Enhanced Power Factor and Increased Conductivity of Aluminum Doped Zinc Oxide Thin Films for Thermoelectric Applications.

We report the structural, electrical and thermopower properties of un-doped and Al doped zinc oxide (ZnO) thin films. Al doping was carried out using 25 keV Al+ implantation with 0.1, 1 and 2% Al into ZnO. X-ray diffraction measurements showed that the lattice parameters were larger than the bulk values, which is consistent with the incorporation of Al atoms at interstitials. Al doping increased the electrical conductivity from 100 (Ωcm)-1 in the un-doped ZnO film to 598 (Ωcm)-1 in the 2% Al doped ZnO film. Electron doping by Al resulted in an increase in the carrier concentration and it had an advantageous effect on the mobility where it was highest for 2% doping. The absolute value of the Seebeck coefficient systematically increased for un-doped, 1% and 2% Al doped ZnO films where the room temperature values were -50.8, -60.9 and -66.3 µV/K, respectively. The power factor increased significantly from 2.58 × 10-5 W/mK2 in un-doped ZnO film to 2.63 × 10-4 W/mK2 in 2% Al doped ZnO film. Our results suggest that the ion beam method is a suitable technique to enhance the thermoelectric properties of ZnO.

Non-publication and publication bias in reproductive medicine: a cohort analysis.

STUDY QUESTION: Does publication bias or non-publication exist in fertility trials presented as conference abstracts? SUMMARY ANSWER: This study did not detect any publication bias; however, it did identify a high level of non-publication, with only 49% of abstracts reaching full-text publication four or more years after abstract presentation. WHAT IS KNOWN ALREADY: Systematic reviews of randomized controlled trials (RCTs) are the foundation of evidence based medicine. Non-publication or publication deficit refer to the failure to publish trial results. A publication bias exists when there is any tendency on the parts of the investigators or editors to fail to publish study results on the basis or strength of the study findings. Both present a serious problem for researchers, clinicians and policymakers alike, and ultimately impact on patient care. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study identified 337 fertility RCTs presented as conference abstracts between 2007 and 2010, as captured by an electronic search of the Cochrane Gynaecology and Fertility Database. After excluding ineligible trials and duplicates, 224 abstracts remained. PARTICIPANTS/MATERIALS, SETTING, METHODS: A search for the full-text papers of each abstract was undertaken in Pubmed, MEDLINE, Embase, CINAHL and Google in May 2015 using a probabilistic approach. Trial authors were contacted to query the publication status of abstracts when no full-text was identified. The association between individual variables and the probability of publication, and time to publication, was assessed using logistic regression and Cox regression, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 224 included abstracts, only 110 (49%; 95% CI: 42.6, 55.6) were found to be published as full-text articles. Publication bias was not identified in this cohort; studies with positive results had a similar probability of reaching full-text publication 52/113 (46%; 95% CI: 37.0, 55.3) as studies with non-positive (negative or null) results 58/111 (52%; 95% CI: 17.8, 33.9) (adjusted odds ratio (AOR): 1.02; 95% CI: 0.53, 1.97). Similarly, the time from abstract presentation to full-text publication was similar in studies with positive and non-positive results. Oral presentations were more likely to be published, and to be published sooner, than poster presentations (poster presentation AOR: 0.31; 95% CI: 0.15, 0.61 and adjusted hazard ratio (AHR): 0.57; 95% CI: 0.38, 0.86). Studies that were not registered were less likely to be published and to have delayed publication, than studies which were registered either prospectively or retrospectively (AOR: 0.14; 95% CI: 0.04, 0.44 and AHR: 0.43; 95% CI: 0.25, 0.72). Abstracts which were presented a longer time ago also had a higher probability of reaching full-text publication (P  = 0.01). LIMITATIONS, REASONS FOR CAUTION: Commencing with a cohort of RCTs from ethics committee registers may provide a better picture of the extent of non-publication and publication bias, as not all trials reach the stage of abstract presentation. It is also possible that the search did not identify all published trials, as some may have been published after the follow-up period. WIDER IMPLICATIONS OF THE FINDINGS: This study did not identify any publication bias. However, only half of the abstracts in this cohort have been published as full-text articles, four or more years after their presentation at a conference. This is similar to publication rates reported previously for fertility trials, and is despite increasing awareness of the importance of publishing trial results, and subsequent requirements for all RCTs to be registered prior to trial initiation. A better understanding of the reasons for non-publication should assist in facilitating the prompt full-text publication of RCTs in the future. STUDY FUNDING/COMPETING INTEREST(S): Funding provided from the University of Auckland. All authors declare they have no conflicts of interest in relation to this article. TRIAL REGISTRATION NUMBER: Not applicable.

Mifamurtide in metastatic and recurrent osteosarcoma: a patient access study with pharmacokinetic, pharmacodynamic, and safety assessments.

PURPOSE: This non-randomized, patient-access protocol, assessed both safety and efficacy outcomes following liposomal muramyl-tripeptide-phosphatidylethanolamine (L-MTP-PE; mifamurtide) in patients with high-risk, recurrent and/or metastatic osteosarcoma. METHODS: Patients received mifamurtide 2 mg/m(2) intravenously twice-weekly ×12 weeks, then weekly ×24 weeks with and without chemotherapy. Serum concentration-time profiles were collected. Adverse events within 24 hours of drug administration were classified as infusion-related adverse events (IRAE); other AEs and overall survival (OS) were assessed. RESULTS: The study began therapy in January 2008; the last patient completed therapy in October 2012. Two hundred five patients were enrolled; median age was 16.0 years and 146/205 (71%) had active disease. Mifamurtide serum concentrations declined rapidly in the first 30 minutes post-infusion, then in a log-linear manner 2-6 hours post-dose; t1/2 was 2 hours. There were no readily apparent relationships between age and BSA-normalized clearance, half-life, or pharmacodynamic effects, supporting the dose of 2 mg/m(2) mifamurtide across the age range. Patients reported 3,679 IRAE after 7,482 mifamurtide infusions. These were very rarely grade 3 or 4 and most commonly included chills + fever or headache + fatigue symptom clusters. One- and 2-year OS was 71.7% and 45.9%. Patients with initial metastatic disease or progression approximated by within 9 months of diagnosis (N = 40) had similar 2-year OS (39.9%) as the entire cohort (45.9%) CONCLUSIONS: Mifamurtide had a manageable safety profile; PK/PD of mifamurtide in this patient access study was consistent with prior studies. Two-year OS was 45.9%. A randomized clinical trial would be required to definitively determine impact on patient outcomes.

Iron(II) spin crossover complexes of tetradentate Schiff-bases: tuning T1/2 by choice of formyl-heterocycle component.

Four new tetradentate Schiff-base ligands were prepared in situ from the 1 : 2 condensation of 1,3-diaminopropane and either 2-thiazolecarboxaldehyde (L2thiazole), 4-thiazolecarboxaldehyde (L4thiazole), 4-oxazolecarboxaldehyde (L4oxazole), or 5-bromopyridine-2-aldehyde (L5Br-pyridine), and complexed with [Fe(NCS)2(pyridine)4] to give four monometallic FeII complexes, [Fe(Lheterocycle)(NCS)2]. Structural characterisation shows the expected octahedral FeII centres in all cases, with Lheterocycle occupying the equatorial plane and the two thiocyanate ligands trans to each other, resulting in an N6 coordination sphere. Solid state magnetic measurements showed that the two complexes with the thiazole-based ligands exhibit the beginning of a spin transition above 300 K, with T1/2 = 350 K for [Fe(L4thiazole)(NCS)2] and 400 K for [Fe(L2thiazole)(NCS)2], whereas the 4-oxazole-based ligand gives [Fe(L4oxazole)(NCS)2] which remains high spin at all measured temperatures (50-400 K). Interestingly, [Fe(L5Br-pyridine)(NCS)2] crystallised as two solvent-free polymorphs: magnetic measurements on samples with both polymorphs present showed a two step SCO with an abrupt transition at T1/2 = 245 K assigned to the transition in polymorph A (as this was also seen in a sample of pure polymorph A), and a gradual transition at T1/2 = 304 K assigned to polymorph B. These findings show that the order of increasing ligand field strength for these heterocycles is 4-oxazole ≪ 5Br-pyridine < 4-thiazole < 2-thiazole.

Ironsand (Titanomagnetite-Titanohematite): Chemistry, Magnetic Properties and Direct Applications for Wireless Power Transfer.

Ironsand is an abundant and inexpensive magnetic mineral resource. However, the magnetic properties of unprocessed ironsand are often inadequate for any practical applications. In this work, the applicability of ironsand for use as a component in a soft magnetic composite for large-scale inductive power transfer applications was investigated. After magnetic separation, the chemical, structural and magnetic properties of ironsand sourced from different locations were compared. Differences observed in the DC magnetic properties were consistent with changes in the chemical compositions obtained from X-ray Absorption Near-Edge Spectroscopy (XANES), which suggests varying the titanohematite to titanomagnetite content. Increased content in titanomagnetite and magnetic permeability correlated well with the total Fe content in the materials. The best-performing ironsand with the highest permeability and lowest core losses was used alongside Mn,Zn-Ferrite particles (ranging from ∼100 µm to 2 mm) to fabricate toroid cores with varying magnetic material loading. It was shown that ironsand can be used to replace up to 15 wt.% of the magnetic materials with minimal impact on the composite magnetic performance, thus reducing the cost. Ironsand was also used as a supporting material in a single-rail wireless power transfer system, effectively increasing the power transfer, demonstrating potential applications to reduce flux leakage.

Modelling the radioluminescence of Sm2+ and Sm3+ in the dosimeter material NaMgF3:Sm.

Photoluminescence (PL) and radioluminescence (RL) measurements were made on NaMgF3:Sm before, during and after exposure to high doses of ionising radiation. Magnetic measurements prior to irradiation showed that approximately 10% of the total Sm concentration was in the divalent state. The RL from Sm3+ was found to increase while the Sm2+ RL decreased with increasing x-ray dose before reaching steady-state values for high doses. This behaviour is opposite to that previously reported for Sm3+ and Sm2+ PL. We show that this apparent discrepancy can be accounted for by a RL model where there is a hole trap, an electron trap, and direct x-ray induced carrier recombination at Sm2+ and Sm3+. Furthermore, a good fit to the dose-dependence of all of the Sm RL emissions can be obtained by assuming that the relevant electron and hole traps are close to Sm3+. Our model accounts for F3-centre production during irradiation that affects some of the Sm3+ RL emissions via reabsorption of the RL by the F3-centres. Thus, the rate of F3-centre production can be conveniently monitored by the RL intensity ratio, I RL(567 nm)/I RL(650 nm). Additionally, the Sm2+ RL emissions may be expressed as [1.94 × I RL(721 nm)] - I RL(695 nm) to determine the real-time dose rate, independent of dose history.

Electrospun, Oriented, Ferromagnetic Ni 1-x Fe x Nanofibers.

Electrospinning has been used to fabricate ferromagnetic Ni0.47Fe0.53 nanofiber mats that were composed of individual, orientated Ni0.47Fe0.53 nanofibers. The key steps were processing a polyvinylpyrrolidone nanofiber template containing ferric nitrate and nickel acetate metal precursors in Ar at 300°C and then 95% Ar: 5% H2 at 600°C. The Ni0.47Fe0.53 fibers were nanostructured and contained Ni0.47Fe0.53 nanocrystals with average diameters of ~14 nm. The Ni0.47Fe0.53 ferromagnetic mats had a high saturation magnetic moment per formula unit that was comparable to those reported in other studies of nanostructured Ni1-x Fe x . There is a small spin-disordered fraction that is typically seen in nanoscale ferromagnets and is likely to be caused by the surface of the nanofibers. There was an additional magnetic contribution that could possibly stem from a small Fe1-z Ni z O phase fraction surrounding the fibers. The coercivity was found to be enhanced when compared with the bulk material.

Corrigendum: Electrospun, Oriented, Ferromagnetic Ni 1-x Fe x Nanofibers.

[This corrects the article DOI: 10.3389/fchem.2020.00047.].

Strontium ranelate improves bone strength in ovariectomized rat by positively influencing bone resistance determinants.

SUMMARY: Treatment of adult ovariectomized (OVX) rats with strontium ranelate prevented vertebral biomechanics degradation as a result of the prevention of bone loss and micro-architecture deterioration associated to an effect on intrinsic bone material quality. Strontium ranelate influenced the determinants of bone strength by prevention of ovariectomy-induced changes which contribute to explain strontium ranelate antifracture efficacy. INTRODUCTION: Strontium ranelate effects on the determinants of bone strength in OVX rats were evaluated. METHODS: Adult female Sprague-Dawley rats were OVX, then treated daily for 52 weeks with 125, 250, or 625 mg strontium ranelate/kg. Bone strength, mass, micro-architecture, turnover, and intrinsic quality were assessed. RESULTS: Strontium ranelate prevented ovariectomy-induced deterioration in mechanical properties with energy necessary for fracture completely maintained vs. SHAM at 625 mg/kg/day, which corresponds to the clinical dose. This was related to a dose-dependent effect on bone volume, higher trabeculae number, and lower trabecular separation in strontium ranelate vs. OVX. Load and energy required to induce lamella deformation were higher with strontium ranelate than in OVX and in SHAM, indicating that the bone formed with strontium ranelate is able to withstand greater damage before fracture. Bone formation was maintained high or even increased in strontium ranelate as shown by mineralizing surfaces and alkaline phosphatase while strontium ranelate led to reductions in deoxypyridinoline. CONCLUSION: Strontium ranelate administered at 625 mg/kg/day for 52 weeks prevented OVX-induced biomechanical properties deterioration by influencing the determinants of bone strength: it prevented bone loss and micro-architecture degradation in association with an effect on intrinsic bone quality. These beneficial effects on bone contribute to explain strontium ranelate antifracture efficacy.

Unusual 209Bi NMR quadrupole effects in topological insulator Bi2Se3.

Three-dimensional topological insulators are an important class of modern materials, and a strong spin-orbit coupling is involved in making the bulk electronic states very different from those near the surface. Bi2Se3 is a model compound, and 209Bi NMR is employed here to investigate the bulk properties of the material with focus on the quadrupole splitting. It will be shown that this splitting measures the energy band inversion induced by spin-orbit coupling in quantitative agreement with first-principle calculations. Furthermore, this quadrupole interaction is very unusual as it can show essentially no angular dependence, e.g., even at the magic angle the first-order splitting remains. Therefore, it is proposed that the magnetic field direction is involved in setting the quantization axis for the electrons, and that their life time leads to a new electronically driven relaxation mechanism, in particular for quadrupolar nuclei like 209Bi. While a quantitative understanding of these effects cannot be given, the results implicate that NMR can become a powerful tool for the investigation of such systems.

Loss of cancellous bone mass and connectivity in ovariectomized rats can be restored by combined treatment with parathyroid hormone and estradiol.

To evaluate the potential use of a combination of antiresorption and bone formation-promoting agents as a treatment for postmenopausal osteoporosis, we examined the effects of combined and separate administration of estrogen (17 beta-estradiol, 30 micrograms/kg per d, s.c.) and parathyroid hormone (rPTH [1-34], 40 micrograms/kg per d, s.c.) on the proximal tibia of ovariectomized (Ovx) rats. The treatments lasted for 4 wk and were initiated 1, 3, and 5 wk after surgery. Ovx resulted in rapid loss of cancellous bone volume (Cn-BV/TV) as well as trabecular connectivity, as determined by two dimensional strut analysis. When administered in a preventive mode, treatment beginning 1 wk post-Ovx, estrogen or PTH treatment alone preserved Cn-BV/TV and trabecular connectivity, and combined estrogen and PTH treatment caused a 40% increment in Cn-BV/TV while maintaining comparable trabecular connectivity with that seen in the Sham-operated animals. When administered in a curative mode to rats with established osteoporosis, treatments beginning 3 or 5 wk post-Ovx, estrogen or PTH treatment alone prevented further loss of connectivity and Cn-BV/TV, whereas the combined treatment resulted in as much as a 300% improvement in one of the parameters of trabecular connectivity, node to node strut length, and a 106% increase in Cn-BV/TV, with respect to the bone status at the initiation of treatment. The beneficial effects of this combined treatment derive from estrogen's ability to prevent accelerated bone resorption and, simultaneously, PTH's promotion of bone formation. These data demonstrate, in an animal model, that therapies can be devised to cure the skeletal defects associated with established osteoporosis.

Effects of reciprocal treatment with estrogen and estrogen plus parathyroid hormone on bone structure and strength in ovariectomized rats.

Intermittent administration of PTH has been found to be an effective anabolic agent in cancellous bone. We have reported previously that combined treatment with PTH and estrogen in estrogen-deficient rats was beneficial in correcting established osteopenia. To determine if the beneficial effects of PTH therapy can be preserved by estrogen alone and whether PTH therapy can be effective in treating osteopenic subjects stabilized with estrogen, we have undertaken a "crossover" study in the rat model of estrogen-deficiency induced osteopenia. Six-month-old female rats were ovariectomized and after 5 wk treated for 8 wk with vehicle, 30 micrograms/kg per day of rPTH(1-34) plus 15 micrograms/kg per day of 17 beta-estradiol or 17 beta-estradiol alone. One group from each treatment regimen was then sacrificed and for an additional 8 weeks the remaining rats were (a) maintained on their previous treatment; (b) "crossed over" to their reciprocal treatment; or (c) administered vehicle only. At the end of this second 8-wk treatment period all rats were sacrificed. Bone mineral density of the distal femur, histomorphometric measurements of the proximal tibia and mechanical testing of the distal femur and selected vertebral bodies were performed. Our results demonstrated that (a) the gains in bone mass, trabecular connectivity and mechanical strength induced by PTH can be maintained by estrogen alone, but are reversed when both agents are withdrawn; and (b) rats with established osteopenia, maintained on estrogen treatment alone, can derive the full beneficial effects from the addition of PTH to the treatment at a later date. These data indicate that combined and/or sequential use of antiresorptive and anabolic agents may be a promising approach to the treatment of osteoporosis.

Efficacy and safety of rasburicase, a recombinant urate oxidase (Elitek), in the management of malignancy-associated hyperuricemia in pediatric and adult patients: final results of a multicenter compassionate use trial.

The recombinant urate oxidase, rasburicase (Elitek, Sanofi-Synthelabo, Inc.), has recently received regulatory approval for the prevention and treatment of hyperuricemia in children with leukemia, lymphoma, and solid tumors. Prior to approval, 682 children and 387 adults in the US and Canada received rasburicase on compassionate-use basis. Uric acid concentration declined rapidly in both adult and pediatric patients after rasburicase treatment. Similar responses were observed in patients treated with subsequent courses. Possible drug-related adverse events, including allergic reactions, were uncommon. These data confirm that rasburicase is effective and safe for the treatment and prophylaxis of children and adults with malignancy-associated hyperuricemia.

A high affinity, calmodulin-responsive (Ca2+ + Mg2+)-ATPase in isolated bone cells.

Although acute alterations in Ca2+ fluxes may mediate the skeletal responses to certain humoral agents, the processes subserving those fluxes are not well understood. We have sought evidence for Ca2+-dependent ATPase activity in isolated osteoblast-like cells maintained in primary culture. Two Ca2+-dependent ATPase components were found in a plasma membrane fraction: a high affinity component (half-saturation constant for Ca2+ of 280 nM, Vmax of 13.5 nmol/mg per min) and a low affinity component, which was in reality a divalent cation ATPase, since Mg2+ could replace Ca2+ without loss of activity. The high affinity component exhibited a pH optimum of 7.2 and required Mg2+ for full activity. It was unaffected by potassium or sodium chloride, ouabain or sodium azide, but was inhibited by lanthanum and by the calmodulin antagonist trifluoperazine. This component was prevalent in a subcellular fraction which was also enriched in 5'-nucleotidase and adenylate cyclase activities, suggesting the plasma membrane as its principal location. Osteosarcoma cells, known to resemble osteoblasts in their biological characteristics and responses to bone-seeking hormones, contained similar ATPase activities. Inclusion of purified calmodulin in the assay system caused small non-reproducible increases in the Ca2+-dependent ATPase activity of EGTA-washed membranes. Marked, consistent calmodulin stimulation was demonstrated in membranes exposed previously to trifluoperazine and then washed in trifluoperazine-free buffer. These results indicate the presence of a high affinity, calmodulin-sensitive Ca2+-dependent ATPase in osteoblast-like bone cells. As one determinant of Ca2+ fluxes in bone cells, this enzyme may participate in the hormonal regulation of bone cell function.

Layered tungsten oxide-based organic-inorganic hybrid materials: an infrared and Raman study.

Tungsten oxide-organic layered hybrid materials have been studied by infrared and Raman spectroscopy and demonstrate a difference in bonding nature as the length of the interlayer organic "spacer" molecule is increased. Ethylenediamine-tungsten oxide clearly displays a lack of terminal -NH3(+) ammonium groups which appear in hybrids with longer organic molecules, thus indicating that the longer chains are bound by electrostatic interactions as well as or in place of the hydrogen bonding that must be present in the shorter chain ethylenediamine hybrids. The presence of organic molecules between the tungsten oxide layers, compared with the layered tungstic acid H2WO4, shows a decrease in the apical W=O bond strength, as might be expected from the aforementioned electrostatic interaction.

A phase I clinical, pharmacological, and biological trial of interleukin 6 plus granulocyte-colony stimulating factor after ifosfamide, carboplatin, and etoposide in children with recurrent/refractory solid tumors: enhanced hematological responses but a high incidence of grade III/IV constitutional toxicities.

A Phase I trial was conducted to determine the safety, biological activity, and hematopoietic recovery by the combination of interleukin 6 (IL-6) and granulocyte-colony stimulating factor (G-CSF) after myelosuppressive chemotherapy in children. Patients <22 years of age at diagnosis with either recurrent or refractory solid tumors received ifosfamide 1,800 mg/m2/day x 5 days, carboplatin 400 mg/m2/ day x 2 days, and etoposide 100 mg/m2/day x 5 days, followed by daily s.c. G-CSF (5 microg/kg/day) and IL-6 (2.5, 3.75, or 5.0 microg/kg/day). Pharmacokinetic, proinflammatory mediator levels, hematopoietic colony assays, and cytokine receptor expression studies were performed during course one. Nineteen patients were evaluable for toxicity and received IL-6 at doses of 2.5 (n = 8), 3.75 (n = 5), or 5.0 (n = 6) microg/kg/day. Dose-limiting constitutional toxicity occurred in two of six patients at 5.0 microg/kg/day, two of five patients at 3.75 microg/kg/day, and two of eight patients at 2.5 microg/kg/day. The maximum tolerated dose (MTD) exceeded the lowest dose tested. Because of lack of drug availability, an MTD was not established. The maximum concentration of IL-6 (2.5 microg/kg/day) was 0.799 +/- 1.055 ng/ml (mean +/- SD). During the first course, the median time to absolute neutrophil count > or = 1,000/mm3 and platelets > or = 100,000 mm3 was estimated at 19 and 23 days, respectively. Peripheral blood progenitor cells expressing receptors to IL-3, IL-6, and G-CSF increased significantly over baseline (P < 0.05). After the first dose of IL-6, IFN-gamma levels were abnormal in 13 patients, and IL-1beta levels were abnormal in 10 patients. IL-6 has a high incidence of constitutional toxicity and a lower MTD in children compared with adults. In vivo use of IL-6 in children after chemotherapy remains limited. However, IL-6 may be more optimally investigated in children under ex vivo conditions.

Assessment of effects of lanthanum carbonate with and without phosphate supplementation on bone mineralization in uremic rats.

AIMS: Previous studies have indicated that impaired bone mineralization in 5/6 th nephrectomized rats given high doses of lanthanum carbonate is due to phosphorus depletion caused by excessive binding to, and reduced absorption of, dietary phosphate. This study aimed to test this hypothesis by: 1) directly comparing the effects of a supratherapeutic dose of lanthanum carbonate or dietary phosphorus restriction on bone mineralization in a rodent model of chronic renal failure (CRF); and 2) investigating whether phosphorus supplementation would prevent the bone mineralization defect associated with lanthanum carbonate treatment. METHODS AND MATERIALS: Male Sprague-Dawley rats were subjected to sham surgery or a two-step 5/6th nephrectomy to induce CRF and randomized across five treatment groups: sham, CRF, CRF + dietary phosphorus deficiency, CRF + lanthanum carbonate (1000 mg/kg/ day), and CRF + lanthanum carbonate + parenteral phosphorus repletion. RESULTS: Rats with 5/6th nephrectomy had elevated serum creatinine, blood urea concentration, and urine volume and protein, consistent with impaired renal function, and increased urinary phosphorus and serum parathyroid hormone, consistent with hyperparathyroidism. Lanthanum carbonate and dietary phosphate insufficiency induced parallel changes in serum and urine markers of phosphate homeostasis and increased osteoid formation. These changes induced by lanthanum carbonate were normalized by systemic phosphate supplementation. CONCLUSIONS: These findings provide further support for the concept that supratherapeutic doses of lanthanum carbonate induce effects on bone mineralization in uremic rats via an indirect pharmacological mechanism (phosphate depletion) and not via direct bone toxicity.

Oral 1,25-dihydroxyvitamin D administration in osteoporotic women: effects of estrogen therapy.

Estrogen has been shown to modify calcium and skeletal homeostasis. In this study, we tested the ability of estrogen to influence the effects of short-term 1,25(OH)2D administration on biochemical indices of bone formation and resorption in a cross-sectional analysis of untreated (n = 10) and estrogen-treated (n = 14) osteoporotic women. Patients were given oral 1,25(OH)2D (Rocaltrol) 0.5 microgram twice a day for 5 days. Serum and urine were sampled at baseline and then 1 h after the first daily Rocaltrol dose for the 5 days of the study. 1,25(OH)2D levels rose similarly in both groups with plateaus reached by the third day of the investigation. Serum PTH levels decreased by the first sampling period (1 h after first Rocaltrol dose; p < 0.008 both groups) and continued to fall gradually in both groups. There were no changes in serum calcium but serum phosphorus rose by the second day (p < 0.05 both groups) and remained elevated throughout the remainder of the protocol. Serum bone Gla protein increased approximately 40% (p < 0.05) with no group differences. In contrast, total alkaline phosphatase and carboxy-terminal propeptide of type I collagen did not increase in either group. Furthermore, there were no significant increments in any bone resorption indicators, including serum tartrate-resistant acid phosphatase and cross-linked carboxy-terminal telopeptide of type I collagen, as well as urine hydroxyproline and pyridinoline. Serum IGF-1 levels also remained unchanged in both groups. We conclude that oral 1,25(OH)2D administration decreased 1-84PTH levels, probably due to a suppression of parathyroid production, and did not stimulate bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)

High-dose glucocorticoids in multiple sclerosis patients exert direct effects on the kidney and skeleton.

The effects of acute pharmacologic steroid treatment on skeletal and mineral metabolism were assessed in 56 multiple sclerosis patients who were to receive 1 g intravenous methylprednisolone for 10 days, followed by a 4 day intravenous and 28 day oral glucocorticoid taper. Serum and urine samples were obtained at baseline and then within 3 days, 1, 2, and 3 weeks after beginning steroids. A subset of patients (n = 11) had sampling throughout the 6 weeks of steroid administration and up to 8 weeks afterward. All mean basal biochemistries were normal except 25(OH)D, which was in the "insufficient" range (25-50 nM) at 10 nM. During and after steroid administration, there were no changes in ionized calcium, 25(OH)D, urinary hydroxyproline, or pyridinoline. There was an increase in 1,25(OH)2D and a decrease in serum phosphorus, accompanied by an increase in urinary phosphate clearance, within 3 days of administration (p < 0.006). Serum osteocalcin (BGP) decreased to below assay sensitivity limits within 3 days of steroid administration (p < 0.0002), increasing thereafter but remaining at 50% of baseline by the third week. PTH(1-84) increased to a peak at week 2 (p < 0.02), after both the 1,25(OH)2D peak and the serum phosphorus nadir. Tartrate-resistant acid phosphatase, urinary calcium, and urinary cyclic AMP all increased above baseline (p < 0.05) with a pattern similar to that of PTH. To investigate further the immediate effects of steroid administration, serum samples were obtained at the same four times on both the day before and the day after the first intravenous methylprednisolone dose in a randomly chosen subset of patients (n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

Prostaglandins change cell shape and increase intercellular gap junctions in osteoblasts cultured from rat fetal calvaria.

Mounting experimental evidence indicates that osteoblasts may be cellular intermediaries in the local activation of bone remodeling. To elucidate the role of these cells in activation, we examined the effects of prostaglandins (PGs), known resorption stimulators, on cell shape and intercellular junctional relationships in osteoblasts cultured from rat fetal calvaria. Exposure to PGE2 and PGE1, promoters of bone resorption, rapidly (within 20 min) converted the osteoblasts from a flattened to a stellate shape (shape change), and markedly increased the appearance of intercellular (gap) junctions within 10 min. Both effects were directly related to the prostaglandin concentration, as little as 1 nM being effective. PGE1, but not PGB1, PGF1 alpha, PGD2, and PGF2 alpha, mimicked the substantial effect of PGE2 on shape change. Shape change and gap junction formation appear to arise independently. PTH, an inducer of shape change, did not affect the number of gap junctions appreciably. Colchicine, a microtubule polymerization inhibitor, and trifluoperazine, an inhibitor of calmodulin action, blunted PGE2-mediated shape change but not the effect of PGE2 on gap junctions. Shape change and gap junction formation may be important events in local activation, shape changes in surface osteoblasts serving to expose bone surfaces which are chemotactic for osteoclasts and gap junctions propagating locally initiated activation messages.