did not affect plasma levels of both metabolites. Fasting reduced plasma triglyceride concentration significantly. IGF-I infusion also decreased the level of plasma triglyceride. Plasma IGF-I concentration of young chickens was halved by fasting for 1 d. IGF-I infusion using an osmotic minipump for 1 d increased plasma IGF-I concentration in fasted chicks to the level of fed chicks. Fasting decreased body weight and the loss of body weight was significantly ameliorated by IGF-I infusion. There was a significant interaction between dietary treatment and IGF-I infusion in the fractional rate of breast muscle protein synthesis. There was no effect of IGF-I infusion on muscle protein synthesis in fed chicks. Muscle protein synthesis reduced by fasting was ameliorated by IGF-I infusion, but did not reach to the level of fed control. Muscle weight of fasted chicks infused with IGF-I was similar to fasted birds without IGF-I infusion, which suggests that muscle protein degradation would be increased by IGF-I infusion as well as protein synthesis in fasted chicks.

• The Korean Journal of Nuclear Medicine
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• v.14 no.1
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• pp.1-8
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• 1980

Serum TSH levels were measured by radioimmunoassay before and after intravenous administration of synthetic thyrotropin-releasing hormone (TRH) to 15 normal subjects and 55 patients with primary thyroid disease (14 patients with euthyroidism, 24 patients with thyrotoxicosis and 17 patients with hypothyroidism) to evaluate pituitary TSH reserve and its diagnostic availability. The observed results were as follows. 1. In normal subjects, serum TSH responses to synthetic TRH were $3.2{\pm}1.0$ at 0min (baseline TSH level), $8.0{\pm}4.0$ at 10min, $11.7{\pm}5.0$ at 20min, $13.7{\pm}7.1$ at 30min, $9.7{\pm}5.0$ at 60min., $5.2{\pm}2.0$ at 120min. and $3.6{\pm}0.4{\mu}U/ml$ at 180 min. Serum TSH peaked at $20{\sim}30$ minutes and returned nearly to baseline at 180minutes. 2. In euthyroid group, serum TSH responses to synthetic TRH were $3.3{\pm}1.6$ at 0min, $8.6{\pm}8.0$ at 10min, $10.9{\pm}8.5$ at 20min, $12.5{\pm}8.4$ at 30min, $9.0{\pm}5.9$ at 60min, $5.6{\pm}2.6$ at 120min and $3.5{\pm}1.3{\mu}U/ml$ at 180min. No significant difference revealed between euthyroid group and normal subjects (p>0.05). 3. In hyperthyroid group, serum TSH responses to synthetic TRH were $1.5{\pm}0.6$ at 0min, $2.2{\pm}0.8$ at 10min., $2.3{\pm}1.0$ at 20min., $2.4{\pm}1.5$ at 30min., $2.1{\pm}1.1$ at 60min., $1.9{\pm}0.2$ at 120min. and $1.5{\pm}0.8{\mu}U/ml$ at 180min., No response to TRH showed. 4. In hypothyroid group, mean values of serum TSH response to synthetic TRH were 42.0 at 0min., 60.6 at 10min., 124.8 at 20min., 123.0 at 30min., 101.6 at 60min., 64.3 at 120min. and $15.5{\mu}U/ml$ at 180 min., Patients with primary hypothyroidism showed an exaggerated TSH response to synthetic TRH despite their high basal TSH. 5. Side effects attending synthetic TRH administration were transient nausea (59.0%), desire to micturate (59.0%), feeling of flushing(19.7%), dizziness (45.9%), metallic taste (9.8%) and headache (19.7%). Any side effect didn't show in 16.4%. These symptoms began almost immediately after TRH intravenous injection and lasted several minutes, and not related to dose or response in the person experiencing it.

• Herbal Formula Science
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• v.20 no.2
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• pp.29-35
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• 2012

Objectives : To provide the information of preservation method for herbal decoction, we evaluated the anti-inflammatory effects according to preservation temperature and period of Pyungwi-san (PWS, Ping wei-san) decoction. Methods : The anti-inflammatory activity of PWS was investigated by carrageenin-induced paw edema in SD rats. At 0 month, PWS extract was administrated 100, 300 and 1000 mg/kg/day orally for seven days prior to induction of edema. Edema was induced by subcutaneous injection of 1% carrageenin into the right hind paw. The paw volume was measured at 4 hr following carrageenin-induced paw edema in rats. At 6 and 12 months, PWS extracts according to preservation temperatures (room temperature, $4^{\circ}C$ and $-20^{\circ}C$) were administrated in rats and then carrageenin-induced paw edema volume was measured. Results : PWS showed inhibitory effect on carrageenin-induced paw edema in rats and the optimal dose was 1000 mg/kg/day at 0 month of storage. At 6 month of storage, PWS storaged at $4^{\circ}C$ and $-20^{\circ}C$ were inhibited paw edema but that storaged at room temperature was not reduced paw edema in rats. Conclusions : These results suggest that PWS decoction pouch has anti-inflammatory activities at both $4^{\circ}C$ and $-20^{\circ}C$ during 6 month storage.