SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
A novel, three-dimensional copper diphosphonate Cu4(CH3C(OH)(PO3)2)2(C4H4N2)(H2O)4 (1) incorporating an organic pyrazine ligand has been hydrothermally synthesized, which exhibits antiferromagnetic ordering below 4.2 K and metamagnetic behavior.
The kinetics of the reaction between dioxouranium(VI) and benzene-1,2-diphosphonic acid (BzDPA) has been investigated by stopped-flow spectrophotometry. The rate of reaction of uranyl ions with Arsenazo III (2,7-bis(2,2'-arsonophenylazo)-1,8-dihydroxynaphthalene-3,6-disulfonic acid) in 50:50 methanol-water solutions was also determined. Both formation and dissociation rate constants for the 1:1 complex between uranyl-BzDPA in acidic solutions were resolved. To gain insight into the effect of solvation on the progress of the reaction, the system was studied in triply distilled water, in 50:50 methanol-water, 80:20 methanol-water and in 50:50 tert-butanol-water as a function of temperature at pH 1.0. The rates of complex formation and dissociation reactions decrease as methanol substitutes for water in the medium and further decrease as tert-butanol replaces methanol as co-solvent. Activation parameters are most consistent with an associative process governing the progress of both complex formation and dissociation reactions. Introduction of alcoholic co-solvents results in notably more negative activation entropies for both complex formation and dissociation reactions, while the activation enthalpies are only slightly reduced in the mixed methanol-water medium. These results are compared with the kinetic features of other U(VI) systems.
Decreased intestinal absorption of Ca2+ occurs in response to treatment with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP). The effect is due to decreased 1-hydroxylation of calcidiol (25-hydroxycholecalciferol) in the kidney. In an attempt to establish whether impairment of vitamin D metabolism at steps beyond kidney hydroxylation occurs due to treatment with EHDP, chicks were depleted of vitamin D and were treated with calcitriol (1,25-dihydroxycholecalciferol) as their sole source of the vitamin. The chicks were then divided into two groups, one being treated with EHDP while the second group served as control. Intestinal absorption of Ca2+ in the EHDP-treated group was found to be impaired, along with decreases in concentrations of calbindin D28K (the 28,000-Mr vitamin D-dependent Ca2+-binding protein). When the chicks were dosed with [3H]calcitriol, significantly lower concentrations of the sterol were detected in the duodena of EHDP-treated birds. Measurement of levels of receptors for calcitriol in duodena showed no difference between groups, but levels of calcitriol in sera were considerably lower in the EHDP-treated group along with the elevated biliary and urinary excretion of glucuronidated conjugates. It is therefore concluded that treatment with EHDP results in increased catabolism of calcitriol in addition to the known suppression of the renal production of the hormone.
1. Ligated intestinal segments from rats treated with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at the daily dose of 16 mumol (identical to 1 mg of phosphorus)/kg subcutaneously for 7 days show an increased rate of calcium absorption. 2. This dose of EHDP enhances the intestinal accumulation of a vitamin D3 metabolite with the chromatographic characteristics of 1,25-dihydroxycholecalciferol.
1. The short- and longer-term effects of ethane-1-hydroxy-1,1-diphosphonate (EHDP), an inhibitor of crystal growth and potential preventive agent against urinary tract stones in man, have been studied. 2. Measurement of urinary excretion of EHDP was used to define the best dosage regimen. When 4.4 mmol of EHDP mmol of EHDP was given in four divided doses the murinary concentration of EHDP achieved was high enough (10-5 mol/1) to inhibit the crystallization of calcium crystals throughout the day. 3. Nine patients with recurrent calcium stones were given this dose of EHDP daily for 12 months and seven were then studied for a further 12 months under placebo. During treatment with EHDP, inhibitory activity in urine towards precipitation of calcium phosphate was restored from low values to greatly above normal. This could be accounted for by the inhibitory effect of EHDP itself, coupled with an increase in urinary inorganic pyrophosphate. After stopping EHDP the excretion of EHDP rapidly fell to undetectable levels but the excretion of pryophosphate remained elevated throughout the 12 months of placebo treatment. EHDP also induced a rise in plasma phosphate and an increase in the urinary excretion of oxalic acid and uric acid, but these changes were all fully reversible when EHDP was stopped. 4. The average rate of stone formation per patient per year decreased from 2.4 to 0.2 during treatment with EHDP and remained low during the following 24 months. However, the dose needed for this effect is known to affect bone turnover and mineralization.
1. The effects of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) and colchicine on acid--base balance were examined in intact and nephrectomized rats. 2. Both drugs increased extracellular hydrogen ion concentrations and depressed extracellular bicarbonate concentrations in nephrectomized rats compared with controls but did not alter these parameters in intact animals. 3. Intracellular hydrogen ion concentrations in the skeletal muscle of nephrectomized rats given EHDP were higher than those of control animals. 4. It is postulated that colchicine and EHDP inhibit skeletal buffering of non-volatile acids produced endogenously in nephrectomized rats.
1. Protein-binding assays have been used to measure plasma 1,25-dihydroxy-vitamin D [1,25-(OH)2D] as well as 25-hydroxy-vitamin D [25-(OH)D] in rats given 10 mg of phosphorus (P) day(-1) kg(-1) as ethane-1-hydroxy-1,1-diphosphonate (EHDP). 2. In control animals given a normal laboratory chow plasma 25-(OH)D and 1,25-(OH)2D were about 40 nmol/l and 300 pmol/l respectively. 3. EHDP produced a decrease of plasma 1,25-(OH)2D to below 50 pmol/l in 2 days. 4. Both in control and in EHDP-treated rats plasma 1,25-(OH)2D increased when dietary calcium (Ca) was restricted to 0.1%, or dietary P to 0.2%, indicating that the well-known stimulatory effect of Ca or P deprivation was at least partially effective in EHDP-treated rats. 5. In response to an increase of the oral supply of vitamin D3 to 65 nmol/day the plasma level of 25-(OH)D rose in both control and EHDP groups. Plasma 1,25-(OH)2D was not increased above the normal value in control rats. In EHDP-treated rats, however, plasma 1,25-(OH)2D rose to a level equal to that in controls, suggesting that the effect of EHDP on plasma 1,25-(OH)2D can be overcome at high precursor concentration.
99mTechnetium methylene diphosphonate (MDP) bone isotope may accumulate in many extra-osseous sites due to a variety of both benign and malignant conditions. This finding on a bone scan can be crucial to the diagnosis and may not be apparent in other imaging or the clinical evaluation of the patient. We present a pictorial review sampling some of the many causes of extra-osseous 99mTc MDP accumulation.
Treatment of osteoporosis with a complete reconstruction of the normal three dimensional architecture of trabecular bone is an unsolved problem. In addition to the well established fluoride therapy new concepts in the treatment of osteoporosis were developed. There is growing interest in the so called ADFR concept (activation, depression of resorption, formation, repeat the cycle) as a physiological stimulation of osteoblastic bone formation. The histological results following ADFR treatment in 8 patients are reported. After 12 months of treatment with parathyroid hormone [1-38)hPTH) (stimulation of the basic metabolic units) and the diphosphonate EHDP (depression of osteoclastic resorption) no change of remodelling processes at the trabecular bone surface could be observed. The results demonstrate many doubts in the importance of the ADFR concept for the treatment of osteoporosis.
Incubation of purified rat brain tubulin with guanosine 5'-methylene diphosphonate [GMP(CH2)P] (1 mM), a GDP analog resistant to hydrolysis, results in the polymerization of 20-30% of the total tubulin present. Analogous incubations with GDP (1 mM) do not result in tubulin polymerization. Polymerization with GMP(CH2)P occurs in the presence of alkaline phosphatase (EC 3.1.3.1) under conditions that completely hydrolyze the likely phosphate donors (GTP, GDP, and GMP) as well as the potential product [GMP(CH2)PP] of the transphosphorylase activity present in purified tubulin preparations. Tubulin polymerization in vitro thus can occur in the absence of gamma-phosphate and phosphate bond hydrolysis at the exchangeable nucleotide-binding site of tubulin. Polymerization of tubulin by GMP(CH2)P is neither prevented nor reversed by concentrations of calcium (2 mM) that prevent microtubule assembly and disrupt already formed microtubules induced by GTP. However, tubulin polymerized with GMP(CH2)P is readily depolymerized by cold (4 degrees, 30 min). The possible involvement of GTP alpha-beta bond hydrolysis must be considered seriously as playing a role in the process of microtubule depolymerization.
PURPOSE: To investigate the immunological basis for the prolonged corneal allograft survival after subconjunctival injections of liposomes filled with dichloromethylene diphosphonate (Cl2MDP-LIP). METHODS: F344 rats received orthotropic DA corneal grafts. One group of rats was treated with subconjunctival injections of Cl2MDP-LIP on days 0, 2, 4, 6 and 8 postoperatively, the control groups received no treatment. Nineteen or 42 days postoperatively cytotoxic T lymphocyte (CTL) activity was measured in the lymph nodes draining the grafted and the contralateral eyes, in the spleen and the mesenteric lymph nodes. Sera taken at the same time points were tested for presence of lytic alloantibodies. RESULTS: On day 19 CTL activity in submandibular lymph nodes draining the grafted eyes was similar in the 2 groups. In the mesenteric lymph nodes high CTL activity was found in the untreated rats and low in the Cl2MDP-LIP rats. The spleen showed high CTL activity in the untreated group but no activity in the liposome group. Forty two days postoperatively a decline in CTL activity was seen in both groups. Complement dependent anti-donor antibodies were absent in the Cl2MDP-LIP group at both time points whereas antibodies were present on days 19 and 42 in the untreated group. CONCLUSIONS: Repeated subconjunctival injection of Cl2MDP-LIP restricts the induction of cellular cytotoxicity against donor antigens to the regional lymph nodes and suppresses cytotoxic antibody formation.
The beneficial effect of ethane 1-hydroxy-1, 1-diphosphonate (EHDP) in restoring the inhibition of bone formation in cases of acute uranium intoxication is presented. Bone formation was studied histomorphometrically in a model of alveolar bone healing. After tooth extraction, 40 rats were divided into 4 groups that received (1) no further treatment, (2) 10 daily intraperitoneal injections of 7.5 mg/kg of body weight of EHDP, (3) an intraperitoneal injection of 2.0 mg/kg of body weight of uranyl nitrate, and (4) the same treatment as was provided rats in groups 2 and 3. The results showed that the healing of bone did not occur in exposed animals, whereas healing in EHDP-treated exposed animals did not differ from that of nonexposed controls. This effect might result from a blocking and/or competitive action of EHDP and/or the stimulation that EHDP elicits at the doses and in the administration period studied.
We have used cryoelectron microscopy to try to understand the structural basis for the role of GTP hydrolysis in destabilizing the microtubule lattice. We have measured a structural difference introduced into microtubules by replacing GTP with guanylyl-(alpha,beta)-methylene-diphosphonate (GMPCPP). In a stable GMPCPP microtubule lattice, the moiré patterns change and the tubulin subunits increase in size by 1.5 A. This information provides a clue to the role of hydrolysis in inducing the structural change at the end of a microtubule during the transition from a growing to a shrinking phase.
The aim of this study is to investigate the myeloprotective effects of different amifostine regimens in rabbits undergoing high-dose treatment with 186Rhenium-(tin)1,1-hydroxyethylidene diphosphonate (186Re-HEDP) and to analyze the impact of amifostine on the bone uptake of the radiopharmaceutical. All animals were treated with 1000 MBq 186Re-HEDP. Group ReA received 500 mg amifostine prior to radionuclide therapy, group ReA3 received 3 x 200 mg amifostine 24 hours and 30 minutes prior to and 24 hours after radionuclide therapy. Group ReC served as control receiving no amifostine. Scintigrams were acquired to quantify the skeletal uptake of 186Re-HEDP, and platelet and leucocyte counts were measured. The mean decrease in platelets was 36% +/- 2%, 37% +/- 3%, and 61% +/- 5% for ReA, ReA3, and ReC, respectively. The decrease in ReC was significantly higher than in amifostine-treated animals with no difference between ReA and ReA3. For the leucocytes the mean decrease was 75% +/- 12%, 82% +/- 5%, and 73% +/- 4%, with no significant differences between the respective groups. Bone uptake of 186Re-HEDP was significantly reduced by 50% in ReA and ReA3 compared to ReC. Thus, the 3-day amifostine regimen had no advantage over the single dose regimen, with both regimens reducing bone uptake and yielding a platelet-protective but no leucoprotective effect.
Detectability of bone metastases from differentiated thyroid carcinoma by technetium-99m hydroxymethylene diphosphonate ([99m]Tc-HMDP) bone scan is considered to be poor. Thallium-201 (201Tl) is also widely used for detecting metastatic lesions. Our present study was aimed at the evaluation of the combined use of (99m)Tc-HMDP and 201Tl imaging in successful detection of bone metastases from differentiated thyroid carcinoma. Twenty-seven thyroidectomized thyroid cancer patients (19 females, 8 males; 12 papillary type, 15 follicular type) with 77 bone lesions were included in this retrospective study. All of these patients received ablative doses of radioiodine. Thyroidal origin of the lesions was proved by positive iodine-131 (131I) uptake. In 131I-negative lesions, histological proof or absence of tumor markers other than thyroglobulin was considered when computed tomography (CT) and/or magnetic resonance imaging (MRI) suggested metastatic nature of the lesions. Of the 77 lesions, 58 (75.3%) were positive and 19 were negative in the (99m)Tc-HMDP bone scintigraphy, whereas 53 lesions (68.9%) could be detected by 201Tl scintigraphy. However, within the 19 (99m)Tc-HMDP-negative lesions, 14 showed abnormal accumulation of 201Tl, and within the 24 201Tl negative lesions, 19 were positive in (99m)Tc-HMDP scan. This resulted in a combined sensitivity of 93.5%. Our present study concludes that combined (99m)Tc-HMDP and 201Tl imaging is a sensitive and effective method for detecting bone metastases from thyroid carcinoma.
The role of macrophages in the toxicity and efficacy of liposomal amphotericin B (L-Amp B) was studied in a murine aspergillosis model infection. Macrophages and polymorphonuclear phagocytes (PMN cells) were depleted in the liver and spleen of mice by the administration of liposome encapsulated dichloromethylene diphosphonate. Macrophage depletion had no effect on the lethality of Fungizone, a commercial deoxycholate preparation of Amp B, but significantly increased the lethality of L-Amp B (P < 0.01). Macrophage depletion led to an increase in the fungal loads in the lung, liver and kidney (P < 0.05) and to an increase in the virulence of aspergillosis (P < 0.05). Tissue distribution analysis of L-Amp B revealed that in macrophage/PMN-depleted mice there was a decrease in the concentration of Amp B in the liver, with concomitant increases in the circulation, spleen and lung, both in the uninfected and in the infected conditions. The results clearly demonstrate that depletion of macrophage/PMN cells increases the virulence of aspergillosis, as well as the toxicity of L-Amp B. Moreover, L-Amp B treatment does not improve the survival rate of macrophage/PMN-depleted mice subjected to aspergillosis challenge.
White Leghorn cockerols were fed a semipurified diet (containing fluoride at 0 to 800 ppm) from the day of hatching. The birds were also injected daily with solutions containing ethane-1-hydroxy-1,1-diphosphonate (EHDP) at concentrations ranging from 5 to 20 mg as phosphorus/kg of body weight or isotonic saline. Changes in bone mineral composition and plasma Ca, Mg and F were determined as well as alterations in bone pyrophosphatase and the amounts of bone cyclic-3',5'-adenosine monophosphate (cAMP). Since dietary fluoride in high amounts is known to stimulate new bone formation, the purpose of the study was to assess whether a potent inhibitor of mineralization, such as EHDP, might alter the response to high dietary fluoride. Although bone fluoride and magnesium were increased in relationship to dietary fluoride, the administration of EHDP had little effect on these changes at low to moderate levels of fluoride. The levels of soluble bone pyrophosphatase were not greatly influenced by changes in dietary fluoride. Administration of EHDP at 20 mg P/kg, however, typically decreased the levels of bone pyrophosphatase. Bone cAMP did not appear to be influenced by either dietary fluoride or EHDP. Using tissue culture techniques, the effects of fluoride on calcium uptake and release from embryonic chick bone were also studied. The presence of 1 mM fluoride in the medium appeared to stimulate calcium uptake and reduced calcium release from chick bone. In general, the results were in keeping with previous suggestions that the major effect of fluoride on bone is the formation of fluoroapatite and subsequent effects this may have on other metabolic alterations.
There are only a few papers in the literature in which parameters related to bone strength are examined over wide range of fluoride concentrations. In this report, chicks were used and fed diets containing fluoride added at 0, 50, 200, or 800 ppm in preparation for measurements on bone strength. The diets were fed for 20 days. After 10 days, the birds were also injected daily with solutions containing either isotonic saline or 5 mg of ethane-1-hydroxy-1,1-diphosphonate (EHDP) as phosphorus/kg body weight or 10 mg of EHDP as phosphorus/kg body weight. The effects of added fluoride and EHDP on bone morphology and the biomechanical properties of bone were then examined. The rate of bone formation was assessed using histological and tetracycline labeling techniques. Administration of high fluoride and/or EHDP resulted in significant changes in bone morphology. The changes effected by the administration of EHDP appeared independent of fluoride induced changes. Biomechanical studies also indicated that both high levels of fluoride and EHDP caused a significant reduction in bone torsional breaking strength. The reductions in breaking strength were independent of changes in body size.