• Asian Pacific Journal of Cancer Prevention
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• 제15권10호
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• pp.4147-4152
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• 2014

Standard therapy for advanced head and neck cancer consists of a combination of surgery and radiation. However, survival of this patient population has not improved during the past 20 years. Many different multimodality treatment schedules have been proposed, and chemotherapy is often used with the intent of organ preservation. The present study was intended to establish the efficacy of concomitant chemoradiation with a single agent carboplatin in advanced head and neck cancers.The objectives were to investigate the feasibility of concomitant administration of carboplatin, monitor acute toxicity during radiotherapy, and determine subacute side effects, such as wound healing following surgery after chemoradiotherapy. A prospective study was conducted wherein a total of 40 patients with stage III and IV squamous cell carcinomas of oral cavity, oropharynx, hypopharynx and larynx were enrolled. All patients were treated with external beam radiotherapy and weekly carboplatin area under curve (AUC of 5). Radiotherapy was given in single daily fractions of 1.8-2 grays (Gy) to a total dose of 66-72 Gy. Salvage surgery was performed for any residual or recurrent locoregional disease. Neck dissection was recommended for all patients with neck disease showing less than a complete response after chemoradiation. A total of 40 patients were enrolled of whom 32 were males and 8 were females. Highest incidence of cancer was seen in the 5th-6th decades of life with a median age of 47.7 years. Oropharyngeal tumours constituted a maximum of 21 patients followed by hypopharynx in 10, larynx in 7 and oral cavity in 2. 80% of the patients had a neck node on presentation of which 40% had N2-N3 nodal status. TNM staging revealed that 58% of patients were in stage III and 43% in stage IV. Evaluation of acute toxicity revealed that 50% had grade II mucositis, 25% grade III mucositis, 2.5% grade IV mucositis. 50% of patients had grade I skin reactions, 65% of patients had grade I thrombocytopenia, and 24% of patients had grade I anaemia. After completion of treatment 65% of patients had complete response at the primary and regional sites, and 35% of patients had a partial response of whom 23% underwent neck dissection and 5% of them underwent salvage surgery at the primary site. At the end of one year there were six deaths and four recurrences and 70% were free of disease. Concurrent chemoradiation with carboplatin provided good locoregional control for locally advanced head and neck cancers. This regimen, although toxic, is tolerable with appropriate supportive intervention. Primary site conservation is possible in many patients. Chemoradiotherapy appears to have an emerging role in the primary management of head and neck cancers.

• Natural Product Sciences
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• 제29권2호
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• pp.74-82
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• 2023

Nepeta sibirica L. or Siberian catmint is a medicinal plant species used in Mongolian traditional medicine for curing human different disorders and veterinary practices. The previous study of the whole plant concentrated on the determination of its essential oil composition and reported that the major ones are sesquiterpenes, including nepetalactone. The aim of this study was to reveal a new biological activity of the above-ground parts of N. sibirica L. and compare the activity of different extracts correlating with the content of biologically active compounds and evaluate their toxicity. For this purpose, anti-oxidative and acetylcholinesterase inhibitory activities of the above-ground parts of N. sibirica L. aqueous and ethanol (EtOH) (40%, 70%) extracts were assayed spectrophotometrically. The aqueous extract showed positive anti-oxidative activity by both tested DPPH and FRAP assays with IC₅₀ 134.24 ± 1.42 mg/mL and FRAP value 1385.15 ± 8.12 µmol/L at 200 ㎍/mL, in contrast to 40% and 70% EtOH extracts. The 70% EtOH extract presented the highest acetylcholinesterase inhibitory activity (IC₅₀ 77.29 ± 0.38 mg/mL) followed by 40% EtOH extract (176.72 ± 0.35 mg/mL) and aqueous extract (275.41 ± 0.23 mg/mL). Total phenolics were found to be gallic acid equivalent, % 3.74 ± 0.05 (70% EtOH), 3.94 ± 0.04 (40% EtOH), and 3.79 ± 0.16 (aqueous), whereas the total flavonoids as a rutin equivalent, % as 2.01 ± 0.12, 1.44 ± 0.17 and 1.99 ± 0.02, each. The aqueous extract showed the best anti-oxidative and lowest activity against the acetylcholinesterase; however, the 70% EtOH extract showed the opposite effects than that of the aqueous. No mortality incidence was visible at various doses, indicating that the oral median lethal dose of aqueous and 70% EtOH extracts were considered greater than 5000 mg/kg. N. sibirica L. belongs to the non-toxic category of the OECD 423 classification.

• 생명과학회지
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• 제27권2호
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• pp.194-201
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• 2017

유채는 십자화과로 분류되는 유지작물로써 전 세계적으로 재배되는 작물이다. 이전 연구결과에서 가뭄저항성을 증대시키는 것으로 보고된 애기장대의 ${\beta}$-glucosidase 1 (AtBG1) 유전자를 도입함으로써 가뭄저항성 형질전환 유채를 개발하였다. 새로 개발된 형질전환 작물들은 그 이용에 대한 안전성에 대하여 어떠한 정보도 제공되지 않기 때문에 작물의 안정성에 대한 증명이 필수적이다. 이러한 안정성 평가는 작물의 역사적 사용과 과학적 증거를 기초로 한다. 이번 연구에서는 AtBG1이 도입된 형질전환 유채의 급성투여독성시험을 통하여 암수 마우스 각각에서 한계투여 용량을 확인하는 것을 목적으로 하였다. 이를 위해 OECD의 급성독성의 권고안에 따라 AtBG1 단백질을 암수 각각 5마리의 ICR 마우스에 몸무게 1 kg 당 2,000 mg을 부형제에 녹여 강제구강투여 하였다. 투여일부터 14일 동안 운동성, 병리학적 이상, 몸무게를 측정하였고 마지막 14일에는 안락사 후에 부검을 통해 AtBG1 투여군과 비투여군의 차이를 확인하였다. 이상의 실험을 통하여 AtBG1 단백질이 운동성, 병리학적 이상, 몸무게 및 부검 결과에서 대조구와 실험구, 두 그룹간의 특이적인 차이를 보이지 않음을 확인하였다. 또한 AtBG1 단백질은 급성독성의 측면에서 안전한 물질로 판단되며, 한계허용치 용량이 2,000 mg을 상회함을 확인하였다. 따라서, 이는 차후 AtBG1 도입 유채의 인체위해성 평가 자료로 사용될 수 있을 것으로 사료된다.

• 농약과학회지
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• 제15권2호
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• pp.218-229
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• 2011

레피멕틴은 살충제이다. 레피멕틴에 대한 독성을 평가하고 일일섭취허용량을 설정하기 위하여 다양한 인축독성 시험성적서를 검토하였다. 레피멕틴의 대사시험결과, 주로 대변을 통해 배설되었으며, 급성독성은 낮았고, 피부, 안점막자극성과 피부감작성은 없었다. 90일 반복투어경구독성(랫드, 개, 마우스), 만성독성(랫드, 개), 발암성시험(랫드)에서 혈액 및 혈액 생화학적변화를 나타냈으나, 번식독성, 유전독성, 발암성 및 기형독성은 없는 것으로 평가되었다. 따라서, 레피멕틴의 최대무작용량(NOAEL)은 랫드 2년 발암성시혐의 최대무작용량 2.02 mg/kg bw/day로 안전계수 100을 설정하여 일일섭취허용량 0.02 mg/kg bw/day로 설정하였다.

• 대한임상독성학회지
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• 제10권2호
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• pp.91-96
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• 2012

Purpose: A retrospective study with a literature review was conducted to identify the clinical characteristics and prognosis after the acute ingestion of glacial acetic acid. Methods: The medical records of 20 patients,who had presented to the emergency department of Ajou University Hospital complaining of the acute ingestion of glacial acetic acid between January 2006 and December 2011, were examined retrospectively. Results: Among the 172 patients admitted for caustics injury, 20 patients ingested glacial acetic acid. The mean age of the patients was $55{\pm}23.5$, and the mean volume of the acid was $84.5{\pm}71.3$ ml. The clinical features included 1) oral ulcers in 12 patients (63.2%), 2) respiratory difficulties in 11 patients (57.9%), 3) oliguria in 8 patients (42.1%), 4) renal toxicity in 7 patients (36.8%), 5) hepatic failure in 7 patients (36.8%), 6) disseminated intravascular boagulopathyin 7 patients (36.8%), 7) low blood pressure in 8 patients (42.1%), and 8) mental changes in 9 patients (47.4%). Ten patients required endotracheal intubation. Nine patients were admitted to the intensive care unit, and 5 patients expired. Conclusion: The ingestion of glacial acetic acid can cause severe symptoms, such as metabolic acidosis, multiple organ failure and upper airway swelling frequently and has a high mortality rate. Therefore, aggressive treatment, including endotracheal intubation, should be considered at the early stages.

• Biomolecules & Therapeutics
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• 제32권5호
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• pp.601-610
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• 2024

Tofacitinib, a Janus kinase (JAK) inhibitor used to treat rheumatoid arthritis, is metabolized through hepatic cytochrome P450 (CYP), specifically CYP3A1/2 and CYP2C11. Prolonged administration of rheumatoid arthritis medications is generally associated with an increased risk of renal toxicity. Loganin (LGN), an iridoid glycoside, has hepatorenal regenerative properties. This study investigates the potential of LGN to mitigate acute kidney injury (AKI) and its effects on the pharmacokinetics of tofacitinib in rats with cisplatin-induced AKI. Both intravenous and oral administration of tofacitinib to AKI rats significantly increased the area under the plasma concentration-time curve from time 0 to infinity (AUC) compared with control (CON) rats, an increase attributed to the decelerated non-renal clearance (CL_NR) and renal clearance (CL_R) of tofacitinib. Administration of LGN to AKI rats, however, protected kidneys from severe impairment, restoring the pharmacokinetic parameters (AUC, CL_NR, and CL_R) of tofacitinib to those observed in untreated CON rats, with partial recovery of kidney function, as evidenced by an increase in creatinine clearance. Possible interactions between drugs and natural components should be considered, especially when co-administering both a drug and a natural extract containing LGN or iridoid glycosides to patients with kidney injury.

• 농약과학회지
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• 제14권4호
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• pp.490-498
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• 2010

살균제 isotianol의 독성을 평가하고 일일섭취허용량을 설정하기 위하여 급성독성시험 등 시험성적서를 검토하였다. Isotianil은 소변과 대변을 통해 빠르게 대사되었다. 급성경구독성은 저독성이었으며 피부자극, 안점막자극성은 없는 것으로 나타났다. 피부감작성은 약한 감작성으로 판단되었으며, 유전독성은 없었다. 랫드와 개 만성독성시험 결과 간의 무게, 혈액학 및 임상생화학적 변화가 관찰되었다. 또한 생식독성과 기형독성에는 영향이 없었다. Isotianil은 12개월 만성독성시험의 최대무작용량이 2.83 mg/kg/bw/day로 가장 민감하였고, 안전계수 100을 적용하여 일일섭취허용량을 0.028 mg/kg/bw/day로 설정하였다.

• Advances in Traditional Medicine
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• 제7권2호
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• pp.197-204
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• 2007

The present study focused on the establishment of micropropagation protocol for the high value Pluchea (P.) indica (L.) Less., genotype, an important medicinal plant and evaluation of the diuretic activity of the leaf extract of the tissue cultured plant. Leaf explants, nodal segments and shoot tips were cultured in MS medium supplemented with auxin and cytokinin and their combinations. With the objective of inducing callus giving rise to new adult plants, naphthalene acetic acid was found to be most effective for (80%) for callus induction. The methanolic extract of leaves of the micropropagated P. indica was investigated for its diuretic activity in Wistar albino rats. Urinary excretion parameters were studied for evaluation of diuretic activity using Frusemide (20 mg/kg, p.o.) as standard. The extract showed significant diuretic activity at the doses of 100, 200 and 300 mg/kg. p.o. An oral acute toxicity study for the extract was carried out and the $LD_{50}$ value was found to be 2,825 mg/kg body weight.

• 생명과학회지
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• 제26권10호
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• pp.1207-1213
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• 2016

오미자(Schisandrae Fructus)와 상엽(Mori folium)은 한국, 중국, 일본을 포함한 아시아 지역에서 오랫동안 식품자원 및 전통 의약제로 광범위하게 사용되어 왔다. 최근 연구에 따르면 오미자와 상엽은 항균, 항염증, 항산화, 면역기능 조절 및 혈관신생억제 등과 같은 많은 효능을 가지는 것으로 알려져 있다. 그러나 오미자(SF), 상엽(MF) 에탄올 단독추출물 및 복합추출물(medicinal herber mixture, MHMIX)에 대한 독성 및 안전성에 대해서는 거의 알려져 있지 않은 실정이다. 따라서 본 연구에서는 SF, MF 및 MHMIX가 유발하는 급성독성 및 안전성을 확인하였다. 이를 위하여 ICR mice를 대상으로 SF, MF 및 MHMIX 5,000 mg/kg을 최고농도로 설정하여 단회 경구 투여하였으며, 투여 후 14일 동안의 치사율, 체중 변화, 임상증상, 음수율 및 사료섭취량과 함께 부검 소견, 장기무게 변화, 혈액학 및 혈액생화학적 검사를 실시하였다. 결과에서 나타난 바와 같이 SF, MF 및 MHMIX의 투여 후 치사율, 임상증상, 체중 및 부검 소견 상의 유의적인 변화는 관찰되지 않았다. 또한 SF, MF 및 MHMIX 투여에 따른 각 장기의 무게, 혈액학적 및 혈청학적 임상 화학적 지표에도 유의적인 변화는 관찰할 수 없었다. 따라서 SF, MF 및 MHMIX는 단회 경구 투여에 따른 치사량이 5,000 mg/kg 이상일 것으로 추정되어 ICR 마우스에 대하여 급성독성이 없는 비교적 안전한 물질이라는 것을 알 수 있었으며, 향후 천연물 소재로서의 효능 규명을 통한 활용이 기대된다.

• 한국식품영양과학회지
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• 제44권1호
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• pp.24-28
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• 2015

청국장에서 분리한 항균활성이 우수한 Bacillus subtilis JNS의 probiotics로서의 활용성을 검증하기 위해 단기투여에 의한 안전성을 확인하고자 실험을 실시하였다. 경구투여용 존데를 이용하여 임상적용 경로인 경구로 투여하였으며, 최고투여용량은 2,000 mg/kg으로 설정하였다. ICR계 암수 마우스에서 14일간 관찰한 결과 일반증상, 사망률, 체중, 임상증상 및 육안적 소견 등에서 무처리 대조군과 비교해서 유의성 있는 차이를 보이지 않았다. 부검 후의 주요 장기에 대한 육안적 검사에서 또한 대조군과 비교하여 이상소견이나 병변이 관찰되지 않았다. 이상의 결과로부터 시험물질인 B. subtilis JNS는 경구투여 시 ICR계 암수 마우스에서 독성학적인 변화가 관찰되지 않았으며, 경구투여가 2,000 mg/kg 이상인 저독성의 안전한 물질로 사료된다.