• 대한임상독성학회지
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• 제16권2호
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• pp.149-156
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• 2018

Purpose: The purpose of this study was to determine whether hepatotoxicity could be predicted early using biochemical markers in patients with acetaminophen (AAP) poisoning and to assess the usefulness of predictive factors for acute liver injury or hepatotoxicity. Methods: This study was a retrospective observational study involving a medical records review. The participants were patients who were admitted to the emergency department (ED) with AAP overdose at two hospitals over a 10-year period. Demographic data, age, time from ingestion to visit, initial AAP level, initial hepatic aminotransferases, and initial prothrombin time were recorded. Acute liver injury was defined as a peak serum ALT >50 U/L or double the admission value, and hepatotoxicity was defined as a peak ALT >1,000 U/L. Receiver operating characteristic curve analyses were performed to compare the prognostic performance among variables. Results: A total of 97 patients were admitted to the ED with AAP overdose, of whom 26 had acute liver injury and 6 had hepatotoxicity. Acute liver injury was associated with the time interval after taking the drug, and hepatotoxicity was associated with the initial PT and the ALT level. The scoring system proposed by the authors has a significant ability to predict both acute liver injury and hepatotoxicity. Conclusion: To predict the prognosis of AAP poisoning patients, the time interval after taking AAP was important, and initial prothrombin time and ALT level were useful tests. Also a scoring system combining variables may be useful.

• BMB Reports
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• 제52권3호
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• pp.190-195
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• 2019

Acetaminophen (APAP) overdose can cause hepatotoxicity by inducing mitochondrial damage and subsequent necrosis in hepatocytes. Sirtuin2 (Sirt2) is an $NAD^+$-dependent deacetylase that regulates several biological processes, including hepatic gluconeogenesis, as well as inflammatory pathways. We show that APAP decreases the expression of Sirt2. Moreover, the ablation of Sirt2 attenuates APAP-induced liver injuries, such as oxidative stress and mitochondrial damage in hepatocytes. We found that Sirt2 deficiency alleviates the APAP-mediated endoplasmic reticulum (ER) stress and phosphorylation of the p70 ribosomal S6 kinase 1 (S6K1). Moreover, Sirt2 interacts with and deacetylates S6K1, followed by S6K1 phosphorylation induction. This study elucidates the molecular mechanisms underlying the protective role of Sirt2 inactivation in APAP-induced liver injuries.

• 대한임상독성학회지
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• 제20권2호
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• pp.39-44
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• 2022

N-Acetylcysteine (NAC) is the standard antidote treatment for preventing hepatotoxicity caused by acetaminophen (AAP) poisoning. This review summarizes the recent evidence for the treatment of AAP poisoning. Several alternative intravenous regimens of NAC have been suggested to improve patient safety by reducing adverse drug reactions and medication errors. A two-bag NAC infusion regimen (200 mg/kg over 4 h, followed by 100 mg/kg over 16 h) is reported to have similar efficacy with significantly reduced adverse reactions compared to the traditional 3-bag regimen. Massive AAP poisoning due to high concentrations (more than 300-lines in the nomogram) needs to be managed with an increased maintenance dose of NAC. In addition to NAC, the combination therapy of hemodialysis and fomepizole is advocated for severe AAP poisoning cases. In the case of a patient presenting with an altered mental status, metabolic acidosis, elevated lactate, and an AAP concentration greater than 900 mg/L, hemodialysis is recommended even if NAC is used. Fomepizole decreases the generation of toxic metabolites by inhibiting CYP2E1 and may be considered an off-label use by experienced clinicians. Since the nomogram cannot be applied to sustained-release AAP formulations, all potentially toxic sustained-release AAP overdoses should receive a full course of NAC regimen. In case of ingesting less than the toxic dose, the AAP concentration is tested twice at an interval of 4 h or more; NAC should be administered if either value is above the 150-line of the nomogram.

• 분석과학
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• 제29권3호
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• pp.126-135
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• 2016

상수원으로 유출될 가능성이 높은 잔류의약물질 대상으로 정수처리공정의 단위 공정별 잔류의 약물질 제어 효율을 평가하였다. 응집 공정에서는 Sulfonamide계 항생제는 22.6~42.1 % 제거 되었으며, Naproxen 28.2 %, Acetaminophen 20 %가 제거되었다. Trimethoprim은 4.4 %, Erythromycin은 2.4 %로 낮은 제거율을 보여 주었으며, Aspirin은 전혀 제거되지 않았다. 염소처리와 응집 혼합 공정을 적용하였을 때, 염소 주입량이 증가할수록 제거율이 증가되었다. 염소주입농도 3 mg/L일 때 Sulfonamide계 항생제, Acetaminophen, Naproxen은 100 %, Trimethoprim은약 98%로높은제거효율을나타내었으며 Erythromycin은 약 55 %, Aspirin은 약 10 %로 낮은 제거율을 보여 주었다. 분말활성탄 흡착 공정을 적용하였을 때, 분말활성탄 주입 농도가 증가할수록 제거율이 증가되었다. Sulfonamide계 항생제의 경우 1 mg/L에서 약 18~50 % 제거율을 보였으며, 25 mg/L에서는 약 80 % 이상으로 제거율이 증가하였다. 정수처리 공정에서 잔류의약물질의 효율적인 처리를 위한 염소처리와 흡착, 응집 공정의 적정 주입농도를 평가한 결과 염소 3 mg/L, 분말활성탄 10 mg/L, 응집제 15 mg/L을 적용했을 때 약 90 % 이상이 제거되었다.

• 대한본초학회지
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• 제27권2호
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• pp.85-91
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• 2012

Objective : Myeongganbo (MGB) composited with Hovenia Semen, Puerariae Radix and Dioscoreae Rhizoma is the prescription for protection of liver function. The purpose of this study was to investigate the effects of MGB extract against acetaminophen (APAP)-induced liver injury in mice. Methods : MGB extract was prepared by extracting with hot distilled water. The extract was freeze-dried following filtration through vacuum distillation system. Mice fasted for overnight were orally administrated with or without MGB extract of different doses (25-200 mg/kg/day). After 30 min, APAP was orally applied with a single dose (400 mg/kg). The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured in plasmas of mice. Glutathione (GSH), glutathione peroxidase GSH-px), cyclooxygenase-2 (COX-2) activity and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) level were investigated in liver homogenates. Liver sections were stained with haematoxylin & eosin, anti-TNF-${\alpha}$ and anti-mouse COX-2 antibodies. Results : APAP treatment remarkably increased AST and ALT activities in plasma but inhibited GSH and GSH-px levels in liver homogenates. Also, liver injury was significantly accelerated by APAP treatment. Furthermore, APAP remarkably elevated COX-2 activity and TNF-${\alpha}$ levels in liver homogenates. However, administration of MGB extract was able to counteract these effects. Histological studies provided supportive evidence for biochemical and molecular analysis Conclusions : These results suggest that MGB extract has potent hepatoprotective effect against APAP-induced liver injury, these properties may contribute to liver disease care.

• Journal of Periodontal and Implant Science
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• 제30권1호
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• pp.1-11
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• 2000

Although various analgesics have been administrated for postoperative pain control, postoperative pain has not been adequately controlled . The purpose of this study was to evaluate the effects and patient's satisfaction of $Myprodol^{(R)}$(combination analgesics with codeine, ibuprofen, paracetamol) compared to Acetamionphen and placebo drug after periodontal surgery and dental implant surgery. We studied 98 cases of outpatients which were composed of 67 cases of flap operation(which separated to 3 groups: Placebo group(n=25), $Myprodol^{(R)}$ group(n=22), Acetaminophen group(n=20)) and 21 cases of dental implant surgery(which separated to 3 groups : Placebo group(n=10), $Myprodol^{(R)}$ group(n=12), Acetaminophen group(n=9)). We evaluated the postoperative pain(Pain 1), Pain after first drug administraion(Pain 2), the degrees of pain reduction(pain 3), patient's satisfaction for drug, and side-effects. We obtained following results; 1. In Pain 1, making a comparison among groups, there was no significant difference in both cases of flap operation-group and dental implant surgery-group 2. In Pain 2, establishing a comparison among groups, there was no significant difference in flap operation-group, but significant difference was seen between placebo group and $Myprodol^{(R)}$ group in cases of dental implant surgery group(P<0.05). 3. In Pain 3, making a comparison among groups, $Myprodol^{(R)}$ group showed significant differences compared to placebo group and Acetaminophen group in both cases of flap operation group and dental implant surgery group(P<0.05). 4. In patient's satisfactory score, making a comparison among groups, there were significant differences between placebo group and $Myprodol^{(R)}$ group in cases of flap operation group and between $Myprodol^{(R)}$ group and Acetaminophen group in cases of dental implant surgery group(P<0.05). 5. Making a comparison in side-dffect, no significant differrence was seen. Our conclusion is that $Myprodol^{(R)}$ is a effective oral analgesics to the patients who underwent periodontal surgery or implant surgery for it's synergism among three dugs.

• Journal of Ginseng Research
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• 제29권3호
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• pp.131-137
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• 2005

백삼과 홍삼 추출물이 APAP에 의한 산화적 급성 간손상에 대한 보호효과를 마우스를 대상으로 검토한 결과 다음과 같은 결론을 얻었다. 1. 백삼과 홍삼 추출물의 간장보호 활성에 관한 기전을 규명하고자 항산화효소인 SOD, CAT의 활성도는 APAP를 복강 주사한 실험군에서 대조군에 비해 효소활성이 감소하였고, 백삼과 홍삼추출물을 전처리한 실험군에서는 APAP군에 비해 효소 활성도가 증가하는 경향을 보였다. 2. 지질과산화물의 함량은 APAP를 복강 주사한 실험군이 대조군에 비해 유의성 있게 증가하였고 백삼과 홍삼 추출물을 전처리한 실험군에서는 APAP군에 비해 지질과산화물의 생성을 유의성 있게 억제하였다. 3. 백삼과 홍삼 추출물의 투여량을 각각 50mg/kg, 250mg/kg으로 최대 5일간 전처리하여 APAP의 급성 간손상에 대한 보호효과를 조사한 결과 인삼 추출물의 투여량에는 크게 영향을 받지 않는 것으로 보였다. 따라서 백삼과 홍삼 추출물은 APAP의 활성 대사체에 의한 급성 산화적 간손상을 억제하였으며, 이는 인삼 추출물 성분이 항산화 효소와 항산화물질로 구성된 항산화 방어 체계를 통한 것임을 알 수 있다. 본 연구의 결과를 바탕으로 백삼과 홍삼 추출물이 간장 보호제로서의 개발 가능성이 있으며, APAP중독에 매우 효과적인 치료제로서 임상에서 활용될 수 있다고 생각된다.

• 대한임상독성학회지
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• 제16권2호
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• pp.68-74
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• 2018

Purpose: In 2012, a revised guideline for acute acetaminophen overdose was proposed in the UK, recommending that the treatment threshold should be lowered to 100 mcg/ml at 4 hours after ingestion without risk stratification of hepatotoxicity. However, the poison centers in some developing countries do not have laboratory resources to provide serum drug levels in time. The primary aim of the study is to evaluate the cut-off value of reported dose per kilogram to determine when N-acetylcysteine treatment is warranted under the revised guideline. Methods: Data were collected retrospectively from the toxicology registry of an urban emergency medical center between 1st January 2010 and 30th June 2017. Inclusion criteria were single acute overdose of more than 75 mg/kg in 15 hours from ingestion and over 14 years of age. Subgroups were created by 25 mg/kg increments of reported dose, then sensitivity, specificity, positive predictive value and negative predictive value were calculated for the cut-off values of 100 mg/kg, 125 mg/kg, 150 mg/kg and 175 mg/kg for toxic serum level over '100-treatment line'. Results: A total of 99 patients were enrolled in the study; 24 patients showed toxic serum levels (24.2%). Zero of 17 patients with an ingestion dose under 100 mg/kg showed toxic level (0%), and 0 of 15 under 125 mg/kg (0%), 2 of 14 under 150 mg/kg (14.3%), and 4 of 12 under 175 mg/kg (33.3%) had toxic levels. The higher the ingested dose per kilogram of weight, the higher the frequency of the toxic serum concentration on the first test (${\chi}^2$ test for trend, ${\chi}^2=22.66$, p-value<0.001) and the sensitivity of each value was 100%, 100%, 92% and 76%. Conclusion: In acute single acetaminophen intoxication, the ingestion dose of 100 mg/kg of weight will be useful in determining the need for the N-acetylcysteine antidote in the indigent laboratory environment.

• 공업화학
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• 제32권3호
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• pp.299-304
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• 2021

본 연구에서는 mung bean starch (MBS), polyvinyl alcohol (PVA), sodium benzoate (S), glycerol (GL), melanin (MEL)을 이용하여 광열 효과가 있는 기능성 acetaminophen (AP) 각인 MBS 기반 바이오 소재를 제조하고 약물 방출 특성을 조사하였다. 제조된 AP 각인 바이오 소재의 물리화학적 특성은 FE-SEM과 FT-IR을 통해 분석하였다. 또한, NIR (near infrared) laser (1.5 W/cm²) 조사에 따른 기능성 바이오 소재의 광열 효과 및 AP 방출 특성을 조사하였다. 바이오 소재에 NIR laser를 조사하였을 때, MEL이 첨가 바이오 소재는 첨가하지 않은 바이오 소재보다 2배 이상 높은 온도상승을 보였다. 표준 버퍼 용액과 인공 피부를 사용하여 기능성 AP 각인 바이오 소재의 AP 방출 특성 조사결과, NIR laser를 조사하였을 때, MEL 첨가 바이오 소재는 첨가하지 않은 바이오 소재보다 AP 방출율이 1.2배 높은 것을 확인하였다. 이 결과로부터, 기능성 바이오 소재는 급성 진통 치료를 위한 바이오 소재로 활용될 수 있을 것으로 판단된다.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 1996년도 제19회정기학술대회(The 19th Symposium of the Korean Society of Environmental Toxicology)
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• pp.54-54
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• 1996