• Title/Summary/Keyword: time course toxicity

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A Case of Amiodarone-Induced Pulmonary Toxicity After a Long Course of a Low Dose Therapy (장기간 사용한 저용량 Amiodarone에 의한 폐독성 1예)

  • Ryu, Jung-Il;Lee, Wan-Suk;Hyun, Dae-Sung;Lee, Sang-Chae;Shin, Tae-Rim
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.6
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    • pp.656-661
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    • 2002
  • Amidarone is one of the most commonly prescribed anti-arrythmic agents for almost all arrythmias, whether atrial or ventricular in origin. There are several side effects associated with amiodarone therapy. These include corneal deposits, abnormal liver function tests, hyper and hypothyroidism, bluish discolorations of the skin, bone marrow suppression, coagulopathies, peripheral neuropathies, and pulmonary toxicity. Amiodarone-induced pulmonary toxicity(APT), which was first described in 1980, is potentially serious side effects that are believed to develop in 5% of patients. Doctors often assume that APT occurs only when high amiodarone doses are used for a long time, but in practice a low maintenance dose of amiodarone may also be toxic. In this report, a case of amiodarone-induced pulmonary toxicity after a long course of a low dose therapy for refractory supraventricular arrythmia is described.

Cardiovascular Manifestations and Clinical Course after Acute Carbon Monoxide Poisoning (급성 일산화탄소 중독에 의한 심혈관계 독성의 임상 양상 및 경과)

  • Lee, In Soo;Jung, Yoon Seok;Min, Young Gi;Kim, Gi Woon;Choi, Sang Cheon
    • Journal of The Korean Society of Clinical Toxicology
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    • v.10 no.2
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    • pp.103-110
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    • 2012
  • Purpose: The aim of this study was to evaluate the cardiovascular manifestations and clinical course in patients with acute carbon monoxide poisoning. Methods: A retrospective study was conducted over a 36 month period on consecutive patients who visited an emergency medical center and were diagnosed with acute carbon monoxide poisoning. A standardized data extraction protocol was performed on the selected patients. Results: A total of 293 patients were selected during the study period. Cardiac manifestations were observed in 35.2% (n=103) of the patients: hypotension in 11 patients (3.8%), ECG abnormalities in 44 patients (15.0%) and cardiac enzyme abnormalities in 103 patients (35.2%). Echo cardiography was performed on 56 patients with cardiac toxicity: 12 patients had abnormal results (5 patients with global hypokinesia and 7 patients with regional wall akinesia). Five patients died within 3 hours after ED admission, and the remaining patients were discharged alive. At 3 months after discharge, none of these patients had died.The SOFA scores in the severe cardiac toxicity group and non-severe cardiac toxicity group at the time of arrival were $2.53{\pm}2.29$ and $2.19{\pm}2.12$, respectively (p=0.860). Conclusion: Cardiovascular manifestations occur after acute CO poisoning at arateof 35.2%. Even those with severe cardiovascular toxicity recovered well within 10 days after admission. Therefore, the importance of cardiac toxicity after acute CO poisoning is not significant in itself in the clinical course, and the short-term prognosis of cardiac toxicity is unlikely to be unfavorable in acute CO poisoning.

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Acute Hepatotoxicity and Toxicokinetics of Acetaminophen in Mice (마우스에서 아세트아미노펜의 급성간독성과 독물동태학)

  • 서경원;류정상;김효정
    • Toxicological Research
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    • v.13 no.3
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    • pp.237-245
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    • 1997
  • As the development of a pharmaceutical product is a dynamic process which involves continuousfeed-back between non-clinical and clinical studies, the integration of pharmacokinetics into toxicity testing became increasingly important in recent years. Toxicokinetic measurements in the toxicity studies is considered to be an important scientific approach in the interpretation of the toxicology findings and the promotion of rational study design development. Primarily this research project was conducted to determine the systemic exposure achieved in acute toxicity test and its relationship to dose level and the time course of the toxicity study. Acute hepatotoxicity study and its relevant toxicokinetic study in mice were performed using acetarninophen (AA) as a model compound. The correlation between acute hepatotoxicity indices and toxicokinetic parameters following intraperitoneally administration of various dosages of AA in mice was evaluated and discussed minutely in the text. Based on these studies, single-dose toxicity testing of AA including kinetic studies was evaluated in ICR mice for 7 days and interpreted in the text. Our results from the integration of toxicokinetic monitoring into single-dose toxicity study enable to elucidate the relation of the exposure achieved in toxicity study to toxicological findings and assist in the selection of appropriate dose levels for use in repeated-dose toxicity or later studies.

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Effect of Route of Trihalomethanes (THM) Administration on Renal Toxicity in Male Rat

  • Chung, Jin-Ho;Lee, Soo-Hwan
    • Archives of Pharmacal Research
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    • v.14 no.2
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    • pp.188-192
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    • 1991
  • Single non-lethal doses of chloroform $(CHCL_3)$ dichlorobromomethane $(CHCL_2Br)$, dibromochloromethane $(CHCIBr_2)$, or bromoform $(CHBr_3)$ were administered to male rats. Routes of exposure including single intraperitional (ip) and subcutaneous (sc) injection were used in order to permit comparison of severity of THM effects and renal toxicity was assessed at varied times following treatment. On an equimolar basis, sc administration of $CHBr_3$ (either 12 or 3 mmoles/kg) is more effective at increasing KW/BW than ip $CHCI_3$ treatment. Plasma urea nitrogen (BUN) following ip THM injections are markedly increased with all four THM at 24 hours post treatment. BUN response to $CHCL_2Br$ and $CHCIBr_3$-effected BUN levels have essentially returned to those of vehicle control. THM sc treatment results in a BUN response similar to that seen following ip treatment, with only the time course being different. With the exception of $CHCL_3$, sc and ip-treatments appear to be equally effective in evoking absolute BUN elevations. These results suggest that THM administration induce renal toxicity dependent upon the route or exposure.

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A Preliminary Study for Development of a Bioassay Protocol Using the Sperm of a Starfish, Asterias amurensis

  • Ryu, Tae-Kwon;Lee, Chang-Hoon;Park, Jin-Woo
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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    • 2003.10a
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    • pp.158-158
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    • 2003
  • Bioassays using gametes of sea urchins are widely used in ecotoxicological assessments of marine environments. Since most of sea urchin species in Korean coastal water spawn from spring to autumn, bioassay with them during the winter is impossible. In the course of developing standard methods for bioassays with Korean species, we found a winter-spawning starfish, Asterias amurensis, Since reproductive mode of asteroids is similar to echinoids, the bioassay protocol for sea urchins could be applied similarly to the starfish. Here, we tested and determined several conditions for the acceptability of bioassay with A. amurensis. The least required time for formation of fertilization membrane of fertilized eggs to be easily distinguished from unfertilized ones was 60 min. The threshold of sperm to egg ratio that could make acceptable fertilization rates in controls was 3000. The allowed time for manipulation of sperm after dilution in seawater was at most 3 hr. The optimal exposure time of sperms when the response against toxicant solution was relatively stable was in the range of 20-60 min. The tolerance range of sperms to the salinity of test solution was 26-38 psu. The sensitivity of A. amurensis sperm was intermediate among marine organisms commonly used in aquatic toxicity tests. The sperm bioassay with A. amurensis can be satisfactorily applied to toxicity assessments of marine environments.

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Nasal and Pulmonary Toxicity of Titanium Dioxide Nanoparticles in Rats

  • Kwon, Soonjin;Yang, Young-Su;Yang, Hyo-Seon;Lee, Jinsoo;Kang, Min-Sung;Lee, Byoung-Seok;Lee, Kyuhong;Song, Chang-Woo
    • Toxicological Research
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    • v.28 no.4
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    • pp.217-224
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    • 2012
  • In recent decades, titanium dioxide ($TiO_2$) nanoparticles have been used in various applications, including paints, coatings, and food. However, data are lacking on the toxicological aspects associated with their use. The aim of this study was to assess the inhalation toxicity of $TiO_2$ nanoparticles in rats by using inhalation exposure. Male Wistar rats were exposed to $TiO_2$ nanoparticles for 2 weeks (6 hr/day, 5 days/week) at a mean mass concentration of $11.39{\pm}0.31mg/m^3$. We performed time-course necropsies at 1, 7, and 15 days after exposure. Lung inflammation and injury were assessed on the basis of the total and individual cell counts in bronchoalveolar lavage fluid (BALF), and by biochemical assays, including an assay for lactate dehydrogenase (LDH). Furthermore, histopathological examination was performed to investigate the lungs and nasal cavity of rats. There were no statistically significant changes in the number of BALF cells, results of biochemical assays of BALF and serum, and results of cytokine analysis. However, we did observe histopathological changes in the nasal cavity tissue. Lesions were observed at post-exposure days 1 and 7, which resolved at post-exposure day 15. We also calculated the actual amounts of $TiO_2$ nanoparticles inhaled by the rats. The results showed that the degree of toxicity induced by $TiO_2$ nanoparticles correlated with the delivered quantities. In particular, exposure to small particles with a size of approximately 20 nm resulted in toxicity, even if the total particle number was relatively low.

Preventive Effects of Zinc Pretreatment in the Time-course of Cadmium-induced Testicular Toxicity in the Rat (아연 전처리가 시간 경과에 따른 카드뮴 유도 고환 독성에 미치는 보호 효과)

  • Jekal, Seung-Joo;Lee, Kyung-Sun;Chung, Ok-Bong;Im, Hyo-Bin
    • Korean Journal of Clinical Laboratory Science
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    • v.41 no.3
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    • pp.111-122
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    • 2009
  • Cadmium (Cd) is known to exert gonadotoxic and spermiotoxic effects. The present study was performed to investigate the morphological effects and metallothionein (MT) expression by zinc pretreatment in the course of time of cadmium-induced testicular injury in rat. Fifty male Spraque-Dawley rats weighing 160~180 g were divided into two groups : saline-pretreated cadmium group and zinc-pretreated cadmium group. Rats of two groups received subcutaneous injection of saline and 100 mg/kg $ZnSO_4$ at 0, 2, 5 and 8 hrs intervals respectively. Cadmium chloride (4.5 mg/kg $CdCl_2$) was administrated intraperitoneally at 2 hrs after zinc injection and rats were killed 0, 12, 24, 48 and 72 hrs later. Testicular tissue damages, interstitial (Leydig) cells status and MT expression were determined using hematoxylin-eosin stained sections and a computerized image analysis system on sections immunostained with a mouse anti-metallothionein respectively. Zinc pretreatment was significantly reduced testicular damages in five pathological categories after cadmium administation. The number of surviving interstitial cells was significantly higher in the zinc-pretreated group than in the saline-preatreated group at 48 and 72 hrs after cadmium administration. Non-damaged testis showed the positivity of MT staining in spermatogenic cells, Sertoli cells and endothelium of blood vessel, but not in the Leydig cells. The positivity of MT staining in saline-pretreated group was significantly reduced at 24 hrs after cadmium administration, whereas zinc-pretreated group showed strong MT positive staining similar to the 0 hr by 42 hrs after cadmium administration. In damaged testis, MT positive staining was also observed in the Leydig cells of both groups. These results suggest that a major preventive effect of zinc against cadmium-induced testicular toxicity may be due to its ability to reduce the cytotoxicity of cadmium in spermatogenic cells and Leydig cells by inhibiting the susceptibility of the testis to cadmium but not MT production by cadmium.

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Preventive Effects of Zinc Pretreatment in the Time-course of Cadmium-induced Testicular Toxicity in the Rat (아연 전처리가 시간 경과에 따른 카드뮴 유도 고환 독성에 미치는 보호 효과)

  • Jekal, Seung-Joo;Lee, Kyung-Sun;Chung, Ok-Bong;Im, Hyo-Bin
    • Korean Journal of Clinical Laboratory Science
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    • v.42 no.3
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    • pp.136-148
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    • 2010
  • Cadmium (Cd) is known to exert gonadotoxic and spermiotoxic effects. The present study was performed to investigate the morphological effects and metallothionein (MT) expression by zinc pretreatment in the course of time of cadmium-induced testicular injury in rat. Fifty male Spraque-Dawley rats weighing 160-180 g were divided into two groups: saline-pretreated cadmium group and zinc-pretreated cadmium group. Rats of two groups received subcutaneous injection of saline and 100 mg/kg $ZnSO_4$ at 0, 2, 5 and 8 hrs intervals respectively. Cadmium chloride (4.5 mg/kg $CdCl_2$) was administrated intraperitoneally at 2 hr after zinc injection and rats were killed 0, 12, 24, 48 and 72 hrs later. Testicular tissue damages, Interstitial (Leydig) cells status and MT expression were determined using hematoxylin-eosin stained sections and a computerized image analysis system on sections immunostained with a mouse anti-metallothionein respectively. Zinc pretreatment was significantly reduced testicular damages in five pathological categories after cadmium administation. The number of surviving interstitial cells was significantly higher in the zinc-pretreated group than in the saline-preatreated group at 48 and 72 hrs after cadmium administration. Non-damaged testis showed the positivity of MT staining in spermatogenic cells, Sertoli cells and endothelium of blood vessel, but not in the Leydig cells. The potitivity of MT staining in saline-pretreated group was significantly reduced at 24 hrs after cadmium administration, whereas zinc-pretreated group showed strong MT positive staining similar to the 0 hr by 42 hrs after cadmium administration. In damaged testis, MT positive staining was also observed in the Leydig cells of both groups. These results suggest a major preventive effect of zinc against cadmium-induced testiculat toxicity may be due to its ability to reduce the cytotoxicity of cadmium in spermatogenic cells and Leydig cells by inhibiting the susceptibility of the testis to cadmium but not MT production by cadmium.

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Severe Liver Toxicity Caused by Amatoxin (Case Series) (심한 간독성을 보인 amatoxin 중독 증례)

  • Suh Joo-Hyun;Kim Sung-Jin;Chung Young-Kuk;Choi Woong-Gil;Kwon Young-Se;Roh Hyung-Keun
    • Journal of The Korean Society of Clinical Toxicology
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    • v.4 no.1
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    • pp.73-77
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    • 2006
  • Poisoning with mushroom containing amatoxin may be a real medical emergency and is characterized by long incubation time lag, gastrointestinal symptoms, hepatotoxic phase and sometimes death. We report a family of parents and two children who ingested wild mushroom and recovered from varying degrees of hepatotoxicity. After eating cooked wild mushroom and its soup, they all developed abdominal pain, vomiting and diarrhea 11 hours later, Their liver enzymes reached peak level between 48 and 72 hours after the ingestion. Among the family members, 5-year-old girl showed the most severe hepatic toxicity of AST/ALT 14,099/13,176 IU/L. They were all treated with supportive measures including repeated activated charcoal and penicillin G and recovered from the hepatotoxicity between 7 and 28 days after the ingestion. Being based on the shape and a typical course of the amatoxin poisoning, we presume that this wild mushroom belongs to Amanita virosa.

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