• The Korean Journal of Pain
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• 제37권3호
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• pp.211-217
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• 2024

Background: Tolerance to the analgesic effects of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) is a major concern for relieving pain. Thus, it is highly valuable to find new pharmacological strategies for prolonged therapeutic procedures. Biguanide-type drugs such as metformin (MET) are effective for neuroprotection and can be beneficial for addressing opioid tolerance in the treatment of chronic pain. It has been proposed that analgesic tolerance to NSAIDs is mediated by the endogenous opioid system. According to the cross-tolerance between NSAIDs, especially sodium salicylate (SS), and opiates, especially morphine, the objective of this study was to investigate whether MET administration can reduce tolerance to the anti-nociceptive effects of SS. Methods: Fifty-six male Wistar rats were used in this research (weight 200-250 g). For induction of tolerance, SS (300 mg/kg) was injected intraperitoneally for 7 days. During the examination period, animals received MET at doses of 50, 75, or 100 mg/kg for 7 days to evaluate the development of tolerance to the analgesic effect of SS. The hot plate test was used to evaluate the drugs' anti-nociceptive properties. Results: Salicylate injection significantly increased hot plate latency as compared to the control group, but the total analgesic effect of co-treatment with SS + Met50 was stronger than the SS group. Furthermore, the effect of this combination undergoes less analgesic tolerance over time. Conclusions: It can be concluded that MET can reduce the analgesic tolerance that is induced by repeated intraperitoneal injections of SS in Wister rats.

• Biomolecules & Therapeutics
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• 제23권3호
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• pp.251-260
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• 2015

Propofol is an anesthetic agent that gained wide use because of its fast induction of anesthesia and rapid recovery post-anesthesia. However, previous studies have reported immediate neurodegeneration and long-term impairment in spatial learning and memory from repeated neonatal propofol administration in animals. Yet, none of those studies has explored the sex-specific long-term physical changes and behavioral alterations such as social (sociability and social preference), emotional (anxiety), and other cognitive functions (spatial working, recognition, and avoidance memory) after neonatal propofol treatment. Seven-day-old Wistar-Kyoto (WKY) rats underwent repeated daily intraperitoneal injections of propofol or normal saline for 7 days. Starting fourth week of age and onwards, rats were subjected to behavior tests including open-field, elevated-plus-maze, Y-maze, 3-chamber social interaction, novel-object-recognition, passive-avoidance, and rotarod. Rats were sacrificed at 9 weeks and hippocampal protein expressions were analyzed by Western blot. Results revealed long-term body weight gain alterations in the growing rats and sex-specific impairments in spatial (female) and recognition (male) learning and memory paradigms. A markedly decreased expression of hippocampal NMDA receptor GluN1 subunit in female- and increased expression of AMPA GluR1 subunit protein expression in male rats were also found. Other aspects of behaviors such as locomotor activity and coordination, anxiety, sociability, social preference and avoidance learning and memory were not generally affected. These results suggest that neonatal repeated propofol administration disrupts normal growth and some aspects of neurodevelopment in rats in a sex-specific manner.

• 대한한방내과학회지
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• 제30권2호
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• pp.270-287
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• 2009

Objective : Yinjinchunggan-tang(YJCGT) is reported previously as having theraputic effects on hepatitis such as anti-implammatory, anti-apoptotic, anti-viral(HBV), etc. Though this prescription is not studied on its anti-fibrogenic effect, it is still expected to have the effect in the liver. Thus, this study was performed to investigate the anti-fibrogenic effect of YJCGT on thioacetamide(TAA)-induced liver fibrosis in rats. Method: Rat liver fibrosis was induced by intraperitoneal TAA injection(150mg/kg) 3 times a week for 5 weeks. After the YJCGT (YJCGT 1g/kg, YJCGT 2g/kg)-treatment, body weight, liver and spleen weights, liver function test, the complete blood count and the portal pressure were studied. In addition, gene expressions of ASMA, procollagen type Ia2, MMP2, TIMP1 and TIMP2, all of which are known to be associated with liver fibrosis, were analyzed by RT-PCR. After YJCGT (YJCGT 1g/kg, YJCGT 2g/kg) treatment, percentages of collagen in TAA-induced rat liver tissue were measured by image analyzer. Results : The body weight of the normal group increased more than that of the control and YJCGT-treated groups. The AST level of the YJCGT lg/kg-treated group significantly decreased compared to that of the control. The ALT and the GGT levels of the YJCGT 2g/kg-treated group significantly increased compared to those of the control. In the YJCGT-treated groups. WBC, RBC and Hgb elevated by TAA injection decreased but platelet count increased. In the YJCGT lg/kg-treated group, the portal pressure elevated by TAA injection significantly decreased. The significant decreases in the gene expressions of procollagen type Ia2, MMP2 and TIMP2 were observed in the YJCGT-treated groups. In histological findings. TAA injections caused severe liver fibrosis, but the YJCGT treatment significantly reduced the amounts of hepatic collagens. Conclusions: These results suggest that YJCGT has beneficial effects on the treatment of patients with liver cirrhosis as well as chronic hepatitis. Further study should be done to decide the optimal concentration of the YJCGT for the treatment of liver cirrhosis.

• 대한한방내과학회지
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• 제32권2호
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• pp.153-169
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• 2011

Objectives : This study was performed to investigate the anti-fibrogenic effect and the effect on cell growth and apoptosis in YJCGT, YJCGT YSO and YJCGT YSCO on thioacetamide-induced rat liver tissue and the immortalized human hepatic cell line LX2. Materials and Methods : LX2 cells were treated with various concentrations (0, 50, 150, 300 ug/ml) of YJCGT, Y+YSO, and Y+YSCO extract for 24, 48 and 72 hours. After the treatment, cell viability was measured by using MTT assay. Caspase inhibitor assay, and cell viability were determined by a colorimetric assay with PMS/MTS solution. Rat liver fibrosis was induced by intraperitoneal thioacetamide injection 150 mg/kg 3 times a week for 5 weeks. After the treatment, body weight, liver & spleen weights, liver function test, the complete blood cell count and the change of portal pressure were studied. After YJCGT, Y+YSO, and Y+YSCO treatment, percentages of collagen in thioacetamide-induced rat liver tissue were measured. Results : The viability of the LX2 cell decreased in a dose- and time-dependent manner. Exposure of LX2 cells to YJCGT, YJCGT+YSO and YJCGT+YSCO induced caspase-3 activation, but co-treatment of YJCGT, YJCGT+YSO and YJCGT+YSCO with the pan-caspase inhibitor Z-VAD-FMK, and the caspase-3 inhibitor Z-DEVE-FMK, blocked apoptosis. There was no difference in rat body weight between the thioacetamide only group and the YJCGT, YJCGT+YSO and YJCGT+YSCO groups. In the YJCGT, YJCGT YSO and YJCGT YSCO groups, the serum level of GPT significantly went down compared with the thioacetamide only group. In the YJCGT, Y+YSO, Y+YSCO groups, white blood cell elevated by thioacetamide injection decreased but RBC, Hgb, and Hct increased. In the Y+YSO group, the portal pressure elevated by thioacetamide injection significantly decreased. In the histological finding, thioacetamide injections caused severe fibrosis, but YJCGT, Y+YSO, and Y+YSCO treatment significantly reduced the amounts of hepatic collagens. Conclusions : YJCGT, Y+YSO, and Y+YSCO inhibit the growth of LX2 cells by inducing apoptosis through caspase activity. YJCGT, Y+YSO, and Y+YSCO have beneficial effects on the treatment of cirrhotic patients as well as patients with chronic hepatitis.

• 동의생리병리학회지
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• 제18권2호
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• pp.474-483
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• 2004

To know the effects between Cd inhalation toxicity and extract of Radix Achyranthis Bidentatae, 4 rat groups were exposed to Cd aerosol in air using whole-body inhalation exposure for 6 hours/day, 5 days/week, and 4 weeks. Cd concentration in air was 1.03㎎/㎥ and mass median diameter(MMD) was 1.69㎛. 3 different dose intraperitoneal injections of extract of Radix Achyranthis Bidentatae to 3 inhalation exposure groups was done for 4 weeks and the results were as follows: The highest body weight gain for 4 weeks and food intake per day were from inhalation exposure group I and the highest lung and liver weight were also from inhalation exposure group I. The highest kidney weight was from inhalation exposure group III. The lowest Cd content in lung was 33.49㎍/g from inhalation exposure group I. The lowest Cd concentration in blood was 9.36㎍/㎗ from inhalation exposure control. Cd concentrations of 40.02㎍/g in liver and 69.18㎍/g in kidney were the lowest from inhalation exposure group I and III, respectively. The lowest Cd concentration in liver was 21.08㎍/g from inhalation exposure group III and The lowest Cd concentration in kidney was 15.78㎍/g from inhalation exposure group II. For weekly Cd concentration in urine, the value of the fourth week from inhalation exposure group III was the highest. For weekly Cd concentration in feces, the value of the first week from inhalation exposure group III was the highest. The highest metallothionein concentration in lung was 53.42 ㎍/g from inhalation exposure group III and the highest metallothionein concentration in liver was 188.18㎍/g from inhalation exposure group III. The highest metallothionein concentration in kidney was 143.92㎍/g from inhalation exposure group III. The highest Hct, Hb, and WBC values were from inhalation exposure group II and the highest RBC value was from inhalation exposure group III.

• 한국가축번식학회지
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• 제11권3호
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• pp.155-160
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• 1987

This study was carried out to determine the effects of cryoprotectants, freezing and thawing rates on the survival of 8-cell mouse embryos. The female ICR mice were induced to superovulated by intraperitoneal injections of 5 i.u. PMSG and 5 i.u. HCG given 48h apart and then were paired with males of the same strain. They were killed and embryos were flushed from the oviducts and uteri on 3 days after injection of HCG. Embryos were flushed with modified Dulbecco's phosphate buffered saline and equilibrated with 1.5M-dimethyl sulfoxide (DMSO) or 1.5M-glycerol by 3-step procedure. The freezing rates of the embryos were 1$^{\circ}C$/min from room temperature to -5$^{\circ}C$ and the embryos were seeded at -5$^{\circ}C$. After being held for 3 min at the seeding temperature, the rates were 0.3$^{\circ}C$/min from -5$^{\circ}C$ to -35$^{\circ}C$. From -35$^{\circ}C$ to -7$0^{\circ}C$, the rates were divided into 0.1$^{\circ}C$/min, 1$^{\circ}C$/min and 1$0^{\circ}C$/min, respectively. After being held for 5 min at -7$0^{\circ}C$, the embryos were plunged directly into liquid nitrogen. The embryos were thawed at 4$^{\circ}C$/min and 12$^{\circ}C$/min from -196$^{\circ}C$ to 37$^{\circ}C$, and for 2 min in 37$^{\circ}C$ water bath, respectively. The average number of ovulation points and embryos recovered were 42.7 and 34 appearing 79.5% recovery rate. Eight cell embryos in the embryos recovered were 26.3. The survival rates of embryos according to the freezing rates in the presence of 1.5M-DMSO were 73.5~80.6% at 0.1$^{\circ}C$/min, 75.0~79.5% at 1$^{\circ}C$/min and 52.8~54.7% at 1$0^{\circ}C$/min, but in the presence of 1.5M-glycerol were 62.9~67.6% at 0.1$^{\circ}C$/min, 61.4~68.3% at 1$^{\circ}C$/min and 25.5~30.2% at 1$0^{\circ}C$/min. The survival rates of embryos were not affected by the thawing rates.

• Journal of Radiation Protection and Research
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• 제19권3호
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• pp.230-234
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• 1994

본 연구에서는 마우스에 이미 오염된 방사성스트론들(Sr-85)을 제거하는데 수용성카이토산이 어느정도 효과가 있는지 알아보고자 하였다. Sr-85를 정맥주사한 경우 주사후 1일째의 체내 잔류량은 $72.9{\pm}5.7%$, 5일째는 $57.7{\pm}1.9%$, 7일째는 $54.2{\pm}1.4%$로 서서히 감소하였으며, Sr-85를 복강내 주사한 경우는 주사후 5일째 $54.4{\pm}1.2%$, 15일째 $50.6{\pm}0.8%$로 정맥주사에 비해 낮은 잔류량을 보였다(5일째 잔류량의 비교, P<0.05). 0.3% 수용성카이토산을 1회 정맥주사해준 제2군 및 10% 수용성카이토산을 식이중에 섞어 먹인 제5군은 각각의 대조군에 비해 체내 잔류방사능의 차이가 없었으나(P>0.05), 0.3% 수용성카이토산을 3일간 정맥주사 한 제3군과 3% 수용성카이토산을 이틀 간격으로 15일간 복강내 주사한 계6군에서는 각각의 대조군에 비해 낮은 잔류방사능을 보였다(P<0.01). 결론적으로 수용성카이토산을 연속적으로 정맥투여하거나 복강내 투여하는 경우에는 스트론튬의 골대사촉진 또는 골중의 스트론튬과의 반응등을 통해 그 배출을 촉진시킬 것으로 사료되었다.

• 대한한의학방제학회지
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• 제21권1호
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• pp.99-110
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• 2013

Objectives : This study was designed to investigate the effect of a herbal preparation HJ01 consisting of Salicornia herbacea, Citri Reticulatae Pericarpium, Crataegi Fructus and Glycyrrhizae Radix on adipocyte differentiation in OP9 cells and on poloxamer 407(P-407)-induced hyperlipidemia in mice. Methods : 1. MTT assay was used to evaluate the potential cytotoxicity of Salicornia herbacea, Citri Reticulatae Pericarpium, Crataegi Fructus, Glycyrrhizae Radix and HJ01, respectively. 2. Bone-marrow derived OP9 cells were treated with HJ01, and the alterations in fat storage in the cells were determined by the Oil red O assay. 3. The protein level of CAAAT/enhancer binding protein alpha($C/EBP{\alpha}$), as a adipocyte differentiation marker, was examined using western blot analysis in differentiated OP6 cells. 4. Adult male C57BL6 mice received intraperitoneal injections of P407 to induce hyperlipidemia, simultaneously, were treated with HJ01 for 4 weeks. Then the cholesterol (TC), triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-c) levels in sera and liver tissues were measured. Results : 1. The MTT assay exhibited that Salicornia herbacea, Citri Reticulatae Pericarpium, Crataegi Fructus, Glycyrrhizae Radix and HJ01 showed no significant cytotoxicity in tested dosages. 2. Ten days' treatment with HJ01 markedly inhibited the increases in fat storage in differentiated OP6 cells. 3. Four weeks' treatment with HJ01 down-regulated the protein level of CAAAT/enhancer binding protein alpha($C/EBP{\alpha}$) but up-regulated the levels of adiponectin in differentiated OP9 cells. 5. HJ01 inhibited the accumulation of TC and TG in liver tissues and increased serum levels of TC in hyperlipidemic mice. Conclusions : These results suggest that HJ01 can in vitro inhibit adipocyte differentiation and fat storage in OP6 cells, in vivo improve the hyperlipidemia induced by P-407 in mice, which may be mediated by promoting glucose uptake and improving a lipid metabolite profile.

• 동의생리병리학회지
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• 제17권3호
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• pp.700-710
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• 2003

For the experiment of the effects between cadmium aerosol inhalation toxicity and ethyl acetate extracts of Folium Mori, 4 inhalation exposure groups of rat were exposed to cadmium aerosol in air by whole-body inhalation exposure for 6 hours/day, 5 days/week, and 4 weeks. Cadmium concentration in the air was 0.96㎎/㎥ and mass median diameter (MMD) was 2.48㎛ with 1.85 of geometric standard deviation(GSD). Intraperitoneal injections of ethyl acetate extracts of Folium Mori to inhalation exposure groups were performed for 4 weeks and the results were as follows: The highest body weight gain for 4 weeks and food intake per day were 159.29/4 weeks in treated group III and 18.45g/day in treated group I, respectively. The highest lung and liver weights were 1.31 g in treated group I and 9.42g in treated group III, respectively. The highest kidney weight was 2.21g from treated group I. The lowest cadmium content in lung was 86.39㎍/g from treated group III and the lowest cadmium concentration in blood was 2.72㎍/㎗ from treated group II. Cadmium concentrations of 22.09㎍/g in liver and 24.82㎍/g in kidney were the lowest from inhalation exposure group I and III, respectively. For weekly cadmium concentration in urine, the value of the fourth week from treated group III was the highest, 1.35㎍/㎖. For weekly cadmium concentration in feces, the values of the second and fourth week from treated group I were the highest, 1.11㎍/g. The highest metallothionein concentration in lung was 31.85㎍/g from treated group III and the highest metallothionein concentration in liver was 205.77㎍/g from treated group III. The highest metallothionein concentration in kidney was 206.55㎍/g from treated group III. The highest Hct and Hb values were 38.26% and 11.63g/㎗ from treated group III, respectively. The highest RBC and WBC values were 7.68×106/㎣ and 9.85×10³/㎣ from treated group I, respectively.

• 대한바이러스학회지
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• 제28권1호
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• pp.71-78
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• 1998

Vaccinia virus is the prototype orthopoxvirus that has been used as a vaccine strain for small pox. This virus has been used to express a variety of cellular and viral genes in mammalian cells at high levels. Interleukin-4 (IL-4) has been found to stimulate the proliferation of T cells and enhance the cytolytic activity of cytotoxic T lymphocytes. To test the immunotherapeutic potential of IL-4 delivered in vivo by poxvirus, a recombinant vaccinia virus expressing the murine IL-4 gene (RVVmIL-4) was constructed. A high level of IL-4 production was confirmed by infecting HeLa cells and measuring IL-4 in cell culture supernatant by ELISA. As a tumor model, two cell lines were used; the murine T leukemic line P388 and the murine breast cancer line TS/A. CDF1 mice were intraperitoneally inoculated with $1\;{\times}\;10^5$ cells of P388. Mice were injected at the same site with $5\;{\times}\;10^5\;PFU$ of recombinant vaccinia virus; first, 3 days after the injection of tumor cells and thereafter once every week for 3 weeks. Intraperitoneal injections of RVVmIL-4 significantly prolonged the survival time of mice inoculated with tumor cells. All mice injected with RVVmIL-4 remained alive for 30 days after the postinoculation of tumor cells, while 100% and 70% of the animals injected with saline or wild type vaccinia virus died, respectively. In another tumor model using TS/A, tumor was established by subcutaneously inoculating $2{\times}10^5$ tumor cells to BALB/c mice. After tumor formation was confirmed on day 4 in all mice, $5\;{\times}\;10^6\;PFU$ of RVVmIL-4 was inoculated subcutaneously three times, once every week for 3 weeks. The TS/A tumor was eradicated in two of the nine mice. Seven of the nine mice treated with RVVmIL-4 developed a tumor, but tumor growth was significantly delayed compared to those treated with saline or wild type vaccinia virus. These results indicate that recombinant vaccinia viruses may be used as a convenient tool for delivering immunomodulator genes to a variety of tumors.