bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermal Rearrangements of (Arylimino)diaziridines by Simultaneous Cascades of Pericyclic Reactions
Authors: Quast Helmut , Ross Karl‐Heinz , Philipp Gottfried 
Published: February 2010

Abstract(Arylimino)diaziridines rearrange in several cascade reactions at temperatures 60–100 °C. Those that possess unoccupied ortho positions yield fluorescent 3‐amino‐2H‐indazoles and 2‐amino‐1H‐benzimidazoles. If both ortho positions are blocked by methyl groups, indazoles are not formed and deeply yellow 2‐imino‐2,3‐dihydro‐3aH‐benzimidazoles are formed, which partly dimerize through Diels–Alder reaction or regenerate the aromatic system by formal loss of CH2. In addition, one of the methyl groups of 2,6‐dimethylphenyl rings is involved in a [1,7] H shift affording orthoquinonoid intermediates which undergo 1,6‐electrocyclization to furnish 2‐amino‐3,4‐dihydroquinazolines. The formation of five‐membered ring heterocycles is interpreted in terms of valence isomerization by [1,3] N shift to yield elusive 1‐aryl‐3‐iminodiaziridines as first step. These immediately experience triaza‐Cope rearrangement to benzimidazole derivatives or electrocyclic opening of the N–C bond to generate conjugated azomethine imines (1,5‐dipoles), followed by their 1,5‐electrocyclization to indazoles. First‐order rate constants of the decay of (arylimino)diaziridines refer to the [1,3] N shifts as rate‐determining steps. They are larger than the corresponding rate constants for alkylsubstituted iminodiaziridines.
Journal of Bone and Mineral Research
Authors: DR. Briançon D. , D'Aranda P. , Quillet P. , Duplan B. , Chapuy M. C. , Arlot M. , Meunier P. J. 
Published: February 2010

Abstract
To assess whether an interval of a few hours would be advisable between an intake of sodium fluoride (NaF) and that of calcium salts when treating osteoporotic patients with vertebral collapse, we carried out three pharmacokinetic studies in 12 healthy fasting volunteer subjects to compare the fluoride bioavailability provided by NaF alone and NaF combined with two calcium salts. The results were as follows: (1) When NaF is accompanied by calcium, the fluoride peak level is lower and delayed. (2) Fluoride absorption varied greatly among individuals in both experiments, but none of the 6 subjects proved to be nonabsorbers. (3) The areas under the curves obtained with each of the three preparations were not significantly different, but 24-h urinary fluoride was significantly lower in volunteers receiving simultaneously NaF and calcium salts than in volunteers receiving only NaF.
Journal of Bone and Mineral Research
Authors: Dr. Zerwekh Joseph E. , Padalino Paulette K. , Pak Charles Y. C. , Morris Alan C. , Gottschalk Frank 
Published: February 2010

Abstract
We examined the effect of fluoride (F) on intracellular ionic calcium [Ca2+]i in normal human osteoblasts maintained in culture. Cells were grown on glass coverslips to near-confluency and loaded with the Ca-sensitive dye, fura-2AM. Fluorescence changes were monitored in single cells using an inverted microscope coupled by fiberoptic to a microspectrofluoremeter. The addition of F (100 ng/mL) to the medium promoted a rapid and significant increase in free [Ca2+]i from a resting level of 245 ± 36 SE nM to a peak concentration of 440 ± 51 nM (p &lt; 0.04). This increase in [Ca2+]i began at 10–20 s after addition of F and was maximal by 30 s. Intracellular [Ca2+]i levels then returned to near resting values by 60–80 s after F addition. This response was evident with as little as 25 ng/ml of fluoride and was dose dependent up to 500 ng/ml. At concentrations greater than 500 ng/ml, there appeared to be an attenuation of the rise in [Ca2+]i. The observed rise in [Ca2+]i was dependent on extracellular calcium since lowering extracellular calcium concentration or incubation with calcium channel blockers abolished the response. This observation supports a role of increased [Ca2+]i as one of the initial events of fluoride on action osteoblasts.
Journal of Bone and Mineral Research
Authors: Schnitzler Christine M. , Mesquita Julia M. , Gear Ann K. , Robson Heather J. , Wing Jeffrey R. , Smyth Amelia E. 
Published: February 2010

Abstract
We attempted to identify risk factors for the development of lower limb stress fractures during fluoride therapy for osteoporosis (OP). We compared 18 patients who developed 41 such fractures (26 periarticular, 6 femoral neck, 5 long bone shaft, 1 greater trochanter and 3 pubic rami fractures) during fluoride therapy, with 24 similarly treated patients who did not develop stress fractures. Treatment consisted of sodium fluoride 0.99 mg/kg per day, elemental calcium 1 g/day, and vitamin D. We obtained a previous fracture history, annual radiographs of the spine (fractures), hands (metacarpal cortical index, MCI) and pelvis (Singh index, femoral cortical index), three-monthly serum fluoride and alkaline phosphatase levels, and pretreatment transiliac bone biopsies (routine histomorphometry). The stress fracture group was found to have, before treatment: lower MCI (p &lt; 0.05), lower trabecular bone volume (p &lt; 0.05), a lower number of trabeculae (p &lt; 0.05), greater trabecular separation (p &lt; 0.05), less extensive eroded surfaces (p &lt; 0.05), a lower double/single tetracycline label ratio (p &lt; 0.05); and during treatment: more new spinal fractures (p &lt; 0.05) and higher serum alkaline phosphatase levels (p &lt; 0.01). We conclude that stress fracture patients had more severe trabecular and cortical OP and possibly a poorer bone-forming capacity before therapy than patients without stress fractures. We suspect that fluoride therapy may temporarily further weaken bone and so lead to stress fractures in severely osteoporotic patients. To prevent stress fractures we recommend that fluoride therapy be commenced before OP is profound and that lower fluoride dosage, or intermittent therapy be employed in patients with cortical as well as trabecular OP, especially when alkaline phosphatase levels rise above 1.6 times the upper limit of normal, or when new spinal fractures develop.
Journal of Bone and Mineral Research
Authors: Melton L. Joseph 
Published: February 2010

Abstract
Age-related fractures, especially hip fractures, produce sufficient morbidity and mortality to make osteoporosis a disease worth preventing, and accurate techniques exist to identify groups at high risk of fracture by virtue of low bone mass. While the need for prevention is evident, no specific program of fluoride use for this purpose has been devised, and epidemiologic data provide little support for the notion that exposure to fluoride reduces hip fracture incidence. At present, fluoride cannot be recommended as a prophylactic agent for the fractures that are the primary adverse health outcome of osteoporosis.
Journal of Bone and Mineral Research
Authors: Kraenzlin M. E. , Kraenzlin C. , Farley S. M. G. , Fitzsimmons R. J. , Baylink D. J. 
Published: February 2010

Abstract
In this study, the relationship between fluoride pharmacokinetics and the response in spinal bone density to fluoride treatment was studied in 14 patients with primary osteoporosis treated with fluoride for at least 1 year. Serum concentrations and urinary excretion of fluoride were determined after ingestion of 10 mg fluoride as monofluorophosphate. The pharmacokinetic parameters were calculated according to a linear one-compartment open model. The fasting serum fluoride level was 8.8 ± 0.98 μmol/liter. The peak serum fluoride level was 20.5 ± 1.4 μmol/liter and was reached within 2 h after ingestion of fluoride. When the patients were divided into good and poor responders, based on whether they did or did not exhibit a change in spinal bone density of 13 mg/cc per year or more, we found that good responders had decreased renal fluoride clearance (−62 ± 13%, p &lt; .02), increased maximum change in serum fluoride (+38 ± 18%, p &lt; .01), increased extrarenal clearance (+62 ± 57%, p &lt; .05) and increased change in serum alkaline phosphatase (ALP) (+241 ± 169%, p &lt; 0.02) compared with poor responders. Our data suggest that one factor accounting for a good response is a relatively high serum level of fluoride. However, although the maximum change in serum fluoride was greater in good responders compared with poor responders, variations in fluoride levels could not explain all of the variation in spinal bone density. Therefore, we propose that in addition to differences in serum fluoride, other factors are also responsible for the good response.
Journal of Bone and Mineral Research
Authors: Professor Carter Dennis R. , Beaupré Gary S. 
Published: February 2010

Abstract
Bone mass and architecture in appendicular and most axial sites is controlled primarily by the tissue-loading history. We introduce a conceptual framework for understanding how fluoride treatment alters this control and can cause systemic increases in bone mass. Due to possible adverse influences of fluoride on the mineralized tissue physical characteristics, however, the increase in bone mass does not necessarily result in an increase in bone strength. Using engineering analyses of bone trabeculae, we calculate the losses in trabecular strength which can be caused by the presence of hypomineralized or hypermineralized fluorotic tissue. Significant increases in bone volume fraction and bone mass may be required to overcome these strength deficits.
Journal of Bone and Mineral Research
Authors: DR. Ekstrand Jan , Spak Carl-Johan 
Published: February 2010

Abstract
This report reviews some aspects of fluoride pharmacokinetics in relation to the treatment of osteoporosis. The bioavailability of conventional plain NaF tablets has been shown to be close to 100, for sustained-release NaF tablets close to 90%, and for enteric-coated NaF tablets 65%. The simultaneous intake of food and/or calcium tablets reduces the bioavailability by 30 to 40%. Fluoride renal clearance is influenced by both urinary pH and flow and the clinical consequences of this is discussed. Studies on plasma kinetics of fluoride during chronic fluoride intake suggests that a plasma sample taken at mid-dosage intervals will give reproducible “mean steady-state” levels. It is suggested that improvements of the clinical benefit of fluoride therapy in osteoporosis might be achieved if the dosage regimen were based on the pharmacokinetic properties of the fluoride preparation used as well as plasma fluoride monitoring.
Journal of Bone and Mineral Research
Authors: Okuda A. , Kanehisa J. , Heersche J. N. M. 
Published: February 2010

Abstract
It is not clear to what extent the increased bone mass observed in vertebral trabecular bone of fluoride-treated mammals is a consequence of effects of fluoride on the number and activity of osteoclasts or of osteoblasts. In the present communication, we have analyzed the effects of NaF on the activity of isolated rabbit osteoclasts cultured on thin slices of devitalized compact bovine bone. Osteoclastic resorption was quantitated by counting the number of resorption lacunae and measuring their surface area and their depth using scanning electron microscopy. Our results show that NaF in concentrations of 0.5–1.0 mM decreased the number of resorption lacunae made by individual osteoclasts and decreased the resorbed area per osteoclast. We argue that the concentration of fluoride in these experiments may be within the range “seen” by osteoclasts in mammals treated for prolonged periods with approximately 1 mg of NaF/kg body weight (bw) per day.
Journal of Bone and Mineral Research
Authors: Boivin Georges , Chavassieux Pascale , Chapuy Marie-Claire , Meunier Pierre J. , Baud Charles A. 
Published: February 2010

Abstract
Histomorphometric analysis of undecalcified sections was performed in transiliac biopsy cores taken from 29 patients (16 men, 13 women, aged 51 ± 17 years) suffering from skeletal fluorosis due to chronic exposure to fluoride. The origin of the exposure, known in 20 patients, was either hydric (endemic or sporadic), or industrial, or in a few cases iatrogenic. Measured on calcined bone using a specific ion electrode, bone fluoride content was significantly high in each specimen (mean ± SD: 0.79 ± 0.36% of bone ash) as compared to control values (&lt; 0.10%). The radiologically evident osteosclerosis observed in each patient was confirmed by the significant increase of cancellous bone volume (40.1 ± 11.2 vs. 19.0 ± 2.8% in controls, p &lt; 0.0001). There were significant increases in cortical width (1292 ± 395 vs. 934 ± 173 μm, p &lt; 0.0001) and porosity (14.4 ± 6.4 vs. 6.5 ± 1.7%, p &lt; 0.002), but without reduction of cortical bone mass. Osteoid parameters were significantly increased in fluorotic patients. The increase in cancellous osteoid perimeter was almost threefold greater than that noted in cancellous eroded perimeter. The fluorotic group had a greater number of osteoblasts than controls, with a very high proportion of flat osteoblasts. In 15 patients doubly labeled with tetracycline, the mineral apposition rate was significantly decreased, while mineralization lag time significantly increased. Bone formation rate and adjusted apposition rate were significantly decreased in skeletal fluorosis. Cancellous wall width was normal in fluorosis but the formation period and active formation period were significantly increased. Skeletal fluorosis is thus characterized by an unbalanced coupling in favor of bone formation, and also by a great number of osteoblasts with a high proportion of flat osteoblasts. These osteoblasts have a very increased formation period mainly due to a prolonged inactive formation period. Our results support the view that fluoride may have a dual effect on osteoblasts: an increased birthrate at the tissue level, and a toxic effect at the individual cell level. The addition of these two effects represents, however, a marked increase of bone formation at the organ level.
Cross‐cutting moraines reveal evidence for North Atlantic influence on glaciers in the tropical Andes
Authors: Smith Jacqueline A. , Rodbell Donald T. 
Published: February 2010

AbstractSurface exposure dating of boulders on an exceptionally well‐preserved sequence of moraines in the Peruvian Andes reveals the most detailed record of glaciation heretofore recognised in the region. The high degree of moraine preservation resulted from dramatic changes in the flow path of piedmont palaeoglaciers at the southern end of the Cordillera Blanca (10° 00′ S, 77° 16′ W), which, in turn, generated a series of cross‐cutting moraines. Sixty 10Be surface exposure ages indicate at least four episodes of palaeoglacier stabilisation (>65, ca. 65, ca. 32 and ca. 18–15 ka) and several minor advances or stillstands on the western side of the Nevado Jeulla Rajo massif. The absence of ages close to the global Last Glacial Maximum (ca. 21 ka) suggests that if an advance culminated at that time any resulting moraines were subsequently overridden. The timing of expanded ice cover in the central Peruvian Andes correlates broadly with the timing of massive iceberg discharge (Heinrich) events in the North Atlantic Ocean, suggesting a possible causal connection between southward migration of the Intertropical Convergence Zone during Heinrich events and a resultant increase in precipitation in the tropical Andes. Copyright © 2010 John Wiley & Sons, Ltd.
Heterodyne interferometric polarization coherent anti‐Stokes Raman scattering (HIP‐CARS) spectroscopy
Authors: Orsel K. , Garbacik E. T. , Jurna M. , Korterik J. P. , Otto C. , Herek J. L. , Offerhaus H. L. 
Published: February 2010

AbstractWe demonstrate a new technique that combines polarization sensitivity of the coherent anti‐Stokes Raman scattering (CARS) response with heterodyne amplification for background‐free detection of CARS signals. In this heterodyne interferometric polarization CARS (HIP‐CARS), the major drawbacks of polarization and heterodyne CARS are rectified. Using a home‐built picosecond optical parametric oscillator, we are able to address vibrational stretches between 600 and 1650 cm−1 and record continuous high‐resolution Raman equivalent HIP‐CARS spectra. Copyright © 2010 John Wiley & Sons, Ltd.
Corrosion behavior of polypyrrole/hydroxyapatite nanocomposite thin films electropolymerized on NiTi substrates in simulated body fluid
Authors: Torabi M. , Sadrnezhaad S. K. 
Published: February 2010

AbstractHydroxyapatite (HAp) nanoparticles synthesized via microwave irradiation. Polypyrrole (PPy)/HAp nanocomposite was obtained using electropolymerization on nitinol (Ni) titanium (Ti) substrates. Fourier transform infrared was employed to characterize the nanocomposite formation. Electrochemical properties of the nanocomposite were investigated using polarization and electrochemical impedance spectroscopy (EIS) in simulated body fluid (SBF, 37 ± 0.1 °C). It was concluded that the NiTi specimen coated with PPy/HAp nanocomposite, has higher corrosion resistance than the NiTi coated with pure PPy in the SBF; however, NiTi was better than both coated NiTi. EIS results confirmed corrosion properties. Also, EIS was used to predict the morphology of the coatings. It predicted fine and compact morphology of the nanocomposite that was confirmed using scanning electron microscopy.
Fatigue behaviour of welded joints from magnesium alloy (AZ31) according to the local strain concept
Authors: Karakas Ö. , Gülsöz A. , Kaufmann H. , Sonsino C. M. 
Published: February 2010

AbstractIn the present study, the results of fatigue tests with the magnesium alloy AZ31 (ISO‐MgAl3Zn1) in the material states base metal, heat affected zone and weld metal obtained under strain control at room temperature within a range from 2·102 to 5·106 cycles are presented. The fatigue behaviour was characterized by the Coffin–Manson–Basquin equations and the stress – strain behaviour by the Ramberg–Osgood equation. The data can be used to assess welded magnesium joints according to the local strain concept.
Inflammation and Parkinson's disease pathogenesis
Authors: Przedborski Serge 
Published: February 2010

AbstractInflammation is a neuropathological feature of parkinsonian brains and also in experimental models of the disease. It is believed that activated glial cells, which compose the majority of this inflammatory response contribute to the neurodegenerative process through the production of toxic molecules. Therapeutic strategies geared toward reducing inflammation and inhibiting the production of these glial‐derived toxic molecules may be a promising neuroprotective strategy for the treatment of Parkinson's disease and related conditions. © 2010 Movement Disorder Society
Examining Braak's hypothesis by imaging Parkinson's disease
Authors: Brooks David J. 
Published: February 2010

AbstractIn this review, in vivo patterns of structural, metabolic, and neurotransmitter binding changes revealed by imaging in both symptomatic Parkinson's disease (PD) and at‐risk subjects are compared with those predicted at different Braak stages. It is concluded that the dysfunction revealed by imaging in PD is only partially in line with the sequential ascending topography of Lewy body pathology reported by Braak, suggesting that neurons in different brain regions are likely to be selectively vulnerable to the presence of intracellular synuclein aggregates. © 2010 Movement Disorder Society
The behavior of α‐synuclein in neurons
Authors: Fortin Doris L. , Nemani Venu M. , Nakamura Ken , Edwards Robert H. 
Published: February 2010

AbstractDespite considerable evidence linking α‐synuclein with membranes in vitro, it has proven difficult to demonstrate membrane association of the protein in vivo. α‐Synuclein localizes to the nerve terminal, but biochemical experiments have not revealed a tight association with membranes. To address the dynamics of the protein in live cells, we have used photobleaching and found that α‐synuclein exhibits high mobility, although distinctly less than an entirely soluble protein. Further, neural activity controls the distribution of α‐synuclein, causing its dispersion from the synapse. In addition to the presumed role of α‐synuclein dynamics in synaptic function, changes in its physiological behavior may underlie the pathological changes associated with Parkinson's disease. © 2010 Movement Disorder Society
Enhancing neuroplasticity in the basal ganglia: The role of exercise in Parkinson's disease
Authors: Petzinger Giselle M. , Fisher Beth E. , Van Leeuwen Jon‐Eric , Vukovic Marta , Akopian Garnik , Meshul Charlie K. , Holschneider Daniel P. , Nacca Angelo , Walsh John P. , Jakowec Michael W. 
Published: February 2010

AbstractEpidemiological and clinical trials have suggested that exercise is beneficial for patients with Parkinson's disease (PD). However, the underlying mechanisms and potential for disease modification are currently unknown. This review presents current findings from our laboratories in patients with PD and animal models. The data indicate that alterations in both dopaminergic and glutamatergic neurotransmission, induced by activity‐dependent (exercise) processes, may mitigate the cortically driven hyper‐excitability in the basal ganglia normally observed in the parkinsonian state. These insights have potential to identify novel therapeutic treatments capable of reversing or delaying disease progression in PD. © 2010 Movement Disorder Society
The nonmotor symptoms of Parkinson's disease—An overview
Authors: Lim Shen‐Yang , Lang Anthony E. 
Published: February 2010

AbstractNonmotor symptoms (NMS) are very common in Parkinson's disease (PD) and may result in significant disability. The increased focus on these important clinical features represents a major advance in the care of PD patients. In this article, we provide an overview of recent developments in the field. © 2010 Movement Disorder Society
Therapeutic directions for Parkinson's disease
Authors: Shoulson Ira 
Published: February 2010

AbstractThe focus on disease‐modifying treatments and cures for Parkinson's disease (PD) has raised expectations for quantum leaps and overshadowed incremental gains that have been slowly achieved. Large multi‐center clinical trials such as DATATOP and PRECEPT keep on generating new knowledge that is relevant to clinical care as well as experimental therapeutics. The largely unforeseen relationship between circulating uric acid and the occurrence and progression of PD was developed and confirmed in these clinical trials. Systematic follow‐up of clinical trial cohorts after conclusion of the interventional phase provides added value that continues to inform about natural history, state and trait biomarkers, and genotype‐phenotype relationships. These efforts are enhanced by data mining, public reporting, and timely sharing of data and biological samples. © 2010 Movement Disorder Society
A molecular basis for the increased vulnerability of substantia nigra dopamine neurons in aging and Parkinson's disease
Authors: Chan C. Savio , Gertler Tracy S. , Surmeier D. James 
Published: February 2010

AbstractParkinson's disease (PD) is a common neurodegenerative disorder of unknown etiology. There is no cure or proven strategy for slowing the progression of the disease. Although there are signs of pathology in many brain regions, the core symptoms of PD are attributable to the selective degeneration of dopaminergic neurons in the substantia nigra pars compacta. A potential clue to the vulnerability of these neurons is an increasing reliance with age upon L‐type Ca2+channels with a pore‐forming Cav1.3 subunit to support autonomous activity. This reliance could pose a sustained stress on mitochondrial ATP generating oxidative phosphorylation, accelerating cellular aging and death. Systemic administration of isradipine, a dihydropyridine blocker of these channels, forces dopaminergic neurons in rodents to revert to a juvenile, L‐type Ca2+channel independent mechanism to generate autonomous activity. This “rejuvenation” confers protection against toxins that produce experimental Parkinsonism, pointing to a potential neuroprotective strategy for PD. Their decades‐long track record of safe use in the treatment of hypertension makes dihydropyridines particularly attractive as a therapeutic tool in PD. © 2010 Movement Disorder Society