Alstonia scholaris(L.)R.Br.,an evergreen tropical plant rich in indole alkaloids with significant physiological activity,is traditionally used to treat respiratory diseases in China.This study was conducted to establi...Alstonia scholaris(L.)R.Br.,an evergreen tropical plant rich in indole alkaloids with significant physiological activity,is traditionally used to treat respiratory diseases in China.This study was conducted to establish the toxicity profile of the alkaloid extract(TA)of A.scholaris leaves in non-rodents.After oral administration of a single dose(4 g/kg.bw),a num-ber of transient symptoms,such as unsteady gait,drooling,emesis,and reddening of peri-oral mucosa,were observed,but no treatment-related mortality.A sub-chronic toxicity study with a range of doses of TA(20,60 and 120 mg/kg.bw)was conducted for a 13-week treatment period,followed by 4-week recovery observation.Except for emesis and drooling in majority of animals in 120 mg/kg.bw treatment group,no clinical changes were observed in TA-treated animals.Data from electrocardiography,bone marrow,urine,fecal,hematology and clinical chemistry analyses were comparable between TA-treated and control animals.No significant differences in the relative organ weights and histopathological characteristics were evident between the TA-treated and control groups.Accordingly,the non-observed-adverse-effect-level(NOAEL)of TA was established as 120 mg/kg.bw.Our results add further knowledge to the safety database for indole alkaloid extracts from A.scholaris with potential utility as novel drug candidates.展开更多
Combinational therapy of lamivudine and oxymatrine has been employed in the battle against hepatitis B virus in clinical setting. However, the pharmacokinetic behavior of the drug or active metabolism in intravenous/o...Combinational therapy of lamivudine and oxymatrine has been employed in the battle against hepatitis B virus in clinical setting. However, the pharmacokinetic behavior of the drug or active metabolism in intravenous/oral co-administration regime is poorly investigated. Herein,we evaluated the pharmacokinetic characteristic through a tailor-designed 3 way crossoverLatin square experiment in adult male beagle dogs. Six dogs were randomly treated by intravenous administration of lamivudine(2.5 mg/kg), oxymatrine(15 mg/kg) and combinational dosage, named as intravenous regime. Meanwhile the other six dogs were orally administrated with lamivudine(2.5 mg/kg), oxymatrine(15 mg/kg) and combinational dosage,named as oral regime. The pharmacokinetic feature in simultaneous oral treatment appeared to have no significant difference when compared with individual administration,even including matrine, the active metabolite of oxymatrine. In intravenous regime, the main pharmacokinetic parameters of simultaneous administration were nearly consistent with intravenous regime remedy. The collaborated application of lamivudine and oxymatrine contributed to non-distinctive pharmacokinetic fluctuations of beagle dogs in intravenous/oral regime, compared with individual employment, which established a vital base for the clinical co-administration against hepatitis B. Furthermore, the present study demonstrated that the determination of pharmacokinetics between combinational and individual therapy might assist in the development of drug compatibility in clinical therapy.展开更多
OBJECTIVE To compare the pharmacokinetics and pharmacodynamics of PEG30-rhG-CSF administered to beagle dogs at three different dosages with PEG20-rhG-CSF administered at one dosage,and to provide an experimental basis...OBJECTIVE To compare the pharmacokinetics and pharmacodynamics of PEG30-rhG-CSF administered to beagle dogs at three different dosages with PEG20-rhG-CSF administered at one dosage,and to provide an experimental basis for clinical trials.METHODS Beagle dogs received single,subcutaneous doses of PEG30-rhG-CSF at 100,200 and 400 μg/kg or PEG20-rhG-CSF at 200 μg/kg.PEG30-rhG-CSF and PEG20-rhG-CSF concentrations in serum were analyzed using an enzyme-linked immunosorbent assay(ELISA).WBC,ANC and PLT counts of whole blood samples were measured using fully automated analytic instrumentation.Pharmacokinetic and pharmacodynamic parameters were calculated using DAS 2.0 statistical analysis so ware.RESULTS The pharmacokinetic parameters of PEG30-rhG-CSF calculated from the serum concentration data determined by ELISA were as follows:the mean elimination half-life(t1/2ke) was 40.6 h(33.5～45.4 h);the mean time to reach peak concentration(Tmax) was 19.2 h(11.7～24.0 h);the drug clearance from the serum(CL) was decreased with increasing doses;the peak concentration(Cmax) and the area under the serum concentration-time curve(AUC) were increased with increasing doses.For PEG20-rhG-CSF,the half-life was shorter(12 h) and Tmax was achieved much earlier(10 h) relative to PEG30-rhG-CSF.The AUC of PEG30-rhG-CSF was much greater than that of PEG20-rhG-CSF,and the relative bioavailability with a subcutaneous injection was 158.7%.Administration of single doses of PEG30-rhG-CSF resulted in substantial increases in the absolute neutrophil count(ANC).The time to reach ANCmax(ANCTmax) was 72 h.The maximum observed absolute neutrophil counts(ANCmax) and the area over the baseline effect curve(AOBEC) was increased with increasing doses.The effect-elimination half-life(t1/2E) ranged from 60 h to 80 h a er subcutaneous administration.The PLT count was slightly elevated 8～12 h a er s.c.injection,and declined a er 24 h.CONCLUSION The mean elimination half-life of PEG30-rhG-CSF was longer than that of PEG20-rhG-CSF at the same dose,and the other main pharmacokinetic and pharmacodynamic parameters of PEG30-rhG-CSF,including Cmax,ANCmax,AUC and AOBEC were much greater than those following PEG20-rhG-CSF injection.展开更多
Objective： To evaluate the effectiveness of regenerous tissue and bone substitute in autogenous tooth transplantation in the larger recipient socket. Methods：In 3 Beagle dogs, 18 incisors were transplanted to the re...Objective： To evaluate the effectiveness of regenerous tissue and bone substitute in autogenous tooth transplantation in the larger recipient socket. Methods：In 3 Beagle dogs, 18 incisors were transplanted to the recipient sockets, 2 mm wider mesio-distally. The regenerous tissue group, the bone substitute group and the control group contained 7, 7 and 4 teeth respectively. No additional material was used in control group. Clinical and radiographic examinations were done every month and were sacrificed 3 months later. Subsequently, decalcified sections were prepared for routine histological evaluation. Ordinal scores for root surface resorption were analyzed using the Kruskal-Wallis test. Results：All donor teeth survived. A statistically significant difference was found among all three treatment groups（P= 0.0001）. The proliferating tissue in space positively affected the periodontal healing without any resorption. Inflammatory resorption of the root surface and formation of new bone were observed in the bone substitute group. Surface resorptions of the roots were found in the control group. Conclusion：Proliferating tissues enhance the regeneration of periodontal tissues in larger recipient sockets and prevent root resorption. Sinbone HT is beneficial for the stabilization of the transplanted teeth in larger sockets.展开更多
The oculomotor nerves of beagle dogs received electrical stimulation at 0.3-2.0 V. After recording compound muscle action potentials of the inferior oblique muscle, the oculomotor nerve was quickly cut off and a direc...The oculomotor nerves of beagle dogs received electrical stimulation at 0.3-2.0 V. After recording compound muscle action potentials of the inferior oblique muscle, the oculomotor nerve was quickly cut off and a direct end-to-end anastomosis was then performed. As a result, the stimulating elec-trode was smoothly inserted and placed, and ideal bioelectrical signals of the interior oblique muscle were acquired. After oculomotor nerve injury, compound muscle action potentials of the inferior oblique muscle were significantly decreased in beagle dogs. These findings suggest that an animal model of oculomotor nerve injury was successfully established for electrophysiological studies.展开更多
基金The authors are grateful to Yunnan Major Science and Technology Project(2019ZF003,2019FY003004)the National Key Research and Development Program of China(2017YFC1704007)the general program of applied basic research of Yunnan province(2019FB116)for partial financial support.
文摘Alstonia scholaris(L.)R.Br.,an evergreen tropical plant rich in indole alkaloids with significant physiological activity,is traditionally used to treat respiratory diseases in China.This study was conducted to establish the toxicity profile of the alkaloid extract(TA)of A.scholaris leaves in non-rodents.After oral administration of a single dose(4 g/kg.bw),a num-ber of transient symptoms,such as unsteady gait,drooling,emesis,and reddening of peri-oral mucosa,were observed,but no treatment-related mortality.A sub-chronic toxicity study with a range of doses of TA(20,60 and 120 mg/kg.bw)was conducted for a 13-week treatment period,followed by 4-week recovery observation.Except for emesis and drooling in majority of animals in 120 mg/kg.bw treatment group,no clinical changes were observed in TA-treated animals.Data from electrocardiography,bone marrow,urine,fecal,hematology and clinical chemistry analyses were comparable between TA-treated and control animals.No significant differences in the relative organ weights and histopathological characteristics were evident between the TA-treated and control groups.Accordingly,the non-observed-adverse-effect-level(NOAEL)of TA was established as 120 mg/kg.bw.Our results add further knowledge to the safety database for indole alkaloid extracts from A.scholaris with potential utility as novel drug candidates.
基金the National Natural Science Foundation of China(Nos.30901996,81173009 and 81302722)the General Project in Education Department of Liaoning Province(No.L2013390)the Specific Science Foundation of Shenyang Pharmaceutical University(Nos.ZCJJ2014409 and ZCJJ2013402).
文摘Combinational therapy of lamivudine and oxymatrine has been employed in the battle against hepatitis B virus in clinical setting. However, the pharmacokinetic behavior of the drug or active metabolism in intravenous/oral co-administration regime is poorly investigated. Herein,we evaluated the pharmacokinetic characteristic through a tailor-designed 3 way crossoverLatin square experiment in adult male beagle dogs. Six dogs were randomly treated by intravenous administration of lamivudine(2.5 mg/kg), oxymatrine(15 mg/kg) and combinational dosage, named as intravenous regime. Meanwhile the other six dogs were orally administrated with lamivudine(2.5 mg/kg), oxymatrine(15 mg/kg) and combinational dosage,named as oral regime. The pharmacokinetic feature in simultaneous oral treatment appeared to have no significant difference when compared with individual administration,even including matrine, the active metabolite of oxymatrine. In intravenous regime, the main pharmacokinetic parameters of simultaneous administration were nearly consistent with intravenous regime remedy. The collaborated application of lamivudine and oxymatrine contributed to non-distinctive pharmacokinetic fluctuations of beagle dogs in intravenous/oral regime, compared with individual employment, which established a vital base for the clinical co-administration against hepatitis B. Furthermore, the present study demonstrated that the determination of pharmacokinetics between combinational and individual therapy might assist in the development of drug compatibility in clinical therapy.
基金National High Technology Research and Development Program of China(No.2007BAI14IB04)Major State Basic Research Development Program(No.2004CB518902)
文摘OBJECTIVE To compare the pharmacokinetics and pharmacodynamics of PEG30-rhG-CSF administered to beagle dogs at three different dosages with PEG20-rhG-CSF administered at one dosage,and to provide an experimental basis for clinical trials.METHODS Beagle dogs received single,subcutaneous doses of PEG30-rhG-CSF at 100,200 and 400 μg/kg or PEG20-rhG-CSF at 200 μg/kg.PEG30-rhG-CSF and PEG20-rhG-CSF concentrations in serum were analyzed using an enzyme-linked immunosorbent assay(ELISA).WBC,ANC and PLT counts of whole blood samples were measured using fully automated analytic instrumentation.Pharmacokinetic and pharmacodynamic parameters were calculated using DAS 2.0 statistical analysis so ware.RESULTS The pharmacokinetic parameters of PEG30-rhG-CSF calculated from the serum concentration data determined by ELISA were as follows:the mean elimination half-life(t1/2ke) was 40.6 h(33.5～45.4 h);the mean time to reach peak concentration(Tmax) was 19.2 h(11.7～24.0 h);the drug clearance from the serum(CL) was decreased with increasing doses;the peak concentration(Cmax) and the area under the serum concentration-time curve(AUC) were increased with increasing doses.For PEG20-rhG-CSF,the half-life was shorter(12 h) and Tmax was achieved much earlier(10 h) relative to PEG30-rhG-CSF.The AUC of PEG30-rhG-CSF was much greater than that of PEG20-rhG-CSF,and the relative bioavailability with a subcutaneous injection was 158.7%.Administration of single doses of PEG30-rhG-CSF resulted in substantial increases in the absolute neutrophil count(ANC).The time to reach ANCmax(ANCTmax) was 72 h.The maximum observed absolute neutrophil counts(ANCmax) and the area over the baseline effect curve(AOBEC) was increased with increasing doses.The effect-elimination half-life(t1/2E) ranged from 60 h to 80 h a er subcutaneous administration.The PLT count was slightly elevated 8～12 h a er s.c.injection,and declined a er 24 h.CONCLUSION The mean elimination half-life of PEG30-rhG-CSF was longer than that of PEG20-rhG-CSF at the same dose,and the other main pharmacokinetic and pharmacodynamic parameters of PEG30-rhG-CSF,including Cmax,ANCmax,AUC and AOBEC were much greater than those following PEG20-rhG-CSF injection.
基金Jiangsu Provincial Education Department Fund(No.06 KJD320124)
文摘Objective： To evaluate the effectiveness of regenerous tissue and bone substitute in autogenous tooth transplantation in the larger recipient socket. Methods：In 3 Beagle dogs, 18 incisors were transplanted to the recipient sockets, 2 mm wider mesio-distally. The regenerous tissue group, the bone substitute group and the control group contained 7, 7 and 4 teeth respectively. No additional material was used in control group. Clinical and radiographic examinations were done every month and were sacrificed 3 months later. Subsequently, decalcified sections were prepared for routine histological evaluation. Ordinal scores for root surface resorption were analyzed using the Kruskal-Wallis test. Results：All donor teeth survived. A statistically significant difference was found among all three treatment groups（P= 0.0001）. The proliferating tissue in space positively affected the periodontal healing without any resorption. Inflammatory resorption of the root surface and formation of new bone were observed in the bone substitute group. Surface resorptions of the roots were found in the control group. Conclusion：Proliferating tissues enhance the regeneration of periodontal tissues in larger recipient sockets and prevent root resorption. Sinbone HT is beneficial for the stabilization of the transplanted teeth in larger sockets.
基金the National Natural Science Foundation of China, No.30571907the Shanghai Natural Science Foundation, No.05QMH1409
文摘The oculomotor nerves of beagle dogs received electrical stimulation at 0.3-2.0 V. After recording compound muscle action potentials of the inferior oblique muscle, the oculomotor nerve was quickly cut off and a direct end-to-end anastomosis was then performed. As a result, the stimulating elec-trode was smoothly inserted and placed, and ideal bioelectrical signals of the interior oblique muscle were acquired. After oculomotor nerve injury, compound muscle action potentials of the inferior oblique muscle were significantly decreased in beagle dogs. These findings suggest that an animal model of oculomotor nerve injury was successfully established for electrophysiological studies.
