• Title/Summary/Keyword: human toxicity

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Electrophysiological Functions of Intracellular Amyloid β in Specific for Cultured Human Neurones and its Impairment Properties

  • Merlin, Jayalal L.P.
    • Journal of Integrative Natural Science
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    • v.6 no.3
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    • pp.143-150
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    • 2013
  • Prevailing role of intracellular amyloid ${\beta}$ ($iA{\beta}$) in Alzheimer's disease (AD) initiation and progression attracts more and more attention in recent years. To address whether $iA{\beta}$ induces early alterations of electrophysiological properties in cultured human primary neurons, we delivered $iA{\beta}$ with adenovirus and measured the electrophysiological properties of infected neurons with whole-cell recordings. Our results show that $iA{\beta}$ induces an increase in neuronal resting membrane potentials, a decrease in $K^+$ currents and a hyperpolarizing shift in voltage-dependent activation of $K^+$ currents. These results suggest the electrophysiological impairments induced by $iA{\beta}$ may be responsible for its neuronal toxicity.

Human Tumor Xenograft Models for Preclinical Assessment of Anticancer Drug Development

  • Jung, Joohee
    • Toxicological Research
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    • v.30 no.1
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    • pp.1-5
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    • 2014
  • Xenograft models of human cancer play an important role in the screening and evaluation of candidates for new anticancer agents. The models, which are derived from human tumor cell lines and are classified according to the transplant site, such as ectopic xenograft and orthotopic xenograft, are still utilized to evaluate therapeutic efficacy and toxicity. The metastasis model is modified for the evaluation and prediction of cancer progression. Recently, animal models are made from patient-derived tumor tissue. The patient-derived tumor xenograft models with physiological characters similar to those of patients have been established for personalized medicine. In the discovery of anticancer drugs, standard animal models save time and money and provide evidence to support clinical trials. The current strategy for using xenograft models as an informative tool is introduced.

Preparation and Cytotoxicity Comparison of Type A Gelatin Nanoparticles with Recombinant Human Gelatin Nanoparticles

  • Won, Young-Wook;Kim, Yong-Hee
    • Macromolecular Research
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    • v.17 no.7
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    • pp.464-468
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    • 2009
  • Gelatin nanoparticles derived from bovine or porcine have been developed as various types of drug delivery system, and they need to be cross-linked to maintain their physicochemical properties in aqueous environments. Although gelatin is a widely used material in pharmaceutical industries, the safety issue of animal-origin gelatins, such as transmissible mad cow disease and anaphylaxis, remains to be solved. The purpose of this study was to prepare type A gelatin (GA) nanoparticles by modified, two-step, desolvation method and compare the toxicity of the resulting GA nanoparticles with recombinant human gelatin (rHG) nanoparticles. The GA nanoparticles were characterized, and drug loading and release pattern were measured. FITC-BSA, a model protein, was efficiently loaded in the nanoparticles and then released in a biphasic and sustained release pattern without an initial burst. In particular, the cell viability of the GA nanoparticles was less than that of the rHG nanoparticles. This finding suggests that rHG nanoparticles should be considered as an alternative to animal-origin gelatin nanoparticles in order to minimize the safety problems.

Antiviral Activity of Papaverine and Nucleoside Analogs on the Human Cytomegalovirus Infection (Human Cytomegalovirus 감염에 대한 파파베린과 뉴클레오사이드 유사체의 항바이러스 효과)

  • ;Albrecht, T.
    • Korean Journal of Microbiology
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    • v.29 no.1
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    • pp.25-33
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    • 1991
  • Antiviral activities of papaverine and nucleoside analogs, 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG) and acyclovir, against human cytomegalovirus (HCMV) infection were compared in vitro. Papaverine and DHPG were effective in reducing infectious HCMV yields with $ED_{50}{\s}$ (effective dose 50: the concentraion at which 50% of virus yields was obtained) of approximately 1.02 and $0.45{\mu}{\M}$, respectively; while acyclovir was less effective with an $ED_{50}$ of about $10.4{\mu}{\M}$The relative cytotoxicity of these drugs was evaluated under the same conditions used to measure infectious HCMV yields. Papaverine and DHPG demonstrated little cellular toxicity as measured by their effect on the viability of confluent cells at concentrations in the range of those demonstrating potent inhibition of HCMV replication. Similarly, protein synthesis was largely unaffected by these drugs in stationary mock-infected cells as measured by the incorporation of isotopically labelled amino acids. In contrast, cellular DNA synthesis was invariably reduced in the presence of either drug. HCMV-specific DNA synthesis was also strongly inhibited by papaverine and DHPG.

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The Effect of Human Recombinant Superoxide Dismutase Conjugated with Polyethylene Glycol on the Hepatic Toxicity of Acetaminophen (HrSOD-폴리에칠렌 접합체의 아세트아미노펜 간독성에 미치는 영향)

  • Yong, Chul-Soon;Park, Kyong-Ah;Oh, Doo-Man
    • Journal of Pharmaceutical Investigation
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    • v.25 no.4
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    • pp.313-322
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    • 1995
  • The covalent conjugation of human recombinant superoxide dismutase (hrSOD) with trichloros-triazine activated polyethylene glycol (PEG) 5000 formed soluble conjugates with molecular weight of 92KD, which retained $90{\sim}98%$ of original activity with a markedly prolonged plasma half-life of enzyme activity. The effect of hrSOD-PEG conjugates on acetaminophen (ACP)-induced hepatotoxicity was tested in male rats which were pretreated with 3-methylcholanthrene. HrSOD-PEG conjugates inhibited the hepatotoxicity produced by ACP, on the other hand, native hrSOD had no protective effect. The above results indicated that oxygen radicals might participate in the mechanism of the ACP-induced hepatotoxicity and that polymer conjugated-protein drugs with prolonged half-lives could be employed as an effective therapeutic agent.

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Ethnobotany, Phytochemistry, and Pharmacology of Angelica decursiva Fr. et Sav.

  • Ali, Md Yousof;Seong, Su Hui;Jannat, Susoma;Jung, Hyun Ah;Choi, Jae Sue
    • Natural Product Sciences
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    • v.25 no.3
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    • pp.181-199
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    • 2019
  • Angelica decursiva Fr. et Sav. (Umbelliferae) has traditionally been used to treat different diseases due to its antitussive, analgesic, and antipyretic activities. It is also a remedy for thick phlegm, asthma, and upper respiratory infections. Recently, the leaf of A. decursiva has been consumed as salad without showing any toxicity. This plant is a rich in different types of coumarin derivatives, including dihydroxanthyletin, psoralen, dihydropsoralen, hydroxycoumarin, and dihydropyran. Its crude extracts and pure constituents possess anti-inflammatory, anti-diabetic, anti-Alzheimer disease, anti-hypertension, anti-cancer, antioxidant, anthelmintic, preventing cerebral stroke, and neuroprotective activities. This valuable herb needs to be further studied and developed not only to treat these human diseases, but also to improve human health. This review provides an overview of current knowledge of A. decursiva metabolites and their biological activities to prioritize future studies.

Review for Selenium-fortified Functional Products of Livestock (셀레늄 강화 기능성 축산물에 관한 고찰)

  • Kim, W.Y.
    • Journal of Practical Agriculture & Fisheries Research
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    • v.5 no.1
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    • pp.36-56
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    • 2003
  • Selenium(Se) is an essential trace element in the human body. Main function of this element is a catalytic part of antioxidant enzymes that protect cells against the attacks of free radicals that are produced during normal metabolism of the body. Se is also essential for normal function of the immune system and thyroid gland. It also appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV(human immunodeficiency virus) progression to AIDS. It is also required for sperm motility and reduces the depression. Therefore, it is very meaningful that livestock producers generate Se-fortified animal products, such as Se-egg, Se-milk, Se-pork, Se-chicken and Se-beef from the point of producers as well as human heath. However, regulation on Se usage and Se-fortified food/feed is far from being clear in Korea even though Se should be carefully monitored because of its toxicity. Thus, one has to be aware of Se properties when designing Se-fortified animal products.

Guidelines for Manufacturing and Application of Organoids: Lung

  • Kyungtae Lim;Mi-Ok Lee;Jinwook Choi;Jung-Hyun Kim;Eun-Mi Kim;Chang Gyu Woo;Chaeuk Chung;Yong-Hee Cho;Seok-Ho Hong;Young-Jae Cho;Sun-Ju Ahn
    • International Journal of Stem Cells
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    • v.17 no.2
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    • pp.147-157
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    • 2024
  • The objective of standard guideline for utilization of human lung organoids is to provide the basic guidelines required for the manufacture, culture, and quality control of the lung organoids for use in non-clinical efficacy and inhalation toxicity assessments of the respiratory system. As a first step towards the utilization of human lung organoids, the current guideline provides basic, minimal standards that can promote development of alternative testing methods, and can be referenced not only for research, clinical, or commercial uses, but also by experts and researchers at regulatory institutions when assessing safety and efficacy.

Genernal Pharmacological and Acute/Subacute Toxicity Test of House Dust Mite Extract in Mice, Rats, and Guinea pigs (마우스, 랫트, 해명에서 집먼지 진드기 추출물의 일반 약리시험과 급성 및 아급성 독성에 관한 연구)

  • 노재열;김경환
    • Toxicological Research
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    • v.14 no.2
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    • pp.183-191
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    • 1998
  • It has been reported that 50~70% of child asthma, bronchial asthma in adult, and allergic rhinitis are caused by house dust mite. The antigen extracted from house dust mite has been used for effective treatment against allergic diseases and for clinical test. This house dust mite antigen has been entirely imported from abroad. However, the composition and content of all the antigen imported vary from a brand to other brand. Thus, we need to standardize the composition and content of the antigen by developing it domestically. We proceeded pre-clinically general pharmacological test and toxicological test that are required for the eventual human use by utilizing the house dust mite cultured in Korea. In order to obtain information on general pharmacological tests such as its toxic signs in tissues or organs which are mainly affected, we examined the effect of house dust mite on the tensions of the isolated tissues and heart rates of cardiac muscle by recording with force displacement transducer of polygragh (Glass Model 7). We determined lethality of antigen extracted from house dust mite in mice and guinea pigs. We examined acute and subacute toxicity by administrating house dust mite extract of 500, 100, 20 times of the expected clinical dose. In male and female mice and guinea pigs, given a sigle intraperitoneal dose of antigen, $LD_{50}$ values were over 5.0 $\textrm{m}{\ell}$/kg, respectively. In animals administrated with house dust mite, there were no significant change of clinical symptom, body weight, food consumption, water consumption, eye examinations, urinalysis, blood biochemistry, and histopathological examinations in any animals tested. We found no toxic effect of this house dust mite. These results show that the house dust mite cultured by us could be used in the development of medicine against allergic diseases caused by the antigen of house dust mite.

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Toxicity of Puffer Fish, Arothron firmamentum (Byeolbok) and Lagocephalus spp. in Korea (연안 어시장에서 유통되는 별복(Arothron firmamentum)과 밀복류(Lagocephalus spp.)의 독성)

  • Kim, Ji-Hoe;Son, Kwang-Tae;Mok, Jong-Soo;Kim, Ju-Gyeong;Jo, Mi-Ra;Shim, Kil-Bo;Lee, Tae-Seek
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.41 no.5
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    • pp.309-314
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    • 2008
  • The toxicity of five species of puffer fish, Arothron firmamentum (Byeolbok), Lagocephalus gloveri (Heukmilbok), L. wheeleri (Eunmilbok), L. inermis (Minmilbok) and L. lunaris (Milbok), collected from fish markets in Korea, was determined using a mouse bioassay. In A. firmamentum, the proportion of toxic specimens containing >10 MU/g was 87.5% in the ovaries, and 10.0% in the skin; no toxicity was detected in the muscle, fin, liver, intestine and gallbladder using the mouse bioassay. The highest toxin levels were found to be 87 MU/g in the ovaries, and 13 MU/g in the skin. Toxic specimens containing >10 MU/g were not detected from samples taken from any of the organs in L. wheeleri and L. inermis. In L. gloveri, most specimens were found to be non-toxic, but toxin levels of 11-72 MU/g were detected from within the skin, fins, and intestines in one specimen. In L. lunaris, the proportion of toxic specimens was 50.0% in the ovaries, and 7.1% in the gallbladder; no toxicity was detected in the other organs by the mouse bioassay. The highest toxin levels were 75 MU/g in the ovaries, and 14 MU/g in the gallbladder. Therefore, the toxicities of edible muscle and skin in the five species of puffer fish marketed in Korea were found to be within acceptable levels for human consumption.