The purpose of this study is to characterize the tissue distribution, excretion and pharmacokinetics profiles of R-hap in healthy Wistar rats. R-hap was radiolabeled by the IODO-GEN method. Tissue distribution and uri...The purpose of this study is to characterize the tissue distribution, excretion and pharmacokinetics profiles of R-hap in healthy Wistar rats. R-hap was radiolabeled by the IODO-GEN method. Tissue distribution and urinary, fecal and biliary excretion patterns of ^125I-R-hap were investigated following a single i.v. bolus injection. Pharmacokinetics properties of ^125I-R-hap were also examined after a single i.v. bolus injection. The trichloroacetic acid （TCA） precipitated radioactivity was widely distributed and rapiclly diminished in most tissues. Kidney contained the highest radioactivity among all organs and the distribution of ^125I-R-hap to fat was minimal. The cumulative excretion of ^125I-R-hap reached 71.81% ± 2.15% of the administered radioactivity at 48 h and 94.71% ± 1.50% at 120 h. Urinary excretion was the dominant route of elimination following i.v. administration, as 80.64% ± 1.47% and 14.07% ± 0.95% of administered radioactivity were recovered in urine and feces, respectively, in intact rats over 120 h. The mean areas under the plasma concentration-time curve was （8818.4 ± 576.1） Bq/h/mL. The results of tissue distribution, excretion and pharmacokinetics of R-hap in rats provided biopharmaceutical basis for the design of future clinical trials.展开更多
AIM: To study the morphological positive expression of antrial natriuretic peptide (ANP)-synthesizing cells and ultrastructural localization and the relationship between ANP-synthesizing cells and microvessel density ...AIM: To study the morphological positive expression of antrial natriuretic peptide (ANP)-synthesizing cells and ultrastructural localization and the relationship between ANP-synthesizing cells and microvessel density in the stomach of rats and to analyze the distribution of the three histologically distinct regions of ANP-synthesizing cells. METHODS: Using immunohistochemical techniques, we studied positive expression of ANP-synthesizing cells in rat stomach. A postembedding immunogold microscopy technique was used for ultrastructural localization of ANP-synthesizing cells. Microvessel density in the rat stomach was estimated using tannic acid-ferric chloride (TAFC) method staining. Distribution of ANP-synthesizing cells were studied in different regions of rat stomach histochemically. RESULTS: Positive expression of ANP-synthesizing cells were localized in the gastric mucosa of rats. Localization of ANP-synthesizing cells identified them to be enterochrochromaffin cells (EC) by using a postembedding immunogold electron microscopy technique. EC cells were in the basal third of the cardiac mucosa region. ANP-synthesizing cells existed in different regions of rat stomach and its density was largest in the gastric cardiac region, and the distribution order of ANP-synthesizing cells in density was cardiac region, pyloric region and fundic region in mucosa layer. We have also found a close relationship between ANP-synthesizing cells and microvessel density in gastric mucosa of rats using TAFC staining. CONCLUSION: ANP-synthesizing cells are expressedin the gastric mucosa. EC synthesize ANP. There is a close relationship between ANP-synthesizing cells and microvessel density in gastric mucosa of rats.The distribution density of ANP-synthesizing cells is largest in the gastric cardiac region.展开更多
We observed in a pilot study that there was a transient elevation of brain natriuretic peptide (BNP) level shortly after the transplantation in the patient with ischemic heart failure, which is unexplainable by the si...We observed in a pilot study that there was a transient elevation of brain natriuretic peptide (BNP) level shortly after the transplantation in the patient with ischemic heart failure, which is unexplainable by the simultaneous increase of the cardiac output and six-minute walk distance. Similar findings were observed in the phase I trial. We postulated on the basis of the finding of Fukuda in vitro that this transient elevation of BNP level against the improvement of cardiac function and exercise capacity might indicate cardiomyogenesis in patients after mesenchymal stem cell transplantation. Further study is warranted to verify the hypothesis.展开更多
Objective: To observe the therapeutic effect of electroacupuncture (EA) on plasma angiotensin (Ang Ⅱ), aldosterone (ALD) and atrial natriuretic polypeptide (ANP) contents in experimental cerebral infarction rabbits f...Objective: To observe the therapeutic effect of electroacupuncture (EA) on plasma angiotensin (Ang Ⅱ), aldosterone (ALD) and atrial natriuretic polypeptide (ANP) contents in experimental cerebral infarction rabbits for analyzing the underlying mechanism of acupuncture in ameliorating blood supply of the brain tissue. Methods: A total of 80 rabbits were randomized into control (n = 8), pseudo-operation (n = 24), model (n = 24) and EA (n = 24) groups. Cerebral infarction model was established by infusion of self-thrombus into the carotid artery. EA (1 mA, 2 Hz) was applied to 'Baihui'(百会 GV 20) and 'Shuigou'(水沟 GV 26) for 30 min, once every 12 hours. Plasma Ang Ⅱ, ALD and ANP contents were detected with radioimmunoassay method. In the later 3 groups, blood samples were taken at 6 h, 24 h and 48 h after cerebral ischemia. Results: Compared with control and pseudo-operation groups, Ang Ⅱ and ALD contents of model group at 6 h, 24 h and 48 h after cerebral ischemia increased significantly while plasma ANP of the 3 time-courses of model group decreased considerably (P<0.01). In comparison with model group, results showed that Ang-Ⅱ and ALD contents of EA group decreased significantly whereas ANP level of EA group increased strikingly (P<0.01). Conclusion: Electroacupuncture has the effects of raising plasma ANP level and lowering plasma Ang-Ⅱ and ALD in cerebral infarction rabbits.展开更多
Growth and energy budget of the polychaete,Neanthes japonica,at various temperatures(17,20,23,26 and 29℃) were investigated in this study. The growth,as indicated by final dry weight and specific growth rate(SGR),inc...Growth and energy budget of the polychaete,Neanthes japonica,at various temperatures(17,20,23,26 and 29℃) were investigated in this study. The growth,as indicated by final dry weight and specific growth rate(SGR),increased with increasing temperature,with the maximum level at 26℃,and then decreased significantly at 29℃. A similar trend was observed in feeding rate,food conversion efficiency(FCE) and apparent digestive rate(ADR). However,no significant differences were detected in ADR among all the temperature treatments. In the pattern of energy allocation,faeces energy was only a small component of energy budget and had little influence on the proportion of food energy allocated to growth. The metabolic energy accounted for a large portion of energy intake for each temperature treatment. The nitrogen excretion was appreciable with changing temperature. The two expenditure terms(respiration energy and excretion energy) in energy budget were the major factors influencing the proportion of food energy allocated to growth. These results revealed that temperature affected the growth of N. japonica mainly by influencing feeding rate and FCE. In addition,regression equations describing the relationship between feeding rate,faecal production,SGR,FCE and temperature were obtained. The optimum temperatures for feeding rate,FCE and SGR were estimated at 25.01℃,24.24℃ and 24.73 ℃,respectively,from the regression equations.展开更多
As an important bis-benzylisoquinoline alkaloid isolated from the bulbous root ofStephania tetrandra S. Moore, tetrandrine （Tet） is widely used for the treatment of malignant tumor due to its properties of reversing...As an important bis-benzylisoquinoline alkaloid isolated from the bulbous root ofStephania tetrandra S. Moore, tetrandrine （Tet） is widely used for the treatment of malignant tumor due to its properties of reversing the multidrug resistance and apoptosis induction. In the present study, we aimed to evaluate the pharmacokinetics, tissue distribution and excretion of Tet in rats. Drug concentration in plasma and tissues was measured by high performance liquid chromatography （HPLC）, and the experimental data were analyzed using pharmacokinetic software DAS 2.0. The results showed that the plasma protein binding rate of Tet was 68.7%, indicating a higher protein binding drug. Tissue distribution was found in a descending order as follows： lung〉heart〉liver〉kidney〉spleen. Renal excretion was a major route of excretion, and the urine, bile and fecal excretion accounted for 25.73% of the administered dose. A UC0-∞ of Tet in the liver was 20 times greater than that in plasma, indicating that Tet had a higher affinity for the liver. Moreover, CL in the liver was the lowest among all tissues, indicating that Tet with slow elimination might result in the accumulation. Therefore, we need to adjust the dose for patients who have dysfunction in liver and kidney. In addition, therapeutic drug monitoring in long-term clinical treatment, if necessary, should be carried out.展开更多
Drug discovery is a costly and time-consuming process, with very few novel molecular entities approved for clinical use today. With the advancement of computational chemistry, integrated X-ray crystallography and nucl...Drug discovery is a costly and time-consuming process, with very few novel molecular entities approved for clinical use today. With the advancement of computational chemistry, integrated X-ray crystallography and nuclear magnetic resonance spectroscopy technology, more and more potential therapeutic agents for the treatment of human diseases are discovered. Furthermore, multiple medicinal chemistry approaches have been developed in support of early drug discovery. However, there is still much can be done in the early phase of drug discovery to improve the chances of success of a drug candidate. This paper reviews the discovery and evaluation of new chemical entities in the early stages of drug development.展开更多
基金National Natural Sciences Foundation of China(Grant No.30371669)National High Technology Research and Development Program of China(863 Program,Grant No.2003AA2Z347B).
文摘The purpose of this study is to characterize the tissue distribution, excretion and pharmacokinetics profiles of R-hap in healthy Wistar rats. R-hap was radiolabeled by the IODO-GEN method. Tissue distribution and urinary, fecal and biliary excretion patterns of ^125I-R-hap were investigated following a single i.v. bolus injection. Pharmacokinetics properties of ^125I-R-hap were also examined after a single i.v. bolus injection. The trichloroacetic acid （TCA） precipitated radioactivity was widely distributed and rapiclly diminished in most tissues. Kidney contained the highest radioactivity among all organs and the distribution of ^125I-R-hap to fat was minimal. The cumulative excretion of ^125I-R-hap reached 71.81% ± 2.15% of the administered radioactivity at 48 h and 94.71% ± 1.50% at 120 h. Urinary excretion was the dominant route of elimination following i.v. administration, as 80.64% ± 1.47% and 14.07% ± 0.95% of administered radioactivity were recovered in urine and feces, respectively, in intact rats over 120 h. The mean areas under the plasma concentration-time curve was （8818.4 ± 576.1） Bq/h/mL. The results of tissue distribution, excretion and pharmacokinetics of R-hap in rats provided biopharmaceutical basis for the design of future clinical trials.
文摘AIM: To study the morphological positive expression of antrial natriuretic peptide (ANP)-synthesizing cells and ultrastructural localization and the relationship between ANP-synthesizing cells and microvessel density in the stomach of rats and to analyze the distribution of the three histologically distinct regions of ANP-synthesizing cells. METHODS: Using immunohistochemical techniques, we studied positive expression of ANP-synthesizing cells in rat stomach. A postembedding immunogold microscopy technique was used for ultrastructural localization of ANP-synthesizing cells. Microvessel density in the rat stomach was estimated using tannic acid-ferric chloride (TAFC) method staining. Distribution of ANP-synthesizing cells were studied in different regions of rat stomach histochemically. RESULTS: Positive expression of ANP-synthesizing cells were localized in the gastric mucosa of rats. Localization of ANP-synthesizing cells identified them to be enterochrochromaffin cells (EC) by using a postembedding immunogold electron microscopy technique. EC cells were in the basal third of the cardiac mucosa region. ANP-synthesizing cells existed in different regions of rat stomach and its density was largest in the gastric cardiac region, and the distribution order of ANP-synthesizing cells in density was cardiac region, pyloric region and fundic region in mucosa layer. We have also found a close relationship between ANP-synthesizing cells and microvessel density in gastric mucosa of rats using TAFC staining. CONCLUSION: ANP-synthesizing cells are expressedin the gastric mucosa. EC synthesize ANP. There is a close relationship between ANP-synthesizing cells and microvessel density in gastric mucosa of rats.The distribution density of ANP-synthesizing cells is largest in the gastric cardiac region.
文摘We observed in a pilot study that there was a transient elevation of brain natriuretic peptide (BNP) level shortly after the transplantation in the patient with ischemic heart failure, which is unexplainable by the simultaneous increase of the cardiac output and six-minute walk distance. Similar findings were observed in the phase I trial. We postulated on the basis of the finding of Fukuda in vitro that this transient elevation of BNP level against the improvement of cardiac function and exercise capacity might indicate cardiomyogenesis in patients after mesenchymal stem cell transplantation. Further study is warranted to verify the hypothesis.
文摘Objective: To observe the therapeutic effect of electroacupuncture (EA) on plasma angiotensin (Ang Ⅱ), aldosterone (ALD) and atrial natriuretic polypeptide (ANP) contents in experimental cerebral infarction rabbits for analyzing the underlying mechanism of acupuncture in ameliorating blood supply of the brain tissue. Methods: A total of 80 rabbits were randomized into control (n = 8), pseudo-operation (n = 24), model (n = 24) and EA (n = 24) groups. Cerebral infarction model was established by infusion of self-thrombus into the carotid artery. EA (1 mA, 2 Hz) was applied to 'Baihui'(百会 GV 20) and 'Shuigou'(水沟 GV 26) for 30 min, once every 12 hours. Plasma Ang Ⅱ, ALD and ANP contents were detected with radioimmunoassay method. In the later 3 groups, blood samples were taken at 6 h, 24 h and 48 h after cerebral ischemia. Results: Compared with control and pseudo-operation groups, Ang Ⅱ and ALD contents of model group at 6 h, 24 h and 48 h after cerebral ischemia increased significantly while plasma ANP of the 3 time-courses of model group decreased considerably (P<0.01). In comparison with model group, results showed that Ang-Ⅱ and ALD contents of EA group decreased significantly whereas ANP level of EA group increased strikingly (P<0.01). Conclusion: Electroacupuncture has the effects of raising plasma ANP level and lowering plasma Ang-Ⅱ and ALD in cerebral infarction rabbits.
基金supported by the National Natural Sci-ence Foundation of China (No. 30490233).
文摘Growth and energy budget of the polychaete,Neanthes japonica,at various temperatures(17,20,23,26 and 29℃) were investigated in this study. The growth,as indicated by final dry weight and specific growth rate(SGR),increased with increasing temperature,with the maximum level at 26℃,and then decreased significantly at 29℃. A similar trend was observed in feeding rate,food conversion efficiency(FCE) and apparent digestive rate(ADR). However,no significant differences were detected in ADR among all the temperature treatments. In the pattern of energy allocation,faeces energy was only a small component of energy budget and had little influence on the proportion of food energy allocated to growth. The metabolic energy accounted for a large portion of energy intake for each temperature treatment. The nitrogen excretion was appreciable with changing temperature. The two expenditure terms(respiration energy and excretion energy) in energy budget were the major factors influencing the proportion of food energy allocated to growth. These results revealed that temperature affected the growth of N. japonica mainly by influencing feeding rate and FCE. In addition,regression equations describing the relationship between feeding rate,faecal production,SGR,FCE and temperature were obtained. The optimum temperatures for feeding rate,FCE and SGR were estimated at 25.01℃,24.24℃ and 24.73 ℃,respectively,from the regression equations.
基金The Scientific Research Fund Project of Heilongjiang University of Chinese Medicine(Grant No.201408)
文摘As an important bis-benzylisoquinoline alkaloid isolated from the bulbous root ofStephania tetrandra S. Moore, tetrandrine （Tet） is widely used for the treatment of malignant tumor due to its properties of reversing the multidrug resistance and apoptosis induction. In the present study, we aimed to evaluate the pharmacokinetics, tissue distribution and excretion of Tet in rats. Drug concentration in plasma and tissues was measured by high performance liquid chromatography （HPLC）, and the experimental data were analyzed using pharmacokinetic software DAS 2.0. The results showed that the plasma protein binding rate of Tet was 68.7%, indicating a higher protein binding drug. Tissue distribution was found in a descending order as follows： lung〉heart〉liver〉kidney〉spleen. Renal excretion was a major route of excretion, and the urine, bile and fecal excretion accounted for 25.73% of the administered dose. A UC0-∞ of Tet in the liver was 20 times greater than that in plasma, indicating that Tet had a higher affinity for the liver. Moreover, CL in the liver was the lowest among all tissues, indicating that Tet with slow elimination might result in the accumulation. Therefore, we need to adjust the dose for patients who have dysfunction in liver and kidney. In addition, therapeutic drug monitoring in long-term clinical treatment, if necessary, should be carried out.
基金The Shanghai Committee of Science and Technology (Grant No.11DZ2260600)the Fundamental Research Funds for the Central Universities
文摘Drug discovery is a costly and time-consuming process, with very few novel molecular entities approved for clinical use today. With the advancement of computational chemistry, integrated X-ray crystallography and nuclear magnetic resonance spectroscopy technology, more and more potential therapeutic agents for the treatment of human diseases are discovered. Furthermore, multiple medicinal chemistry approaches have been developed in support of early drug discovery. However, there is still much can be done in the early phase of drug discovery to improve the chances of success of a drug candidate. This paper reviews the discovery and evaluation of new chemical entities in the early stages of drug development.
