Effect of Technetium-99 Conjugated with Methylene Diphosphonate on IgM-RF,IgG-RF and IgA-RF

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.

^(99m)TC-Methylene diphosphonate uptake at injury site correlates with osteoblast differentiation and mineralization during bone healing in mice

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.

Three New Silver Alkylenediphosphonates with Pillar-like Open-frameworks

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.

Effect of dichloromethylene diphosphonate on liver regeneration following thioacetamide-induced necrosis in rats

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.

The value of ^(99m)Tc methylene diphosphonate bone scintigraphy in diagnosing relapsing polychondritis

Relapsing polychondritis （RP） is a recurrent disease involving cartilage mainly of the ear,nose, larynx, trachea, and bronchus. The typical manifestations of the disease in the ear and nose can be easily recognized, but the symptoms could be ignored or easily confused with those of other diseases when the cartilage of other sites is involved. Thus, it is necessary to develop a new technique for the diagnosis of this disease. Few cases of abnormal accumulation of radioactivity at cartilage shown by ^99mTc methylene diphosphonate （MDP） bone scintigraphy are described in the literature. In this report, we present 4 patients of whom 3 had positive findings on ^99mTc MDP bone scintigraphy with an assessment of ^99mTc MDP bone scintigraphy in the diagnosis of RP.

^(99)Tc-MDP对骨重建的影响

双膦酸盐主要用于治疗以破骨细胞活性增加为病理特征的代谢性骨病,包括Paget's骨病(派杰氏病),肿瘤骨转移,恶性肿瘤引起的高钙血症和骨质疏松。从P-O-P结构的焦磷酸盐到P-C-P结构的第三代双膦酸盐,其抗骨吸收的作用随碳链接侧链的延长而增强。锝[99Tc]亚甲基二膦酸盐(99Tc-MDP)是双膦酸盐的一种,其主要成分是锝[99Tc]经氯化亚锡还原后与亚甲基二膦酸盐形成的螯合物,具有稳定的P-C-P键,被骨生成区和带有炎症的骨与软骨组织摄取,不仅有效降低血中免疫调节因子、抑制病理复合物产生;而且多项国内外研究发现,99Tc-MDP免疫调节同时具有抑制破骨细胞活性及修复破骨的作用,引起骨质疏松研究者的关注。本文综述了99Tc-MDP对骨重建影响的研究进展。

Systematic review of atorvastatin for the treatment of Alzheimer's disease

OBJECTIVE： To assess the clinical efficacy and safety of atorvastatin in the treatment of Alzheimer＇s disease. DATA SOURCES： Medline （1948/2011-04）, Embase （1966/2011-04）, Cochrane Library （Issue 3, 2011）, Chinese National Knowledge Infrastructure （1989/2011-04）, and the Chinese Biomedical Literature Database （1979/2011-04） were searched for randomized clinical trials regardless of language. Abstracts of conference papers were manually searched. Furthermore, Current Controlled Trials （http：//controlled-trials.com）, Clinical Trials.gov （http：//clinicaltrials.gov）, and Chinese Clinical Trial Registry （http：//www.chictr.org） were also searched. Key words included AIzheimer disease, dementia, cognition, affection, memory dysfunction, hydroxymethylglutaryI-CoA reductase inhibitors, atorvastatin and statins. DATA SELECTION： Randomized controlled trials of grade A or B according to quality evaluation criteria of the Cochrane Collaboration were selected, in which atorvastatin and placebo were used to evaluate the effects of atorvastatin in the treatment of Alzheimer＇s disease. Study methodological quality was evaluated based on criteria described in Cochrane Reviewer＇s Handbook 5.0.1. Revman 5.1 software was used for data analysis. MAIN OUTCOME MEASURES： Clinical efficacy, safety, withdrawal from the studies, and withdrawal due to adverse effects. RESULTS： Two randomized controlled trials were included, one was scale A, and the other was scale B. All patients （n = 710, age range 50-90 years） were diagnosed as probable or possible mild to moderate Alzheimer＇s disease according to standard criteria and treated with atorvastatin 80 mg/d or placebo. There was no difference between the two groups in the final follow-up for Clinical Global Impression of Change scale （WMD = 0.13, 95%CI： 0.15 to 0.40）, the Alzheimer＇s Disease Assessment Scale-cognitive subscale （WMD = 1.05, 95%C1：-3.06 to 6.05）, Mini-Mental State Examination Scale （WMD = 0.77, 95%CI： 0.57 to 2.10）, and the Neuropsychiatric Instrument （WMD = 2.07, 95%CI： 1.59 to 5.73）. The rates of abnormal liver function, withdrawal from treatment, and withdrawal due to adverse effects were higher in the treatment group （OR = 7.86, 95%CI： 2.50 24.69; OR = 4.70, 95%CI： 2.61 8.44; and OR = 5.47, 95%CI： 3.01-9.94; respectively） compared with the placebo group. CONCLUSION： There is insufficient evidence to recommend atorvastatin for the treatment of mild to moderate AIzheimer＇s disease, because there was no benefit on general function, cognitive function or mental/behavior abnormality outcome measures. Efficacy and safety need to be confirmed by larger and higher quality randomized controlled trials, especially for moderate to severe Alzheimer＇s disease, because results of this systematic review may be limited by selection bias, implementation bias, as well as measurement bias.

Effects of diphosphonic acid on ilmenorutile collecting property and research of action mechanism

The effects of several collectors and their dosage on pure ilmenorutile atdifferent pH values were studied and the collecting strength of several representative collectorswas investigated. The experimental results indicate that diphosphonic acid is a good collector forilmenorutile and the recovery of ilmenorutile ranges from 90.87 percent to 91.70 percent when thepulp pH value is 2.0-4.0 and the dosage is 75 mg/L. The sequence of collecting ability for severalcollectors is as follows: diphosphonic acid> TF279 > cyclic allryl hydroximic acid > benzyl arsenicacid> salicylic hydroximic acid> alkyl hydroximic acid. Meanwhile, IAS (infrared absorptionspectrum) and XPS (X-ray photoelectron spectroscopy) were used to detect and analyze the actionmechanism of diphosphonic acid on ilmenorutile. IAS results showed that the characteristicabsorption peak relating to P=O as well as P-O vibration occurred between wave numeber 1140 and 1032cm^(-1), and diphosphonic acid had adsorbed on the surface of ilmenorutile. XPS results indicatedthat the binding energy of P2P peak of ilmenorutile had changed 0.45 eV after treated bydiphosphonic acid. This proves that the adsorption is mainly chemical adsorption.

Collecting property of diphosphonic acid for niobite

The effect of several collectors on the niobite synthetized under the condition of varying pH values and dosages were studied. The collecting property of several representative collectors was also investigated. The experimental result shows that di- phosphonic acid is a good collector for niobite. Its recovery is about 84.24%-91.17% when the pH value of the pulp is less than 5.0 and the dosage of diphosphonic acid is 140 mg/L. The sequences of the selectivity and collecting capacity of the collectors were compared. Infrared absorption spectrum (IAS) and X-ray photoelectron spectroscopy (XPS) were used to detect and analyze the ad- sorption mechanism of diphosphonic acid on the surface of niobite. The IAS result indicates that diphosphonic acid is indeed ad- sorbed on the surface of niobite, and the XPS result shows that the binding energy of P2p peak of niobite treated by diphosphonic acid has changed 2.85 eV. It confirms that the adsorption belongs to a chemisorption type.

Flotation of niobite,fersmite,and ilmenorutile

The flotation ofniobite, fersmite, and ilmenorutile was studied using 3 collectors with various concentration and pulp pH. The collecting property of different representative collectors was investigated. Experimental results show that diphosphonic acid is an effective collector for valuable niobium-containing minerals. A flotation recovery of 90.87%-91.7% is obtained with 75 mg/L diphosphonic acid at pH 2-4. The chemical adsorption of diphosphonic acid on these 3 minerals＇ surface might lead to the high recovery efficiency of the minerals, which is proved by IR and X-ray photoelectron spectroscopy spectra.