Objective To study the pharmacokinetics of intravenous magnesium isoglycyrrhizinate injection in health volunteers with HPLC-UV. Methods Single doses of 2OOmg magnesium isoglycyrrhizinate were administrated to 10 heal...Objective To study the pharmacokinetics of intravenous magnesium isoglycyrrhizinate injection in health volunteers with HPLC-UV. Methods Single doses of 2OOmg magnesium isoglycyrrhizinate were administrated to 10 health volunteers by i. v. infusion. The concentrations of magnesium isoglycyrrhizinate in plasma were assayed by HPLC-UV method. The pharmacokinetic parameters of magnesium isoglycyrrhizinate injection were calculated by program 3P87. Results The main pharmacokinetic parameters of intravenous magnesium isoglycyrrhizinate were as follows: cmax ( 67. 58 ± 8. 84 ) mg/L, T1/2α ( 1.46 ± 0. 35 ) h, T1/2β ( 23. 95 ± 4. 72 ) h, Vd ( 2. 921 ± 0. 382) L, CL (0. 186 ±0. 048) L/h,k10(0. 064 ±0. 016) h^-1, AUC0-T(1015.29 ±225. 14) mg·h^-1·L^-1 ,respectively. Conclusion We have successfully used the analytical method for magnesium isoglycyrrhizinate to study its pharmacokinetical properties of health volunteers after i. v. infusion. The method is found to be simple, accurate, stable and sensitive for application in clinical pharmacokinetics study. The concentration-time plot was fitted to a two-compartment open model with first-order elimination.展开更多
Since the approval of rituximab in 1997, monoclonal antibodies(mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great...Since the approval of rituximab in 1997, monoclonal antibodies(mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great strides that have been made in molecular biology and in biotechnology over the past several decades. Currently, there are 14 approved mAb products for oncology indications, and there are ten additional mAbs in late stages of clinical trials. Compared to traditional chemotherapeutic agents, mAbs have several advantages, including a long circulating half-life and high target specificity. Antibodies can serve as cytotoxic agents when administered alone, exerting a pharmacologic effect through several mechanisms involving the antigen binding(Fab) and/or Fc domains of the molecule, and mAbs may also be utilized as drug carriers, targeting a toxic payload to cancer cells. The extremely high affinity of mAbs for their targets, which is desirable with respect to pharmacodynamics(i.e., contributing to the high therapeutic selectivity of mAb), often leads to complex, non-linear, target-mediated pharmacokinetics. In this report, we summarize the pharmacokinetic and pharmacodynamics of mAbs that have been approved and of mAbs that are nearing approval for oncology indications, with particular focus on the molecular and cellular mechanisms responsible for their disposition and efficacy.展开更多
Neural information processing is tightly coupled to both energy consumption and derivation from substrates.In this study,the energy function of the neuron during the action potential(AP)is described and analyzed.It ha...Neural information processing is tightly coupled to both energy consumption and derivation from substrates.In this study,the energy function of the neuron during the action potential(AP)is described and analyzed.It has been observed that energy consumption during the AP does not match predictions of the conventional theory of neural energy dynamics.On short time scales,neural energy expenditure shifts between positive and negative phases.During the AP,the energy source switches from neuronal stores(positive expenditure or net consumption)to exploitation of external substrates,specifically the glucose and oxygen carried in cerebral blood(the negative consumption phase).Based on the idea of reductionism,this paper demonstrates how ion channels,membrane pumps and transporters,ionotropic and metabotropic receptor signaling pathways,astrocyte glycolysis and the production lactate,and the glutamate-glutamine cycle all serve to relate cerebral blood flow and neuronal metabolism to neuronal activity and so maintain neuronal energy charge during the AP.展开更多
Phytochrome-dependent light signaling has been studied in several fungi.In Aspergillus nidulans lightstimulated phytochrome activates the high-osmolarity glycerol(HOG)signaling pathway and thereby controls the express...Phytochrome-dependent light signaling has been studied in several fungi.In Aspergillus nidulans lightstimulated phytochrome activates the high-osmolarity glycerol(HOG)signaling pathway and thereby controls the expression of a large number of genes,many of which are related to stress responses.In a genome-wide expression analysis in A.nidulans we found that phytochrome,fph A,is under strict expression control of the central regulator of the sulfur-starvation response,Met R.This transcriptional regulator is required for the expression of genes involved in inorganic sulfur assimilation.In the presence of organic sulfur,Met R is probably ubiquitinated and possibly degraded and the transcription of sulfur-assimilation genes,e.g.,sulfate permease,is turned off.The expression analysis described here revealed,however,that Met R additionally controls the expression of hundreds of genes,many of which are required for secondary metabolite production.We also show that met R mutation phenocopies fph A deletion,and five other histidine-hybrid kinases are down-regulated in the met R1 mutant.Furthermore,we found that light and phytochrome regulate the expression of at least three carbon–sulfur hydrolases.This work is a further step towards understanding the interplay between light sensing and metabolic pathways.展开更多
文摘Objective To study the pharmacokinetics of intravenous magnesium isoglycyrrhizinate injection in health volunteers with HPLC-UV. Methods Single doses of 2OOmg magnesium isoglycyrrhizinate were administrated to 10 health volunteers by i. v. infusion. The concentrations of magnesium isoglycyrrhizinate in plasma were assayed by HPLC-UV method. The pharmacokinetic parameters of magnesium isoglycyrrhizinate injection were calculated by program 3P87. Results The main pharmacokinetic parameters of intravenous magnesium isoglycyrrhizinate were as follows: cmax ( 67. 58 ± 8. 84 ) mg/L, T1/2α ( 1.46 ± 0. 35 ) h, T1/2β ( 23. 95 ± 4. 72 ) h, Vd ( 2. 921 ± 0. 382) L, CL (0. 186 ±0. 048) L/h,k10(0. 064 ±0. 016) h^-1, AUC0-T(1015.29 ±225. 14) mg·h^-1·L^-1 ,respectively. Conclusion We have successfully used the analytical method for magnesium isoglycyrrhizinate to study its pharmacokinetical properties of health volunteers after i. v. infusion. The method is found to be simple, accurate, stable and sensitive for application in clinical pharmacokinetics study. The concentration-time plot was fitted to a two-compartment open model with first-order elimination.
文摘Since the approval of rituximab in 1997, monoclonal antibodies(mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great strides that have been made in molecular biology and in biotechnology over the past several decades. Currently, there are 14 approved mAb products for oncology indications, and there are ten additional mAbs in late stages of clinical trials. Compared to traditional chemotherapeutic agents, mAbs have several advantages, including a long circulating half-life and high target specificity. Antibodies can serve as cytotoxic agents when administered alone, exerting a pharmacologic effect through several mechanisms involving the antigen binding(Fab) and/or Fc domains of the molecule, and mAbs may also be utilized as drug carriers, targeting a toxic payload to cancer cells. The extremely high affinity of mAbs for their targets, which is desirable with respect to pharmacodynamics(i.e., contributing to the high therapeutic selectivity of mAb), often leads to complex, non-linear, target-mediated pharmacokinetics. In this report, we summarize the pharmacokinetic and pharmacodynamics of mAbs that have been approved and of mAbs that are nearing approval for oncology indications, with particular focus on the molecular and cellular mechanisms responsible for their disposition and efficacy.
基金supported by the National Natural Science Foundation of China(Grant Nos.1123200511002055)the Ministry of Education Doctoral Foundation(Grant No.20120074110020)
文摘Neural information processing is tightly coupled to both energy consumption and derivation from substrates.In this study,the energy function of the neuron during the action potential(AP)is described and analyzed.It has been observed that energy consumption during the AP does not match predictions of the conventional theory of neural energy dynamics.On short time scales,neural energy expenditure shifts between positive and negative phases.During the AP,the energy source switches from neuronal stores(positive expenditure or net consumption)to exploitation of external substrates,specifically the glucose and oxygen carried in cerebral blood(the negative consumption phase).Based on the idea of reductionism,this paper demonstrates how ion channels,membrane pumps and transporters,ionotropic and metabotropic receptor signaling pathways,astrocyte glycolysis and the production lactate,and the glutamate-glutamine cycle all serve to relate cerebral blood flow and neuronal metabolism to neuronal activity and so maintain neuronal energy charge during the AP.
基金supported by the German Science Foundation(DFG Fi459/19-1)。
文摘Phytochrome-dependent light signaling has been studied in several fungi.In Aspergillus nidulans lightstimulated phytochrome activates the high-osmolarity glycerol(HOG)signaling pathway and thereby controls the expression of a large number of genes,many of which are related to stress responses.In a genome-wide expression analysis in A.nidulans we found that phytochrome,fph A,is under strict expression control of the central regulator of the sulfur-starvation response,Met R.This transcriptional regulator is required for the expression of genes involved in inorganic sulfur assimilation.In the presence of organic sulfur,Met R is probably ubiquitinated and possibly degraded and the transcription of sulfur-assimilation genes,e.g.,sulfate permease,is turned off.The expression analysis described here revealed,however,that Met R additionally controls the expression of hundreds of genes,many of which are required for secondary metabolite production.We also show that met R mutation phenocopies fph A deletion,and five other histidine-hybrid kinases are down-regulated in the met R1 mutant.Furthermore,we found that light and phytochrome regulate the expression of at least three carbon–sulfur hydrolases.This work is a further step towards understanding the interplay between light sensing and metabolic pathways.