• Title/Summary/Keyword: ACUTE TOXICITY

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Acute Phase Retinal Phototoxicity Induced by Blue Fluorescent Light (토끼에서의 청형광 광선에 의한 실험적 급성 망막독성)

  • Park, Young-Hoon;Cha, Soon-Cheol;Hahn, Duk-Kee
    • Journal of Yeungnam Medical Science
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    • v.12 no.1
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    • pp.75-83
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    • 1995
  • Even though phototherapy is an effective means of treating hyperbilirubinemia, adequate binocular shields are essential to prevent light hazard of retina during phototherapy. The phototherapy to young albino rabbits was performed under various conditions; exposured for 12, 24, and 48 hours, continuity or intermittence of irradiation, and use of shields. Although there was no definite pathologic change in indirect ophthalmoscopic examination, severe damage was seen at electron microscopic level. In all experimental groups, swelling and edema of photoreceptor were seen at right after phototherapy. Futhermore, more severe damage was seen in case of intermittent irradiated group and prolong exposed group. In mydriatic eyes, severity of damage was similiar to non mydriatic eyes, but area of retinal damage was more extensive than non-mydriatic eyes. In control group which was protected by binocular shields during phototherapy, no significant abnormality was found.

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Symptomatic Hypocalcemia Associated with Dioscorea tokoro Toxicity (도코로(Tokoro)마 중독과 관련한 저 칼슘혈증)

  • Yoon, Jae Chol;Lee, Jae Baek;Jeong, Tae Oh;Jo, Si On;Jin, Young Ho
    • Journal of The Korean Society of Clinical Toxicology
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    • v.17 no.1
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    • pp.42-45
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    • 2019
  • Dioscorea tokoro has long been used in Korean traditional medicine as a pain killer and anti-inflammatory agent. A 53-year-old male who consumed water that had been boiled with raw tubers of D. tokoro as tea presented with numbness and spasm of both hands and feet. Laboratory results showed hypocalcemia, hypoparathyroidism, and vitamin D insufficiency. During his hospital stay, colitis, acute kidney injury, and toxic encephalopathy developed. The patient received calcium gluconate intravenous infusion and oral calcium carbonate with alfacalcidol. His symptoms improved gradually, but hypocalcemia persisted despite the calcium supplementation. We suggest that ingestion of inappropriately prepared D. tokoro can cause symptomatic hypocalcemia in patients with unbalanced calcium homeostasis.

Bright Light Therapy in the Morning or at Mid-Day in the Treatment of Non-Seasonal Bipolar Depressive Episodes (LuBi): Study Protocol for a Dose Research Phase I / II Trial

  • Geoffroy, Pierre Alexis;El Abbassi, El Mountacer Billah;Maruani, Julia;Etain, Bruno;Lejoyeux, Michel;Amad, Ali;Courtet, Philippe;Dubertret, Caroline;Gorwood, Philip;Vaiva, Guillaume;Bellivier, Frank;Chevret, Sylvie
    • Psychiatry investigation
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    • v.15 no.12
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    • pp.1188-1202
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    • 2018
  • Objective This study protocol aims to determine, using a rigorous approach in patients with bipolar disorder (BD) and non-seasonal major depressive episode (MDE), the characteristics of bright light therapy (BLT) administration (duration, escalation, morning and mid-day exposures) depending on the tolerance (hypomanic symptoms). Methods Patients with BD I or II and treated by a mood stabilizer are eligible. After 1 week of placebo, patients are randomized between either morning or mid-day exposure for 10 weeks of active BLT with glasses using a dose escalation at 7.5, 10, 15, 30 and 45 minutes/day. A further follow-up visit is planned 6 months after inclusion. Patients will be included by cohorts of 3, with at least 3 days of delay between them, and 1 week between cohorts. If none meet a dose limiting toxicity (DLT; i.e hypomanic symptoms), the initiation dose of the next cohort will be increased. If one patient meet a DLT, an additionnal cohort will start at the same dose. If 2 or 3 patients meet a DLT, from the same cohort or from two cohorts at the same dose initiation, the maximum tolerated dose is defined. This dose escalation will also take into account DLTs observed during the intra-subject escalation on previous cohorts, with a "Target Ceiling Dose" defined if 2 DLTs occured at a dose. Discussion Using an innovative and more ergonomic device in the form of glasses, this study aims to better codify the use of BLT in BD to ensure a good initiation and tolerance.

Acute Exposure to Karenia mikimotoi Induces Oxidative Stress and Reduces Immune Parameters in the Marine Medaka Oryzias javanicus

  • Seong Duk Do;Yun Kyung Shin;Jae-Sung Rhee
    • Journal of Marine Life Science
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    • v.8 no.2
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    • pp.190-195
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    • 2023
  • In this research, the marine medaka Oryzias javanicus underwent a 96 h exposure to two concentrations of the red tide dinoflagellate Karenia mikimotoi (1,000 and 5,000 cells mL-1), and the temporal variations in biochemical responses related to antioxidant and immunity parameters were assessed in the liver tissue. The study revealed a significant increase in ichthyotoxicity with elevated cell concentrations of K. mikimotoi, especially evident at 96 h in marine medaka exposed to 5,000 cells mL-1. At 1,000 cells mL-1 of K. mikimotoi, the opercular respiratory rate showed a significant increase, whereas exposure to 5,000 cells mL-1 resulted in a lowered rate. The intracellular malondialdehyde content was significantly elevated in response to both cell concentrations at 96 h. Regarding glutathione content, levels were significantly increased by exposure to both cell concentrations. Catalase and superoxide dismutase enzymatic activities experienced an increase at 1,000 cells mL-1 of K. mikimotoi, while their activities were reduced at 5,000 cells mL-1 at 96 h. The analysis of two immunity parameters, alternative complement pathway and lysozyme, demonstrated significantly reduced activities in the liver tissue exposed to 5,000 cells mL-1 of K. mikimotoi. These findings aim to enhance the understanding of K. mikimotoi toxicity in marine fish by offering insights into biochemical responses associated with harmful algal blooms.

Identification of the mechanism for dehalorespiration of monofluoroacetate in the phylum Synergistota

  • Lex E. X. Leong;Stuart E. Denman;Seungha Kang;Stanislas Mondot;Philip Hugenholtz;Chris S. McSweeney
    • Animal Bioscience
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    • v.37 no.2_spc
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    • pp.396-403
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    • 2024
  • Objective: Monofluoroacetate (MFA) is a potent toxin that blocks ATP production via the Krebs cycle and causes acute toxicity in ruminants consuming MFA-containing plants. The rumen bacterium, Cloacibacillus porcorum strain MFA1 belongs to the phylum Synergistota and can produce fluoride and acetate from MFA as the end-products of dehalorespiration. The aim of this study was to identify the genomic basis for the metabolism of MFA by this bacterium. Methods: A draft genome sequence for C. porcorum strain MFA1 was assembled and quantitative transcriptomic analysis was performed thus highlighting a candidate operon encoding four proteins that are responsible for the carbon-fluorine bond cleavage. Comparative genome analysis of this operon was undertaken with three other species of closely related Synergistota bacteria. Results: Two of the genes in this operon are related to the substrate-binding components of the glycine reductase protein B (GrdB) complex. Glycine shares a similar structure to MFA suggesting a role for these proteins in binding MFA. The remaining two genes in the operon, an antiporter family protein and an oxidoreductase belonging to the radical S-adenosyl methionine superfamily, are hypothesised to transport and activate the GrdB-like protein respectively. Similar operons were identified in a small number of other Synergistota bacteria including type strains of Cloacibacillus porcorum, C. evryensis, and Pyramidobacter piscolens, suggesting lateral transfer of the operon as these genera belong to separate families. We confirmed that all three species can degrade MFA, however, substrate degradation in P. piscolens was notably reduced compared to Cloacibacillus isolates possibly reflecting the loss of the oxidoreductase and antiporter in the P. piscolens operon. Conclusion: Identification of this unusual anaerobic fluoroacetate metabolism extends the known substrates for dehalorespiration and indicates the potential for substrate plasticity in amino acid-reducing enzymes to include xenobiotics.

Identifying immunodominant multi-epitopes from the envelope glycoprotein of the Lassa mammarenavirus as vaccine candidate for Lassa fever

  • Adekunle Babajide Rowaiye;Ezinne Janefrances Nwonu;Titilayo Mercy Asala;Amoge Chidinma Ogu;Doofan Bur;Chimaobi Chukwu;Angus Nnamdi Oli;Tarimoboere Agbalalah
    • Clinical and Experimental Vaccine Research
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    • v.11 no.3
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    • pp.249-263
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    • 2022
  • Purpose: Lassa fever is a zoonotic acute viral hemorrhagic disease caused by Lassa virus (LASV). There is currently no licensed vaccine for the prevention of the disease. This study is aimed at discovering immunodominant epitopes from the envelope glycoprotein of the Lassa mammarenavirus and designing of a multi-epitope vaccine candidate (VC). Materials and Methods: The amino acid sequences of the envelope glycoprotein of 26 strains of LASV from five countries were selected. After evaluation for antigenicity, immunogenicity, allergenicity, and toxicity, immunodominant CD8, CD4, and linear B lymphocytes were also selected. The selected epitopes were modelled and a molecular docking with the appropriate major histocompatibility complex (MHC) proteins was performed. Using an adjuvant and linkers, a multi-epitope VC was designed. The VC was evaluated for its physicochemical and immunological properties and structurally refined, validated, and mutated (disulphide engineering). The complex formed by the VC and the toll-like receptor-4 receptor was subjected to molecular dynamic simulation (MDS) followed by in silico cloning in a plasmid vector. Results: A VC with 203 sequences, 22.13 kDa weight, isoelectric point of 9.85 (basic), instability index value of 27.62, aliphatic index of 68.87, and GRAVY value of -0.455 (hydrophilic) emerged. The VC is predicted to be non-allergenic with antigenicity, MHC I immunogenicity, and solubility upon overexpression values of 0.81, 2.04, and 0.86 respectively. The VC also has an estimated half-life greater than 10 hours in Escherichia coli and showed stability in all the parameters of MDS. Conclusion: The VC shows good promise in the prevention of Lassa fever but further tests are required to validate its safety and efficacy.

Anti-inflammatory Activity of Sargassum micracanthum Water Extract (잔가시 물 추출물의 항염증 효과)

  • Jeong, Da Hyun;Kang, Bo Kyeong;Kim, Koth Bong Woo Ri;Kim, Min Ji;Ahn, Dong Hyun
    • Journal of Applied Biological Chemistry
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    • v.57 no.3
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    • pp.227-234
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    • 2014
  • The anti-inflammatory effect of Sargassum micracanthum water extract (SMWE) was investigated using lipopolysaccharide (LPS)-induced inflammatory response in this study. The murine macrophage cell line RAW 264.7 cells were used and MTT assay was performed to measure the cell proliferation ability. The secretion of nitric oxide (NO), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6), and IL-$1{\beta}$ was measured in LPS-induced RAW 264.7 cells by ELISA. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear transcription factor-kappa B p65 protein was studied by immunoblotting. The Balb/c mice were used for an acute toxicity test, and imprinting control region mice were purchased to evaluate a croton oil-induced ear edema. As a result, there was no cytotoxicity in the macrophage proliferation treated with SMWE compared to the control. NO levels decreased with increasing concentration of SMWE and were inhibited over 50%. Moreover, the secretion of IL-6, TNF-${\alpha}$, and IL-$1{\beta}$ was suppressed in a dose-dependent manner, especially, IL-$1{\beta}$ inhibition activity was over 50% at 50 ${mu}g$/mL. The formation of ear edema of mice was reduced at the highest dose tested compared to that in the control. Moreover, in acute toxicity test, no moralities occurred in mice administered 5,000 mg/kg body weight of SMWE over 2 weeks observation period. These results suggested that SMWE may have significant effects on inflammatory factors and be potential anti-inflammatory therapeutic materials.

Evaluation of Fish Acute Toxicity and Preliminary Risk Assessment of Plant Extracts, Sophora, Neem and Derris (유기농업자재 고삼, 님 및 데리스 추출물의 어류에 대한 독성과 위해성 평가)

  • Park, Kyung-Hun;Oh, Jin-A;Paik, Min-Kyoung;Son, Mi-Yeon;Lim, Joung-Taek;Jin, Jung-hwa;Hong, Soonsung;Cho, Nam-jun;Han, Sang-Gyun;Kim, Byung-Seok
    • The Korean Journal of Pesticide Science
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    • v.19 no.3
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    • pp.255-263
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    • 2015
  • Promoting the organic farming, much of the plant extracts used for controlling pests and fungi have been imported from China, India and Myanmar. But, it is so worrisome that aquatic animals such as muddy loach inhabiting in paddy field and common carps in river exposed to the pests and fungi likely be harmed. This study was conducted in order to evaluate the risks of aquatic animals influenced by the three plant extracts, i.e. Sophora flavescens, Azadirachta indica and Derris elliptica. The toxicities of common carp (Cyprinus Carpio), muddy loach (Misgurnus anguillicaudatus) and PEC (Predicted environmental concentration) exposed to the three plant extracts were estimated by the typical spray volume method. Risks were determined by the toxicity value as 48-hr $LC_{50}$ (Lethal concentration, median) or NOEC (No observed effect concentration) into PEC. 48-hr $LC_{50}$ of Common carp and NOEC by Sophora flavescens extracts was 7.9 and 6.2 mg/L, 26.8 and 21.8 mg/L by Azadirachta indica extracts and 47.0 and < 24.0 mg/L by Derris elliptica extracts, respectively. 48-hr $LC_{50}$ of Muddy loach and NOEC by Sophora flavescens extracts was 16.9 and 10.0 mg/L, 35.6 and 30.0 mg/L by Azadirachta indica extracts, and 73.9 and < 40 mg/L by Derris elliptica extracts, respectively. Therefore, acute toxicities of the three plant extracts for aquatic animals were proved to be very low level. PEC of Sophora flavescens extracts in paddy, drainage and river water was 68.0~3.0, 11.33~0.50 and 3.0~0.0018 mg/L, respectively. TER of Sophora flavescens extracts in the three water was 0.2~5.6, 1.5~33.8 and 2.6~4388.9, respectively. PEC of Azadirachta indica extracts in paddy, drainage and river water was 90.9~1.2, 15.2~0.2 and 4.8~0.00075 mg/L, respectively. TER of Azadirachta indica extracts in the three water was 0.4~29.7, 2.3~178.0 and 4.5~35733.3, respectively. PEC of Derris elliptica extracts in river water was 0.0063 mg/L. TER of Derris elliptica extracts in river water was 5222~15667.

Fish Safety and Antimicrobial Activity of Natural Sulfur Solution on Aquatic Microorganisms (Saprolegnia parasitica) Isolated from Misgurnus mizolepis (미꾸라지(Misgurnus mizolepis)에서 분리된 수생균 (Saprolegnia parasitica)에 대한 천연유황수의 항균 활성 및 처리에 대한 어류 안전성)

  • Yi, Seung-Won;Lee, Seung-Hyeop;Lee, Sang-Jong;Kim, Mi-Hee;Lee, Hye-Hyun;Chu, Saet-Byul;Kim, Kyung-Hee;Lee, Hee Jung
    • Korean Journal of Environmental Biology
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    • v.35 no.2
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    • pp.116-122
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    • 2017
  • Basic dyes such as malachite green and methylene blue have been used as disinfectants to control water fungal infections since the 1930s. However, after succeeding reports of carcinogenicity and bioaccumulation of the dye, their use was forbidden in lieu of public health. This study undertook to evaluate the therapeutic effect of sulfur solution processed by effective microorganisms (EM-PSS) against Saprolegnia parasitica infection, and its safety in fish. In vitro antifungal evaluation of EM-PSS inhibited the growth of S. parasitica mycelia at concentrations of 50 ppm or higher. The acute toxicity test of EM-PSS to the mud fish (Misgurnus mizolepis) measured a no effect concentration (NOEC) at 100 ppm, the lowest effect concentration (LOEC) at 125 ppm, and the half-lethal concentration ($LC_{50}$) at 125 ppm in juvenile and 250 ppm in the immature stage. In addition, the ecotoxicity test of EM-PSS using Daphnia magna inhibited swimming of D. magna at concentrations of 100 ppm or less. Lastly, the EM-PSS prevented infection of S. parasitica to mud fish, at concentrations of 50 ppm. Furthermore, at 100 ppm concentration, the EM-PSS showed no acute toxicity on mud fish, nor any eco-toxic effects on D. magnano. Therefore, we conclude that carcinogenic disinfectants such as malachite green and methylene blue could be replaced by EM-PSS to remove S. parasitica in mud fish farming, and might be a potential eco-friendly disinfectant in aquaculture.

Effect of 17β-estradiol on Ecdysteroid Pathway Related Genes in the Brackish Water Flea Diaphanosoma celebensis (17β-estradiol이 기수산 물벼룩의 Ecdysteroid 경로에 미치는 영향)

  • In, Soyeon;Yoo, Jewon;Cho, Hayoung;Lee, Young-Mi
    • Journal of Marine Life Science
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    • v.5 no.2
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    • pp.35-42
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    • 2020
  • 17β-estradiol (E2) is a natural hormone secreted by ovary, and continuously discharged from household and livestock wastewater into aquatic environment. Due to its strong estrogenic activity, it has adverse effects on development and reproduction in crustacean as an endocrine disrupting chemical. Although ecdysteroid signaling pathway play a key role in development in crustacean, little information on transcriptional modulation of ecdysteroid-related genes in response to E2 is available in small crustacean. Here, we investigated the acute toxicity of E2 to obtain 24-h LCx values in the brackish water flea Diaphanosoma celebensis. Time-dependent expression patterns of seven ecdysteroid pathway - related genes (CYP314a1, EcRA, EcRB, USP, ERR, Vtg, VtgR) were further examined using quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR). As results, 24-h LC50 and LC10 values were 9.581 mg/l and 4.842 mg/l, respectively. The mRNA expression of CYP314a1, EcRA, USP, VtgR was significantly up-regulated at 12 or 24 h after exposure to E2. These findings indicate that E2 can affect their molting and reproduction by modulating the expression of ecdysteroid pathway - related in D. celebensis. This study will be useful for better understanding of molecular mode of action of endocrine disrupting chemicals on molting process in small crustacean.