Effects of thymoquinone on alpha-amanitin induced hepatotoxicity in human C3A hepatocytes

Abstract Thymoquinone (TQ) has shown hepatoprotective effects in various experimental studies. We aimed to investigate the possible beneficial effects of TQ regarding its prevention of alpha-amanitin induced hepatotoxicity in human C3A hepatocytes. After administering alpha-amanitin in a concentrations of 1 and 10µg/mL on the cells in a hepatocyte cell line, TQ was administered in various concentrations (10, 5, 1, 0.5, 0.1, 0.05, 0.01, 0.005 µg/mL). The MTT test was used to determine cell viability. For the groups given only TQ at various concentrations, the cell viability rates at 48 hours post-administration were found at 82.6, 98.3, 102.1, 102.5, 99.4, 99.4, 101.9 and 106.3%, respectively. For the group with 1μg/mL alpha-amanitin and various TQ concentrations, the cell viability rates were found at 74.6, 88.5, 87.4, 88.7, 85.7, 86.8, 88.4, and 92.9%, respectively. For the group with 10μg/mL alpha-amanitin and various TQ concentrations, the cell viability rates for each TQ subgroup were found at 65.2, 79.2, 81.4, 81.1, 81.8, 81.8, 82.2 and 91.9%, respectively. Our study is the first in vitro study that investigates TQ's effects on alpha-amanitin induced hepatotoxicity. Although TQ had beneficial effect in low doses did not significantly increase cell viability in liver damage due to alpha-amanitin toxicity.

Administration of paracetamol versus dipyrone by intravenous patient-controlled analgesia for postoperative pain relief in children after tonsillectomy / Administração de paracetamol versus dipirona em analgesia controlada pelo paciente por via intravenosa para alívio da dor no pós-operatório de crianças após tonsilectomia

BACKGROUND AND OBJECTIVE: We compared the efficacy of intravenous (IV) paracetamol versus dipyrone via patient-controlled analgesia (PCA) for postoperative pain relief in children. METHODS: The study was composed of 120 children who had undergone elective tonsillectomy after receiving general anesthesia. Patients were divided into 3 groups according to the dosage of postoperative intravenous-patient-controlled analgesia: paracetamol, dipyrone, or placebo. Pain was evaluated using a 0- to 100-mm visual analog scale and 1- to 4-pain relief score at 30 min, 1, 2, 4, 6, 12, and 24 h postoperatively. Pethidine (0.25 mg kg-1) was administered intravenously to patients requiring rescue analgesia. Pethidine requirements were recorded during the first 24 h postoperatively, and treatment related adverse effects were noted. RESULTS: Postoperative visual analog scale scores were significantly lower with paracetamol group compared with placebo group at 6 h (p < 0.05), dipyrone group compared with placebo group at 30 min and 6 h (p < 0.05). No significant differences regarding visual analog scale values at 1, 2, 4, 12, and 24 h were found. No significant differences were found between groups with respect to pain relief score (p > 0.05). Postoperative pethidine requirements were significantly lower with paracetamol and dipyrone groups compared with placebo group (62.5%, 68.4% vs 90%, p < 0.05). No significant differences were found between groups with respect to nausea, vomiting and the any other adverse effects of the drugs (p > 0.05). CONCLUSIONS: Paracetamol and dipyrone have well tolerability profile and effective analgesic properties when administered IV-PCA for postoperative analgesia in children after tonsillectomy.

JUSTIFICATIVA E OBJETIVO: Comparamos a eficácia da administração de paracetamol versus dipirona em analgesia controlada pelo paciente (PCA) por via intravenosa (IV) para alívio da dor no período pós-operatório em crianças. MÉTODOS: O estudo foi composto por 120 crianças submetidas à tonsilectomia sob anestesia geral. Os pacientes foram divididos em três grupos de acordo com a dose IV de analgesia controlada pelo paciente no pós-operatório: paracetamol, dipirona ou placebo. A dor foi avaliada com uma escala visual analógica de 0-100 mm e escore de 1-4 para alívio da dor nos tempos de 30 minutos, uma, duas, quatro, seis, 12 e 24 horas de pós-operatório. Petidina (0,25 mg kg-1) foi administrada IV aos pacientes que precisaram de analgesia de resgate. A necessidade de petidina foi registrada durante as primeiras 24 horas de pós-operatório e os efeitos adversos relacionados ao tratamento foram registrados. RESULTADOS: Os escores da escala visual analógica no pós-operatório foram significativamente menores no grupo paracetamol em comparação com o grupo placebo em seis horas (p < 0,05) e no grupo dipirona em comparação com o grupo placebo em 30 minutos e seis horas (p < 0,05). Não houve diferença significativa em relação aos valores da escala visual analógica nos tempos avaliados de uma, duas, quatro, 12 e 24 horas. Não houve diferença significativa entre os grupos quanto ao escore de alívio da dor (p > 0,05). A necessidade de petidina foi significativamente menor nos grupos paracetamol e dipirona em comparação com o grupo placebo (62,5%, 68,4% vs. 90%, p < 0,05). Não houve diferença significativa entre os grupos em relação à incidência de náusea, vômito e outros efeitos adversos dos medicamentos (p > 0,05). CONCLUSÕES: Paracetamol e dipirona têm um perfil de boa tolerabilidade e propriedades analgésicas eficazes quando administrados IV para ACP no pós-operatório de crianças após tonsilectomia.

BRAF, KIT, NRAS, GNAQ and GNA11 mutation analysis in cutaneous melanomas in Turkish population.

Background: KIT and mitogen-activated protein kinase cascade are important for melanomagenesis. In the present study, we analyzed the frequency of BRAF, NRAS, KIT, GNAQ and GNA11 gene mutations and investigated their association with clinicopathological features of melanomas in Turkish population. Materials and Methods: Forty-seven primary cutaneous melanomas were included in our study. Sanger sequencing method was used for mutation analysis in all cases. Results: Mean age was 62.1 (29-101) years. Female:male ratio was 17:30. Among 47 melanomas, 14 (29.8%) BRAF, 10 (21.3%) NRAS, 4 (8.5%) KIT and 1(2.1%) GNAQ gene mutations were detected. Two of the KIT mutations were found in acral lentiginous melanoma (ALM). In the head and neck region, mutation frequency was signifi cantly lower than in other locations (P = 0.035). The only GNAQ gene mutation (p.Q209L) was detected in a melanoma arising from blue nevus located on the scalp. None of the melanomas harbored NRAS exon 2, KIT exon 13/17/18, GNAQ exon 4 and GNA11 exon 4/5 mutations. Overall mutation frequency did not show signifi cant difference between metastatic (8/14, 57.1%) and nonmetastatic (18/33, 54.5%) patients. We did not observe any signifi cant association between mutation status and gender or age of various patients. Conclusions: Our results support that BRAF and NRAS gene mutations are common in cutaneous melanomas. The activating mutations of KIT gene are rare and especially seen in ALM. GNAQ and GNA11 mutations are infrequent in cutaneous melanomas and may be associated only with melanomas arising from blue nevus.

Paracetamol e dipirona por via endovenosa aplicados à analgesia pós-operatória de pacientes pediátricos submetidos à amigdelectomia em hospital-dia: um estudo prospectivo, randomizado, duplo-cego, placebo controlado / Intravenous paracetamol and dipyrone for postoperative analgesia after day-case tonsillectomy in children: a prospective, randomized, double blind, placebo controlled study

O manejo da dor pós-amigdelectomia pode ser feito com uma série de medicamentos. OBJETIVO: O presente estudo duplo-cego placebo controlado pretendeu avaliar a eficácia de paracetamol e dipirona administrados por via endovenosa na analgesia de pacientes pediátricos pós-amigdelectomia. MÉTODO: Cento e vinte crianças com idades entre três e seis anos submetidas à amigdelectomia com ou sem adenoidectomia e/ou entubação foram randomizadas para receber infusões de paracetamol (15 mg/kg), dipirona (15 mg/kg) ou placebo (0,9% NaCl) durante a cirurgia. As avaliações foram executadas com 0,25, 0,50, 1, 2, 4, 6h de pós-operatório. Petidina 0,25 mg/kg foi utilizada como analgésico de resgate. Dose acumulada de petidina foi o desfecho primário. Medições de intensidade da dor, alívio da dor, nível de sedação, náusea e vômitos, hemorragia no pós-operatório e outros efeitos adversos foram anotados. RESULTADOS: Nenhuma diferença significativa foi encontrada na dose acumulada de petidina entre os grupos paracetamol e dipirona. A dose acumulada de petidina foi significativamente menor nos grupos paracetamol e dipirona em comparação ao grupo placebo. Nenhuma diferença significativa foi observada entre os escores de dor no pós-operatório dos grupos durante o estudo. CONCLUSÃO: Paracetamol endovenoso tem eficácia analgésica semelhante à da dipirona endovenosa; ambos ajudam a reduzir a necessidade de opioides na analgesia pós-operatória de pacientes pediátricos submetidos à amigdelectomia em hospital-dia.

Tonsillectomy is associated with severe postoperative pain for which, several drugs are employed for management. OBJECTIVE: In this double-blind, placebo-controlled study we aimed to evaluate the efficacy of intravenous paracetamol and dipyrone when used for post-tonsillectomy analgesia in children. METHOD: 120 children aged 3-6 yr, undergoing tonsillectomy with or without adenoidectomy and/or ventilation tube insertion were randomized to receive intraoperative infusions of paracetamol (15 mg/kg), dipyrone (15 mg/kg) or placebo (0.9% NaCl). Evaluation was carried out at 0.25, 0.50, 1, 2, 4, 6h postoperatively. Pethidine 0.25 mg/kg was utilized as rescue analgesic. Cumulative pethidine requirement was the primary outcome. Pain intensity measurement, pain relief, sedation level, nausea and vomiting, postoperative bleeding and any other adverse effects were noted. RESULTS: No significant difference was found in pethidine requirement between paracetamol and dipyrone groups. Cumulative pethidine requirement was significantly less in paracetamol and dipyrone groups vs. placebo. No significant difference was observed between groups in postoperative pain intensity scores throughout the study. CONCLUSION: Intravenous paracetamol is found to have a similar analgesic efficacy as intravenous dipyrone and they both help to reduce the opioid requirement for postoperative analgesia in pediatric day-case tonsillectomy.