Density functional theory method has been employed to investigate the structures of the prototypical technetium-labeled diphosphonate complex 99mTc-MDP, where MDP represents methylenediphosphonic acid. A total of 14 t...Density functional theory method has been employed to investigate the structures of the prototypical technetium-labeled diphosphonate complex 99mTc-MDP, where MDP represents methylenediphosphonic acid. A total of 14 trial structures were generated by allowing for the geometric, conformational, charge, and spin isomerism. Based on the optimized structures and calculated energies at the B3LYP/LANL2DZ level, two stable isomers were determined for the title complex. And they were further studied systematically in comparison with the experimental structure. The basis sets 6-31G＊（LANL2DZ for Tc）, 6-31G＊（cc-pVDZ-pp for Tc）, and DGDZVP have also been employed in combination with the B3LYP functional to study the basis set effect on the geometries of isomers. The optimized structures agree well with the available experimental data, and the bond lengths are more sensitive to the basis set than the bond angles. The charge distributions were studied by the Mulliken population analysis and natural bond orbital analysis. The results reflect a significant ligand-to-metal electron donation.展开更多
The distribution of ^(125)I recombinant E. coli L-asparaginase in tissues ororgans and the excretion in urine, feces and bile were studied with in vivo radioactive tracertechnique. The amount of radioactivity excreted...The distribution of ^(125)I recombinant E. coli L-asparaginase in tissues ororgans and the excretion in urine, feces and bile were studied with in vivo radioactive tracertechnique. The amount of radioactivity excreted in urine, feces and bile within 24 h afterintravenous administration of ^(125)I recombinant E. col L-asparaginase to rats was 68.95% ,4.44%and 5.36% of the dose respectively. ^(125)I recombinant E. coli L-asparaginase in plasma samples wasdetermined. The levels of structural intact molecule in plasma samples were evaluated by SDS-PAGEand bio-imaging analyzer system. Pharmacokinetic parameters were assessed with a model-dependentmethod. The concentration-time curves of recombinant E. coli L-asparaginase after intravenousinjection at 1 250 IU·kg^(-1), 2 500, IU·kg^(-1), 5 000 IU·kg^(-1) to rats were consistent withthe two-compartment model. The first and terminal elimination t_(1/2) were 0.52 ~ 0.63 h and 2.39 ~2.76 h respectively. AUC was linearly related to the doses. The results of distribution in tissuesor organs and excretion in urine suggested that the metabolites of the enzyme were cleared bymechanisms of urinary excretion. Pharmacokinetics parameters of recombinant E. coli L- asparaginasein rats are warranted for the design of future clinical trials.展开更多
AIM:To assess the clinical role of monoclonal immunoscintigraphy for the detection of metastasis and recurrence of colorectal cancer.METHODS:Monoclonal immunoscintigraphy was performed in patients operated on for colo...AIM:To assess the clinical role of monoclonal immunoscintigraphy for the detection of metastasis and recurrence of colorectal cancer.METHODS:Monoclonal immunoscintigraphy was performed in patients operated on for colorectal adenocar-cinoma suspected of local recurrence and metastatic disease.The results were compared with conventional diagnostics.RESULTS:Immunoscintigraphic investigation was done in 53 patients.Tumor recurrence occurred in 38 patients,and was confirmed by other diagnostic modalities in 35.In 15 patients,immunoscintigraphic findings were negative,and confirmed in 14 with other diagnostic methods.Comparative analysis confirmed good correlation of immunoscintigraphic findings and the results of conventional diagnostics and the level of tumor marker carcinoembryonic antigen.Statistical analysis of parameters of radiopharmaceutical groups imacis,indimacis and oncoscint presented homogenous characteristics all of three radiopharmaceuticals.The analysis of immunoscintigraphic target focus was clearly improved using tomography.CONCLUSION:Immunoscintigraphy is highly specific and has a good predictive value in local recurrence of colorectal cancer.展开更多
Samarium-153- EDTMP (ethylene diamine tetramethylene phosphonate), for its promising biological properties, has been proved as a palliating therapeutic agent for bone tumor in human beings. 153Sin with high radionucl...Samarium-153- EDTMP (ethylene diamine tetramethylene phosphonate), for its promising biological properties, has been proved as a palliating therapeutic agent for bone tumor in human beings. 153Sin with high radionuclear purity and specific activity of 5.18 GBq (140 mCi)/mg Sm2O3 was prepared by irradiating naturalSm2O3(152Sm, 26.7%) sample, replacing costly enriched samarium oxide target, at a flux of 4x 1013n.cm-2.s-1 for 110 h. The yield of 153Sm complexing with EDTMP is greater than 98% at PH 8￣10 in boiling water bath for 30 min, and not significantly decreases within one week after 153Sm-EDTMP complex formation.展开更多
AIM： TO assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus （HCV） infection.METHODS： One hundred chronic HCV infection patients failed in interferon treatment were enr...AIM： TO assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus （HCV） infection.METHODS： One hundred chronic HCV infection patients failed in interferon treatment were enrolled and randomly assigned to receive combined intravenous and oral antioxidants or placebo, or oral treatment alone, Primary end points were liver enzymes, HCV-RNA levels and histology.RESULTS： Combined oral and intravenous antioxidant therapy was associated with a significant decline in ALT levels in 52% of patients who received antioxidant therapy vs 20% of patients who received placebo （P = 0.05）. Histology activity index （HAI） score at the end of treatment was reduced in 48% of patients who received antioxidant therapy vs 26% of patients who received placebo （P = 0.21）. HCV-RNA levels decreased by l-log or more in 28% of patients who received antioxidant therapy vs 12% who received placebo （P = NS）. In part 11 of the trial, oral administration of antioxidants was not associated with significant alterations in any of the end points.CONCLUSION： Antioxidant therapy has a mild beneficial effect on the inflammatory response of chronic HCV infection patients who are non-responders to interferon. Combined antiviral and antioxidant therapy may be beneficial for these patients.展开更多
Solid phase exchange radioiodination method was used to label the compound.Pharmacokinetics was studied in rats and the data were dealt with by computer. The results indicate that the compound would be a potential myo...Solid phase exchange radioiodination method was used to label the compound.Pharmacokinetics was studied in rats and the data were dealt with by computer. The results indicate that the compound would be a potential myocardial imaging agent.展开更多
This work is devoted to obtaining radionuclide-labeled microspheres for radionuclide therapy as a therapeutic drug with a selective method of delivery. The nature of magnetic microspheres and quantitative elemental co...This work is devoted to obtaining radionuclide-labeled microspheres for radionuclide therapy as a therapeutic drug with a selective method of delivery. The nature of magnetic microspheres and quantitative elemental composition radiopreparats was considered. We have developed a new method of producing radionuclide-labeled microspheres （radiopharmaceutical ^140Nd-microspheres） for radionuclide therapy.展开更多
The use of Animal House Facilities of IPEN-CNEN/SP （Nuclear and Energetic Research Institute-National Nuclear Energy Commission/SP, Brazil） has provided rats and mice with controlled sanitary quality for research an...The use of Animal House Facilities of IPEN-CNEN/SP （Nuclear and Energetic Research Institute-National Nuclear Energy Commission/SP, Brazil） has provided rats and mice with controlled sanitary quality for research and quality control in the production of radiopharmaceuticals lots, produced at IPEN, following rules of CONCEA-Brazilian National Council for Animal Experimentation Control and approved in CEUA （Ethics Committee on the Use of Animals）, before they are sent to hospitals and clinics spread out in Brazil, for use in nuclear medicine. The production and the supply of high quality laboratory animals have fundamental importance for the accomplishment of vanguard scientific research, with reproducibility and universality. The quality of those animals depends, largely, on the available facilities for their production and lodging, to assure the demanded sanitary control and animal＇s welfare, in agreement with the ethical principles that control the activity. Therefore, the facilities design is of vital importance so that the mentioned requirements can be reached. Nevertheless, pigs and miniature pigs have gained importance as large animal models in medicine. With their size, organ capacity, and physiology resembling in several aspects that of humans, pigs are well suited for preclinical experiments and long-term safety studies. Minipigs will be used for preclinical testing of radiopharmaceuticals and assays radioactive materials for cardiac tests. This paper describes the premises and preliminary activities that have been performed at IPEN for the design of new Animal House Facilities dedicated to keeping minipigs taking into account fundamental aspects such as： animal＇s welfare, sanitation, genetic, in agreement with the ethical principles that control the activity and environmental concerns.展开更多
The potential use of radionuclides in therapy has been recognized for many decades. A number of radionuclides, such as iodine-131（^131I）, phosphorous-32（^32P）, strontium-90（^90Sr）, and yttrium-90（^90Y）, have b...The potential use of radionuclides in therapy has been recognized for many decades. A number of radionuclides, such as iodine-131（^131I）, phosphorous-32（^32P）, strontium-90（^90Sr）, and yttrium-90（^90Y）, have been used successfully for the treatment of many benign and malignant disorders. Recently, the rapid growth of this branch of nuclear medicine has been stimulated by the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain and neuroendocrine and other malignant or non-malignant tumours. Today, the field of radionuclide therapy is enjoying an exciting phase and is poised for greater growth and development in the coming years. For example, in Asia, the high prevalence of thyroid and liver diseases has prompted many novel developments and clinical trials using targeted radionuclide therapy. This paper reviews the characteristics and clinical applications of the commonly available therapeutic radionuclides, as well as the problems and issues involved in translating novel radionuclides into clinical therapies.展开更多
Objective： To observe effects of the drug-containing serum ofBu Shen Zhuang Gu Capsule （BSZGC 补肾壮骨胶囊 Capsule for Tonifying the Kidney to Strengthen the Bones） on proliferation of the rat＇s osteoclasts and ta...Objective： To observe effects of the drug-containing serum ofBu Shen Zhuang Gu Capsule （BSZGC 补肾壮骨胶囊 Capsule for Tonifying the Kidney to Strengthen the Bones） on proliferation of the rat＇s osteoclasts and tartrate-resistant acid phosphatase （TRACP） activity in vitro so as to delve into the mechanisms of its preventive and therapeutic actions on osteoporosis. Methods： Forty female Sprague-Dawley rats aged three months were randomly divided into high dosage BSZGC group, medium dosage BSZGC group, low dosage BSZGC group, and the control group. BSZGC was orally administered into the rats of high, medium, and low dosage groups at different dosages for 12 days, and isometric normal saline was orally administered to the rats of the control group. The drug-containing serum and control serum were prepared. Osteoclasts isolated mechanically from the femur and tibia of Sprague-Dawley rats aged one week were cultured with medium added with different drug-containing sera and control serum. The growth of osteoclasts was observed under an inverted phase-contrast microscope, and optic density （OD） value of osteoclasts was determined by MTT colorimetric assay. TRACP activity was measured by the diazol method. Results： OD value of osteoclasts in the high dosage drug-containing serum group, medium dosage drug-containing serum group, and low dosage drug-containing serum group was significantly lower than that in the control serum group （P〈0.05） with a dose-effect correlation. TRACP activity in high dosage drug-containing serum group, medium dosage drug-containing serum group, low dosage drug-containing serum group was significantly lower than that of the control serum group （P〈0.01）, and no significant differences in TRACP activity were not found among the different dosages drug-containing serum groups. Conclusions： BSZGC can inhibit the proliferation of the osteoclasts and reduce TRACP activity, which may be one of the mechanisms of its preventive and theraoeutic actions on osteooorosis.展开更多
基金This work was supported by the National Natural Science Foundation of China （No.20801024 and No.21001055）, the Natural Science Foundation of Jiangsu Province （No.BK2009077）, and the Science Foundation of Health Department of Jiangsu Province （No.H200963）.
文摘Density functional theory method has been employed to investigate the structures of the prototypical technetium-labeled diphosphonate complex 99mTc-MDP, where MDP represents methylenediphosphonic acid. A total of 14 trial structures were generated by allowing for the geometric, conformational, charge, and spin isomerism. Based on the optimized structures and calculated energies at the B3LYP/LANL2DZ level, two stable isomers were determined for the title complex. And they were further studied systematically in comparison with the experimental structure. The basis sets 6-31G＊（LANL2DZ for Tc）, 6-31G＊（cc-pVDZ-pp for Tc）, and DGDZVP have also been employed in combination with the B3LYP functional to study the basis set effect on the geometries of isomers. The optimized structures agree well with the available experimental data, and the bond lengths are more sensitive to the basis set than the bond angles. The charge distributions were studied by the Mulliken population analysis and natural bond orbital analysis. The results reflect a significant ligand-to-metal electron donation.
基金ProjectsupportedbytheNationalNinth FivePlanKeyProjectFoundation No 96 90 2 0 1 2 5
文摘The distribution of ^(125)I recombinant E. coli L-asparaginase in tissues ororgans and the excretion in urine, feces and bile were studied with in vivo radioactive tracertechnique. The amount of radioactivity excreted in urine, feces and bile within 24 h afterintravenous administration of ^(125)I recombinant E. col L-asparaginase to rats was 68.95% ,4.44%and 5.36% of the dose respectively. ^(125)I recombinant E. coli L-asparaginase in plasma samples wasdetermined. The levels of structural intact molecule in plasma samples were evaluated by SDS-PAGEand bio-imaging analyzer system. Pharmacokinetic parameters were assessed with a model-dependentmethod. The concentration-time curves of recombinant E. coli L-asparaginase after intravenousinjection at 1 250 IU·kg^(-1), 2 500, IU·kg^(-1), 5 000 IU·kg^(-1) to rats were consistent withthe two-compartment model. The first and terminal elimination t_(1/2) were 0.52 ~ 0.63 h and 2.39 ~2.76 h respectively. AUC was linearly related to the doses. The results of distribution in tissuesor organs and excretion in urine suggested that the metabolites of the enzyme were cleared bymechanisms of urinary excretion. Pharmacokinetics parameters of recombinant E. coli L- asparaginasein rats are warranted for the design of future clinical trials.
基金Supported by A Grant of the Ministry of Science of the Republic of Serbia,No.175018
文摘AIM:To assess the clinical role of monoclonal immunoscintigraphy for the detection of metastasis and recurrence of colorectal cancer.METHODS:Monoclonal immunoscintigraphy was performed in patients operated on for colorectal adenocar-cinoma suspected of local recurrence and metastatic disease.The results were compared with conventional diagnostics.RESULTS:Immunoscintigraphic investigation was done in 53 patients.Tumor recurrence occurred in 38 patients,and was confirmed by other diagnostic modalities in 35.In 15 patients,immunoscintigraphic findings were negative,and confirmed in 14 with other diagnostic methods.Comparative analysis confirmed good correlation of immunoscintigraphic findings and the results of conventional diagnostics and the level of tumor marker carcinoembryonic antigen.Statistical analysis of parameters of radiopharmaceutical groups imacis,indimacis and oncoscint presented homogenous characteristics all of three radiopharmaceuticals.The analysis of immunoscintigraphic target focus was clearly improved using tomography.CONCLUSION:Immunoscintigraphy is highly specific and has a good predictive value in local recurrence of colorectal cancer.
文摘Samarium-153- EDTMP (ethylene diamine tetramethylene phosphonate), for its promising biological properties, has been proved as a palliating therapeutic agent for bone tumor in human beings. 153Sin with high radionuclear purity and specific activity of 5.18 GBq (140 mCi)/mg Sm2O3 was prepared by irradiating naturalSm2O3(152Sm, 26.7%) sample, replacing costly enriched samarium oxide target, at a flux of 4x 1013n.cm-2.s-1 for 110 h. The yield of 153Sm complexing with EDTMP is greater than 98% at PH 8￣10 in boiling water bath for 30 min, and not significantly decreases within one week after 153Sm-EDTMP complex formation.
文摘AIM： TO assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus （HCV） infection.METHODS： One hundred chronic HCV infection patients failed in interferon treatment were enrolled and randomly assigned to receive combined intravenous and oral antioxidants or placebo, or oral treatment alone, Primary end points were liver enzymes, HCV-RNA levels and histology.RESULTS： Combined oral and intravenous antioxidant therapy was associated with a significant decline in ALT levels in 52% of patients who received antioxidant therapy vs 20% of patients who received placebo （P = 0.05）. Histology activity index （HAI） score at the end of treatment was reduced in 48% of patients who received antioxidant therapy vs 26% of patients who received placebo （P = 0.21）. HCV-RNA levels decreased by l-log or more in 28% of patients who received antioxidant therapy vs 12% who received placebo （P = NS）. In part 11 of the trial, oral administration of antioxidants was not associated with significant alterations in any of the end points.CONCLUSION： Antioxidant therapy has a mild beneficial effect on the inflammatory response of chronic HCV infection patients who are non-responders to interferon. Combined antiviral and antioxidant therapy may be beneficial for these patients.
文摘Solid phase exchange radioiodination method was used to label the compound.Pharmacokinetics was studied in rats and the data were dealt with by computer. The results indicate that the compound would be a potential myocardial imaging agent.
文摘This work is devoted to obtaining radionuclide-labeled microspheres for radionuclide therapy as a therapeutic drug with a selective method of delivery. The nature of magnetic microspheres and quantitative elemental composition radiopreparats was considered. We have developed a new method of producing radionuclide-labeled microspheres （radiopharmaceutical ^140Nd-microspheres） for radionuclide therapy.
文摘The use of Animal House Facilities of IPEN-CNEN/SP （Nuclear and Energetic Research Institute-National Nuclear Energy Commission/SP, Brazil） has provided rats and mice with controlled sanitary quality for research and quality control in the production of radiopharmaceuticals lots, produced at IPEN, following rules of CONCEA-Brazilian National Council for Animal Experimentation Control and approved in CEUA （Ethics Committee on the Use of Animals）, before they are sent to hospitals and clinics spread out in Brazil, for use in nuclear medicine. The production and the supply of high quality laboratory animals have fundamental importance for the accomplishment of vanguard scientific research, with reproducibility and universality. The quality of those animals depends, largely, on the available facilities for their production and lodging, to assure the demanded sanitary control and animal＇s welfare, in agreement with the ethical principles that control the activity. Therefore, the facilities design is of vital importance so that the mentioned requirements can be reached. Nevertheless, pigs and miniature pigs have gained importance as large animal models in medicine. With their size, organ capacity, and physiology resembling in several aspects that of humans, pigs are well suited for preclinical experiments and long-term safety studies. Minipigs will be used for preclinical testing of radiopharmaceuticals and assays radioactive materials for cardiac tests. This paper describes the premises and preliminary activities that have been performed at IPEN for the design of new Animal House Facilities dedicated to keeping minipigs taking into account fundamental aspects such as： animal＇s welfare, sanitation, genetic, in agreement with the ethical principles that control the activity and environmental concerns.
文摘The potential use of radionuclides in therapy has been recognized for many decades. A number of radionuclides, such as iodine-131（^131I）, phosphorous-32（^32P）, strontium-90（^90Sr）, and yttrium-90（^90Y）, have been used successfully for the treatment of many benign and malignant disorders. Recently, the rapid growth of this branch of nuclear medicine has been stimulated by the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain and neuroendocrine and other malignant or non-malignant tumours. Today, the field of radionuclide therapy is enjoying an exciting phase and is poised for greater growth and development in the coming years. For example, in Asia, the high prevalence of thyroid and liver diseases has prompted many novel developments and clinical trials using targeted radionuclide therapy. This paper reviews the characteristics and clinical applications of the commonly available therapeutic radionuclides, as well as the problems and issues involved in translating novel radionuclides into clinical therapies.
文摘Objective： To observe effects of the drug-containing serum ofBu Shen Zhuang Gu Capsule （BSZGC 补肾壮骨胶囊 Capsule for Tonifying the Kidney to Strengthen the Bones） on proliferation of the rat＇s osteoclasts and tartrate-resistant acid phosphatase （TRACP） activity in vitro so as to delve into the mechanisms of its preventive and therapeutic actions on osteoporosis. Methods： Forty female Sprague-Dawley rats aged three months were randomly divided into high dosage BSZGC group, medium dosage BSZGC group, low dosage BSZGC group, and the control group. BSZGC was orally administered into the rats of high, medium, and low dosage groups at different dosages for 12 days, and isometric normal saline was orally administered to the rats of the control group. The drug-containing serum and control serum were prepared. Osteoclasts isolated mechanically from the femur and tibia of Sprague-Dawley rats aged one week were cultured with medium added with different drug-containing sera and control serum. The growth of osteoclasts was observed under an inverted phase-contrast microscope, and optic density （OD） value of osteoclasts was determined by MTT colorimetric assay. TRACP activity was measured by the diazol method. Results： OD value of osteoclasts in the high dosage drug-containing serum group, medium dosage drug-containing serum group, and low dosage drug-containing serum group was significantly lower than that in the control serum group （P〈0.05） with a dose-effect correlation. TRACP activity in high dosage drug-containing serum group, medium dosage drug-containing serum group, low dosage drug-containing serum group was significantly lower than that of the control serum group （P〈0.01）, and no significant differences in TRACP activity were not found among the different dosages drug-containing serum groups. Conclusions： BSZGC can inhibit the proliferation of the osteoclasts and reduce TRACP activity, which may be one of the mechanisms of its preventive and theraoeutic actions on osteooorosis.
