AIM: To study the effect of dichloromethylene diphos-phonate (DMDP), a selective Kupffer cell toxicant in reference to liver damage and postnecrotic liver regeneration in rats induced by sublethal dose thioacetamide (...AIM: To study the effect of dichloromethylene diphos-phonate (DMDP), a selective Kupffer cell toxicant in reference to liver damage and postnecrotic liver regeneration in rats induced by sublethal dose thioacetamide (TA). METHODS: Rats, intravenously (iv ) pre-treated with a single dose of DMDP (10 mg/kg), were intraperitoneally (ip ) injected with TA 6.6 mmol/kg (per 500 mg/kg body weight). Hepatocytes were isolated from rats at 0, 24, 48 and 72 h following TA intoxication and blood and liver samples were obtained. To evaluate the mecha-nisms involved in the postnecrotic regenerative state, DNA distribution and ploidy time course were assayed in isolated hepatocytes. Circulating cytokine tumor necrosis factor-alpha (TNF-α) was assayed in serum and determined by reverse transcriptase-polymerase chain reaction in liver extract. RESULTS: The effect of DMDP induced noticeable changes in postnecrotic regeneration, causing an increased percentage of hepatocytes in the cell cycle S phase. The increase at 24 h in S1 population in rats pretreated with DMDP + TA was significantly (P < 0.05) different compared with that of the TA group (18.07% vs 8.57%). Hepatocytes increased their proliferation as a result of these changes. Also, TNF-α expression and serum level were increased in rats pre-treated with DMDP. Thus, DMDP pre-treatment reduced TA-induced liver injury and accelerated postnecrotic liver regeneration. CONCLUSION: These results demonstrate that Kupffer cells are involved in TA-induced liver, as well as in post-necrotic proliferative liver states.展开更多
Three new silver alkylenediphosphonates, [Ag2（HO3PCH2CH2CH2CH2PO3H）] 1, [Ag4（O3PCH2CH2CH2CH2PO3）] 2 and [Ag4（O3PCH2CH2CH2PO3（H2O）] 3, have been hydrotherreally synthesized and characterized by X-ray single-crys...Three new silver alkylenediphosphonates, [Ag2（HO3PCH2CH2CH2CH2PO3H）] 1, [Ag4（O3PCH2CH2CH2CH2PO3）] 2 and [Ag4（O3PCH2CH2CH2PO3（H2O）] 3, have been hydrotherreally synthesized and characterized by X-ray single-crystal and powder diffraction, elemental analyses, IR and thermogravimetric analyses （TGA）. The structures of these compounds are all threedimensional pillar-like open-frameworks with 18-membered [Ag2O4P4C8] channels for compound 1 and 2, and 16-member [Ag2O4P4C6] channels for compound 3. Both 2 and 3 contain interesting twodimensional Ag（Ⅰ） networks based on Ag...Ag interactions. 1,4-Butylene- and 1,3-propylene diphosphonate groups of 2 and 3 bond the first and second maximum metal atoms among metal organodiphosphonates with linking sixteen and fifteen silver（Ⅰ） atoms, respectively. In addition, the coordinated water molecules of 3 can be reversibly removed and recovered.展开更多
To explore the effect of technetium-99 conjugated with methylene diphosphonate ( 99 Tc-MDP) on IgM-RF, IgG-RF and IgA-RF (RFs), 47 cases were selected for study, including 33 patients with rheumatoid arthritis (RA...To explore the effect of technetium-99 conjugated with methylene diphosphonate ( 99 Tc-MDP) on IgM-RF, IgG-RF and IgA-RF (RFs), 47 cases were selected for study, including 33 patients with rheumatoid arthritis (RA) and 15 patients with joint pain/arthritis. After 99 Tc-MDP for drips model being given to the patients by intravenous drip 0.2 g daily for 5 days, the injection A and B models of 99 Tc-MDP were used to the patients by intravenous injection one set daily for 10 days, that was one course of treatment. The next course started after 10 days. Each case used it from 2 to 4 courses of treatment. The RFs in serum were determined by the method of enzyme-linked immunoabsorption assay (ELISA) before and after 2 and 4 courses of treatment. In the patients with RA, the concentrations of IgM-RF were 296.2±108.4 IU/ml, 189.5±92.3 IU/ml and 107.8±72.5 IU/ml; the concentrations of IgG-RF were 325.6±126.2 IU/ml, 209.7±98.2 IU/ml and 160.2±80.8 IU/ml; the concentrations of IgA-RF were 330.4±136.3 IU/ml, 210.7±89.2 IU/ml and 148.8±72.2 IU/ml before and after 2 and 4 courses of treatment, respectively. The concentrations of the above RFs were significantly lower after 2 and 4 courses than those before treatment ( P <0.05 and P <0.01). There was no significant difference in RFs concentrations in the patients with joint pain/arthritis before and after use of 99 Tc-MDP. In the patients with positive RFs before treatment, the RFs concentrations were decreased significantly after 2 and 4 courses of treatment ( P <0.05 and P <0.01). There was no obvious change of RFs concentrations in the patients with negative RFs after treatment of 99 Tc-MDP. It was concluded that 99 Tc-MDP could obviously reduce the abnormally high concentrations of RFs, but not influence the normal RFs, which indicated that 99 Tc-MDP has an important effect on controlling the activities of RA.展开更多
99mTc-Methylene diphosphonate （99mTc-MDP） is widely used in clinical settings to detect bone abnormalities. However, the mechanism of 99mTc-MDP uptake in bone is not well elucidated. In this study, we utilized a mou...99mTc-Methylene diphosphonate （99mTc-MDP） is widely used in clinical settings to detect bone abnormalities. However, the mechanism of 99mTc-MDP uptake in bone is not well elucidated. In this study, we utilized a mouse tibia injury model, single-photon emission computed tomography （gamma scintigraphy or SPECT）, ex vivo micro-computed tomography, and histology to monitor 99mTc-MDP uptake in injury sites during skeletal healing. In an ex vivo culture system, calvarial cells were differentiated into osteoblasts with osteogenic medium, pulsed with 99mTc-MDP at different time points, and quantitated for 99mTc-MDP uptake with a gamma counter. We demonstrated that 99mTc-MDP uptake in the injury sites corresponded to osteoblast generation in those sites throughout the healing process. The 99mTc-MDP uptake within the injury sites peaked on day 7 post-injury, while the injury sites were occupied by mature osteoblasts also starting from day 7. ~mTc-MDP uptake started to decrease 14 days post-surgery, when we observed the highest level of bony tissue in the injury sites. We also found that 99mTc-MDP uptake was associated with osteoblast maturation and mineralization in vitro. This study provides direct and biological evidence for 99mTc-MDP uptake in osteoblasts during bone healing in vivo and in vitro.展开更多
背景:阿仑膦酸钠升高绝经后妇女骨密度的效果较为显著,伊班膦酸钠是新近研制的第三代二膦酸盐。由于两种药物的给药途径、时间均不相同,关于其疗效差异性存在一定的争论,但缺乏足够的循证医学依据。目的:分析伊班膦酸钠在治疗绝经后骨...背景:阿仑膦酸钠升高绝经后妇女骨密度的效果较为显著,伊班膦酸钠是新近研制的第三代二膦酸盐。由于两种药物的给药途径、时间均不相同,关于其疗效差异性存在一定的争论,但缺乏足够的循证医学依据。目的:分析伊班膦酸钠在治疗绝经后骨质疏松与阿仑膦酸钠对比的临床疗效。方法:通过检索自1994年8月至2014年8月期间中国学术期刊全文数据库(CNKI)、美国国立医学图书馆生物医学信息检索系统(Pubmed)、万方数据库(CECDB)、英国医学会电子全文期刊数据库(BMA)、中文科技期刊数据库(VIP)、维普中文科技期刊全文数据库(CQVIP)、中国生物医学文献数据库(CBM)、荷兰医学文摘数据库(EMbase)、学术期刊集成全文数据库(ASP)、考克兰图书馆(The Cochrane Library)、西文生物医学期刊文献数据库(EMCC)等数据库内相关的随机对照试验(RCT),对所纳入研究文献进行资料提取及严格的质量评测,使用Stata/SE version 12.0软件对所纳入的研究进行Meta分析。结果与结论:(1)最终纳入RCT共10篇、共725例患者,其中379例使用伊班膦酸钠,346例使用阿仑膦酸钠;(2)Meta分析结果显示:与使用阿仑膦酸钠的患者相比,在使用伊班膦酸钠治疗半年后患者腰椎骨密度含量显著升高[P=0.174、I^2=29.4%,WMD=0.03、95%CI=(0.01,0.04)];1年内的骨折发生率显著降低[P=5.810、I^2=0%,OR=0.32、95%CI=(0.10,1.00)];(3)对于经治疗1年时的腰椎骨密度及经治疗半年内的骨折发生率,Meta分析显示两种药物未见显著差异性;(4)与阿仑膦酸钠相比,使用伊班膦酸钠治疗绝经后骨质疏松可提升经治疗6个月后患者腰椎骨密度,降低治疗1年内患者的骨折概率,疗效确切。展开更多
文摘AIM: To study the effect of dichloromethylene diphos-phonate (DMDP), a selective Kupffer cell toxicant in reference to liver damage and postnecrotic liver regeneration in rats induced by sublethal dose thioacetamide (TA). METHODS: Rats, intravenously (iv ) pre-treated with a single dose of DMDP (10 mg/kg), were intraperitoneally (ip ) injected with TA 6.6 mmol/kg (per 500 mg/kg body weight). Hepatocytes were isolated from rats at 0, 24, 48 and 72 h following TA intoxication and blood and liver samples were obtained. To evaluate the mecha-nisms involved in the postnecrotic regenerative state, DNA distribution and ploidy time course were assayed in isolated hepatocytes. Circulating cytokine tumor necrosis factor-alpha (TNF-α) was assayed in serum and determined by reverse transcriptase-polymerase chain reaction in liver extract. RESULTS: The effect of DMDP induced noticeable changes in postnecrotic regeneration, causing an increased percentage of hepatocytes in the cell cycle S phase. The increase at 24 h in S1 population in rats pretreated with DMDP + TA was significantly (P < 0.05) different compared with that of the TA group (18.07% vs 8.57%). Hepatocytes increased their proliferation as a result of these changes. Also, TNF-α expression and serum level were increased in rats pre-treated with DMDP. Thus, DMDP pre-treatment reduced TA-induced liver injury and accelerated postnecrotic liver regeneration. CONCLUSION: These results demonstrate that Kupffer cells are involved in TA-induced liver, as well as in post-necrotic proliferative liver states.
基金This research was supported by grants from the State Key Laboratory of Structure Chemistry, Fujian Institute of Research on the Structure of Matter, the National Ministry of Science and Technology of China (001CB1089), Chinese Academy of Sciences (CAS), the National Science Foundation of China (20273073, 20333070 and 90206040), the National Science Foundation of Fujian Province (2003J042, 2004J041, Z0513022 and 2004HZ01-1)
文摘Three new silver alkylenediphosphonates, [Ag2（HO3PCH2CH2CH2CH2PO3H）] 1, [Ag4（O3PCH2CH2CH2CH2PO3）] 2 and [Ag4（O3PCH2CH2CH2PO3（H2O）] 3, have been hydrotherreally synthesized and characterized by X-ray single-crystal and powder diffraction, elemental analyses, IR and thermogravimetric analyses （TGA）. The structures of these compounds are all threedimensional pillar-like open-frameworks with 18-membered [Ag2O4P4C8] channels for compound 1 and 2, and 16-member [Ag2O4P4C6] channels for compound 3. Both 2 and 3 contain interesting twodimensional Ag（Ⅰ） networks based on Ag...Ag interactions. 1,4-Butylene- and 1,3-propylene diphosphonate groups of 2 and 3 bond the first and second maximum metal atoms among metal organodiphosphonates with linking sixteen and fifteen silver（Ⅰ） atoms, respectively. In addition, the coordinated water molecules of 3 can be reversibly removed and recovered.
文摘To explore the effect of technetium-99 conjugated with methylene diphosphonate ( 99 Tc-MDP) on IgM-RF, IgG-RF and IgA-RF (RFs), 47 cases were selected for study, including 33 patients with rheumatoid arthritis (RA) and 15 patients with joint pain/arthritis. After 99 Tc-MDP for drips model being given to the patients by intravenous drip 0.2 g daily for 5 days, the injection A and B models of 99 Tc-MDP were used to the patients by intravenous injection one set daily for 10 days, that was one course of treatment. The next course started after 10 days. Each case used it from 2 to 4 courses of treatment. The RFs in serum were determined by the method of enzyme-linked immunoabsorption assay (ELISA) before and after 2 and 4 courses of treatment. In the patients with RA, the concentrations of IgM-RF were 296.2±108.4 IU/ml, 189.5±92.3 IU/ml and 107.8±72.5 IU/ml; the concentrations of IgG-RF were 325.6±126.2 IU/ml, 209.7±98.2 IU/ml and 160.2±80.8 IU/ml; the concentrations of IgA-RF were 330.4±136.3 IU/ml, 210.7±89.2 IU/ml and 148.8±72.2 IU/ml before and after 2 and 4 courses of treatment, respectively. The concentrations of the above RFs were significantly lower after 2 and 4 courses than those before treatment ( P <0.05 and P <0.01). There was no significant difference in RFs concentrations in the patients with joint pain/arthritis before and after use of 99 Tc-MDP. In the patients with positive RFs before treatment, the RFs concentrations were decreased significantly after 2 and 4 courses of treatment ( P <0.05 and P <0.01). There was no obvious change of RFs concentrations in the patients with negative RFs after treatment of 99 Tc-MDP. It was concluded that 99 Tc-MDP could obviously reduce the abnormally high concentrations of RFs, but not influence the normal RFs, which indicated that 99 Tc-MDP has an important effect on controlling the activities of RA.
基金supported by the Van Andel Research Instituteby a grant to BOW from the NIH/NIAMS (AR053293)
文摘99mTc-Methylene diphosphonate （99mTc-MDP） is widely used in clinical settings to detect bone abnormalities. However, the mechanism of 99mTc-MDP uptake in bone is not well elucidated. In this study, we utilized a mouse tibia injury model, single-photon emission computed tomography （gamma scintigraphy or SPECT）, ex vivo micro-computed tomography, and histology to monitor 99mTc-MDP uptake in injury sites during skeletal healing. In an ex vivo culture system, calvarial cells were differentiated into osteoblasts with osteogenic medium, pulsed with 99mTc-MDP at different time points, and quantitated for 99mTc-MDP uptake with a gamma counter. We demonstrated that 99mTc-MDP uptake in the injury sites corresponded to osteoblast generation in those sites throughout the healing process. The 99mTc-MDP uptake within the injury sites peaked on day 7 post-injury, while the injury sites were occupied by mature osteoblasts also starting from day 7. ~mTc-MDP uptake started to decrease 14 days post-surgery, when we observed the highest level of bony tissue in the injury sites. We also found that 99mTc-MDP uptake was associated with osteoblast maturation and mineralization in vitro. This study provides direct and biological evidence for 99mTc-MDP uptake in osteoblasts during bone healing in vivo and in vitro.
文摘背景:阿仑膦酸钠升高绝经后妇女骨密度的效果较为显著,伊班膦酸钠是新近研制的第三代二膦酸盐。由于两种药物的给药途径、时间均不相同,关于其疗效差异性存在一定的争论,但缺乏足够的循证医学依据。目的:分析伊班膦酸钠在治疗绝经后骨质疏松与阿仑膦酸钠对比的临床疗效。方法:通过检索自1994年8月至2014年8月期间中国学术期刊全文数据库(CNKI)、美国国立医学图书馆生物医学信息检索系统(Pubmed)、万方数据库(CECDB)、英国医学会电子全文期刊数据库(BMA)、中文科技期刊数据库(VIP)、维普中文科技期刊全文数据库(CQVIP)、中国生物医学文献数据库(CBM)、荷兰医学文摘数据库(EMbase)、学术期刊集成全文数据库(ASP)、考克兰图书馆(The Cochrane Library)、西文生物医学期刊文献数据库(EMCC)等数据库内相关的随机对照试验(RCT),对所纳入研究文献进行资料提取及严格的质量评测,使用Stata/SE version 12.0软件对所纳入的研究进行Meta分析。结果与结论:(1)最终纳入RCT共10篇、共725例患者,其中379例使用伊班膦酸钠,346例使用阿仑膦酸钠;(2)Meta分析结果显示:与使用阿仑膦酸钠的患者相比,在使用伊班膦酸钠治疗半年后患者腰椎骨密度含量显著升高[P=0.174、I^2=29.4%,WMD=0.03、95%CI=(0.01,0.04)];1年内的骨折发生率显著降低[P=5.810、I^2=0%,OR=0.32、95%CI=(0.10,1.00)];(3)对于经治疗1年时的腰椎骨密度及经治疗半年内的骨折发生率,Meta分析显示两种药物未见显著差异性;(4)与阿仑膦酸钠相比,使用伊班膦酸钠治疗绝经后骨质疏松可提升经治疗6个月后患者腰椎骨密度,降低治疗1年内患者的骨折概率,疗效确切。
