• Title/Summary/Keyword: systemic administration

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Effect of Samhwangsashimtang Extract on Lipopolysaccharide-Stimulated Inflammatory Response and Macrophage Activity (삼황사심탕(三黃瀉心湯) 추출물의 lipopolysaccharide 유도에 의한 염증 조절과 대식세포 활성에 대한 연구)

  • Kang, Hee;Kwon, Han-Al;So, Hyung-Jin;Lee, Jeong-Min;Lew, Jae-Hwan;Choi, Ho-Young
    • The Korea Journal of Herbology
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    • v.27 no.6
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    • pp.23-28
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    • 2012
  • Objectives : Samhwangsashim-tang(SHSST), a mixture of Rhei radix et rhizoma, Scutellariae radix, and Coptidis rhizoma, has been regarded as being able to treat bleeding, gastric discomfort, dry mouth, insomnia and purpura due to Blood Heat. Currently, this herbal formula is applied to gastritis, gastric ulcer, hypertension, atherosclerosis or other types of vascular inflammatory disorders. Methods : We extracted this herbal mixture with 30% ethanol and examined for its effects on systemic inflammatory responses and in vitro macrophage activity. Mice were orally given to SHSST for 7 days and then lipopolysaccharide(LPS) was intraperitoneally injected. Tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) levels in serum were measured 1 h after LPS challenge. Peritoneal macrophages were isolated from thioglycollate-injected mice and used for in vitro cellular activity. Cell death was measured using the MTT method and annexin V/propidium iodide staining. LPS-stimulated signaling molecules necessary for TNF-${\alpha}$ expression were determined by Western blotting. Results : Oral administration of SHSST for 7 days resulted in a significant reduction in LPS-stimulated TNF-${\alpha}$ release into serum. In vitro treatment of SHSST was cytotoxic in a concentration-dependent manner. However, SHSST caused a concentration-dependent reduction in necrosis and increase in apoptosis in mouse peritoneal macrophages. SHSST inhibited the activation of NF-${\kappa}B$, p38 and JNK signaling molecules in response to LPS. Conclusion : Taken together, our results demonstrated that SHSST was effective in lowering LPS-stimulated TNF-${\alpha}$ serum levels, possibly through its modulation of NF-${\kappa}B$, p38 and JNK in macrophages.

Antiasthmatic effects on Pinellia ternate Breitenbach(PTB) water extracts against airway inflammation and hyperresponsiveness induced by diesel exhaust particles with ovalbumin sensitization in BALB/c mice (생쥐에서 ovalbumin과 디젤배기가스 입자로 유도된 기도염증과 기도 과민성에 대한 반하 물 추출물의 항천식 효과)

  • Kim, Seung Hyung;Lim, Heung Bin
    • The Korea Journal of Herbology
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    • v.28 no.1
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    • pp.65-71
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    • 2013
  • Objectives : Asthma is a chronic, complex respiratory disease, caused by airway obstruction, airway eosinophilic inflammation(AEI), and airway hyperresponsiveness(AHR). This study was conducted to determine whether oral administration of crude water extracts of Pinellia ternate Breitenbach(PTB) has an antiasthmatic potential in the treatment of asthma in mice. Methods : Asthmatic AEI and AHR were induced by systemic sensitization to ovalbumin(OVA) by intratracheal instillation with 0.1 mg/mL suspension of diesel exhaust particles(DEP) once a week for 10 weeks in BALB/c mice. Crude PTB water extracts(50 mg/kg and 200 mg/kg) were orally administered 5 times a week for 10 weeks. Cyclosporin(10 mg/kg) was administrered the same manner as a positive control. Results : Long-term treatment with crude PTB water extracts suppressed the infiltration of inflammatory cells, including eosinophils, into airways from blood. It also reduced asthmatic AEI and AHR by attenuating the increase in the levels of cytokines such as interleukin(IL)-4, IL-5 and IL-13 in bronchoalveolar lavage fluid(BALF), as well as the levels of histamine and OVA-specific IgE in blood. However, the effect of crude PTB water extracts(200 mg/kg) was not likely to be stronger than that of cyclosporin(10 mg/kg). Conclusion : These results suggest that crude PTB water extracts have inhibitory effects on AEI and AHR in a mouse model of asthma and may act as a potential Th2 cytokine antagonist, and have a therapeutic effect on allergic asthma.

A Case Report of UDCA and Injinho-tang Co-administration for Liver Damage Caused by Rifampin (Rifampin으로 인한 간손상에 UDCA와 인진호탕 병용투여 증례 보고)

  • Seyeon Lee;Hansung Yoon;Kibeom Ku;Mariah Kim;Irang Nam;Minhwa Kim;Changwoo Han
    • The Journal of Internal Korean Medicine
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    • v.44 no.5
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    • pp.1011-1016
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    • 2023
  • We have experienced a case in which herbal medicine was administered to treat drug-induced liver damage and would like to introduce it. A 49-year-old man exhibited a positive result in the interferon-gamma release assay. He had never suffered from tuberculosis in the past, and the route and time of infection could not be confirmed. He had no respiratory or systemic symptoms suggestive of active tuberculosis, and a chest X-ray examination showed no active lung lesions, so he was diagnosed with latent tuberculosis infection. He was confirmed to be within the normal range in the liver function test, renal function test, and complete blood cell count test, and started taking rifampin (600 mg qd). In the screening test performed on the 19th day of taking the drug, other test items were normal, but alanine aminotransferase (ALT) increased to 50 U/L (reference value: 4-40 U/L). In a test performed on the 29th day of taking the drug, ALT was clearly elevated to 102 U/L. Ursodeoxycholic acid and Injinho-tang were taken together with rifampin, and the patient's progress was observed. In a test performed 14 days later, ALT decreased to 26 U/L, within the normal range. It is presumed that Injinho-tang may have partially contributed to alleviating liver damage in this case.

Anti-SARS-CoV-2 receptor binding domain antibodies after the second dose of Sinovac and AstraZeneca vaccination

  • Marisca Evalina Gondokesumo;Anita Purnamayanti;Puri Safitri Hanum;Winnie Nirmala Santosa;Ardyan Prima Wardhana;Christina Avanti
    • Clinical and Experimental Vaccine Research
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    • v.12 no.3
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    • pp.224-231
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    • 2023
  • Purpose: The Sinovac and AstraZeneca vaccines are the primary coronavirus disease 2019 vaccines in Indonesia. Antibody levels in vaccine-injected individuals will decline substantially over time, but data supporting the duration of such responses are limited. Therefore, this study aims to quantitatively evaluate antibody responses resulting from the completion of Sinovac and AstraZeneca administration in Indonesian adults. Materials and Methods: Participants were divided into two groups based on their vaccine type. Both groups were then assessed on the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (anti-SRBD) concentrations. The anti-SRBD level was measured using Elecsys anti-SARS-CoV-2 S assay and analyzed every month until 3 months after the second vaccination. Results: The results presented significant differences (p=0.000) in immunoglobulin G (IgG) titers among the vaccines' measurement duration, where all samples observed a decrease in IgG titers over time. The mean titer levels of anti-SRBD IgG in the group given Sinovac were high in the first month after vaccination and decreased by 55.7% in 3 months. AstraZeneca showed lesser immune response with a slower decline rate. Adverse effects following immunization (AEFI) showed that systemic reactions are the most reported in both vaccines, with a higher percentage in the second dose of AstraZeneca type vaccines. Conclusion: Sinovac induced more significant titers of anti-SRBD IgG 1 month after the second dose but generated fewer AEFIs. In contrast, AstraZeneca generated more AEFIs, in mild to moderate severity, but provided lower levels of anti-SRBD IgG.

Residual Characteristics and Safety Assessments of Bifenthrin, Carbendazim and Metconazole in Angelica gigas Nakai (당귀 중 bifenthrin, carbendazim, metconazole의 잔류 특성 및 안전성 평가)

  • Jeong, Hye Rim;Noh, Hyun Ho;Lee, Jae Yun;Park, Hyo Kyoung;Jin, Me Jee;Kim, Jin Chan;Hong, Su Myeong;Kyung, Kee Sung
    • The Korean Journal of Pesticide Science
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    • v.21 no.1
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    • pp.97-105
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    • 2017
  • This study was carried out to determine residual characteristics and to evaluate safety of bifenthrin, carbendazim and metconazole in minor crop, Angelica gigas Nakai. The test pesticides were sprayed onto the crop according to the combinations of spray days before harvest and frequency and then sampling was performed at the harvest day. Non-systemic pesticide bifenthrin was not detected in all samples, whereas systemic pesticides, carbendazim and metconazole, were detected from the crop in the range of from 0.14 to 0.49 and from 0.19 to 0.26, respectively. These results indicated that residual characteristics of the test pesticides in Angelica gigas Nakai were affected by their systemic properties. Also, residual concentration of carbendazim and metconazole in the crop was increased as more spraying frequency and spraying more closer to harvest day. And residual concentration of carbendazim in the crop on the last spraying day was 2.1 times higher than that of metconazole because nominal spraying dose of carbendazim was higher than that of metconazole by 1.9 times. The residue levels of the test pesticides in the crop were evaluated to be safe, considering their %ADIs were less than 0.9%.

A comparison study of the effects of loratadine-pharmacopuncture and loratadine-oral administration based on traditional Korean medicine theory on anaphylactic reaction in mice

  • Kim, Hyun-Min;Kim, Hyun-Min;Lee, Min-Jung;Cho, Min-Gi;Kang, Deok;Kim, Yu-Kyung;Kim, Changmin;Kang, Do-Hyun;Jeong, Si-Hwa;Ahn, Ik-Gyun;Hwang, Jun-Hyeok;Kim, Jae-Hyun;Lee, Hyun-Jin;Jang, Jun-Yeong;Park, Ho-Jung;Kang, Sin woo;Youm, Jieun;Baek, Seung-won;Kim, Eu Jin;Shin, Moon-Kou;Park, Chan;Son, Chang-Bin;Yim, Tae-Bin;Lim, Jung Hyun;Hong, Sung-eun;Choi, Jun-Hyuk;Kim, Jun-Dong;Yoon, Dong-ju;Lee, Dong-Min;Yu, Soo-Min;Hong, Ye-Im;Lee, Yeong-Seok;Koo, Bon-Cheol;Park, Hyoung-Jun;Uem, Chae-Yoon;Kim, Min-Jeong;Oh, Jayoung;Park, NamGyeong;Kim, Eun-Jong;Cho, Whi-Sung;Lee, Ho-Sung;Kim, Tae-oh;Yoon, Cheol;Kwon, Sung-Keun;Jeong, Dong-Hyeon;Lee, Changwon;Yu, Sang-Yeol;Shon, Chae-won;Jeon, Gyu-Ri;Hong, Yang-Seok;Moon, Phil-Dong
    • CELLMED
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    • v.8 no.1
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    • pp.5.1-5.4
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    • 2018
  • Pharmacopuncture, or herbal acupuncture, is a new form of therapy derived from combinations of two traditional therapeutic methods, herbal medicine and acupuncture therapy. To compare the efficacy between loratadine-pharmacopuncture (LP) and loratadine-oral administration (LO), the effect of loratadine was investigated in murine models. Anti-anaphylactic effects of loratadine treatments were investigated in compound 48/80-induced systemic anaphylactic reaction and passive cutaneous anaphylaxis (PCA). LP treatment significantly inhibited the compound 48/80-induced systemic anaphylactic reaction and PCA. The effect between LP and LO were on a similar level. These results indicate that LP can be used as an alternative method for LO in case of emergency.

Cytotoxicity and Apoptosis of Various Concentrations of Doxorubicin in Methylcholanthrene- induced Rat Fibrosarcoma(MCA) Cells (Methylcholanthrene 유도 섬유육종세포주에서 Doxorubicin 농도에 따른 세포독성과 자멸사의 변화)

  • 정진용;왕영필;나석주
    • 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.

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Effects of Lycii fructus Extracts on the Erectile Dysfunction by Chronic Ethanol Consumption in Rats (에탄올 음용으로 유도된 발기부전 동물모델에 대한 구기자 추출물의 개선효과)

  • Jung, Se Hee;Kim, Jung Hoon;Oh, Hong Geun;Shin, Eun Hye;Lee, Bong Gun;Park, Sang Hoon;Moon, Dae In;Park, Young Mi;Han, Ju Hee;Han, Jong Hyun;Park, Kwang Hyun;Park, Jong Sang;Han, Seung Jun;Ryu, Do Gon;Gwon, Gang Beom;Lee, Young Rae;Kim, Ok Jin;Lee, Hak Yong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.27 no.5
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    • pp.625-630
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    • 2013
  • Erectile dysfunction (ED) is a highly prevalent disorder that affects millions of men worldwide. ED is now considered an early manifestation of atherosclerosis, and consequently, a precursor of systemic vascular disease. Lycii fructus extracts (LFE) were administered for 4 weeks to assess the improving effects on ED. Animals were divided into one normal group and four LFE-treated groups (0, 0.3, 0.6, and 1.2 g/kg). We induced ED in the study animals by oral administration of 20% ethanol instead of water everyday for 4 weeks. This study was designed to investigate the effects of LFE on the mRNA levels of inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) expression; NO levels of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP); blood profile; and erectile response of the corpus cavernosum of the rat penis. The libido of the LFE-administered male rats was higher than that of the ethanol control group. The erectile response of the corpus cavernosum was restored after LFE administration, to a level similar to the normal group. In addition, the iNOS in the corpus cavernosum of the male rats administered LFE decreased. In contrast, compared to the control group, LFE-administered male rats showed increased eNOS, NO and cGMP levels in the corpus cavernosum. These results indicate that LFE effectively restored ethanol-induced ED in male rats.

LOW PERMEABILITY THROUGH THE BLOOD-BRAIN BARRIER OF MORPHINE GLUCURONIDES.

  • Kang, Young-Sook;Ulrich Bickel;Oliver P. Schumacher;Karlheinz Voigt
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.246-246
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    • 1996
  • The glucuronide conjugates of morphine have been claimed to exert significant neuropharmacological effects. Morphine-6-glucuronide (M6G) may be a potent opioid agonist in vivo, and morphine-3-glucuronide (M3G) may act as a weak opioid antagonist. The present study addressed the permeability of the blood-brain barrier (BBB) for these metabolites compared to morphine. Tracers were prepared by enzymatic glucuronidation of U-methyl-$^3$H]-morphine. Brain uptake in rats was measured by the internal carotid artery perfusion technique and after i.v. bolus injections. In the perfusion experiments morphine showed a permeability-surface area product (PS) of 3.52${\pm}$0.61 ${\mu}$L min$\^$-1/ g$\^$-1/ Uptake seems to be mediated by passive diffusion and was not saturable by 100 ${\mu}$M morphine in the perfusate. The BBB permeability of [$^3$H]-M3G and [$^3$H]-M6G was too low to be quantified after 5 min of perfusion. Brain uptake of [$^3$H]-M3G and [$^3$H]-M6G 60 min after i.v. bolus injection reached 0.0060${\pm}$0.0003 and 0.0030${\pm}$0.0005% injected dose per g, respectively. From these brain concentrations and from the corresponding plasma concentration - time curves, BBB PS values of 0.14${\pm}$ 0.02 ${\mu}$L min$\^$-1/g$\^$-1/ and 0.11 ${\pm}$ 0.01 ${\mu}$L min$\^$-1/g$\^$-1/, respectively, were calculated. The ratio of BBB PS values is complementary to the analgesic potencies of morphine and M6G after different routes of administration. The low PS of MSG explains, why it is approximate]y equipotent to morphine after systemic injection, although it is about 2 orders of magnitude more potent than morphine after administration directly into the central nervous system.

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Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats

  • Lee, JooBuom;Lee, Kyungsun;Choe, Keunbum;Jung, Hyunseob;Cho, Hyunseok;Choi, Kiseok;Kim, Taegon;Kim, Seojin;Lee, Hyeong-Seok;Cha, Mi-Jin;Song, Si-Whan;Lee, Chul Kyu;Chun, Gie-Taek
    • Toxicological Research
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    • v.31 no.4
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    • pp.371-392
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    • 2015
  • TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of $1000{\mu}g/kg/day$. Rats received TS-DP2 intravenously at doses of 250, 500, and $1000{\mu}g/kg/day$ once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 $500{\mu}g/kg/day$ and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was $250{\mu}g/kg/day$, and no observed adverse effect level (NOAEL) in females was $250{\mu}g/kg/day$ in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures ($AUC_{0-24h}$ and $C_0$) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.