• Title/Summary/Keyword: Drug toxicity

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Microbiological Assay for the Detection of Chloramphenicol in Meat and Milk (식육 및 우유 중 클로람페니콜의 미생물학적 검출법에 관한 연구)

  • 손성완;조병훈;진남섭;박종명;박근식
    • Journal of Food Hygiene and Safety
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    • v.8 no.4
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    • pp.215-223
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    • 1993
  • Chloramphenicol (CAP) is a very effective broad-spectrum antibiotic which had been widely used in animal production. However, the drug is not approved in many countries for use in food-producing animals because of its potential toxicity and the possibility of residues in food products. In this study, a modified microbiological assay was developed for the sensitive detection of CAP residues in meat and milk. The method was characterized by the extraction of CAP with ethyl acetate, addition of $0.15\;\mu\textrm{g}$ oxytetracycline/ml in the phosphate buffer diluent (pH 6.0), a luteus ATCC 9341. The lowest levels of CAP detected in muscle tissues and milk were $0.025\;\mu\textrm{g}/ml\;and\;0.05\;\mu\textrm{g}/g$, respectively. Recovery rates free CAP from milk were 68.5%, from bovine muscle 65.1%, from swine muscle 63.8%, and from chicken muscle 59.4%, respectively, and the coefficients of variation were 1.8~15.1%. The results showed that the detection limits of CAP residues in animal products could significantly be improved by the modified microbiological assay than the conventional ones.

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Study for Possibility of N,N,N-Trimethylphytosphingosine (TMP) for Management of Chronic Skin Diseases (N,N,N-Trimethylphytosphingosine (TMP)의 염증성 피부질환 치료제 가능성에 관한 연구)

  • Seo, Won-Sang;Oh, Han-Na;Park, Woo-Jung;Um, Sang-Young;Kang, Sang-Mo
    • KSBB Journal
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    • v.29 no.1
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    • pp.36-41
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    • 2014
  • Skin disease is one of the most common diseases and its incidence is increasing dramatically in modern society. Specially, many attempts have been made to treat chronic skin inflammation diseases, such as psoriasis and atopic dermatitis, but effective therapies for the immune cell-mediated skin diseases, including psoriasis and atopic dermatitis have not been developed. Until recently, several drug candidates which were claimed to be effective for skin diseases have been reported, but most of them are not used to treat chronic skin disease. Especially, Psoriasis is characterized by excessive growth and aberrant differentiation of keratinocytes, but is fully reversible with appropriate therapy. The trigger of the keratinocyte response is thought to be activation of the cellular immune system, with T cells and various immune-related cytokines. Formation of new blood vessels starts with early psoriatic changes and disappears with disease clearance. Several angiogenic mediators are up-regulated in psoriasis development. Contact- and mediator-dependent factors derived from keratinocytes, mast cells and immune cells may contribute to the strong blood vessel formation of psoriasis. New technologies and experimental models provide new insights into the role of angiogenesis in psoriasis pathogenesis. TMP and its derivatives themselves effectively inhibited in vitro cell migration, tube formation, and the expression of angiogenic factors. However, TMP and its derivatives induced side effects including hemolysis and local side effects. Therefore, in an attempt to reduce the toxicity and the undesirable side effects of TMP and derivatives, a liposomal formulation was prepared and tested for its effectiveness. TMP and derivatives liposomes retained the effectiveness of TMP in vitro while side effects were reduced. These results support the conclusion that TMP effectively inhibits in vitro angiogenesis, with the possibility that use as a psoriasis relief agent.

4-Hydroxybenzaldehyde Restricts the Intracellular Growth of Toxoplasma gondii by Inducing SIRT1-Mediated Autophagy in Macrophages

  • Lee, Jina;Choi, Jae-Won;Han, Hye Young;Kim, Woo Sik;Song, Ha-Yeon;Byun, Eui-Baek;Byun, Eui-Hong;Lee, Young-Ha;Yuk, Jae-Min
    • Parasites, Hosts and Diseases
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    • v.58 no.1
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    • pp.7-14
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    • 2020
  • Toxoplasma gondii is an intracellular protozoan parasite that infects approximately one third of the human population worldwide. Considering the toxicity and side effects of anti-toxoplasma medications, it is important to develop effective drug alternatives with fewer and less severe off-target effects. In this study, we found that 4-hydroxybenzaldehyde (4-HBA) induced autophagy and the expression of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) in primary murine bone marrow-derived macrophages (BMDMs). Interestingly, treatment of BMDMs with 4-HBA significantly reduced the number of macrophages infected with T. gondii and the proliferation of T. gondii in infected cells. This effect was impaired by pretreating the macrophages with 3-methyladenine or wortmannin (selective autophagy inhibitors) or with sirtinol or EX527 (SIRT1 inhibitors). Moreover, we found that pharmacological inhibition of SIRT1 prevented 4-HBA-mediated expression of LC3-phosphatidylethanolamine conjugate (LC3-II) and the colocalization of T. gondii parasitophorous vacuoles with autophagosomes in BMDMs. These data suggest that 4-HBA promotes antiparasitic host responses by activating SIRT1-mediated autophagy, and 4-HBA might be a promising therapeutic alternative for the treatment of toxoplasmosis.

Cloning, Purification, and Characterization of Recombinant Human Extracellular Superoxide Dismutase in SF9 Insect Cells

  • Shrestha, Pravesh;Yun, Ji-Hye;Kim, Woo Taek;Kim, Tae-Yoon;Lee, Weontae
    • Molecules and Cells
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    • v.39 no.3
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    • pp.242-249
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    • 2016
  • A balance between production and degradation of reactive oxygen species (ROS) is critical for maintaining cellular homeostasis. Increased levels of ROS during oxidative stress are associated with disease conditions. Antioxidant enzymes, such as extracellular superoxide dismutase (EC-SOD), in the extracellular matrix (ECM) neutralize the toxicity of superoxide. Recent studies have emphasized the importance of EC-SOD in protecting the brain, lungs, and other tissues from oxidative stress. Therefore, EC-SOD would be an excellent therapeutic drug for treatment of diseases caused by oxidative stress. We cloned both the full length (residues 1-240) and truncated (residues 19-240) forms of human EC-SOD (hEC-SOD) into the donor plasmid pFastBacHTb. After transposition, the bacmid was transfected into the Sf9-baculovirus expression system and the expressed hEC-SOD purified using FLAG-tag. Western blot analysis revealed that hEC-SOD is present both as a monomer (33 kDa) and a dimer (66 kDa), as detected by the FLAG antibody. A water-soluble tetrazolium (WST-1) assay showed that both full length and truncated hEC-SOD proteins were enzymatically active. We showed that a potent superoxide dismutase inhibitor, diethyldithiocarbamate (DDC), inhibits hEC-SOD activity.

The Effects of Cortex Mori on NO, $TNF-{\alpha}$ and $IL-1{\alpha}$ production by macrophage (상백피(桑白皮)가 대식세포의 NO, $TNF-{\alpha}$$IL-1{\alpha}$ 생산에 미치는 영향)

  • Ahn, Jae-Kyu;Ahn, Duk-Kyun;Cho, Jae-Chon
    • The Journal of Korean Medicine
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    • v.19 no.2
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    • pp.485-501
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    • 1998
  • Cortex Mori (Moros alba L.), the root bark of mulberry tree has been used as an autiphlogistic, diuretic and expectorant in herval medicine. Recently, a few papers reported that phenolic extract of Cortex Mori had the hypotensive, hypoglycemic, antiviral and anticancer effects, and hot water extract of Cortex Mori(CM) had inhibitory effect on the degranulation and histamine release from activated mast cells. These previous studies suggest a possibility that CM has an antidotal activity against inflammation which was mediated mainly by macrophage-secreting inflammatory factors. This study was performed to evaluate the influences of CM on carrageenan-induced edema in vivo and release of inflammatory mediators such as NO, TNF and IL-1 by macrophages stimulated with LPS or $IFN-{\gamma}$ in vitro. Subcutaneous injections of carrageenan into the mouse paw rapidly induced local edema by increasing vascular permeability, but single intraperitoneal injection of CM extract at 30 minutes before carrageenan suppressed the development of edema. NO and TNF production from macrophage stimulated by LPS or $IFN-{\gamma}$ were significantly suppressed, especially TNF secretion by up to 3-4 folds. LPS stimulated IL-1 production was also inhibited, but not significantly. Cell viability assay verified that the inhibition was not due to general cell toxicity. These results suggest that reduction of NO, TNF and IL-1 production may be one of the means by which CM prevent inflammation associated diseases.

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Incidence of Liver Function Test Abnormality among Patients Hospitalized in an Oriental Hospital (한방병원에 입원한 환자군에서 간기능 검사 이상자의 빈도 조사)

  • Han, Chang-Woo;Kim, Su-Young;Min, Kwan-Sik;Lee, Jin-Hyuk;Lee, Sang-Ho;Youn, You-Suk
    • The Journal of Korean Medicine
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    • v.31 no.2
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    • pp.109-113
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    • 2010
  • Objectives: Liver function tests are used as screening tests for liver injuries, but their inaccuracy on positive predictive values can result in numerous false positive results. We investigated the incidence of liver function test abnormalities of patients who came to an oriental medicine hospital, in order to present a practical way to rule out false positive results for other studies designed to investigate the safety of Korean herb medicine. Methods: We analyzed the medical records and liver function test results proceeded at admission of all in-patients admitted to Jaseng Oriental Medicine Hospital, from July 2008 to June 2009. Results: Among 1,117 inpatients, 941 executed liver function tests on admission, and 40 were excluded due to their diagnosed liver disease. 747 (82.9%) of 901 enrolled patients were within the normal range of all liver function tests, and 140 (15.5%) and 14 (1.6%) were classified as "abnormalities of liver tests" and "liver injury" respectively, according to the CIOMS (Council for International Organizations of Medical Sciences) criteria. Conclusions: According to the results, among the outcomes of liver function tests proceeded among the patients admitted to the oriental medicine hospital, excluding who were diagnosed with liver disease, 17.1% showed abnormality. This means simple liver function test results are not sufficient in determining liver toxicity of Korean herb medicine (KHM).

The treatment of pediatric chronic myelogenous leukemia in the imatinib era

  • Lee, Jae-Wook;Chung, Nack-Gyun
    • Clinical and Experimental Pediatrics
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    • v.54 no.3
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    • pp.111-116
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    • 2011
  • Childhood chronic myelogenous leukemia (CML) is a rare hematologic disease, with limited literature on the methods of treatment. Previously, allogeneic hematopoietic stem cell transplantation (HSCT) was considered the only curative treatment for this disease. Treatment with imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase (TKI), has resulted in prolonged molecular response with limited drug toxicity. Imatinib is now implemented in the primary treatment regimen for children, but the paucity of evidence on its ability to result in permanent cure and the potential complications that may arise from long-term treatment with TKIs have prevented imatinib from superseding HSCT as the primary means of curative treatment in children. The results of allogeneic HSCT in children with CML are similar to those observed in adults; HSCT-related complications such as transplant-related mortality and graft-versus-host disease remain significant challenges. An overall consensus has been formed with regards to the need for HSCT in patients with imatinib resistance or those with advanced-phase disease. However, issues such as when to undertake HSCT in chronic-phase CML patients or how best to treat patients who have relapsed after HSCT are still controversial. The imatinib era calls for a reevaluation of the role of HSCT in the treatment of CML. Specific guidelines for the treatment of pediatric CML have not yet been formulated, underscoring the importance of prospective studies on issues such as duration of imatinib treatment, optimal timing of HSCT and the type of conditioning utilized, possible treatment pre-and post-HSCT, and the role of second-generation TKIs.

Dendropanax morbifera and Rubus coreanus Miq. Extracts Inhibits the Formation of Uric Acid Crystal by Reducing Xanthine Oxidase Activity

  • Hurh, Joon;Simu, Shakina Yesmin;Han, Yaxi;Ahn, Jong-Chan;Yang, Deok-Chun
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.04a
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    • pp.95-95
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    • 2018
  • Uric acid is the end product of purine metabolism in human body, originating from hypoxanthine after enzyme catalysis by Xanthine oxidase (XOD). Hyperuricemia results as a result of either over-generation of uric acid or a reduction in its excretion. In silico modelling methods such as Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) prediction, Autodock 4.2.6 program were used to study the potential inhibitory compounds of XOD. Also we investigated the inhibition of XOD activity by using the extracts of Dendropanax morbifera and Rubus coreanus Miq spectrophotometrically. According to ADMET data, several compounds from D. morbifera and R. coreanus plants, were found to be more potent in inhibiting the XOD activity than allopurinol. XOD inhibitory activity is evaluated by quantifying the formation of uric acid by measuring the absorbance at 290 m ($A_{290}$).D. morbifera extract inhibited XOD activity at $250{\mu}g/ml$, however the extracts from R. coreanus has inhibited XOD activity at $25{\mu}g/ml$. The major compound of R. coreanus, ellagic acid significantly increased the inhibition rate from $9{\mu}g/ml$ and showed a 71% suppression rate at $15{\mu}g/ml$. Finally, these results suggested a potential inhibitory activities of the extracts from D. morbifera and R. coreanus Miq, but further research is needed to validate to ensure their safe usage as drug.

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Changes in Glucose Concentrations and Activities of Cholinesterase in Serum, Brain and Spinal cord in Mice following Orally Administration of Parathion (Parathion을 경구투여한 Mouse의 체내 Cholinesterase 활성도 및 Glucose함량 조사)

  • 도재철;이창우;차우양;손재권;정종식
    • Korean Journal of Veterinary Service
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    • v.15 no.1
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    • pp.58-66
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    • 1992
  • The insecticide p-nitropheny diethyl thiophospate is alse known by the symbol E.605 and a legion of trade names including “parathion”. The insecticide is widely used in agriculture, but it is highly toxic and now clear that parathion behaves like a cholinergic drug by inhibiting the enzyme cholinesterase. In order to know acute toxicity and the changes of glucose concentrations and activity according to time lapsed in female mice given orally single with the half dose to $LD_{50}$ of parathion, glucose contents and cholinesterase activities in serum as well as cholinesterase activities in whole brain and spinal cord were investigated, otherwise median lethal dose ($LD_{50}$) of parathion given orally against female mice was determined. The results obtained were summerized as follows ; 1. $LD_{50}$ value of parathion given orally to female mice was 7.1mg/kg(95% confidence limits, 3.8-13.1mg/kg) 2. The inhibition rate of cholinesterase activities in serum of parathion-administrated mice according to time lapsed were peakly decreased to 61% after 30 minutes in comparison to control group, but activities were completely recovered after 48 hours. 3. The inhibition rate of cholinesterase activities in whole brain of parathion-administrated mice according to time lapsed were peakly decreased to 49% after 2 hours in completely recovered after 24 hours. 4. The inhibition rate of cholinesterase activities in spinal cord of parathion-administrated mice according to time lapsed were peakly decreased to 57% after 2 hours in comparison to control group, but activities were completely recovered after 48 hours. 5. The changes of glucose contents in serum of parathion-administrated mice according to time lapsed and in directly after death due to parathion poisoning were no significantly difference.

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Beneficial Effect of Glycyrrhizae Radix Extract on Ischemia-Induced Acute Renal Failure in Rabbits (토끼의 허혈성 신부전 대한 감초(甘草) 추출물의 억제 효과)

  • Kim, Gyung-Ho;Kim, Min-Ho;Yun, Yeo-Chung;Kim, Young-Gyun;Cho, Su-In
    • The Korea Journal of Herbology
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    • v.20 no.3
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    • pp.43-49
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    • 2005
  • Objectives : The present study was carried out to determine if Glycyrrhizae Radix extract exerts beneficial effect against the ischemia-induced acute renal failure in rabbits. Glycyrrhizae Radix was known to reinforce the function of the spleen and replenish Qi, remove heat and counteract toxicity, dispel phlegm and relieve cough, alleviate spasmodic pain, and to moderate drug actions. It's indications are weakness of the spleen and the stomach marked by lassitude and weakness; cardiac palpitation and shortness of breath; cough with much phlegm: spasmodic pain in the epigastrium, abdomen and limbs: carbuncles and sores. It is often used for reducing the toxic or drastic actions of other drugs. Methods : Antioxidative effect of 3% concentration of Glycyrrhizae Radix extract was measured. Rabbits were treated with Glycyrrhizae Radix extract via i.v., followed by renal ischemia/reperfusion, and the changes of urine volume, serum creatinine levels, glomerular filtration rate(GFR), fractional Na+ excretion$(FE\;Na^+)\;and\;K^+\;excretion(FE\;K^+)$ in ischemia/reperfusion induced acute renal failure were measured. Results : Renal ischemia/reperfusion caused increase of serum creatinine level, which was accompanied by a reduction in glomerular filtration rate(GFR). The fractional excretion of $Na^+\;and\;K^+$ increased in ischemia-induced animals, which was partially prevented by Glycyrrhizae Radix extract treatment. Conclusions : These results indicate that lipid peroxidation plays a critical role in ischemia-induced acute renal failure. Glycyrrhizae Radix extract exerts the protective effect against acute renal failure induced by renal ischemia/reperfusion, and its effect may be attributed to an antioxidant action.

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