The present study investigated acute and subchronic toxicity and safety pharmacology of modified pulsatilla granules（MPG）to provide a basis for a comprehensive understanding of MPG toxicity.The results of acute toxi...The present study investigated acute and subchronic toxicity and safety pharmacology of modified pulsatilla granules（MPG）to provide a basis for a comprehensive understanding of MPG toxicity.The results of acute toxicity testing showed that the median lethal dose of MPG was more than 5 000 mg kg^-1,suggesting that MPG was considered as practically non-toxic.The subchronic toxicity study for 30 days was conducted by daily oral administration at doses of 375,750 and 1 500 mg kg^-1 in Sprague-Dawley rats.The results of subchronic toxicity study showed that the body weight and relative organ weight were not significantly changed by administration of MPG.The clinical chemistry study showed that MPG could induce kidney and liver damages.In histopathological,mild lesions in liver and kidney were also observed,suggesting that the liver and kidney might be potential target organs of MPG.In the safety pharmacology study,MPG did not exhibited any side effects to rats in cardiovascular system,respiratory system and central nervous system.These results suggested that MPG could be considered safe for veterinary use.展开更多
Introduction: We still rely on clinical diagnosis for initiating empirical antibiotic therapy and await blood culture for confirmation of infection, species identification and drug sensitivity. Differential blood cell...Introduction: We still rely on clinical diagnosis for initiating empirical antibiotic therapy and await blood culture for confirmation of infection, species identification and drug sensitivity. Differential blood cell count (WBC and neutrophils) and recording of toxic granules in the neutrophils are established methods for indirect diagnosis of infection though they are not used in the diagnosis of sepsis per se. Serum Procalcitonin is considered as a good biomarker in the management of sepsis. Materials and Methods: Whole blood and serum were used for laboratory analysis. We have combined the detection of toxic granules in the peripheral blood smear and serum PCT levels for diagnosis and monitoring the recovery of a patient with septic shock. A 63 year old laminectomy patient was transferred 2 days after the surgery to our hospital with several co-morbidities and complications. He was in septic shock and was put on Continuous Renal Replacement Therapy, with ionotropic support and IV fluids via nasogastric feeding and administration of Activated Protein C. Blood culture and daily measurements of serum Procalcitonin, differential blood cells count, and observation of toxic granules in neutrophils were done. Results: The blood culture showed infection due to K. pneumoniae resistant to carbapenems. WBC and Neutrophil counts were quite variable and showed incoherent response to treatment. Serum PCT was 24.57 ng/mL on the next day of admission and it peaked at 30.2 ng/mL on day 3. Its level started decreasing from the 4th day. Toxic granules disappeared when serum PCT levels reached < 1 ng/mL. The patient responded well to treatment and he was discharged on the 16th day upon request. Conclusion: This case is presented as an example of managing sepsis with a combination of a conventional hematology marker and a modern biomarker. Resource poor hospitals with inadequate microbiology services, may evaluate and use these two biomarkers not only for the total management of sepsis but also to reduce the cost of critical care.展开更多
In our previous study,we prepared the granules by embedding artemisinin into alginate-chitosan using microcapsule technology.These granules can release artemisinin sustainably and have a strong inhibitory effect on th...In our previous study,we prepared the granules by embedding artemisinin into alginate-chitosan using microcapsule technology.These granules can release artemisinin sustainably and have a strong inhibitory effect on the growth of both single Microcystis aeruginosa and mixed algae.To safely and effectively use artemisinin sustained-release granules to control algal blooms,the ecotoxicity was studied by assessing their acute and chronic toxicity to Daphnia magna(D.magna)and Danio rerio(D.rerio),along with their antioxidant activities.The results showed that the 48-h median effective concentration(EC50)of pure artemisinin to D.magna was 24.54 mg/L and the 96-h median lethal concentration(LC50)of pure artemisinin to D.rerio was 68.08 mg/L.Both values were classified as intermediate toxicity according to the Organization for Economic Co-operation and Development(OECD).The optimal algae inhibitory concentration of artemisinin sustained-release granules(1 g/L)had low acute toxicity to both D.magna and D.rerio.The sustained-release granules had higher chronic toxicity to D.magna than to D.rerio.Partial indices of D.magna were inhibited by granules when the concentrations were larger than 0.1 g/L.Low granule concentration had an inductive effect on antioxidant enzyme activities in D.magna and D.rerio.With the increase of the exposure concentration and time,the enzyme activity presented a trend of first increasing and then decreasing,and the overall changes were significant.The change trend and range of enzyme activity indicated that the granules could cause serious oxidative stress to D.magna and D.rerio,and the changes were consistent with the results of toxicity experimentation.展开更多
[Objectives]To study the long-term toxicity of Maxing Erchen Zhike granules to rats after intragastric administration,so as to provide reference for its preclinical safety evaluation.[Methods]Total 80 rats were random...[Objectives]To study the long-term toxicity of Maxing Erchen Zhike granules to rats after intragastric administration,so as to provide reference for its preclinical safety evaluation.[Methods]Total 80 rats were randomly and evenly divided into high-dose group(1.2 mL/100 g,120 g/kg),middle-dose group(96.0 g/kg),low-dose group(72.0 g/kg)and blank control group.The rats in the treatment groups were administered with corresponding doses of Maxing Erchen Zhike granules,and those in the blank control group were given with equal-amount normal saline.The administration lasted for 30 consecutive days.During the experiment,the rats'feed intake,activity,feces and other conditions and toxicity reactions were observed every day.After 24 h of the last administration,12 rats(half male and half female)were randomly selected from each group.Each of the rats was anesthetized with 10%chloral hydrate solution(0.3 mL/100 g)through intraperitoneal injection and subjected to abdominal aorta blood collection(two tubes)for hematological examination and blood biochemical examination(serum).Then,the main organs of the rats were weighed,and pathological examinations were performed.After that,the main organs were weighed and pathological examination was performed.The remaining rats in each group were discontinued and observed for 14 d.On the 15th d,they were subjected to the same treatment,and the body weight,organ coefficients,hematological indices,blood biochemical indices and pathological indices were examined.[Results]After 30 d of administration,there was no abnormality in the appearance and behavior of the animals.There was no significant difference in the daily consumption of feed among the groups,and there was no special case of weight gain.Among the blood biochemical indices,the ALB and ALT levels of each administration group were significantly different from those of the blank control group(P<0.05).The results of histopathological examination show that there was one case of interstitial pneumonia in each of the high-dose group,middle-dose group and blank control group.After 14 d that the administration was stopped,one case of focal myocarditis appeared in the high-dose group,and one case of interstitial pneumonia appeared in the middle-dose group.[Conclusions]Maxing Erchen Zhike granules are safe to be administered to rats at 100 times the clinical dose.and there should be no safety hazards clinically when used at conventional doses.展开更多
Background:To evaluate the acute toxicity of the experienced prescription Lucao Wenban granules on mice and provide a theoretical basis for clinical medication safety.Methods:The mice were not deprived of water for 16...Background:To evaluate the acute toxicity of the experienced prescription Lucao Wenban granules on mice and provide a theoretical basis for clinical medication safety.Methods:The mice were not deprived of water for 16 h after fasting,and were intragastrically given the experienced prescription Lucao Wenban granules at the maximum mass concentration(0.55 g/mL)and the maximum volume(0.04 mL/g body weight)2 times within 24 hours.The toxicity was observed and recorded within 14 days after administration.At the end of the experiment,the biochemical indexes of mice were detected.The liver,heart,spleen,lung,and kidney were dissected and observed after executing mice to weigh the wet weight and calculate the coefficient of viscera.Results:There was no death after the mice were given 342.32 g/kg of crude medicine of the experienced prescription Lucao Wenban granules.No significant differences were detected in body weight,biochemical indexes,visceral index between the experiment group and the control group.Conclusion:There is no acute toxicity in mice.The maximum tolerable dose is 342.32 g/kg,which is 144 times of clinical dose.展开更多
Objective: To observe and assess the efficacy enhancing and toxicity attenuating effect of Nuzhen Yangyin Granule (NYG) to the anti-parkinsonism (paralysis agitans) therapy with medopa and ar-tane. Methods: Adopting t...Objective: To observe and assess the efficacy enhancing and toxicity attenuating effect of Nuzhen Yangyin Granule (NYG) to the anti-parkinsonism (paralysis agitans) therapy with medopa and ar-tane. Methods: Adopting the randomized double-blinded method, the effect of adding NYG to 30 patients with Parkinsonism in the treated group,展开更多
OBJECTIVE:To study the anti-inflammatory and anti-tussive effects of Qingfei Dayuan granules(清肺达原颗粒,QFDY),and to evaluate the acute and sub-chronic toxicity of QFDY.METHODS:Anti-inflammatory effects were evaluat...OBJECTIVE:To study the anti-inflammatory and anti-tussive effects of Qingfei Dayuan granules(清肺达原颗粒,QFDY),and to evaluate the acute and sub-chronic toxicity of QFDY.METHODS:Anti-inflammatory effects were evaluated by murine model of xylene induced ear edema in mice.Ear swelling degree was calculated and tumor necrosis factor-α,interleukin-1βand interleukin-6 were determined.Anti-tussive evaluations were carried out in the mouse cough model induced by ammonia liquor.Latent period cough and number of cough within 3 min were counted.In acute toxicity study,the rats were randomly divided into test group and solvent control group.Body weighs,food intakes and general clinical signs were monitored.In the sub-chronic toxicity study,QFDY was administered to rats at 0,4,8 and 16 g/kg per day for 28 and 30 d of post treatment was conducted.Mortalities,clinical signs,body weight changes,food intakes,ophthalmological examinations,hematological parameters,biochemical indicators,electrolyte indicators,urinalyses and histopathological examinations were monitored.RESULTS:QFDY significantly inhibited the development of ear edema in anti-inflammatory assay and decreased cough frequency caused by ammonia liquor.The results presented a dose-effect relationship.In acute toxicity study,no abnormality exhibited at dose of 24.0 g/kg per day during the 14-d observation period.In the sub-chronic toxicity study,higher reticulocyte count,lymphocyte and lower Cl-,blood urea nitrogen were analyzed compared with the solvent control group.But the differences were considered to be incidental and not clinically toxic.Obvious dose-effect relationship of urine color was observed,and the three test groups at the end of the experiments resulted in significant increase in urobilinogen,bilirubin,ketone body and urine leukocyte.However,all the positive indicators returned to normal in the recovery period.Therefore,no toxicological changes were found during the study period.CONCLUSION:QFDY showed significant anti-inflammatory and anti-tussive effects in mice.The lethal dose(LD50)of per oral QFDY in rats was estimated to be more than 24.0 g/kg per day and the no observed adverse effect level was over 16 g/kg per day,which suggested that QFDY is relatively safe for oral medication at the present dose on rats.Our experimental results provide a reference for the further development and research of QFDY.展开更多
基金supported by the National Natural Science Foundation of China (31372477)the International Cooperation Projects of Sichuan Province, China (2014HH0058, 2013HH0042)the Sichuan Youth Science and Technology Innovation Research Team for waterfowl disease prevention and control, China (2013TD0015)
文摘The present study investigated acute and subchronic toxicity and safety pharmacology of modified pulsatilla granules（MPG）to provide a basis for a comprehensive understanding of MPG toxicity.The results of acute toxicity testing showed that the median lethal dose of MPG was more than 5 000 mg kg^-1,suggesting that MPG was considered as practically non-toxic.The subchronic toxicity study for 30 days was conducted by daily oral administration at doses of 375,750 and 1 500 mg kg^-1 in Sprague-Dawley rats.The results of subchronic toxicity study showed that the body weight and relative organ weight were not significantly changed by administration of MPG.The clinical chemistry study showed that MPG could induce kidney and liver damages.In histopathological,mild lesions in liver and kidney were also observed,suggesting that the liver and kidney might be potential target organs of MPG.In the safety pharmacology study,MPG did not exhibited any side effects to rats in cardiovascular system,respiratory system and central nervous system.These results suggested that MPG could be considered safe for veterinary use.
文摘Introduction: We still rely on clinical diagnosis for initiating empirical antibiotic therapy and await blood culture for confirmation of infection, species identification and drug sensitivity. Differential blood cell count (WBC and neutrophils) and recording of toxic granules in the neutrophils are established methods for indirect diagnosis of infection though they are not used in the diagnosis of sepsis per se. Serum Procalcitonin is considered as a good biomarker in the management of sepsis. Materials and Methods: Whole blood and serum were used for laboratory analysis. We have combined the detection of toxic granules in the peripheral blood smear and serum PCT levels for diagnosis and monitoring the recovery of a patient with septic shock. A 63 year old laminectomy patient was transferred 2 days after the surgery to our hospital with several co-morbidities and complications. He was in septic shock and was put on Continuous Renal Replacement Therapy, with ionotropic support and IV fluids via nasogastric feeding and administration of Activated Protein C. Blood culture and daily measurements of serum Procalcitonin, differential blood cells count, and observation of toxic granules in neutrophils were done. Results: The blood culture showed infection due to K. pneumoniae resistant to carbapenems. WBC and Neutrophil counts were quite variable and showed incoherent response to treatment. Serum PCT was 24.57 ng/mL on the next day of admission and it peaked at 30.2 ng/mL on day 3. Its level started decreasing from the 4th day. Toxic granules disappeared when serum PCT levels reached < 1 ng/mL. The patient responded well to treatment and he was discharged on the 16th day upon request. Conclusion: This case is presented as an example of managing sepsis with a combination of a conventional hematology marker and a modern biomarker. Resource poor hospitals with inadequate microbiology services, may evaluate and use these two biomarkers not only for the total management of sepsis but also to reduce the cost of critical care.
基金supported by the National Natural Science Foundation of China(Grants No.91647206 and 51779079)the Program for Changjiang Scholars and Innovative Research Team at Hohai University(Grant No.IRT13061)+1 种基金the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the Top-notch Academic Programs Project of Jiangsu Higher Education Institutions(TAPP).
文摘In our previous study,we prepared the granules by embedding artemisinin into alginate-chitosan using microcapsule technology.These granules can release artemisinin sustainably and have a strong inhibitory effect on the growth of both single Microcystis aeruginosa and mixed algae.To safely and effectively use artemisinin sustained-release granules to control algal blooms,the ecotoxicity was studied by assessing their acute and chronic toxicity to Daphnia magna(D.magna)and Danio rerio(D.rerio),along with their antioxidant activities.The results showed that the 48-h median effective concentration(EC50)of pure artemisinin to D.magna was 24.54 mg/L and the 96-h median lethal concentration(LC50)of pure artemisinin to D.rerio was 68.08 mg/L.Both values were classified as intermediate toxicity according to the Organization for Economic Co-operation and Development(OECD).The optimal algae inhibitory concentration of artemisinin sustained-release granules(1 g/L)had low acute toxicity to both D.magna and D.rerio.The sustained-release granules had higher chronic toxicity to D.magna than to D.rerio.Partial indices of D.magna were inhibited by granules when the concentrations were larger than 0.1 g/L.Low granule concentration had an inductive effect on antioxidant enzyme activities in D.magna and D.rerio.With the increase of the exposure concentration and time,the enzyme activity presented a trend of first increasing and then decreasing,and the overall changes were significant.The change trend and range of enzyme activity indicated that the granules could cause serious oxidative stress to D.magna and D.rerio,and the changes were consistent with the results of toxicity experimentation.
基金Scientific Research Project of the First Affiliated Hospital of Guangxi University of Chinese Medicine(2017ZJ006)Key Research and Development Project of Department of Science and Technology of Guangxi Zhuang Autonomous Region(AB19110003).
文摘[Objectives]To study the long-term toxicity of Maxing Erchen Zhike granules to rats after intragastric administration,so as to provide reference for its preclinical safety evaluation.[Methods]Total 80 rats were randomly and evenly divided into high-dose group(1.2 mL/100 g,120 g/kg),middle-dose group(96.0 g/kg),low-dose group(72.0 g/kg)and blank control group.The rats in the treatment groups were administered with corresponding doses of Maxing Erchen Zhike granules,and those in the blank control group were given with equal-amount normal saline.The administration lasted for 30 consecutive days.During the experiment,the rats'feed intake,activity,feces and other conditions and toxicity reactions were observed every day.After 24 h of the last administration,12 rats(half male and half female)were randomly selected from each group.Each of the rats was anesthetized with 10%chloral hydrate solution(0.3 mL/100 g)through intraperitoneal injection and subjected to abdominal aorta blood collection(two tubes)for hematological examination and blood biochemical examination(serum).Then,the main organs of the rats were weighed,and pathological examinations were performed.After that,the main organs were weighed and pathological examination was performed.The remaining rats in each group were discontinued and observed for 14 d.On the 15th d,they were subjected to the same treatment,and the body weight,organ coefficients,hematological indices,blood biochemical indices and pathological indices were examined.[Results]After 30 d of administration,there was no abnormality in the appearance and behavior of the animals.There was no significant difference in the daily consumption of feed among the groups,and there was no special case of weight gain.Among the blood biochemical indices,the ALB and ALT levels of each administration group were significantly different from those of the blank control group(P<0.05).The results of histopathological examination show that there was one case of interstitial pneumonia in each of the high-dose group,middle-dose group and blank control group.After 14 d that the administration was stopped,one case of focal myocarditis appeared in the high-dose group,and one case of interstitial pneumonia appeared in the middle-dose group.[Conclusions]Maxing Erchen Zhike granules are safe to be administered to rats at 100 times the clinical dose.and there should be no safety hazards clinically when used at conventional doses.
基金Integrating Traditional Chinese and Western medicine(ZDBZ-ZXY-201601).
文摘Background:To evaluate the acute toxicity of the experienced prescription Lucao Wenban granules on mice and provide a theoretical basis for clinical medication safety.Methods:The mice were not deprived of water for 16 h after fasting,and were intragastrically given the experienced prescription Lucao Wenban granules at the maximum mass concentration(0.55 g/mL)and the maximum volume(0.04 mL/g body weight)2 times within 24 hours.The toxicity was observed and recorded within 14 days after administration.At the end of the experiment,the biochemical indexes of mice were detected.The liver,heart,spleen,lung,and kidney were dissected and observed after executing mice to weigh the wet weight and calculate the coefficient of viscera.Results:There was no death after the mice were given 342.32 g/kg of crude medicine of the experienced prescription Lucao Wenban granules.No significant differences were detected in body weight,biochemical indexes,visceral index between the experiment group and the control group.Conclusion:There is no acute toxicity in mice.The maximum tolerable dose is 342.32 g/kg,which is 144 times of clinical dose.
文摘Objective: To observe and assess the efficacy enhancing and toxicity attenuating effect of Nuzhen Yangyin Granule (NYG) to the anti-parkinsonism (paralysis agitans) therapy with medopa and ar-tane. Methods: Adopting the randomized double-blinded method, the effect of adding NYG to 30 patients with Parkinsonism in the treated group,
基金Department of Science and Technology of Hubei Province:Preclinical Study on Qingfei Dayuan granules (No.2021BGE017)
文摘OBJECTIVE:To study the anti-inflammatory and anti-tussive effects of Qingfei Dayuan granules(清肺达原颗粒,QFDY),and to evaluate the acute and sub-chronic toxicity of QFDY.METHODS:Anti-inflammatory effects were evaluated by murine model of xylene induced ear edema in mice.Ear swelling degree was calculated and tumor necrosis factor-α,interleukin-1βand interleukin-6 were determined.Anti-tussive evaluations were carried out in the mouse cough model induced by ammonia liquor.Latent period cough and number of cough within 3 min were counted.In acute toxicity study,the rats were randomly divided into test group and solvent control group.Body weighs,food intakes and general clinical signs were monitored.In the sub-chronic toxicity study,QFDY was administered to rats at 0,4,8 and 16 g/kg per day for 28 and 30 d of post treatment was conducted.Mortalities,clinical signs,body weight changes,food intakes,ophthalmological examinations,hematological parameters,biochemical indicators,electrolyte indicators,urinalyses and histopathological examinations were monitored.RESULTS:QFDY significantly inhibited the development of ear edema in anti-inflammatory assay and decreased cough frequency caused by ammonia liquor.The results presented a dose-effect relationship.In acute toxicity study,no abnormality exhibited at dose of 24.0 g/kg per day during the 14-d observation period.In the sub-chronic toxicity study,higher reticulocyte count,lymphocyte and lower Cl-,blood urea nitrogen were analyzed compared with the solvent control group.But the differences were considered to be incidental and not clinically toxic.Obvious dose-effect relationship of urine color was observed,and the three test groups at the end of the experiments resulted in significant increase in urobilinogen,bilirubin,ketone body and urine leukocyte.However,all the positive indicators returned to normal in the recovery period.Therefore,no toxicological changes were found during the study period.CONCLUSION:QFDY showed significant anti-inflammatory and anti-tussive effects in mice.The lethal dose(LD50)of per oral QFDY in rats was estimated to be more than 24.0 g/kg per day and the no observed adverse effect level was over 16 g/kg per day,which suggested that QFDY is relatively safe for oral medication at the present dose on rats.Our experimental results provide a reference for the further development and research of QFDY.
