Objective:To explore the half-effective dose(ED_(50))of remazolam toluenesulfonate combined with subthreshold amounts of esketamine for inhibiting cardiovascular response to tracheal intubation in elderly patients.Met...Objective:To explore the half-effective dose(ED_(50))of remazolam toluenesulfonate combined with subthreshold amounts of esketamine for inhibiting cardiovascular response to tracheal intubation in elderly patients.Method:We included 42 patients,aged 65-75,who required general anesthesia and single-lumen endotracheal intubation for elective surgery.The first patient was administered remazolam toluenesulfonate at a dose of 0.20 mg/kg.Once the patient lost consciousness,their alertness/sedation score(OAA/S score)was≤1,and their BIS score was≤60,and a subthreshold dose(0.3 mg/kg)of esketamine was given.The subsequent doses were adjusted using a sequential approach based on the cardiovascular response to tracheal intubation observed in the previous patient.The dose was modified in increments or decrements of 0.01 mg/kg.The ED_(50)and 95%CI of remazolam toluenesulfonate were calculated using the Dixon and Massey sequential distribution test method.Result:The inhibition of endotracheal intubation response was positively correlated with the dose of remazolam toluenesulfonate,and the depth of sedation could not be achieved when the amount was≤0.22 mg/kg.The ED_(50)of remazolam toluenesulfonate combined with a subthreshold dose of esketamine in inhibiting cardiovascular response to tracheal intubation in elderly patients was 0.30(0.28,0.33)mg/kg.There was no statistically significant difference in blood pressure between the induction of anesthesia and before the operation.Conclusion:When compounded with 0.3 mg/kg esketamine,the ED_(50)of Remazolam toluenesulfonate in inhibiting cardiovascular response to endotracheal intubation in elderly patients was 0.30 mg/kg(95%CI0.28-0.33 mg/kg).展开更多
The lethal dose LD<sub>50</sub> represents the most important experimental value for acute toxicity. The simple logarithmic calculation of -log<sub>10</sub> LD<sub>50</sub> = value ...The lethal dose LD<sub>50</sub> represents the most important experimental value for acute toxicity. The simple logarithmic calculation of -log<sub>10</sub> LD<sub>50</sub> = value leads to the possible poison power pLD. As with the pH or pK value, respectively, for acid or the scale of earthquake intensities the logarithm helps making large differences of orders of magnitude easier to understand since they are more comparable. The higher the pLD value, the higher is the power of poison. An increase of the pLD value by 1 stands for a tenfold increase in toxicity. The lethal acute dose for water, one of the most important and at the same time non-toxic substances of all, is about one tenth of the body weight. This leads to a possible pLD value for water of 1, an ideal starting value for a logarithmic poison scale.展开更多
Somina (herbal preparation) prepared by Hamdard Laboratories (Waqf) Pakistan is a mixture of five different medicinal plants, widely prescribed for the treatment of mental illness. For acute toxicity, the Karber arith...Somina (herbal preparation) prepared by Hamdard Laboratories (Waqf) Pakistan is a mixture of five different medicinal plants, widely prescribed for the treatment of mental illness. For acute toxicity, the Karber arithmetic method for the calculation of LD50 and Hodge and Sterner toxicity scale was used. In this study, different doses (10, 100, 285, 500, 1000, 5000 and 10,000 mg/kg) of the extract was administered orally to the different groups of rats and mice. Signs of toxicity and possible death of animals were monitored for 24 hrs to calculate the median lethal dose (LD50) of somina. At the end of the study, all the animals in all the dose groups were sacrificed and the internal organ-body was compared with values from the control group. The LD50 was found to be >10,000 mg/kg body weight upon oral administration in mice and rats as no mortality was observed after single dose administration. According to Hodge and Sterner toxicity scale, the obtained value of LD 50 > 10,000 mg/kg classified the Somina as Practically non-toxic herbal medicine.展开更多
Background: About 50 species of scorpions cause fatal scorpionism worldwide.Most of these are members of the Buthidae family, and include, among others,Mesobuthus eupeus, Androctonus crassicauda, Leiurus abdullahbayra...Background: About 50 species of scorpions cause fatal scorpionism worldwide.Most of these are members of the Buthidae family, and include, among others,Mesobuthus eupeus, Androctonus crassicauda, Leiurus abdullahbayrami, Leiurus quinquestriatus, Tityus pachyurus and Androctonus australis. Because high doses of scorpion venom and antivenom can cause death and hypersensitive reactions, there is a need to develop a formula that can be used to calculate both lethal and effective doses for scorpion venom and antivenom, respectively, thereby obviating the need for laboratory experiments.Methods: In view of this, a literature search was carried out with the aim of modifying the formula(LD_(50)=ED_(50)/3× W_a × 10^(-4))for calculation of the median lethal dose(LD_(50)) of scorpion venom and the ED_(50) of antivenom. The human equivalent dose(HED) formula was assessed for extrapolation of LD_(50) and ED_(50) from animals to human for comparison and relevance with the new formula.Results: The findings showed that the newly developed formula(LD_(50)= ED_(50)^(1/3)×W_a× 10^(-4)) yielded results that are very close to the reported values. Therefore, the newly developed and HED formulas can be used for calculation of LD_(50) and ED_(50) values for scorpion venom and antivenom, respectively.Conclusion: The new formula yielded better results than the HED formula, confirming its predictive validity, precision, and reliability, thereby obviating the need for rigorous experiments and justifying the principles of reduction, refinement, and replacement(3 Rs).展开更多
文摘Objective:To explore the half-effective dose(ED_(50))of remazolam toluenesulfonate combined with subthreshold amounts of esketamine for inhibiting cardiovascular response to tracheal intubation in elderly patients.Method:We included 42 patients,aged 65-75,who required general anesthesia and single-lumen endotracheal intubation for elective surgery.The first patient was administered remazolam toluenesulfonate at a dose of 0.20 mg/kg.Once the patient lost consciousness,their alertness/sedation score(OAA/S score)was≤1,and their BIS score was≤60,and a subthreshold dose(0.3 mg/kg)of esketamine was given.The subsequent doses were adjusted using a sequential approach based on the cardiovascular response to tracheal intubation observed in the previous patient.The dose was modified in increments or decrements of 0.01 mg/kg.The ED_(50)and 95%CI of remazolam toluenesulfonate were calculated using the Dixon and Massey sequential distribution test method.Result:The inhibition of endotracheal intubation response was positively correlated with the dose of remazolam toluenesulfonate,and the depth of sedation could not be achieved when the amount was≤0.22 mg/kg.The ED_(50)of remazolam toluenesulfonate combined with a subthreshold dose of esketamine in inhibiting cardiovascular response to tracheal intubation in elderly patients was 0.30(0.28,0.33)mg/kg.There was no statistically significant difference in blood pressure between the induction of anesthesia and before the operation.Conclusion:When compounded with 0.3 mg/kg esketamine,the ED_(50)of Remazolam toluenesulfonate in inhibiting cardiovascular response to endotracheal intubation in elderly patients was 0.30 mg/kg(95%CI0.28-0.33 mg/kg).
文摘The lethal dose LD<sub>50</sub> represents the most important experimental value for acute toxicity. The simple logarithmic calculation of -log<sub>10</sub> LD<sub>50</sub> = value leads to the possible poison power pLD. As with the pH or pK value, respectively, for acid or the scale of earthquake intensities the logarithm helps making large differences of orders of magnitude easier to understand since they are more comparable. The higher the pLD value, the higher is the power of poison. An increase of the pLD value by 1 stands for a tenfold increase in toxicity. The lethal acute dose for water, one of the most important and at the same time non-toxic substances of all, is about one tenth of the body weight. This leads to a possible pLD value for water of 1, an ideal starting value for a logarithmic poison scale.
基金supported by Major Program of National Natural Science Foundation of China (82192910)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-C-202009 and ZYYCXTD-D-202207)。
文摘Somina (herbal preparation) prepared by Hamdard Laboratories (Waqf) Pakistan is a mixture of five different medicinal plants, widely prescribed for the treatment of mental illness. For acute toxicity, the Karber arithmetic method for the calculation of LD50 and Hodge and Sterner toxicity scale was used. In this study, different doses (10, 100, 285, 500, 1000, 5000 and 10,000 mg/kg) of the extract was administered orally to the different groups of rats and mice. Signs of toxicity and possible death of animals were monitored for 24 hrs to calculate the median lethal dose (LD50) of somina. At the end of the study, all the animals in all the dose groups were sacrificed and the internal organ-body was compared with values from the control group. The LD50 was found to be >10,000 mg/kg body weight upon oral administration in mice and rats as no mortality was observed after single dose administration. According to Hodge and Sterner toxicity scale, the obtained value of LD 50 > 10,000 mg/kg classified the Somina as Practically non-toxic herbal medicine.
文摘Background: About 50 species of scorpions cause fatal scorpionism worldwide.Most of these are members of the Buthidae family, and include, among others,Mesobuthus eupeus, Androctonus crassicauda, Leiurus abdullahbayrami, Leiurus quinquestriatus, Tityus pachyurus and Androctonus australis. Because high doses of scorpion venom and antivenom can cause death and hypersensitive reactions, there is a need to develop a formula that can be used to calculate both lethal and effective doses for scorpion venom and antivenom, respectively, thereby obviating the need for laboratory experiments.Methods: In view of this, a literature search was carried out with the aim of modifying the formula(LD_(50)=ED_(50)/3× W_a × 10^(-4))for calculation of the median lethal dose(LD_(50)) of scorpion venom and the ED_(50) of antivenom. The human equivalent dose(HED) formula was assessed for extrapolation of LD_(50) and ED_(50) from animals to human for comparison and relevance with the new formula.Results: The findings showed that the newly developed formula(LD_(50)= ED_(50)^(1/3)×W_a× 10^(-4)) yielded results that are very close to the reported values. Therefore, the newly developed and HED formulas can be used for calculation of LD_(50) and ED_(50) values for scorpion venom and antivenom, respectively.Conclusion: The new formula yielded better results than the HED formula, confirming its predictive validity, precision, and reliability, thereby obviating the need for rigorous experiments and justifying the principles of reduction, refinement, and replacement(3 Rs).
