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Sample records for alendronate improve metaphyseal

  1. Improving the Metaphysical Argument against Free Will ...

    African Journals Online (AJOL)

    Galen Strawson and Saul Smilansky have offered a well-known argument that free will does not exist because the control involved is so robust that it would require influence over an infinite series of prior decisions. (Strawson 1986, 1994, 2002, Smilansky 2000, 2002) Unfortunately, while this metaphysical argument has ...

  2. Systemic alendronate treatment improves fixation of press-fit implants: a canine study using nonloaded implants

    DEFF Research Database (Denmark)

    Jensen, Thomas B; Bechtold, Joan E; Chen, Xinqian

    2007-01-01

    investigated the influence of oral alendronate treatment on early implant fixation in two implant interface settings representing sites of an implant that are in contact with surrounding bone, and other sites without intimate bone contact. One plasma-sprayed cylindrical titanium implant (6 mm diameter...... of alendronate treatment. Bone ongrowth (bone in contact with implant surface) was estimated using the linear intercept technique and shear strength was calculated as the slope on a load-displacement curve. For the press fit implants, alendronate treatment significantly increased bone ongrowth from 24% to 29......Bone resorption associated with local trauma occurring during insertion of joint prostheses is recognized as an early event. Being an osteoclastic inhibitor, alendronate is a potential candidate means to decrease early periprosthetic bone resorption and thereby improve implant fixation. We...

  3. Alendronate Can Improve Bone Alterations in Experimental Diabetes by Preventing Antiosteogenic, Antichondrogenic, and Proadipocytic Effects of AGEs on Bone Marrow Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Sara Rocío Chuguransky

    2016-01-01

    Full Text Available Bisphosphonates such as alendronate are antiosteoporotic drugs that inhibit the activity of bone-resorbing osteoclasts and secondarily promote osteoblastic function. Diabetes increases bone-matrix-associated advanced glycation end products (AGEs that impair bone marrow progenitor cell (BMPC osteogenic potential and decrease bone quality. Here we investigated the in vitro effect of alendronate and/or AGEs on the osteoblastogenic, adipogenic, and chondrogenic potential of BMPC isolated from nondiabetic untreated rats. We also evaluated the in vivo effect of alendronate (administered orally to rats with insulin-deficient Diabetes on long-bone microarchitecture and BMPC multilineage potential. In vitro, the osteogenesis (Runx2, alkaline phosphatase, type 1 collagen, and mineralization and chondrogenesis (glycosaminoglycan production of BMPC were both decreased by AGEs, while coincubation with alendronate prevented these effects. The adipogenesis of BMPC (PPARγ, intracellular triglycerides, and lipase was increased by AGEs, and this was prevented by coincubation with alendronate. In vivo, experimental Diabetes (a decreased femoral trabecular bone area, osteocyte density, and osteoclastic TRAP activity; (b increased bone marrow adiposity; and (c deregulated BMPC phenotypic potential (increasing adipogenesis and decreasing osteogenesis and chondrogenesis. Orally administered alendronate prevented all these Diabetes-induced effects on bone. Thus, alendronate could improve bone alterations in diabetic rats by preventing the antiosteogenic, antichondrogenic, and proadipocytic effects of AGEs on BMPC.

  4. Metaphysics I

    OpenAIRE

    Lebech, Mette

    2003-01-01

    Metaphysics I is a course currently taught in the Faculty of Philosophy, NUIM. It attempts to answer three questions: 'What is metaphysics?', 'What happened as metaphysics was Christianised?' and 'What happenerd as metaphysics was Modernized?', while discussing texts of Aristotle, Thomas Aquinas, Edmund Husserl and Edith Stein.

  5. Metaphysics and medical ethics.

    Science.gov (United States)

    Parkin, C

    1995-01-01

    I take issue with Frank Leavitt's sketch of a pragmatic criterion for the relevance of metaphysics to medical ethics. I argue that appeal to the potential for confusion generated by metaphysical subtlety establishes a need for better communication rather than shows philosophical insight beside the point. I demonstrate that the proposed Criterion of Relevance has absurd consequences, and I claim that the relevance of philosophical doctrines, whether ethical or metaphysical, is best accounted for in terms of improved understanding. PMID:7608933

  6. Alendronate-Loaded Modified Drug Delivery Lipid Particles Intended for Improved Oral and Topical Administration

    OpenAIRE

    Lacramioara Ochiuz; Cristian Grigoras; Marcel Popa; Iulian Stoleriu; Corneliu Munteanu; Daniel Timofte; Lenuta Profire; Anca Giorgiana Grigoras

    2016-01-01

    The present paper focuses on solid lipid particles (SLPs), described in the literature as the most effective lipid drug delivery systems that have been introduced in the last decades, as they actually combine the advantages of polymeric particles, hydrophilic/lipophilic emulsions and liposomes. In the current study, we present our most recent advances in the preparation of alendronate (AL)-loaded SLPs prepared by hot homogenization and ultrasonication using various ratios of a self-emulsifyin...

  7. Improvement of cancellous bone microstructure in patients on teriparatide following alendronate pretreatment.

    Science.gov (United States)

    Fahrleitner-Pammer, Astrid; Burr, David; Dobnig, Harald; Stepan, Jan J; Petto, Helmut; Li, Jiliang; Krege, John H; Pavo, Imre

    2016-08-01

    An increase in procollagen type I amino-terminal propeptide (PINP) early after teriparatide initiation was shown to correlate with increased lumbar spine areal BMD and is a good predictor of the anabolic response to teriparatide. Few data exist correlating PINP and bone microstructure, and no data exist in patients on teriparatide following prior potent antiresorptive treatment. This exploratory analysis aimed to investigate the effects of teriparatide on cancellous bone microstructure and correlations of bone markers with microstructure in alendronate-pretreated patients. This was a post hoc analysis of changes in bone markers and three-dimensional indices of bone microstructure in paired iliac crest biopsies from a prospective teriparatide treatment study in postmenopausal women with osteoporosis who were either treatment-naïve (TN, n=16) or alendronate-pretreated (ALN, n=29) at teriparatide initiation. Teriparatide (20μg/day) was given for 24months; biopsies were taken at baseline and endpoint, and serum concentrations of PINP and type 1 collagen cross-linked C-telopeptide (βCTX) were measured at intervals up to 24months. In the TN and ALN groups, respectively, mean (SD) increases in three-dimensional bone volume/tissue volume were 105 (356)% (P=0.039) and 55 (139)% (Pteriparatide therapy irrespective of prior antiresorptive use. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Alendronate-Loaded Modified Drug Delivery Lipid Particles Intended for Improved Oral and Topical Administration

    Directory of Open Access Journals (Sweden)

    Lacramioara Ochiuz

    2016-06-01

    Full Text Available The present paper focuses on solid lipid particles (SLPs, described in the literature as the most effective lipid drug delivery systems that have been introduced in the last decades, as they actually combine the advantages of polymeric particles, hydrophilic/lipophilic emulsions and liposomes. In the current study, we present our most recent advances in the preparation of alendronate (AL-loaded SLPs prepared by hot homogenization and ultrasonication using various ratios of a self-emulsifying lipidic mixture of Compritol 888, Gelucire 44/14, and Cremophor A 25. The prepared AL-loaded SLPs were investigated for their physicochemical, morphological and structural characteristics by dynamic light scattering, differential scanning calorimetry, thermogravimetric and powder X-ray diffraction analysis, infrared spectroscopy, optical and scanning electron microscopy. Entrapment efficacy and actual drug content were assessed by a validated HPLC method. In vitro dissolution tests performed in simulated gastro-intestinal fluids and phosphate buffer solution pH 7.4 revealed a prolonged release of AL of 70 h. Additionally, release kinetics analysis showed that both in simulated gastrointestinal fluids and in phosphate buffer solution, AL is released from SLPs based on equal ratios of lipid excipients following zero-order kinetics, which characterizes prolonged-release drug systems.

  9. Low-energy extracorporeal shockwave therapy (ESWT) improves metaphyseal fracture healing in an osteoporotic rat model.

    Science.gov (United States)

    Mackert, Gina A; Schulte, Matthias; Hirche, Christoph; Kotsougiani, Dimitra; Vogelpohl, Julian; Hoener, Bernd; Fiebig, Teresa; Kirschner, Stefanie; Brockmann, Marc A; Lehnhardt, Marcus; Kneser, Ulrich; Harhaus, Leila

    2017-01-01

    As result of the current demographic changes, osteoporosis and osteoporotic fractures are becoming an increasing social and economic burden. In this experimental study, extracorporeal shock wave therapy (ESWT), was evaluated as a treatment option for the improvement of osteoporotic fracture healing. A well-established fracture model in the metaphyseal tibia in the osteoporotic rat was used. 132 animals were divided into 11 groups, with 12 animals each, consisting of one sham-operated group and 10 ovariectomized (osteoporotic) groups, of which 9 received ESWT treatment. Different energy flux intensities (0.15 mJ/mm2, 0.35 mJ/mm2, or 0.55 mJ/mm2) as well as different numbers of ESWT applications (once, three times, or five times throughout the 35-day healing period) were applied to the osteoporotic fractures. Fracture healing was investigated quantitatively and qualitatively using micro-CT imaging, quantitative real-time polymerase chain reaction (qRT-PCR) analysis, histomorphometric analysis and biomechanical analysis. The results of this study show a qualitative and quantitative improvement in the osteoporotic fracture healing under low-energy (energy flux intensity: 0,15 mJ/mm2) ESWT and with fewer treatment applications per healing period. In conclusion, low-energy ESWT seems to exhibit a beneficial effect on the healing of osteoporotic fractures, leading to improved biomechanical properties, enhanced callus-quantity and -quality, and an increase in the expression of bone specific transcription factors. The results suggest that low-energy ESWT, as main treatment or as adjunctive treatment in addition to a surgical intervention, may prove to be an effective, simple to use, and cost-efficient option for the qualitative and quantitative improvement of osteoporotic fracture healing.

  10. Low-energy extracorporeal shockwave therapy (ESWT improves metaphyseal fracture healing in an osteoporotic rat model.

    Directory of Open Access Journals (Sweden)

    Gina A Mackert

    Full Text Available As result of the current demographic changes, osteoporosis and osteoporotic fractures are becoming an increasing social and economic burden. In this experimental study, extracorporeal shock wave therapy (ESWT, was evaluated as a treatment option for the improvement of osteoporotic fracture healing.A well-established fracture model in the metaphyseal tibia in the osteoporotic rat was used. 132 animals were divided into 11 groups, with 12 animals each, consisting of one sham-operated group and 10 ovariectomized (osteoporotic groups, of which 9 received ESWT treatment. Different energy flux intensities (0.15 mJ/mm2, 0.35 mJ/mm2, or 0.55 mJ/mm2 as well as different numbers of ESWT applications (once, three times, or five times throughout the 35-day healing period were applied to the osteoporotic fractures. Fracture healing was investigated quantitatively and qualitatively using micro-CT imaging, quantitative real-time polymerase chain reaction (qRT-PCR analysis, histomorphometric analysis and biomechanical analysis.The results of this study show a qualitative and quantitative improvement in the osteoporotic fracture healing under low-energy (energy flux intensity: 0,15 mJ/mm2 ESWT and with fewer treatment applications per healing period.In conclusion, low-energy ESWT seems to exhibit a beneficial effect on the healing of osteoporotic fractures, leading to improved biomechanical properties, enhanced callus-quantity and -quality, and an increase in the expression of bone specific transcription factors. The results suggest that low-energy ESWT, as main treatment or as adjunctive treatment in addition to a surgical intervention, may prove to be an effective, simple to use, and cost-efficient option for the qualitative and quantitative improvement of osteoporotic fracture healing.

  11. Modulation of gastric pH by a buffered soluble effervescent formulation: A possible means of improving gastric tolerability of alendronate.

    Science.gov (United States)

    Hodges, L A; Connolly, S M; Winter, J; Schmidt, T; Stevens, H N E; Hayward, M; Wilson, C G

    2012-08-01

    Gastrointestinal side-effects of alendronate (ALN) are believed to be associated with oesophageal lodging of tablets and perhaps reflux of gastric contents with alendronate under strongly acidic pH conditions. This leads to unfavourable posture restrictions when dosing. This clinical study evaluated gastric emptying and gastric pH after administration of Fosamax(®) tablets and a novel effervescent ALN formulation with a high buffering capacity. This novel formulation, EX101, was developed to potentially improve gastric tolerance. Gastric pH was monitored by nasogastric probes. Gastric emptying was determined simultaneously by scintigraphic imaging of (99m)Tc-DTPA labelled formulations. Both formulations tested rapidly cleared the oesophagus and there were no statistically significant or physiologically relevant differences in gastric emptying times. Mean pH at time to 50% gastric emptying of the radiolabel was significantly higher in EX101-treated subjects compared to those treated with Fosamax(®). At time to 90% gastric emptying of the radiolabel, mean pH values were comparable. Mucosal exposure to ALN at pH less than 3 is irritating to gastro-oesophageal tissue. Ingestion of Fosamax(®) resulted in ALN being present in the stomach at a pH below 3 within minutes. EX101 minimised the possibility of exposing the oesophagus (in case of reflux) to acidified ALN. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Metaphysics of Logical Realism

    OpenAIRE

    محمدرضا عبداله نژاد

    2016-01-01

    Despite the often false impression that the analytic philosophy as an anti-metaphysical movement has nothing to do with metaphysics, there can be found good reasons to grant the metaphysical dispositions of analytic philosophers, and thereby, to minimize the anti-metaphysical nature of analytic philosophy in its all phases. Since analytic philosophy is a historical movement the main nature of which developed through several stages, the very kinds of metaphysical dispositions within each one o...

  13. Nodular scleritis following alendronate therapy.

    Science.gov (United States)

    Tabbara, Khalid F

    2008-01-01

    To report a case of nodular scleritis following alendronate sodium. A 54 year-old male was treated with alendronate sodium 70 mg orally once per week. Eight weeks later, he experienced pain and redness of the right eye. Biomicroscopy was performed. Patient was found to have inferonasal nodular scleritis. Laboratory work-up was unrevealing. Patient was given 4 mg of subtenon's triamcinolone acetate in the area of the nodular scleritis and had complete resolution. Two weeks following rechallenge with alendronate sodium resulted in recurrence of his scleritis. Alendronate led to nodular scleritis and rechallenge caused recurrence of scleritis.

  14. Alendronate in early postmenopausal women

    DEFF Research Database (Denmark)

    Ravn, Pernille; Weiss, S R; Rodriguez-Portales, J A

    2000-01-01

    consented to continue and completed the extension. We are reporting data from groups using the dose of alendronate currently approved for osteoporosis prevention (5 mg) or from the group in which alendronate treatment was withdrawn: 52 women received alendronate (5 mg) for 5 yr (group I), 56 received 3 yr......We studied the effect on bone mass of alendronate treatment for 5 yr and its withdrawal. Four hundred and forty-seven postmenopausal women with normal bone mass entered a 3-yr randomized trial followed by a 2-yr open label extension. Three hundred and eleven women completed the first 3 yr, and 263...

  15. Efficacy of Alendronate for Preventing Collapse of Femoral Head in Adult Patients with Nontraumatic Osteonecrosis

    Directory of Open Access Journals (Sweden)

    Yu-Cai Hong

    2014-01-01

    Full Text Available The purpose of the current review was to determine the efficacy of alendronate for preventing collapse of femoral head in adult patients with nontraumatic avascular osteonecrosis of femoral head (ANFH. Five randomized controlled trials (RCTs involving 305 hips were included in this review, of which 3 studies investigated alendronate versus control/placebo and the other 2 studies compared the combination of alendronate and extracorporeal shockwave therapy (ESWT with ESWT alone. Our results suggested that even the patients with extensive necrosis encountered much less collapse in the alendronate group than control group. In these RCTs, their data also indicated a positive short- and middle-term efficacy of alendronate treatment in joint function improvement and hip pain diminishment. With the presence of the outlier study, only insignificant overall efficacy of alendronate could be observed with substantial heterogeneities. In addition, we did not find any additive benefits of alendronate in combination with ESWT for preventing collapse compared to ESWT alone. In conclusion, there is still lack of strong evidence for supporting application of alendronate in adult patients with nontraumatic ANFH, which justified that large scale, randomized, and double-blind studies should be developed to demonstrate the confirmed efficacies, detailed indication, and optimized strategy of alendronate treatment.

  16. Cancer and metaphysics.

    Science.gov (United States)

    Zajicek, G

    2001-08-01

    Metaphysics, is generally a pleasant, and harmless intellectual endeavor. Even if leading to wrong conclusions, nobody is hurt. Suppose that contrary to general belief, the Big Bang (1) never happened and the world is eternal. No harm is done. Some philosophers, like Kant, enjoyed life despite the fact that, nature, or the thing in itself, eluded their understanding (2). But suppose that the thing in itself is your patient, and you apply metaphysical reasoning for his treatment, metaphysics may occasionally be damaging. This is particularly pertinent to cancer, a disease that is haunted by false metaphysical statements. Since cancer is part of medicine, the present discourse deals with medical metaphysics. Medicine provides a simple way, or rule of thumb, for distinguishing between correct and wrong medical metaphysical statements. If they harm the patient, they are wrong, and if they aid him, they are correct. Statements that do not affect a patient's well being, e.g., 'Big Bang may be hazardous to your health', are of no apparent value and doubtful. Since treatment outcome is generally uncertain, the physician continually searches for new ideas that may aid his patient, even if they are metaphysical. In diseases, like cancer, that elude his understanding, his adherence to metaphysics intensifies, and he is ready to consider even doubtful suggestions for treatment. Yet by relaxing the rules of thumb for evaluating metaphysical concepts, he gradually slips into the irrational domain. Copyright 2001 Harcourt Publishers Ltd.

  17. The place of metaphysics in the historiography of science

    Science.gov (United States)

    Agassi, Joseph

    1996-04-01

    Legitimating the use of metaphysics in scientific research constituted a farreaching methodological revolution, invalidating the inductivist demands that science be guided by empirical information alone. Thus, science became tentative. The revolution was established when pioneering historians of science, Max Jammer among them, exhibited the working of metaphysics in scientific research. This raises many problems, since most metaphysical ideas are poor as compared with scientific ones. Yet taking science to be the effort to explain facts in a comprehensive manner, makes some metaphysics unavoidable, and presents the better metaphysics as the possible frameworks within which older scientific theories may be reinterpreted and improved and newer ones may be developed.

  18. Metaphysics and Learning

    Science.gov (United States)

    Verran, Helen

    2007-01-01

    Is it possible to learn and simultaneously articulate the metaphysical basis of that learning? In my contribution to the forum I tell of how I came to recognise that bilingual Yoruba children could articulate the contrasting metaphysical framings of Yoruba and English numbering. The story introduces an arena I call "ontics" that recognises the…

  19. Diagnostic PET Imaging of Mammary Microcalcifications Using64Cu-DOTA-Alendronate in a Rat Model of Breast Cancer.

    Science.gov (United States)

    Ahrens, Bradley J; Li, Lin; Ciminera, Alexandra K; Chea, Junie; Poku, Erasmus; Bading, James R; Weist, Michael R; Miller, Marcia M; Colcher, David M; Shively, John E

    2017-09-01

    The development of improved breast cancer screening methods is hindered by a lack of cancer-specific imaging agents and effective small-animal models to test them. The purpose of this study was to evaluate 64 Cu-DOTA-alendronate as a mammary microcalcification-targeting PET imaging agent, using an ideal rat model. Our long-term goal is to develop 64 Cu-DOTA-alendronate for the detection and noninvasive differentiation of malignant versus benign breast tumors with PET. Methods: DOTA-alendronate was synthesized, radiolabeled with 64 Cu, and administered to normal or tumor-bearing aged, female, retired breeder Sprague-Dawley rats for PET imaging. Mammary tissues were subsequently labeled and imaged with light, confocal, and electron microscopy to verify microcalcification targeting specificity of DOTA-alendronate and elucidate the histologic and ultrastructural characteristics of the microcalcifications in different mammary tumor types. Tumor uptake, biodistribution, and dosimetry studies were performed to evaluate the efficacy and safety of 64 Cu-DOTA-alendronate. Results: 64 Cu-DOTA-alendronate was radiolabeled with a 98% yield. PET imaging using aged, female, retired breeder rats showed specific binding of 64 Cu-DOTA-alendronate in mammary glands and mammary tumors. The highest uptake of 64 Cu-DOTA-alendronate was in malignant tumors and the lowest uptake in benign tumors and normal mammary tissue. Confocal analysis with carboxyfluorescein-alendronate confirmed the microcalcification binding specificity of alendronate derivatives. Biodistribution studies revealed tissue alendronate concentrations peaking within the first hour, then decreasing over the next 48 h. Our dosimetric analysis demonstrated a 64 Cu effective dose within the acceptable range for clinical PET imaging agents and the potential for translation into human patients. Conclusion: 64 Cu-DOTA-alendronate is a promising PET imaging agent for the sensitive and specific detection of mammary tumors as

  20. Metaphysical Experience and Constitutive Error in Adorno's "Meditations on Metaphysics"

    NARCIS (Netherlands)

    Skirke, C.

    2012-01-01

    That current ideals of cognition impoverish experience is a classical observation, and complaint, of the early Frankfurt School. Adorno reacts to this phenomenon in several ways, among them his conception of metaphysical experiences. Metaphysical experiences are conventionally understood as

  1. The metaphysics of evolution.

    Science.gov (United States)

    Dupré, John

    2017-10-06

    This paper briefly describes process metaphysics, and argues that it is better suited for describing life than the more standard thing, or substance, metaphysics. It then explores the implications of process metaphysics for conceptualizing evolution. After explaining what it is for an organism to be a process, the paper takes up the Hull/Ghiselin thesis of species as individuals and explores the conditions under which a species or lineage could constitute an individual process. It is argued that only sexual species satisfy these conditions, and that within sexual species the degree of organization varies. This, in turn, has important implications for species' evolvability. One important moral is that evolution will work differently in different biological domains.

  2. Mechanisms, determination and the metaphysics of neuroscience.

    Science.gov (United States)

    Soom, Patrice

    2012-09-01

    In this paper, I evaluate recently defended mechanistic accounts of the unity of neuroscience from a metaphysical point of view. Considering the mechanistic framework in general (Sections 2 and 3), I argue that explanations of this kind are essentially reductive (Section 4). The reductive character of mechanistic explanations provides a sufficiency criterion, according to which the mechanism underlying a certain phenomenon is sufficient for the latter. Thus, the concept of supervenience can be used in order to describe the relation between mechanisms and phenomena (Section 5). Against this background, I show that the mechanistic framework is subject to the causal exclusion problem and faces the classical metaphysical options when it comes to the relations obtaining between different levels of mechanisms (Section 6). Finally, an attempt to improve the metaphysics of mechanisms is made (Section 7) and further difficulties are pointed out (Section 8). Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. On neuropsychoanalytic metaphysics.

    Science.gov (United States)

    Talvitie, Vesa; Ihanus, Juhani

    2011-12-01

    Neuropsychoanalysis focuses on the neural counterparts of psychoanalytically interesting phenomena and has left the difference in the metaphysical presuppositions between neuroscience and psychoanalysis unexamined. The authors analyse the logical possibilities concerning the relation between the brain and the mental unconscious in terms of the serial, parallel, epiphenomenalist and Kantian conceptions, and conclude that none of them provides a satisfactory ground for neuropsychoanalysis. As far as psychoanalytic explanations refer to the mental unconscious, they cannot be verified with the help of neuroscience. Neither is it possible to form a picture of how a neuro-viewpoint might be of help for psychoanalytic theorizing. Neuropsychoanalysis has occasionally been seen as a reductionist affair, but the authors suggest that neuropsychoanalysts themselves lean on the hybrid conception, which combines neuroscientific and psychoanalytic viewpoints. The authors state arguments in favour of the interfield conception of neuropsychoanalysis that takes seriously the metaphysical tensions between neuroscience and psychoanalysis. Copyright © 2011 Institute of Psychoanalysis.

  4. Effect of heparin and alendronate coating on titanium surfaces on inhibition of osteoclast and enhancement of osteoblast function

    International Nuclear Information System (INIS)

    Moon, Ho-Jin; Yun, Young-Pil; Han, Choong-Wan; Kim, Min Sung; Kim, Sung Eun; Bae, Min Soo; Kim, Gyu-Tae; Choi, Yong-Suk; Hwang, Eui-Hwan; Lee, Joon Woo; Lee, Jin-Moo; Lee, Chang-Hoon; Kim, Duck-Su; Kwon, Il Keun

    2011-01-01

    Highlights: → We examine bone metabolism of engineered alendronate attached to Ti surfaces. → Alendronate-immobilized Ti enhances activation of osteoblast differentiation. → Alendronate-immobilized Ti inhibits osteoclast differentiation. → Alendronate-immobilized Ti may be a bioactive implant with dual functions. -- Abstract: The failure of orthopedic and dental implants has been attributed mainly to loosening of the implant from host bone, which may be due to weak bonding of the implant material to bone tissue. Titanium (Ti) is used in the field of orthopedic and dental implants because of its excellent biocompatibility and outstanding mechanical properties. Therefore, in the field of materials science and tissue engineering, there has been extensive research to immobilize bioactive molecules on the surface of implant materials in order to provide the implants with improved adhesion to the host bone tissue. In this study, chemically active functional groups were introduced on the surface of Ti by a grafting reaction with heparin and then the Ti was functionalized by immobilizing alendronate onto the heparin-grafted surface. In the MC3T3-E1 cell osteogenic differentiation study, the alendronate-immobilized Ti substrates significantly enhanced alkaline phosphatase activity (ALP) and calcium content. Additionally, nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation of RAW264.7 cells was inhibited with the alendronate-immobilized Ti as confirmed by TRAP analysis. Real time PCR analysis showed that mRNA expressions of osteocalcin and osteopontin, which are markers for osteogenesis, were upregulated in MC3T3-E1 cells cultured on alendronate-immobilized Ti. The mRNA expressions of TRAP and Cathepsin K, markers for osteoclastogenesis, in RAW264.7 cells cultured on alendronate-immobilized Ti were down-regulated. Our study suggests that alendronate-immobilized Ti may be a bioactive implant with dual functions to enhance osteoblast

  5. Temporal Experience and Metaphysics

    Directory of Open Access Journals (Sweden)

    Graham Peebles

    Full Text Available ABSTRACT The well-known phenomenological argument draws metaphysical conclusions about time, specifically about change through time and the resulting passage or flow of time, from our temporal experience. The argument begins with the phenomenological premise that there is a class of properties which underlies our experience of time and change through time, and its conclusion is that these properties are not merely experienced but exemplified. I argue that the phenomenological argument is best served by the adoption of a representational theory of perception. I then present a representational theory of temporal experience.

  6. Evidence for Using Alendronate to Treat Adult Avascular Necrosis of the Femoral Head: A Systematic Review

    Science.gov (United States)

    Luo, Ru-Bin; Lin, Tiao; Zhong, Hui-Ming; Yan, Shi-Gui; Wang, Jian-An

    2014-01-01

    Osteonecrosis or avascular osteonecrosis (AVN) of the femoral head is a devastating multifactorial disease that affects 20 000 persons each year in the United States. The purpose of this systematic review was to determine the efficacy and safety of alendronate for adult AVN during short- and long-term follow-up. Electronic databases were searched for randomized or nonrandomized clinical trials, cohort, case-control studies, and series of cases in which alendronate was used for treatment of adult AVN of the femoral head. Relevant articles with adequate data on reduction of pain, improvement of articular function, slowing of bone collapse progression, or need for total hip arthroplasty (THA) were included after applying inclusion and exclusion criteria. Eight articles involving 788 hips with evidence level 1b to 3b were included in this systematic review. Most studies suggested a positive short-term efficacy of alendronate treatment in reducing pain, improving articular function, slowing of bone collapse progression, and delaying the need for THA for adult AVN patients. The favorable long-term results were also presented in those treated patients after 10-year follow-up. In addition, there were no severe adverse effects associated with alendronate treatment observed during short- and long-term follow-up, and most of the included studies suggested use of alendronate in early AVN with small necrotic lesion to achieve better outcomes. The findings support consideration of alendronate use for adult AVN, particularly with early stage and small necrotic size. The lack of large-scale, randomized, and double-blind studies justifies new studies to demonstrate the detailed indication and the optimized strategy of alendronate treatment. Level of evidence: Level 3a. PMID:25424061

  7. Ontological engineering versus metaphysics

    Science.gov (United States)

    Tataj, Emanuel; Tomanek, Roman; Mulawka, Jan

    2011-10-01

    It has been recognized that ontologies are a semantic version of world wide web and can be found in knowledge-based systems. A recent time survey of this field also suggest that practical artificial intelligence systems may be motivated by this research. Especially strong artificial intelligence as well as concept of homo computer can also benefit from their use. The main objective of this contribution is to present and review already created ontologies and identify the main advantages which derive such approach for knowledge management systems. We would like to present what ontological engineering borrows from metaphysics and what a feedback it can provide to natural language processing, simulations and modelling. The potential topics of further development from philosophical point of view is also underlined.

  8. Raloxifene but not alendronate can compensate the impaired osseointegration in osteoporotic rats.

    Science.gov (United States)

    Faverani, Leonardo Perez; Polo, Tárik Ocon Braga; Ramalho-Ferreira, Gabriel; Momesso, Gustavo Antonio Correa; Hassumi, Jaqueline Suemi; Rossi, Ana Cláudia; Freire, Alexandre Rodrigues; Prado, Felippe Bevilacqua; Luvizuto, Eloá Rodrigues; Gruber, Reinhard; Okamoto, Roberta

    2018-01-01

    Alendronate and raloxifene, a bisphosphonate and a selective estrogen modulator, respectively, are established osteoporosis therapies. Current evidence suggests that simultaneous application of osteoporosis therapies modulates osseointegration. However, alendronate shows inconsistent findings and raloxifene has not been studied comprehensively. This study aimed to evaluate the bone dynamics and molecular and microstructural features at the peri-implant bone interface in osteoporotic rats. Thirty female rats underwent ovariectomy and were fed a diet low in calcium and phosphate and treated with alendronate or raloxifene for 30 days or underwent fictional ovariectomy surgery (SHAM) prior to implant insertion in the tibia; osteoporosis therapies continued thereafter. After 42 days, peri-implant bone was evaluated by histometric and micro-CT analysis. Fluorochrome incorporation and gene expression was determined to evaluate bone turnover. We report here that alendronate had no impact on bone-to-implant contacts and the mineral apposition rate. The RANKL/OPG ratio and local bone volume, however, were increased compared to the untreated osteoporotic rats. Even though signaling to bone resorption activity through RANKL production was observed in the alendronate group, the blockade of bone resorption activity that occurs in decorrence to alendronate activity took place and resulted in an increase in bone volume. Raloxifene significantly increased osseointegration in osteoporotic rats, as indicated by bone-to-implant contacts, mineral apposition, and local bone volume. Raloxifene, however, had no considerable impact on the RANKL/OPG ratio compared to untreated osteoporotic rats. As expected, the SH group showed higher bone-to-implant contacts and mineral apposition rates than the untreated osteoporotic rats. These findings suggest that raloxifene but not alendronate can compensate for the impaired osseointegration in osteoporotic rats. Regarding the superiority of

  9. Alendronate

    Science.gov (United States)

    ... pain bloody vomit or vomit that looks like coffee grounds black, tarry, or bloody stools fever blisters or ... pain bloody vomit or vomit that looks like coffee grounds difficulty swallowing or pain when swallowing bloody or ...

  10. Crystalline calcium alendronate obtained by octacalcium phosphate digestion: a new chance for local treatment of bone loss diseases?

    Science.gov (United States)

    Boanini, Elisa; Torricelli, Paola; Gazzano, Massimo; Fini, Milena; Bigi, Adriana

    2013-09-06

    Octacalcium phosphate (OCP) interaction with alendronate (AL) solution results in the complete digestion of OCP: calcium ion is recruited by the bisphosphonate to yield quantitative precipitation of crystalline calcium alendronate monohydrate. This compound improves osteoblast differentiation and inhibits osteoclast proliferation and activity, both alone and, even more, in combination with OCP. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Metaphyseal cupping: a case report.

    Science.gov (United States)

    Wiss, D A

    1981-06-01

    A case of metaphyseal cupping of bone that probably occurred as the result of an impaired blood supply to the leg of an infant is reported. Avascularity and premature closure of the central segment of the growth plate is the proposed pathogenesis. The blood supply, growth and development of the ends of growing bones are discussed and the radiographie features of metaphyseal cupping are described. Copyright 2013, SLACK Incorporated.

  12. The Everyday Condition of Metaphysics

    Directory of Open Access Journals (Sweden)

    Ştefan Afloroaei

    2010-12-01

    Full Text Available The question I intend to answer is whether one can speak of a tacit metaphysics, not expressed conceptually, but nevertheless common. If the answer is positive and providing that it is specific to day-to-day life, such metaphysics may be called everyday metaphysics. To this end, I review the meaning of everyday life and its ambivalent character. Next, I present several milestones in the debate on the subject, from authors who have focused on a kind of usual, common or ‘natural’ metaphysics. Lastly, I formulate the idea under consideration, namely that everyday life implies or underlies a certain metaphysics. I note that it is an implicit metaphysics – not expressed formally – and rather free. Embraced in experience with a certain degree of freedom, it is recognisable by means of certain representations active in our mind, by the manner of speaking or of understanding and by the common forms of expression. Its vibrancy, concrete and relaxed character makes it highly evocative of the mental life of an era. It ensures a truly essential difference in our everyday mode of being.

  13. Adsorption and conformational change of myoglobin on biomimetic hydroxyapatite nanocrystals functionalized with alendronate.

    Science.gov (United States)

    Iafisco, Michele; Palazzo, Barbara; Falini, Giuseppe; Foggia, Michele Di; Bonora, Sergio; Nicolis, Stefania; Casella, Luigi; Roveri, Norberto

    2008-05-06

    The chemical conjugation of bisphosphonates (BPs), specifically alendronate, to hydroxyapatite could be an effective means to impart to it fine-tuned bioactivity. Horse heart myoglobin (Mb), a well-characterized protein, has been adsorbed onto biomimetic hydroxyapatite nanocrystals (nHA) and onto the nHA/alendronate conjugate powdered samples. The obtained materials have potential use in bone implantation and as prospective drug-delivery devices. The kinetic absorption of Mb onto nHA is dramatically affected by its functionalization with alendronate. The covering of the nHA surface by alendronate inhibits the adsorption of myoglobin. The adsorption mechanisms of the protein were studied by spectroscopic techniques (UV-vis and surface-enhanced Raman spectroscopy). The results indicate that the protein changes conformation upon adsorption on the inorganic substrate. In particular, the interaction with nHA alters the coordination state of the iron in the heme through the formation of a hexacoordinated low-spin Mb heme, possibly involving the distal histidine. Instead, the covering of the nHA surface by alendronate does not adsorb the protein but preserves the coordination state of the heme moiety. This study could be of significance either in the field of biomaterials science, in particular, to fine tune a bone-specific drug delivery device and to test nHA as a new support for heterogeneous catalysis, improving the understating of enzyme immobilization.

  14. Enhanced Oral Delivery of Bisphosphonate by Novel Absorption Enhancers: Improvement of Intestinal Absorption of Alendronate by N-Acyl Amino Acids and N-Acyl Taurates and Their Absorption-Enhancing Mechanisms.

    Science.gov (United States)

    Nakaya, Yuka; Takaya, Mayu; Hinatsu, Yuta; Alama, Tammam; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2016-12-01

    Bisphosphonates (BPs) are carbon-substituted pyrophosphate analogs that exhibit a high affinity to hydroxyapatite and specifically inhibit bone resorption. Alendronate sodium (sodium 4-amino-1-hydroxybutylidene-1,1-bisphosphonate trihydrate) is a typical BP compound in clinical use. BPs have very low bioavailability, typically intestinal absorption is further reduced by co-administered drugs or food. In this study, we examined the effects of N-acyl amino acids and N-acyl taurates on the small intestinal absorption of alendronate. All N-acyl amino acids and N-acyl taurates increased the small intestinal absorption of alendronate, especially 1% (wt/vol) sodium palmitoyl sarcosinate (PN), which elicited a 14-fold increase. In addition, the absorption-enhancing effects of these enhancers were reversible and they may not cause continuous and irreversible membrane toxicity in the rat small intestine. Furthermore, we examined the absorption-promoting mechanisms of PN and found that it increased the membrane fluidity of the lipid bilayers. In addition, it was found that PN may open the tight junctions by reducing the expression level of claudin-4, which is a major tight junction protein. These findings indicate that these enhancers are useful for promoting the intestinal absorption of alendronate. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  15. Fictional metaphysics of fiction: Metaphysics and imagination in the humanities

    OpenAIRE

    Johann-Albrecht Meylahn

    2017-01-01

    A very simplified description of physics could be, according to Wikipedia, natural science that involves the study of matter and its motion and behaviour through space and time. In relation to this simplified description of physics, metaphysics would then be that which gives matter, or metaphysics would be the reflection on the space and time in which matter is given. Yet, how are space and time connected? It is in language, or more specifically narrative (fiction), that space and time are co...

  16. Conceptual Realism. The Structure of Metaphysical Thought

    NARCIS (Netherlands)

    Mulder, J.M.

    2014-01-01

    Metaphysics is now a respectable discipline within analytic philosophy: metaphysical realists are proposing their various theories as to the ultimate structure of reality. However, their project is also being fundamentally questioned, by metaphysical anti-realists. This ambivalent situation is due

  17. The Scientific Metaphysics of Charles S. Peirce

    DEFF Research Database (Denmark)

    Sørensen, Bent; Thellefsen, Torkild Leo

    scientific results and conceptions of his time, but also, like Immanuel Kant, to set metaphysics on the path of a science. This collection of articles investigates central themes and difficulties in the metaphysics of Peirce - some of the articles clarify aspects of his metaphysics, others also show...

  18. Metaphyseal bands in osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Suresh S

    2010-01-01

    Full Text Available An increasing number of patients with osteogenesis imperfecta are undergoing pamidronate therapy to prevent the incidence of fragility fractures. The authors herein report a child aged 3 years who received five cycles of pamidronate, resulting in metaphyseal bands, known as "zebra lines."

  19. Fatalism as a Metaphysical Thesis

    Directory of Open Access Journals (Sweden)

    Ulrich Meyer

    Full Text Available ABSTRACT Even though fatalism has been an intermittent topic of philosophy since Greek antiquity, this paper argues that fate ought to be of little concern to metaphysicians. Fatalism is neither an interesting metaphysical thesis in its own right, nor can it be identified with theses that are, such as realism about the future or determinism.

  20. String theory : physics or metaphysics?

    CERN Document Server

    Veneziano, Gabriele

    2010-01-01

    I will give arguments for why the enormous progress made during the last century on understanding elementary particles and their fundamental interactions suggests strings as the truly elementary constituents of Nature. I will then address the issue of whether the string paradigm can in principle be falsified or whether it should be considered as mere metaphysics.

  1. Interzones of Law and Metaphysics

    DEFF Research Database (Denmark)

    Mossin, Christiane

    and sources of authority. On the basis of a historical-conceptual understanding of law according to which law, social structure and metaphysical presumptions are inescapably intertwined, the dissertation derives from the binding provisions of law certain essential features of social order. More precisely...

  2. Towards a Metaphysics of Complexity

    Science.gov (United States)

    Robinson, Keith

    2005-01-01

    In this paper, I combine aspects of process philosophy and elements from philosophies of difference in order to give some indication of how we might begin to construct a metaphysics of contemporary science. I will focus on the work of Whitehead and Deleuze as representatives of each respective tradition and try to show how their work can be…

  3. Alendronate promotes osteoblast differentiation and bone formation in ovariectomy-induced osteoporosis through interferon-β/signal transducer and activator of transcription 1 pathway

    Science.gov (United States)

    Ma, Xiaoqing; Xu, Zhongyang; Ding, Shaofeng; Yi, Guangkun; Wang, Qian

    2018-01-01

    Alendronate is commonly used for the treatment of postmenopausal osteoporosis; however, the underlying pathological molecular mechanisms of its action remain unclear. In the present study, the alendronate-treated signaling pathway in bone metabolism in rats with ovariectomy induced by osteoporosis was investigated. Rats with osteoporosis were orally administered alendronate or phosphate-buffered saline (control). In addition, the interferon-β (IFN-β)/signal transducer and activator of transcription 1 (STAT1) signaling pathway was investigated in osteoblasts following treatment with alendronate in vitro and in vivo. During the differentiation period, IFN-β (100 ng/ml) was used to treat the osteoblast cells, and the activity, viability and bone metabolism-associated gene expression levels (STAT1, p-STAT1, Fra1, TRAF6 and SOCS1) were analyzed in osteoblast cells. Histopathological changes were used to evaluate osteoblasts, osteoclasts, inflammatory phase of bone healing and osteonecrotic areas. The results demonstrated that alendronate significantly inhibited the activity of osteoporotic osteoclasts by stimulating expression of IFN-β, as well as markedly improved the viability and activity of osteoblasts compared with the control group. In addition, alendronate increased the expression and phosphorylation levels of STAT1 in osteoclasts, enhanced osteoblast differentiation, upregulated the expression levels of alkaline phosphatase and osteocalcin, and increased the expression of osteoblast differentiation-associated genes (osteocalcin, osterix and Runx2). Inhibition of IFN-β expression canceled the benefits of alendronate-mediated osteoblast differentiation. Notably, alendronate enhanced bone formation in rats with osteoporosis induced by ovariectomy. In conclusion, these findings suggest that alendronate can regulate osteoblast differentiation and bone formation in rats with osteoporosis induced by ovariectomy through upregulation of IFN-β/STAT1 signaling

  4. Musical Ontology: Critical, not Metaphysical

    Directory of Open Access Journals (Sweden)

    Jonathan A. Neufeld

    2014-01-01

    Full Text Available The ontology of musical works often sets the boundaries within which evaluation of musical works and performances takes place. Questions of ontology are therefore often taken to be prior to and apart from the evaluative questions considered by either performers as they present works to audiences or an audience’s critical reflection on a performance. In this paper I argue that, while the ontology of musical works may well set the boundaries of legitimate evaluation, ontological questions should not be considered as prior to or apart from critical evaluation. Rather, ontological claims are a type of critical evaluation made within musical practices. I argue that philosophers of music might learn from the debate in political philosophy about the difficulty of setting the limits of public reason in a way that remains open to a plurality of legitimate evaluative perspectives. Just as pre-political or metaphysical identification of the boundaries of public reason fail to accommodate the fact of pluralism in contemporary democratic politics, so too does a metaphysical identification of the boundaries of legitimate evaluation of musical works and performances fail to accommodate the fact of pluralism in contemporary musical practices. I apply John Rawls’s formulation of political liberalism, arguing that musical ontology should be critical, not metaphysical.

  5. Prevention of aromatase inhibitor-induced bone loss with alendronate in postmenopausal women: The BATMAN Trial.

    Science.gov (United States)

    Lomax, Anna J; Yee Yap, Saw; White, Karen; Beith, Jane; Abdi, Ehtesham; Broad, Adam; Sewak, Sanjeev; Lee, Chooi; Sambrook, Philip; Pocock, Nicholas; Henry, Margaret J; Yeow, Elaine G; Bell, Richard

    2013-12-01

    Postmenopausal women on aromatase inhibitors (AI) are at risk of aromatase inhibitor-associated bone loss (AIBL) and fractures. In 2005 Osteoporosis Australia proposed an algorithm for bisphosphonate intervention. Three hundred and three postmenopausal women with early breast cancer (EBC) were enrolled (osteoporotic, n=25; osteopaenic, n=146; normal bone mineral density (BMD), n=126). Weekly alendronate (70 mg) treatment efficacy as triggered by the algorithm in preventing bone loss was evaluated. All patients received anastrozole (1 mg daily), calcium and vitamin D. All osteoporotic patients received alendronate at baseline. Eleven out of the 146 (7.5%) osteopaenic patients commenced alendronate within 18 months of participation and eleven commenced after. One hundred and twenty four out of the 146 (84.9%) osteopaenic patients and all 126 with normal baseline BMD did not trigger the algorithm. At three years, lumbar spine mean BMD increased (15.6%, p<0.01) in the osteoporotic group. BMD in the osteopaenic group with early intervention significantly increased at three years (6.3%, p=0.02). No significant change was seen in the late intervention group. No change was observed in those with osteopaenia without alendronate. There was a significant drop in lumbar spine (-5.4%) and hip (-4.5%) mean BMD, in the normal BMD group, none of whom received alendronate. Fracture data will be presented. In postmenopausal women with endocrine-responsive EBC, BMD improved over time when a bisphosphonate is administered with anastrozole in osteoporotic patients using an osteoporosis schedule. Subjects with normal baseline BMD experienced the greatest BMD loss, although none became osteoporotic.

  6. Transhumanism, metaphysics, and the posthuman god.

    Science.gov (United States)

    Bishop, Jeffrey P

    2010-12-01

    After describing Heidegger's critique of metaphysics as ontotheology, I unpack the metaphysical assumptions of several transhumanist philosophers. I claim that they deploy an ontology of power and that they also deploy a kind of theology, as Heidegger meant it. I also describe the way in which this metaphysics begets its own politics and ethics. In order to transcend the human condition, they must transgress the human.

  7. Metaphysics after Metaphysics: The Limitative Conception of First Philosophy in Kant

    OpenAIRE

    Günter Zöller

    2003-01-01

    The essay examines Kant’s Enlightenment conception of metaphysics as a science (Wissenschaft) to be kept free of ideological prejudice and extrarational cognitive resources and to be established under the conditions of public, intersubjectively valid discourse. I analyze Kant’s self-interpretation of his transcendental philosophy as “metaphysics of metaphysics” and argue for the extensional partial identity of the critique of metaphysics and the metaphysics so rendered possible. In particular...

  8. On Darwin's 'metaphysical notebooks'. II: "Metaphysics" and final cause.

    Science.gov (United States)

    Calabi, L

    2001-01-01

    The first part of this paper was published in Rivista di Biologia/Biology Forum 94 (2001). In the second part below an examination is made of the meaning of the term Metaphysics in some passages of the Darwinian Notebooks for the years 1836-1844. Metaphysics no longer defines a field of philosophical enquiries mainly concerning the being and the essence after the manner of Aristotle; it now refers to a kind of philosophy of mind after the manner of J. Locke's criticism of the Hypokeimenon. However Aristotle's Metaphysics also encompasses a treatment of the idea of causes, and of final cause particularly, in the explanation of events, and in the explanation of natural phenomena especially. The criticism of the idea of final cause in the interpretation of the world of life is one of Darwin's foundational acts in his early years. When conceiving his Système du monde, in the last years of the XVIII Century, Laplace could think that God is a hypothesis not really needed by science, as we are told. For the knowledge of organic nature to attain the status of science, it remained to be shown that since--certain of the exemplariness of Newton's Principles as much as cautious before the mystery of life--did not need the hypothesis of final ends in order to understand and explain the productions of the living nature: not only in the form of that final cause (the First Cause, the Vera Causa) in which Natural Theology still rested, but also in the form of nature's inner finality which still moulded Whewell's Kantian philosophy. Such demonstration is a very important subject in Darwin's early enquiries, where he criticises finalism as a projection of self-conceiving Man, likely inherited from a knowing of causality in nuce to be found also in animals.

  9. Alendronate treatment in the revision setting, with and without controlled implant motion

    DEFF Research Database (Denmark)

    Søballe, Kjeld; Chen, Xinqian; Jensen, Thomas B

    2007-01-01

    conditions, even with alendronate. With alendronate and stabilized implants, increased bone was observed near the sclerotic shell of the revision cavity, but it was reduced with alendronate when the implant was unstable. Interpretation Our findings suggest that it may be difficult for alendronate...

  10. Dewey's Naturalistic Metaphysics: Expostulations and Replies

    Science.gov (United States)

    Friedman, Randy L.

    2011-01-01

    Critics of Dewey's metaphysics point to his dismissal of any philosophy which locates ideals in a realm beyond experience. However, Dewey's sustained critique of dualistic philosophies is but a first step in his reconstruction and recovery of the function of the metaphysical. Detaching the discussion of values from inquiry, whether scientific,…

  11. Effects of odanacatib on bone matrix mineralization in rhesus monkeys are similar to those of alendronate

    Directory of Open Access Journals (Sweden)

    Barbara M. Misof

    2016-12-01

    Full Text Available Odanacatib (ODN is a selective and reversible inhibitor of cathepsin K which is an important enzyme for the degradation of collagen I. Aim of the present work was the head-to-head comparison between the effects of ODN and alendronate (ALN on bone mineralization density distribution (BMDD, based on quantitative backscattered electron imaging in relation to changes in histomorphometric mineralizing surface per bone surface (MS/BS in 12–22 years old ovariectomized rhesus monkeys. Trabecular and cortical BMDD derived parameters from vertebrae and proximal tibiae were compared among vehicle (VEH, n = 8, odanacatib low dose (ODN-L, n = 8, odanacatib high dose (ODN-H, n = 8, and alendronate (ALN, n = 6 treated animals. Additionally, data from an intact, non-treated group of animals are shown (INT, n = 8. In trabecular bone from the vertebra and metaphyseal tibia, the BMDD of the ODN and ALN treatment groups was shifted toward higher mineralization densities (p < 0.001 consistent with the significant reduction of MS/BS (p < 0.05 in ODN-H and ALN compared to VEH. Vertebral trabecular CaMean (average degree of mineralization was significantly higher in ODN-L (+6.5%, ODN-H (+6.1%, and ALN (+6.7%, all p < 0.001. Tibial osteonal cortical bone revealed also significantly increased CaMean for ODN-L (+1.4%, p < 0.05, ODN-H (+2.2%, p < 0.05, and ALN (+3.4%, p < 0.001 versus VEH, while primary cortical bone (devoid of secondary osteons did not show any significant differences between the study groups. The percentage of primary bone area in the tibial cross-sections (on average 45 ± 12% was also not significantly different between the study groups (p = 0.232. No significant differences in any BMDD parameters of all studied skeletal sites between ODN and ALN treatment were found. Correlation analysis revealed that MS/BS was highly predictive for trabecular BMDD in vertebral bone. The higher MS/BS, the lower was CaMean. Our findings are

  12. Interzones of Law and Metaphysics

    DEFF Research Database (Denmark)

    Mossin, Christiane

    The dissertation analyzes a contemporary battlefield of law, the field of EU social rights, from a political-philosophical point of view. It is the conviction of the dissertation that law is deeply and inescapably conceptually connected with fundamental features of social order. The interrelations...... between the two do not merely concern the rights and obligations explicitly laid down in the law, but fundamental presumptions regarding the nature of human beings, overall purposes of social order, hierarchical and dynamic features of society and the possibility at all of regulation, its logics...... and sources of authority. On the basis of a historical-conceptual understanding of law according to which law, social structure and metaphysical presumptions are inescapably intertwined, the dissertation derives from the binding provisions of law certain essential features of social order. More precisely...

  13. The Value Question in Metaphysics.

    Science.gov (United States)

    Kahane, Guy

    2012-07-01

    Much seems to be at stake in metaphysical questions about, for example, God, free will or morality. One thing that could be at stake is the value of the universe we inhabit-how good or bad it is. We can think of competing philosophical positions as describing possibilities, ways the world might turn out to be, and to which value can be assigned. When, for example, people hope that God exists, or fear that we do not possess free will, they express attitudes towards these possibilities, attitudes that presuppose answers to questions about their comparative value. My aim in this paper is to distinguish these evaluative questions from related questions with which they can be confused, to identify structural constraints on their proper pursuit, and to address objections to their very coherence. Answers to such evaluative questions offer one measure of the importance of philosophical disputes.

  14. The Value Question in Metaphysics

    Science.gov (United States)

    Kahane, Guy

    2012-01-01

    Much seems to be at stake in metaphysical questions about, for example, God, free will or morality. One thing that could be at stake is the value of the universe we inhabit—how good or bad it is. We can think of competing philosophical positions as describing possibilities, ways the world might turn out to be, and to which value can be assigned. When, for example, people hope that God exists, or fear that we do not possess free will, they express attitudes towards these possibilities, attitudes that presuppose answers to questions about their comparative value. My aim in this paper is to distinguish these evaluative questions from related questions with which they can be confused, to identify structural constraints on their proper pursuit, and to address objections to their very coherence. Answers to such evaluative questions offer one measure of the importance of philosophical disputes. PMID:23024399

  15. Effects of teriparatide versus alendronate for treatment of postmenopausal osteoporosis

    Science.gov (United States)

    Wang, Ya-Kang; Qin, Si-Qing; Ma, Tao; Song, Wei; Jiang, Ren-Qi; Guo, Jian-Bin; Li, Kun; Zhang, Yu-Min

    2017-01-01

    Abstract Objectives: Osteoporosis remains a clinical challenge. Teriparatide is an anabolic drug and alendronate is an antiresorptive agent; both are used in the treatment of osteoporosis. Comprehensive reviews investigating the comparative safety and efficacy of teriparatide versus alendronate are scarce. Therefore, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the safety and efficacy of teriparatide versus alendronate for the treatment of postmenopausal osteoporosis. Methods: We conducted a comprehensive literature review of the PubMed, EMBASE, Cochrane Controlled Trials Registry, and the China Academic Journal Network Publishing databases for relevant RCTs of teriparatide versus alendronate in postmenopausal osteoporosis patients. Outcome measures were percentage change in lumbar spine and femoral neck bone mineral density (BMD) and incidence of vertebral and nonvertebral fractures. Effect size was reported as weighted mean differences (WMDs) for continuous outcomes and odds ratios (OR) for dichotomous outcomes, with associated 95% confidence intervals (CIs). Results: Six trials involving 618 patients were included. The meta-analysis demonstrated a significant increase in lumbar spine BMD (WMD: 3.46, 95% CI: 2.15–4.77, P osteoporosis patients treated with teriparatide compared with alendronate for 6 to 18 months. These beneficial effects were apparent in the lumbar spine at 12 months of treatment (WMD: 4.49, 95% CI: 2.57–6.40, P osteoporosis. The efficacy and safety of long-term teriparatide and alendronate treatment in postmenopausal osteoporosis should be further investigated in clinical trials. PMID:28538396

  16. Treatment of osteoporosis after alendronate or risedronate

    DEFF Research Database (Denmark)

    Eiken, P; Vestergaard, P

    2016-01-01

    Alendronate (ALN) and risedronate (RIS) are ideal as first-choice therapy options in the treatment of postmenopausal osteoporosis. What to do for patients who do not respond adequately to bisphosphonates has not been conclusively determined, but transitioning to other therapies should be considered....... The aim of this article is to describe potential alternatives for patients switching from ALN or RIS to other therapies for osteoporosis. A systematic search of PubMed was conducted to find papers that evaluate the effects of switching therapies on fractures, bone mineral density (BMD), or bone turnover...... markers. Results from 11 studies that prospectively assessed treatment after ALN or RIS in women with postmenopausal osteoporosis were reviewed. All studies are of short duration (all 24 months or less) and assess the topic of transitioning therapy from ALN or RIS. None of the studies had the statistical...

  17. A proper metaphysics for cognitive performance.

    Science.gov (United States)

    Van Orden, Guy C; Moreno, Miguel A; Holden, John G

    2003-01-01

    The general failure to individuate component causes in cognitive performance suggests the need for an alternative metaphysics. The metaphysics of control hierarchy theory accommodates the fact of self-organization in nature and the possibility that intentional actions are self-organized. One key assumption is that interactions among processes dominate their intrinsic dynamics. Scaling relations in response time variability motivate this assumption in cognitive performance.

  18. Socialcultural background of formation of classical metaphysics

    OpenAIRE

    I. Z. Derzhko

    2014-01-01

    The classical model of philosophy has shaped ideas about its nature and aims that were laid in ancient metaphysics, but have been substantially amended by civilizational change. Socialcultural background of philosophy became trends that began to emerge in late medieval culture has particularly flourished there during modern times. Sphere of existence is important for the development of any spiritual phenomenon. For metaphysics it is the idea of humanity, acting as a kind of cultural protest a...

  19. Metaphysics and medical ethics: a reply.

    Science.gov (United States)

    Gillett, G

    1994-01-01

    The total longitudinal form view of human beings is a metaphysical view which aims to locate our moral judgements about human embryos in a broader set of attitudes and characterisations. On this basis it has explanatory power and a real function in that it grounds our ethical discussion of embryos in other discourses. Contra Leavitt, this grounding suggests a broader criterion of relevance for metaphysical discussion than asking 'what comes out of' such a discussion for a particular ethical dilemma. PMID:8035442

  20. On the metaphysics of experimental physics

    CERN Document Server

    Rogers, K

    2005-01-01

    This provocative and critical work addresses the question of why scientific realists and positivists consider experimental physics to be a natural and empirical science. Taking insights from contemporary science studies, continental philosophy, and the history of physics, this book describes and analyses the metaphysical presuppositions that underwrite the technological use of experimental apparatus and instruments to explore, model, and understand nature. By revealing this metaphysical foundation, the author questions whether experimental physics is a natural and empirical science at all.

  1. Alendronate-coated long-circulating liposomes containing 99mtechnetium-ceftizoxime used to identify osteomyelitis

    Directory of Open Access Journals (Sweden)

    Ferreira DS

    2015-03-01

    Full Text Available Diego dos Santos Ferreira,1 Fernanda Alves Boratto,1 Valbert Nascimento Cardoso,2 Rogéria Serakides,3 Simone Odília Fernandes,2 Lucas Antônio Miranda Ferreira,1 Mônica Cristina Oliveira1 1Department of Pharmaceutical Products, Faculty of Pharmacy, 2Department of Clinical and Toxicological Analyses, Faculty of Pharmacy, 3Veterinary School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil Abstract: Osteomyelitis is a progressive destruction of bones caused by microorganisms. ­Inadequate or absent treatment increases the risk of bone growth inhibition, fractures, and sepsis. Among the diagnostic techniques, functional images are the most sensitive in detecting osteomyelitis in its early stages. However, these techniques do not have adequate specificity. By contrast, radiolabeled antibiotics could improve selectivity, since they are specifically recognized by the bacteria. The incorporation of these radiopharmaceuticals in drug-delivery systems with high affinity for bones could improve the overall uptake. In this work, long-circulating and alendronate-coated liposomes containing 99mtechnetium-radiolabeled ceftizoxime were prepared and their ability to identify infectious foci (osteomyelitis in animal models was evaluated. The effect of the presence of PEGylated lipids and surface-attached alendronate was evaluated. The bone-targeted long-circulating liposomal 99mtechnetium–ceftizoxime showed higher uptake in regions of septic inflammation than did the non-long-circulating and/or alendronate-non-coated liposomes, showing that both the presence of PEGylated lipids and alendronate coating are important to optimize the bone targeting. Scintigraphic images of septic or aseptic inflammation-bearing Wistar rats, as well as healthy rats, were acquired at different time intervals after the intravenous administration of these liposomes. The target-to-non-target ratio proved to be significantly higher in the osteomyelitis

  2. Internal Realism: Putnam's Alternative to Metaphysical Realism

    Directory of Open Access Journals (Sweden)

    J Akbari Takhtameshlou

    2014-02-01

    Full Text Available Hilary Putnam, who was once one of the representatives and proponents of scientific and metaphysical realism, became an unrelenting opponent of metaphysical realism during the mid-70s. Having argued against alethic and ontological dimensions of metaphysical realism, he proposed “internal realism” as an alternative to it. Putnam's major objection to the alethic dimension of metaphysical realism was that this philosophy brings about an unbridgeable gap between the truth of a proposition and our epistemic justifications for it. As to the ontological dimension of metaphysical realism, he proposed the criticism to the effect that according to this philosophical position the world consists of “ready-made” objects. Putnam poses these criticisms because, as he argues, firstly, truth cannot be considered anything but the ideal justification and secondly, the world is not made of ready-made objects, but rather it is we that cut up the world into different objects when we take a conceptual scheme. Indeed, according to Putnam assuming any "external perspective", whether about truth or about ontology, is meaningless. Having introduced and reviewed Putnam's arguments in rejecting metaphysical realism, this article explains and examines the basic elements of internal realism. The results of this article show that Putnam's objections against metaphysical realism lack the necessary credibility and strength and at the same time his proposed alternative (internal realism has serious problems that made to be addressed. By his chosen conception of truth, internal realism, cannot touch its stated purpose i.e. the removal of a huge gap between the truth of a statement and our knowledge of it. The ontological claims of internal realism are not, indeed, the reliable and true consequences of the thesis of conceptual relativity, which is considered as Putnam’s main base in this regard, but rather it is more a consequence of mistaking the

  3. Alendronate functionalized mesoporous hydroxyapatite nanoparticles for drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Li, Dongdong, E-mail: lidongchem@sina.cn [State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China); Zhu, Yuntao; Liang, Zhiqiang [State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China)

    2013-06-01

    Highlights: ► The synthesized mesoporous hydroxyapatite has nanostructure and bioactivity. ► The materials have high surface area and amino group. ► The materials show higher drug loading and slower release rate than pure HAP. - Abstract: Mesoporous nanosized hydroxyapatite (HAP) functionalized by alendronate (ALN) was synthesized using cationic surfactant CTAB as template. The structural, morphological and textural properties were fully characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR) and N{sub 2} adsorption/desorption. Then the obtained materials were performed as drug delivery carriers using ibuprofen (IBU) as a model drug to investigate their drug storage/release properties in simulated body fluid (SBF). The materials showed relatively slower release rate compared with HAP due to the ionic interaction between -NH{sub 3}{sup +} on the matrix and -COO{sup −}belongs to IBU. The system provides a new concept for improving the drug loading or slowing down the release rate.

  4. Hydrophobically Modified Glycol Chitosan Nanoparticles for Targeting Breast Cancer Microcalcification Using Alendronate Probes

    Science.gov (United States)

    Vishnu, Kamalakannan

    In 2016, invasive breast cancer was diagnosed in about 246,660 women and 2,600 men. An additional 61,000 new cases of in situ breast cancer was diagnosed in women. Microcalcifications are most common abnormalities detected by mammography for breast cancer, present in about 30% of all malignant breast lesions. Tumor specific biomarkers are used for targeting these abnormalities. Nanoparticles with multimodal and combinatorial therapies and conjunction of bio-ligands for specific molecular targeting using surface modifications effectually deliver a variety of drugs and are simultaneously used to image tumor progression. Alendronate, a germinal bisphosphonate conjugation as a targeting ligand would improve the nanoparticle's direct binding to hydroxyapatite (HA) mimicking calcified spots in breast cancer lesions. In this study, the hydrophobically modified glycol chitosan (HGC) micelle was modified with alendronate surface functionalization using a biotin-avidin interaction to improve the nanomicelle's calcification targeting ability. Biotinylated, avidinlyated hydrophobically modified iv glycol chitosan particles were linked to biotinylated alendronate via a strong biotin-avidin linkage. Cyanine 3, a red fluorescent dye was conjugated to the amine groups on HGC for visualization of micelles. The size of the nanoparticles measured was 254.0 +/- 0.43 nm and 209.7 +/- 1.0 nm for Cy3- BHGCA and Cy3-BHGCA-BALN nanoparticles respectively. The average surface charge was measured to be +26.9 +/- 0.19 mV and +27.68 +/- 0.20 mV for Cy3-BHGCA and Cy3-BHGCA- BALN nanoparticles respectively. Binding affinity using hydroxyapatite (HA) revealed that both Cy3 BHGCA BALN and Cy3 BHGCA nanoparticles displayed 95% binding in 24 hours. However, the biotin quenched nanoparticle Cy3 BHGCAB displayed 68% binding in 24 hours. The synthesis and binding chemistry was verified using Fourier transform infrared spectroscopy (FTIR).

  5. Metaphyseal impaction fractures in acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Manson, D.; Cockshott, W.P.; Martin, R.F.

    1989-01-01

    Patients with acute lymphatic leukaemia frequently are osteoporotic. A small subset of these develop disabling metaphyseal transverse fractures, usually bilateral and in the lower limb. These impaction fractures have a characteristic appearance and develop in recently laid down bone. They may develop ab initio of during therapy, Magnesium deficiency is found in these patients.

  6. Metaphysical Realism: A Conceptual Analysis | Emedolu | Sophia ...

    African Journals Online (AJOL)

    Metaphysical realism is a common sense disposition that maintains that there exist objects in the world with their structure-defining properties, and that scientific theories try to explain reality exactly the way it is. The crucial question for this paper is whether the human mind does not make any contribution in the very art of ...

  7. Quine, Putnam, and the Naturalization of Metaphysics

    NARCIS (Netherlands)

    Verhaegh, Sander; Baumgartner, S.; Heisenberg, T.; Krebs, S.

    2014-01-01

    Naturalists argue that metaphysics ought to be in some sense continuous with science. Putnam has claimed that if we push naturalism to its limits, we have to conclude with Quine that reference is indeterminate. Since Putnam believes Quine’s thesis to be extremely counterintuitive, he regards

  8. What is Metaphysical Equivalence? | Miller | Philosophical Papers

    African Journals Online (AJOL)

    Theories are metaphysically equivalent just if there is no fact of the matter that could render one theory true and the other false. In this paper I argue that if we are judiciously to resolve disputes about whether theories are equivalent or not, we need to develop testable criteria that will give us epistemic access to the obtaining ...

  9. Metaphysical Beliefs as Predictors of Death Anxiety.

    Science.gov (United States)

    Naidu, R. K.; Sinha, Ambalika

    1992-01-01

    Investigated impact of four metaphysical beliefs (existence of God, attributes of God, afterlife, consequences of suffering) on death anxiety. Householders (n=120), one-half of whom lived in high exposure to death sight areas, responded to pictures depicting death and nondeath scenes to measure death anxiety. Subjects from low exposure areas…

  10. The Role of Metaphysical Naturalism in Science

    Science.gov (United States)

    Mahner, Martin

    2012-01-01

    This paper defends the view that metaphysical naturalism is a constitutive ontological principle of science in that the general empirical methods of science, such as observation, measurement and experiment, and thus the very production of empirical evidence, presuppose a no-supernature principle. It examines the consequences of metaphysical…

  11. The discourse of Jurgen Habermas: metaphysics after Kant

    OpenAIRE

    D. O. Shyshkin

    2014-01-01

    The purpose of the article is to implement the explication of one of the sub-sections of the work of Jurgen Habermas «Postmetaphysical thinking», which is called «Metaphysics after Kant». This work of the German philosopher is a milestone to mark the location of metaphysics, problems of metaphysics and differences in the position of metaphysics for Kant and after him. Some abstracts demonstrate how the discourse of Habermas and proves protective provisions postkantian metaphysics that violate...

  12. Determination of death: Metaphysical and biomedical discourse

    Directory of Open Access Journals (Sweden)

    Irayda Jakušovaitė

    2016-01-01

    Full Text Available The prominence of biomedical criteria relying on brain death reduces the impact of metaphysical, anthropological, psychosocial, cultural, religious, and legal aspects disclosing the real value and essence of human life. The aim of this literature review is to discuss metaphysical and biomedical approaches toward death and their complimentary relationship in the determination of death. A critical appraisal of theoretical and scientific evidence and legal documents supported analytical discourse. In the metaphysical discourse of death, two main questions about what human death is and how to determine the fact of death clearly separate the ontological and epistemological aspects of death. During the 20th century, various understandings of human death distinguished two different approaches toward the human: the human is a subject of activities or a subject of the human being. Extinction of the difference between the entities and the being, emphasized as rational–logical instrumentation, is not sufficient to understand death thoroughly. Biological criteria of death are associated with biological features and irreversible loss of certain cognitive capabilities. Debating on the question “Does a brain death mean death of a human being?” two approaches are considering: the body-centrist and the mind-centrist. By bridging those two alternatives human death appears not only as biomedical, but also as metaphysical phenomenon. It was summarized that a predominance of clinical criteria for determination of death in practice leads to medicalization of death and limits the holistic perspective toward individual's death. Therefore, the balance of metaphysical and biomedical approaches toward death and its determination would decrease the medicalization of the concept of death.

  13. Development of docetaxel and alendronate-loaded chitosan ...

    African Journals Online (AJOL)

    Development of docetaxel and alendronate-loaded chitosan-conjugated polylactide-co-glycolide nanoparticles: In vitro characterization in osteosarcoma cells. ... The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader).

  14. Development of docetaxel and alendronate-loaded chitosan ...

    African Journals Online (AJOL)

    Development of docetaxel and alendronate-loaded chitosan-conjugated polylactide-co-glycolide nanoparticles: In vitro characterization in osteosarcoma cells. ... typical time-dependent cellular uptake and also displayed superior cytotoxicity in MG-63 cells compared with blank NPs, which were safe and biocompatible.

  15. Urine Calcium and Bone Mineral Density in Calcium Stone-Forming Patients Treated with Alendronate and Hydrochlorothiazide.

    Science.gov (United States)

    Arrabal-Martín, Miguel; González-Torres, Samuel; Cano-García, María Del Carmen; De Haro-Muñoz, Tomás; Abad-Menor, Félix; Arrabal-Polo, Miguel Ángel; Cózar-Olmo, José Manuel

    2016-01-01

    The objective was to evaluate the effect of hydrochlorothiazide and alendronate on urine calcium and bone mineral density in calcium stone-forming patients. A prospective, non-randomized, non-observational comparative study was performed; this study included 111 patients with recurrent calcium stones, divided into 3 groups according to the treatment received. Group 1: 36 patients were treated with alendronate, 70 mg/week; Group 2: 34 patients were treated with alendronate, 70 mg/week + hydrochlorothiazide, 50 mg/day; Group 3: 41 patients were treated with hydrochlorothiazide, 50 mg/day. All patients received recommendations on diet and fluid intake. Other variables of bone mineral density were studied and analyzed, including bone remodeling markers and urinary calcium before and after 2 years of treatment. The statistical analysis was performed using the SPSS 17.0 program, with a statistical significance of p hydrochlorothiazide treatment offers the best results along with the improvement in bone mineral density and decrease in urine calcium in patients with recurrent calcium stones. © 2016 S. Karger AG, Basel.

  16. The many Metaphysics within Physics. Essay review of 'The Metaphysics within Physics' by Tim Maudlin

    Science.gov (United States)

    Suárez, Mauricio

    Tim Maudlin's new book The Metaphysics within Physics (Oxford University Press, 2007) collects six essays by one of the most thoughtful and original minds working in the philosophy of physics nowadays. Some had previously circulated informally for years. For example, Chapter 1 ('A Modest Proposal Concerning Laws, Counterfactuals and Explanations') is as old as my own philosophical career-I recall reading a draft in the early 1990s. The mere publication of such a long-awaited collection is therefore already good news. In addition, the degree of coherence and the lack of redundancy are greater than one would expect from a collection of disparate essays written at diverse times and with a range of different targets. The whole book can be understood coherently as an extended argument in favor of a particular 'physics-based' methodology for inquiry in metaphysics. This methodology recommends a detailed and thorough analysis of current physics as a benchmark for any thesis, dispute or argument in metaphysics. It follows that proper metaphysical inquiry must be suitably informed not just about the current state of play in analytical metaphysics but also about the current state of development of the relevant part of present day physics.

  17. Abstract Objects in a Metaphysical Perspective

    Directory of Open Access Journals (Sweden)

    Aleksandr Kulieshov

    2018-02-01

    Full Text Available The article presents an unconventional although not absolutely unprecedented view on abstract objects defending the position of metaphysical realism. It is argued that abstract objects taken in purely ontological sense are the forms of objects. The forms possess some common characteristics of abstract objects, they can exist not in physical space and time and play a grounding role in their relation to concrete objects. It is stated that commonly discussed abstract objects – properties, kinds, mathematical objects – are forms.

  18. Metaphysics and medical education: taking holism seriously.

    Science.gov (United States)

    Wilson, Bruce

    2013-06-01

    Medical education is now suffused with concepts that have their source outside the traditional scientific and medical disciplines: concepts such as holism, connectedness and reflective practice. Teaching of these, and other problematic concepts such as medical uncertainty and error, has been defined more by the challenge they pose to the standard model rather than being informed by a strong positive understanding. This challenge typically involves a critical engagement with the idea of objectivity, which is rarely acknowledged as an inherently metaphysical critique. Consequently, these ideas prove to be difficult to teach well. I suggest that the lack of an integrating, positive narrative is the reason for teaching difficulty, and propose that what is needed is an explicit commitment to teach the metaphysics of medicine, with the concept of holism being the fulcrum on which the remaining concepts turn. An acknowledged metaphysical narrative will encompass the scientific realism that medical students typically bring to their tertiary education, and at the same time enable a bigger picture to be drawn that puts the newer and more problematic concepts into context. © 2013 John Wiley & Sons Ltd.

  19. Alveolar bone dynamics in osteoporotic rats treated with raloxifene or alendronate: confocal microscopy analysis

    Science.gov (United States)

    Ramalho-Ferreira, Gabriel; Faverani, Leonardo Perez; Grossi-Oliveira, Gustavo Augusto; Okamoto, Tetuo; Okamoto, Roberta

    2015-03-01

    In this study, the characteristics of the alveolar bone of rats with induced osteoporosis were examined. Thirty-two rats were divided into four groups according to the induction of osteoporosis and drugs administered: OG, osteoporotic rats without treatment (negative control); SG, rats which underwent sham surgery ovariectomy (SHAM); alendronate (AG), osteoporotic rats treated with alendronate; and RG, osteoporotic rats treated with raloxifene (RG). On the 8th day after ovariectomy and SHAM surgeries, drug therapy was started with AG or RG. On the 52nd day, 20 mg/kg calcein was administered to all of the rats, and on the 80th day, 20 mg/kg alizarin red was administered. Euthanasia was performed on the 98th day. The bone area marked by fluorochromes was calculated and data were subjected to two-way ANOVA test and Tukey's post-hoc test (p<0.05). The comparison of the induced osteoporosis groups showed no statistically significant differences in bone turnover only between RG and SG (p=0.074) and AG and OG (p=0.138). All other comparisons showed significant differences (p<0.001). The largest bone turnover was observed in RG and SG groups. RG was the medication that improved the dynamics of the alveolar bone of rats with induced osteoporosis, resembling that of healthy rats.

  20. Effects of local alendronate sodium gel as an adjunct to scaling and root planing on smokers with chronic periodontitis: a pilot study

    Directory of Open Access Journals (Sweden)

    Farin Kiany

    2017-04-01

    Full Text Available Background: Chemical treatments for the modulation of host response are applied along with mechanical modalities as adjunctive to periodontal treatment. The objective of this pilot study was to investigate the effects of locally-delivered alendronate sodium gel in adjunction to scaling and root planning on periodontal indices and bone formation within vertical defects of smokers with chronic periodontitis. Methods and Materials: In this study vertical defects (n=8 with depth>5 mm have been investigated. After performing the phase I of periodontal treatment, alendronate sodium gel (1% was applied into the periodontal pockets. The whole procedure was repeated after 4 weeks. Periodontal indices (plaque and bleeding, probing depth, gingival recession, and radiographic parameter (depth of bony defect were measured at the beginning and following 6 months. Results: Compared to pre-treatment, the probing depth, radiographic depth of bony defect and bleeding and plaque indices were significantly reduced by local application of alendronate sodium gel (P=0.026; P=0.012 and P=0.007 respectively. Gingival recession showed significant increase (P=0.011. Conclusion: Local alendronate sodium gel (1% plays an important role in the improvement process of periodontal indices and bone formation within vertical bony defects of smoker patients with chronic periodontitis.

  1. Esophageal and gastric cancer incidence and mortality in alendronate users

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Pazianas, Michael; Eiken, Pia Agnete

    2012-01-01

    Recent studies have reached conflicting conclusions regarding the risk of esophageal cancer with oral bisphosphonates. Prior studies did not record the number of cancer deaths or endoscopy rates, which could be higher in bisphosphonate users and lead to more cancers being diagnosed at a stage when...... their esophageal or gastric location could be accurately distinguished. We conducted a register-based, open cohort study using national healthcare data for Denmark. Upper endoscopy frequency, cancer incidence and mortality was examined in 30,606 alendronate users (female, age 50¿+¿) and 122,424 matched controls....... Primary outcomes were esophageal cancer incidence and death due to esophageal cancer. The analysis showed that alendronate users were more likely to have undergone recent upper endoscopy (4.1 vs 1.7%, p¿...

  2. Fixation principles in metaphyseal bone--a patent based review.

    Science.gov (United States)

    Curtis, R; Goldhahn, J; Schwyn, R; Regazzoni, P; Suhm, N

    2005-03-01

    Osteoporotic changes start in cancellous bone due to the underlying pathophysiology. Consequently, the metaphyses are at a higher risk of "osteoporotic" fracture than the diaphysis. Furthermore, implant purchase to fix these fractures is also affected by the poor bone quality. In general, researchers and developers have worked on three different approaches to address the problem of fractures to osteoporotic bone: adapted anchoring techniques, improved load distribution as well as transfer with angular stable screws, and augmentation techniques using bone substitutes. A patent-based review was performed to evaluate which ideas were utilized to improve fixation in osteoporotic, metaphyseal bone, especially in the proximal femur, and to analyze whether the concept had entered clinical use. Anchoring devices that are either extramedullary or intramedullary have a long clinical history. However, demanding surgical techniques and complications, especially in poor quality bone, are justification that such implants and their corresponding surgical techniques need to be improved upon. Expanding elements have been evaluated in the laboratory. The results are promising and the potential of this approach has yet to be fully exploited in the clinics. Internal fixators with angular stable screws open the door for many new anchorage ideas and have great potential for further optimization of load distribution and transfer. Augmentation techniques may improve anchorage in osteoporotic bone. However, the properties of bone substitute materials will need to be modified and improved upon in order to meet the demanding requirements. If we summarise the development process and the clinical use of implants to date, we have to clearly state that more factors than simply biomechanical advantage will determine the clinical success of a new fixation principle or a new implant. Instead, fracture treatment of patients with osteoporosis really needs an interdisciplinary approach!

  3. Alendronate in the prevention of collapse of the femoral head in nontraumatic osteonecrosis: a two-year multicenter, prospective, randomized, double-blind, placebo-controlled study.

    Science.gov (United States)

    Chen, Chung-Hwan; Chang, Je-Ken; Lai, Kuo-An; Hou, Sheng-Mou; Chang, Chih-Hao; Wang, Gwo-Jaw

    2012-05-01

    Osteonecrosis is one of the major debilitating skeletal disorders. Most patients with osteonecrosis of the femoral head eventually need surgery, usually total hip arthroplasty (THA), within a few years of onset. Previous studies showed that alendronate has a pharmacologic effect in reducing osteoclast activity and that it significantly reduced the incidence of collapse of the femoral head in the osteonecrotic hip. The purpose of this study was to determine the cumulative incidence of THA in patients with osteonecrosis of the femoral head and the time-to-event after treatment with alendronate versus placebo during the study period. A 2-year multicenter, prospective, randomized, double-blind study was performed. From June 2005 to December 2006, 64 patients were enrolled and randomly assigned to the alendronate or placebo group. In patients with bilateral hip osteonecrosis who met the inclusion criteria, both hips were counted in the analyses. Five patients were excluded from the analysis because they did not comply with any of the study regimens. Seven patients were ineligible because they were not diagnosed as having stage IIC or stage IIIC disease according to the University of Pennsylvania system. Thus, a total of 52 patients (65 hips) were assessed in this study. Disease progression was evaluated by radiography and magnetic resonance imaging (MRI). The Harris Hip Score and the Short Form 36 health survey were used to rate hip function and quality of life, respectively. There was no significant difference in radiographic and MRI data between the 2 study groups. Four of 32 hips in the alendronate treatment group underwent THA, while 5 of 33 hips in the placebo group had THA (P = 0.837). No differences were noted in disease progression, Harris Hip Scores, or Short Form 36 scores between the 2 groups. Alendronate has no obvious effect on preventing the necessity for THA, reducing disease progression, or improving life quality. Copyright © 2012 by the American

  4. Mendelssohn and Kant on Mathematics and Metaphysics

    OpenAIRE

    Callanan, John Joseph

    2014-01-01

    The difference between the method of metaphysics and the method of mathematics was an issue of central concern for Kant in both the Pre-Critical and Critical periods. I will argue that when Kant speaks of the ‘philosophical method’ in the Doctrine of Method in the Critique of Pure Reason (CPR), he frequently has in mind not his own methodology but rather the method of conceptual analysis associated with rationalism. The particular target is Moses Mendelssohn’s picture of analysis contained in...

  5. Alendronate and estrogen-progestin in the long-term prevention of bone loss

    DEFF Research Database (Denmark)

    Ravn, Pernille; Bidstrup, M; Wasnich, R D

    1999-01-01

    BACKGROUND: Up to 3 years of treatment with alendronate, 5 mg/d, prevents postmenopausal bone loss. OBJECTIVE: To determine whether the effect of alendronate is sustained at 4 years of treatment and persists after treatment is discontinued. DESIGN: Randomized, controlled trial. SETTING: United St...

  6. Metaphysical outlooks in physics and the anthropic principle.

    Science.gov (United States)

    Dallaporta, N.

    In order to justify the various assumptions current in present day cosmology, it is necessary for each of them to build a frame of metaphysical postulates much more involved and artificial than the opposite straightforwardly metaphysical view of a universe built according to an a priori plan, requiring a planning intelligence adequate to have conceived it.

  7. Naturalizing the Metaphysics of Species: A Perspective on the ...

    African Journals Online (AJOL)

    The idea of naturalizing metaphysics stretches back to Locke and Newton. Recently it has been revived by Ross and Ladyman et al (2007) in 'Every Thing Must Go'. At the heart of the doctrine is the idea that metaphysics should be constrained by actual science (science which is current and institutionally valid). It is my ...

  8. The Problem of Being in Metaphysics | Kanu | African Research ...

    African Journals Online (AJOL)

    What is being? This was and still is one of the fundamental questions within the area of metaphysics. The researcher in this piece studies the dynamics of the problem of being in metaphysics. A historical approach is adopted to this study. The researcher goes through the Ancient, Medieval, Modern and Contemporary ...

  9. Hylozoism as an Interpretive Principle in African Metaphysics ...

    African Journals Online (AJOL)

    Hylozoism as an Interpretive Principle in African Metaphysics. ... is only used as an interpretive principle in African Metaphysics; unlike the widely held assumption by some popular proponents that inanimate beings have elein vitale, that is, life-force. ... LWATI: A Journal of Contemporary Research, 8(1), 319-327, 2011 ...

  10. The metaphysics market - pushing language as platonic (not to ...

    African Journals Online (AJOL)

    This is the fourth of a series of studies in which prototypical conceptions of language are subversively turned inside out. It has to be read together with the first three, The Metaphysics Market: 1 Merchandizing Language as Matter (= SPIL PLUS li, 1989), The Metaphysics Market: 2 Billing Language as Behavioural (= SPIL ...

  11. The metaphysics market - selling language as soul | Botha ...

    African Journals Online (AJOL)

    This is the third of a series of studies in which prototypical conceptions of language are subversively turned inside out. It has to be read together with the first two, The Metaphysics Market: 1 Merchandizing Language as Matter (= SPIL 20, 1989) and The Metaphysics Market: 2 Billing Language as Behavioural (= SPIL 21, ...

  12. The Functionality of Being in Pantaleon's Operative Metaphysics vis ...

    African Journals Online (AJOL)

    The area of operative metaphysics speaks of a metaphysical system that does not just exist as an ivory tower apart from people's experience, but one that could be applied to a concrete historical circumstance. This piece studies the concept of being as understood by Pantaleon Iroegbu, as being qua belongingness.

  13. The metaphysics market - stocking language as something social ...

    African Journals Online (AJOL)

    This is the fifth of a series of studies in which prototypical conceptions of language are turned inside out. It has to be read together with the first four, The Metaphysics Market: 1 Merchandizing Language as Matter C= SPIL 20, 1989), The Metaphysics Market: 2 Billing Language as Behavioural (= SPIL 21, 1990), The ...

  14. Alendronate prevents postmenopausal bone loss in women without osteoporosis. A double-blind, randomized, controlled trial. Alendronate Osteoporosis Prevention Study Group

    DEFF Research Database (Denmark)

    McClung, M; Clemmesen, B; Daifotis, A

    1998-01-01

    BACKGROUND: Preventing bone loss associated with menopause and aging and maintaining the normal micro-architecture of bone provide important opportunities for the prevention of osteoporosis and fractures. OBJECTIVE: To determine the safety and efficacy of alendronate, an aminobisphosphonate, for ...

  15. The Effect of Alendronate and Calcitonin Treatments on Bone Mineral Density and Quality of Life in Women With Postmenopausal Osteoporosis

    Directory of Open Access Journals (Sweden)

    F. Taşçıoğlu

    2002-06-01

    Full Text Available The aim of this study was to compare the effect of alendronate and calcitonin treatments on bone mineral density (BMD and quality of life of women with postmenopausal osteoporosis. One hundred ninety-three patients were randomly assigned to two groups: 93 patients received daily doses of 10 mg alendronate and calcium 1000 mg, and 98 patients used intranasal salmon calcitonin (sCt at a dosage of 200 IU/day and they also received daily doses of 1000 mg calcium supplements. DXA was used for the measurement of BMD of the lumbar spine and proximal femur before and after the study period. SF-36 was used as a measure of health-related quality of life. At the end of the treatment, ALN produced significant increases in BMD at the lumbar spine (p< 0.001, femur neck (p<0.05, trochanteric region (p<0.001 and at the Ward triangle (p<0.05. In contrast, intranasal sCt treatment resulted in a significant bone loss in the femur neck (p<0.01 and Ward triangle (p<0.05, and only a significant increase in BMD of the lumbar spine was observed with calcitonin treatment(p< 0.05. Quality of life as assessed by SF-36 improved significantly in both groups(p<0.05. In conclusion, alendronate seemed to be more effective than calcitonin, increasing both spinal and femoral BMD, for the treatment of postmenopausal osteoporosis. Both treatments were found to be effective for the improvement of quality of life.

  16. Diderot’s ontology and Hollywood metaphysics

    Directory of Open Access Journals (Sweden)

    Božovič Miran

    2013-01-01

    Full Text Available Diderot’s universe is somewhat weird, often dreamlike and hallucinatory, and his ontology fluid and elusive. It comprises the existing, the non-existent and even contradictory entities, the boundaries between which cannot always be clearly delimited. This universe in which nothing is of the essence of a particular being and everything is more or less something or other, resembles the amorphous and oneiric world of Zhuangzi in which nothing is clearly defined, while essenceless things, floating in uncertainty and indeterminacy, literally blend into one another. The author examines what the early Hollywood comedies of Preston Sturges and the Marx brothers can teach us about the metaphysics and the principles at work in this complex and intricate world.

  17. Audism: exploring the metaphysics of oppression.

    Science.gov (United States)

    Bauman, H-Dirksen L

    2004-01-01

    This article traces the development of the concept of "audism" from its inception in the mid-1970s by exploring three distinct dimensions of oppression: individual, institutional, and metaphysical. Although the first two aspects of audism have been identified, there is a deeply rooted belief system regarding language and human identity that is yet to be explored within the context of audism. This article attempts to expose how our particular historical and philosophical constructions of language and being have created what French philosopher Jacques Derrida calls phonocentrism. Although Derrida does not discuss audism, his deconstruction of the Western notion of language provides a lens through which we can better see the orientation that has provided fertile ground out of which individual and institutional audism has flourished.

  18. The Metaphysics of Chinese Information Philosophy

    DEFF Research Database (Denmark)

    Liqian, Zhou; Brier, Søren

    2015-01-01

    Compared with other transdisciplinary frames of information Wu Kun’s philosophy of information differs in its metaphysical framework in that it has a background in a conception of Dialectics of Nature coming from the old Stalin textbook system but also a part of the renewal of thinking in China...... appearing through the thought liberty movement in the 1980s, which among other things also added a modern view of information to Chinese thinking. Still it is a philosophy in a distinctive Chinese style. Wu’s philosophical system begins by re-dividing the field of existence and founding a new ontological...... area or aspect of being, which he called the world of information and named it objective unreality. This, ontological framework, different from that in the West, made the concept of information in his system different from the information concept in Shannon’s and even Wiener’s sense. Wu’s philosophy...

  19. Transition from Critical Ontology To Metaphysical Foundations of Natural Science

    Directory of Open Access Journals (Sweden)

    Juan Csno De Pablo

    2015-03-01

    Full Text Available The Critique of Pure Reason out lines an a priori ontology of nature. We find in the Critique the category of substance, which is totally a priori. However, the metaphysical principles of natural science come from the notion of matter, which is empirical. This article shows the transition carried out by Kant between two areas of knowledge. For this purpose, we will relate two Kantian texts: Prologomena to Any Future Metaphysics Which Shall Lay Claim to Being a Science and Metaphysical Foundations of Natural Science.

  20. OUT-OF-BODY EXPERIENCE, PURE BEING AND METAPHYSICS

    Directory of Open Access Journals (Sweden)

    I. V. Karivets

    2016-12-01

    Full Text Available Purpose. The author will show that metaphysical concepts and the concepts of empirical sciences derive from experience. The only difference is that metaphysical concepts derive from unusual experience, i.e. out-of-body experience, while empirical sciences – from usual one. The example set metaphysical concept of pure being. Methodology. In order to obtain this goal the author uses two methods. The first one is comparative method. With the help of this method the stories of men who experienced clinical death and returned to life are compared with the famous philosophers’ metaphysical statements (Plato, Descartes, and Bonaventura. The second one is transpersonal method. It helps to study the peculiarities of the extraordinary experience in the state of clinical death or mystical ecstasy. Such experience lies in experience of transcendence, pure being as light, ultimate awareness of truth, which are identical to the metaphysical statements of philosophers and mystics. These ultimate experiences belong to different people, who lived and grown in different cultures, but nevertheless metaphysical statements of philosophers or mystics and statements of the ordinary people who experienced clinical death are the same. Therefore we can say that out-of-body experience is transpersonal. Originality. Metaphysics is neither speculative nor withdrawn from experience of a human being sphere. It arises from out-of-body experience while empirical sciences – from usual experience. Therefore, metaphysical concepts, in particular, pure being, are empirical, because they are based also on (extraordinary experience. In general, metaphysics becomes possible on the basis of out-of-body experience. Conclusions. In this article the author argues that the concepts of metaphysics are not a priori because they originate from out-of-body experience that is from the experience of the distinction between body and soul or body and mind. As a result of such experience

  1. The tragic and the metaphysical in philosophy and psychoanalysis.

    Science.gov (United States)

    Stolorow, Robert D; Atwood, George E

    2013-06-01

    This article elaborates a claim, first introduced by Wilhelm Dilthey, that metaphysics represents an illusory flight from the tragedy of human finitude. Metaphysics, of which psychoanalytic metapsychologies are a form, transforms the unbearable fragility and transience of all things human into an enduring, permanent, changeless reality, an illusory world of eternal truths. Three "clinical cases" illustrate this thesis in the work and lives of a philosopher and two psychoanalytic theorists: Friedrich Nietzsche and his metaphysical doctrine of the eternal return of the same, Sigmund Freud and his dual instinct theory, and Heinz Kohut and his theoretical language of the self. It is contended that the best safeguard against the pitfalls of metaphysical illusion lies in a shared commitment to reflection on the constitutive contexts of all our theoretical ideas.

  2. The abundant world: Paul Feyerabend's metaphysics of science.

    Science.gov (United States)

    Brown, Matthew J

    2016-06-01

    The goal of this paper is to provide an interpretation of Feyerabend's metaphysics of science as found in late works like Conquest of Abundance and Tyranny of Science. Feyerabend's late metaphysics consists of an attempt to criticize and provide a systematic alternative to traditional scientific realism, a package of views he sometimes referred to as "scientific materialism." Scientific materialism is objectionable not only on metaphysical grounds, nor because it provides a poor ground for understanding science, but because it implies problematic claims about the epistemic and cultural authority of science, claims incompatible with situating science properly in democratic societies. I show how Feyerabend's metaphysical view, which I call "the abundant world" or "abundant realism," constitute a sophisticated and challenging form of ontological pluralism that makes interesting connections with contemporary philosophy of science and issues of the political and policy role of science in a democratic society. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Relativistic Constraints for a Naturalistic Metaphysics of Time

    OpenAIRE

    Evans, Peter W.

    2010-01-01

    The traditional metaphysical debate between static and dynamic views in the philosophy of time is examined in light of considerations concerning the nature of time in physical theory. Adapting the formalism of Rovelli (1995, 2004), I set out a precise framework in which to characterise the formal structure of time that we find in physical theory. This framework is used to provide a new perspective on the relationship between the metaphysics of time and the special theory of relativity by emph...

  4. Gould on species, metaphysics and macroevolution: A critical appraisal.

    Science.gov (United States)

    Boucher, Sandy C

    2017-04-01

    Stephen Jay Gould's views on the ontology of species were an important plank of his revisionist program in evolutionary theory. In this paper I cast a critical eye over those views. I focus on three central aspects of Gould's views on species: the relation between the Darwinian and the metaphysical notions of individuality, the relation between the ontology of species and macroevolution, and the issue of contextualism and conventionalism about the metaphysics of species. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Classic metaphyseal lesion following external cephalic version and cesarean section

    Energy Technology Data Exchange (ETDEWEB)

    Lysack, John T.; Soboleski, Don [Department of Diagnostic Radiology, Queen' s University, Kingston General Hospital, 76 Stuart Street, K7L 2V7, Kingston, Ont. (Canada)

    2003-06-01

    We report a case of an otherwise healthy neonate diagnosed at birth with a classic metaphyseal lesion of the proximal tibia following external cephalic version for frank breech presentation and a subsequent urgent cesarean section. Although the classic metaphyseal lesion is considered highly specific for infant abuse, this case demonstrates the importance of obtaining a history of obstetric trauma for neonates presenting to the imaging department for suspected non-accidental injury. (orig.)

  6. Classic metaphyseal lesion following external cephalic version and cesarean section

    International Nuclear Information System (INIS)

    Lysack, John T.; Soboleski, Don

    2003-01-01

    We report a case of an otherwise healthy neonate diagnosed at birth with a classic metaphyseal lesion of the proximal tibia following external cephalic version for frank breech presentation and a subsequent urgent cesarean section. Although the classic metaphyseal lesion is considered highly specific for infant abuse, this case demonstrates the importance of obtaining a history of obstetric trauma for neonates presenting to the imaging department for suspected non-accidental injury. (orig.)

  7. Metaphyseal fractures mimicking abuse during treatment for clubfoot

    Energy Technology Data Exchange (ETDEWEB)

    Grayev, A.M.; Boal, D.K.B. [Milton S. Hershey Medical Center, Penn State University College of Medicine, Hershey, PA (United States); Wallach, D.M.; Segal, L.S. [Milton S. Hershey Medical Center, Penn State University College of Medicine, Hershey, PA (United States)

    2001-08-01

    Background. Metaphyseal injuries resembling the classic metaphyseal lesion (CML) of abuse may occur as the result of serial casting during treatment of clubfoot deformity. Mentioned in the orthopedic literature in 1972, this iatrogenic fracture has not been described in the radiologic literature nor has the similarity to injuries occurring with abuse been previously recognized. Objective. To describe the mechanism and radiographic appearance of metaphyseal injury observed during serial casting of clubfoot. Note similarities to the CML of abuse. Materials and methods. Eight children ranging in age from 1 to 4 months underwent casting for clubfoot. Five orthopedic surgeons from three different institutions performed the casting. Two patients had spina bifida and one, arthrogryposis. A complete skeletal survey was performed on one child who was abused; there was no suspicion of abuse in the remaining seven. Results. All children manifest injury with periosteal new bone. One child had clear evidence of abuse with 24 rib fractures. X-rays of lower extremities in short leg casts revealed bilateral tibial metaphyseal fractures. Four other children had metaphyseal fractures resembling the CML of abuse, and three developed an area of sclerosis within the metaphysis. Conclusion. In the setting of serial casting for equinovarus deformity, metaphyseal injury even the CML of abuse may be noted. Since inflicted injuries are almost always unobserved and explanations rarely offered, the fact that the CML occurs as a result of orthopedic manipulation may offer some further insight concerning the pathogenesis of this well-described abuse injury. (orig.)

  8. Metaphyseal fractures mimicking abuse during treatment for clubfoot

    International Nuclear Information System (INIS)

    Grayev, A.M.; Boal, D.K.B.; Wallach, D.M.; Segal, L.S.

    2001-01-01

    Background. Metaphyseal injuries resembling the classic metaphyseal lesion (CML) of abuse may occur as the result of serial casting during treatment of clubfoot deformity. Mentioned in the orthopedic literature in 1972, this iatrogenic fracture has not been described in the radiologic literature nor has the similarity to injuries occurring with abuse been previously recognized. Objective. To describe the mechanism and radiographic appearance of metaphyseal injury observed during serial casting of clubfoot. Note similarities to the CML of abuse. Materials and methods. Eight children ranging in age from 1 to 4 months underwent casting for clubfoot. Five orthopedic surgeons from three different institutions performed the casting. Two patients had spina bifida and one, arthrogryposis. A complete skeletal survey was performed on one child who was abused; there was no suspicion of abuse in the remaining seven. Results. All children manifest injury with periosteal new bone. One child had clear evidence of abuse with 24 rib fractures. X-rays of lower extremities in short leg casts revealed bilateral tibial metaphyseal fractures. Four other children had metaphyseal fractures resembling the CML of abuse, and three developed an area of sclerosis within the metaphysis. Conclusion. In the setting of serial casting for equinovarus deformity, metaphyseal injury even the CML of abuse may be noted. Since inflicted injuries are almost always unobserved and explanations rarely offered, the fact that the CML occurs as a result of orthopedic manipulation may offer some further insight concerning the pathogenesis of this well-described abuse injury. (orig.)

  9. Beyond the realism debate: The metaphysics of 'racial' distinctions.

    Science.gov (United States)

    Lemeire, Olivier

    2016-10-01

    The current metaphysical race debate is very much focused on the realism question whether races exist. In this paper I argue against the importance of this question. Philosophers, biologists and anthropologists expect that answering this question will tell them something substantive about the metaphysics of racial classifications, and will help them to decide whether it is justified to use racial categories in scientific research and public policy. I argue that there are two reasons why these expectations are not fulfilled. First of all, the realism question about race leads to a very broad philosophical debate about the semantics of general terms and the criteria for real kinds, rather than to a debate about the metaphysics of racial categories specifically. Secondly, there is a type of race realism that is so toothless that it is almost completely uninformative about the metaphysics of race. In response to these worries, I argue that the metaphysical race debate should rather be focused on the question in what way and to what extent 'racial' distinctions can ground the epistemic practices of various scientific disciplines. I spell out what I mean by this, and go on to demonstrate that trying to answer this question leads to a more fruitful metaphysical debate. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Socialcultural background of formation of classical metaphysics

    Directory of Open Access Journals (Sweden)

    I. Z. Derzhko

    2014-09-01

    Full Text Available The classical model of philosophy has shaped ideas about its nature and aims that were laid in ancient metaphysics, but have been substantially amended by civilizational change. Socialcultural background of philosophy became trends that began to emerge in late medieval culture has particularly flourished there during modern times. Sphere of existence is important for the development of any spiritual phenomenon. For metaphysics it is the idea of humanity, acting as a kind of cultural protest against the domination of religion. This caused criticism of the medieval way of life and thinking. The idea of human revival based on spirit of antiquity has grounded. Disclaimer theological philosophy medieval variant type is as opposed to free philosophizing, coupled with poetry and literature, University dogmatic philosophy. There were a «rediscovery» of Plato, Aristotle reinterpretation. Philosophers explored a problem of human emotions and relationships, considering the person as a whole being, which is inherent in the mind, which cannot be considered without bodily desires and emotions. Change of the values awakened activity of the human person, led its transformation settings concerning himself and the surrounding world. Thus objectively obtained expression and ideological embodiment of civilization in a need of a new type of man - to a much greater extent compared to medieval activity, initiative, freedom, rationality, responsibility. Under the influence of such attitudes changes within religion gradually took place. Through the efforts of thinkers like Luther, Calvin, Munzer there were laid ideas of the Reformation that go far beyond its borders, gaining general cultural nature. The Church was increasingly losing control over everyday human existence. Gradually standards of a free, relaxed life became conventional; requirements of the body, «earthly» spirit demands fulfilling played a huge role. Thought and Culture of the Renaissance reflects

  11. LRP5 polymorphisms and response to alendronate treatment in Chinese postmenopausal women with osteoporosis.

    Science.gov (United States)

    Zhou, Pei Ran; Liu, Hai Juan; Liao, Er Yuan; Zhang, Zhen Lin; Chen, De Cai; Liu, Jian; Wu, Wen; Xing, Xiao Ping; Xia, Wei Bo; Xu, Ling; Li, Mei

    2014-04-01

    To investigate the association between LRP5 gene polymorphisms and response to alendronate in Chinese osteoporotic women. Six hundred and thirty nine Chinese postmenopausal women with osteopenia or osteoporosis were included and received alendronate treatment. The A1330V polymorphism of LRP5 was investigated. Bone mineral density (BMD) and bone turnover markers (ALP and β-isomerized carboxy-telopeptide of type I collagen [β-CTX]) were measured before and after treatment. The correlation of LRP5 polymorphisms with changes in BMD and bone turnover biomarkers were analyzed after treatment. After 12 months of treatment, participants with CC and CT genotypes had a larger increase in lumbar spine BMD and a larger decrease in serum β-CTX and ALP levels than those with TT genotype (all p LRP5 is possibly correlated with response to alendronate treatment in Chinese women with osteoporosis, and the TT genotype could possibly predict a weak response to alendronate.

  12. Bilateral atypical femoral fractures after long-term alendronate therapy: a case report.

    Science.gov (United States)

    Bamrungsong, Tachchai; Pongchaiyakul, Chatlert

    2010-05-01

    Bisphosphonates therapy has been shown to decrease the risk of vertebral, non-vertebral, and hip fractures in postmenopausal women. However the long-term safety of bisphosphonates use has been questioned. Recent reports have demonstrated the association between long-term alendronate therapy with low-energy subtrochanteric fracture or diaphyseal femoral fractures in a small number of patients. The author reported the first case of bilateral atypical femoral fractures in postmenopausal women with osteoporosis receiving long-term alendronate therapy.

  13. Radiodensitometric and DXA analyses for the measurement of bone mineral density after systemic alendronate therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lucisano, Marilia Pacifico; Nelson-Filho, Paulo; Silva, Raquel Assed Bezerra da; Silva, Lea Assed Bezerra da, E-mail: nelson@forp.usp.br [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Fac. de Odontologia. Dept. de Clinica Pediatrica, Preventiva e Odontologia Comunitaria; Morse, Leslie [Department of Physical Medicine and Rehabilitation, School of Medicine, Harvard Univ., Boston, MA (United States); Battaglino, Ricardo [Department of Skeletal Biology, Forsyth Institute, Cambridge, MA (United States); Watanabe, Plauto Christopher Aranha [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Fac. de Odontologia. Dept. de Morfologia, Estomacologia e Fisiologia

    2013-05-15

    Precise techniques for the measurement of maxillary bone mineral density (BMD) are useful for the early diagnosis of systemic diseases. The aim of this study was to compare in vivo the efficacy of dual energy x-ray absorptiometry (DXA) and radiographic densitometry for the measurement of BMD after systemic administration of sodium alendronate. Wistar rats were randomly allocated to a control group (n = 5), which received distilled water, and a sodium alendronate group (n = 8), which received two doses of chemically pure sodium alendronate (1 mg/kg) per week. After 8 weeks, the animals were euthanized, the tibias were removed, and the BMD of the proximal tibial metaphysis was analyzed radiographically and by DXA. The data were subjected to statistical analysis by the Kruskal-Wallis test at a significance level of 5%. Both of the techniques revealed that the alendronate-treated group had a significantly higher BMD (p < 0.05) than the control group after 8 weeks of treatment. Comparing the groups with and without alendronate therapy revealed increases of 14.9% and 29.6% in BMD, as detected radiographically and by DXA, respectively. In conclusion, both of the methods were able to detect an increase in BMD of the proximal tibial metaphysis after alendronate therapy. (author)

  14. Spectrofluorimetric Determination of Alendronate by Conjugation with the Rhodamine B Sulfonyl Group

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Yun Seong; Park, Ji Hye; Jin, Geun Woo; Park, Jong Sang [Seoul National University, Seoul (Korea, Republic of)

    2011-05-15

    The method involving the use of the highly active chromophore, RBSC group, as the conjugation agent is useful for analyzing alendronate, and limit of detection (LOD)/LOQ values suggest that RBSC is about 8 times more sensitive than the FCS NadDPA-2Zn{sup 2+}. The efficacy of the FCS method depends on the degree of binding and the binding constant (K{sub a}) because the electrostatic attraction between alendronate and NadDPA-2Zn{sup 2+} is weak. K{sub a} is affected by several conditions in the sample solution, such as temperature, pH and presence of competing molecules. Moreover, the fluorescence sensitivity of NadDPA-2Zn{sup 2+} is not sufficient because of its low extinction coefficient. In contrast, the conjugation between alendronate and RBSC does not have these limitations. Furthermore, higher sensitivity (detection limit, < 1 ng/mL) can be expected if a chromophore group with greater fluorescent activity is used for conjugation with alendronate. Alendronate, one of the bisphosphonate group of drugs, is used in the treatment of bone metastasis and several bone disorders, such as Paget's disease and osteoporosis, in post-menopausal women and older people. Generally, because the concentrations of alendronate in the therapeutic range are very low for intravenous and transdermal administration, its quantitative estimation is quite difficult.

  15. The classic metaphyseal lesion and traumatic injury

    International Nuclear Information System (INIS)

    Thackeray, Jonathan D.; Wannemacher, Jacob; Adler, Brent H.; Lindberg, Daniel M.

    2016-01-01

    It is widely accepted that the classic metaphyseal lesion (CML) is a traumatic lesion, strongly associated with abuse in infants. Nevertheless, various non-traumatic origins for CMLs continue to be suggested in medical and legal settings. No studies to date systematically describe the association of CMLs with other traumatic injuries. The primary objective of this study is to examine the association of CMLs with other traumatic injuries in a large data set of children evaluated for physical abuse. This was a retrospectively planned secondary analysis of data from a prospective, observational study of children <120 months of age who underwent evaluation by a child abuse physician. For this secondary analysis, we identified all children ≤12 months of age with an identified CML and determined the number and type of additional injuries identified. Descriptive analysis was used to report frequency of additional traumatic injuries. Among 2,890 subjects, 119 (4.1%) were identified as having a CML. Of these, 100 (84.0%) had at least one additional (non-CML) fracture. Thirty-three (27.7%) had traumatic brain injury. Nearly half (43.7%) of children had cutaneous injuries. Oropharyngeal injuries were found in 12 (10.1%) children. Abdominal/thoracic injuries were also found in 12 (10.1%) children. In all, 95.8% of children with a CML had at least one additional injury; one in four children had three or more categories of injury. CMLs identified in young children are strongly associated with traumatic injuries. Identification of a CML in a young child should prompt a thorough evaluation for physical abuse. (orig.)

  16. Exercise prevented the lansoprazole-induced reduction of anti-osteoporotic efficacy of alendronate in androgen deficiency rats.

    Science.gov (United States)

    Cegieła, Urszula; Pytlik, Maria; Folwarczna, Joanna; Miozga, Rafał; Piskorz, Szymon; Nowak, Dorota

    2014-01-01

    Clinical studies indicate that proton pump inhibitors (PPIs), used long-term in elderly patients, increase the risk of osteoporotic fractures, and decrease the anti-fracture efficacy of alendronate. The aim of the present study was to examine the effect of physical exercise on the anti-osteoporotic efficacy of alendronate administered concurrently with lansoprazole, a PPI, in male rats with androgen deficiency induced by orchidectomy. Male Wistar rats at 3 months of age were divided into: sham-operated control rats, orchidectomized (ORX) control rats, ORX rats receiving alendronate, ORX rats receiving alendronate and lansoprazole, ORX rats receiving alendronate and subjected to exercise, and ORX rats receiving alendronate and lansoprazole and subjected to exercise. The orchidectomy or sham-operation was performed 7-8 days before the start of drug administration. The rats were subjected to the exercise on the treadmill 1 hour/day for 7 weeks (6 days a week). Alendronate sodium (3 mg/kg p.o.) and lansoprazole (4 mg/kg p.o.) were administered once daily for 7 weeks (6 days a week). Mechanical properties of the tibial metaphysis and femoral neck were assessed. Bone turnover markers, histomorphometric parameters, bone mass and mass of bone mineral were also studied. Lansoprazole weakened the anti-osteoporotic efficacy of alendronate. The exercise increased the alendronate effect. Similar changes were observed in the rats treated with lansoprazole and alendronate, subjected to exercise; no deleterious effects of lansoprazole were observed. In conclusion, the exercise prevented the lansoprazole-induced reduction the anti-osteoporotic efficacy of alendronate in orchidectomized rats.

  17. Alendronate reduces the daily consumption of insulin (DCI) in patients with senile type I diabetes and osteoporosis.

    Science.gov (United States)

    Maugeri, D; Panebianco, P; Rosso, D; Calanna, A; Speciale, S; Santangelo, A; Rizza, I; Motta, M; Lentini, A; Malaguarnera, M

    2002-01-01

    The use of Alendronate for the treatment of senile diabetes with osteopenia or osteoporosis is a common practice today, although the reasons for the success of this treatment are not completely understood. We investigated 40 elderly female patients, over 70 years of age, divided in two Groups (A and B) 20 cases of each, with insulin-dependent senile diabetes and fair metabolic balance, with an average disease duration of 30 +/- 4 years. They all had osteoporosis shown by the mean T-score of bone mineral densitometry. The Groups were treated as follows, Group A with 10 mg/day of Alendronate per os, with morning fasting plus a supplementation of calcium and vitamin D3, while the Group B received only calcium and vitamin D3 per os. Bone mineral density (BMD) expressed in mg/cm2, and in terms of T-score and Z-score at the spine (L1-L4) was monitored over time after 12 and 24 months, using dexa technique with a Lunar DPX densitometer. Moreover, the variation of daily consumption of insulin (DCI) of all the study population was calculated 12 and 24 months after the start of treatments. The data of Group A showed an improvement of osteoporosis, as evidenced by the increase of BMD at both times of measurement, accompanied by a significant reduction in the DCI (-21.6% by the 12th month, and -36.2% by the end of the observation period). In the Group B only small, statistically insignificant changes were observed in both the BMD and DCI. The most plausible explanation of reduction of DCI in Group A seems to be that Alendronate has improved the clinical symptoms of osteoporosis (pain, rigidity, and reduction of movements) through its action on the bone mass recovery and slowing down the bone turnover and under these conditions the diabetic patients improved their own physical performance. The better and more extensive movements certainly produced a reduction in the DCI, since a correct and adequate physical activity does contribute to an improved glucose metabolism.

  18. The wave function essays on the metaphysics of quantum mechanics

    CERN Document Server

    Albert, David Z

    2013-01-01

    This is a new volume of original essays on the metaphysics of quantum mechanics. The essays address questions such as: What fundamental metaphysics is best motivated by quantum mechanics? What is the ontological status of the wave function? Does quantum mechanics support the existence of any other fundamental entities, e.g. particles? What is the nature of the fundamental space (or space-time manifold) of quantum mechanics? What is the relationship between the fundamental ontology of quantum mechanics and ordinary, macroscopic objects like tables, chairs, and persons? This collection includes a comprehensive introduction with a history of quantum mechanics and the debate over its metaphysical interpretation focusing especially on the main realist alternatives.

  19. The Metaphysical Instincts & Spiritual Bypassing in Integral Psychology

    Directory of Open Access Journals (Sweden)

    Bahman A.K. Shirazi

    2013-09-01

    Full Text Available Instincts are innate, unconscious means by which Nature operates in all forms of life including animals and human beings. In humans however, with progressive evolution of consciousness, instincts become increasingly conscious and regulated by egoic functions. Biological instincts associated with the lower-unconscious such as survival, aggressive, and reproductive instincts are well known in general psychology. The higher-unconscious, which is unique to human beings, may be said to have its own instinctual processes referred to here as the ‘metaphysical instincts’. In traditional spiritual practices awakening the metaphysical instincts has often been done at the expense of suppressing the biological instincts—a process referred to as spiritual bypassing. This essay discusses how the metaphysical instincts initially expressed as the religious impulse with associated beliefs and behaviors may be transformed and made fully conscious, and integrated with the biological instincts in integral yoga and psychology in order to achieve wholeness of personality.

  20. A critical introduction to the metaphysics of time

    CERN Document Server

    Curtis, Benjamin

    2016-01-01

    What is the nature of time? Does it flow? Do the past and future exist? Drawing connections between historical and present-day questions, A Critical Introduction to the Metaphysics of Time provides an up-to-date guide to one of the most central and debated topics in contemporary metaphysics. Introducing the views and arguments of Parmenides, Plato, Aristotle, Descartes, Newton and Leibniz, this accessible introduction covers the history of the philosophy of time from the Pre-Socratics to the beginning of the 20th Century. The historical survey presents the necessary background to understanding more recent developments, including McTaggart's 1908 argument for the unreality of time, the open future, the perdurance/endurance debate, the possibility of time travel, and the relevance of current physics to the philosophy of time. Informed by cutting-edge philosophical research, A Critical Introduction to the Metaphysics of Time evaluates influential historical arguments in the context of contemporary developments. ...

  1. A special healing pattern in stable metaphyseal fractures.

    Science.gov (United States)

    Chen, Wen Tao; Han, Da Cheng; Zhang, Pei Xun; Han, Na; Kou, Yu Hui; Yin, Xiao Feng; Jiang, Bao Guo

    2015-04-01

    Metaphyseal fractures heal in a rapid fashion that is different from the bone shaft healing process. Animal studies have focused on diaphyseal fractures. We investigated the metaphyseal fracture-healing process in rabbits. 60 rabbits (divided into 12 groups) underwent proximal tibial osteotomy, anatomical reduction, and fixation with screws. After surgery, the proximal tibiae were harvested at different time points for histology. No obvious osteonecrosis or bone resorption were found 2 weeks after surgery. From day 5 to week 5, woven bone or new trabeculae formed. From week 2, remodeling into lamellar bone started and reached a peak at week 6. These 3 stages overlapped. Histomorphometry showed that the structure changed as a unimodal curve. The healing process of metaphyseal fractures appears to differ from the commonly studied healing process in diaphyseal fractures. It is rapid, and can be divided into 4 histological stages: cellular activation and differentiation, formation of woven bone, transformation of woven bone into lamellar bone, and further remodeling.

  2. Acute bilateral uveitis and right macular edema induced by a single infusion of zoledronic acid for the treatment of postmenopausal osteoporosis as a substitution for oral alendronate: a case report.

    Science.gov (United States)

    Tian, Yiming; Wang, Rui; Liu, Lianyuan; Ma, Chunming; Lu, Qiang; Yin, Fuzai

    2016-02-11

    Zoledronic acid-induced uveitis (ZAIU) is rare but severe, and has been recently considered part of an acute phase reaction. Only 15 cases have been reported since 2005. Here we describe a case with macular edema, which is the first reported case observed after long-term alendronate tolerance. A 63-year-old Asian woman received her first intravenous zoledronic acid treatment for the management of postmenopausal osteoporosis as a more convenient substitute for oral alendronate. Twenty-four hours later, bilateral eye irritations, periorbital swelling, blurred vision, and diplopia presented. The complete blood count and transaminase levels were normal, but the erythrocytic sedimentation, C-reactive protein, and serum C4 levels were elevated. On detailed ophthalmological examination, a diagnosis of bilateral acute uveitis and macular edema in the right eye was made. The ocular symptoms were not improved until administration of topical and oral steroids. Complete resolution was achieved. There was no rechallenge of bisphosphonates, and no recurrence at 6 months follow-up. Based on an extensive review, abnormal fundus is rarely reported, especially in cases of macular edema. Rechallenge with zoledronic acid in five cases induced no additional uveitis, and changing the medication to pamidronate in another patient was also tolerated. Interestingly, our patient suffered from uveitis soon after intravenous zoledronate exposure after a two-year tolerance to oral alendronate. This is the first report of zoledronic acid induced uveitis with macular edema after long-term alendronate tolerance. Prior oral alendronate may not entirely prevent ZAIU. Steroids are usually necessary in the treatment of ZAIU. Bisphosphonate rechallenge is not fully contraindicated, and prior steroid administration may be a more reasonable treatment choice according to the available evidence.

  3. Metaphysics as the Science of Essence: E. J. Lowe and Thomas Aquinas

    Directory of Open Access Journals (Sweden)

    Alejandro Pérez

    2013-12-01

    Full Text Available Metaphysics after being ignored for years has returned to the center of the stage in contemporary philosophy. Thomas Aquinas has lived a very similar story, which gave birth to analytical Thomism. Despite the work done in this line of research, the metaphysics of Aquinas has been heavily ignored. However, the metaphysics of Thomas Aquinas has an advantage, little discussed among Thomists and “Tomasinos”, and it is the fact that it is essentialist metaphysics. So, in keeping with the work of metaphysical E. J. Lowe, who presents his metaphysics as “serious essentialist” it is shown here that the metaphysics of Aquinas has the same virtues of “serious essentialism”, which allows to postulate it as a valid and plausible position for contemporary metaphysics.

  4. Information in Reality: Logic and Metaphysics

    Directory of Open Access Journals (Sweden)

    Joseph E. Brenner

    2011-10-01

    Full Text Available The recent history of information theory and science shows a trend in emphasis from quantitative measures to qualitative characterizations. In parallel, aspects of information are being developed, for example by Pedro Marijuan, Wolfgang Hofkirchner and others that are extending the notion of qualitative, non-computational information in the biological and cognitive domain to include meaning and function. However, there is as yet no consensus on whether a single acceptable definition or theory of the concept of information is possible, leading to many attempts to view it as a complex, a notion with varied meanings or a group of different entities. In my opinion, the difficulties in developing a Unified Theory of Information (UTI that would include its qualitative and quantita-tive aspects and their relation to meaning are a consequence of implicit or explicit reliance on the principles of standard, truth-functional bivalent or multivalent logics. In reality, information processes, like those of time, change and human con-sciousness, are contradictory: they are regular and irregular; consistent and inconsistent; continuous and discontinuous. Since the indicated logics cannot accept real contradictions, they have been incapable of describing the multiple but interre-lated characteristics of information. The framework for the discussion of information in this paper will be the new extension of logic to real complex processes that I have made, Logic in Reality (LIR, which is grounded in the dualities and self-dualities of quantum physics and cos-mology. LIR provides, among other things, new interpretations of the most fundamental metaphysical questions present in discussions of information at physical, biological and cognitive levels of reality including, especially, those of time, continuity vs. discontinuity, and change, both physical and epistemological. I show that LIR can constitute a novel and general ap-proach to the non-binary properties of

  5. METAPHYSICAL REVOLUTION OF DESCARTES AND TRANSFORMATION OF THE ANTHROPOLOGICAL PROJECT

    Directory of Open Access Journals (Sweden)

    Anatolii M. Malivskyi

    2015-05-01

    Full Text Available The purpose is to reveal and comprehend forms of influence metaphysical' revolution for a way of interpretation of the anthropological project by Descartes on the basis of investigations of modern dekartes's researchers, that is the recognition of a fundamental role of metaphysics. Methodology. As methodological base modern investigations of dekartes's researchers accenting a fundamental role of metaphysics and expediency of unbiassed judgment of heritage of the great thinker are used. The scientific novelty. The transformation of the anthropological project is outlined as manifestation of metaphysical revolution. It is about a transcendencecy of naive anthropology (as an embodiment of reductive mindset, that is interpretations of human nature as its corporality and transition to metaphysical anthropology which consists in upholding of unconditional priority of human thinking as associated with God. As result of transition concentration of attention on intense human nature, that is at tension between sensuality and intelligence, aspiration to truth and tendency to delusion, between Life and Nothing, etc. Conclusions. The appeal to the incomplete anthropological project of Descartes on the basis of innovative researches allows proving the thesis about influence of metaphysical revolution on a way of its interpretation. The main forms of oriented to science ideals of naive anthropology, trust in evidence of the senses, atheism, interpretation of science as the main form of detection rationality of human nature, which Descartes tends constructively to overcome in the text of "meditation", are highlighted. During creation of metaphysical anthropology the attention of the thinker is drawn by the fact of impossibility of comprehension of human nature by means of natural-science rationality and expediency of the appeal to metaphysics. The subject of attention of the thinker is the tension between sensuality and intelligence, need

  6. [The mark of envy: metaphysics and embryology according to Descartes].

    Science.gov (United States)

    Gaudemard, Lynda

    2012-01-01

    This paper explores the interaction between medicine and metaphysics in modern natural philosophy and especially in Descartes' philosophy. I argue that Descartes hypothetical account of birthmarks in connection with his embryology provides an argumentative proof of the metaphysical necessity of a substantial union between mind and body, which however does not threaten his doctrine of the real distinction between these two substances. It would appear that his argument relies on a temporal conception of alethic modalities and provides a new answer to Henricus Regius who in 1641 claimed that, for Descartes, the human being is an ensper accidens.

  7. A fast and simple spectrofluorometric method for the determination of alendronate sodium in pharmaceuticals

    Directory of Open Access Journals (Sweden)

    Jafar Ezzati Nazhad Dolatabadi

    2014-03-01

    Full Text Available Introduction: Alendronate sodium enhances bone formation and increases osteoblast proliferation and maturation and leads to the inhibition of osteoblast apoptosis. Therefore, a rapid and simple spectrofluorometric method has been developed and validated for the quantitative determination of it. Methods: The procedure is based on the reaction of primary amino group of alendronate with o-phthalaldehyde (OPA in sodium hydroxide solution. Results: The calibration graph was linear over the concentration range of 0.0-2.4 μM and limit of detection and limit of quantification of the method was 8.89 and 29 nanomolar, respectively.The enthalpy and entropy of the reaction between alendronate sodium and OPA showed that the reaction is endothermic and entropy favored (ΔH = 154.08 kJ/mol; ΔS = 567.36 J/mol K which indicates that OPA interaction with alendronate is increased at elevated temperature. Conclusion: This simple method can be used as a practical technique for the analysis of alendronate in various samples.

  8. In vitro disintegration studies of weekly generic alendronate sodium tablets (70 mg) available in the US.

    Science.gov (United States)

    Dansereau, Richard J; Crail, Debbie J; Perkins, Alan C

    2009-02-01

    Bisphosphonates as a class have the potential to cause upper gastrointestinal irritation. Although the generic alendronate sodium tablets are bioequivalent to the branded product, a potential concern is that the pharmaceutical attributes of the various generic formulations my affect the potential for local irritation and tolerability. The in vitro disintegration times were determined using the method described in the US Pharmacopeia 30 (USP 30). The disintegration of three generic alendronate sodium tablets 70 mg available in the United States was compared to that of the branded product. The mean disintegration times of the generic alendronate sodium tablets ranged from 9 to 10 s for the Barr lots to 108 s for the Watson lot. The disintegration time of the branded product (Fosamax) was 53 s. The three Barr lots and one Teva lot had rapid disintegration times which were similar to the disintegration standards (disintegrating tablets. Since there is no established disintegration time for alendronate sodium tablets there can be no assurance that the generic tablets are equivalent to the branded product in terms of esophageal exposure. However, the in vitro disintegration times have not been correlated with in vivo disintegration performance. Copies of generic alendronate sodium tablets are approved based on the results of single-dose bioavailability studies in healthy subjects and this is not considered adequate to establish similar disintegration characteristics.

  9. Fall and Rise of Aristotelian Metaphysics in the Philosophy of Science

    Science.gov (United States)

    Lamont, John

    2009-01-01

    The paper examines the fortunes of Aristotelian metaphysics in science and the philosophy of science. It considers the Enlightenment claim that such a metaphysics is fundamentally unscientific, and that its abandonment was essential to the scientific revolution. The history of the scientific revolution and the metaphysical debates involved in it…

  10. The Futility of Any Anti-Metaphysical Position | Okoro | Lagos Notes ...

    African Journals Online (AJOL)

    This essay explains why it is difficult or even impossible to reject metaphysics. By this we do not mean that metaphysical theories cannot be refuted; what we rather mean to say is that it is absolutely futile to deny the existence of metaphysics and its importance to human life. To do so would amount to the denial of the human ...

  11. Preparation of collagen/hydroxyapatite/alendronate hybrid hydrogels as potential scaffolds for bone regeneration.

    Science.gov (United States)

    Ma, Xin; He, Zhiwei; Han, Fengxuan; Zhong, Zhiyuan; Chen, Liang; Li, Bin

    2016-07-01

    Development of biomimetic scaffolds represents a promising direction in bone tissue engineering. In this study, we designed a two-step process to prepare a type of biomimetic hybrid hydrogels that were composed of collagen, hydroxyapatite (HAP) and alendronate (ALN), an anti-osteoporosis drug. First, water-soluble ALN-conjugated HAP (HAP-ALN) containing 4.0wt.% of ALN was synthesized by treating HAP particles with ALN. Hydrogels were then formed from HAP-ALN conjugate and collagen under physiological conditions using genipin (GNP) as the crosslinker. Depending on the ALN/collagen molar ratio and GNP concentration, the gelation time of hydrogels ranged from 5 to 37min. Notably, these hybrid hydrogels exhibited markedly improved mechanical property (storage modulus G'=38-187kPa), higher gel contents, and lower swelling ratios compared to the hydrogels prepared from collagen alone under similar conditions. Moreover, they showed tunable degradation behaviors against collagenase. The collagen/HAP-ALN hybrid hydrogels supported the adhesion and growth of murine MC3T3-E1 osteoblastic cells well. Such tough yet enzymatically degradable hybrid hydrogels hold potential as scaffolds for bone tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Preparation and biological studies of 68Ga-DOTA-alendronate

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    Ashraf Fakhari

    2016-07-01

    Full Text Available Objective(s: In line with previous research on the development of conjugated bisphosphonate ligands as new bone-avid agents, in this study, DOTA conjugated alendronate (DOTA-ALN was synthesized and evaluated after labeling with gallium-68 (68Ga.Methods: DOTA-ALN was synthesized and characterized, followed by 68Ga-DOTA-ALN preparation, using DOTA-ALN and 68GaCl3 (pH: 4-5 at 92-95°C for 10 min. Stability tests, hydroxyapatite assay, partition coefficient calculation,biodistribution studies, and imaging were performed on the developed agent in normal rats.Results: The complex was prepared with high radiochemical purity (>99% as depicted by radio thin-layer chromatography; specific activity: 310-320GBq/mmol after solid phase purification and was stabilized for up to 90 min with a logP value of -2.91. Maximum ligand binding (65% was observed in the presence of 50 mg of hydroxyapatite; a major portion of the activity was excreted through the kidneys. With the exception of excretory organs, gastrointestinal tract organs, including the liver, intestine, and colon, showed significant uptake; however, the bone uptake was low (

  13. Metaphysical Concept of Secularization versus Islamic Concept of Secularization

    Directory of Open Access Journals (Sweden)

    Volkan ERTİT

    2017-12-01

    Full Text Available In early 21st century, the question “Is Turkey becoming secularized contrary to popular belief?” was one of the discussions occupying Turkish public opinion. These discussions led to the encounter of two different concepts of secularization, “theological (Islamic” and "metaphysical", and to put forward different claims using the same concept. Hence, it became evidentwas understood that a discussion was necessary to understand what secularization is and what it is not before starting any debate on Turkey's secularization. That is because the metaphysical discussion that defines secularization as the decline in the social influence of metaphysical realm (religion, religion-like mechanisms, folk religions, superstitious beliefs, etc. is overshadowed by the Islamic definition describing secularization as "irreligiousness" or "non-Islamism". Therefore, discussingTo understand the social transformation in Turkey, this article attempts to explain that metaphysical rather than theological definition of secularization is necessary for understanding the social implications of the process of modernization.

  14. Modes of Learning: Whitehead's Metaphysics and the Stages of Education

    Science.gov (United States)

    Allan, George

    2012-01-01

    Educators are familiar with Alfred North Whitehead's three stages of education: romance, precision, and generalization. Philosophers are familiar with his metaphysical theories about the primacy of temporal processes. In "Modes of Learning," George Allan brings these two sides of Whitehead's thought together for the first time in a book…

  15. Metaphysical Modality, Modality of Predicate and the Theory of

    Directory of Open Access Journals (Sweden)

    l nabavi

    2010-05-01

    This paper discusses the historical overview of the metaphysical modality firstly and then shows that the theory of "Decisive Necessity” is true and justified in a model of modal logic with equivalent accessibility relation and homogeneous possible world view (fixed domain.

  16. The Metaphysics and Epistemology of Singular Terms | Borg ...

    African Journals Online (AJOL)

    Can we draw apart questions of what it is to be a singular term (a metaphysical issue) from questions about how we tell when some expression is a singular term (an epistemological matter)? Prima facie, it might seem we can't: language, as a man-made edifice, might seem to prohibit such a distinction, and, indeed, some ...

  17. Peirce’s Scientific and Spiritual Process Metaphysics

    DEFF Research Database (Denmark)

    Brier, Søren

    Peirce saw as his primary task to develop a comprehensive metaphysical and epistemological system in which a new theory of categories, developed after Kant and Hegel, was defined in a completely new way. His triadic category theory was connected to a dynamic triadic web of semiotics viewed as the...

  18. The metaphysics market - billing language as behavioural | Botha ...

    African Journals Online (AJOL)

    This is the second of a series of studies in which prototypical conceptions of language are subversively turned inside out. It has to be read in tandem with the first. The Metaphysics Market: 1 Merchandizing Language as Matter (= SPIL and SPIL PLUS 14, 1989). I would like to thank Walter Winckler for contributing generously ...

  19. The Problem of Personal Identity in Metaphysics | Kanu | AFRREV ...

    African Journals Online (AJOL)

    Although Western Philosophical tradition ascribes the invention of the problem of identity to John Locke, it has remained one of the fundamental questions within the parameters of enquiry in Metaphysics, Epistemology and Philosophy of Mind. It is one that has remained evergreen right from the Pre-Socratic Epoch to the ...

  20. Conceptual and Metaphysical Origins and Relevance of Temporal Logic

    DEFF Research Database (Denmark)

    Jakobsen, David; Øhrstrøm, Peter

    2016-01-01

    Logic has sometimes been seen as an alternative to metaphysics and to speculation. In this paper it is argued that a different story should be told when it comes to temporal logic and tense-logic in particular. A.N. Prior’s first formulation of tense logic was mainly established in order to quali...

  1. Risk of hip, subtrochanteric, and femoral shaft fractures among mid and long term users of alendronate

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Eiken, Pia; Prieto-Alhambra, Daniel

    2016-01-01

    OBJECTIVES: To determine the skeletal safety and efficacy of long term (≥10 years) alendronate use in patients with osteoporosis. DESIGN: Open register based cohort study containing two nested case control studies. SETTING: Nationwide study of population of Denmark. PARTICIPANTS: 61 990 men...... to fracture cases by sex, year of birth, and year of initiation of alendronate treatment. Conditional logistic regression models were fitted to calculate odds ratios with and without adjustment for comorbidity and comedications. Sensitivity analyses investigated subsequent treatment with other drugs...... ratio (MPR, a proxy for compliance) >80%) compared with poor adherence (MPR

  2. Metaphysics as praxis : Rereading Dōgen's Metaphysics through Deleuzian pragmatism and Pratītyasamutpāda

    NARCIS (Netherlands)

    Hiramoto, S.

    2017-01-01

    This thesis interprets the Japanese Buddhist master, Dōgen's metaphysical ideas concerning Buddha-nature, Total-function, and temporality, with the help of Deleuze's pragmatism, in a manner congruent with the central Buddhist doctrine of pratītyasamutpāda. In doing so, the research attempts to

  3. Osteoporosis and thyrotropin-suppressive therapy: reduced effectiveness of alendronate.

    Science.gov (United States)

    Panico, Annalisa; Lupoli, Gelsy Arianna; Fonderico, Francesco; Marciello, Francesca; Martinelli, Addolorata; Assante, Roberta; Lupoli, Giovanni

    2009-05-01

    Many reports of the effect of exogenous thyroxine therapy on bone mineral density (BMD) show a relationship between excess thyroid hormone administration and osteoporosis. The aim of this study was to evaluate the effect of antibone resorptive agents, in particular alendronate (ALN) on BMD in postmenopausal osteoporotic women with thyroid carcinoma who were receiving long-term thyrotropin (TSH)-suppressive therapy with thyroxine. Seventy-four postmenopausal women with low BMD (T-score or =0.05 and < or =0.1 microU/mL) for about 3-9 years were selected for the study. The patients were divided into three groups according to the length of levothyroxine (LT(4)) treatment prior to the beginning of the study: group A (TSH-suppressive therapy for about 3 years), group B (for about 6 years), and group C (for about 9 years). These patients were compared with 74 matched women not taking LT(4). All patients and controls were treated with bisphosphonates, calcium, and vitamin D for 2 years and evaluated. After 24 months of treatment group A showed a 7.8% increase in lumbar BMD; group B, a 4.6% increase; and group C, a 0.86% increase. In the control group BMD increased 8.2%. A significant difference was found in both lumbar and femoral BMD increase among the three groups: group C had a lower BMD increase than group A (p < 0.001) and B (p < 0.001). In postmenopausal women who were receiving adequate amounts of calcium and vitamin D in their diet ALN was less effective for those who were also receiving TSH-suppressive doses of LT(4) for either 6 or 9 years. The positive effect of ALN on BMD was less for longer periods of LT(4) treatment. It seems likely that other bisphosphonates would also be less effective in increasing BMD in postmenopausal women receiving TSH-suppressing doses of LT(4).

  4. Effect of insulin combined alendronate sodium on bone mineral density and levels of serum BAP, TRAP-5b and BGP in aged patients with type 2 diabetes mellitus with osteoporosis

    Directory of Open Access Journals (Sweden)

    Fang Wang

    2016-06-01

    Full Text Available Objective: To explore the effect of insulin combined alendronate sodium on bone mineral density and levels of serum BAP, TRAP-5b and BGP in aged patients with type 2 diabetes mellitus with osteoporosis. Methods: A total of 136 patients with type 2 diabetes mellitus with osteoporosis in January 2014 to January 2016 in our hospital for the treatment were selected, and randomly divided into 4 groups, each of 40 cases. Caltrate D was given as a basic treatment to all the patients, and the control group was given the treatment of insulin, and the metformin group was given the treatment of metformin, and the combination group was given the treatment of metformin combined alendronate, and the experiment group was given the treatment of insulin combined alendronate. BMD of the femoral neck and the serum levels of BAP, TRAP-5b and BGP were detected and recorded before the treatment and after one year’s treatment. Results: On index of bone mineral density, the control group and the metformin group showed no significant differences; the combination group was slightly improved, but showed no statistical significance; After the treatment, the bone mineral density of the experiment was significantly improved. On index of bone turnover, the levels of serum BAP and BGP all had been improved and the level of TRAP-5b all was reduced then before the treatment in the control group, the combination group and the experiment group, but only the experiment group showed significant differences; On index of bone turnover, the experiment group were better than other groups, the differences were statistical significant. Conclusions: It has greater clinical curative effect that insulin combined alendronate sodium in the treatment of aged patients with type 2 diabetes mellitus with osteoporosis, it can effectively balance the metabolism of bone, safe and reliable, and it is worthy of application.

  5. Successful teriparatide treatment of atypical fracture after long-term use of alendronate without surgical procedure in a postmenopausal woman: a case report.

    Science.gov (United States)

    Huang, Hsuan-Ti; Kang, Lin; Huang, Peng-Ju; Fu, Yin-Chih; Lin, Sung-Yen; Hsieh, Chih-Hsin; Chen, Jian-Chih; Cheng, Yuh-Min; Chen, Chung-Hwan

    2012-12-01

    Bisphosphonates are used as first-line therapy for postmenopausal osteoporosis owing to their potent inhibition of bone resorption. Long-term use of bisphosphonates may lead to low-energy femoral subtrochanteric or shaft fractures in a very few patients. The aim of this study was to describe the clinical course of a patient treated with alendronate for 3 years who developed an atypical femoral fracture and to hypothesize the beneficial effects of teriparatide on the healing of the patient's atypical femoral fracture. A 63-year-old Asian woman had a lumbar osteoporotic fracture and received 70 mg of alendronate for 3 years. Pain and soreness in the thigh presented initially and exacerbated thereafter. X-ray revealed a right femoral diaphysis stress fracture. She then received teriparatide for the treatment of osteoporosis and the femoral atypical fracture. Pain and tenderness improved remarkably after teriparatide treatment for 1 month, and these symptoms disappeared after teriparatide treatment for 9 months. The patient also received raloxifen as further therapy, and the fracture line had completely disappeared by 15 months after treatment. Even though a previous study has reported that teriparatide healed stress fractures in a rat model and even with the time course of fracture healing in our patient, we are still not certain that teriparatide played a primary role in the positive response to therapy. Vitamin D therapy, calcium, and alendronate discontinuation may have played secondary roles. This case report may serve to introduce a direction for future research into the pharmacological treatment of atypical femoral fractures. Surgical treatment of incomplete atypical femoral fractures may be a safer method.

  6. Alendronate has a residual effect on bone mass in postmenopausal Danish women up to 7 years after treatment withdrawal

    DEFF Research Database (Denmark)

    Bagger, Yu Z; Tankó, László B; Alexandersen, Peter

    2003-01-01

    for 7, 5, or 3 yr, respectively. Bone mineral density of the lumbar spine, hip, and forearm was measured by dual-energy x-ray absorptiometry. Biochemical markers of bone turnover were induced serum C-terminal telopeptides of type I collagen (CTX) and osteocalcin. Women who received alendronate (2...... was found in women treated with alendronate 20 mg per day for 2 yr (9.7%, P=0.01 vs. placebo). The rate of bone loss after alendronate withdrawal was comparable to the bone loss observed in the placebo group. Bone markers tended to reverse back to normal levels, but were still affected even several years...

  7. Characteristics of patients who suffer major osteoporotic fractures despite adhering to alendronate treatment

    DEFF Research Database (Denmark)

    Abrahamsen, B; Rubin, Katrine Hass; Eiken, Pia Agnete

    2013-01-01

    Antiresorptive treatment reduces the risk of fractures, but most patients remain at elevated risk. We used health registers to identify predictors of new major osteoporotic fractures in patients adhering to alendronate. Risk factors showed a different pattern than in the general population and in...... and included dementia, ulcer disease, and Parkinson's disease....

  8. Risk of hip, subtrochanteric, and femoral shaft fractures among mid and long term users of alendronate

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Eiken, Pia; Prieto-Alhambra, Daniel

    2016-01-01

    OBJECTIVES: To determine the skeletal safety and efficacy of long term (≥10 years) alendronate use in patients with osteoporosis. DESIGN: Open register based cohort study containing two nested case control studies. SETTING: Nationwide study of population of Denmark. PARTICIPANTS: 61 990 men...... ratio (MPR, a proxy for compliance) >80%) compared with poor adherence (MPR

  9. Changes in bone density and turnover after alendronate or estrogen withdrawal

    DEFF Research Database (Denmark)

    Wasnich, Richard D; Bagger, Yu Z; Hosking, David J

    2004-01-01

    OBJECTIVE: To compare bone mineral density (BMD) and bone turnover changes after therapy withdrawal in postmenopausal women treated with alendronate or estrogen-progestin. DESIGN: In this randomized, blinded, multinational, placebo-controlled trial, 1,609 healthy postmenopausal women ages 45 to 59...

  10. Injectable nanoparticle-loaded hydrogel system for local delivery of sodium alendronate

    Czech Academy of Sciences Publication Activity Database

    Posadowska, U.; Pařízek, Martin; Filová, Elena; Wlodarczyk-Biegun, M.; Kamperman, M.; Bačáková, Lucie; Pamula, E.

    2015-01-01

    Roč. 485, 1-2 (2015), s. 31-40 ISSN 0378-5173 R&D Projects: GA MZd(CZ) NT13297 Institutional support: RVO:67985823 Keywords : sodium alendronate * PLGA * nanoparticles Subject RIV: EI - Biotechnology ; Bionics Impact factor: 3.994, year: 2015

  11. Foucauldian diagnostics: space, time, and the metaphysics of medicine.

    Science.gov (United States)

    Bishop, Jeffrey P

    2009-08-01

    This essay places Foucault's work into a philosophical context, recognizing that Foucault is difficult to place and demonstrates that Foucault remains in the Kantian tradition of philosophy, even if he sits at the margins of that tradition. For Kant, the forms of intuition-space and time-are the a priori conditions of the possibility of human experience and knowledge. For Foucault, the a priori conditions are political space and historical time. Foucault sees political space as central to understanding both the subject and objects of medicine, psychiatry, and the social sciences. Through this analysis one can see that medicine's metaphysics is a metaphysics of efficient causation, where medicine's objects are subjected to mechanisms of efficient control.

  12. Internal Realism: Putnam\\'s Alternative to Metaphysical Realism

    Directory of Open Access Journals (Sweden)

    J Akbari Takhtameshlou

    2014-03-01

    Having introduced and reviewed Putnam's arguments in rejecting metaphysical realism, this article explains and examines the basic elements of internal realism. The results of this article show that Putnam's objections against metaphysical realism lack the necessary credibility and strength and at the same time his proposed alternative (internal realism has serious problems that made to be addressed. By his chosen conception of truth, internal realism, cannot touch its stated purpose i.e. the removal of a huge gap between the truth of a statement and our knowledge of it. The ontological claims of internal realism are not, indeed, the reliable and true consequences of the thesis of conceptual relativity, which is considered as Putnam’s main base in this regard, but rather it is more a consequence of mistaking the linguistic issues with ontological ones.

  13. Can classic metaphyseal lesions follow uncomplicated caesarean section?

    Energy Technology Data Exchange (ETDEWEB)

    O' Connell, AnnaMarie [Children' s University Hospital, Radiology Department, Dublin 1 (Ireland); Donoghue, Veronica B. [Children' s University Hospital, Radiology Department, Dublin 1 (Ireland); National Maternity Hospital, Radiology Department, Dublin (Ireland)

    2007-05-15

    Classic metaphyseal lesion (CML) is the term given to a fracture that most often occurs in the posteromedial aspect of the distal femur, proximal tibia, distal tibia, and proximal humerus in infants; this finding is strongly associated with non-accidental injury. To demonstrate that the CML may occur following simple lower segment caesarean section (LSCS). A review of 22 years of an obstetric practice that delivers 8,500 babies per year. We identified three neonates born by elective LSCS, each with distal femoral metaphyseal fractures on postpartum radiographs. All caesarean sections were elective and uncomplicated. External cephalic version was not employed preoperatively. Postpartum radiographs demonstrated a fracture of the distal femoral metaphysis in each neonate, typical of a CML. We propose that a CML can occur in the setting of a simple, elective and uncomplicated LSCS where no external cephalic version is employed. (orig.)

  14. The metaphysical lessons of synthetic biology and neuroscience.

    Science.gov (United States)

    Baertschi, Bernard

    2015-01-01

    In this paper, I examine some important metaphysical lessons that are often presented as derived from two new scientific disciplines: synthetic biology and neuroscience. I analyse four of them: the nature of life, the existence of a soul (the mind-body problem), personhood, and free will. Many caveats are in order, and each 'advance' or each case should be assessed for itself. I conclude that a main lesson can nevertheless be learned: in conjunction with modern science, neuroscience and synthetic biology allow us to enrich old metaphysical debates, to deepen and even renew them. In particular, it becomes less and less plausible to consider life, mind, person, and agency as non-natural or non-physical entities. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  15. Cost-effectiveness of denosumab versus oral alendronate for elderly osteoporotic women in Japan.

    Science.gov (United States)

    Mori, T; Crandall, C J; Ganz, D A

    2017-05-01

    We constructed a Markov microsimulation model among hypothetical cohorts of community-dwelling elderly osteoporotic Japanese women without prior hip or vertebral fractures over a lifetime horizon. Compared with weekly oral alendronate for 5 years, denosumab every 6 months for 5 years is cost-saving or cost-effective at a conventionally accepted threshold. The objective of the study was to examine the cost-effectiveness of subcutaneous denosumab every 6 months for 5 years compared with weekly oral alendronate for 5 years in Japan. We calculated incremental cost-effectiveness ratios [ICERs] (2016 US dollars [$] per quality-adjusted life year [QALY]), using a Markov microsimulation model among hypothetical cohorts of community-dwelling osteoporotic Japanese women without prior hip or vertebral fractures at various ages of therapy initiation (65, 70, 75, and 80 years) over a lifetime horizon from three perspectives: societal, healthcare sector, and government. Denosumab was cost-saving compared with alendronate at ages 75 and 80 years from any of the three perspectives. The ICERs of denosumab compared with alendronate were $25,700 and $5000 per QALY at ages 65 and 70 years from a societal perspective and did not exceed a willingness-to-pay of $50,000 per QALY from the other two perspectives. In deterministic sensitivity analyses, results were sensitive to changes in the effectiveness of denosumab for reducing hip fracture and clinical vertebral fracture and the rate ratio of non-persistence with denosumab compared to alendronate. In probabilistic sensitivity analyses, the probabilities of denosumab being cost-effective compared with alendronate were 89-100% at a willingness-to-pay of $50,000 per QALY. Among community-dwelling elderly osteoporotic women in Japan, denosumab every 6 months for 5 years is cost-saving or cost-effective at a conventionally accepted threshold of willingness-to-pay at all ages examined, compared with weekly alendronate for 5

  16. Probing the limits of reality: the metaphysics in science fiction

    Science.gov (United States)

    Taylor, John L.

    2003-01-01

    Science fiction provides a genre in which metaphysical questions concerning the ultimate structure of reality regularly arise. In addressing these questions, contemporary scientists tend to assume that the questions are of a scientific nature and should be handled solely by reference to our best theories. In this paper, it is argued that we cannot afford to neglect the role of conceptual analysis - a distinctively philosophical task - in thinking critically about the possibilities that science fiction claims to describe.

  17. A systematic review of current osteoporotic metaphyseal fracture animal models.

    Science.gov (United States)

    Wong, R M Y; Choy, M H V; Li, M C M; Leung, K-S; K-H Chow, S; Cheung, W-H; Cheng, J C Y

    2018-01-01

    The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models. A literature search was performed on the Pubmed, Embase, and Web of Science databases, and relevant articles were selected. A total of 19 studies were included. Information on the animal, induction of osteoporosis, fracture technique, site and fixation, healing results, and utility of the model were extracted. Fracture techniques included drill hole defects (3 of 19), bone defects (3 of 19), partial osteotomy (1 of 19), and complete osteotomies (12 of 19). Drill hole models and incomplete osteotomy models are easy to perform and allow the study of therapeutic agents but do not represent the usual clinical setting. Additionally, biomaterials can be filled into drill hole defects for analysis. Complete osteotomy models are most commonly used and are best suited for the investigation of therapeutic drugs or noninvasive interventions. The metaphyseal defect models allow the study of biomaterials, which are associated with complex and comminuted osteoporotic fractures. For a clinically relevant model, we propose that an animal model should satisfy the following criteria to study osteoporotic fracture healing: 1) induction of osteoporosis, 2) complete osteotomy or defect at the metaphysis unilaterally, and 3) internal fixation. Cite this article : R. M. Y. Wong, M. H. V. Choy, M. C. M. Li, K-S. Leung, S. K-H. Chow, W-H. Cheung, J. C. Y. Cheng. A systematic review of current osteoporotic metaphyseal fracture animal models. Bone Joint Res 2018;7:6-11. DOI: 10.1302/2046-3758.71.BJR-2016-0334.R2. © 2018 Wong et al.

  18. Beware of mereologists bearing gifts: prolegomena to a medical metaphysics.

    Science.gov (United States)

    Khushf, George

    2013-10-01

    This essay considers implications of formal mereologies and ontologies for medical metaphysics. Edward Fried's extensional mereological account of the human body is taken as representative of a prominent strand in analytic metaphysics that has close affinities with medical positivism. I show why such accounts fail. First, I consider how Fried attempts to make sense of the medical case of Barney Clark, the first recipient of an artificial heart, and show that his analytic metaphysical categories do not have the right kind of fit with the case. A proper medical metaphysic should involve a richer two way dialogue with medicine, and it should not just "apply" formal accounts worked out in other settings. Second, I argue that any effort to account for real wholes with extensional mereological sums requires all sorts of ad hoc, supplementary mechanisms that do the real work, and the full repertoire of these mechanisms involves inconsistencies and semantic shifts. Finally, I consider an alternative strand of work on non-extensional whole/part relations that is closer to medicine and that can deepen reflection on some core problems in bioethics, for example, associated with the determination of death when an organism ceases to function as a whole. In addition to the utility such formal ontologies have for addressing traditional problems such as the determination of death, philosophers of medicine should appreciate the increasingly influential role such formal tools are playing in the development of data system ontologies. Assumptions integral to these ontologies have far reaching implications for the way future research and practice in medicine will be conducted, and much greater critical reflection is needed on the full range of issues associated with the development and use of such medical ontologies.

  19. Semantics and metaphysics in informatics: toward an ontology of tasks.

    Science.gov (United States)

    Figdor, Carrie

    2011-04-01

    This article clarifies three principles that should guide the development of any cognitive ontology. First, that an adequate cognitive ontology depends essentially on an adequate task ontology; second, that the goal of developing a cognitive ontology is independent of the goal of finding neural implementations of the processes referred to in the ontology; and third, that cognitive ontologies are neutral regarding the metaphysical relationship between cognitive and neural processes. Copyright © 2011 Cognitive Science Society, Inc.

  20. Defining human death: an intersection of bioethics and metaphysics.

    Science.gov (United States)

    Manninen, Bertha Alvarez

    2009-01-01

    For many years now, bioethicists, physicians, and others in the medical field have disagreed concerning how to best define human death. Different theories range from the Harvard Criteria of Brain Death, which defines death as the cessation of all brain activity, to the Cognitive Criteria, which is based on the loss of almost all core mental properties, e.g., memory, self-consciousness, moral agency, and the capacity for reason. A middle ground is the Irreversibility Standard, which defines death as occurring when the capacity for consciousness is forever lost. Given all these different theories, how can we begin to approach solving the issue of how to define death? I propose that a necessary starting point is discussing an even more fundamental question that properly belongs in the philosophical field of metaphysics: we must first address the issue of diachronic identity over time, and the persistence conditions of personal identity. In this paper, I illustrate the interdependent relationship between this metaphysical question and questions concerning the definition of death. I also illustrate how it is necessary to antecedently attend to the metaphysical issue of defining death before addressing certain issues in medical ethics, e.g., whether it is morally permissible to euthanize patients in persistent vegetative states or procure organs from anencephalic infants.

  1. Conscience claims, metaphysics, and avoiding an LGBT eugenic.

    Science.gov (United States)

    Brummett, Abram

    2018-04-23

    Novel assisted reproductive technologies (ART) are poised to present our society with strange new ethical questions, such as whether lesbian, gay, bisexual, and transgender (LGBT) couples should be allowed to produce children biologically related to both parents, or whether trans-women who want to experience childbirth should be allowed to receive uterine transplants. Clinicians opposed to offering such technologies to LGBT couples on moral grounds are likely to seek legal shelter through the conscience clauses enshrined in U.S. law. This paper begins by briefly discussing some novel ART on the horizon and noting that it is unclear whether current conscience clauses will permit fertility clinics to deny such services to LGBT individuals. A compromise approach to conscience is any view that sees the value of respecting conscience claims within limits. I describe and critique the constraints proposed in the recent work of Wicclair, NeJaime and Siegel as ultimately begging the question. My purpose is to strengthen their arguments by suggesting that in the controversial situations that elicit claims of conscience, bioethicists should engage with the metaphysical claims in play. I argue that conscience claims against LGBT individuals ought to be constrained because the underlying metaphysic-that God has decreed the LGBT lifestyle to be sinful-is highly implausible from the perspective of a naturalized metaphysic, which ought to be the lens through which we evaluate conscience claims. © 2018 John Wiley & Sons Ltd.

  2. Comparative Resistance to Teriparatide-Induced Bone Resorption With Denosumab or Alendronate.

    Science.gov (United States)

    Tsai, Joy N; Zhu, Yuli; Foley, Katelyn; Lee, Hang; Burnett-Bowie, Sherri-Ann; Neer, Robert M; Leder, Benjamin Z

    2015-07-01

    In postmenopausal osteoporotic women, denosumab fully inhibits teriparatide-induced bone resorption at approved doses. This property of denosumab is distinct from that of alendronate and likely contributes to the efficacy of combination denosumab and teriparatide therapy. Whether denosumab fully inhibits bone resorption when challenged by a higher dose of teriparatide is unknown. We aimed to define the comparative ability of denosumab and alendronate to block the acute proresorptive effects of high-dose teriparatide. In this randomized controlled trial, bone resorption (serum C-telopeptide [CTX]) was measured in 25 postmenopausal women prior to and 4 hours after a single 40-μg sc teriparatide injection. Subjects then received either a single injection of denosumab 60 mg or oral alendronate 70 mg weekly for 8 weeks. After 8 weeks, serum CTX was again measured before and 4 hours after a teriparatide a 40-μg injection. The primary outcome was the between-group difference in the teriparatide-induced change in CTX from baseline to week 8. At baseline, 40 μg of teriparatide induced similar 4-hour increases in mean CTX in both groups (alendronate 47% ± 14%, denosumab 46% ± 16%). After 8 weeks, teriparatide was still able to stimulate bone resorption in women treated with alendronate (mean CTX increase of 43% ± 29%) but not in women treated with denosumab (-7% ± 11%; P teriparatide to increase bone resorption acutely. These results suggest that combining denosumab with a more potent anabolic stimulus may result in greater separation between bone resorption and formation and hence greater increases in bone mass.

  3. Reduced RANKL expression impedes osteoclast activation and tooth eruption in alendronate-treated rats.

    Science.gov (United States)

    Bradaschia-Correa, Vivian; Moreira, Mariana M; Arana-Chavez, Victor E

    2013-07-01

    The creation of the eruption pathway requires the resorption of the occlusal alveolar bone by osteoclasts and signaling events between bone and dental follicle are necessary. The aim of the present study has been to evaluate the effect of alendronate on osteoclastogenesis and the expression of the regulator proteins of osteoclast activation, namely RANK, RANKL and OPG, in the bone that covers the first molar germ. Newborn Wistar rats were treated daily with 2.5 mg/kg alendronate for 4, 8, 14, 21 and 28 days, whereas controls received sterile saline solution. At the time points cited, maxillae were fixed, decalcified and processed for light and electron microscopic analysis. TRAP histochemistry was performed on semi-serial sections and the osteoclasts in the occlusal half of the bony crypt surface were counted. TUNEL analysis was carried out on paraffin sections. The occlusal bone that covers the upper first molar was removed in additional 4- and 8-day-old alendronate-treated and control rats in which the expression of RANK, RANKL and OPG was analyzed by SDS-polyacrylamide gel electrophoresis and Western blotting. TRAP-positive osteoclasts were more numerous in the alendronate group at all time points, despite their unactivated phenotype and the presence of apoptotic cells. RANKL expression in the alendronate specimens was inhibited at all time points, unlike in controls. Our findings indicate that the expression of RANKL in the occlusal portion of the bony crypt is unrelated to osteoclast recruitment and differentiation but is crucial to their activation during the creation of the eruption pathway.

  4. Metaphyseal locking plate as an external fixator for open tibial fracture: Clinical outcomes and biomechanical assessment.

    Science.gov (United States)

    Ma, Ching-Hou; Wu, Chin-Hsien; Jiang, Jiun-Ru; Tu, Yuan-Kun; Lin, Ting-Sheng

    2017-02-01

    This study aimed to evaluate the outcome of using a metaphyseal locking plate as a definitive external fixator for treating open tibial fractures based on biomechanical experiments and analysis of clinical results. A metaphyseal locking plate was used as an external fixator in 54 open tibial fractures in 52 patients. The mean follow-up was 38 months (range, 20-52 months). Moreover, static axial compression and torsional tests were performed to evaluate the strength of the fixation techniques. The average fracture healing time was 34.5 weeks (range, 12-78 weeks). At 4 weeks postoperatively and at the final follow-up, the average Hospital for Special Surgery knee score was 85 (range, 81-100) and 94 (range, 88-100), respectively, and the American Orthopaedic Foot and Ankle Society score was 88 (range, 80-100) and 96 (range, 90-100), respectively. Based on the static test result, the axial stiffness was significantly different among groups (p=0.002), whereas the torsional stiffness showed no significant difference (p=0.068). Clinical outcomes show that the use of locking plate as a definitive external fixator is an alternative choice for tibial fractures after obtaining appropriate fracture reduction. However, external locked plating constructs were not as strong as standard locked plating constructs. Therefore, the use of external locked plating constructs as a definitive treatment warrants further biomechanical study for construct strength improvement. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Tc-99m Radiolabeled Alendronate Sodium Microemulsion: Characterization and Permeability Studies across Caco-2 Cells.

    Science.gov (United States)

    Elitez, Yetkin; Ekinci, Meliha; Ilem-Ozdemir, Derya; Gundogdu, Evren; Asikoglu, Makbule

    2017-06-12

    Alendronate sodium (ALD) is used orally but it is poorly absorbed from the gastrointestinal (GI) tract. For this reason, microemulsion system was chosen to evaluate ALD from the GI tract after oral delivery. This study was aimed to prepare water-in-oil (w/o) microemulsion formulation of ALD and evaluate the permeability of ALD microemulsion from Caco-2 cell lines with radioactive and non-radioactive studies. The ALD microemulsion was developed by using pseudo-ternary phase diagram and composed of Soybean oil, Colliphor EL, Tween 80, Transcutol and distilled water. The prepared ALD microemulsion was characterized by physical appearance, droplet size, viscosity, pH, electrical conductivity and refractive index. The stability of the formulation was investigated for 6 months at 25±2°C/60±5% of relative humidity (RH) as well as at 40±2°C/75±5% RH. After that 1 mg of ALD was radiolabeled with 99mTc and added to microemulsion. The permeability studies were performed with both 99mTc-ALD microemulsion and ALD microemulsion. The experimental results suggested that ALD microemulsion presented adequate stability with droplet size varying from 37.8±0.9 to 39.9±1.2 nm during incubation time. In addition, ALD microemulsion was radiolabeled with high labeling efficiency (>95%). In non-radioactive study, ALD permeability was found to be 45 μg.mL-1 and microemulsion has high permeability percentage when compared to another study. The novel w/o microemulsion formulation has been developed for oral delivery of ALD. Based on the results, permeability of ALD could be significantly improved by the microemulsion formulation. In addition, 99mTc-ALD microemulsion in capsule can be used for bone disease treatment and diagnosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Understanding the influence of alendronate on the morphology and phase transformation of apatitic precursor nanocrystals.

    Science.gov (United States)

    Zhang, Guiling; Huang, Rong; Li, Zhicheng; Yang, Xianyan; Chen, Xiaoyi; Xia, Wei; Sun, Xiaoliang; Yang, Guojing; Gao, Changyou; Gou, Zhongru

    2012-08-01

    Bisphosphonates (BPs) are a class of synthetic pyrophosphate analogs that can prevent the loss of bone mass, given orally to treat postmenopuasal osteoporosis. It is not clear yet if the benefits of BPs include the possibility of affecting bone apatitic precursors transition for bone consolidation except for encouraging osteoclasts to undergo apoptosis. Furthermore, the complexity of the in vivo system makes it difficult to isolate and study such extracellular topographical cues that trigger bone turnover response. Herein, we proposed a wet-chemical approach employing alendronate sodium (AS) as a guide of hydroxyapatite (HA) precursor growth and conversion which was initiated from the nucleantion of octacalcium phosphate (OCP) in a cell membrane-mimicking surfactant micelle aqueous system. The nanocrystal clusters of dicalcium phosphate dihydrate (DCPD) and OCP nanocryatals were readily precipitated within a relatively narrow AS concentration range (2-8 μM). However, such low concentrations of AS seemed to stabilize the more acidic phases, and to delay the transformation into HA, to an extent which increased on increasing AS concentration. In contrast, at a slight higher concentrations (16-32 μM), AS promoted HA precipitation after ageing for 1h. It was found that the effect of AS on the phase selectivity of apatitic precursors was concentration-dependent within a prolonged ageing time stage (0.5-168 h). The AS-assisted reactions in vitro offer an expedient way to understand the underlying implementarity between bone and BPs for bone consolidation, and to improve our understanding of benefit of BP dosages on bone turnover and trauma healing. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Feng Youlan’s Interpretation of Western Philosophy:A Critical Examination from the Perspective of Metaphysical Methodology

    Directory of Open Access Journals (Sweden)

    Derong Chen

    2015-04-01

    Full Text Available The paper aims to display a limited observation of Feng’s interpretation of Western philosophy through the window of metaphysical methodology. This paper concentrates on Feng’s interpretation of Western philosophy from the perspective of metaphysical methodology and aims to display a limited observation of Feng’s interpretation of Western philosophy through the window of metaphysical methodology. Based on a brief review the recent studies of Feng Youlan and Western philosophy, this paper analyzes the progress and insufficient aspects in current studies on this issue and particularly clarifies what are the metaphysics and metaphysical methods in the context of Feng Youlan’s philosophy. In clarifying Feng’s interpretation of Western philosophy from the perspective of methodology, this paper further critically analyzes the Feng’s positive metaphysical methods and negative metaphysical methods, and assumes that Feng’s negative metaphysical methods essentially is a kind of attitudes towards metaphysics but neither a kind of metaphysics nor a kind of metaphysical methods. Instead of characterizing metaphysical methods as positive and negative as Feng did, this paper suggests an alternative division of metaphysical methods: direct and indirect methods of dealing with metaphysical issues.

  8. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group

    DEFF Research Database (Denmark)

    Hosking, D; Chilvers, C E; Christiansen, C

    1998-01-01

    increases in bone mineral density. Alendronate did not increase bone mineral density of the forearm, but it slowed the loss. The responses to estrogen-progestin were 1 to 2 percentage points greater than those to the 5-mg dose of alendronate. Alendronate was well tolerated, with a safety profile similar...... to that of placebo or estrogen-progestin. CONCLUSIONS: Alendronate prevents bone loss in postmenopausal women under 60 years of age to nearly the same extent as estrogen-progestin.......BACKGROUND: Estrogen-replacement therapy prevents osteoporosis in postmenopausal women by inhibiting bone resorption, but the balance between its long-term risks and benefits remains unclear. Whether other antiresorptive therapies can prevent osteoporosis in these women is also not clear. METHODS...

  9. Teriparatide Versus Alendronate for the Preservation of Bone Mineral Density After Total Hip Arthroplasty - A randomized Controlled Trial.

    Science.gov (United States)

    Kobayashi, Naomi; Inaba, Yutaka; Uchiyama, Makoto; Ike, Hiroyuki; Kubota, So; Saito, Tomoyuki

    2016-01-01

    In this study, the effect of teriparatide for the prevention of bone mineral density (BMD) loss after THA was compared with alendronate in a randomized controlled trial. Forty-eight patients were assigned to three groups, namely, the teriparatide, alendronate, and no medication groups. Dual-energy x-ray absorptiometry (DEXA) was performed at 1 week post-surgery as a baseline reference, followed by subsequent measurements at 12, 24, and 48 weeks postoperatively. For periprosthetic BMD loss, a significant effect of teriparatide was demonstrated, though its effect was similar to alendronate. On the other hand, higher lumbar BMD was observed in the teriparatide group than in the alendronate group at 48 weeks post-surgery. Teriparatide administration may be one reasonable option for osteoporotic patient to preserve the periprosthetic BMD after THA. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Time trends for alendronate prescription practices in women with chronic obstructive pulmonary disease and women exposed to systemic glucocorticoids

    DEFF Research Database (Denmark)

    Brask-Lindemann, Dorthe; Eiken, P; Eskildsen, P

    2013-01-01

    Summary Chronic obstructive pulmonary disease (COPD) and systemic glucocorticoid exposure are well-known risk factors of osteoporosis. We evaluated alendronate prescription practices related to COPD and exposure to systemic corticosteroids from 1996 to 2008 and showed an increasing targeting...... of alendronate treatment in patients with COPD and patients with systemic corticosteroid exposure. Introduction COPD and systemic glucocorticoid exposure are well-known risk factors of osteoporosis and fragility fracture, but osteoporosis is often underdiagnosed and undertreated in these patients. This study...... aims to evaluate alendronate prescription practices related to COPD and/or to exposure to systemic glucocorticoids among Danish women. Methods A total of 388,314 female subjects >50 years old, 64,719 of whom initiated treatment with alendronate, and 323,595 age- and gender-matched controls were...

  11. Johann Christoph Sturm's universal mathematics and metaphysics (German Title: Universalmathematik und Metaphysik bei Johann Christoph Sturm)

    Science.gov (United States)

    Leinsle, Ulrich G.

    In order to understand Sturm's concept of a universal mathematics as a replacement or complement of metaphysics, one first has to examine the evolution of the idea of a mathesis universalis up to Sturm, and his concept of metaphysics. According to the understanding of those times, natural theology belongs to metaphysics. The last section is concerned with Sturm's statements on the existence of God and his assessments for a physico-theology.

  12. Fall and Rise of Aristotelian Metaphysics in the Philosophy of Science

    Science.gov (United States)

    Lamont, John

    2009-06-01

    The paper examines the fortunes of Aristotelian metaphysics in science and the philosophy of science. It considers the Enlightenment claim that such a metaphysics is fundamentally unscientific, and that its abandonment was essential to the scientific revolution. The history of the scientific revolution and the metaphysical debates involved in it is examined, and it is argued that the eclipse of Aristotelian views was neither complete, nor merited. The evolution of Humeian and positivist accounts of science is described, and it is shown how the severe problems with these accounts, together with a revival of Aristotelian concepts in philosophy, have led to the rebirth of broadly Aristotelian accounts of the metaphysics underlying science.

  13. Alendronate Sodium as Enteric Coated Solid Lipid Nanoparticles; Preparation, Optimization, and In Vivo Evaluation to Enhance Its Oral Bioavailability.

    Directory of Open Access Journals (Sweden)

    Khaled Mohamed Hosny

    Full Text Available Treatment of osteoporosis with alendronate sodium has several challenges. The first challenge is the low bioavailability. The second main challenge is side effects, which include oesophageal ulceration. The aim of this research was to reformulate alendronate sodium as enteric coated solid lipid nanoparticles in order to enhance its bioavailability, and preventing the free alendronate sodium from coming into direct contact with the gastrointestinal mucosa, and thereby reducing the possibility of side effects. Enteric coated solid lipid nanoparticles were prepared according to the Box-Behnken design employing Design expert® software, and characterized for size, morphology, and entrapment efficiency. The optimized formula was coated with an Eudragit S100 and evaluated for drug release in acidic and basic media, stability studies and pharmacokinetic evaluations on rabbits. The results indicated that, using Derringer's desirability functional tool for optimization, the highest entrapment efficiency value of 74.3% and the smallest size value of 98 nm were predicted under optimum conditions with a desirability value of 0.917. The optimized nanoparticles released alendronate sodium only at an alkaline pH. The pharmacokinetic evaluation revealed that alendronate sodium bioavailability was enhanced by more than 7.4-fold in rabbits. In conclusion, enteric coated solid lipid nanoparticles is a promising formula for the delivery of alendronate sodium, eliminating its oesophageal side effects and enhancing its bioavailability.

  14. Effects of teriparatide versus alendronate for treatment of postmenopausal osteoporosis: A meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Wang, Ya-Kang; Qin, Si-Qing; Ma, Tao; Song, Wei; Jiang, Ren-Qi; Guo, Jian-Bin; Li, Kun; Zhang, Yu-Min

    2017-05-01

    Osteoporosis remains a clinical challenge. Teriparatide is an anabolic drug and alendronate is an antiresorptive agent; both are used in the treatment of osteoporosis. Comprehensive reviews investigating the comparative safety and efficacy of teriparatide versus alendronate are scarce. Therefore, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the safety and efficacy of teriparatide versus alendronate for the treatment of postmenopausal osteoporosis. We conducted a comprehensive literature review of the PubMed, EMBASE, Cochrane Controlled Trials Registry, and the China Academic Journal Network Publishing databases for relevant RCTs of teriparatide versus alendronate in postmenopausal osteoporosis patients. Outcome measures were percentage change in lumbar spine and femoral neck bone mineral density (BMD) and incidence of vertebral and nonvertebral fractures. Effect size was reported as weighted mean differences (WMDs) for continuous outcomes and odds ratios (OR) for dichotomous outcomes, with associated 95% confidence intervals (CIs). Six trials involving 618 patients were included. The meta-analysis demonstrated a significant increase in lumbar spine BMD (WMD: 3.46, 95% CI: 2.15-4.77, P osteoporosis patients treated with teriparatide compared with alendronate for 6 to 18 months. These beneficial effects were apparent in the lumbar spine at 12 months of treatment (WMD: 4.49, 95% CI: 2.57-6.40, P osteoporosis. The efficacy and safety of long-term teriparatide and alendronate treatment in postmenopausal osteoporosis should be further investigated in clinical trials.

  15. Patients' substantialization of disease, the hybrid symptom and metaphysical care.

    Science.gov (United States)

    Pârvan, Alexandra

    2015-06-01

    In the context of current scholarship concerned with facilitating integration between the biomedical and the patient-centred models of care, the article suggests that disease brings about an ontological disruption in patients, which is not directly addressed in either model, and may interfere with treatment and therapy outcomes if not met with a type of care termed here as 'metaphysical'. The receipt of diagnosis and medical care can give patients the sense that they are ontologically diminished, or less of a human, and along with physicians' approaches to and discourses about disease, may prompt them to seek ontological restoration or security in the same way as psychologically traumatized patients sometimes do: by treating the disease and/or the experience of harm associated with it as a thing that exists per se. I call this 'substantialization' of disease (or harm) and draw on Augustine's theory of non-substantial deficiencies (physiological and moral) and on Plato's and Plotinus's different takes on such defects in order to discuss what substantialization can do for patients. Based on literature that examines patients' ways of talking about and living with their disease, I speculate that substantialization can generate a 'hybrid symptom', consisting in patterns of exercising agency which may predispose to non-adherence. Ways in which physicians could provide metaphysical care are proposed, along with an understanding of chronic patients as hybrid ontological and agentic units, which draws on theories of enactive cognition. I opine that metaphysical care may facilitate integration between the depersonalized and personalized models of care. © 2014 John Wiley & Sons, Ltd.

  16. Basic structures of reality essays in meta-physics

    CERN Document Server

    McGinn, Colin

    2011-01-01

    In Basic Structures of Reality, Colin McGinn deals with questions of metaphysics, epistemology, and philosophy of mind from the vantage point of physics. Combining general philosophy with physics, he covers such topics as the definition of matter, the nature of space, motion, gravity, electromagnetic fields, the character of physical knowledge, and consciousness and meaning. Throughout, McGinn maintains an historical perspective and seeks to determine how much we really know of the world described by physics. He defends a version of "structuralism": the thesis that our knowledge is p

  17. Like an Image: Sensibility and Reflexivity in Descartes’ Metaphysics

    Directory of Open Access Journals (Sweden)

    Augustin Dumont

    2014-06-01

    Full Text Available This paper aims at questioning the role of image and imagination in Descartes’ Metaphysics, especially in the Meditations on First Philosophy, by holding both a certain doctrinal or theoretical discourse on image/imagination and the Cartesian use of images/imagination. Besides the fact that this rarely considered perspective prevents from freezing the original text, this strategy allows to highlight the ambiguity of theses notions, revealed through what is doing by the act of imagining compared to the act of conceiving with the understanding.

  18. Infanticide for handicapped infants: sometimes it's a metaphysical dispute.

    Science.gov (United States)

    Long, T A

    1988-01-01

    Since 1973 the practice of infanticide for some severely handicapped newborns has been receiving more open discussion and defence in the literature on medical ethics. A recent and important argument for the permissibility of infanticide relies crucially on a particular concept of personhood that excludes the theological. This paper attempts to show that the dispute between the proponents of infanticide and their religious opponents cannot be resolved because one side's perspective on the infant is shaped by a metaphysics that is emphatically rejected by the other. In such a situation philosophical argument is powerless to bring about a resolution because there can be no refutation of one side by the other. PMID:2969052

  19. Rejecting medical humanism: medical humanities and the metaphysics of medicine.

    Science.gov (United States)

    Bishop, Jeffrey P

    2008-03-01

    The call for a narrative medicine has been touted as the cure-all for an increasingly mechanical medicine. It has been claimed that the humanities might create more empathic, reflective, professional and trustworthy doctors. In other words, we can once again humanise medicine through the addition of humanities. In this essay, I explore how the humanities, particularly narrative medicine, appeals to the metaphysical commitments of the medical institution in order to find its justification, and in so doing, perpetuates a dualism of humanity that would have humanism as the counterpoint to the biopsychosociologisms of our day.

  20. Science and Metaphysics in the Three Religions of the Book

    Directory of Open Access Journals (Sweden)

    Toby E. Huff

    2000-12-01

    Full Text Available The three religions of the Book trace their origins back to the same Abrahamic experience, but only one, Christianity, developed a metaphysical framework consistent with that of modern science. Both Judaism and Islam during their formative years, and continuously up to modern times, considered Greek philosophy and science alien wisdom, jeopardizing their sacred scriptures. The different path followed by Christianity is due to the influence of Hellenistic thought during Christianity's early formative period. Both Judaism and Islam were spared the direct mediation of Greek culture and ideas because both Judaism and Islam developed geographically and linguistically isolated from the Greek influences during the reception of their scriptures.

  1. Modulation of adhesion-dependent cAMP signaling by echistatin and alendronate

    Science.gov (United States)

    Fong, J. H.; Ingber, D. E.

    1996-01-01

    We measured intracellular cAMP levels in cells during attachment and spreading on different extracellular matrix (ECM) proteins. Increases in cAMP were observed within minutes when cells attached to fibronectin, vitronectin, and a synthetic RGD-containing fibronectin peptide (Petite 2000), but not when they adhered to another integrin alpha nu beta 3 ligand, echistatin. Because echistatin also inhibits bone resorption, we measured the effects of adding another osteoporosis inhibitor, alendronate, in this system. Alendronate inhibited the cAMP increase induced by ligands that primarily utilize integrin alpha nu beta 3 (vitronectin, Peptite 2000), but not by fibronectin which can also use integrin alpha 5 beta 1. These results show that cell adhesion to ECM can increase intracellular cAPM levels and raise the possibility that inhibitors of osteoporosis may act, in part, by preventing activation of this pathway by integrins.

  2. Development and characterization of a gastroretentive dosage form composed of chitosan and hydroxyethyl cellulose for alendronate

    OpenAIRE

    Chen YC; Ho HO; Chiu CC; Sheu MT

    2013-01-01

    Ying-Chen Chen,1,* Hsiu-O Ho,1,* Chiao-Chi Chiu,1 Ming-Thau Sheu1,2 1School of Pharmacy, College of Pharmacy, Taipei Medical University, 2Clinical Research Center and Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan*These authors contributed equally to this workAbstract: In this study, alendronate, the most commonly used biphosphonate for treating osteoporosis, was formulated as gastroretentive dosage form (GRDF) tablets to enhance its oral bioav...

  3. Effects of combination treatment with alendronate and raloxifene on skeletal properties in a beagle dog model.

    Science.gov (United States)

    Allen, Matthew R; McNerny, Erin; Aref, Mohammad; Organ, Jason M; Newman, Christopher L; McGowan, Brian; Jang, Tim; Burr, David B; Brown, Drew M; Hammond, Max; Territo, Paul R; Lin, Chen; Persohn, Scott; Jiang, Lei; Riley, Amanda A; McCarthy, Brian P; Hutchins, Gary D; Wallace, Joseph M

    2017-01-01

    A growing number of studies have investigated combination treatment as an approach to treat bone disease. The goal of this study was to investigate the combination of alendronate and raloxifene with a particular focus on mechanical properties. To achieve this goal we utilized a large animal model, the beagle dog, used previously by our laboratory to study both alendronate and raloxifene monotherapies. Forty-eight skeletally mature female beagles (1-2 years old) received daily oral treatment: saline vehicle (VEH), alendronate (ALN), raloxifene (RAL) or both ALN and RAL. After 6 and 12 months of treatment, all animals underwent assessment of bone material properties using in vivo reference point indentation (RPI) and skeletal hydration using ultra-short echo magnetic resonance imaging (UTE-MRI). End point measures include imaging, histomorphometry, and mechanical properties. Bone formation rate was significantly lower in iliac crest trabecular bone of animals treated with ALN (-71%) and ALN+RAL (-81%) compared to VEH. In vivo assessment of properties by RPI yielded minimal differences between groups while UTE-MRI showed a RAL and RAL+ALN treatment regimens resulted in significantly higher bound water compared to VEH (+23 and +18%, respectively). There was no significant difference among groups for DXA- or CT-based measures lumbar vertebra, or femoral diaphysis. Ribs of RAL-treated animals were smaller and less dense compared to VEH and although mechanical properties were lower the material-level properties were equivalent to normal. In conclusion, we present a suite of data in a beagle dog model treated for one year with clinically-relevant doses of alendronate and raloxifene monotherapies or combination treatment with both agents. Despite the expected effects on bone remodeling, our study did not find the expected benefit of ALN to BMD or structural mechanical properties, and thus the viability of the combination therapy remains unclear.

  4. Effects of combination treatment with alendronate and raloxifene on skeletal properties in a beagle dog model.

    Directory of Open Access Journals (Sweden)

    Matthew R Allen

    Full Text Available A growing number of studies have investigated combination treatment as an approach to treat bone disease. The goal of this study was to investigate the combination of alendronate and raloxifene with a particular focus on mechanical properties. To achieve this goal we utilized a large animal model, the beagle dog, used previously by our laboratory to study both alendronate and raloxifene monotherapies. Forty-eight skeletally mature female beagles (1-2 years old received daily oral treatment: saline vehicle (VEH, alendronate (ALN, raloxifene (RAL or both ALN and RAL. After 6 and 12 months of treatment, all animals underwent assessment of bone material properties using in vivo reference point indentation (RPI and skeletal hydration using ultra-short echo magnetic resonance imaging (UTE-MRI. End point measures include imaging, histomorphometry, and mechanical properties. Bone formation rate was significantly lower in iliac crest trabecular bone of animals treated with ALN (-71% and ALN+RAL (-81% compared to VEH. In vivo assessment of properties by RPI yielded minimal differences between groups while UTE-MRI showed a RAL and RAL+ALN treatment regimens resulted in significantly higher bound water compared to VEH (+23 and +18%, respectively. There was no significant difference among groups for DXA- or CT-based measures lumbar vertebra, or femoral diaphysis. Ribs of RAL-treated animals were smaller and less dense compared to VEH and although mechanical properties were lower the material-level properties were equivalent to normal. In conclusion, we present a suite of data in a beagle dog model treated for one year with clinically-relevant doses of alendronate and raloxifene monotherapies or combination treatment with both agents. Despite the expected effects on bone remodeling, our study did not find the expected benefit of ALN to BMD or structural mechanical properties, and thus the viability of the combination therapy remains unclear.

  5. Comparison of the alendronate and irradiation with a light-emitting diode (LED) on murine osteoclastogenesis.

    Science.gov (United States)

    Sohn, Hong Moon; Ko, Youngjong; Park, Mineon; Kim, Bora; Park, Jung Eun; Kim, Donghwi; Moon, Young Lae; Lim, Wonbong

    2017-01-01

    Photomodulation therapy (PBMT) using light-emitting diode (LED) has been proposed as an alternative to conventional osteoporosis therapies. Our aim was to determine the effect of irradiation with a light-emitting diode on receptor activator of NF-κB ligand (RANKL)-mediated differentiation of mouse bone marrow macrophages into osteoclasts and compare it to alendronate treatment. The cells were irradiated with LED at 635±10 nm, 9-cm spot size, 5 mW/cm 2 , and 18 J for 60 min/day in a CO 2 incubator. The differentiation of irradiated and untreated RANKL-stimulated bone marrow macrophages into osteoclasts was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and by molecular methods. These included assessing messenger RNA (mRNA) expression of osteoclastic markers such as TRAP, c-Fos, Atp6v0d2, DC-STAMP, NFATc1, cathepsin K, MMP9 and OSCAR; phosphorylation of various MAPKs, including extracellular signal-regulated kinase ERK1/2, P38, and JNK; NF-κB translocation; and resorption pit formation. Results were compared to those obtained with sodium alendronate. Production of reactive oxygen species was measured by a 2',7'-dihydrodichlorofluorescein diacetate assay. LED irradiation and alendronate inhibited mRNA expression of osteoclast-related genes, such as TRAP, c-Fos, and NFATc1, and reduced the osteoclast activity of RANKL-stimulated bone marrow macrophages. LED irradiation, but not alendronate, also inhibited the production of reactive oxygen species (ROS); phosphorylation of ERK, P38, and IκB; and NF-κB translocation. These findings suggest that LED irradiation downregulates osteoclastogenesis by ROS production; this effect could lead to reduced bone loss and may offer a new therapeutic tool for managing osteoporosis.

  6. Alendronate, a double-edged sword acting in the mevalonate pathway

    OpenAIRE

    TRICARICO, PAOLA MAURA; GIRARDELLI, MARTINA; KLEINER, GIULIO; KNOWLES, ALESSANDRA; VALENCIC, ERICA; CROVELLA, SERGIO; MARCUZZI, ANNALISA

    2015-01-01

    Aminobisphosphonate aledronate is a compound commonly used clinically for the treatment of osteoporosis and other bone diseases, as a result of it preventing bone resorption. However, in previous years it has also been used to obtain cellular and animal models of a rare genetic disorder termed Mevalonate Kinase Deficiency (MKD). MKD is caused by mutations affecting the mevalonate kinase enzyme, in the cholesterol pathway and alendronate can be used to biochemically mimic the genetic defect as...

  7. The disclosure of a metaphysical horizon, or how to escape dialectics

    African Journals Online (AJOL)

    In a footnote to The Inoperative Community French philosopher Jean-Luc Nancy wonders how to escape Hegelian dialectics. Because Nancy in his later work often returns to this attempt of a 'disclosure of our metaphysical horizon', we not only consider this note as a crucial one in his attempt to 'disclose' our metaphysical ...

  8. Hydroxyapatite nanocrystals functionalized with alendronate as bioactive components for bone implant coatings to decrease osteoclastic activity

    Science.gov (United States)

    Bosco, Ruggero; Iafisco, Michele; Tampieri, Anna; Jansen, John A.; Leeuwenburgh, Sander C. G.; van den Beucken, Jeroen J. J. P.

    2015-02-01

    The integration of bone implants within native bone tissue depends on periprosthetic bone quality, which is severely decreased in osteoporotic patients. In this work, we have synthesized bone-like hydroxyapatite nanocrystals (nHA) using an acid-base neutralization reaction and analysed their physicochemical properties. Subsequently, we have functionalized the nHA with alendronate (nHAALE), a well-known bisphosphonate drug used for the treatment of osteoporosis. An in vitro osteoclastogenesis test was carried out to evaluate the effect of nHAALE on the formation of osteoclast-like cells from monocytic precursor cells (i.e. RAW264.7 cell line) showing that nHAALE significantly promoted apoptosis of osteoclast-like cells. Subsequently, nHA and nHAALE were deposited on titanium disks using electrospray deposition (ESD), for which characterisation of the deposited coatings confirmed the presence of alendronate in nHAALE coatings with nanoscale thickness of about 700 nm. These results indicate that alendronate linked to hydroxyapatite nanocrystals has therapeutic potential and nHAALE can be considered as an appealing coating constituent material for orthopaedic and oral implants for application in osteoporotic patients.

  9. Effects of alendronate on tooth eruption and molar root formation in young growing rats.

    Science.gov (United States)

    Bradaschia-Correa, Vivian; Massa, Luciana F; Arana-Chavez, Victor E

    2007-12-01

    Tooth eruption consists of the movement of teeth from the bony crypt in which they initiate their development to the occlusal plane in the oral cavity. Interactions between the tooth germ and its surrounding alveolar bone occur in order to offer spatial conditions for its development and eruption. This involves bone remodeling during which resorption is a key event. Bisphosphonates are a group of drugs that interfere with the resorption of mineralized tissues. With the purpose of investigating the effects of sodium alendronate (a potent bisphosphonate inhibitor of osteoclast activity) on alveolar bone during tooth development and eruption, we gave newborn rats daily doses of this drug for 4, 14, and 30 days. Samples of the maxillary alveolar process containing the tooth germs were processed for light, transmission, and scanning electron microscopy and were also submitted to tartrate-resistant acid phosphatase histochemistry and high-resolution colloidal-gold immunolabeling for osteopontin. Inhibition of osteoclast activity by sodium alendronate caused the absence of tooth eruption. The lack of alveolar bone remodeling resulted in primary bone with the presence of latent osteoclasts and abundant osteopontin at the interfibrillar regions. The developing bone trabeculae invaded the dental follicle and reached the molar tooth germs, provoking deformities in enamel surfaces. No root formation was observed. These findings suggested that alendronate effectively inhibited tooth eruption by interfering with the activation of osteoclasts, which remained in a latent stage.

  10. Process analytical technology to understand the disintegration behavior of alendronate sodium tablets.

    Science.gov (United States)

    Xu, Xiaoming; Gupta, Abhay; Sayeed, Vilayat A; Khan, Mansoor A

    2013-05-01

    Various adverse events including esophagus irritations have been reported with the use of alendronate tablets, likely attributed to the rapid tablet disintegration in the mouth or esophagus. Accordingly, the disintegration of six alendronate tablet drug products was studied using a newly developed testing device equipped with in-line sensors, in addition to the official compendial procedure for measuring the disintegration time. The in-line sensors were used to monitor the particle count and solution pH change to assess the onset and duration of disintegration. A relatively large variation was observed in the disintegration time of the tested drug products using the compendial method. The data collected using the in-line sensors suggested that all tested drug products exhibited almost instantaneous onset of disintegration, under 2 s, and a sharp drop in solution pH. The drop in pH was slower for tablets with slower disintegration. The in-house prepared alendronate test tablets also showed similar trends suggesting rapid solubilization of the drug contributed to the fast tablet disintegration. This research highlights the usefulness of the newly developed in-line analytical method in combination with the compendial method in providing a better understanding of the disintegration and the accompanying drug solubilization processes for fast disintegrating tablet drug products. Copyright © 2013 Wiley Periodicals, Inc.

  11. LEIBNIZ AND THE POLYP, OR THE METAPHYSICAL PUZZLE OF LIFE

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    Arthur Dony

    2017-06-01

    Full Text Available LEIBNIZ AND THE POLYP, OR THE METAPHYSICAL PUZZLE OF LIFE   In this paper, I propose to explore the link between experience and reason in the problem of the apprehension of life. My general claim is that philosophical issues are necessarily involved in a theory of living organisms, since identifying a certain entity as a living being is to go beyond its manifestations. In part I, I argue that the empirical approach of the natural sciences cannot fully account for the peculiarity of life, showing that the different criteria used to distinguish the living from the non‐living, as those proposed in biology, may turn out to be inadequate. In the second part, I elaborate on these issues by focusing on the Leibnizian theory of living beings. In particular, I will emphasize how Leibniz’s theory exemplifies the problematic relationship between the observable properties of organized matter and the inner (or metaphysical properties of the living as such. Finally, I will propose to consider the discovery of the polyp in the eighteenth century as a case of particular interest and a challenge to the classical conceptions of the living, insofar as it raises the crucial questions of unity and individuality, which are of utmost importance with regard to the ontological status of life. 

  12. "Bewitching" or confusing methaphysics? The demarcation between science and metaphysics according to Karl Popper

    Directory of Open Access Journals (Sweden)

    M. Elaine Botha

    1986-03-01

    Full Text Available The problems of both classical and modern theory of knowledge, according to Popper, reside in the problem of demarcation: a problem closely re­ lated to the problem of induction. The paper argues the view that Popper's view of metaphysics is ambiguous, requiring another criterion to distinguish between "good " and "bad " metaphysics. The sources of the problem are pinpointed, and Popper's distinction between three types of theory outlined. The article then explores the distinction between types of theories and the issues of falsification, testability and refutation, before going on to a consideration of the relationship between science and metaphysics, and w eighing up the issue of good ancid metaphysics. From this emerges clearly that the second "criterionot demarcation" is needed to make precisely this distinction; also in view of Popper's u n ­ clear, even ambiguous, view of metaphysics.

  13. Biochemical markers can predict the response in bone mass during alendronate treatment in early postmenopausal women. Alendronate Osteoporosis Prevention Study Group

    DEFF Research Database (Denmark)

    Ravn, Pernille; Clemmesen, B; Christiansen, C

    1999-01-01

    Data from the Danish cohort (n = 67) of a multicenter trial of oral alendronate in the prevention of postmenopausal osteoporosis were used to evaluate the capacity of the biochemical markers to predict changes in bone mineral density (BMD). A panel of markers were measured: serum N-terminal midfr......Data from the Danish cohort (n = 67) of a multicenter trial of oral alendronate in the prevention of postmenopausal osteoporosis were used to evaluate the capacity of the biochemical markers to predict changes in bone mineral density (BMD). A panel of markers were measured: serum N...... at month 6 in the biochemical markers for predicting prevention of bone loss in the spine over 2 years. The cutpoints used were a 30% (N-MID OC) or 50% (all other markers) decrease from baseline. Sensitivity levels were 82% (N-MID OC), 98% (total OC), 78% (sCL and NTX), and 89% (uCL). Specificities were 91...... at the spine were similar: sensitivity, 82%; specificity, 55%; and positive predictive value, 79%. In conclusion, short-term changes in biochemical markers were valid predictors of long-term changes in BMD. Short-term changes in the sensitive biochemical markers revealed a predictive capacity similar to bone...

  14. In Vitro and In Vivo Evaluation of Commercially Available Fibrin Gel as a Carrier of Alendronate for Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Beom Su Kim

    2017-01-01

    Full Text Available Alendronate (ALN is a bisphosphonate drug that is widely used for the treatment of osteoporosis. Furthermore, local delivery of ALN has the potential to improve the bone regeneration. This study was designed to investigate an ALN-containing fibrin (fibrin/ALN gel and evaluate the effect of this gel on both in vitro cellular behavior using human mesenchymal stem cells (hMSCs and in vivo bone regenerative capacity. Fibrin hydrogels were fabricated using various ALN concentrations (10−7–10−4 M with fibrin glue and the morphology, mechanical properties, and ALN release kinetics were characterized. Proliferation and osteogenic differentiation of and cytotoxicity in fibrin/ALN gel-embedded hMSCs were examined. In vivo bone formation was evaluated using a rabbit calvarial defect model. The fabricated fibrin/ALN gel was transparent with Young’s modulus of ~13 kPa, and these properties were not affected by ALN concentration. The in vitro studies showed sustained release of ALN from the fibrin gel and revealed that hMSCs cultured in fibrin/ALN gel showed significantly increased proliferation and osteogenic differentiation. In addition, microcomputed tomography and histological analysis revealed that the newly formed bone was significantly enhanced by implantation of fibrin/ALN gel in a calvarial defect model. These results suggest that fibrin/ALN has the potential to improve bone regeneration.

  15. Effect of Weekly Alendronate on Knee Symptoms in Patients with Osteoporosis and Knee Osteoarthritis Coexistence - Original Investigation

    Directory of Open Access Journals (Sweden)

    Levent Ediz

    2010-04-01

    Full Text Available Aim: The aim of this study was to examine the effect of alendronate 70 mg weekly on knee symptoms in elderly women with osteoporosis and knee OA coexistence. Material and Methods: Elderly women who diagnosed as osteoporosis between 60-75 years old, underwent radiography of the knee if they reported symptoms of knee OA. Radiographs were read for Kellgren and Lawrence grade and individual features of OA. Osteoporotic patients with Knee OA treated with 70 mg alendronate once weekly for one year. Knee symptoms were assessed by interview before the treatment and 6 and 12 months after the treatment, and knee pain severity was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC, Lequense index, VAS at rest and at movement. Results: Alendronate 70 mg once weekly use was associated with less severity of knee pain as assessed by WOMAC scores, Lequense index, VAS at rest and at movement at 6th and 12th month assessments. Conclusion: This current study has shown that Alendronate 70 mg once weekly use was associated with less severity of knee symptoms in elderly women with osteoporosis and knee OA coexistence. Additional long-term randomised, placebo controlled clinical trials are needed to confirm this effect of weekly Alendronate. (From the World of Osteoporosis 2010;16:17-21

  16. Treatment of epiphyseo-metaphyseal fractures in children with an original implant. The threaded pin with an adjustable lock (Fixano).

    Science.gov (United States)

    Gicquel, Philippe; Giacomelli, Marie-Christine; Karger, Claude; Clavert, Jean-Michel

    2005-02-01

    Improvement of stability of internal fixation of epiphyseo-metaphyseal fractures in children with an implant characterized by its small diameter, easy utilization and its versatility. It avoids the drawbacks of screw fixation particularly in respect to the growth plate. Potentially all epiphyseo-metaphyseal fractures in children. None. Crossing of the growth cartilage by small pins (screwed on a special key is slid over the end of the pin and put in contact with bone. It is squeezed until the key breaks off. The pins are then shortened. Since November 1999 these pins have been used for six olecranon fractures. In January 2002 we extended the indication to other fracture sites. Between January 2002 and July 2003 this system has been used 37 times (six olecranon fractures, eleven lateral condylar fractures and 13 medial epicondylar fractures of the elbow, and seven fractures of the ankle). A total of 43 fractures were treated (20 girls, 23 boys, average age 9.8 +/- 3.6 years) Average duration of follow-up 16.8 +/- 4.7 months. The assessment of results was based on technical, radiographic, and functional aspects. The overall results were good, in particular in respect to the stability of implants and the functional results. No secondary displacement, nor nonunion were observed; the pins were removed in all children at 6 weeks. The ease of handling the implants and the good clinical and radiologic results led us to propose these pins for routine use in epiphyseal and epiphyseo-metaphyseal fractures in children. Some improvements, however, are indicated principally, in particular in respect to the control of compression achieved by the adjustable lock.

  17. Determination of pKa values of alendronate sodium in aqueous solution by piecewise linear regression based on acid-base potentiometric titration.

    Science.gov (United States)

    Ke, Jing; Dou, Hanfei; Zhang, Ximin; Uhagaze, Dushimabararezi Serge; Ding, Xiali; Dong, Yuming

    2016-12-01

    As a mono-sodium salt form of alendronic acid, alendronate sodium presents multi-level ionization for the dissociation of its four hydroxyl groups. The dissociation constants of alendronate sodium were determined in this work by studying the piecewise linear relationship between volume of titrant and pH value based on acid-base potentiometric titration reaction. The distribution curves of alendronate sodium were drawn according to the determined pKa values. There were 4 dissociation constants (pKa 1 =2.43, pKa 2 =7.55, pKa 3 =10.80, pKa 4 =11.99, respectively) of alendronate sodium, and 12 existing forms, of which 4 could be ignored, existing in different pH environments.

  18. Critics to Metaphysics by Modern Philosophers: A Discourse on Human Beings in Reality

    Directory of Open Access Journals (Sweden)

    Frederikus Fios

    2016-01-01

    Full Text Available We have entered the 21st century that is popularly known as the era of the development of modern science and technology. Philosophy provides naming for contemporary era as postmodern era. But do we suddenly come to this day and age? No! Because humans are homo viator, persona that does pilgrimage in history, space and time. Philosophy has expanded periodically in the long course of history. Since the days of classical antiquity, philosophy comes with a patterned metaphysical paradigm. This paradigm survives very long in the stage history of philosophy as maintained by many philosophers who hold fast to the philosophical-epistemic claim that philosophy should be (das sollen metaphysical. Classical Greek philosopher, Aristotle was a philosopher who claims metaphysics as the initial philosophy. Then, Immanuel Kant, Hegel, Heidegger, Marx even Habermas offer appropriate shades of metaphysical philosophy versus spirit of the age. Modern philosophers offer a new paradigm in the way of doing philosophy. The new spirit of modern philosophers declared as if giving criticism on traditional western metaphysics (since Aristotle that are considered irrelevant. This paper intends to show the argument between traditional metaphysical and modern philosophers who criticize metaphysics. The author will make a philosophical synthesis to obtain enlightenment to the position of human beings in the space of time. Using the method of Hegelian dialectic (thesis-antiteses-synthesis, this topic will be developed and assessed in accordance with the interests of this paper. 

  19. MR evaluation of 'Metaphyseal' change in Legg-Calve-Perthes disease

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Haeng Jin; Na, Jae Boem; Shin, Chang Min; You, Jin Jong; Chung, Sung Hoon [Gyeongsang National Univ. College of Medicine, Chinju (Korea, Republic of)

    2001-06-01

    To determine the metaphyseal changes occurring in Legg-Calve-Perthes(LCP) disease using MRI. Between 1992 to 1999, 80 LCP patients (87 hips) underwent MR imaging and plain radiography. All MR images were reviewed, bone marrow signal intensity, the size and locatiion of the metaphyseal cyst and its epiphyseal necrosis grade determined. Metaphyses were abnormal in 43hips (49%), while bone marrow edema was present in 28 (32%) and a metaphyseal cyst in 30 (34%). Metaphyseal cysts were classified as either 'true' (n=9) or 'false' (n=21) according to the enhancement pattern. The maximum diameters of true and false cysts were 1.1{+-}0.3 cm and 1.1{+-}0.4 cm, respectively. Their most commom location was the anterior column; a true cyst occurred there in 7cases (78%), and false cyst in 16 (76%). Using the Waldenstrom classification, seven of the nine hips wih a true cyst (78%), were found to be at the avascular stage and 15 of the 21 with a false cyst (71%) were at the fragmentation stage. Seven of these nine (78%) and 19 of these 21 (90%) were Catterall grade IV. According to the findings of MR imaging, the metaphyseal changes occurring in LCP disease were bone marrow edema and metaphyseal cyst. This latter was visualized mainly in the anterior column and severely affected hip, and was classified as 'true' or 'false'.

  20. Particles, particle labels, and quanta: The toll of unacknowledged metaphysics

    Energy Technology Data Exchange (ETDEWEB)

    Redhead, M. (Cambridge Univ. (United Kingdom)); Teller, P. (Univ. of California, Davis (United States))

    1991-01-01

    The practice of describing multiparticle quantum systems in terms of labeled particles indicates that the authors think of quantum entities as individuatable. The labels, together with particle indistinguishability, create the need for symmetrization or antisymmetrization (or, in principle, higher-order symmetries), which in turn results in surplus formal structure' in the formalism, formal structure which corresponds to nothing in the real world. The authors argue that these facts show quanta to be unindividuatable entities, things in principle incapable of supporting labels, and so things which support no factual difference if two of them are thought of as being switched. When thinking of the metaphysics of quanta, one should eschew the misleading labels of the tensor product Hilbert space formalism and prefer the ontologically more faithful description of the Fock space formalism. This conception eliminates puzzles about the quantum statistics of bosons.

  1. Pragmatism, metaphysics, and bioethics: beyond a theory of moral deliberation.

    Science.gov (United States)

    Pamental, Matthew

    2013-12-01

    Pragmatism has been understood by bioethicists as yet another rival in the "methods wars," as yet another theory of moral deliberation. This has led to criticism of pragmatic bioethics as both theoretically and practically inadequate. Pragmatists' responses to these objections have focused mainly on misunderstandings of pragmatism's epistemology. These responses are insufficient. Pragmatism's commitment to radical empiricism gives it theoretical resources unappreciated by critics and defenders alike. Radical empiricism, unlike its more traditional ancestors, undercuts the gaps between theory and practice, and subjective and objective accounts of experience, and in so doing provides the metaphysical and epistemological basis for a thoroughgoing empirical naturalism in ethics. Pragmatism's strength as an approach to moral problems thus emerges as a result of a much wider array of resources than contemporary interpreters have acknowledged, which makes it a richer, deeper framework for understanding moral deliberation in general and bioethical decision making in particular.

  2. Spreading disease: a controversy concerning the metaphysics of disease.

    Science.gov (United States)

    D'Amico, R

    1998-01-01

    This article concerns the metaphysics of disease. Is disease a fixed feature of the world or a social value or preference? I argue that disease is not a value-laden concept and thus debates concerning it differ fundamentally from debates concerning health, harm, or suffering where evaluative judgements are central. I show how the so-called social constructionist view of disease has been motivated both by ethical concerns with medical practices and general theoretical doubts about scientific naturalism. If I can show that ethical concerns about medical treatment can be answered without adopting social constructionism, that leaves only the broader theoretical question of naturalism. I cannot completely answer those theoretical doubts, but I show that the theoretical motivation is less convincing when it is separated from the moral challenge often accompanying it. I conclude that a convincing defense of the non-naturalistic conception of disease is rarely attempted and proves more difficult and counter-intuitive than its proponents assume.

  3. The effect of alendronate sodium on carotid artery intima-media thickness and lipid profile in women with postmenopausal osteoporosis.

    Science.gov (United States)

    Celiloglu, Murat; Aydin, Yunus; Balci, Pinar; Kolamaz, Turkan

    2009-01-01

    Observational and experimental studies support that osteoporosis and atherosclerosis are two related phenomena. The aim of the present study was to investigate the probable effect of alendronate sodium, which is used in the treatment of osteoporosis, on carotid artery intima-media thickness (IMT), the lipid profile, and apolipoprotein A-I (ApoA-I) and apolipoprotein B (ApoB) levels, which are known to have a role in the atherosclerotic process. Carotid artery IMT was measured in 39 women in whom alendronate 70 mg/week was started due to osteoporosis and in 33 control participants at the start and the 6th and 12th months of the study. Triglyceride, high-density lipoprotein, low-density lipoprotein, ApoA-I, and ApoB levels were also measured at the same time points, and ApoB/ApoA-I rates were calculated. Among the basal values, only the ApoA-I level was significantly lower in the alendronate group (P 0.05) and 96.2 [4.2], 101.5 [4.5] (P > 0.05) in the control group and 145.1 [4.0], 173.7 [4.3] (P 0.05) in the control group and 0.703 [0.04] is to 0.498 [0.0] (P < 0.05) in the alendronate group. We concluded that alendronate sodium resulted in a significant decrease in IMT during a 1-year period compared with matched controls. Also, alendronate was associated with a positive effect on the ApoB/ApoA-I ratio.

  4. Effects of long-term alendronate treatment on bone mineralisation, resorption parameters and biomechanics of single human vertebral trabeculae

    Directory of Open Access Journals (Sweden)

    M Krause

    2014-09-01

    Full Text Available Due to their well-established fracture risk reduction, bisphosphonates are the most frequently used therapeutic agent to treat osteoporosis. Bisphosphonates reduce fracture risk by suppressing bone resorption, but the lower bone turnover could have a negative impact on bone quality at the tissue level. Here, we directly assess the structural and mechanical characteristics of cancellous bone from the lumbar vertebrae (L5 in non-treated osteoporotic controls (n = 21, mid-term alendronate-treated osteoporotic patients (n = 6, and long-term alendronate-treated osteoporotic patients (n = 7. The strength and toughness of single trabeculae were evaluated, while the structure was characterised through measurements of microdamage accumulation, mineralisation distribution, and histological indices. The alendronate-treated cases had a reduced eroded surface (ES/BS, p < 0.001 and a higher bone mineralisation in comparison to non-treated controls (p = 0.037, which is indicative of low turnover associated with treatment. However, the amount of microdamage and the mechanical properties were similar among the control and treatment groups. As the tissue mineral density (TMD increased significantly with alendronate treatment compared to non-treated osteoporotic controls, the reduction in resorption cavities could counterbalance the higher TMD allowing the alendronate-treated bone to maintain its mechanical properties and resist microdamage accumulation. A multivariate analysis of the possible predictors supports the theory that multiple factors (e.g., body mass index, TMD, and ES/BS can impact the mechanical properties. Our results suggest that long-term alendronate treatment shows no adverse impact on mechanical cancellous bone characteristics.

  5. Effects of antifracture drugs in postmenopausal, male and glucocorticoid-induced osteoporosis--usefulness of alendronate and risedronate.

    Science.gov (United States)

    Iwamoto, Jun; Takeda, Tsuyoshi; Sato, Yoshihiro

    2007-11-01

    The purpose of this paper is to discuss the effects of antifracture drugs on postmenopausal, male and glucocorticoid-induced osteoporosis, focussing on the efficacy and safety of alendronate and risedronate. A search of the literature was conducted using PubMed for strictly conducted systematic reviews published from 1995 to present with homogeneity, meta-analyses with homogeneity, and randomized controlled trials (RCTs) with a narrow confidence interval. According to the results of the systematic reviews and meta-analyses, alendronate and risedronate are useful for the prevention of vertebral and non-vertebral fractures in postmenopausal women with osteoporosis. The results of RCTs have shown the antifracture efficacy of raloxifene and ibandronate against vertebral fractures and that of strontium and parathyroid hormone against vertebral and non-vertebral fractures in postmenopausal women with osteoporosis. In addition, the long-term safety of alendronate, risedronate and raloxifene has been established. On the other hand, RCTs have shown that, only alendronate prevents vertebral fractures in men with osteoporosis, and that alendronate and risedronate can prevent vertebral fractures in patients receiving glucocorticoid treatment. There seems to be less evidence of the antifracture efficacy of the drugs in male and glucocorticoid-induced osteoporosis. They have limitations related to long-term compliance, gastrointestinal intolerance and poor and variable absorption form gastrointestinal tract. Thus, intermittent intravenous administration of bisphosphonates such as ibandronate and zoledronate or subcutaneous administration of denosumab might address some of these problems, although the antifracture efficacy of these drugs needs be established. However, antifracture efficacy and long-term safety are important points in the choice of drugs for the treatment of osteoporosis. Thus, the evidence derived from the literature, based on strict evidence-based medicine

  6. Surgically treated osteonecrosis and osteomyelitis of the jaw and oral cavity in patients highly adherent to alendronate treatment

    DEFF Research Database (Denmark)

    Eiken, P A; Prieto-Alhambra, D; Eastell, R

    2017-01-01

    . INTRODUCTION: ONJ is a rare event in users of oral bisphosphonates. Our aims were to evaluate if the risk of surgically treated ONJ increases with longer or more compliant treatment with alendronate for osteoporosis and to identify risk factors for surgically treated ONJ. METHODS: Open nationwide register......-based cohort study containing one nested case-control study. Patients were treatment-naïve incident users of alendronate 1996-2007 in Denmark, both genders, aged 50-94 at the time of beginning treatment (N = 61,990). Participants were followed to 31 December 2013. RESULTS: Over a mean of 6.8 years, 107...

  7. Comparing tolerability and efficacy of generic versus brand alendronate: a randomized clinical study in postmenopausal women with a recent fracture.

    Directory of Open Access Journals (Sweden)

    Joop P W van den Bergh

    Full Text Available INTRODUCTION: An increasing number of generic alendronate formulations have become available. Although expected to have the same tolerability and efficacy, head-to head comparison of generic and brand alendronate was never performed. Therefore, we compared the tolerability and efficacy of generic and brand alendronate. METHODS: In a randomized double-blinded single centre cross-over study in 37 postmenopausal women (mean age 65.4±6.4 years with osteoporosis were treated with generic and branded alendronate during 24 (2x12 weeks. Tolerance was evaluated by the Gastro intestinal Symptom Rating Scale (GSRS and self-reported side effects. Efficacy was assessed by serum bone turnover markers, carboxy terminal telopeptide (CTX and procollagen type I N-terminal propeptide (PINP. No wash out period was allowed (ethical reasons. Because of possible carry over effect only data of the first 12 weeks were analyzed using linear mixed models. RESULTS: There were no significant differences in overall tolerance (GSRS between treatment groups. However, for subscale abdominal pain, patients using generic had a significantly higher mean GSRS score at week 4 (estimated mean difference (B: 0.40; 95%CI: 0.05 to 0.74, p = 0.024. The level of bone turnover markers significantly decreased over 12 weeks of follow-up for generic and branded alendronate (p < 0.001. Mean level of CTX was significantly lower with branded at week 4 (B: 121.3; 95%CI: 52.0 to 190.5, but not at week 12 (B: 53.6; 95%CI:-3.7 to 110.9. No significant differences were found for PINP at week 4 or 12. CONCLUSIONS: Bone turnover markers were significantly reduced with branded and generic alendronate. With branded, CTX was significantly lower at 4 weeks. Generic caused significantly higher abdominal pain scores in the first 4 weeks of treatment. Therefore, generic alendronate may not have the same tolerability and efficacy as branded alendronate in the first weeks after starting treatment in patients

  8. Comparing Tolerability and Efficacy of Generic versus Brand Alendronate: A Randomized Clinical Study in Postmenopausal Women with a Recent Fracture

    Science.gov (United States)

    van den Bergh, Joop P. W.; Bouts, Marian E.; van der Veer, Eveline; van der Velde, Robert Y.; Janssen, Marcel J. W.; Geusens, Piet P.; Winkens, Bjorn; Oldenhof, Nico J. J.; van Geel, Tineke A. C. M.

    2013-01-01

    Introduction An increasing number of generic alendronate formulations have become available. Although expected to have the same tolerability and efficacy, head-to head comparison of generic and brand alendronate was never performed. Therefore, we compared the tolerability and efficacy of generic and brand alendronate. Methods In a randomized double-blinded single centre cross-over study in 37 postmenopausal women (mean age 65.4±6.4 years) with osteoporosis were treated with generic and branded alendronate during 24 (2x12) weeks. Tolerance was evaluated by the Gastro intestinal Symptom Rating Scale (GSRS) and self-reported side effects. Efficacy was assessed by serum bone turnover markers, carboxy terminal telopeptide (CTX) and procollagen type I N-terminal propeptide (PINP). No wash out period was allowed (ethical reasons). Because of possible carry over effect only data of the first 12 weeks were analyzed using linear mixed models. Results There were no significant differences in overall tolerance (GSRS) between treatment groups. However, for subscale abdominal pain, patients using generic had a significantly higher mean GSRS score at week 4 (estimated mean difference (B): 0.40; 95%CI: 0.05 to 0.74, p = 0.024). The level of bone turnover markers significantly decreased over 12 weeks of follow-up for generic and branded alendronate (p B: 121.3; 95%CI: 52.0 to 190.5), but not at week 12 (B: 53.6; 95%CI:-3.7 to 110.9). No significant differences were found for PINP at week 4 or 12. Conclusions Bone turnover markers were significantly reduced with branded and generic alendronate. With branded, CTX was significantly lower at 4 weeks. Generic caused significantly higher abdominal pain scores in the first 4 weeks of treatment. Therefore, generic alendronate may not have the same tolerability and efficacy as branded alendronate in the first weeks after starting treatment in patients with a recent fracture. Trial Registration Dutch Trial Register NTR number 1867 http

  9. Inhalation of alendronate nanoparticles as dry powder inhaler for the treatment of osteoporosis.

    Science.gov (United States)

    Sultana, Shaheen; Talegaonkar, Sushma; Ali, Rashid; Mittal, Gaurav; Ahmad, Farhan Jalees; Bhatnagar, Aseem

    2012-01-01

    The precipitation technique was used to prepare non-polymeric alendronate nanoparticles. The influence of various formulation parameters on the average particle size was investigated and the effect of various stabilizers (PVA, tween, chitosan, alginate, PEG, HPMC, poloxomers) was evaluated. The selection of surfactant was a key factor to produce particles with desired properties. Poloxomer F68 was found best in achieving the minimum particle size and providing physical stability to the drug. On basis of preliminary trials, a central composite design was employed to study the effect of independent variables, drug concentration (X₁), antisolvent volume (X₂), stirring speed (X₃), and stabilizer concentration (X₄) on the average particle size. The drug and stabilizer concentrations exhibited a more significant effect on a dependent variable. The particle size varied from 62 to 803.3 nm depending upon the significant terms. The validation of optimization study, performed using six confirmatory runs, indicated very high degree of prognostic ability of response surface methodology, with mean percentage error (±SD) as -2.32 ± 2.47. The minimum particle size (44.11 nm) was predicted at 10 mg/ml drug concentration, 20 ml antisolvent volume, 925 rpm stirring speed, and 8.5% stabilizer concentration with 98.16% experimental validity. Respirable fraction for optimized nanosized alendronate (43.85% ± 0.52%) was significantly higher when compared with commercial alendronate (17.6 ± 0.32). Mass median aerodynamic diameter of designed particles was 3.45 µm with geometric standard deviation of 2.10.

  10. Development and characterization of a gastroretentive dosage form composed of chitosan and hydroxyethyl cellulose for alendronate

    Directory of Open Access Journals (Sweden)

    Chen YC

    2013-12-01

    Full Text Available Ying-Chen Chen,1,* Hsiu-O Ho,1,* Chiao-Chi Chiu,1 Ming-Thau Sheu1,2 1School of Pharmacy, College of Pharmacy, Taipei Medical University, 2Clinical Research Center and Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan*These authors contributed equally to this workAbstract: In this study, alendronate, the most commonly used biphosphonate for treating osteoporosis, was formulated as gastroretentive dosage form (GRDF tablets to enhance its oral bioavailability. GRDF tablets were characterized with the effects of different molecular weights (MWs of chitosan (CS and hydroxyethyl cellulose (HEC at various ratios on swelling, floating, and physical integrity. The CS component was formed using various acids: acetic, lactic, malic, succinic, and citric, and a high viscosity grade of HEC was selected. The results demonstrated that the swelling ratios of the formulations comprising high MW CS were lower than those of low or medium MW CS when salts were formed with any countering acids except for acetic acid. The decreasing ranking of the swelling rates was: CS-citrate > CS-malate > CS-lactate > CS-succinate > CS-acetate. A negative correlation was found between the pKa of the respective countering acid and the swelling rate. The swelling rate was promoted if an acidic salt of CS with a lower water content was incorporated, while it became slower when tablet hardness was higher or the compression force to form tablets was increased. Although HEC did not contribute to swelling or floating, it played a role in maintaining structural integrity. A prolonged dissolution profile of alendronate GRDF tablets developed in this study was observed.Keywords: gastroretentive dosage form, chitosan, hydrogel, hydroxyethyl cellulose, swelling, alendronate

  11. Zenker's diverticulitis secondary to alendronate ingestion: a rare cause of recurrent dysphagia.

    Science.gov (United States)

    Sharma, Rajiv; DeCross, Arthur J

    2011-02-01

    Acute dysphagia/odynophagia developed in a 79-year-old female patient secondary to what we believe was a caustic injury to a large Zenker's diverticulum (ZD) in the setting of long-term alendronate use. She reported severe dysphagia and odynophagia of 1-week duration. She had experienced a similar episode 10 months earlier that had resolved after stopping alendronate temporarily. Although she was able to handle secretions, she was unable to swallow solids or liquids. She was noted to be dehydrated. On endoscopy, a large and markedly inflamed ZD was identified. There was no visual esophageal mucosal injury within the esophagus. Alendronate therapy was discontinued, and parenteral nutrition and proton pump inhibitors were initiated. Her symptoms resolved within 1 week, and she was able to resume oral intake. Case report. University Hospital. Case report. Bisphosphonate therapy is commonly used to treat osteoporosis and is therefore an increasingly prevalent component of the medication list of elderly patients. These medications may cause significant caustic injury and are therefore administered with strong caution in the setting of dysphagia or known structural abnormalities of the esophagus. The fear is that tablets may become entrapped within a diverticulum and lead to intense acute inflammatory changes. Health care providers should be aware of potential complications with ulcerogenic medications in patients with ZD. These medications should be administered with caution in the setting of dysphagia or known structural abnormalities of the esophagus. When patients with history of dysphagia are evaluated for their suitability to receive oral bisphosphonate therapy, care should be taken to investigate the etiology of dysphagia. Evaluation should focus not only on the tubular esophagus, but also on excluding a Zenker's pharyngeal diverticulum with appropriate contrast imaging. Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc

  12. Spontaneous Subtrochanteric Femoral Stress Fracture Related to Alendronate : A Case Report

    Directory of Open Access Journals (Sweden)

    Paul CC Chew

    2013-03-01

    Full Text Available Spontaneous atypical fractures of the femur have been reported in patients on long-term antiresorptive bisphosphonate therapy. Here, we report a case of subtrochanteric stress fracture in a seventy-year-old female patient on long-term alendronate therapy, and accompanying management challenges. Potential measures to prevent this complication of antiresorptive treatment for osteoporosis include the following: setting strict criteria for prescribing antiresorptive therapy, limiting the duration of continuous antiresorptive therapy, and increasing the use of bone anabolic agents.

  13. The nature of Suárez's Metaphysics. Disputationes Metaphysicae and Their Main Systematic Strains

    Czech Academy of Sciences Publication Activity Database

    Heider, Daniel

    2009-01-01

    Roč. 6, č. 1 (2009), s. 99-110 ISSN 1214-8407 Institutional research plan: CEZ:AV0Z90090514 Keywords : Suárez * metaphysics * being * unity * concept * Scotus * Aquinas Subject RIV: AA - Philosophy ; Religion

  14. Murk Jansen's metaphyseal chondrodysplasia with long-term follow-up

    Energy Technology Data Exchange (ETDEWEB)

    Silverthorn, K.G.; Houston, C.S.; Duncan, B.P.

    1987-02-01

    The fourteenth reported patient with Murk Jansen's metaphyseal chondrodysplasia is presented, with a remarkable followup from birth to the age of 15 years. Numerous invasive procedures were performed in pursuit of erroneous provisional diagnoses. Five of these patients presented in infancy with radiographic metaphyseal changes similar to rickets, but with preservation of the provisional zone of calcification. Following infancy, these patients reveal the more typical short-limbed dwarfism, with fusiform joints and bowed extremities.

  15. On How physics Could impact on the Metaphysics of Space and Time

    OpenAIRE

    Alireza Mansouri

    2015-01-01

    This paper aims to illustrate the mutual inter-relation of physics and metaphysics in the context of the philosophy of space and time. We especially emphasize, in this paper, that scientific development could impact on our position regarding the reality of space and time. To illustrate this point, we investigate the mutual inter-relation of physics and metaphysics in the modern developments of physics, i.e. neo-Newtonian structure, special and general relativity (GR). This paper ends up antic...

  16. Pharmacologically Inactive Bisphosphonates as an Alternative Strategy for Targeting Osteoclasts: In Vivo Assessment of 5-Fluorodeoxyuridine-Alendronate in a Preclinical Model of Breast Cancer Bone Metastases.

    Science.gov (United States)

    Schem, Christian; Tower, Robert J; Kneissl, Philipp; Rambow, Anna-Christina; Campbell, Graeme M; Desel, Christine; Damm, Timo; Heilmann, Thorsten; Fuchs, Sabine; Zuhayra, Maaz; Trauzold, Anna; Glüer, Claus C; Schott, Sarah; Tiwari, Sanjay

    2017-03-01

    Bisphosphonates have effects that are antiresorptive, antitumor, and antiapoptotic to osteoblasts and osteocytes, but an effective means of eliciting these multiple activities in the treatment of bone metastases has not been identified. Antimetabolite-bisphosphonate conjugates have potential for improved performance as a class of bone-specific antineoplastic drugs. The primary objective of the study was to determine whether an antimetabolite-bisphosphonate conjugate will preserve bone formation concomitant with antiresorptive and antitumor activity. 5-FdU-ale, a highly stable conjugate between the antimetabolite 5-fluoro-2'-deoxyuridine and the bisphosphonate alendronate, was tested for its therapeutic efficacy in a mouse model of MDA-MB231 breast cancer bone metastases. In vitro testing revealed osteoclasts to be highly sensitive to 5-FdU-ale. In contrast, osteoblasts had significantly reduced sensitivity. Tumor cells were resistant in vitro but in vivo tumor burden was nevertheless significantly reduced compared with untreated mice. Sensitivity to 5-FdU-ale was not mediated through inhibition of farnesyl diphosphate synthase activity, but cell cycle arrest was observed. Although serum tartrate-resistant acid phosphatase (TRAP) levels were greatly reduced by both drugs, there was no significant decrease in the serum bone formation marker osteocalcin with 5-FdU-ale treatment. In contrast, there was more than a fivefold decrease in serum osteocalcin levels with alendronate treatment (p bisphosphonates offers flexibility in creating potent bone-targeting drugs with cytostatic, bone protection properties that show limited nephrotoxicity. This unique class of drugs may offer distinct advantages in the setting of targeted adjuvant therapy and chemoprevention of bone diseases. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

  17. [Extensometry and primary anchorage of femur implants. Study of the upper metaphyseal intracortical support of the B.P.R cement-less implant].

    Science.gov (United States)

    Delecrin, J; Passuti, N; Royer, J; Rogez, J M; Bainvel, J V

    1989-01-01

    This study uses extensometry to compare the distribution of strain on a fresh femur before and after implantation of various titanium prostheses: one is a cementless implant with metaphyseal endosteal support; the second is a cemented prosthesis with and without calcar collar contact; the last is a titanium implant with fixation by screens. The precision of the measurements have been improved particularly in the proximal metaphyseal area using bidirectional gauges. The system of loading permits comparison of the different implants and the results obtained with the B.P.R. prosthesis compared with the cemented implant without calcar contact are very close. The effect of the collar appears very limited despite the optimal conditions of the in vivo implantation that improve the calcar-collar contact. The screw implant increases the stress shielding of the proximal area of the femur. The different steps of the experiment illustrate the strain distribution in relation to the implantation of the devices and the contact bone prosthesis. The significant endosteal fixation of the B.P.R. prosthesis in the proximal metaphyseal area allows a better primary anchorage which increases distribution of the stress and therefore results in better secondary fixation by bony ingrowth.

  18. Development and characterization of a gastroretentive dosage form composed of chitosan and hydroxyethyl cellulose for alendronate.

    Science.gov (United States)

    Chen, Ying-Chen; Ho, Hsiu-O; Chiu, Chiao-Chi; Sheu, Ming-Thau

    2014-01-01

    In this study, alendronate, the most commonly used biphosphonate for treating osteoporosis, was formulated as gastroretentive dosage form (GRDF) tablets to enhance its oral bioavailability. GRDF tablets were characterized with the effects of different molecular weights (MWs) of chitosan (CS) and hydroxyethyl cellulose (HEC) at various ratios on swelling, floating, and physical integrity. The CS component was formed using various acids: acetic, lactic, malic, succinic, and citric, and a high viscosity grade of HEC was selected. The results demonstrated that the swelling ratios of the formulations comprising high MW CS were lower than those of low or medium MW CS when salts were formed with any countering acids except for acetic acid. The decreasing ranking of the swelling rates was: CS-citrate > CS-malate > CS-lactate > CS-succinate > CS-acetate. A negative correlation was found between the pKa of the respective countering acid and the swelling rate. The swelling rate was promoted if an acidic salt of CS with a lower water content was incorporated, while it became slower when tablet hardness was higher or the compression force to form tablets was increased. Although HEC did not contribute to swelling or floating, it played a role in maintaining structural integrity. A prolonged dissolution profile of alendronate GRDF tablets developed in this study was observed.

  19. An NMR metabolomic study on the effect of alendronate in ovariectomized mice.

    Directory of Open Access Journals (Sweden)

    Shin-Yu Chen

    Full Text Available Alendronate sodium (Fosamax is most widely used for the prevention and treatment of osteoporosis. It is a type of anti-resorptive agent that reduces the risk of fractures by changing bone turnover and bone mineral density. We investigated the effect of Fosamax on a mouse model of osteoporosis. Twenty-seven female C57BL/6JNarl mice were divided into three groups: sham, ovariectomized (OVX and OVX + Fosamax (Fosamax. After 23 weeks, bone density of femurs was analyzed using microcomputed tomography (micro-CT, and serum was analyzed for osteoblast and osteoclast activity, as well as metabolites using nuclear magnetic resonance (NMR spectroscopy. Fosamax increased bone mineral density and cortical bone thickness, and decreased osteoblast activity slightly. Fosamax did not significantly change osteoclast activity. Serum metabolomics revealed that Fosamax had profound effects on overall metabolism, as significantly higher concentrations of metabolites associated with energy metabolism (including TCA-cycle intermediates and glucose, 3-hydroxybutyrate, taurine, allantoin, acetate, and ethanol, as well as lower concentrations of aspartate were observed in the Fosamax-treated mice compared with the OVX mice. These results suggest that alendronate may work by increasing bone density through altered metabolic activity.

  20. Influence of the local application of sodium alendronate gel on osseointegration of titanium implants.

    Science.gov (United States)

    Guimarães, M B; Bueno, R S; Blaya, M B G; Shinkai, R S A; Marques, L M H

    2015-11-01

    The aim of this study was to perform a comparative analysis of aspects of the osseointegration of titanium implants placed with and without the local application of a bisphosphonate agent, after 28 days in vivo. The study involved the placement of 50 commercially pure titanium implants in the middle third of the tibia of 10 rabbits, with the right tibia used as the control and the left as the test site. Sodium alendronate gel was applied locally in the test group and sterile saline solution in the control group. After euthanasia, 10 implants from each group were analyzed for maximum removal torque. The remainder of the sample was processed to obtain non-decalcified slides, approximately 30μm thick, for histomorphological and histomorphometric analyses, including bone-implant contact (%BIC). Data were analyzed at the 5% level of significance. The removal torque values of the test group were, on average, half those obtained in the control group. The test group showed a lower %BIC and notable changes in bone quality. It is concluded that the initial events in the osseointegration of titanium implants are not favoured by the local application of sodium alendronate gel in rabbits. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  1. Alendronate augments interleukin-1β release from macrophages infected with periodontal pathogenic bacteria through activation of caspase-1

    International Nuclear Information System (INIS)

    Deng Xue; Tamai, Riyoko; Endo, Yasuo; Kiyoura, Yusuke

    2009-01-01

    Nitrogen-containing bisphosphonates (NBPs) are anti-bone-resorptive drugs with inflammatory side effects that include osteomyelitis and osteonecrosis of the jaw. Oral bacteria have been considered to be a trigger for these NBP-associated jaw bone diseases. The present study examined the effects of alendronate (a typical NBP) and clodronate (a non-NBP) on the production of proinflammatory cytokines by macrophages infected with Porphyromonas gingivalis and Tannerella forsythia, which are important pathogens of periodontal diseases. Pretreatment with alendronate augmented IL-1β, but not TNFα, production by macrophages infected with P. gingivalis or T. forsythia. This augmentation of IL-1β production was inhibited by clodronate. Furthermore, caspase-1, a promoter of IL-1β production, was activated by treatment with alendronate, and caspase-1 inhibitor reduced the production of IL-1β induced by alendronate and P. gingivalis. These results suggest that NBPs augment periodontal pathogenic bacteria-induced IL-1β release via caspase-1 activation, and this phenomenon may contribute to the development of NBP-associated inflammatory side effects including jaw osteomyelitis. Co-treatment with clodronate may prevent and/or reduce these inflammatory effects induced by NBPs

  2. Antiresorption implant coatings based on calcium alendronate and octacalcium phosphate deposited by matrix assisted pulsed laser evaporation.

    Science.gov (United States)

    Boanini, Elisa; Torricelli, Paola; Forte, Lucia; Pagani, Stefania; Mihailescu, Natalia; Ristoscu, Carmen; Mihailescu, Ion N; Bigi, Adriana

    2015-12-01

    The integration of an implant material with bone tissue depends on the chemistry and physics of the implant surface. In this study we applied matrix assisted pulsed laser evaporation (MAPLE) in order to synthesize calcium alendronate monohydrate (a bisphosphonate obtained by calcium sequestration from octacalcium phosphate by alendronate) and calcium alendronate monohydrate/octacalcium phosphate composite thin films on titanium substrates. Octacalcium phosphate coatings were prepared as reference material. The powders, which were synthesized in aqueous medium, were suspended in deionised water, frozen at liquid nitrogen temperature and used as targets for MAPLE experiments. The transfer was conducted with a KrF* excimer laser source (λ = 248 nm, τFWHM ≤ 25 ns) in mild conditions of temperature and pressure. XRD, FTIR and SEM analyses confirmed that the coatings contain the same crystalline phases as the as-prepared powder samples. Osteoblast derived from stem cells and osteoclast derived from monocytes of osteoporotic subjects were co-cultured on the coatings up to 14 days. Osteoclast displayed significantly reduced proliferation and differentiation in the presence of calcium alendronate monohydrate, pointing to a clear role of the coatings containing this bisphosphonate on inhibiting excessive bone resorption. At variance, osteoblast production of alkaline phosphatase and type I pro-collagen were promoted by the presence of bisphosphonate, which also decreased the production of interleukin 6. The positive influence towards osteoblast differentiation was even more enhanced in the composite coatings, thanks to the presence of octacalcium phosphate. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Alendronate has a residual effect on bone mass in postmenopausal Danish women up to 7 years after treatment withdrawal

    DEFF Research Database (Denmark)

    Bagger, Yu Z; Tankó, László B; Alexandersen, Peter

    2003-01-01

    for 7, 5, or 3 yr, respectively. Bone mineral density of the lumbar spine, hip, and forearm was measured by dual-energy x-ray absorptiometry. Biochemical markers of bone turnover were induced serum C-terminal telopeptides of type I collagen (CTX) and osteocalcin. Women who received alendronate (2...

  4. Efficacy of teriparatide in the treatment of nontraumatic osteonecrosis of the femoral head: a retrospective comparative study with alendronate.

    Science.gov (United States)

    Arai, Ryuta; Takahashi, Daisuke; Inoue, Masahiro; Irie, Tohru; Asano, Tsuyoshi; Konno, Takuya; Terkawi, Mohamad Alaa; Onodera, Tomohiro; Kondo, Eiji; Iwasaki, Norimasa

    2017-01-19

    Collapse of the femoral head associated with nontraumatic osteonecrosis (NOFH) is one of the most common causes of disability in young adult patients. Excessive bone resorption by osteoclast coincident with the suppression of osteogenesis are believed to be responsible for collapse progression. Alendronate that inhibits bone resorption by inducing osteoclast apoptosis has been traditionally used for treating NOFH; however, several reports documented serious complications by the use of this drug. On the other hand, teriparatide activates osteoblasts leading to an overall increase in bone volume, and is expected to reduce the progression of femoral head collapse in NOFH. Therefore, the present study was undertaken to examine pharmacological effects of teriparatide on collapse progression of NOFH and to compare these effects with alendronate. We conducted a retrospective study in our facility for comparing the pharmacological effects of teriparatide and alendronate on 32 NOFH patients diagnosed with osteoporosis. Between 2007 and 2013, patients were treated with daily administration of 20 μg teriparatide (15 patients: 18 hips), or with 35 mg of alendronate once a week (17 patients: 22 hips). The mean period of follow-up was 18.7 months. The progression of collapse was evaluated prior to the administration and later every three months by anteroposterior radiographs. Collapse progression with > 1 mm was defined as advanced collapse, while with femoral head. The registration number in UMIN Clinical Trial Registry is UMIN000017582 . The date of registration is May 5, 2015.

  5. Overcoming O: Dewey and the Problem of Bion's Metaphysics.

    Science.gov (United States)

    Soffer-Dudek, Nir

    2015-10-01

    Bion guides us to eschew memory, desire, and understanding in order to become one with O-the ultimate reality of the analytic moment. However, his directions are valid only to the extent that such a meta-reality actually exists. Otherwise there is nothing to unite with and no reason to shun memory or desire. The present work inquires whether we may provide Bion's technique with a less speculative philosophy, specifically Dewey's pragmatist theory of aesthetics. It begins with reviewing the similarities between the two writers' methods, highlighting their shared emphasis on openness to the unknown. Yet listening to their intonations reveals that they actually convey opposite ideas as to what this "unknown" may be. Whereas Dewey sanguinely portrays the possibilities of the "yet-unknown," Bion emphasizes the dread of our inescapable encounter with the unknowable. This dread is embodied in his concept of O. Thus, rather than being merely a metaphysical speculation, O communicates Bion's conviction that fear forms the core of our existence. Banishing O from the counseling room may indeed aid his method in becoming accessible to a wider audience; at the same time, however, doing so might also deprive it of the very context that gives it meaning. © 2015 by the American Psychoanalytic Association.

  6. Fundamental awareness: A framework for integrating science, philosophy and metaphysics.

    Science.gov (United States)

    Theise, Neil D; Kafatos, Menas C

    2016-01-01

    The ontologic framework of Fundamental Awareness proposed here assumes that non-dual Awareness is foundational to the universe, not arising from the interactions or structures of higher level phenomena. The framework allows comparison and integration of views from the three investigative domains concerned with understanding the nature of consciousness: science, philosophy, and metaphysics. In this framework, Awareness is the underlying reality, not reducible to anything else. Awareness and existence are the same. As such, the universe is non-material, self-organizing throughout, a holarchy of complementary, process driven, recursive interactions. The universe is both its own first observer and subject. Considering the world to be non-material and comprised, a priori, of Awareness is to privilege information over materiality, action over agency and to understand that qualia are not a "hard problem," but the foundational elements of all existence. These views fully reflect main stream Western philosophical traditions, insights from culturally diverse contemplative and mystical traditions, and are in keeping with current scientific thinking, expressible mathematically.

  7. Method and metaphysics in Clements's and Gleason's ecological explanations.

    Science.gov (United States)

    Eliot, Christopher

    2007-03-01

    To generate explanatory theory, ecologists must wrestle with how to represent the extremely many, diverse causes behind phenomena in their domain. Early twentieth-century plant ecologists Frederic E. Clements and Henry A. Gleason provide a textbook example of different approaches to explaining vegetation, with Clements allegedly committed, despite abundant exceptions, to a law of vegetation, and Gleason denying the law in favor of less organized phenomena. However, examining Clements's approach to explanation reveals him not to be expressing a law, and instead to be developing an explanatory structure without laws, capable of progressively integrating causal complexity. Moreover, Clements and Gleason largely agree on the causes of vegetation; but, since causal understanding here underdetermines representation, they differ on how to integrate recognized causes into general theory--that is, in their methodologies. Observers of the case may have mistakenly assumed that scientific representation across the disciplines typically aims at laws like Newton's, and that representations always reveal scientists' metaphysical commitments. Ironically, in the present case, this assumption seems to have been made even by observers who regard Clements as nai ve for his alleged commitment to an ecological law.

  8. Four queries concerning the metaphysics of early human embryogenesis.

    Science.gov (United States)

    Howsepian, A A

    2008-04-01

    In this essay, I attempt to provide answers to the following four queries concerning the metaphysics of early human embryogenesis. (1) Following its first cellular fission, is it coherent to claim that one and only one of two "blastomeric" twins of a human zygote is identical with that zygote? (2) Following the fusion of two human pre-embryos, is it coherent to claim that one and only one pre-fusion pre-embryo is identical with that postfusion pre-embryo? (3) Does a live human being come into existence only when its brain comes into existence? (4) At implantation, does a pre-embryo become a mere part of its mother? I argue that either if things have quidditative properties or if criterialism is false, then queries (1) and (2) can be answered in the affirmative; that in light of recent developments in theories of human death and in light of a more "functional" theory of brains, query (3) can be answered in the negative; and that plausible mereological principles require a negative answer to query (4).

  9. Philosophical Creationism: Thomas Aquinas’ Metaphysics of Creatio ex Nihilo

    Directory of Open Access Journals (Sweden)

    Andrzej Maryniarczyk

    2016-03-01

    Full Text Available All philosophers, beginning with the pre-Socratics, through Plato and Aristotle, and up to Thomas Aquinas, accepted as a certain that the world as a whole existed eternally. The foundation for the eternity of the world was the indestructible and eternal primal building material of the world, a material that existed in the form of primordial material elements (the Ionians, in the form of ideas (Plato, or in the form of matter, eternal motion, and the first heavens (Aristotle. The article outlines the main structure of the philosophical theory of creation ex nihilo developed by St. Thomas Aquinas and indebted to his metaphysical thought. It shows the wisdom-based and ratiocinative foundation of the rational cognition of reality—reality that comes from the personal creative act of God. It concludes that the perception that the beings called to existence by the personal act of God the Creator are intelligible is the ultimate rational justification for the fact that our human cognition, love, and spiritual creativity are rational.

  10. Beyond positivism: a metaphysical basis for clinical practice?

    Science.gov (United States)

    Herman, J

    1992-09-01

    Medicine does not have its own unified body of scientific knowledge. Instead, physicians who are oriented to research make sporadic incursions into the basic sciences such as genetics, biochemistry, immunology, epidemiology, physiology, pharmacology and so on. These latter, taken together, comprise biomedicine which is said to have adopted the positivist epistemology or the Cartesian/Newtonian one that regards the scientist as an uninvolved observer of nature. In effect, medical science has come to rest on a theory of knowledge which links meaning to probability and considers prediction as the scientist's chief task. Like its predecessor, the probability theory of meaning rejects metaphysical speculation and remains connected to observations made, directly or indirectly, by means of the five senses. Despite some brilliant successes touching on relatively uncommon disorders, biomedicine cannot explain most day-to-day clinical activity. An understanding of what transpires between patient and doctor, of its diagnostic potential and therapeutic weight requires hermeneutic, or phenomenological, inquiry which brings about changes in both parties to it. Such a science, as ontological speculation has been called, cannot be deciphered by an epistemology couched in the imagery of physics and chemistry.

  11. Effect of methylprednisolone pulse therapy with and without alendronate on biochemical markers of bone turnover in patients with Graves' ophthalmopathy.

    Science.gov (United States)

    Gasińska, Teresa; Borowska, Anna; Wichary, Hanna; Dec, Renata

    2012-01-01

     Immunosuppression with glucocorticoids is the method of choice in the treatment of active Graves' ophthalmopathy (GO). However, glucocorticoid therapy may have side effects, among others, it affects bone metabolism.  The aim of the study was to compare the effect of methylprednisolone pulse therapy (MPPT) with and without alendronate on bone turnover markers in patients with GO with normal and reduced bone mineral density (BMD).  The study included 53 patients with GO and 20 sex- and age‑matched healthy controls. Twenty patients with normal BMD (17 women, 3 men, aged 45 ±1.0 years) received only MPPT (8 g intravenously during 4 weeks). The remaining patients, with reduced BMD, were randomly assigned either to MPPT without alendronate (10 women, 2 men, aged 47 ±1.0 years) or MPPT with alendronate (18 women, 3 men, aged 47 ±1.0 years). BMD of the lumbar spine and femoral neck was assessed using dual energy X‑ray absorptiometry  (DEXA) before treatment. The markers of bone formation (serum osteocalcin, carboxyterminal propeptide of type I collagen [PICP], alkaline phospatase) and the markers of bone resorption (serum carboxyterminal telopeptide of type I collagen [ICTP], cross‑linked C‑terminal telopeptide of type I collagen [CTX], serum calcium [Ca] and potassium [P], as well as urinary excretion of deoxypyridinoline, Ca, and P) were determined before and after treatment.  MPPT caused a decrease in bone formation markers and an increase in some bone resorption markers. MPPT with alendronate decreased bone formation and bone resorption markers.  A negative effect of MPPT on bone turnover is observed both in patients with GO with normal and with reduced BMD. Simultaneous use of MPPT and alendronate in patients with GO and reduced BMD suppresses bone resorption caused by methylprednisolone.

  12. Pharmacokinetics of coadministration of levothyroxine sodium and alendronate sodium new effervescent formulation.

    Science.gov (United States)

    Bone, H G; Walter, M A; Hurley, M E; Epstein, S

    2017-05-01

    No clinically important pharmacokinetic interference of alendronate occurred between a new effervescent formulation of alendronate and levothyroxine when coadministered. The combination does not materially affect levothyroxine absorption. Concurrent treatment of osteoporosis with alendronate (Aln) and hypothyroidism with levothyroxine (LT4) may be problematic because both drugs are to be taken separately after fasting overnight. The primary objective was to assess pharmacokinetic interactions between a new effervescent formulation of Aln (Aln-NEF) and LT4. A randomized, open-label, 3-way crossover study was conducted in 30 healthy adults (15 women). Subjects were dosed 3 times, separated by 35 days, after overnight fasts, with Aln-NEF alone (70 mg), LT4 alone (600 μg), or Aln-NEF and LT4 concurrently. Samples were analyzed for plasma Aln and serum LT4. Pharmacokinetic drug-drug interaction was assessed using 90% confidence intervals (CIs) for the test/reference ratio of the geometric means for area under the concentration-time curve from time zero to last measureable time point (AUC 0-t ) and maximum concentration (C max ). Results were compared to the default no-effect boundaries of 80 to 125% for the ratio Aln-NEF and LT4 concurrently/Aln-NEF alone and the ratio Aln-NEF and LT4 concurrently/LT4 alone. Geometric mean ratios (Aln-NEF with LT4/Aln-NEF alone) were 0.927 (90% CI 0.795-1.081) for AUC 0-8 and 0.912 (90% CI 0.773-1.077) for C max , demonstrating LT4 does not appreciably affect the pharmacokinetics of Aln. Geometric mean ratios (LT4 with Aln-NEF/LT4 alone) were 1.049 (90% CI 0.983-1.119) for AUC 0-48 and 1.075 (90% CI 1.006-1.148) for C max , demonstrating LT4 is bioequivalent between the 2 treatments. Coadministration of Aln-NEF and LT4 was well tolerated. There was no clinically important pharmacokinetic interference between the Aln-NEF formulation and LT4. Aln-NEF does not materially affect LT4 absorption.

  13. Management of metaphyseal bone loss in revision knee arthroplasty.

    Science.gov (United States)

    Mancuso, Francesco; Beltrame, Arianna; Colombo, Elia; Miani, Enrick; Bassini, Fabrizio

    2017-06-07

    Revision total knee arthroplasty (TKA) is usually made more complex by the presence of bone defects, which may be caused by periprosthethic infection, polyethylene wear, implant loosening or fractures. The main aim of the present work is to review the available literature to understand the current options to manage with the bone loss during knee revisions. Available English literature for bone defects in revision TKAs has been evaluated looking at treatment options and their results in terms of clinical and radiological outcomes and failure rates. Anderson Orthopaedic Research Institute (AORI) classification is the most frequently used because it helps in the choice of the most suitable treatment. Several options are available in the management of metaphyseal bone loss in revision knee arthroplasty. For small and contained defects (AORI type 1) cement with or without screws and auto- or allograft morcellized bone are available. In uncontained but mild defects (AORI type 2A) metal augments should be use while large and uncontained defects (AORI type 2B and 3) are best addressed with structural allograft or metal filling devices (cones and sleeves). Stemmed components, either cemented or cementless, are recommended to reduce the strain at the interface implant-host. The treatment of bone defects in revision TKAs has evolved during the last years providing different options with good results at a short/medium term follow up. With the increasing revision burden, further scientific evidence is requested to identify the best approach for each patient. Long-term clinical outcome as well as implant survival after revision TKA are still sub-optimal and depend upon many factors including cause for revision, surgical approach, type of implants used and various patient factors.

  14. Alendronate-Eluting Biphasic Calcium Phosphate (BCP) Scaffolds Stimulate Osteogenic Differentiation

    Science.gov (United States)

    Kim, Sung Eun; Lee, Deok-Won; Kang, Eun Young; Jeong, Won Jae; Lee, Boram; Jeong, Myeong Seon; Kim, Hak Jun; Park, Kyeongsoon; Song, Hae-Ryong

    2015-01-01

    Biphasic calcium phosphate (BCP) scaffolds have been widely used in orthopedic and dental fields as osteoconductive bone substitutes. However, BCP scaffolds are not satisfactory for the stimulation of osteogenic differentiation and maturation. To enhance osteogenic differentiation, we prepared alendronate- (ALN-) eluting BCP scaffolds. The coating of ALN on BCP scaffolds was confirmed by scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). An in vitro release study showed that release of ALN from ALN-eluting BCP scaffolds was sustained for up to 28 days. In vitro results revealed that MG-63 cells grown on ALN-eluting BCP scaffolds exhibited increased ALP activity and calcium deposition and upregulated gene expression of Runx2, ALP, OCN, and OPN compared with the BCP scaffold alone. Therefore, this study suggests that ALN-eluting BCP scaffolds have the potential to effectively stimulate osteogenic differentiation. PMID:26221587

  15. Alendronate-Eluting Biphasic Calcium Phosphate (BCP Scaffolds Stimulate Osteogenic Differentiation

    Directory of Open Access Journals (Sweden)

    Sung Eun Kim

    2015-01-01

    Full Text Available Biphasic calcium phosphate (BCP scaffolds have been widely used in orthopedic and dental fields as osteoconductive bone substitutes. However, BCP scaffolds are not satisfactory for the stimulation of osteogenic differentiation and maturation. To enhance osteogenic differentiation, we prepared alendronate- (ALN- eluting BCP scaffolds. The coating of ALN on BCP scaffolds was confirmed by scanning electron microscopy (FE-SEM, energy-dispersive X-ray spectroscopy (EDS, and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR. An in vitro release study showed that release of ALN from ALN-eluting BCP scaffolds was sustained for up to 28 days. In vitro results revealed that MG-63 cells grown on ALN-eluting BCP scaffolds exhibited increased ALP activity and calcium deposition and upregulated gene expression of Runx2, ALP, OCN, and OPN compared with the BCP scaffold alone. Therefore, this study suggests that ALN-eluting BCP scaffolds have the potential to effectively stimulate osteogenic differentiation.

  16. Alendronate sodium hydrate (oral jelly for the treatment of osteoporosis: review of a novel, easy to swallow formulation

    Directory of Open Access Journals (Sweden)

    Imai K

    2013-06-01

    Full Text Available Kazuhiro Imai Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan Abstract: Osteoporosis is a skeletal disorder characterized by loss of bone mass, decreased bone strength, and an increased risk of bone fracture. The disease progresses with age, especially in postmenopausal women. Japan is one of the most rapidly aging societies worldwide. Japanese individuals over 65 years of age constituted 23.0% of the population in 2010 and 25.1% to 25.2% as of 2013. The estimated number of people with osteoporosis in Japan is currently 13 million. Bisphosphonates increase bone mineral density by inhibiting osteoclast-mediated bone resorption, thereby reducing the risk of fractures. Alendronate sodium hydrate (alendronate is a bisphosphonate that potently inhibits bone resorption and is used to treat osteoporosis. Sufficient water is required to take an alendronate oral tablet; insufficient water could result in digestive system diseases, such as esophageal ulceration. Elderly patients with swallowing difficulty may choke on the tablet. Taking a tablet with oral jelly is a method to prevent digestive system disease and reduce the choking hazard. Once-weekly alendronate oral jelly was approved in 2012 by the Ministry of Health, Labour, and Welfare of Japan as the world's first drug for osteoporosis in a jelly formulation. It consists of a jelly portion and an air portion. The jelly formulation is smoothly discharged by pushing the air portion. Therefore, elderly patients with physical disabilities are able to easily take all of the jelly formulation from the package. In this review, this new formulation of alendronate sodium hydrate (oral jelly is introduced and discussed in terms of osteoporosis treatment. This new formulation provides an alternative so that patients may select a method of dosing tailored to their preferences. Management of osteoporosis involves assessing fracture risk and preventing

  17. Effects of long-term alendronate treatment on postmenopausal osteoporosis bone material properties.

    Science.gov (United States)

    Hassler, N; Gamsjaeger, S; Hofstetter, B; Brozek, W; Klaushofer, K; Paschalis, E P

    2015-01-01

    Raman microspectroscopic analysis of iliac crest from patients that were treated with alendronate (ALN) for 10 years revealed minimal, transient alterations in bone material properties confined to actively forming bone surfaces compared to patients that were on ALN for 5 years. These changes were not encountered in the bulk tissue. Alendronate (ALN) and other bisphosphonates (BPs) are the most widely prescribed therapy for postmenopausal osteoporosis. Despite their overall excellent safety record and efficacy in reducing fractures, questions have been raised regarding potential detrimental effects that may be related to prolonged bone turnover reduction, although no definite cause-effect relationship has been established to date. The purpose of the present study was to evaluate bone material properties in patients that were receiving ALN for 5 or 10 years. Raman microspectroscopic analysis was used to analyze iliac crest biopsies from postmenopausal women with osteoporosis who had been treated with ALN for 5 years and were then re-randomized to placebo (PBO, N = 14), 5 mg/day ALN (N = 10), or 10 mg/day ALN (N = 6) for another 5 years. The parameters monitored and expressed as a function of tissue age were (i) the mineral/matrix ratio (MM), (ii) the relative proteoglycan content (PG), (iii) the relative lipid content (LPD), (iv) the mineral maturity/crystallinity (MMC), and (v) the relative pyridinoline content (PYD). The obtained data indicate that 10-year ALN use results in minimal, transient bone tissue composition changes compared to use for 5 years, confined to actively forming trabecular surfaces, implying potential differences in bone matrix maturation that nevertheless did not result in differences of these values in bulk tissue. The data suggest that prolonged reduction in bone turnover during 10 years of therapy with ALN by itself is unlikely to be associated with adverse effects on bone material properties.

  18. A Study of Relation Between Physics and Metaphysics in the Field of Space and Time's Reality

    Directory of Open Access Journals (Sweden)

    Alireza Mansouri

    2015-02-01

    Full Text Available In this article it is aimed to explain the manner of science and metaphysics' interaction in space and time discussion. We will emphasize on this point that unlike the current perception, the changes in scientific and physics theories can be effective for us in taking philosophical and metaphysical position for space and time. For this purpose, in addition to surveying traditional arguments of essentialists and relationship-oriented about space and time, which are especially mentioned in Leibniz's  and Clarke's letters, interaction between science and metaphysics will be shown, according to new theoretical backgrounds, such as adoption of new Newtonian structure or field theory and general and special relativity theory. In the end, we will be close to this viewpoint that considering new scientific theories, such as general relativity theory of Einstein, essentialists' viewpoint about space and time, in current situation, seems more defendable.

  19. Mind, medicine, and metaphysics: reflections on the reclamation of the human spirit.

    Science.gov (United States)

    Penn, Michael L; Wilson, Lindsay

    2003-01-01

    Following the publication of such works as Auguste Comte's Cour de Philosophie Positive (1830-1842), in which he argued the inherent immaturity of metaphysical discourse, metaphysics, for Western intellectuals--and especially for Western intellectuals committed to science--has largely been abandoned. In recent years, however, we have seen renewed interest in metaphysics among some researchers and clinicians, due, in part, to increasing attempts to integrate diverse fields of study into some unified and coherent understanding of human life. For many psychologists and psychiatrists, this renewed interest is accompanied by an implicit, and sometimes explicit, re-embrace of the notion of the "human spirit." In this paper we explore some of the processes animating this movement and some of the clinical implications that flow from it.

  20. Biomechanics of the classic metaphyseal lesion: finite element analysis

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Andy; Kleinman, Paul K. [Boston Children' s Hospital, Department of Radiology, Harvard Medical School, Boston, MA (United States); Coats, Brittany [University of Utah, Department of Mechanical Engineering, Salt Lake City, UT (United States)

    2017-11-15

    The classic metaphyseal lesion (CML) is strongly associated with infant abuse, but the biomechanics responsible for this injury have not been rigorously studied. Radiologic and CT-pathological correlates show that the distal tibial CML always involves the cortex near the subperiosteal bone collar, with variable extension of the fracture into the medullary cavity. Therefore, it is reasonable to assume that the primary site of bone failure is cortical, rather than intramedullary. This study focuses on the strain patterns generated from finite element modeling to identify loading scenarios and regions of the cortex that are susceptible to bone failure. A geometric model was constructed from a normal 3-month-old infant's distal tibia and fibula. The model's boundary conditions were set to mimic forceful manipulation of the ankle with eight load modalities (tension, compression, internal rotation, external rotation, dorsiflexion, plantar flexion, valgus bending and varus bending). For all modalities except internal and external rotation, simulations showed increased cortical strains near the subperiosteal bone collar. Tension generated the largest magnitude of cortical strain (24%) that was uniformly distributed near the subperiosteal bone collar. Compression generated the same distribution of strain but to a lesser magnitude overall (15%). Dorsiflexion and plantar flexion generated high (22%) and moderate (14%) localized cortical strains, respectively, near the subperiosteal bone collar. Lower cortical strains resulted from valgus bending, varus bending, internal rotation and external rotation (8-10%). The highest valgus and varus bending cortical strains occurred medially. These simulations suggest that the likelihood of the initial cortical bone failure of the CML is higher along the margin of the subperiosteal bone collar when the ankle is under tension, compression, valgus bending, varus bending, dorsiflexion and plantar flexion, but not under internal

  1. Pyle metaphyseal dysplasia in an African child: Case report and review of the literature.

    Science.gov (United States)

    Wonkam, A; Makubalo, N; Roberts, T; Chetty, M

    2016-05-25

    Pyle disease (OMIM 265900), also known as metaphyseal dysplasia, is a rare autosomal recessive disorder with no known gene mutation. We report a case of Pyle disease in a 7-year-old African boy of mixed ancestry who presented with finger and wrist fractures following minor trauma. The radiological findings revealed abnormally broad metaphyses of the tubular bones, known as Erlenmeyer-flask bone deformity, and mild cranial sclerosis, both hallmarks of the condition. We report the first case in a patient with African ancestry, which could help in the gene discovery of this rare autosomal recessive skeletal dysplasia with unknown mutations.

  2. The old with the die. A contribution to metaphysics of quantum mechanics

    International Nuclear Information System (INIS)

    Ijjas, Anna

    2011-01-01

    Since the rise of quantum mechanics also their ideological implications and consequences were discussed. Meanwhile still scarcely a metaphysical problem exists, which was not supposedly solved under calling on quantum theory. Anna Ijjas inquires the usual practice and developes a new model of the assignment of quantum mechanics and metaphysics. She discusses both the physical foundations and the classical philosophical controversies, before she draws consequencies for the relation determination of brain and consciousness, the problem of freedom of will, as well as for the question of the influence of God in the world.

  3. On How physics Could impact on the Metaphysics of Space and Time

    Directory of Open Access Journals (Sweden)

    Alireza Mansouri

    2015-03-01

    Full Text Available This paper aims to illustrate the mutual inter-relation of physics and metaphysics in the context of the philosophy of space and time. We especially emphasize, in this paper, that scientific development could impact on our position regarding the reality of space and time. To illustrate this point, we investigate the mutual inter-relation of physics and metaphysics in the modern developments of physics, i.e. neo-Newtonian structure, special and general relativity (GR. This paper ends up anticipating that it is likely, by considering modern physics, especially GR, that substantivalism to be a more defensible position.

  4. EFFECTS OF LONG-TERM ALENDRONATE TREATMENT ON A LARGE SAMPLE OF PEDIATRIC PATIENTS WITH OSTEOGENESIS IMPERFECTA.

    Science.gov (United States)

    Lv, Fang; Liu, Yi; Xu, Xiaojie; Wang, Jianyi; Ma, Doudou; Jiang, Yan; Wang, Ou; Xia, Weibo; Xing, Xiaoping; Yu, Wei; Li, Mei

    2016-12-01

    Osteogenesis imperfecta (OI) is a group of inherited diseases characterized by reduced bone mass, recurrent bone fractures, and progressive bone deformities. Here, we evaluate the efficacy and safety of long-term treatment with alendronate in a large sample of Chinese children and adolescents with OI. In this prospective study, a total of 91 children and adolescents with OI were included. The patients received 3 years' treatment with 70 mg alendronate weekly and 500 mg calcium daily. During the treatment, fracture incidence, bone mineral density (BMD), and serum levels of the bone turnover biomarkers (alkaline phosphatase [ALP] and cross-linked C-telopeptide of type I collagen [β-CTX]) were evaluated. Linear growth speed and parameters of safety were also measured. After 3 years of treatment, the mean annual fracture incidence decreased from 1.2 ± 0.8 to 0.2 ± 0.3 (Posteogenesis imperfecta PTH = parathyroid hormone.

  5. Estimating the Time to Benefit for Preventive Drugs with the Statistical Process Control Method: An Example with Alendronate.

    Science.gov (United States)

    van de Glind, Esther M M; Willems, Hanna C; Eslami, Saeid; Abu-Hanna, Ameen; Lems, Willem F; Hooft, Lotty; de Rooij, Sophia E; Black, Dennis M; van Munster, Barbara C

    2016-05-01

    For physicians dealing with patients with a limited life expectancy, knowing the time to benefit (TTB) of preventive medication is essential to support treatment decisions. The aim of this study was to investigate the usefulness of statistical process control (SPC) for determining the TTB in relation to fracture risk with alendronate versus placebo in postmenopausal women. We performed a post hoc analysis of the Fracture Intervention Trial (FIT), a randomized, controlled trial that investigated the effect of alendronate versus placebo on fracture risk in postmenopausal women. We used SPC, a statistical method used for monitoring processes for quality control, to determine if and when the intervention group benefited significantly more than the control group. SPC discriminated between the normal variations over time in the numbers of fractures in both groups and the variations that were attributable to alendronate. The TTB was defined as the time point from which the cumulative difference in the number of clinical fractures remained greater than the upper control limit on the SPC chart. For the total group, the TTB was defined as 11 months. For patients aged ≥70 years, the TTB was 8 months [absolute risk reduction (ARR) = 1.4%]; for patients aged <70 years, it was 19 months (ARR = 0.7%). SPC is a clear and understandable graphical method to determine the TTB. Its main advantage is that there is no need to define a prespecified time point, as is the case in traditional survival analyses. Prescribing alendronate to patients who are aged ≥70 years is useful because the TTB shows that they will benefit after 8 months. Investigators should report the TTB to simplify clinical decision making.

  6. Treatment of Degree II Furcation Defects Using Autogenous Grafts with and without Alendronate - A Split Mouth Clinical Study

    Directory of Open Access Journals (Sweden)

    Sujit Kumar

    2014-01-01

    Results: Both the experimental groups showed significant reduction in probing pocket depth, gain in clinical attachment level and mean percentage of horizontal defect fill (41.82% vs 49.09% at 6 months. Experimental sites in group B showed a significant loss in mean vertical defect height compared to experimental group A (1.52% Vs -1.59%. Conclusion: It can be suggested that bisphosphonates such as alendronate sodium have the potential to inhibit the surgery induced bone loss.

  7. Atypical femoral fractures shortly after osteonecrosis of the jaw in a postmenopausal woman taking alendronate for osteoporosis.

    Science.gov (United States)

    Chiu, Wei-Yih; Lee, Jang-Jaer; Tsai, Keh-Sung

    2013-04-01

    Bisphosphonates effectively increase bone mineral density and reduce fracture risk in patients with osteoporosis, but there are concerns about osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFFs) in the long-term users. So far both complications have not been reported as occurring simultaneously in an osteoporotic individual on oral alendronate. The aim of this study was to report a postmenopausal woman presenting with concomitant ONJ and AFF on oral alendronate treatment. SUBJECT, MEASURES, AND RESULT: The patient was a 63-year-old woman with a history of rheumatoid arthritis for 30 years and diabetes for 3 years. Spinal compression fractures at levels L3 and L4 were documented, and she took alendronate 70 mg weekly for 7 years. She is the first case whose dental periapical imaging and pelvic radiography documented her ONJ and AFF, which developed subsequently within 6 months. This case report supports the association of both ONJ and AFF with long-term oral bisphosphonate therapy.

  8. Atypical femoral fracture after long-term alendronate treatment: Report of a case evidenced with magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Chih-Ming Kao

    2012-10-01

    Full Text Available Postmenopausal osteoporosis is commonly treated with alendronate, one of the bisphosphonates used for the prevention and treatment of osteoporotic fractures. However, the correlation between atypical femoral fractures and long-term bisphosphonate therapy has not been clearly identified. We report here the case of a 69-year-old woman with postmenopausal osteoporosis who presented with an atypical femoral subtrochanteric fracture on magnetic resonance imaging (MRI confirmation after having received alendronate therapy for about 3 years. The fracture united after refixation and after administration of alendronate was stopped. Several published reports were reviewed, and some clinical characteristics of this atraumatic fracture were revealed, including the clinical symptoms of thigh pain, stress reaction or stress fracture, and transverse fracture with unicortical beak in an area of cortical hypertrophy. In addition to a regular radiographic survey, MRI, which may provide early information, and bone biopsy for pathologic analysis may be used as tools for early detection and final diagnosis. Once an insufficiency fracture is suspected or proved to be related to bisphosphonate, the withholding of bisphosphonate should be highly recommended to enhance fracture healing. Prophylactic fixation should be considered if fracture healing is not good or if the patient cannot tolerate protection of weight-bearing.

  9. Atypical femoral fracture after long-term alendronate treatment: report of a case evidenced with magnetic resonance imaging.

    Science.gov (United States)

    Kao, Chih-Ming; Huang, Peng-Ju; Chen, Chung-Hwan; Chen, Shu-Jung; Cheng, Yuh-Min

    2012-10-01

    Postmenopausal osteoporosis is commonly treated with alendronate, one of the bisphosphonates used for the prevention and treatment of osteoporotic fractures. However, the correlation between atypical femoral fractures and long-term bisphosphonate therapy has not been clearly identified. We report here the case of a 69-year-old woman with postmenopausal osteoporosis who presented with an atypical femoral subtrochanteric fracture on magnetic resonance imaging (MRI) confirmation after having received alendronate therapy for about 3 years. The fracture united after refixation and after administration of alendronate was stopped. Several published reports were reviewed, and some clinical characteristics of this atraumatic fracture were revealed, including the clinical symptoms of thigh pain, stress reaction or stress fracture, and transverse fracture with unicortical beak in an area of cortical hypertrophy. In addition to a regular radiographic survey, MRI, which may provide early information, and bone biopsy for pathologic analysis may be used as tools for early detection and final diagnosis. Once an insufficiency fracture is suspected or proved to be related to bisphosphonate, the withholding of bisphosphonate should be highly recommended to enhance fracture healing. Prophylactic fixation should be considered if fracture healing is not good or if the patient cannot tolerate protection of weight-bearing. Copyright © 2012. Published by Elsevier B.V.

  10. In vitro disintegration and dissolution studies of once-weekly copies of alendronate sodium tablets (70 mg) and in vivo implications.

    Science.gov (United States)

    Dansereau, Richard J; Crail, Debbie J; Perkins, Alan C

    2008-04-01

    The aim of this study was to evaluate the in vitro disintegration and dissolution of 26 alendronic acid tablets (70 mg) on the market in Canada, Germany, the Netherlands, and the United Kingdom compared to the branded product (Fosamax). The disintegration and dissolution times were determined using the methods described in the United States Pharmacopeia 30 (USP 30). The disintegration of four orally disintegrating tablets (non-bisphosphonates) and branded film-coated risedronate sodium tablets were included for comparison. The mean disintegration times of the alendronic acid tablets ranged from 14 s for Pharmachemie (Netherlands) to 342 s (5.7 min) for Betapharm (Germany). The mean disintegration time of the branded product tablets ranged from 43 to 78 s. Six of the 26 companies market alendronic acid tablets with very rapid disintegration times which are similar to those of orally disintegrating tablets (non-bisphosphonates). The alendronic acid tablets with very rapid mean disintegration times are as follows: Pharmachemie (Netherlands), 14 s; Novopharm (Canada), 13-24 s; GRY-Pharma (Germany), 21 s; Juta Pharma (Germany), 30 s; APS/Teva (United Kingdom), 26 and 37 s; and Teva (UK), 14-29 s. Since there is no established disintegration time for alendronic acid tablets there can be no assurance that the copy tablets are equivalent to the branded product in terms of esophageal drug exposure. However, the in vitro disintegration times have not been correlated with in vivo disintegration and performance. The dissolution of all the bisphosphonate tablets was rapid with greater than 80% dissolved in 15 min and all products conformed to the USP 30 specification. The dissolution of all alendronic acid tablets was rapid and complete and conformed to the established USP 30 specifications which should ensure adequate drug absorption from the copy products. However, copies of alendronic acid tablets are approved based on the results of single-dose bioavailability studies in

  11. The Problem of Absolute Knowledge. Metaphysics as Intellectual Intuition in Classic Modern European Philosophy

    Science.gov (United States)

    Torubarova, Tatyana V.

    2016-01-01

    Classic modern European philosophy explicate, reflect; leaving own history in fundamental metaphysical position, where the existence is understood as conscience. This position is representative in the process of historic development, transition of philosophical thought from R. Dekart to G. Hegel. It appears exactly the field of key metaphysical…

  12. The Age of Milton--Paradise, Metaphysics, and Chivalric Codes: 5114.303.

    Science.gov (United States)

    Hargraves, Richard

    Developed for a high school unit on the age of Milton, this guide is designed to examine the dominant literary modes of thought expressed in Spenser's "The Faerie Queene," Milton's "Comus,""Paradise Lost," and "Paradise Regained," and John Donne's metaphysical poetry. Performance objectives are listed along…

  13. About Being a Friend: Friendship and Metaphysics by Plato, Aristotle, Augustine and Albert the Great

    Directory of Open Access Journals (Sweden)

    Andrés Quero Sánchez

    2014-11-01

    of friendship in his commentaries on the Nicomachian Ethics (both Super Ethica and Ethica and we show how his metaphysics should be considered as Christian Aristotelism, according to the traditional interpretation, which has, as is known, been questioned for decades

  14. Let's keep metaphysics out of medical ethics: a critique of Poplawski and Gillett.

    Science.gov (United States)

    Leavitt, F J

    1992-01-01

    I argue that the concept of 'longitudinal form', which Poplawski and Gillett have introduced into ethical discussions about embryos and gametes, involves too many metaphysical subtleties to be a useful aid to making moral decisions. I conclude by suggesting a criterion for relevance in medical ethics. PMID:1460650

  15. The fine-grained metaphysics of artifactual and biological functional kinds

    NARCIS (Netherlands)

    Carrara, M.; Vermaas, P.E.

    2008-01-01

    In this paper we consider the emerging position in metaphysics that artifact functions characterize real kinds of artifacts. We analyze how it can circumvent an objection by David Wiggins (Sameness and substance renewed, 2001, 87) and then argue that this position, in comparison to expert judgments,

  16. Metaphysical Communication of I. Kant’s Theory of Experience: M. Heidegger

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    Edvardas Rimkus

    2015-07-01

    Full Text Available The article examines the reception of Kantian conception of experience in Martin Heidegger’s book Kant and the Problem of Metaphysics. The context of Immanuel Kant’s theory of experience forms the basis for collation of Kant’s and Heidegger’s philosophies. Epistemological and metaphysical components of Kantian conception of experience are extracted. Two main Kant’s theoretical distinctions are discussed: the difference between the sensual matter of experience and conceptual form of experience; and the difference between the thing-in-itself and appearance. The research is focused on Kantian understanding of experience or empirical cognition, which is a process of synthesis of sensuous data and concepts. Collation of Kant’s and Heidegger’s philosophies and evaluation of Heidegger’s interpretational position appeals to theoretical contexts of metaphysical nominalism and metaphysical realism. The basic conclusion states that Heidegger’s interpretation of Kant’s theory of experience is transfused by the premises of Heidegger’s fundamental Dasein ontology. These premises determine significant transformations of Kant’s philosophy and the omission of some aspects of Kant’s theory of experience.

  17. New Grand Narratives: The Metaphysical Worldview of 'Avatar' and 'Cloud Atlas'

    NARCIS (Netherlands)

    Früchtl, J.

    2016-01-01

    Referring to the films Avatar (2009) and Cloud Atlas (2012), the author will demonstrate that a new era of metaphysical holism follows Postmodernism. These films celebrate a resurrection of the flesh with 3-D technology and a reincarnation of souls with the aesthetic technique of morphing. However

  18. Development and Verification of Novel Porous Titanium Metaphyseal Cones for Revision Total Knee Arthroplasty.

    Science.gov (United States)

    Faizan, Ahmad; Bhowmik-Stoker, Manoshi; Alipit, Vincent; Kirk, Amanda E; Krebs, Viktor E; Harwin, Steven F; Meneghini, R Michael

    2017-06-01

    Porous metaphyseal cones are widely used in revision knee arthroplasty. A new system of porous titanium metaphyseal cones has been designed based on the femoral and tibial morphology derived from a computed tomography-based anatomical database. The purpose of this study is to evaluate the initial mechanical stability of the new porous titanium revision cone system by measuring the micromotion under physiologic loading compared with a widely-used existing porous tantalum metaphyseal cone system. The new cones were designed to precisely fit the femoral and tibial anatomy, and 3D printing technology was used to manufacture these porous titanium cones. The stability of the new titanium cones and the widely-used tantalum cones were compared under physiologic loading conditions in bench top test model. The stability of the new titanium cones was either equivalent or better than the tantalum cones. The new titanium femoral cone construct had significantly less micromotion compared with the traditional femoral cone construct in 5 of the 12 directions measured (P titanium metaphyseal tibial cones demonstrated less micromotion in medial varus/valgus (P = .004) and posterior compressive micromotion (P = .002) compared with the traditional porous tantalum system. The findings of this biomechanical study demonstrate satisfactory mechanical stability of an anatomical-based porous titanium metaphyseal cone system for femoral and tibial bone loss as measured by micromotion under physiologic loading. The new cone design, in combination with instrumentation that facilitates surgical efficiency, is encouraging. Long-term clinical follow-up is warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Abortion, metaphysics and morality: a review of Francis Beckwith's defending life: a moral and legal case against abortion choice.

    Science.gov (United States)

    Nobis, Nathan

    2011-06-01

    In Defending Life: A Moral and Legal Case Against Abortion Choice (2007) and an earlier article in this journal, "Defending Abortion Philosophically"(2006), Francis Beckwith argues that fetuses are, from conception, prima facie wrong to kill. His arguments are based on what he calls a "metaphysics of the human person" known as "The Substance View." I argue that Beckwith's metaphysics does not support his abortion ethic: Moral, not metaphysical, claims that are part of this Substance View are the foundation of the argument, and Beckwith inadequately defends these moral claims. Thus, Beckwith's arguments do not provide strong support for what he calls the "pro-life" view of abortion.

  20. Efficient Transdermal Delivery of Alendronate, a Nitrogen-Containing Bisphosphonate, Using Tip-Loaded Self-Dissolving Microneedle Arrays for the Treatment of Osteoporosis.

    Science.gov (United States)

    Katsumi, Hidemasa; Tanaka, Yutaro; Hitomi, Kaori; Liu, Shu; Quan, Ying-Shu; Kamiyama, Fumio; Sakane, Toshiyasu; Yamamoto, Akira

    2017-08-17

    To improve the transdermal bioavailability and safety of alendronate (ALN), a nitrogen-containing bisphosphonate, we developed self-dissolving microneedle arrays (MNs), in which ALN is loaded only at the tip portion of micron-scale needles by a dip-coating method (ALN(TIP)-MN). We observed micron-scale pores in rat skin just after application of ALN(TIP)-MN, indicating that transdermal pathways for ALN were created by MN. ALN was rapidly released from the tip of MNs as observed in an in vitro release study. The tip portions of MNs completely dissolved in the rat skin within 5 min after application in vivo. After application of ALN(TIP)-MN in mice, the plasma concentration of ALN rapidly increased, and the bioavailability of ALN was approximately 96%. In addition, the decrease in growth plate was effectively suppressed by this efficient delivery of ALN in a rat model of osteoporosis. Furthermore, no skin irritation was observed after application of ALN(TIP)-MN and subcutaneous injection of ALN, while mild skin irritation was induced by whole-ALN-loaded MN (ALN-MN)-in which ALN is contained in the whole of the micron-scale needles fabricated from hyaluronic acid-and intradermal injection of ALN. These findings indicate that ALN(TIP)-MN is a promising transdermal formulation for the treatment of osteoporosis without skin irritation.

  1. The Effect of Alendronate on Proteome of Hepatocellular Carcinoma Cell Lines

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    Amber Ilyas

    2014-01-01

    Full Text Available Cancer is a life threatening disorder effecting 11 million people worldwide annually. Among various types of cancers, Hepatocellular carcinoma (HCC has a higher rate of mortality and is the fifth leading cause of cancer related deaths around the world. Many chemotherapeutic drugs have been used for the treatment of HCC with many side effects. These drugs are inhibitors of different cell regulatory pathways. Mevalonate (MVA pathway is an important cellular cascade vital for cell growth. A variety of inhibitors of MVA pathway have been reported for their anticancerous activity. Bisphosphonates (BPs are members of a family involved in the treatment of skeletal complications. In recent years, their anticancer potential has been highlighted. Current study focuses on exploring the effects of alendronate (ALN, a nitrogen containing BP, on hepatocellular carcinoma cell line using genomic and proteomics approach. Our results identified ten differentially expressed proteins, of which five were up regulated and five were down regulated in ALN treated cells. Furthermore, we also performed gene expression analysis in treated and control cell lines. The study may help in understanding the molecular mechanism involved in antitumor activity of ALN, identification of possible novel drug targets, and designing new therapeutic strategies for HCC.

  2. The influence of alendronate on osseointegration of nanotreated dental implants in New Zealand rabbits.

    Science.gov (United States)

    Tsetsenekou, Efstathia; Papadopoulos, Triantafillos; Kalyvas, Demos; Papaioannou, Nikos; Tangl, Stefan; Watzek, Georg

    2012-06-01

    Growing clinical demands for stronger and faster bone bonding to the implant have motivated the development of methods enhancing osseointegration. Lately, the application of bisphosphonates (bis) in order to optimize bone healing has become a topic of great interest. N-containing bis, such as alendronate (ALN), are the more potent drugs of this class. It was the aim of this study to determine the effect of ALN on the osseointegration of a well-documented nanotreated implant system in a rabbit femoral condyle model. Thirty-two adult female New Zealand White rabbits received one implant (3.25 mm in diameter and 10 mm in length) in their left femoral condyle, a week after they were ovariectomized. Half of them were saline treated (control, group A) and the other half were ALN treated (group B). Rabbits from both groups were euthanized after 6 and 12 weeks, respectively. The specimens were evaluated histologically and histomorphometrically. Upon histological evaluation, no obvious differences were found between the control and the treatment group. Implants showed good integration into the bone tissue surrounding them. There were also no statistically significant differences in bone-to-implant contact and the amount of bone tissue in the immediate neighborhood of the implant at both healing periods. The systemic administration of ALN was not found to affect histological osseointegration of implants in animals with a hormonal status resembling that of postmenopausal healthy women. Further research will be needed to investigate this approach. © 2011 John Wiley & Sons A/S.

  3. Montage, Militancy, Metaphysics: Chris Marker and André Bazin

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    Sarah Cooper

    2010-01-01

    Full Text Available

     

    Abstract (E: This article focuses on the relationship between the work of André Bazin and Chris Marker from the late 1940s through to the late 1950s and beyond. The division between Bazin's ŘRight Bankř affiliation with Les Cahiers du Cinéma on the one hand, and Markerřs ŘLeft Bankř allegiances on the other, is called into question here as my argument seeks to muddy the waters of their conventional ideological separation across the river Seine. Working alliteratively through Markerřs well-known talent for deft montage along with his militancy, I consider Bazinřs praise for Markerřs editing technique Ŕ in spite of famously expressing a preference elsewhere for the long take, and deep focus cinematography Ŕ and I address their political differences and convergences. Yet I also explore the rather more unexpected question of metaphysics in order to further emphasize a closer relationship between these two figures. I chart the emergence of an enduring spiritual bond between critic and filmmaker that surfaces first in Markerřs writings for the left-wing Catholic journal L’EspritProduction, quality control, biodistribution assessment and preliminary dose evaluation of {sup 166}Ho-alendronate as a bone marrow ablative agent

    Energy Technology Data Exchange (ETDEWEB)

    Fakhari, Ashraf [Tehran University of Medical Sciences (Iran, Islamic Republic of). Dept. of Radiopharmacy; Jalilian, Amir Reza; Yousefnia, Hassan; Zolghadri, Samaneh; Samani, Ali Bahrami; Akbari, Mahmoud Reza; Deha, Fariba Johari [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Shafiee-Ardestani, Mahdi; Khalaj, Ali [Tehran University of Medical Sciences (Iran, Islamic Republic of). Dept. of Medicinal Chemistry

    2015-07-01

    In this study, production, quality control and biodistribution studies of {sup 166}Ho-alendronate have been presented and followed by dosimetric evaluation for human based on biodistribution data in wild-type rats. {sup 166}Ho chloride was obtained by thermal neutron irradiation of natural {sup 165}Ho(NO{sub 3}){sub 3} samples. {sup 166}Ho-alendronate complex was prepared by adding the desired amount of alkaline alendronate solution (0.2 mL, 150 mg/mL) to 3-5 mCi of the {sup 166}HoCl{sub 3} solution. Radiochemical purity of the complex was monitored by instant thin layer chromatography (ITLC). {sup 166}Ho-alendronate complex was prepared in high radiochemical purity (> 99%, ITLC) and specific activity of 4.4 GBq/mmol. Stability studies of the complex in the final preparation and in the presence of human serum were performed up to 48 h. The major accumulation of the radio-complex was in the bone tissues followed by absorbed dose evaluation of each human organ by RADAR software used for modelling the radiation dose delivered. The final preparation was administered to wild-type rats and biodistribution of the complex was performed 2-48 h post injection showing major accumulation of the complex in the bone tissue. The highest absorbed dose for {sup 166}Ho-alendronate is observed in bone surface and red marrow with 2.670 and 1.880 mSv/MBq; respectively. These findings suggest that {sup 166}Ho-alendronate has considerable characteristics compared to {sup 166}Ho-DOTMP and can be a possible candidate for bone marrow ablation in patients with multiple myeloma.

  4. Does Alendronate reduce the risk of fracture in men? A meta-analysis incorporating prior knowledge of anti-fracture efficacy in women

    Directory of Open Access Journals (Sweden)

    Papaioannou Alexandra

    2005-07-01

    Full Text Available Abstract Background Alendronate has been found to reduce the risk of fractures in postmenopausal women as demonstrated in multiple randomized controlled trials enrolling thousands of women. Yet there is a paucity of such randomized controlled trials in osteoporotic men. Our objective was to systematically review the anti-fracture efficacy of alendronate in men with low bone mass or with a history of prevalent fracture(s and incorporate prior knowledge of alendronate efficacy in women in the analysis. Methods We examined randomized controlled trials in men comparing the anti-fracture efficacy of alendronate to placebo or calcium or vitamin D, or any combination of these. Studies of men with secondary causes of osteoporosis other than hypogonadism were excluded. We searched the following electronic databases (without language restrictions for potentially relevant citations: Medline, Medline in Process (1966-May 24/2004, and Embase (1996–2004. We also contacted the manufacturer of the drug in search of other relevant trials. Two reviewers independently identified two trials (including 375 men, which met all inclusion criteria. Data were abstracted by one reviewer and checked by another. Results of the male trials were pooled using Bayesian random effects models, incorporating prior information of anti-fracture efficacy from meta-analyses of women. Results The odds ratios of incident fractures in men (with 95% credibility intervals with alendronate (10 mg daily were: vertebral fractures, 0.44 (0.23, 0.83 and non-vertebral fractures, 0.60 (0.29, 1.44. Conclusion In conclusion, alendronate decreases the risk of vertebral fractures in men at risk. There is currently insufficient evidence of a statistically significant reduction of non-vertebral fractures, but the paucity of trials in men limit the statistical power to detect such an effect.

  5. Efficacy and safety of alendronate for the treatment of osteoporosis in diffuse connective tissue diseases in children: a prospective multicenter study.

    Science.gov (United States)

    Bianchi, M L; Cimaz, R; Bardare, M; Zulian, F; Lepore, L; Boncompagni, A; Galbiati, E; Corona, F; Luisetto, G; Giuntini, D; Picco, P; Brandi, M L; Falcini, F

    2000-09-01

    Osteopenia/osteoporosis is being increasingly reported as a complication of many chronic diseases, even in children. In this preliminary study, we evaluated the effect of an oral bisphosphonate (alendronate) on bone mass in children with diffuse connective tissue diseases. Thirty-eight children with low bone mass were treated with alendronate for 1 year; 38 children who had the same primary disorders as the study patients but in a less severe form served as untreated control patients. We were also able to evaluate changes in bone mass (before and after alendronate) in 16 of the treated patients whose bone mineral density (BMD) had been routinely measured before the present study was initiated. BMD increased by a mean +/- SD of 14.9 +/- 9.8% (P < 0.002 versus baseline) in the treated patients (reaching the normal range in 13 patients), while the BMD was 2.6 +/- 5% (not significant versus baseline) in the control group (15 had a decrease). Most interestingly, there was a large increase in BMD (15.3 +/-9.9%) after alendronate therapy in the 16 children who had their BMD followed up in the year before the study, during which time they had shown little increase in BMD (1.03 +/- 6.3%), and often a decrease. Considering their condition, increases in the height of all patients was satisfactory. No new fractures were observed after alendronate therapy was initiated. Bisphosphonates can be considered essential components of the treatment of secondary osteoporosis, not only in adults, but also in pediatric patients. Alendronate has a positive effect on secondary osteopenia/osteoporosis in children with connective tissue diseases.

  6. Prolegomena to any future metaphysics that will be able to come forward as science the Paul Carus translation

    CERN Document Server

    Kant, Immanuel

    1977-01-01

    Kant’s Prolegomena -- its full title, in the eighteenth-century manner, is Prolegomena to Any Future Metaphysics Which Will Be Able to Come Forth as Science -- is a classic in metaphysics and the theory of knowledge. It deals with the perennially baffling questions: How do we know? How much can we know? Its answers to these questions are interesting especially now. We live in one of the recurring periods of intellectual and cultural history that are skeptical and impatient of systems of speculative metaphysics, and a distrust of speculation is the leading motif of the Prolegomena. Though Kant's arguments against speculative metaphysics differ from those of our contemporaries, in some of his results he anticipates their negative conclusions. The Prolegomena, however, is not interesting merely as an historical anticipation of recent views; indeed, as such it has been as it were condemned in advance by Kant (Prolegomena, Introduction). Rather, its chief interest to the student of philosophy is probably the way...

  7. Serum levels of innate immunity cytokines are elevated in dogs with metaphyseal osteopathy (hypertrophic osteodytrophy) during active disease and remission

    OpenAIRE

    Safra, Noa; Hitchens, Peta L.; Maverakis, Emanual; Mitra, Anupam; Korff, Courtney; Johnson, Eric; Kol, Amir; Bannasch, Michael J.; Pedersen, Niels C.; Bannasch, Danika L.

    2016-01-01

    Metaphyseal osteopathy (MO) (hypertrophic osteodystrophy) is a developmental disorder of unexplained etiology affecting dogs during rapid growth. Affected dogs experience relapsing episodes of lytic/sclerotic metaphyseal lesions and systemic inflammation. MO is rare in the general dog population; however, some breeds (Weimaraner, Great Dane and Irish Setter) have a much higher incidence, supporting a hereditary etiology. Autoinflammatory childhood disorders of parallel presentation such as ch...

  8. Being Itself and the Being of Beings : Reading Aristotle’s Critique of Parmenides (Physics 1.3) after Metaphysics

    OpenAIRE

    Backman, Jussi

    2018-01-01

    The essay studies Aristotle’s critique of Parmenides (Physics 1.3) in the light of the Heideggerian account of Platonic-Aristotelian metaphysics as an approach to being (Sein) in terms of beings (das Seiende). Aristotle’s critique focuses on the presuppositions of the Parmenidean thesis of the unity of being. It is argued that a close study of the presuppositions of Aristotle’s own critique reveals an important difference between the Aristotelian metaphysical framework and the ...

  9. The metaphysical club at the Johns Hopkins University (1879-1885).

    Science.gov (United States)

    Behrens, Peter J

    2005-11-01

    Of the earliest American universities, The Johns Hopkins in Baltimore holds a unique position for psychology. At Hopkins, many of America's first psychologists received their graduate training. Of special interest is the Hopkins Metaphysical Club, organized in 1879 by Charles Sanders Peirce. It provided a forum for research and scholarship by faculty and students. Papers related to topics of the "new" psychology began to appear in 1883, about the time G. Stanley Hall was given a 3-year appointment at Hopkins. When Peirce departed Hopkins in 1885, Hall was free to develop psychology in his image and disbanded the club. Nevertheless, the Metaphysical Club played an important role in the emergence of American scientific psychology.

  10. Purpose in the Universe the moral and metaphysical case for ananthropocentric purposivism

    CERN Document Server

    Mulgan, Tim

    2015-01-01

    Two familiar worldviews dominate Western philosophy: materialist atheism and the benevolent God of the Abrahamic faiths. Tim Mulgan explores a third way. Ananthropocentric Purposivism claims that there is a cosmic purpose, but human beings are irrelevant to it. Purpose in the Universe develops a philosophical case for Ananthropocentric Purposivism that it is at least as strong as the case for either theism or atheism. The book borrows traditional theist arguments to defend a cosmic purpose. These include cosmological, teleological, ontological, meta-ethical, and mystical arguments. It then borrows traditional atheist arguments to reject a human-centred purpose. These include arguments based on evil, diversity, and the scale of the universe. Mulgan also highlights connections between morality and metaphysics, arguing that evaluative premises play a crucial and underappreciated role in metaphysical debates about the existence of God, and Ananthropocentric Purposivism mutually supports an austere consequentialis...

  11. Hughlings Jackson and the "doctrine of concomitance": mind-brain theorising between metaphysics and the clinic.

    Science.gov (United States)

    Chirimuuta, M

    2017-09-11

    John Hughlings Jackson (1835-1911) is a major figure at the origins of neurology and neuroscience in Britain. Alongside his contributions to clinical medicine, he left a large corpus of writing on localisation of function in the nervous system and other theoretical topics. In this paper I focus on Jackson's "doctrine of concomitance"-his parallelist theory of the mind-brain relationship. I argue that the doctrine can be given both an ontological and a causal interpretation, and that the causal aspect of the doctrine is especially significant for Jackson and his contemporaries. I interpret Jackson's engagement with the metaphysics of mind as an instance of what I call meta-science-the deployment by scientists of metaphysical positions and arguments which help streamline empirical investigations by bracketing off unanswerable questions and focussing attention on matters amenable to the current tools of experimental research.

  12. Aesthetics as metaphysical meaning-making in the face of death

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    Maija Khandro Butters

    2016-12-01

    Full Text Available In my ethnographic research on death and dying in contemporary Finland, I explore how Finns facing end of life due to a long-term illness or other terminal condition seek to orient themselves and make meaning with cultural tools such as imagery, language, and metaphysical thinking. My primary research material is based on extensive fieldwork at Terhokoti Hospice and in the cancer clinic of Helsinki University Hospital, where I have had numerous conversations with terminally ill patients. This paper seeks to explore the way in which metaphysical aesthetics is assuming the role that religious thinking has traditionally played. When the role of institutional religion is diminishing, it becomes important to understand how emotional and spiritual resolution can be arrived at by means of aesthetics.

  13. A remarkable hematological and molecular response pattern in a patient with polycythemia vera during combination therapy with simvastatin and alendronate

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    Anders Lindholm Sørensen

    2016-01-01

    Full Text Available We report a 57-year old man with polycythemia vera, who had a remarkable hematological and molecular response during treatment with simvastatin and alendronate. The patient was treated with this combination for 56 months, and during this period the patient has been in complete hematological remission. The JAK2-V617F allele burden has dropped from 64% to sustained values below 20%, and follow-up bone marrow biopsies have revealed no change in PV features, without any regular cytoreductive treatment.

  14. Mechanical Failure of Revision Knee Prosthesis at both Femoral and Tibial Modular Metaphyseal Stem Junctions

    OpenAIRE

    Woodgate, Ian G; Rooney, John; Mulford, Johnathan S; Gillies, R Mark

    2016-01-01

    Introduction: This is a report of a mechanical failure of an S-ROM revision total knee prosthesis. The prosthesis was used as a revision implant following deep peri-prosthetic infection in a morbidly obese male. The prosthesis failed on both the femoral and tibial sides at the modular metaphyseal stem junctions and required a further revision using the same type of implant after infection was excluded. Case Presentation: A 57 year old male had previously undergone a left total knee arthroplas...

  15. Crititics to Metaphysics by Modern Philosophers (Discourse on Human Beings in Reality)

    OpenAIRE

    Frederikus Fios

    2016-01-01

    We have entered the 21st century that is popularly known as the era of the development of modern science and technology. Philosophy provides naming for contemporary era as postmodern era. But do we suddenly come to this day and age? No! Because humans are homo viator, persona that does pilgrimage in history, space and time. Philosophy has expanded periodically in the long course of history. Since the days of classical antiquity, philosophy comes with a patterned metaphysical paradigm. T...

  16. The Problem of the Object of Mathematics as Intelligible Substance in Aristotle's Metaphysics

    OpenAIRE

    Cattanei, Elisabetta

    2013-01-01

    The A. examines the problem of intermediat emathematical entities by analyzing Metaphysics l017a9-l4, since, according to Aristotle. this passage is both a source and a critique of Plato's theory. The goal is to identify four cardinal points that may ground a dialogue between two contesting positions regarding this problem. Through them, it becomes evident that Aristotle severs the question of the intelligible nature of mathematical entities by using the conceptual scalpel of his own ousiolog...

  17. Arguments for the Existence of God in the Francisco Suarez’ "Metaphysical Disputations"

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    Galina Vdovina

    2017-12-01

    Full Text Available The article considers arguments for the existence of God that are presented in Francisco Suarez’ treatise Metaphysical Disputations. The work of Suarez contains the most developed and detailed exposition of natural theology that exists in the scholastic tradition. Suarez explicitates the problem, formulating three questions: what is a being that we call God? Is it possible to prove or justify his existence? How is it possible? Suarez answers the first question by showing that we come to a concept of the prime and excellent being through a series of divisions in the concept of being. That prime being is infinite, absolute, necessary and uncreated. The second question is answered by the procedure of that division and its result. In his answer to the third question, Suarez distinguishes physical and metaphysical arguments. According to Suarez, the most significant physical proofs are the argument from motion and the argument from the rational soul. Nevertheless, he demonstrates that purely physical arguments cannot lead us to a being, which we call God. Only metaphysical argument from the principle, everything which is produced, is produces by something else, is really effective. The logic of the metaphysical proof is as follows: first, we have to demonstrate the necessary existence of the first non-produced thing: secondly, we are to show that such a thing can only be one. The first point is proved through the demonstration of an absolutely first cause in each series of causes, the second one is made evident through a demonstration of the impossibility to coexist simultaneously for two equally perfect first causes of equal causing power.

  18. Different methods and metaphysics in early molecular genetics--a case of disparity of research?

    Science.gov (United States)

    Deichmann, Ute

    2008-01-01

    The encounter between two fundamentally different approaches in seminal research in molecular biology--the problems, aims, methods and metaphysics--is delineated and analyzed. They are exemplified by the microbiologist Oswald T. Avery who, in line with the reductionist mechanistic metaphysics of Jacques Loeb, attempted to explain basic life phenomena through chemistry; and the theoretical physicist Max Delbrück who, influenced by Bohr's antimechanistic views, preferred to explain these phenomena without chemistry. Avery's and Delbrück's most important studies took place concurrently. Thus analysis of their contrasting approaches lends itself to examination of the Weltanschauungen view concerning the role of fundamental (metaphysical) assumptions in scientific change, that is, the view that empirical research cannot be neutral in regard to the worldviews of the researchers. This study shows that the initial ostensible disparity (non-integratibility) of the two approaches lasted for just a short time. Ironically it was a student of Delbrück's school, James Watson, who (with Crick) proposed a chemical model, the DNA double helix, as a solution to Delbrück's problem. The structure of DNA has not been seriously challenged over the past half century Moreover, Watson's and Crick's work did not call into question the validity of Delbrück's research, but opened it up to entirely new approaches. The case of Avery and Delbrück demonstrates that after initial obstacles were overcome the different fundamental attitudes and the resulting research practices were capable of integration.

  19. The Schopenhauer's ethical-metaphysical approach os "sympathy”: between Hume and Plotinus

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    Luan Corrêa da Silva

    2017-08-01

    Full Text Available This article aims to establish the basis for understanding "sympathy" in Arthur Schopenhauer's philosophy. In an undeveloped passage, Schopenhauer defines the concept of sympathy as the empirical irruption of the metaphysical identity of the will through the physical plurality of its appearances, which shows a connection completely different from that known we through the principle of reason. In characterizing sympathy, Schopenhauer seems to indicate both a conception of sympathy from the moral feeling, and a cosmological-metaphysical conception of this concept. Following the clue left by the philosopher of the will, these conceptions seem to find an adequate clarification in the thoughts of Hume and Plotinus. Both develop, in their own way, two conceptions of sympathy, which aid and enrich Schopenhauer's approach. While from Hume the conception of the communication of feelings and affections is extracted, Plotinus develops a conception of the sympathy from the primordial unit of the cosmos. In the face of the two positions, which exert mutual and indirect influence on Schopenhauer, a connection between ethics and metaphysics, between the stricto sensu morality of the individual and the lato sensu morality of the cosmos, becomes possible.

  1. Typology reconfigured: from the metaphysics of essentialism to the epistemology of representation.

    Science.gov (United States)

    Love, Alan C

    2009-06-01

    The goal of this paper is to encourage a reconfiguration of the discussion about typology in biology away from the metaphysics of essentialism and toward the epistemology of classifying natural phenomena for the purposes of empirical inquiry. First, I briefly review arguments concerning 'typological thinking', essentialism, species, and natural kinds, highlighting their predominantly metaphysical nature. Second, I use a distinction between the aims, strategies, and tactics of science to suggest how a shift from metaphysics to epistemology might be accomplished. Typological thinking can be understood as a scientific tactic that involves representing natural phenomena using idealizations and approximations, which facilitates explanation, investigation, and theorizing via abstraction and generalization. Third, a variety of typologies from different areas of biology are introduced to emphasize the diversity of this representational reasoning. One particular example is used to examine how there can be epistemological conflict between typology and evolutionary analysis. This demonstrates that alternative strategies of typological thinking arise due to the divergent explanatory goals of researchers working in different disciplines with disparate methodologies. I conclude with several research questions that emerge from an epistemological reconfiguration of typology.

  2. Truth, Art, and the “New Sensuousness”: Understanding Heidegger’s Metaphysical Reading of Nietzsche

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    James Magrini

    2009-06-01

    Full Text Available In the first of four lectures on Nietzsche’s philosophy, “The Will to Poweras Art” (1936-37, Heidegger argues that the unique and importantrelationship between truth and art, which Nietzsche suggests, must beunderstood “with a view to the conquest of nihilism,” i.e., within the historical context of a radically novel interpretation of sensuous reality. Beginning with the project of overturning Platonism as the active countermovement to nihilism, this essay interprets Heidegger’s difficult notion of the discordant relationship between truth (the fixation of semblance and art (the transfiguration of semblance in Nietzsche’s philosophy, emphasizing the supreme importance of art as life’s greatest enhancing force. The analysis is conducted within the context of Nietzsche’s metaphysics as presented by Heidegger, who claims thatas a metaphysical thinker, Nietzsche could not explain such topics as “truth,” “Being,” and “Becoming” in terms beyond the conceptualization of Western philosophy. In spite of that, his thought intimates a movement beyond the constraints of the tradition within which he was entrenched. In addition to providing a detailed exegesis of Heidegger’s lecture course, the problems associated with Heidegger’s metaphysical interpretation of Nietzsche’s philosophy will be discussed, problems that commentators such as Alan Schrift (Nietzsche and the Question of Interpretation believe stem from Heidegger’s stringent and restrictive methodological choices for approaching the reading of Nietzsche.

  3. Effects of teriparatide on cortical histomorphometric variables in postmenopausal women with or without prior alendronate treatment.

    Science.gov (United States)

    Ma, Yanfei L; Zeng, Qing Q; Chiang, Alan Y; Burr, David; Li, Jiliang; Dobnig, Harald; Fahrleitner-Pammer, Astrid; Michalská, Dana; Marin, Fernando; Pavo, Imre; Stepan, Jan J

    2014-02-01

    Cortical bone, the dominant component of the human skeleton by volume, plays a key role in protecting bones from fracture. We analyzed the cortical bone effects of teriparatide treatment in postmenopausal women with osteoporosis who had previously received long-term alendronate (ALN) therapy or were treatment naïve (TN). Tetracycline-labeled paired iliac crest biopsies obtained from 29 ALN-pretreated and 16 TN women were evaluated for dynamic histomorphometric parameters of bone formation at the periosteal, endocortical and intracortical bone compartments, before and after 24months of teriparatide treatment. At baseline, the frequency of specimens without any endocortical and periosteal tetracycline labeling, and the percentage of quiescent osteons, was higher in the ALN than the TN group. Endocortical and periosteal mineralizing surface (MS/BS%), periosteal bone formation rate (BFR/BS), mineral apposition rate (MAR) and the number of intracortical forming osteons were significantly lower in the ALN-pretreated patients than in the TN group. Following teriparatide treatment, the frequency of endocortical and periosteal unlabeled biopsies decreased; in the ALN-pretreated group the percentage of quiescent osteons decreased and, in contrast, forming and resorbing osteons were increased. Teriparatide treatment resulted in significant increases of MAR in the endocortical, and MS/BS% in the periosteal compartment in the ALN-pretreated group. Most indices of bone formation remained lower in the ALN-pretreated group compared with the TN group at study end. Endocortical wall width was increased in both ALN-pretreated and TN groups. Cortical porosity and cortical thickness were significantly increased in the ALN-pretreated group after teriparatide treatment. Our results suggest that 24months of teriparatide treatment increases cortical bone formation and cortical turnover in patients who were either TN or had previous ALN therapy. Copyright © 2013 Elsevier Inc. All rights

  4. Czy sądy metafizyczne mówią coś o świecie? Wittgensteinowskie źródła deflacjonizmu metafizycznego i jego modele [Do metaphysical judgments say something about the world or not? Wittgensteinian roots of deflationary metaphysics and its models

    Directory of Open Access Journals (Sweden)

    Sebastian Kolodziejczyk

    2014-09-01

    Full Text Available Many of contemporary philosophers argue against metaphysics putting forward a thesis that metaphysical claims are deflationary. This way of thinking seems to be not only persuasive but above all it rightly expresses a main difficulty of metaphysical inquires. In this paper I am trying to shed a little light on the problem of deflation of metaphysical judgments. In the first section I refer to some Wittgenstein's ideas from Tractatus logico-philosophicus and I focus on the phenomenon of manifestation as a possible source of deflation of metaphysics. The second section is devoted to the Wittgenstein's concepts of language games on the one hand and rules on the other; both of them are a key to understanding of the deepest dimensions of deflationary metaphysics. The third section is an elaboration of three models of deflation of metaphysical expressions: 1. deflation in regard to the informative status of metaphysical judgments; 2. deflation in regard to the metasemantic properties of judgments about the world, and 3. deflation in regard to the semantic ground of ontological judgments. The fourth and last part of the paper is an exposition of two crucial problems which metaphysics has to face with. I call the first of them 'a problem with conceptualization of the metaphysical experience', whereas the second one is labeled 'a problem with semantic inclusion of metaphysical expressions into judgments about facts'.

  5. Descriptive Metaphysics, Natural Language Metaphysics, Sapir-Whorf, and All That Stuff: Evidence from the Mass-Count Distinction

    Directory of Open Access Journals (Sweden)

    Francis Jeffry Pelletier

    2010-12-01

    . Language 5: 207–214. Reprinted in David Mandelbaum (ed., Selected Writings of Edward Sapir in Language Culture and Personality, 160-166 (Berkeley and Los Angeles: University of California Press, 1968.Schank, Roger. 1972. ‘Conceptual Dependency: A Theory of Natural Language Understanding’. Cognitive Psychology 3: 552–631.http://dx.doi.org/10.1016/0010-0285(7290022-9Sharvy, Richard. 1978. ‘Maybe English has No Count Nouns: Notes on Chinese Semantics’. Studies in Language 2: 345–365.http://dx.doi.org/10.1075/sl.2.3.04shaStrawson, Peter. 1959. Individuals: An Essay in Descriptive Metaphysics. London: Methuen.Strawson, Peter. 1966. The Bounds of Sense. London: Methuen.Vendler, Zeno. 1967. Linguistics in Philosophy. Ithaca, NY: Cornell Univ. Press. Chapter 5. “Nouns and Nominalizations”.Vendler, Zeno. 1972. Res Cogitans. Ithaca, NY: Cornell Univ. Press. Chapter 5. “On What One Knows”.Whorf, Benjamin. 1940a. ‘Linguistics as an Exact Science’. Technology Review 43: 61–63, 80–83. Reprinted in (Whorf 1956, 220–232.Whorf, Benjamin. 1940b. ‘Science and Linguistics’. Technology Review 42: 229–231,247–248. Reprinted in (Whorf 1956, 207–219.Whorf, Benjamin. 1941. ‘The Relation of Habitual Thought and Behavior to Language’. In L. Spier (ed. ‘Language, Culture, and Personality: Essays in Memory of Edward Sapir’, 75–93. Menasha, WI: Sapir Memorial Publication Fund. Reprinted in (Whorf 1956, 134–159.Whorf, Benjamin. 1956. Language, Thought and Reality. Cambridge UP: MIT Press. Edited by J. Carroll.Wierzbicka, Anna. 1988a. ‘Oats and Wheat: Mass Nouns, Iconicity, and Human Categorization’. In Anna Wierzbicka (ed. ‘The Semantics of Grammar’, 499–560. Amsterdam: John Benjamins.Wierzbicka, Anna. 1988b. The Semantics of Grammar. Amsterdam: John Benjamins.Wierzbicka, Anna. 1994. ‘Opening Statement’. In ‘Semantic and Lexical Universals’, 1–3. Philadelphia: J. Benjamins.Wierzbicka, Anna. 1996. Semantics: Primes and Universals

  6. Realitas vs wirklichkeit: the genesis of the two concepts of western metaphysics

    Directory of Open Access Journals (Sweden)

    V. Y. Popov

    2014-01-01

    Full Text Available The terms «reality» and «reality» are used interchangeably, or quite similar to each other іn the modern Ukrainian philosophical literature. However, they have significant substantive differences, which not only with their etymology, but also fundamentally different metaphysical foundations of their origin and use. Category «reality» in the European metaphysics is closely linked substantiality, and not as a process. Category «reality» reflects a dynamic dimension of being, and originates from the «» «Metaphysics» of Aristotle, which later developed into the category of German philosophy Wirklichkeit». In the article it is proved that the notions of «realitas» and «Wirklichkeit» born in the end of the age of high scholasticism, and their founders were Duns Scotus and Eckhart Meister. In particular, the concept of «realitas» is entered Duns Scotus to denote «ultima realitas» («ultimate reality» things that is haecceitas «thisness» individual things. The concept of «realitas» (reality speaking only a subsidiary subsequently in Western ontology acquires metaphysical significance. Eckhart Meister borrows from albert the Great, the term «actualitas» (actuality and translates this word into the language of their sermons as «wercelicheit», which later became «Wirklichkeit». This word in the mouth of a preacher mystic ceases to be a simple translation of «actualitas» turning from the Divine actus purus in «non­action activities». However, these mystical layering subsequently disappear; Сh. Wolf word «Wirklichkeit» means the certainty of the existence or possible implementation. However, in the German classics (I. Kant, G. Hegel a continued separation «Wirklichkeit­Realitt». In Marxism reality more and more identified with the objective reality. Similar processes occur in the English­analytic philosophy (for example L. Wittgenstein. However, the article notes that the problem of the delimitation of the

  7. Mutual augmentation of the induction of the histamine-forming enzyme, histidine decarboxylase, between alendronate and immuno-stimulants (IL-1, TNF, and LPS), and its prevention by clodronate

    International Nuclear Information System (INIS)

    Deng Xue; Yu Zhiqian; Funayama, Hiromi; Shoji, Noriaki; Sasano, Takashi; Iwakura, Yoichiro; Sugawara, Shunji; Endo, Yasuo

    2006-01-01

    Nitrogen-containing bisphosphonates (N-BPs), powerful anti-bone-resorptive drugs, have inflammatory side effects, while histamine is not only an inflammatory mediator, but also an immuno-modifier. In murine models, a single intraperitoneal injection of an N-BP induces various inflammatory reactions, including the induction of the histamine-forming enzyme histidine decarboxylase (HDC) in tissues important in immune responses (such as liver, lungs, spleen, and bone marrow). Lipopolysaccharide (LPS) and the proinflammatory cytokines IL-1 and TNF are also capable of inducing HDC. We reported previously that in mice (i) the inflammatory actions of N-BPs depend on IL-1 (ii) N-BP pretreatment augments both LPS-stimulated IL-1 production and HDC induction, and (iii) the co-administration of clodronate (a non-N-BP) with an N-BP inhibits the latter's inflammatory actions (including HDC induction). Here, we add the new findings that (a) pretreatment with alendronate (a typical N-BP) augments both IL-1- and TNF-induced HDC elevations, (b) LPS pretreatment augments the alendronate-induced HDC elevation, (c) co-administration of clodronate with alendronate abolishes these augmentations, (d) alendronate does not induce HDC in IL-1-deficient mice even if they are pretreated with LPS, and (e) alendronate increases IL-1β in all tissues tested, but not in the serum. These results suggest that (1) there are mutual augmentations between alendronate and immuno-stimulants (IL-1, TNF, and LPS) in HDC induction, (2) tissue IL-1β is important in alendronate-stimulated HDC induction, and (3) combination use of clodronate may have the potential to reduce the inflammatory effects of alendronate (we previously found that clodronate, conveniently, does not inhibit the anti-bone-resorptive activity of alendronate)

  8. Long-term treatment with alendronate increases the surgical difficulty during simple exodontias - an in vivo observation in Holtzman rats.

    Science.gov (United States)

    Conte-Neto, Nicolau; Bastos, Alliny de Souza; Spolidorio, Luis Carlos; Chierici Marcantonio, Rosemary Adriana; Marcantonio, Elcio

    2012-07-26

    Atraumatic teeth extractions protocols are highly encouraged in patients taking bisphosphonates (Bps) to reduce surgical trauma and, consequently, the risk of jaws osteonecrosis development. In this way, this paper aims to report the findings of increased surgical difficulty during simple exodontias in animals treated with bisphosphonates. Sixty male Holtzman rats were randomly distributed into three groups of 20 animals and received daily subcutaneous administration of 1 mg/kg (AL1) or 3 mg/kg (AL3) of alendronate or saline solution (CTL). After 60 days of drug therapy all animals were submitted to first lower molars extractions under general anesthesia. Operatory surgical time and the frequency of teeth fractures were measured as principal outcomes and indicators of surgical difficulty degree. Animals treated with alendronate (AL1 and AL3) were associated to higher operatory times and increased frequency of teeth fractures compared to match controls. The bisphosphonate therapy may be associated with an increased surgical difficulty and trauma following simple exodontias protocols, which is considered a critical issue when it comes to osteonecrosis development.

  9. Effects of short-term alendronate treatment on the three-dimensional microstructural, physical and mechanical properties of dog trabecular bone

    DEFF Research Database (Denmark)

    Hu, J; Ding, Ming; Søballe, K

    2002-01-01

    (femoral condyle). In this study, the effects of alendronate on trabecular bone properties were assessed in dogs at an oral dose of 0.5 mg/kg per day over a 12 week period, and compared with control dogs. Cubic cancellous bone specimens were produced from lumbar vertebrae (L-1 and L-2) and bilateral...

  10. Effects of alendronate and hormone replacement therapy, alone and in combination, on saliva, periodontal conditions and gingival crevicular fluid matrix metalloproteinase-8 levels in women with osteoporosis.

    Science.gov (United States)

    Eviö, S; Tarkkila, L; Sorsa, T; Furuholm, J; Välimäki, M J; Ylikorkala, O; Tiitinen, A; Meurman, J H

    2006-03-01

    To compare the effects of hormone replacement therapy (HRT), alendronate and their combination on oral health of elderly postmenopausal women with osteoporosis. Sixty patients, aged 65-80 years (mean 71 years), with a T-score of bone mineral density of -2.5 s.d. or less at either the lumbar spine or the femoral neck, were randomized to receive 2 mg of estradiol plus 1 mg norethisterone acetate (HRT) (n = 20), 10 mg of alendronate (n = 18), or their combination (n = 22) for 2 years. Periodontal and oral status and mouth symptoms were recorded, and salivary analyses made at the beginning and at the end of the study. Gingival crevicular fluid (GCF) matrix metalloproteinase (MMP-8) levels were determined to address destructive events in periodontal tissue. Resting salivary flow rate decreased by 19% (P periodontal status, stimulated flow rate or composition of saliva during the study. Alendronate decreased resting salivary flow rate but otherwise HRT or alendronate separately or in combination had no effect on oral health in elderly women with osteoporosis.

  11. Effect of Alendronate with β - TCP Bone Substitute in Surgical Therapy of Periodontal Intra-Osseous Defects: A Randomized Controlled Clinical Trial.

    Science.gov (United States)

    Naineni, Rohini; Ravi, Vishali; Subbaraya, Dwijendra Kocherlakota; Prasanna, Jammula Surya; Panthula, Veerendranath Reddy; Koduganti, Rekha Rani

    2016-08-01

    Alendronate (ALN), an aminobisphosphonate, inhibits osteoclastic bone resorption and also stimulates osteogenesis. Beta-Tricalcium Phosphate (β-TCP) is an osteoconductive graft material which provides a scaffold for bone formation and also a widely used drug delivery vehicle for growth factors and antibiotics. Drug delivery vehicles, like β-TCP, improve the potency of the drugs by specific local site delivery of the drug, optimal release characteristics and easy handling. The aim of the this study was to evaluate the bone formation potential of 400μg ALN delivered in β-TCP in the treatment of periodontal intra-osseous defects. Thirty patients with periodontal defects were randomly assigned to 400μg ALN + β-TCP + Saline (test) group and β-TCP + Saline (active-control) group. Clinical parameters like Clinical Attachment Level (CAL) gain, Probing Depth (PD) reduction, post-operative Gingival Recession (GR) were assessed from the baseline, 3 months and 6 months recordings. Radiographic parameters like Linear Bone Growth (LBG), Percentage Bone Fill (%BF), and change in alveolar crest height (ACH) were assessed from baseline and 6 months radiographs. Mean measurements in the ALN test group for CAL gain (3.4 ± 0.74 mm), PD reduction (4.33 ± 0.82 mm), LBG (2.88 ± 0.88 mm), and %BF (51.98 ± 15.84%) were significantly greater with a p-value TCP bone graft material was effective in improving soft tissue parameters, inhibiting alveolar crestal resorption and enhancing bone formation, compared to β-TCP alone.

  12. A comparative study of zoledronic acid and once weekly Alendronate in the management of acute Charcot arthropathy of foot in patients with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    R Bharath

    2013-01-01

    Full Text Available Aim: The aim of this study was to assess and compare the response to two forms of treatment-immobilization with zoledronic acid injection and immobilization with oral weekly Alendronate, in patients with diabetes mellitus and acute Charcot arthropathy (CA of foot in terms of clinical and radiological parameters. Material and Methods: Patients attending the endocrinology and podiatry clinic with history of diabetes mellitus and Acute CA were taken for study. The patients were randomized into two treatment groups. Group Z-zoledronic acid injection along with total contact cast (TCC. Group A-Tab. Alendronate 70 mg. once a week till the complete clinical resolution of acute CA along with TCC. Forty-five patients were randomized and 40 of them completed the study. The primary end point was complete clinical resolution of acute CA-defined as temperature difference between normal and affected foot <1oF. Results: Among the 40 patients, 30 (75% had complete clinical resolution. The mean number of days taken for complete clinical resolution since the initiation of treatment (either Zoledronic acid or Alendronate was approximately 122 days. There was no significant difference in a number of days required for complete clinical resolution, between the two forms of therapy. There was more than 50% reduction in the visual score between the baseline and the final scan. The target to non-target ratio in the skeletal phase also showed an average of 40% reduction from the baseline to the final skeletal scintigraphy. Conclusion: Both Intravenous Zoledronic acid and oral alendronate had comparable efficacy with respect to the time taken for attaining complete clinical resolution of acute CA of foot. However, Alendronate therapy was cost effective among the two. 99m Tc MDP bone scan can be used as an adjuvant to the clinical parameters in assessing the response to therapy.

  13. Three-year experience with combined treatment with alendronate and alfacalcidol in Japanese patients with severe bone loss and osteoporotic fracture

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    Iwamoto J

    2011-06-01

    Full Text Available Jun Iwamoto1, Yoshihiro Sato2, Mitsuyoshi Uzawa3, Tsuyoshi Takeda1, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Neurology, Mitate Hospital, Fukuoka, Japan; 3Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, JapanPurpose: Combined treatment with alendronate and alfacalcidol is more useful to increase bone mineral density (BMD than alendronate or alfacalcidol alone. A retrospective study was conducted to investigate the 3-year outcome of combined treatment with alendronate and alfacalcidol in patients with severe bone loss (BMD ≤ 50% of the young adult mean and osteoporotic fracture.Methods: Thirty-four patients (six men and 28 postmenopausal women with primary or secondary osteoporosis who had been treated with alendronate and alfacalcidol for more than 3 years were analyzed. The lumbar spine or total hip BMD and bone turnover markers were monitored, and the incidence of osteoporotic fractures was assessed.Results: The urinary level of cross-linked N-terminal telopeptides of type I collagen and serum level of alkaline phosphatase significantly decreased (-42.5% at 3 months and -18.9% at 3 years, and the lumbar spine BMD, but not the total hip BMD, significantly increased (14.8% at 3 years, compared with the baseline values. However, the incidence of vertebral and nonvertebral fractures was 26.5% and 2.9%, respectively, suggesting a high incidence of vertebral fractures.Conclusion: The results of the present study suggest that combined treatment with alendronate and alfacalcidol may be useful to reduce bone turnover and increase the lumbar spine BMD in patients with severe bone loss and osteoporotic fracture. However, its efficacy against vertebral fractures appears not to be sufficient. Thus, anabolic agents such as teriparatide should be taken into consideration as first-line drugs in patients with severe osteoporosis.Keywords: osteoporosis

  14. μCT-based, in vivo dynamic bone histomorphometry allows 3D evaluation of the early responses of bone resorption and formation to PTH and alendronate combination therapy.

    Science.gov (United States)

    de Bakker, Chantal M J; Altman, Allison R; Tseng, Wei-Ju; Tribble, Mary Beth; Li, Connie; Chandra, Abhishek; Qin, Ling; Liu, X Sherry

    2015-04-01

    Current osteoporosis treatments improve bone mass by increasing net bone formation: anti-resorptive drugs such as bisphosphonates block osteoclast activity, while anabolic agents such as parathyroid hormone (PTH) increase bone remodeling, with a greater effect on formation. Although these drugs are widely used, their role in modulating formation and resorption is not fully understood, due in part to technical limitations in the ability to longitudinally assess bone remodeling. Importantly, it is not known whether or not PTH-induced bone formation is independent of resorption, resulting in controversy over the effectiveness of combination therapies that use both PTH and an anti-resorptive. In this study, we developed a μCT-based, in vivo dynamic bone histomorphometry technique for rat tibiae, and applied this method to longitudinally track changes in bone resorption and formation as a result of treatment with alendronate (ALN), PTH, or combination therapy of both PTH and ALN (PTH+ALN). Correlations between our μCT-based measures of bone formation and measures of bone formation based on calcein-labeled histology (r=0.72-0.83) confirm the accuracy of this method. Bone remodeling parameters measured through μCT-based in vivo dynamic bone histomorphometry indicate an increased rate of bone formation in rats treated with PTH and PTH+ALN, together with a decrease in bone resorption measures in rats treated with ALN and PTH+ALN. These results were further supported by traditional histology-based measurements, suggesting that PTH was able to induce bone formation while bone resorption was suppressed. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Differences of bone healing in metaphyseal defect fractures between osteoporotic and physiological bone in rats.

    Science.gov (United States)

    Thormann, Ulrich; El Khawassna, Thaqif; Ray, Seemun; Duerselen, Lutz; Kampschulte, Marian; Lips, Katrin; von Dewitz, Helena; Heinemann, Sascha; Heiss, Christian; Szalay, Gabor; Langheinrich, Alexander C; Ignatius, Anita; Schnettler, Reinhard; Alt, Volker

    2014-03-01

    Discrepancies in bone healing between osteoporotic and non-osteoporotic bone remain uncertain. The focus of the current work is to evaluate potential healing discrepancies in a metaphyseal defect model in rat femora. Female Sprague-Dawley rats were either ovariectomized (OVX, n=14) and combined with a calcium-, phosphorus- and vitamin D3-, soy- and phytoestrogen-free diet or received SHAM operation with standard diet rat (SHAM, n=14). Three months post-ovariectomy, DEXA measurement showed a reduction of bone mineral density reflecting an osteoporotic bone status in OVX rats. Rats then underwent a 3 mm wedge-shaped osteotomy at the distal metaphyseal area of the left femur stabilized with a T-shaped mini-plate and allowed to heal for 6 weeks. Biomechanical competence by means of a non-destructive three-point bending test showed significant lower flexural rigidity in the OVX rats at 3 mm lever span compared to SHAM animals (p=0.048) but no differences at 10 mm lever span. Microcomputer tomography (μCT) showed bridging cortices and consolidation of the defect in both groups, however, no measurable differences were found in either total ossified tissue or vascular volume fraction. Furthermore, histology showed healing discrepancies that were characterized by cartilaginous remnant and more unmineralized tissue presence in the OVX rats compared to more mature consolidation appearance in the SHAM group. In summary, bone defect healing in metaphyseal bone slightly differs between osteoporotic and non-osteoporotic bone in the current 3 mm defect model in both 3mm lever span biomechanical testing and histology. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. The Existential Turn: Reappraising Being and Time’s Overcoming of Metaphysics

    OpenAIRE

    Rufus Duits

    2010-01-01

    The task of this paper is to propose an answer to these relatedquestions. It amounts to an attempt to work through conceptually step by step Heidegger’s so called “overcoming of metaphysics”. It is true of course that the locution, “the overcoming of metaphysics”, does not appear in Being and Time. The discourse of the overcoming of metaphysics is held by Heidegger’s commentators to belong to a period post-dating the early work, after the so called Kehre. I shall stubbornly evade this knotty ...

  17. . I. VVEDENSKIYS’ INTERPRETATION OF THE MORAL TEACHING AND METAPHYSICS OF IMMANUEL KANT

    Directory of Open Access Journals (Sweden)

    DMITRY SAMOILOV

    2009-05-01

    Full Text Available The article is devoted to the works and ideas of Russian philosopher-kantianist, professor of philosophy at Sankt-Petersburg University A. I. Vvedenskiy. The author discusses a contribution of Vvedenskiy to the substantiation of «critical metaphysics» of the German philosopher, based on so called «moral faith». Special attention is given to problem of faith and knowledge, to understanding of postulates of practical reason as dogmata of moral faith, to «logicisation» of Kant’s conception by Vvedenskiy

  18. Duhem’s Analysis of Newtonian Method and the Logical Priority of Physics over Metaphysics

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    Eduardo Salles de Oliveira Barra

    2017-06-01

    Full Text Available This article offers a discussion of Duhemian analysis of Newton's method in the Principia considering both the traditional response to this analysis (Popper et alii and the more recent ones (Harper et alii. It is argued that in General Scholium to the Principia, Newton is not advocating what Duhem suggests in his best-known criticism, but he is proposing something very close to the establishment of a logical priority of physics over metaphysics, a familiar thesis defended by the French physicist himself.

  19. The Metaphysics of Morals: between the a priori and a practical anthropology

    Directory of Open Access Journals (Sweden)

    Maria Borges

    2017-12-01

    Full Text Available In this paper, I analyze the place of the Metaphysics of morals in the Kantian system. I claim that this work is the passage between a pure part of ethics and a practical anthropology. Although this book was first conceived to be a pure moral theory - moralia pura-, it ended up dealing with principle of applications of the moral law to sensible moral beings- philosophia moralis applicata. I also hold that the Doctrine of Virtue presents some sensible elements that are important to understand how morality affects us.

  20. Arnold Chiari Malformation With Sponastrime (Spondylar and Nasal Changes, With Striations of the Metaphyses) Dysplasia

    Science.gov (United States)

    Jeong, Je Hoon; Lee, A Leum; Cho, Sung Yoon; Jin, Dong Kyu; Im, Soo-Bin

    2016-01-01

    Abstract SPOndylar and NAsal changes, with STRIations of the Metaphyses (SPONASTRIME) dysplasia (SD) is a dwarfing autosomal recessive syndrome, characterized by a variety of clinical and radiographic features, which form the basis for diagnosis. We describe the presentation of an Arnold Chiari malformation in a patient with a clinical diagnosis of SD. The malformation was successfully treated by decompression of the foramen magnum and elevation of the cerebellum, with complete resolution of pain. We report a rare case of Arnold Chiari malformation in a patient presenting with clinical and radiographic features strongly suggestive of SD and be successfully treated. PMID:27149441

  1. Duration-dependent effects of clinically relevant oral alendronate doses on cortical bone toughness in beagle dogs.

    Science.gov (United States)

    Burr, David B; Liu, Ziyue; Allen, Matthew R

    2015-02-01

    Bisphosphonates (BPs) have been shown to significantly reduce bone toughness in vertebrae within one year when given at clinical doses to dogs. Although BPs also reduce toughness in the cortical bone when given at high doses, their effect on cortical bone material properties when given at clinical doses is less clear. In part, this may be due to the use of small sample sizes that were powered to demonstrate differences in bone mineral density rather than the bone's material properties. Our lab has conducted several studies in which dogs were treated with alendronate at a clinically relevant dose. The goal of this study was to examine these published and unpublished data collectively to determine whether there is a significant time-dependent effect of alendronate on toughness of the cortical bone. This analysis seemed particularly relevant given the recent occurrence of atypical femoral fractures in humans. Differences in the toughness of ribs taken from dogs derived from five separate experiments were measured. The dogs were orally administered saline (CON, 1ml/kg/day) or alendronate (ALN) at a clinical dose (0.2mg/kg/day). Treatment duration ranged from 3months to 3years. Groups were compared using ANOVA, and time trends analyzed with linear regression analysis. Linear regressions of the percent difference in toughness between CON and ALN at each time point revealed a significant reduction in toughness with longer exposure to ALN. The downward trend was primarily driven by a downward trend in post-yield toughness, whereas toughness in the pre-yield region was not changed relative to CON. These data suggest that a longer duration of treatment with clinical doses of ALN results in deterioration of cortical bone toughness in a time-dependent manner. As the duration of treatment is lengthened, the cortical bone exhibits increasingly brittle behavior. This may be important in assessing the role that long-term BP treatments play in the risk of atypical fractures of the

  2. [Change on the rate of children's finger metaphysics in the non-Kaschin-Beck disease areas of China].

    Science.gov (United States)

    Gao, Mei; Liu, Yunqi; Zhou, Lingwang; Liu, Hui; Deng, Qing; Song, Jiucheng; Yu, Jun

    2014-11-01

    36 non-Kaschin-Beck disease villages in five provinces including Jilin, Liaoning, Shaanxi, Shanxi and Inner Mongolia in the severe endemic areas of Kaschin-Beck disease (KBD) were selected. The aim of this project was to provide the basis showing these KBD villages had already eliminated the KBD. Fully digital versatile X-ray radiography systems(DR) was used to shoot children's right hand X-ray, in accordance with the "Kashin-Beck Disease Diagnosis Standard" (WS/T 207-2010) for diagnosis. Results indicated that children showing metaphyseal changes only appeared in 13 of the 36 villages, where the rate of change on metaphyseal was less than or equal to three percent. When KBD had been eliminated in a village, the rate of change on aged 7 to 12 children's metaphyseal would have been less than three percent.

  3. Lower trabecular volumetric BMD at metaphyseal regions of weight-bearing bones is associated with prior fracture in young girls.

    Science.gov (United States)

    Farr, Joshua N; Tomás, Rita; Chen, Zhao; Lisse, Jeffrey R; Lohman, Timothy G; Going, Scott B

    2011-02-01

    Understanding the etiology of skeletal fragility during growth is critical for the development of treatments and prevention strategies aimed at reducing the burden of childhood fractures. Thus we evaluated the relationship between prior fracture and bone parameters in young girls. Data from 465 girls aged 8 to 13 years from the Jump-In: Building Better Bones study were analyzed. Bone parameters were assessed at metaphyseal and diaphyseal sites of the nondominant femur and tibia using peripheral quantitative computed tomography (pQCT). Dual-energy X-ray absorptiometry (DXA) was used to assess femur, tibia, lumbar spine, and total body less head bone mineral content. Binary logistic regression was used to evaluate the relationship between prior fracture and bone parameters, controlling for maturity, body mass, leg length, ethnicity, and physical activity. Associations between prior fracture and all DXA and pQCT bone parameters at diaphyseal sites were nonsignificant. In contrast, lower trabecular volumetric BMD (vBMD) at distal metaphyseal sites of the femur and tibia was significantly associated with prior fracture. After adjustment for covariates, every SD decrease in trabecular vBMD at metaphyseal sites of the distal femur and tibia was associated with 1.4 (1.1-1.9) and 1.3 (1.0-1.7) times higher fracture prevalence, respectively. Prior fracture was not associated with metaphyseal bone size (ie, periosteal circumference). In conclusion, fractures in girls are associated with lower trabecular vBMD, but not bone size, at metaphyseal sites of the femur and tibia. Lower trabecular vBMD at metaphyseal sites of long bones may be an early marker of skeletal fragility in girls. Copyright © 2011 American Society for Bone and Mineral Research.

  4. Looking beyond low bone mineral density: multiple insufficiency fractures in a woman with post-menopausal osteoporosis on alendronate therapy.

    Science.gov (United States)

    Lee, P; van der Wall, H; Seibel, M J

    2007-01-01

    Insufficiency fractures occur most commonly in the pelvic girdle and in the sacrum, followed by the tibia and the femoral neck. Insufficiency fractures of the femoral diaphyses are rare, with only few reported cases in the literature. The strongest associations exist with untreated osteoporosis. We describe an unusual case of multiple insufficiency fractures in a 73-yr-old Chinese woman who presented with a 10-month history of bilateral groin pain and difficulty with walking in the absence of trauma, diagnosed 18 months following the commencement of anti-resorptive therapy with alendronate. The pathogenesis of such insufficiency fractures is poorly understood, but next to low bone mineral density and micro-architectural damage likely involves other components such as changes in bone turnover and patient-related factors (e.g. non-compliance). This case report and review of the literature draws attention to some of the challenges in the diagnosis and management of such rare insufficiency fractures.

  5. Metaphysical Modality, Modality of Predicate and the Theory of "Decisive Necessity”

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    L. Nabavi

    2010-01-01

    Full Text Available Aristotle in the Organon (1949: 9,30 a ,15-19 explicitly states that in a categorical syllogism when the minor premise is absolute (without modality operator and the major is necessary, the conclusion will be necessary too. This Aristotle's view has been the source of many conflicts and disputes in the history of logic. The famous logicians and historians of logic in the twentieth century as "Nicholas Rescher" and "Becker" believe that Aristotle's view is justifiable and defensible (at least compared to the first figure only if, the modality of major premise is considered as the property of predicate (modality de re. Today, we know very well that the modality of predicate is closely linked to Metaphysical and philosophical Modality. “Shihab al-Din al- Suhrawardi” in the theory of "Decisive (Battateh Necessity” by accepting this base, explicitly states that, in the beginning, the modality must be mentioned as a part of the predicate and then the modality of relation or copula is summarized and reduced to necessity. The modern formalization of the most important part of this theory is as follows: ("x (àAx É à Bx º ("x □ (àAx É à BxThis paper discusses the historical overview of the metaphysical modality firstly and then shows that the theory of "Decisive Necessity” is true and justified in a model of modal logic with equivalent accessibility relation and homogeneous possible world view (fixed domain.

  6. To weave the forms of Mystery: Travel, mystical and metaphysical in Sufi poetry

    Directory of Open Access Journals (Sweden)

    Daniel Del Percio

    2015-04-01

    Full Text Available Mystery is not just an enigma but a force, an impulse that gives emphasis to the real. And the ways in which this mystery unfolds are probably endless. In Sufism, travel literature is established as the quintessential poetic mysticism, where the description of incessant movement throughout the world invariably takes the value of metaphysical experience, freedom of spirit, understanding of the presence of the divine in every aspect and at every step of the journey. A mystic is a “nomadic metaphysics”, able to describe the man, the cosmos and God himself as travelers. Among the Sufi mystic poets, stands the figure of Ibn ‘Arabi, Andalusian born in Murcia in 1165 and died in Damascus in 1240. His particular metaphysics, Neoplatonist undeniable base, conceived not as a system but as a poetic movement, is a unique interface between East and West philosophies. This is observable in his works The Seals of Wisdom (Fusus al-Hikam and, especially, The splendor of the fruits of the trip (Kitab al-Isfar ‘an al-asfar nata’iy, which we will study in this work.

  7. Category of time in Christian metaphysics: Gregory of Nyssa and Maximus the Confessor

    Directory of Open Access Journals (Sweden)

    Mikhaylov, Petr

    2015-01-01

    Full Text Available In the article a problem of time is posed as an object of Christian theological reflection developed in a complicated interweaving of philosophical, cultural and religious traditions of the Mediterranean civilization. A typology of the problem is established by a correlation of the category of time with different aspects of temporality – with eternity in Antiquity, with future in Modernity and with present in the thought of different authors belonging to different epochs. The most representative thinkers of Christian metaphysic, viewed against this background, are Gregory of Nyssa (the 4th c. and Maximus the Confessor (the 7th c.. The former has successfully reinterpreted time as being-to-salvation rather than being-to-destruction. Gregory solves the problem of time by introducing an original concept of a dynamical static, or a statical dynamic, using the principle of epektasis as a general tool. In that case, time becomes a kind of spiritual practice. Maximus resolves the problem in a more traditional manner. He speaks about an overcoming of time in the perspective of divine eternity; Gregory on the contrary presupposes its transfiguration. Thereby Christian metaphysic offers a number of possibilities for a theological solution of the eternal question about time.

  8. The Metaphysic of Encounter of Space at the Meet of Persian Miniature with Renaissance Painting

    Directory of Open Access Journals (Sweden)

    abdollah aghaie

    2015-02-01

    Full Text Available Persian miniature, in its turbulent history, has been influenced by a variety of visual traditions. From the middle of the Safavid period, by increasing communications with Western countries, visual traditions of Renaissance came to Iran in different ways. Fundamental changes in Persian miniature's position and form in this period, shows that its contact with renaissance painting, has been a structural facing. The most fundamental part of this facing is seen between two disharmonious understandings of space's concept. The main question of this article is "The Why" of this facing in pictorial space. The approach of this article is to answer to this philosophical question; therefore it is tried to explain this facing in a conceptual way by surveying metaphysics foundations. For this purpose, on the one hand, using the concept of "mathematical matter" in Heidegger's philosophy, it is shown that how the elevation of modern metaphysics caused the emergence of a "quantitative" space in renaissance painting and on the other hand, by analyzing the pictorial, Persian miniature space, it is shown  that how the" qualitative" space of Iranian painting is shaped via gathering its content elements against the absolute and abstract space of renaissance painting

  9. The Metaphysic of Encounter of Space at the Meet of Persian Miniature with Renaissance Painting

    Directory of Open Access Journals (Sweden)

    abdollah aghaie

    2015-03-01

    Full Text Available Persian miniature was showing itself as dynamic during dialogue with “other” visual traditions (Specially Eastern ones. But it seems that meet renaissance painting was a kind of “encounter” to a strange matter for it. The most substantial part of this encounter is incompatibility of whose perception of space. Since that the conception of space is related to basic principle of representation. What this paper has focused on, is “the reason” of this encounter. With the help of philosophical approach this paper is trying to answer the question. So is to shed light on metaphysics foundation that make possible rise of conception of space in both side. By using the conception of “the mathematical” in Heidegger philosophy, it is shown that how ascend of modern metaphysic was lead to quantitative perception of space in renaissance painting, and at the other hand how using a qualitative perception of space in Persian miniature opposing to modern perspective of space.

  10. Darkened Counsel: The Problem of Evil in Bergson’s Metaphysics of Integral Experience

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    Anthony Paul Smith

    2016-12-01

    Full Text Available Henri Bergson's work is often presented as an optimistic philosophy. This essay presents a counter-narrative to that reading by looking to the place of the problem of evil within his integral metaphysics. For, if Bergson’s philosophy is simply optimistic, or simply derives meaning from the wholeness of experience, then it risks a theodical structure which undercuts its ability to speak to contemporary social and political problems of suffering. A theodical structure is one that, at bottom, justifies the experience of suffering by way of a concept of the whole or some concept that functions to subsume everything within it. Suffering is subsumed and given meaning by placing it within a relation, often with a telos that redeems or sublimates the experience of suffering. This takes such a singular experience such as suffering and renders it merely relative to the part it plays within the system of everything. On my reading, Bergson’s philosophy contains a supplement of what we might call pessimism or negativity inherent in his metaphysics as integral experience. This supplement undermines the theodical structure that may be assumed to undercut Bergson’s philosophy when confronted with evil or suffering and is seen most clearly in his critique of the notion of “everything.”

  11. Metaphysical green

    OpenAIRE

    Earon, Ofri

    2011-01-01

    “Sensation of Green is about the mental process like touching, seeing, hearing, or smelling, resulting from the immediate stimulation of landscape forms, plants, trees, wind and water. Sensation of Green triggers a feeling of scale, cheerfulness, calmness and peace. The spatial performance of Sensation of Green is created by a physical interaction between the language of space and the language of nature” The notion of Sensation of Green was developed through a previous study ‘Learning from th...

  12. Metaphysical green

    DEFF Research Database (Denmark)

    Earon, Ofri

    2011-01-01

    example is a tiny Danish summer house from 1918 . The second example is ‘House before House’ , in Tokyo. The third example is a prefabricated house ‘CHU’ . The analysis evaluates the characteristics of diverse tones of green – from green image to green sensation. The analysis is based on the original...... of Sensation of Green is created by a physical interaction between the language of space and the language of nature” The notion of Sensation of Green was developed through a previous study ‘Learning from the Summer House’ investigating the unique architectural characteristics of the Danish summer houses...... the Sensation of Green? Three existing examples are agents to this discussion. The first example is a Danish summer house. The other two are international urban examples. While the summer house articulates the original meaning of Sensation of Green, the urban examples illustrate its urban context. The first...

  13. Copernican Metaphysics

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    Paul Ennis

    2011-06-01

    Full Text Available In the Kritik der reinen Vernunft (1781 Kant introduced the transcendental method on a precarious footing and he never shied away from the fact that the transcendental method is structured, and I mean it in the most direct sense possible, aporetically. The aporetic element, the unstable core within Kantian thought, is the distinction between phenomenal and noumenal content in the chapter entitled "On the ground of the distinction [Unterscheidung] of all objects [Gegenstände] in general into phenomena and noumena" (Kant A236/B295-A260/B315. This distinction is noteworthy for introducing into the philosophical tradition the notion of the thing-in-itself [Ding-an-sich]. Depending on your interests this is either the most profound or absurd of ideas in our tradition. I prefer to think of it as the most productive notion in our tradition. We can see its generative function at work almost immediately when it spurred the German idealists into thinking obscenely ingenious thoughts, but the phenomenal-noumenal distinction, hereafter the aporetic distinction, remains an ever-persistent aporia for all continental thinking after Kant. In this article I want to focus on how the aporetic distinction functions in its generative capacity with an emphasis on its ontological rather than epistemological register. Considered as such I claim that it is possible to identify in the aporetic distinction a generative capacity (or logic or function that is intrinsic to both it and all thought responding to it including, or perhaps especially, the speculative responses.

  14. Metaphysical green

    DEFF Research Database (Denmark)

    Earon, Ofri

    2011-01-01

    example is a tiny Danish summer house from 1918 . The second example is ‘House before House’ , in Tokyo. The third example is a prefabricated house ‘CHU’ . The analysis evaluates the characteristics of diverse tones of green – from green image to green sensation. The analysis is based on the original...... of Sensation of Green is created by a physical interaction between the language of space and the language of nature” The notion of Sensation of Green was developed through a previous study ‘Learning from the Summer House’ investigating the unique architectural characteristics of the Danish summer houses...

  15. Treated Hypertension has No Influence on the Efficacy of Alendronate in the Therapy of Postmenopausal Osteoporosis: A Non-Randomized, Non-Blind, Controlled Prospective Study

    OpenAIRE

    Matziolis, Doerte; Drewke, Monika; Matziolis, Georg; Perka, Carsten

    2011-01-01

    Changes in hormone metabolism during menopause are involved in the development of osteoporosis and arterial hypertension. A mutual influence of these two clinical pictures is evident on the basis of pathophysiological factors. In this study, we investigated whether a drug therapy of hypertension influences the efficacy of a bisphosphonate (alendronate) in the treatment of postmenopausal osteoporosis. For this purpose, 60 female patients were enrolled in the study, 30 of them on drug treatment...

  16. Composite Biomaterial as a Carrier for Bone-Active Substances for Metaphyseal Tibial Bone Defect Reconstruction in Rats

    DEFF Research Database (Denmark)

    Horstmann, Peter Frederik; Raina, Deepak Bushan; Isaksson, Hanna

    2017-01-01

    /hydroxyapatite biomaterial (GBM) could serve as a carrier for local delivery of bone morphogenic protein-2 (BMP-2) and zoledronic acid (ZA) in a tibia defect model in rats. Empty and allograft-filled defects were used as controls. A 3 × 4-mm metaphyseal bone defect was created in the proximal tibia, and the rats were...

  17. Lower Limb Metaphyseal Bone Is Lost in Men with Coeliac Disease and Does Not Relate to Parathyroid Status

    Directory of Open Access Journals (Sweden)

    Michael W. J. Davie

    2016-01-01

    Full Text Available Aims. To investigate regional lower limb bone density and associations with weight, PTH, and bone breakdown in coeliac men. Methods. From whole body DXA scans bone mineral density (BMD was measured in 28 coeliac men, in the lower limb (subdivided into 6 regions, 3 being metaphyseal (mainly trabecular and 2 diaphyseal (mainly cortical. BMD at femoral neck (FN and lumbar spine L2–4, body weight, height, serum calcium, alkaline phosphatase, parathyroid hormone (PTH, and urinary calcium and NTx/Cr, a measure of bone breakdown, were also measured. Age matched healthy men provided values for BMD calculation of z and T scores and for biochemical measurements. Results. Low BMD z scores were found at metaphyseal regions in the leg (p<0.001 and in the FN (p<0.05. The distal metaphyseal region BMD in the leg was lower than spine or FN (p<0.05. PTH, urinary calcium/creatinine, and urinary NTx/Cr were similar to controls. Both metaphyseal and diaphyseal BMD z scores were associated with body weight (p<0.02, but not with either PTH or urinary NTx/Cr. Conclusions. Low BMD lower limb regions comprising mostly trabecular bone occur early in CD and in the absence of elevated PTH or increased bone resorption. Low BMD is associated with low body weight.

  18. Localized cortical thickening of the femoral diaphysis captured on an X-ray before alendronate therapy in two cases of atypical femoral fracture.

    Science.gov (United States)

    Iizuka, Yoichi; Takechi, Rumi; Iizuka, Haku; Omodaka, Takuya; Takagishi, Kenji

    2016-10-01

    We herein report two cases of atypical femoral fracture (AFF). X-ray examinations at the first visit of these two female patients showed a complete fracture of the femoral diaphysis diagnosed as an atypical femoral fracture (AFF). X-rays of these two cases also showed localized cortical thickening of the femoral diaphysis. Both patients had been taking alendronate for more than 3 years because of postmenopausal osteoporosis. We assumed that both of the fractures were associated with the long-term use of alendronate. However, we retrospectively identified localized cortical thickening of the femoral diaphysis on an X-ray taken before the alendronate therapy in both of these cases. Therefore, we suspected a pathogenesis of AFFs in which preexisting stress or an insufficient fracture unrelated to bisphosphonate (BP) therapy and subsequent suppression of bone turnover due to BP administration led to the occurrence of an AFF. The patient underwent surgery using intramedullary nails in both of these cases, followed by the administration of teriparatide, and they were able to walk without any support at the final follow-up examination.

  19. Localized cortical thickening of the femoral diaphysis captured on an X-ray before alendronate therapy in two cases of atypical femoral fracture

    Energy Technology Data Exchange (ETDEWEB)

    Iizuka, Yoichi [Gunma University Graduate School of Medicine, Department of Orthopedic Surgery, Maebashi, Gunma (Japan); Shibukawa General Hospital, Department of Orthopedic Surgery, Shibukawa, Gunma (Japan); Takechi, Rumi [Gunma University Graduate School of Medicine, Department of Orthopedic Surgery, Maebashi, Gunma (Japan); Gunma Cardiovascular Center, Department of Orthopaedic Surgery, Maebashi, Gunma (Japan); Iizuka, Haku; Takagishi, Kenji [Gunma University Graduate School of Medicine, Department of Orthopedic Surgery, Maebashi, Gunma (Japan); Omodaka, Takuya [Gunma University Graduate School of Medicine, Department of Orthopedic Surgery, Maebashi, Gunma (Japan); Gunma Central Hospital, Department of Orthopedic Surgery, Maebashi, Gunma (Japan)

    2016-10-15

    We herein report two cases of atypical femoral fracture (AFF). X-ray examinations at the first visit of these two female patients showed a complete fracture of the femoral diaphysis diagnosed as an atypical femoral fracture (AFF). X-rays of these two cases also showed localized cortical thickening of the femoral diaphysis. Both patients had been taking alendronate for more than 3 years because of postmenopausal osteoporosis. We assumed that both of the fractures were associated with the long-term use of alendronate. However, we retrospectively identified localized cortical thickening of the femoral diaphysis on an X-ray taken before the alendronate therapy in both of these cases. Therefore, we suspected a pathogenesis of AFFs in which preexisting stress or an insufficient fracture unrelated to bisphosphonate (BP) therapy and subsequent suppression of bone turnover due to BP administration led to the occurrence of an AFF. The patient underwent surgery using intramedullary nails in both of these cases, followed by the administration of teriparatide, and they were able to walk without any support at the final follow-up examination. (orig.)

  20. Into the White: Larry Eigner’s Meta-Physical Poetics

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    Sarah Juliet Lauro

    2014-01-01

    Full Text Available Disabled poet Larry Eigner makes striking use of the space of the page to create poetry that operates in a visual as well as linguistic register. Many critics have read Eigner’s oeuvre in light of his physical condition, but no scholar has previously looked to the parallels between the Black Mountain artists’ experiments in abstraction and Black Mountain poet Larry Eigner’s work, though the same influences are clearly evident. Working collaboratively and interdisciplinarily, the authors combine their expertise in the disciplines of literature and art history, reading both the words on the page and the page as picture, in a manner that engages specifically with phenomenological philosophy, to explicate how these poems work on the body of the reader.   Key words: embodiment, abstraction, poetics, typography, metaphysics, phenomenology

  1. KIEVAN PERIOD OF V. V. ZENKOVSKY’S CREATIVE WORK: REFORM OF METAPHYSICAL BACKGROUND OF PSYCHOLOGY

    Directory of Open Access Journals (Sweden)

    V. M. LETTSEV

    2006-06-01

    Full Text Available The article is devoted to the Kiev’s period of creative work of V.V. Zenkovsky, re-markable Christian philosopher, psychologist and pedagogue. The main point of interest of the thinker of that time was a philosophical psychology, i.e. a branch of science direct-ed to the source of psychics and seeking to make clear the nature and basis of mental re-ality. Zenkovsky’s defense of the idea of substantiality of soul and original interpretation of the problem of psychophysical interaction brought him to the deep reform of meta-physical background of psychology. This also became the conceptual basis for his latest investigations in the spheres of pedagogy, theology and pure philosophy

  2. Stress and human spirituality 2000: at the cross roads of physics and metaphysics.

    Science.gov (United States)

    Seaward, B L

    2000-12-01

    Although stress is defined as a perceived threat, the implications of stress go well beyond physical well-being. In the words of Carl Jung, "Every crisis is a spiritual crisis." Western science, so strongly influenced by the Cartesian Principle of Reductionism, has ignored the essence and significance of human spirituality in the health and healing process. Holistic healing honors the integration, balance, and harmony of mind, body, spirit, and emotions, where the whole is greater than the sum of the parts. Stress (unresolved issues of anger and fear) chokes the human spirit, the life force of human energy, which ultimately affects the physical body. From the perspectives of both physics and metaphysics, stress is a disruption in the state of coherence between the layers of consciousness in the human energy field. The emerging paradigm of health reunites mind, body, and spirit, and considers health as a function of coherence among the energy levels of these components.

  3. Migraine and Metaphysics: Sentinels of science in nineteenth-century physics

    DEFF Research Database (Denmark)

    Kjærgaard, Peter C.

    2010-01-01

    In an old boy network of nineteenth-century natural philosophers, all with a background in mathematics from the University of Cambridge, a conspicuous aversion ruled against metaphysics. Within these circles it produced a strong compulsion to define the limits of genuine scientific endeavour....... These attempts were primarily directed against unfounded hypotheses trying to encompass the indefinite and all sorts of aprioristic knowledge, except mathematics. Either by emphasizing the formal aspects of science or linking the formalism to useful applications in the shape of physical models and demands......, if at all, yield a coherent worldview? In this article I will answer that question by looking at how a group of outspoken and influential Cantabrigian Wranglers were carving out intellectual, cultural and political space for themselves and their scientific endeavours while unremittingly patrolling...

  4. Mechanical Failure of Revision Knee Prosthesis at both Femoral and Tibial Modular Metaphyseal Stem Junctions.

    Science.gov (United States)

    Woodgate, Ian G; Rooney, John; Mulford, Johnathan S; Gillies, R Mark

    2016-01-01

    This is a report of a mechanical failure of an S-ROM revision total knee prosthesis. The prosthesis was used as a revision implant following deep peri-prosthetic infection in a morbidly obese male. The prosthesis failed on both the femoral and tibial sides at the modular metaphyseal stem junctions and required a further revision using the same type of implant after infection was excluded. A 57 year old male had previously undergone a left total knee arthroplasty in 1999 for osteoarthritis. He acquired a late deep peri-prosthetic infection with a multi-resistant Staphylococcus epidermidis. The organism was sensitive to vancomycin and rifampicin. A two stage revision was undertaken after clinical signs of infection had resolved and blood parameters had normalized. Intra-operative gram stain was negative for micro-organisms and frozen section of deep tissue was less than five polymorphs per high power field. A cemented S-ROM prosthesis was implanted using a coronal tibial osteotomy and a lateral release for exposure. After three years of the second stage of revision, the patient again presented to the orthopaedic department after reportedly falling on a wet floor six weeks ago. Radiographically, there was a broken tibial wire, osteolysis and pedestal formation around both the femoral and distal tibial stem extensions. The prosthesis was bent at the proximal tibial sleeve and stem junction. The prosthesis was considered loose with mechanical failure. At implant removal, it was noted that the femoral and tibial components at the modular metaphyseal sleeve-stem junction were fractured. Surgeons should be cautious in the use of these implants in morbidly obese patients where the stresses generated maybe above the yield stress of the material and the frictional forces that may overcome the modular taper junction's locking mechanism.

  5. Trabecular Bone Score in Patients With Chronic Glucocorticoid Therapy-Induced Osteoporosis Treated With Alendronate or Teriparatide.

    Science.gov (United States)

    Saag, Kenneth G; Agnusdei, Donato; Hans, Didier; Kohlmeier, Lynn A; Krohn, Kelly D; Leib, Edward S; MacLaughlin, Edmund J; Alam, Jahangir; Simonelli, Christine; Taylor, Kathleen A; Marcus, Robert

    2016-09-01

    To determine the effect of alendronate (ALN) and teriparatide on trabecular bone score (TBS) in patients with glucocorticoid-induced osteoporosis. Patients with chronic glucocorticoid therapy-induced osteoporosis (median 7.5 mg/day prednisone equivalent for ≥90 days) were randomized to receive oral ALN 10 mg/day (n = 214) or subcutaneous teriparatide 20 μg/day (n = 214) for 36 months; 118 patients in the ALN group and 123 patients in the teriparatide group completed treatment. Dual x-ray absorptiometry (DXA) results for 53 patients receiving ALN and 56 patients receiving teriparatide who had DXA scans with adequate resolution to perform TBS analysis and completed 36 months of therapy were blindly analyzed for TBS at baseline and 3, 6, 12, 18, 24, and 36 months. In teriparatide-treated patients, TBS was significantly increased at 18 months compared to baseline, and by 36 months had increased 3.7% (P teriparatide, respectively. In patients with glucocorticoid-induced osteoporosis, both ALN and teriparatide increased lumbar spine BMD. However, trabecular bone score significantly increased with teriparatide but did not significantly change with ALN. The pathogenesis of glucocorticoid-induced osteoporosis is predominantly reduced bone formation. TBS may represent a sensitive measure to discriminate treatment effects of an anabolic versus an antiresorptive drug in glucocorticoid-induced osteoporosis. © 2016, American College of Rheumatology.

  6. Is it possible to delete a philosophical consciousness? Metaphysical aspects of Ssearle’s neurobiological approach of free will

    Directory of Open Access Journals (Sweden)

    Grujić Snežana

    2016-01-01

    Full Text Available In an effort to adjust his theoretical comprehension to the existing natural-scientific paradigm, Searle develops neurobiological naturalism, an approach which should rely on basic facts obtained from the neuroscience researches of living organisms when solving basic philosophical problems. This paper briefly presents this view’s theory leading to the argumentation that Searle’s point of view is of metaphysical characteristics which is exactly what he was trying to avoid. The metaphysical character of Searle’s neurobiological naturalism has been seen through the problem of free will resulting from his understanding of consciousness. The argumentation is based on an analysis of the concepts, the gap and the self, as well as on possible solutions of the problem of free will (hypothesis 1 and 2.

  7. Technology and ecology. From ethics to Metaphysics, from negation of limits to the disclaimer of man

    Directory of Open Access Journals (Sweden)

    Luca Valera

    2016-02-01

    Full Text Available The impact of technologies on human action is a main issue in contemporary philosophy. In this paper I point out some of the key metaphysical and ethical issues of this ongoing technological revolution, highlighting an important change of paradigm: the metaphysical issue now arises within ethics. Today’s technology, indeed, opens up new possibilities: a man overcoming it is now at least conceivable, if not fully viable. The category of dependence is thus replaced by that of auto poiesis, in order to achieve perfection and to eliminate boundaries. In this regard, the technological possibilities are annihilating the «outdated» human subject, as it is profoundly determined by its limits. On the contrary, I show how the concept of limit may be a good starting point for an ontology of difference/identity: the limit, thus, allows us to recognize the identity and the difference. In contemporary environmentalism we can observe the opposite tendency: every individual —even the human being—is functional to the preservation of life (Ecosystem, and it can be, thus, sacrificed. In this regard, the overcoming of human nature coincides with the victory of Nature, i.e., of Life: life is to be protected, at all times, whether it is human or non-human life. The main reason of this fact is our naïve concept of Nature and our conception of the human being as a dangerous agent; the awareness of a great destructive power gained, however, cannot be a sufficient reason to consider the human being a cancer on the planet. In order to reestablish a proper relationship of man with himself and with the world, we finally need to develop an adequate anthropology, which takes into account the human person’s natural and spiritual nature, its limitations and its limits.

  8. Foucault: itinerário metafísico? = Foucault: metaphysical itinerary?

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    Atílio Butturi Junior

    2010-07-01

    Full Text Available O presente artigo pretende discutir, a partir de uma perspectiva heideggeriana, a hipótese contra-foucauldiana de uma metafísica presente no discurso imanentista da arqueogenealogia. Para tanto, constrói um breve itinerário daquilo que se considera o “romantismo foucauldiano”: aponta, primeiramente, a crítica derridiana de umacategorização transcendental do objeto loucura e faz uma contraposição entre esta e as considerações de loucura como ausência de obra; faz um breve recorte dos debates da literaridade e seu abandono, seguindo a retomada do discurso da enkrateia; finalmente, traça um paralelo entre os apontamentos iniciais da arqueologia e a problemática da subjetivação presente nos últimos cursos, centrados no conceito de parrêsia. O fundamental, portanto, é fazer notar uma relação permanente com a metafísica heideggeriana, tanto no que se refere ao projeto de destruição quanto na exigência de um questionamento que transcenda os limites da imanência.Departing from a Heideggerian standpoint, the present article aims at discussing the contra-Foucauldian hypothesis of a metaphysics present in the immanentist discourse of archaeogenealogy. With a view toachieving the goal proposed, the paper builds a brief itinerary of what is considered “Foucauldian romanticism”. Initially, it draws on the Derridian critique of a transcendental categorization of ‘madness’ and opposes it to accounts of madness as absence of labor.Then, the paper offers a brief account of debates on literalness and their abandoning, following the renewed take-over of the enkrateia discourse. Finally, based on the concept of parrêsia, the article establishes some comparisons between the initial findings of archaeology and the issue of subjectivization present in the last courses. Thus, what is fundamental is to render noticeable a permanent relationship with Heideggerian metaphysics, in whatconcerns both the destruction project and the

  9. Unusual bone dysplasia featuring severe platyspondyly and vertebral 'coronal cleft' in infancy, and changes of metaphyseal chondrodysplasia in childhood

    International Nuclear Information System (INIS)

    Currarino, G.; Texas Univ., Dallas

    1986-01-01

    This is the report of a boy who presented at birth with severe generalized platyspondyly, a vertebral ''coronal cleft'', and an abnormal configuration of the pelvis with short and broad iliac and ischial bones and horizontal acetabular roofs. The rest of the skeleton was normal. In the ensuing years the vertebral bodies and pelvis assumed a near normal configuration, but the patient developed changes of metaphyseal chondrodysplasia in the long bones of the lower limbs with progressive shortness of stature. (orig.)

  10. A Japanese-American Sam Spade: The Metaphysical Detective in Death in Little Tokyo, by Dale Furutani

    OpenAIRE

    Portilho Carla

    2017-01-01

    The aim of this essay is to discuss the legacy of the roman noir in contemporary detective fiction produced outside the hegemonic center of power, here represented by the novel Death in Little Tokyo (1996), written by Japanese-American author Dale Furutani. Starting from the concept of the metaphysical detective (Haycraft 76; Holquist 153-156), characterized by deep questioning about narrative, interpretation, subjectivity, the nature of reality and the limits of knowledge, this article propo...

  11. THE THIRD MAN ARGUMENT(PARM.132A1-B2-A ‘PURELY’ METAPHYSICAL EXERCISE?

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    Marcus Nabielek

    2013-11-01

    Full Text Available All commentators of the ‘Parmenides’ agree that the Third Man argument, 132a-b2, raises a difficulty for Plato’s theory of forms. Many commentators, following Vlastos, hold that the argument’s infinite regress is vicious for epistemic reasons. Rickless contends that the infinite regress is vicious for exclusively metaphysical reasons. This essay intends to show that Rickless’ interpretation is inadequate, as well as to vindicate Vlastos’ interpretation.

  12. Evaluation of the topical effect of alendronate on the root surface of extracted and replanted teeth. Microscopic analysis on rats' teeth.

    Science.gov (United States)

    Lustosa-Pereira, Adriana; Garcia, Roberto Brandão; de Moraes, Ivaldo Gomes; Bernardineli, Norberti; Bramante, Clovis Monteiro; Bortoluzzi, Eduardo Antunes

    2006-02-01

    The treatment of choice for tooth avulsion is replantation. The ideal replantation should be realized as quickly as possible, or at least, the avulsed tooth should be kept in an adequate solution to preserve the periodontal ligament attached to the root. If that is not possible, treatment of the radicular surface should be done in order to prevent radicular resorption. The purpose of this study was to test sodium alendronate as a substance for topical treatment of the radicular surface of avulsed teeth in an attempt to prevent the occurrence of dental resorptions. Fifty-four rat maxillary right central incisors were extracted and replanted. Group I--extra-alveolar dry period of 15 min, intracanal dressing with calcium hydroxide (CALEN, S.S. White, Artigos Dentários LTDA, Rio de Janeiro, Brazil) and replantation; Groups II and III - extra-alveolar dry periods of 30 and 60 min, respectively, immersion in 1% sodium hypochlorite for 30 min for removal of the periodontal ligament, washing in saline solution for 5 min, and treatment of the radicular surface with 3.2 mg/l sodium alendronate solution for 10 min. Intracanal dressing with calcium hydroxide and replantation followed. At 15, 60, and 90 days post-reimplantation, the animals were killed and the samples obtained and processed for microscopic analysis. The results indicated that sodium alendronate was able to reduce the incidence of radicular resorption, but not of dental ankylosis. No significant differences were observed regarding variations in the extra-alveolar periods among the groups.

  13. Effects of odanacatib on BMD and safety in the treatment of osteoporosis in postmenopausal women previously treated with alendronate: a randomized placebo-controlled trial.

    Science.gov (United States)

    Bonnick, Sydney; De Villiers, Tobias; Odio, Alberto; Palacios, Santiago; Chapurlat, Roland; DaSilva, Carolyn; Scott, Boyd B; Le Bailly De Tilleghem, Celine; Leung, Albert T; Gurner, Deborah

    2013-12-01

    Odanacatib (ODN) is a selective cathepsin K inhibitor being developed to treat osteoporosis. The effects of ODN were evaluated on bone mineral density (BMD), biochemical markers of bone turnover, and safety in patients previously treated with alendronate. This was a randomized, double-blind, placebo-controlled, 24-month study. The study was conducted at private or institutional practices. Postmenopausal women (n = 243) ≥ 60 years of age with low BMD at the total hip, femoral neck, or trochanter (T-score ≤-2.5 but >-3.5 without prior fracture or ≤-1.5 but >-3.5 with prior fracture) on alendronate for ≥ 3 years. The intervention included ODN 50 mg or placebo weekly. The primary end point was percentage change from baseline of femoral neck BMD at month 24. BMD was assessed by dual-energy x-ray absorptiometry at baseline and 6, 12, and 24 months. Biochemical markers of bone turnover (serum C-telopeptides of type 1 collagen, urinary N-telopeptides of type 1 collagen, serum bone specific alkaline phosphatase, and serum N-terminal propeptide of type 1 collagen) were measured at baseline and 3, 6, 12, 18, and 24 months. In the ODN group, BMD changes from baseline at the femoral neck, trochanter, total hip, and lumbar spine at 24 months (1.7%, 1.8%, 0.8%, and 2.3%, respectively) were significantly different from the placebo group. ODN significantly decreased urinary N-telopeptides of type 1 collagen to creatinine ratio and significantly increased serum N-terminal propeptide of type 1 collagen compared with placebo. Serum C-telopeptides of type 1 collagen was unexpectedly increased with ODN treatment. The safety profile appeared similar between groups. ODN provided incremental BMD gains in osteoporotic women after alendronate treatment.

  14. Postnonclassical analysis of educational sessions in the aspect of ukrainian life: metaphysics stories

    Directory of Open Access Journals (Sweden)

    I. Z. Sklovs’kyy

    2015-12-01

    Full Text Available Identification criteria metaphysical information culture as Postnonclassical understanding of the roles of government and society, the individual that learns the spirit of patriotism as the Millennium updated understanding of ethnic space of post-totalitarian era Ukraine. Economy hopes limits schematism «cog», and then the society honors the professional honesty and integrity demands on themselves and others that are part of mutual responsibility for the future Ukrayiny.V the same time among the leading educators and philosophers of our country took place more or less complete realization that the traditional education system can not provide the curved shape needs to be adequate ekonomiky.Schob modern life, destiny and creativity of our outstanding and philosophers and teachers of the past chasivTse very important in the context of transcendent order to discover the spirit Postnonclassical knowledge as spiritual activity, where turns its commitment to anthropological and historical knowledge - it also shows activity of civilized patriots that in the future the future become Europeans to overcome the level of stereotyping spirit malorossiyskoy menshovartosnosti that should strongly reject evolutionary way their knowledge, this corresponds to the time civilizational and evropeyskyh changes at the turn of the millennium.

  15. The uncertain foundation of neo-Darwinism: metaphysical and epistemological pluralism in the evolutionary synthesis.

    Science.gov (United States)

    Delisle, Richard G

    2009-06-01

    The Evolutionary Synthesis is often seen as a unification process in evolutionary biology, one which provided this research area with a solid common theoretical foundation. As such, neo-Darwinism is believed to constitute from this time onward a single, coherent, and unified movement offering research guidelines for investigations. While this may be true if evolutionary biology is solely understood as centred around evolutionary mechanisms, an entirely different picture emerges once other aspects of the founding neo-Darwinists' views are taken into consideration, aspects potentially relevant to the elaboration of an evolutionary worldview: the tree of life, the ontological distinctions of the main cosmic entities (inert matter, biological organisms, mind), the inherent properties of self-organizing matter, evolutionary ethics, and so on. Profound tensions and inconsistencies are immediately revealed in the neo-Darwinian movement once this broader perspective is adopted. This pluralism is such that it is possible to identify at least three distinct and quasi-incommensurable epistemological/metaphysical frameworks as providing a proper foundation for neo-Darwinism. The analysis of the views of Theodosius Dobzhansky, Bernhard Rensch, and Ernst Mayr will illustrate this untenable pluralism, one which requires us to conceive of the neo-Darwinian research agenda as being conducted in more than one research programme or research tradition at the same time.

  16. Terrorists: analogies and differences with mental diseases. A phenomenological-metaphysical perspective.

    Science.gov (United States)

    Fisogni, Primavera

    2010-01-01

    Are islamic terrorists insane? International scholars generally concede that Al Qaeda members are not mentally ill. But, until now, there has not been a shared consensus and a strong argument that can prove it. This paper intends to throw light on the specific dehumanization of terrorists and to show that they are always responsible for their acts, unlike those who are affected by mental diseases. The members of Al Qaeda deny the world of life and take the distance from its sense and value: in their perspective only subversive action makes sense. However they always maintain a transcendent relation with the world (I-you; I-it). Persons with serious mental diseases have generally lost the sense of their self and the transcendence with the world. Terrorists and people with mental illness share a common separation from the world of life: one is voluntary, the other is the consequence of a number of factors (biological, social, etc.). Terrorists and psychotics have nevertheless something in common: the deprivation of the self. A loss of being that--I argue--is at the origin of the ordinariness of terrorists and the experience of void in psychotics. Two symptoms that reveal the condition of an intimate dryness, from a phenomenological and a metaphysical point of view as a consequence of a distorted relation with the world of life. I shall discuss how ordinariness is strictly related with the blurring definition of terrorism.

  17. Naledi: An example of how natural phenomena can inspire metaphysical assumptions

    Directory of Open Access Journals (Sweden)

    Francois Durand

    2017-09-01

    Full Text Available A new fossil site was discovered in the Rising Star Cave in 2013 in the Cradle of Humankind in South Africa. This site which has yielded 1550 hominin bones so far is considered to be one of the richest palaeoanthropological sites in the world. The deposition of the fossils in a remote part of the cave system, approximately 100 m from the entrance, has resulted in a great deal of speculation. The relative inaccessibility of the site and the number of fossil bones it contained and the fact that virtually all these bones were those of a single species of hominid led to the conclusion that the bones were not deposited because of natural sedimentary processes, but that these phenomena were evidence of purposeful disposal or even burial of the dead by hominins. If this assumption is true, it would be the earliest evidence of a metaphysical awareness in humankind. The tenuous evidence on which this hypothesis rests will be discussed and a more plausible alternative explanation where water and gravity were responsible for the deposition of the remains is forwarded.

  18. From Kant to Schelling to Process Metaphysics: On the Way to Ecological Civilization

    Directory of Open Access Journals (Sweden)

    Arran Gare

    2011-11-01

    Full Text Available The post-Kantians were inspired by Kant’s Critique of Judgment to forge a new synthesis of natural philosophy, art and history that would overcome the dualisms and gulfs within Kant’s philosophy. Focusing on biology and showing how Schelling reworked and transformed Kant’s insights, it is argued that Schelling was largely successful in laying the foundations for this synthesis, although he was not always consistent in building on these foundations. To appreciate this achievement, it is argued that Schelling should not be interpreted as an idealist but as a process metaphysician; as he claimed, overcoming the oppositions between idealism and realism, spiritualism and materialism. It is also argued that as a process metaphysician, Schelling not merely defended an organic view of nature but developed a theory of emergence and a new conception of life relevant to current theoretical and philosophical biology. This interpretation provides a defense of process metaphysics as the logical successor to Kant’s critical philosophy and thereby as the most defensible tradition of philosophy up to the present. It provides the foundations for post-reductionist science, reconciling the sciences, the arts and the humanities, and provides the basis for a more satisfactory ethics and political philosophy. Most importantly, it overcomes the nihilism of European civilization, providing the foundations for a global ecological civilization.

  19. Heidegger, environmental ethics, and the metaphysics of nature: inhabiting the earth in a technological age

    Energy Technology Data Exchange (ETDEWEB)

    Foltz, B.V.

    1985-01-01

    Previous studies of philosophical problems concerning the human disruption and destruction of the natural environment have tended to presuppose (a) that the problems themselves are adequately defined by the natural sciences, and (b) that the proper philosophical approach is by means of an ethics that restricts itself to determining the character and limits of moral obligation. This dissertation (a) argues that modern natural science, which is expected to define the problem of an environmental crisis, itself employs a concept of nature, derived from the metaphysical tradition, that is generative of the very problems to be resolved; (b) develops, on the basis of Heidegger's rethinking of the traditional question of being, a more adequate understanding of nature; and (c) shows that the resolution of these problems can best be accomplished by means of a more broadly conceived ethics that closes the breach between theory and praxis by articulating an appropriate manner of comportment toward entities as a whole (and not soley human, nor even sentient, entities) which displays an integration of thought and action, and which Heidegger calls inhabitation or dwelling.

  20. The Existential Turn: Reappraising Being and Time’s Overcoming of Metaphysics

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    Rufus Duits

    2010-06-01

    Full Text Available The task of this paper is to propose an answer to these relatedquestions. It amounts to an attempt to work through conceptually step by step Heidegger’s so called “overcoming of metaphysics”. It is true of course that the locution, “the overcoming of metaphysics”, does not appear in Being and Time. The discourse of the overcoming of metaphysics is held by Heidegger’s commentators to belong to a period post-dating the early work, after the so called Kehre. I shall stubbornly evade this knotty issue of Heidegger interpretation here. For my purposes it suffices merely if our understanding ofBeing and Time, its content, intent and consequence, can be deepened or expanded if it is read in the light of the task of overcoming metaphysics—or at least in the light of that task as it is to be conceived in the context I shall present here. What is to be understood by the phrase “the overcoming of metaphysics”?

  1. Treatment of distal tibia metaphyseal fractures; plating versus intramedullary nailing: a systematic review of recent evidence.

    Science.gov (United States)

    Iqbal, H J; Pidikiti, P

    2013-09-01

    Treatment of distal tibia metaphyseal fractures is challenging. The purpose of this study was to systematically review the recent literature regarding management of extra-articular distal tibia fractures with a view to compare the outcome of intramedullary nailing with plate fixation. Advanced literature search was performed using Medline (Ovid), Embase (Ovid) and Cochrane databases. Data were extracted regarding number of participants, fracture fixation devices, percentage of open fractures, malunions, nonunions, wound infections and metal removal etc. After inclusion, exclusion criteria, two RCTs and four retrospective comparative studies were deemed suitable for this review. The overall results showed relatively higher rate of infection in plating group as compared to intramedullary nailing. However malalignment was more common with intramedullary nailing. Both techniques can provide adequate treatments in appropriately selected patients. None of the studies had sufficient power to show clinically significant difference. Further studies are required to compare new locking plates with intramedullary nails. Copyright © 2013 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

  2. [Critical Review of Gender Ideology in the Light of Metaphysical Realism].

    Science.gov (United States)

    Burguete Miguel, Enrique Eduardo

    2018-01-01

    The implementing of gender ideology in the imaginary of current welfare-state societies owes much to a long process in the history of thought, which has culminated in an accommodation of post-feminist discourse. This paper sets out the epistemological principles that are present in gender ideology, as a response to both its recent and more-remote antecedents. It is furthermore framed by an urge for emancipation that began with medieval scholasticism, the latest manifestation of which lies in the post-structuralist deconstructionism that outlines the concept of queer. This concept has dissociated the categories of sex and gender to the point of making them irrelevant for the determination of sexual identity, leaving the latter susceptible to being infinitely de- and reconstructed. This article also reviews the liberal-hedonistic context of the new postmodern setting, while showing how the concepts of ″a subjective feeling of happiness″ and ″a life fulfilled″ do not express similar content. The paper goes on to challenge the theory of gender from the perspective of metaphysic realism; stressing that the human being only appears as a real person via the possibility of anticipating another's contemplation, thereby cancelling out the abstraction of pure subjectivity. It finally offers its conclusions, with certain substantive recommendations in the field of education.

  3. The susceptive alendronate-treatment timing and dosage for osteogenesis enhancement in human bone marrow-derived stem cells.

    Directory of Open Access Journals (Sweden)

    Chih-Hsiang Chang

    Full Text Available Recent studies indicated that alendronate enhanced osteogenesis in osteoblasts and human bone marrow-derived stem cells. However, the time- and dose-dependent effects of Aln on osteogenic differentiation and cytotoxicity of hBMSCs remain undefined. In present study, we investigated the effective dose range and timing of hBMSCs. hBMSCs were treated with various Aln doses (1, 5 and 10 µM according to the following groups: group A was treated with Aln during the first five days of bone medium, groups B, C and D were treated during the first, second, and final five days of osteo-induction medium and group E was treated throughout the entire experiment. The mineralization level and cytotoxicity were measured by quantified Alizarin Red S staining and MTT assay. In addition, the reversal effects of farnesyl pyrophosphate and geranylgeranyl pyrophosphate replenishment in group B were also investigated. The results showed that Aln treatment in groups A, B and E enhanced hBMSC mineralization in a dose-dependent manner, and the most pronounced effects were observed in groups B and E. The higher dose of Aln simultaneously enhanced mineralization and caused cytotoxicity in groups B, C and E. Replenishment of FPP or GGPP resulted in partial or complete reverse of the Aln-induced mineralization respectively. Furthermore, the addition of FPP or GGPP also eliminated the Aln-induced cytotoxicity. We demonstrated that hBMSCs are susceptible to 5 µM Aln during the initiation stage of osteogenic differentiation and that a 10 µM dose is cytotoxic.

  4. Effect of alendronate on the progression of periodontitis induced by Porphyromonas gingivalis and Fusobacterium nucleatum: a study in rats.

    Science.gov (United States)

    Storrer, Carmen L Mueller; Deliberador, Tatiana Miranda; Giovanini, Allan Fernando; Crivellaro, Viviane; Zielak, João Cesar; Romito, Giuseppe Alexandre

    2016-12-01

    The study aimed to investigate the effect of alendronate (ALN) on the inhibition of alveolar bone loss in experimental periodontitis in Wistar rats. Periodontitis was induced by oral inoculation of Porphyromonas gingivalis with Fusobacterium nucleatum. The rats (n = 80) were randomized as follows: negative control (n = 10); positive control (n = 10); ALN groups: test 8 (n = 10), test 12 (n = 10), and test 16 (n = 10); and placebo groups: control 8 (n = 10), control 12 (n = 10), and control 16 (n = 10). Two milligrams per kilogram of ALN or placebo was administered twice weekly for 8, 12, and 16 weeks. Bone loss was determined by morphological and histological analyses. One independent, blinded examiner (ICC, 0.91) performed the measurements. The distance from the cement enamel junction to the alveolar bone crest of the second lower molar was measured: distal-vestibular (d), furca (f), mesial-vestibular (h), and area. Histometry was performed on the second contralateral molar. Sections (6 μm) were used to determine the furcation bone area (A-FB). The following statistical analyses were conducted: Mann-Whitney and Kruskal-Wallis. PC group developed periodontitis (p  0.05). ALN was effective against bone loss in relation to A-FB after 12 weeks (p < 0.0001). According to the methodology used, the results suggest that oral administration of ALN could influence alveolar bone loss in rats submitted to experimental periodontitis. ALN could be a potential therapeutic approach when associated with periodontal treatment.

  5. Long-term treatment with alendronate increases the surgical difficulty during simple exodontias – an in vivo observation in Holtzman rats

    Directory of Open Access Journals (Sweden)

    Conte-Neto Nicolau

    2012-07-01

    Full Text Available Abstract Background Atraumatic teeth extractions protocols are highly encouraged in patients taking bisphosphonates (Bps to reduce surgical trauma and, consequently, the risk of jaws osteonecrosis development. In this way, this paper aims to report the findings of increased surgical difficulty during simple exodontias in animals treated with bisphosphonates. Methods Sixty male Holtzman rats were randomly distributed into three groups of 20 animals and received daily subcutaneous administration of 1 mg/kg (AL1 or 3 mg/kg (AL3 of alendronate or saline solution (CTL. After 60 days of drug therapy all animals were submitted to first lower molars extractions under general anesthesia. Operatory surgical time and the frequency of teeth fractures were measured as principal outcomes and indicators of surgical difficulty degree. Results Animals treated with alendronate (AL1 and AL3 were associated to higher operatory times and increased frequency of teeth fractures compared to match controls. Conclusions The bisphosphonate therapy may be associated with an increased surgical difficulty and trauma following simple exodontias protocols, which is considered a critical issue when it comes to osteonecrosis development.

  6. The Possibility of a New Metaphysics for Quantum Mechanics from Meinong's Theory of Objects

    Science.gov (United States)

    Graffigna, Matías

    According to de Ronde it was Bohr's interpretation of Quantum Mechanics (QM) which closed the possibility of understanding physical reality beyond the realm of the actual, so establishing the Orthodox Line of Research. In this sense, it is not the task of any physical theory to look beyond the language and metaphysics supposed by classical physics, in order to account for what QM describes. If one wishes to maintain a realist position (though not nave) regarding physical theories, one seems then to be trapped by an array of concepts that do not allow to understand the main principles involved in the most successful physical theory thus far, mainly: the quantum postulate, the principle of indetermination and the superposition principle. If de Ronde is right in proposing QM can only be completed as a physical theory by the introduction of `new concepts' that admit as real a domain beyond actuality, then a new ontology that goes beyond Aristotelian and Newtonian actualism is needed. It was already in the early 20th century that misunderstood philosopher Alexius von Meinong proposed a Theory of Objects that admits a domain of being beyond existence-actuality. Member of the so called `School of Brentano', Meinong's concerns were oriented to provide an ontology of everything that can be thought of, and at the same time an intentionality theory of how objects are thought of. I wish to argue that in Meinong's theory of objects we find the rudiments of the ontology and the intentionality theory we need to account for QM's basic principles: mainly the possibility of predicating properties of non-entities, or in other words, the possibility of objectively describing a domain of what is, that is different from the domain of actual existence.

  7. An Analysis of the Agency and Providence in Platonic, Aristotelian and Avicennan Metaphysics

    Directory of Open Access Journals (Sweden)

    S. Mahdi Emamijomeh

    2014-01-01

    Full Text Available The questions as to whether the cosmic order of this world is based on action/agent or not? And if an agent is involved and the world and what it contains have to be seen as action, could we declare the cosmic order a providential order? are among the problems which have always occupied the mind of philosophers.      Reading through Platonic corpse leads us to the conclusion that he has founded his metaphysics upon the very idea of world of ideas. According to his works and words, Plato is a proponent of the theory of ideas. As a matter of fact, Plato's metaphysics lies in the theory of ideas. Plato illustrates the general makeup of the world of ideas and the way sensible objects stand in relation with the beings dwelling in the latter world by the well-known cave allegory in the seventh book of Republic. In his view, whatever we find around ourselves not only are not authentic realities but rather they are merely shadows of the truth. Every phenomenon has an essence or reality which is known as its form. The idea of Good overshadows the other ideas insofar as these latter ideas or forms are seen as the effects of the former. It seems we can take God, the One, Absolute Good, Absolute Beauty and Good in itself as expressions of the same reality which Plato has used in different contexts through his works. Along these terms some other notions have also been brought up like intellect, divine intellect, Demiurge, ideas and the particulars of material world. By explaining Plato's taking of these notions and terms, we believe, one can discover Platonic ontological system.    In Republic, Plato argues that God is the creator of ideal bed and all other things, and he is the creator of intelligible entities (ideas. The One or reality as a whole not only contains ideas but the spirit too. The One is the final principle and the source of ideas and is beyond all human attributes. Having said these, it is not clear how reason gets itself related to the

  8. An Analysis of the Agency and Providence in Platonic, Aristotelian and Avicennan Metaphysics

    Directory of Open Access Journals (Sweden)

    Vahideh Hadad

    2013-12-01

    Full Text Available The questions as to whether the cosmic order of this world is based on action/agent or not? And if an agent is involved and the world and what it contains have to be seen as action, could we declare the cosmic order a providential order? are among the problems which have always occupied the mind of philosophers.      Reading through Platonic corpse leads us to the conclusion that he has founded his metaphysics upon the very idea of world of ideas. According to his works and words, Plato is a proponent of the theory of ideas. As a matter of fact, Plato's metaphysics lies in the theory of ideas. Plato illustrates the general makeup of the world of ideas and the way sensible objects stand in relation with the beings dwelling in the latter world by the well-known cave allegory in the seventh book of Republic. In his view, whatever we find around ourselves not only are not authentic realities but rather they are merely shadows of the truth. Every phenomenon has an essence or reality which is known as its form. The idea of Good overshadows the other ideas insofar as these latter ideas or forms are seen as the effects of the former. It seems we can take God, the One, Absolute Good, Absolute Beauty and Good in itself as expressions of the same reality which Plato has used in different contexts through his works. Along these terms some other notions have also been brought up like intellect, divine intellect, Demiurge, ideas and the particulars of material world. By explaining Plato's taking of these notions and terms, we believe, one can discover Platonic ontological system.    In Republic, Plato argues that God is the creator of ideal bed and all other things, and he is the creator of intelligible entities (ideas. The One or reality as a whole not only contains ideas but the spirit too. The One is the final principle and the source of ideas and is beyond all human attributes. Having said these, it is not clear how reason gets itself related to the

  9. High-resolution CT with histopathological correlates of the classic metaphyseal lesion of infant abuse

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Andy; Kleinman, Paul K. [Boston Children' s Hospital, Department of Radiology, Boston, MA (United States); McDonald, Anna G. [Office of the Chief Medical Examiner, Boston, MA (United States); Rosenberg, Andrew E. [University of Miami Hospital, Department of Pathology, Miami, FL (United States); Gupta, Rajiv [Massachusetts General Hospital, Department of Radiology, Boston, MA (United States)

    2014-02-15

    The classic metaphyseal lesion (CML) is a common high specificity indicator of infant abuse and its imaging features have been correlated histopathologically in infant fatalities. High-resolution CT imaging and histologic correlates were employed to (1) characterize the normal infant anatomy surrounding the chondro-osseous junction, and (2) confirm the 3-D model of the CML previously inferred from planar radiography and histopathology. Long bone specimens from 5 fatally abused infants, whose skeletal survey showed definite or suspected CMLs, were studied postmortem. After skeletal survey, selected specimens were resected and imaged with high-resolution digital radiography. They were then scanned with micro-CT (isotropic resolution of 45 μm{sup 3}) or with high-resolution flat-panel CT (isotropic resolutions of 200 μm{sup 3}). Visualization of the bony structures was carried out using image enhancement, segmentation and isosurface extraction, together with volume rendering and multiplanar reformatting. These findings were then correlated with histopathology. Study of normal infant bone clarifies the 3-D morphology of the subperiosteal bone collar (SPBC) and the radiographic zone of provisional calcification (ZPC). Studies on specimens with CML confirm that this lesion is a fracture extending in a planar fashion through the metaphysis, separating a mineralized fragment. This disk-like mineralized fragment has two components: (1) a thick peripheral component encompassing the SPBC; and (2) a thin central component comprised predominantly of the radiologic ZPC. By manipulating the 3-D model, the varying appearances of the CML are displayed. High-resolution CT coupled with histopathology provides elucidation of the morphology of the CML, a strong indicator of infant abuse. This new information may prove useful in assessing the biomechanical factors that produce this strong indicator of abusive assaults in infants. (orig.)

  10. High-resolution CT with histopathological correlates of the classic metaphyseal lesion of infant abuse

    International Nuclear Information System (INIS)

    Tsai, Andy; Kleinman, Paul K.; McDonald, Anna G.; Rosenberg, Andrew E.; Gupta, Rajiv

    2014-01-01

    The classic metaphyseal lesion (CML) is a common high specificity indicator of infant abuse and its imaging features have been correlated histopathologically in infant fatalities. High-resolution CT imaging and histologic correlates were employed to (1) characterize the normal infant anatomy surrounding the chondro-osseous junction, and (2) confirm the 3-D model of the CML previously inferred from planar radiography and histopathology. Long bone specimens from 5 fatally abused infants, whose skeletal survey showed definite or suspected CMLs, were studied postmortem. After skeletal survey, selected specimens were resected and imaged with high-resolution digital radiography. They were then scanned with micro-CT (isotropic resolution of 45 μm 3 ) or with high-resolution flat-panel CT (isotropic resolutions of 200 μm 3 ). Visualization of the bony structures was carried out using image enhancement, segmentation and isosurface extraction, together with volume rendering and multiplanar reformatting. These findings were then correlated with histopathology. Study of normal infant bone clarifies the 3-D morphology of the subperiosteal bone collar (SPBC) and the radiographic zone of provisional calcification (ZPC). Studies on specimens with CML confirm that this lesion is a fracture extending in a planar fashion through the metaphysis, separating a mineralized fragment. This disk-like mineralized fragment has two components: (1) a thick peripheral component encompassing the SPBC; and (2) a thin central component comprised predominantly of the radiologic ZPC. By manipulating the 3-D model, the varying appearances of the CML are displayed. High-resolution CT coupled with histopathology provides elucidation of the morphology of the CML, a strong indicator of infant abuse. This new information may prove useful in assessing the biomechanical factors that produce this strong indicator of abusive assaults in infants. (orig.)

  11. Deus: metafísica e pensar pós-metafísico (God: metaphysics and post-metaphysical thinking - DOI: 10.5752/P.2175-5841.2010v8n16p8

    Directory of Open Access Journals (Sweden)

    Ibraim Vitor de Oliveira

    2010-04-01

    Full Text Available Normal 0 21 false false false MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabela normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;} Editorial - Dossiê: Pensamento pós-metafísico e discurso sobre Deus – (Dossier: Post-metaphysical thought and speech about God Normal 0 21 false false false MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabela normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;} Deus: metafísica e pensar pós-metafísico (God: metaphysics and post-metaphysical thinking - DOI: 10.5752/P.2175-5841.2010v8n16p8 

  12. Metaphyseal and diaphyseal bone loss in the tibia following transient muscle paralysis are spatiotemporally distinct resorption events.

    Science.gov (United States)

    Ausk, Brandon J; Huber, Philippe; Srinivasan, Sundar; Bain, Steven D; Kwon, Ronald Y; McNamara, Erin A; Poliachik, Sandra L; Sybrowsky, Christian L; Gross, Ted S

    2013-12-01

    When the skeleton is catabolically challenged, there is great variability in the timing and extent of bone resorption observed at cancellous and cortical bone sites. It remains unclear whether this resorptive heterogeneity, which is often evident within a single bone, arises from increased permissiveness of specific sites to bone resorption or localized resorptive events of varied robustness. To explore this question, we used the mouse model of calf paralysis induced bone loss, which results in metaphyseal and diaphyseal bone resorption of different timing and magnitude. Given this phenotypic pattern of resorption, we hypothesized that bone loss in the proximal tibia metaphysis and diaphysis occurs through resorption events that are spatially and temporally distinct. To test this hypothesis, we undertook three complimentary in vivo/μCT imaging studies. Specifically, we defined spatiotemporal variations in endocortical bone resorption during the 3weeks following calf paralysis, applied a novel image registration approach to determine the location where bone resorption initiates within the proximal tibia metaphysis, and explored the role of varied basal osteoclast activity on the magnitude of bone loss initiation in the metaphysis using μCT based bone resorption parameters. A differential response of metaphyseal and diaphyseal bone resorption was observed throughout each study. Acute endocortical bone loss following muscle paralysis occurred almost exclusively within the metaphyseal compartment (96.5% of total endocortical bone loss within 6days). Using our trabecular image registration approach, we further resolved the initiation of metaphyseal bone loss to a focused region of significant basal osteoclast function (0.03mm(3)) adjacent to the growth plate. This correlative observation of paralysis induced bone loss mediated by basal growth plate cell dynamics was supported by the acute metaphyseal osteoclastic response of 5-week vs. 13-month-old mice. Specifically

  13. Comparing return to sport activities after short metaphyseal femoral arthroplasty with resurfacing and big femoral head arthroplasties.

    Science.gov (United States)

    Karampinas, Panagiotis K; Papadelis, Eustratios G; Vlamis, John A; Basiliadis, Hlias; Pneumaticos, Spiros G

    2017-07-01

    Young patients feel that maintaining sport activities after total hip arthroplasty constitutes an important part of their quality of life. The majority of hip surgeons allow patients to return to low-impact activities, but significant caution is advised to taking part in high-impact activities. The purpose of this study is to compare and evaluate the post-operative return to daily living habits and sport activities following short-metaphyseal hip and high functional total hip arthroplasties (resurfacing and big femoral head arthroplasties). In a study design, 48 patients (55 hips) were enrolled in three different comparative groups, one with the short-metaphyseal arthroplasties, a second with high functional resurfacing arthroplasties and a third of big femoral head arthroplasties. Each patient experienced a clinical examination and evaluated with Harris Hip Score, WOMAC, Sf-36, UCLA activity score, satisfaction VAS, anteroposterior and lateral X-rays of the hip and were followed in an outpatient setting for 2 years. Statistical analysis revealed no notable differences between the three groups regarding their demographic data however significant differences have been found between preoperative and postoperative clinical scores of each group. Also, we fail to reveal any significant differences when comparing data of all three groups at the final 2 years postoperative control regarding their clinical scores. The overall outcome of all three groups was similar, all the patients were satisfied and returned to previous level of sport activities. Short metaphyseal hip arthroplasties in young patients intending to return to previous and even high impact sport activities, similar to high functional resurfacing, big femoral head arthroplasties. Short stems with hard on hard bearing surfaces might become an alternative to standard stems and hip resurfacing.

  14. Nihilism and Violence in the Age of Technology: A Historical Diagnosis from Heidegger’s Critique of Metaphysics

    Directory of Open Access Journals (Sweden)

    Pablo Pérez Espigares

    2016-10-01

    Full Text Available This article tries to throw light on the ultimate roots of violence currently hitting our technological civilization. For this purpose we will analyze to what extent western philosophical tradition, beginning from its metaphysical core, has restricted the power of nothingness and how, as a consequence, it has favoured a biased view of nihilism that generates the perfect framework for the development of its destructive consequences. Following Heidegger's reflection, we will examine his «essential thinking» proposal as a way to overcome nihilism. We will then be able to arrive at its originary meaning and  penetrate into the essential origin of present-day violence.

  15. Arnold Chiari Malformation With Sponastrime (Spondylar and Nasal Changes, With Striations of the Metaphyses) Dysplasia: A Case Report.

    Science.gov (United States)

    Jeong, Je Hoon; Lee, A Leum; Cho, Sung Yoon; Jin, Dong Kyu; Im, Soo-Bin

    2016-05-01

    SPOndylar and NAsal changes, with STRIations of the Metaphyses (SPONASTRIME) dysplasia (SD) is a dwarfing autosomal recessive syndrome, characterized by a variety of clinical and radiographic features, which form the basis for diagnosis. We describe the presentation of an Arnold Chiari malformation in a patient with a clinical diagnosis of SD. The malformation was successfully treated by decompression of the foramen magnum and elevation of the cerebellum, with complete resolution of pain.We report a rare case of Arnold Chiari malformation in a patient presenting with clinical and radiographic features strongly suggestive of SD and be successfully treated.

  16. The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats

    Energy Technology Data Exchange (ETDEWEB)

    Nicolau, L.A.D. [Núcleo de Pesquisa em Produtos Naturais, Departamento de Farmacologia, Universidade Federal do Piauí, Teresina, PI (Brazil); Silva, R.O.; Damasceno, S.R.B.; Carvalho, N.S.; Costa, N.R.D. [Laboratório de Fisiofarmacologia Experimental, Centro de Pesquisa em Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI (Brazil); Aragão, K.S. [Laboratório de Farmacologia da Inflamação e do Câncer, Departamento de Farmacologia, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Barbosa, A.L.R. [Núcleo de Pesquisa em Produtos Naturais, Departamento de Farmacologia, Universidade Federal do Piauí, Teresina, PI (Brazil); Laboratório de Fisiofarmacologia Experimental, Centro de Pesquisa em Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI (Brazil); Soares, P.M.G.; Souza, M.H.L.P. [Laboratório de Farmacologia da Inflamação e do Câncer, Departamento de Farmacologia, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Medeiros, J.V.R. [Núcleo de Pesquisa em Produtos Naturais, Departamento de Farmacologia, Universidade Federal do Piauí, Teresina, PI (Brazil); Laboratório de Fisiofarmacologia Experimental, Centro de Pesquisa em Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI (Brazil)

    2013-08-16

    Our objective was to investigate the protective effect of Lawesson's reagent, an H{sub 2}S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson's reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson's reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35±9.8 mm{sup 2}); increased levels of TNF-α, IL-1β, and MDA (2311±302.3 pg/mL, 901.9±106.2 pg/mL, 121.1±4.3 nmol/g, respectively); increased MPO activity (26.1±3.8 U/mg); and reduced GSH levels (180.3±21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77±5.3 mm{sup 2}); reduced TNF-α, IL-1β, and MDA formation (1502±150.2 pg/mL, 632.3±43.4 pg/mL, 78.4±7.6 nmol/g, respectively); lowered MPO activity (11.7±2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson's reagent. Our results suggest that Lawesson's reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (K

  17. Science Awareness and Science Literacy through the Basic Physics Course: Physics with a bit of Metaphysics?

    International Nuclear Information System (INIS)

    Rusli, Aloysius

    2016-01-01

    Until the 1980s, it is well known and practiced in Indonesian Basic Physics courses, to present physics by its effective technicalities: The ideally elastic spring, the pulley and moving blocks, the thermodynamics of ideal engine models, theoretical electrostatics and electrodynamics with model capacitors and inductors, wave behavior and its various superpositions, and hopefully closed with a modern physics description. A different approach was then also experimented with, using the Hobson and Moore texts, stressing the alternative aim of fostering awareness, not just mastery, of science and the scientific method. This is hypothesized to be more in line with the changed attitude of the so-called Millenials cohort who are less attentive if not interested, and are more used to multi-tasking which suits their shorter span of attention. The upside is increased awareness of science and the scientific method. The downside is that they are getting less experience of the scientific method which intensely bases itself on critical observation, analytic thinking to set up conclusions or hypotheses, and checking consistency of the hypotheses with measured data. Another aspect is recognition that the human person encompasses both the reasoning capacity and the mental- spiritual-cultural capacity. This is considered essential, as the world grows even smaller due to increased communication capacity, causing strong interactions, nonlinear effects, and showing that value systems become more challenging and challenged due to physics / science and its cosmology, which is successfully based on the scientific method. So students should be made aware of the common basis of these two capacities: the assumptions, the reasoning capacity and the consistency assumption. This shows that the limits of science are their set of basic quantifiable assumptions, and the limits of the mental-spiritual-cultural aspects of life are their set of basic metaphysical (non-quantifiable) assumptions. The

  18. Science Awareness and Science Literacy through the Basic Physics Course: Physics with a bit of Metaphysics?

    Science.gov (United States)

    Rusli, Aloysius

    2016-08-01

    Until the 1980s, it is well known and practiced in Indonesian Basic Physics courses, to present physics by its effective technicalities: The ideally elastic spring, the pulley and moving blocks, the thermodynamics of ideal engine models, theoretical electrostatics and electrodynamics with model capacitors and inductors, wave behavior and its various superpositions, and hopefully closed with a modern physics description. A different approach was then also experimented with, using the Hobson and Moore texts, stressing the alternative aim of fostering awareness, not just mastery, of science and the scientific method. This is hypothesized to be more in line with the changed attitude of the so-called Millenials cohort who are less attentive if not interested, and are more used to multi-tasking which suits their shorter span of attention. The upside is increased awareness of science and the scientific method. The downside is that they are getting less experience of the scientific method which intensely bases itself on critical observation, analytic thinking to set up conclusions or hypotheses, and checking consistency of the hypotheses with measured data. Another aspect is recognition that the human person encompasses both the reasoning capacity and the mental- spiritual-cultural capacity. This is considered essential, as the world grows even smaller due to increased communication capacity, causing strong interactions, nonlinear effects, and showing that value systems become more challenging and challenged due to physics / science and its cosmology, which is successfully based on the scientific method. So students should be made aware of the common basis of these two capacities: the assumptions, the reasoning capacity and the consistency assumption. This shows that the limits of science are their set of basic quantifiable assumptions, and the limits of the mental-spiritual-cultural aspects of life are their set of basic metaphysical (non-quantifiable) assumptions. The

  19. The old with the die. A contribution to metaphysics of quantum mechanics; Der Alte mit dem Wuerfel. Ein Beitrag zur Metaphysik der Quantenmechanik

    Energy Technology Data Exchange (ETDEWEB)

    Ijjas, Anna

    2011-07-01

    Since the rise of quantum mechanics also their ideological implications and consequences were discussed. Meanwhile still scarcely a metaphysical problem exists, which was not supposedly solved under calling on quantum theory. Anna Ijjas inquires the usual practice and developes a new model of the assignment of quantum mechanics and metaphysics. She discusses both the physical foundations and the classical philosophical controversies, before she draws consequencies for the relation determination of brain and consciousness, the problem of freedom of will, as well as for the question of the influence of God in the world.

  20. A short-stem hip implant with metaphyseal anchorage in patients with developmental dysplasia of the hip.

    Science.gov (United States)

    Budde, Stefan; Floerkemeier, Thilo; Thorey, Fritz; Ezechieli, Marco; Claassen, Leif; Ettinger, Max; Bredow, Jan; Windhagen, Henning; Lewinski, Gabriela von

    2016-03-18

    Short-stem implants are routinely used for total hip arthroplasty in younger patients that are more likely to have secondary osteoarthritis than older patients. To investigate the applicability of short-stem hip implants for secondary osteoarthritis due to developmental dysplasia of the hip. This study analyzed the clinical and radiological results of patients with developmental dysplasia of the hip (DDH, 58 hips) and compared them to those of patients with primary osteoarthritis (POA, 59 hips) treated with the metaphyseal total hip arthroplasty (Metha®) short stem with metaphyseal fixation. The mean clinical and radiological follow-up periods were 2.9 ± 1.1 years and 3.8 ± 1.9 years, respectively. The mean Harris Hip Score (HHS) significantly increased in both groups over this period (p< 0.0001). The caput-collum-diaphysis (CCD) angle was significantly lower in the POA group prior to surgery and significantly increased in the POA and and decreased in DDH groups, respectively. The preoperative femoral offset was lower in the DDH group and increased significantly after surgery. The Metha® short stem in patients with DDH allows good reconstruction of joint biomechanics with a good clinical outcome.

  1. Translation from Chinese of Poems 1–9 from 'Wandering Spirit and Metaphysical Thoughts' by Gao Xingjian

    Directory of Open Access Journals (Sweden)

    Mabel Lee

    2017-05-01

    Full Text Available The 2000 Nobel Laureate for Literature, Gao Xingjian, suffered cardiac arrest while directing rehearsals for his mega-scale opera Snow in August that was due to premiere in late 2002 at the National Opera House, Taipei. He recovered, and the opera premiered as scheduled with the help of a co-director before he returned to Paris to direct the Comédie Français premiere of his Quatre quatuors pour un week-end. He underwent surgery in February and March of 2003, but was soon again back at work. The year 2003 had been designated “Gao Xingjian Year” by the City of Marseille, and he would direct his new play Le Quêteur de la Mort at Théâtre du Gymnase, and then his Snow in August at Opéra de Marseille. It was during rehearsals for the former that he collapsed again, and was hospitalized: the play was co-directed by Romain Bonnin, 23–26 September 2003. Large exhibitions of Gao’s artworks had been held earlier that year, but the performance of Snow in August was postponed. During his recuperation for most of 2004, he sometimes wrote poems, some of which he later polished or rewrote for his collection Wandering Spirit and Metaphysical Thoughts (2012. These translations from the Chinese into English of the first 9 poems in Wandering Spirit and Metaphysical Thoughts (2012 are by acclaimed translator Mabel Lee.

  2. The Contingency Of Our Own Beatitude. Some Reflections On Gilson’s The Future Of Augustinian Metaphysics

    Directory of Open Access Journals (Sweden)

    James V. Schall

    2015-03-01

    Full Text Available Inspired by selected passages from Wendell Berry’s story “A Place in Time,” the article discusses Étienne Gilson’s essay “The Future of Augustinian Metaphysics” with a special regard to the relation of habits to metaphysics. The basis of this relation is human being whose life, from the perspective of Augustinian metaphysics, is permanently unsettled. Man is the one mortal being whose perfection does not come with his being, but only with his own input into what it already is. Habits, then, prefect an already constituted human being in what he or she is. Man is not born, however, with habits, but acquires them through acts of the virtues or vices. The article develops the Augustinian idea according to which the moral effort of man to pursue virtues and escape vices results not so much from his natural desire of ‘beatitude’, but rather from the fact of being led to God by God.

  3. A Japanese-American Sam Spade: The Metaphysical Detective in Death in Little Tokyo, by Dale Furutani

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    Portilho Carla

    2017-06-01

    Full Text Available The aim of this essay is to discuss the legacy of the roman noir in contemporary detective fiction produced outside the hegemonic center of power, here represented by the novel Death in Little Tokyo (1996, written by Japanese-American author Dale Furutani. Starting from the concept of the metaphysical detective (Haycraft 76; Holquist 153-156, characterized by deep questioning about narrative, interpretation, subjectivity, the nature of reality and the limits of knowledge, this article proposes a discussion about how these literary works, which at first sight represent a traditionally Anglo-American genre, constitute narratives that aim to rescue the memory, history and culture of marginalized communities. Typical of late modernity detective fiction, the metaphysical detective has none of the positivistic detective’s certainties, as he does not share in his Cartesian notion of totality, being presented instead as a successor of the hardboiled detective of the roman noir. In this article I intend to analyze the paths chosen by the author and discuss how his re-reading of the roman noir dialogues with the texts of hegemonic noire detective fiction, inscribing them in literary tradition and subverting them at the same time.

  4. Book Review: Time and the metaphysics of relativity. William Lane Craig, Kluwer Academic Publisher, Dordrecht, 2000, 292pp. US 92, ISBN 0-792-36668-9

    Science.gov (United States)

    Dorato, Mauro

    In a recent book on " Time and the Metaphysics of Relativity", William Lane Craig uses the concept of time to try to reconstruct strong conceptual links between theology, metaphysics and physics, three vertices of a triangle that until the 17th century have been much less separated than they are today. According to Craig, the task of the philosopher of time is not just to use the prestige of contemporary physical theories to support certain metaphysical views (the A versus the B theory), or, more questionably, certain views of God (his timelessness versus his omni temporality). He also claims that one should be guided by certain a priori theological and metaphysical hypotheses in order to interpret and even evaluate physical theories. In this respect, the main aim of the book is to rehabilitate a neo-lorentzian interpretation of relativity and to show its connection with cosmic time, which Craig questionably regards as a direct measure of God's, tensed, A-theoretical Time. Not by chance, the present volume is part of a remarkable tetralogy, the other three dealing with God, Time and Eternity, The Tensed Theory of Time and The Tenseless Theory of Time.

  5. Changes in strain patterns after implantation of a short stem with metaphyseal anchorage compared to a standard stem: an experimental study in synthetic bone

    Directory of Open Access Journals (Sweden)

    Jens Gronewold

    2014-03-01

    Full Text Available Short stem hip arthroplasties with predominantly metaphyseal fixation, such as the METHA® stem (Aesculap, Tuttlingen, Germany, are recommended because they are presumed to allow a more physiologic load transfer and thus a reduction of stress-shielding. However, the hypothesized metaphyseal anchorage associated with the aforementioned benefits still needs to be verified. Therefore, the METHA short stem and the Bicontact® standard stem (Aesculap, Tuttlingen, Germany were tested biomechanically in synthetic femora while strain gauges monitored their corresponding strain patterns. For the METHA stem, the strains in all tested locations including the region of the calcar (87% of the non-implanted femur were similar to conditions of synthetic bone without implanted stem. The Bicontact stem showed approximately the level of strain of the non-implanted femur on the lateral and medial aspect in the proximal diaphysis of the femur. On the anterior and posterior aspect of the proximal metaphysis the strains reached averages of 78% and 87% of the non-implanted femur, respectively. This study revealed primary metaphyseal anchorage of the METHA short stem, as opposed to a metaphyseal-diaphyseal anchorage of the Bicontact stem.

  6. Metaphyseal osteomyelitis in children: how often does MRI-documented joint effusion or epiphyseal extension of edema indicate coexisting septic arthritis?

    Science.gov (United States)

    Schallert, Erica K; Kan, J Herman; Monsalve, Johanna; Zhang, Wei; Bisset, George S; Rosenfeld, Scott

    2015-07-01

    Joint effusions identified by MRI may accompany osteomyelitis and determining whether the joint effusion is septic or reactive has important implications on patient care. Determine the incidence of epiphyseal marrow edema, joint effusions, perisynovial edema and epiphyseal non-enhancement in the setting of pediatric metaphyseal osteomyelitis and whether this may be used to predict coexisting septic arthritis. Following IRB approval, we retrospectively evaluated children who underwent MRI and orthopedic surgical consultation for suspected musculoskeletal infection between January 2011 and September 2013. Criteria for inclusion in the study were microbiologically/pathologically proven infection, MRI prior to surgical intervention, long bone involvement and age 0-18 years. MRI exams were independently reviewed by two faculty pediatric radiologists to confirm the presence of appendicular metaphyseal osteomyelitis, to evaluate extent of edema, to determine subjective presence of a joint effusion and to assess perisynovial edema and epiphyseal non-enhancement. Any discrepant readings were reviewed in consensus. Charts and operative notes were reviewed to confirm the diagnosis of osteomyelitis and septic arthritis. One hundred and three joints with metaphyseal osteomyelitis were identified (mean age: 7.1 years; M:F 1.3:1), of whom 53% (55/103) had joint effusions, and of those, 75% (41/55) had surgically confirmed septic arthritis. The incidence of coexisting septic arthritis was 40% in the setting of epiphyseal edema, 74% in epiphyseal edema and effusion, 75% with perisynovial edema, 76% with epiphyseal non-enhancement and 77% when all four variables were present. Of these, the only statistically significant variable, however, was the presence of a joint effusion with a P-value of septic arthritis was also encountered when cases were subdivided into intra-articular vs. extra-articular metaphyses (P-value  =  0.0499). No statistically significant difference was

  7. Metaphyseal osteomyelitis in children: how often does MRI-documented joint effusion or epiphyseal extension of edema indicate coexisting septic arthritis?

    International Nuclear Information System (INIS)

    Schallert, Erica K.; Kan, J.H.; Monsalve, Johanna; Zhang, Wei; Bisset, George S.; Rosenfeld, Scott

    2015-01-01

    Joint effusions identified by MRI may accompany osteomyelitis and determining whether the joint effusion is septic or reactive has important implications on patient care. Determine the incidence of epiphyseal marrow edema, joint effusions, perisynovial edema and epiphyseal non-enhancement in the setting of pediatric metaphyseal osteomyelitis and whether this may be used to predict coexisting septic arthritis. Following IRB approval, we retrospectively evaluated children who underwent MRI and orthopedic surgical consultation for suspected musculoskeletal infection between January 2011 and September 2013. Criteria for inclusion in the study were microbiologically/pathologically proven infection, MRI prior to surgical intervention, long bone involvement and age 0-18 years. MRI exams were independently reviewed by two faculty pediatric radiologists to confirm the presence of appendicular metaphyseal osteomyelitis, to evaluate extent of edema, to determine subjective presence of a joint effusion and to assess perisynovial edema and epiphyseal non-enhancement. Any discrepant readings were reviewed in consensus. Charts and operative notes were reviewed to confirm the diagnosis of osteomyelitis and septic arthritis. One hundred and three joints with metaphyseal osteomyelitis were identified (mean age: 7.1 years; M:F 1.3:1), of whom 53% (55/103) had joint effusions, and of those, 75% (41/55) had surgically confirmed septic arthritis. The incidence of coexisting septic arthritis was 40% in the setting of epiphyseal edema, 74% in epiphyseal edema and effusion, 75% with perisynovial edema, 76% with epiphyseal non-enhancement and 77% when all four variables were present. Of these, the only statistically significant variable, however, was the presence of a joint effusion with a P-value of <0.0001 via Fisher exact test. Statistical significance for coexisting septic arthritis was also encountered when cases were subdivided into intra-articular vs. extra-articular metaphyses (P

  8. Metaphyseal osteomyelitis in children: how often does MRI-documented joint effusion or epiphyseal extension of edema indicate coexisting septic arthritis?

    Energy Technology Data Exchange (ETDEWEB)

    Schallert, Erica K.; Kan, J.H.; Monsalve, Johanna; Zhang, Wei; Bisset, George S. [Texas Children' s Hospital, Department of Pediatric Radiology, Houston, TX (United States); Rosenfeld, Scott [Texas Children' s Hospital, Department of Pediatric Orthopedic Surgery, Houston, TX (United States)

    2015-08-15

    Joint effusions identified by MRI may accompany osteomyelitis and determining whether the joint effusion is septic or reactive has important implications on patient care. Determine the incidence of epiphyseal marrow edema, joint effusions, perisynovial edema and epiphyseal non-enhancement in the setting of pediatric metaphyseal osteomyelitis and whether this may be used to predict coexisting septic arthritis. Following IRB approval, we retrospectively evaluated children who underwent MRI and orthopedic surgical consultation for suspected musculoskeletal infection between January 2011 and September 2013. Criteria for inclusion in the study were microbiologically/pathologically proven infection, MRI prior to surgical intervention, long bone involvement and age 0-18 years. MRI exams were independently reviewed by two faculty pediatric radiologists to confirm the presence of appendicular metaphyseal osteomyelitis, to evaluate extent of edema, to determine subjective presence of a joint effusion and to assess perisynovial edema and epiphyseal non-enhancement. Any discrepant readings were reviewed in consensus. Charts and operative notes were reviewed to confirm the diagnosis of osteomyelitis and septic arthritis. One hundred and three joints with metaphyseal osteomyelitis were identified (mean age: 7.1 years; M:F 1.3:1), of whom 53% (55/103) had joint effusions, and of those, 75% (41/55) had surgically confirmed septic arthritis. The incidence of coexisting septic arthritis was 40% in the setting of epiphyseal edema, 74% in epiphyseal edema and effusion, 75% with perisynovial edema, 76% with epiphyseal non-enhancement and 77% when all four variables were present. Of these, the only statistically significant variable, however, was the presence of a joint effusion with a P-value of <0.0001 via Fisher exact test. Statistical significance for coexisting septic arthritis was also encountered when cases were subdivided into intra-articular vs. extra-articular metaphyses (P

  9. Epilepsy, viewed metaphysically: an interpretation of the biblical story of the epileptic boy and of Raphael's transfiguration.

    Science.gov (United States)

    Janz, D

    1986-01-01

    Raphael's last painting reveals, in the upper half of the picture, Christ's transfiguration on Mount Tabor and, in the lower half, the young boy's epileptic seizure at the foot of the mountain in the presence of the other disciples. Raphael depicts both events, which are told in succession in the Gospels, as if they took place at the same time. By synchronizing both scenes Raphael demonstrated a significant correspondence between Christ and the epileptic boy, which reveals the epileptic seizure as a symbolic representation of a transcendent event. This metaphysical aspect of epilepsy depicted by Raphael can also be found in the corresponding biblical passages. In the Gospels, the metamorphosis caused by the epileptic seizure is used as a simile for Christ's transfiguration through suffering, death, and resurrection.

  10. [Epilepsy from a metaphysical perspective: an interpretation of the biblical story of the epileptic boy and Raphael's Transfiguration].

    Science.gov (United States)

    Janz, D

    1994-01-01

    Raphael's last painting reveals, in the upper half of the picture, Christ's transfiguration on Mount Tabor and, in the lower half, the young boy's epileptic seizure at the foot of the mountain in the presence of the other disciples. Raphael depicts both events, which are told in succession in the Gospels, as if they took place at the same time. By synchronizing both scenes, Raphael demonstrated a significant correspondence between Christ and the epileptic boy which reveals the epileptic seizure as a symbolic representation of a transcendental event. This metaphysical aspect of epilepsy depicted by Raphael can also be found in the corresponding biblical passages. In the Gospels, the metamorphosis caused by the epileptic seizure is used as a simile for Christ's transfiguration through suffering, death and resurrection.

  11. Od metafizyki do empirii. Antropologiczno-filozoficzne wizje człowieka [From metaphysics to empiricism. Philosophical anthropology on man

    Directory of Open Access Journals (Sweden)

    Karol Chrobak

    2014-06-01

    Full Text Available This essay focuses on three conceptions of man formulated within the German school of philosophical anthropology. I discuss, one by one, theories by Max Scheler, Helmuth Plessner and Arnold Gehlen. First, I emphasize the common to these theoreticians methodological assumptions consisting primarily in an opposition against the Cartesian dualism and in founding a ground for philosophical analysis in the results of scientific research. Second, I present their conceptions of man stressing at the same time dissimilarities that differ them from each other. These differences concern first and foremost their general orientation: while Scheler’s understanding of man is clearly determined by a metaphysical idea of a permanent essence of man, Plessner’s conception focuses rather on a dynamic, historical way of manifesting of their existence. Philosophy by Gehlen in turn presents a picture of man as a biological being who by their own effort, by emerging institutional reality, stabilizes their existence.

  12. Intramedullary screw fixation with bone autografting to treat proximal fifth metatarsal metaphyseal-diaphyseal fracture in athletes: a case series

    Directory of Open Access Journals (Sweden)

    Tsukada Sachiyuki

    2012-07-01

    Full Text Available Abstract Background Delayed unions or refractures are not rare following surgical treatment for proximal fifth metatarsal metaphyseal-diaphyseal fractures. Intramedullary screw fixation with bone autografting has the potential to resolve the issue. The purpose of this study was to evaluate the result of the procedure. Methods The authors retrospectively reviewed 15 athletes who underwent surgical treatment for proximal fifth metatarsal metaphyseal-diaphyseal fracture. Surgery involved intramedullary cannulated cancellous screw fixation after curettage of the fracture site, followed by bone autografting. Postoperatively, patients remain non weight-bearing in a splint or cast for two weeks and without immobilization for an additional two weeks. Full weight-bearing was allowed six weeks postoperatively. Running was permitted after radiographic bone union, and return-to-play was approved after gradually increasing the intensity. Results All patients returned to their previous level of athletic competition. Mean times to bone union, initiation of running, and return-to-play were 8.4, 8.8, and 12.1 weeks, respectively. Although no delayed unions or refractures was observed, distal diaphyseal stress fractures at the distal tip of the screw occurred in two patients and a thermal necrosis of skin occurred in one patient. Conclusions There were no delayed unions or refractures among patients after carrying out a procedure in which bone grafts were routinely performed, combined with adequate periods of immobilization and non weight-bearing. These findings suggest that this procedure may be useful option for athletes to assuring return to competition level.

  13. Outcome of Displaced Fractures of the Distal Metaphyseal-Diaphyseal Junction of the Humerus in Children Treated With Elastic Stable Intramedullary Nails.

    Science.gov (United States)

    Marengo, Lorenza; Canavese, Federico; Cravino, Mattia; De Rosa, Vincenzo; Rousset, Marie; Samba, Antoine; Mansour, Mounira; Andreacchio, Antonio

    2015-09-01

    The main objective of this study was to retrospectively evaluate the clinical and radiographic outcomes of displaced distal humeral metaphyseal-diaphyseal junction fractures in children treated by elastic stable intramedullary nailing (ESIN). During the study period, 14 consecutive children with fractures of the distal humeral metaphyseal-diaphyseal junction were surgically treated by ESIN. All patients underwent full-length preoperative and postoperative anteroposterior and lateral radiographs of the injured humerus. One year after the index surgery, patients were asked to answer the short version of the Disabilities of the Arm, Shoulder and Hand outcome questionnaire (Quick DASH). During the study period, fractures of the distal metaphyseal-diaphyseal humeral junction represented 1.5% (16/1100) of all humeral fractures. Fourteen patients underwent surgery and met the inclusion criteria. The male to female ratio was 1:1. The average patient age at the time of injury was 9.7 years (range, 3.6 to 13.7 y). The left and right sides were equally affected. The mean follow-up was 28.1 months (range, 20 to 38 mo).Radiologically, no secondary displacement, nail migration, loss of fixation, consolidation delay, nonunion, or refracture was noted. None of the patients showed signs of growth arrest on either radiologic or clinical assessment.All patients returned to their previous daily and sport activities without discomfort or difficulty, and they were free of pain at their last follow-up visits. The injured elbow range of motion was comparable with that of the contralateral side at the last follow-up visit in all patients. The mean Quick DASH score was 0.81 (range, 0 to 6.8). We recommend surgery for displaced fractures of the distal humeral metaphyseal-diaphyseal junction. ESIN results in stable reduction, good rotational control, and faster mobilization. Level IV.

  14. The Concept of a Neutral Starting Point in Thomistic Metaphysics and its Relationship to the Assumptive Character of Knowledge

    Directory of Open Access Journals (Sweden)

    Piotr Duchliński

    2015-12-01

    Full Text Available This article describes how certain Thomists understand the concept of a neutral (i.e. assumption free starting point, and outlines their arguments in favour of it. To be sure, within current epistemology, their position is considered outdated and unpopular: apart from Thomists, nobody would now argue that there is a privileged, assumption free starting point for philosophy. (After all, it is generally thought that any such thing would simply fail to yield determinate results, at least where human cognition or knowledge is concerned. This article, though, poses, and seeks to answer, the question of whether the Thomistic position is intended merely as a methodological commitment, or also as a stage in the pragmatic construction of a metaphysical theory. In the light of a discussion that confronts this with some points from contemporary philosophy of science concerning the theorizing of experience and the assumptive character of scientific knowledge, the author puts forward the following hypothesis as a point of departure for further inquiry: that philosophy itself be understood as a paradigm, in the sense that it be taken to function as a benchmark - a model responsible for organizing human experience as a whole. The considerations presented are of a theoretical-cognitive character, with no claims made regarding the issue of the correct starting point for philosophy.

  15. The metaphysics of D-CTCs: On the underlying assumptions of Deutsch's quantum solution to the paradoxes of time travel

    Science.gov (United States)

    Dunlap, Lucas

    2016-11-01

    I argue that Deutsch's model for the behavior of systems traveling around closed timelike curves (CTCs) relies implicitly on a substantive metaphysical assumption. Deutsch is employing a version of quantum theory with a significantly supplemented ontology of parallel existent worlds, which differ in kind from the many worlds of the Everett interpretation. Standard Everett does not support the existence of multiple identical copies of the world, which the D-CTC model requires. This has been obscured because he often refers to the branching structure of Everett as a "multiverse", and describes quantum interference by reference to parallel interacting definite worlds. But he admits that this is only an approximation to Everett. The D-CTC model, however, relies crucially on the existence of a multiverse of parallel interacting worlds. Since his model is supplemented by structures that go significantly beyond quantum theory, and play an ineliminable role in its predictions and explanations, it does not represent a quantum solution to the paradoxes of time travel.

  16. The effects of prostaglandin E2 in growing rats - Increased metaphyseal hard tissue and cortico-endosteal bone formation

    Science.gov (United States)

    Jee, W. S. S.; Ueno, K.; Deng, Y. P.; Woodbury, D. M.

    1985-01-01

    The role of in vivo prostaglandin E2 (PGE2) in bone formation is investigated. Twenty-five male Sprague-Dawley rats weighing between 223-267 g were injected subcutaneously with 0.3, 1.0, 3.0, and 6.0 mg of PGE2-kg daily for 21 days. The processing of the tibiae for observation is described. Radiographs and histomorphometric analyses are also utilized to study bone formation. Body weight, weights of soft tissues and bones morphometry are evaluated. It is observed that PGE2 depressed longitudinal bone growth, increased growth cartilage thickness, decreased degenerative cartilage cell size and cartilage cell production, and significantly increased proximal tibial metaphyseal hard tissue mass. The data reveal that periosteal bone formation is slowed down at higher doses of PGE2 and endosteal bone formation is slightly depressed less than 10 days post injection; however, here is a late increase (10 days after post injection) in endosteal bone formation and in the formation of trabecular bone in the marrow cavity of the tibial shaft. It is noted that the effects of PGE2 on bone formation are similar to the responses of weaning rats to PGE2.

  17. Short-term alendronate treatment does not maintain a residual effect on spinal fusion with interbody devices and bone graft after treatment withdrawal: an experimental study on spinal fusion in pigs.

    Science.gov (United States)

    Huang, Baoding; Zou, Xuenong; Li, Haisheng; Xue, Qingyun; Bünger, Cody

    2013-02-01

    Whether alendronate treatment has a residual effect on bone ingrowth into porous biomaterial in humans or experimental animals after treatment withdrawal is still unknown. The purpose of this study was to investigate bone ingrowth into porous tantalum and carbon fiber interbody implants after discontinuing alendronate treatment in experimental spinal fusion in pigs. Twenty-four pigs were randomly divided into two groups of each 12 pigs. The pigs underwent anterior intervertebral lumbar arthrodeses at L2-3, L4-5 and L6-7. Each level was randomly allocated to one of the three implants: a porous tantalum ring with pedicle screw fixation, a porous tantalum ring or a carbon fiber cage with anterior staple fixation. The central hole of implants was packed with an autograft. Alendronate was given orally for the first 3 months to one of the two groups. The pigs were observed for 6 months postoperatively. Histology and micro-CT scans were done at the endpoint. The spinal fusion rates of each implant showed no differences between two treatment groups. Furthermore, no differences were found between two groups as for bone ingrowth into the central holes of implants and bone-implant interface in each implant, or as for the pores of tantalum implants. Trabecular bone microarchitecture in the central hole of the carbon fiber cage did not differ between two treatment groups. The application of ALN, with a dose equivalent to that given to humans during the first 3 months after surgery, does not maintain a residual effect on spinal fusion with porous tantalum ring and autograft after treatment withdrawal in a porcine ALIF model.

  18. Metafizinės patirtys Gražinos Cieškaitės lyrikoje | Metaphysical Experiences in Gražina Cieškaitė’s poetry

    Directory of Open Access Journals (Sweden)

    Audinga Peluritytė

    2005-01-01

    Full Text Available This paper analyses and discusses the signs of metaphysical experience in the work of the contemporary Lithuanian poetess Gražina Cieškaitė. The paper was inspired by Vytautas Kavolis’ provoking thought that in Cieškaitė’s poetry attempt is made to analyse and criticise the key myths of Western civilisation, and female mythology, very old and going back to pre-civilisation conscience, is recreated from the shards of the broken myth of Western civilisation. In this paper, Cieškaitė’s work is analysed in several stages that are reflected in the headlines of the sections. Recognisable are the landmarks of metaphysical thinking, mythical personages and plots; discussed are the outcomes of the interaction of eclectic metaphysical and mythical thinking; finally, an attempt is made at recognising the central idea of this metaphysical lyric and at reconstructing the version of myth so closely linked with this idea. All parts of the paper are concerned with the issue of poetic language, and the key features of Cieškaitė’s poetics are recorded. The paper asserts that in Cieškaitė’s work it is really possible to restore an extremely old version of female mythology, which is embodied in the figure of the goddess Aphrodite that had acquired Promethean creative powers. Yet here metaphysical experiences can hardly be generalised as one comprehensive metaphysical theory. In Cieškaitė’s work, metaphysical thinking based on language and logic frequently yields ground to spontaneous mystical experiences, which are not controlled by either logic or language.

  19. The role of galenic innovation in improving treatment compliance and persistence: three case studies.

    Science.gov (United States)

    Zoellner, York; Balp, Maria-Magdalena; Marco, Andrea Gili

    2011-01-01

    The purpose of this study was to explore whether newer galenic formulations with lower treatment burdens are associated with better patient compliance and persistence compared with older more burdensome modalities. Data from the IMS Disease Analyzer database were analyzed retrospectively for two pairs of analogs (alendronate sodium once daily vs once weekly and immediate-release vs extended-release methylphenidate) and one pair of drugs with similar indications but important differences in convenience and dosing instructions (desferrioxamine vs deferasirox). Compliance was calculated as the sum of prescription durations for all prescriptions for each patient over 1 year. Persistence was calculated as the time between first and last prescriptions over 2 years (1 year for deferasirox and desferrioxamine). Data from Germany and the UK were available and used for analysis. Incremental improvements in compliance were +30% in the UK and +26% in Germany for alendronate once weekly vs once daily, +14% in the UK and +19% in Germany for extended-release vs immediate-release methylphenidate, and +15% in Germany for desferrioxamine vs deferasirox. Incremental improvements in persistence were +9 months in the UK and +8 months in Germany for alendronate once weekly vs once daily, +4 months in the UK and +3 months in Germany for extended-release vs immediate-release methylphenidate, and +2 months in Germany for deferasirox vs desferrioxamine. The new formulations that we evaluated were associated with better compliance and persistence compared with older formulations. Despite the fact that some sources of bias could not be excluded, it is likely that these improvements can be attributed to the lower treatment burdens of the galenic formulations of the drugs considered. Further investigation is required to confirm these findings and to determine whether new galenic formulations can improve health outcomes in routine clinical practice.

  20. O alendronato de sódio na prevenção da osteopenia secundária à imobilização gessada, em ratas: avaliação histomorfométrica Alendronate sodium to prevent osteopenia caused by cast immobilization in female rats: histomorphometric evaluation

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    José B. Volpon

    2008-10-01

    Full Text Available OBJETIVO: Analisar, por meio da histomorfometria, o efeito do alendronato de sódio sobre o trabeculado ósseo de ratos, quando administrado simultaneamente com imobilização gessada. MÉTODOS: Foram utilizados quatro grupos com cinco fêmeas de ratos Wistar: 1 imobilizado; 2 não imobilizado + alendronato; 3 imobilizado + alendronato; e 4 controle. A imobilização foi feita com gesso pelvipodálico aplicado até o membro posterior direito e o alendronato foi administrado em doses semanais. O período de observação foi de 28 dias e realizada histomorfometria da metáfise proximal da tíbia, com análise do número de trabéculas, volume ósseo, espessura trabecular e separação trabecular. RESULTADOS: O grupo imobilizado apresentou volume ósseo menor que os demais grupos. Os animais que receberam alendronato semanal, tanto imobilizados, quanto não imobilizados, apresentaram volume ósseo maior que o controle. A espessura trabecular no grupo imobilizado foi menor do que nos grupos controle e não imobilizado que recebeu alendronato, mas não apresentou diferença significativa em relação ao imobilizado com alendronato. O grupo imobilizado apresentou separação trabecular maior que os demais grupos. Os grupos não imobilizado, sem imobilização que recebeu alendronato e imobilizado que recebeu alendronato apresentaram aumento no número de trabéculas em relação ao grupo imobilizado. CONCLUSÃO: A imobilização empregada efetivamente levou à osteopenia, verificada pela diminuição de todos os principais parâmetros histomorfométricos estudados. Estas alterações foram prevenidas pela administração concomitante de alendronato sódico, exceto com relação à espessura trabecular. O alendronato de sódio foi capaz de aumentar os parâmetros morfométricos, mesmo em animais não imobilizados.OBJECTIVE: Using histomorphometric means to analyze the effect of alendronate sodium on the bone trabeculate of rats administered

  1. Effect of odanacatib on bone turnover markers, bone density and geometry of the spine and hip of ovariectomized monkeys: a head-to-head comparison with alendronate.

    Science.gov (United States)

    Williams, Donald S; McCracken, Paul J; Purcell, Mona; Pickarski, Maureen; Mathers, Parker D; Savitz, Alan T; Szumiloski, John; Jayakar, Richa Y; Somayajula, Sangeetha; Krause, Stephen; Brown, Keenan; Winkelmann, Christopher T; Scott, Boyd B; Cook, Lynn; Motzel, Sherri L; Hargreaves, Richard; Evelhoch, Jeffrey L; Cabal, Antonio; Dardzinski, Bernard J; Hangartner, Thomas N; Duong, Le T

    2013-10-01

    Odanacatib (ODN) is a selective and reversible Cathepsin K (CatK) inhibitor currently being developed as a once weekly treatment for osteoporosis. Here, effects of ODN compared to alendronate (ALN) on bone turnover, DXA-based areal bone mineral density (aBMD), QCT-based volumetric BMD (vBMD) and geometric parameters were studied in ovariectomized (OVX) rhesus monkeys. Treatment was initiated 10 days after ovariectomy and continued for 20 months. The study consisted of four groups: L-ODN (2 mg/kg, daily p.o.), H-ODN (8/4 mg/kg daily p.o.), ALN (15 μg/kg, twice weekly, s.c.), and VEH (vehicle, daily, p.o.). L-ODN and ALN doses were selected to approximate the clinical exposures of the ODN 50-mg and ALN 70-mg once-weekly, respectively. L-ODN and ALN effectively reduced bone resorption markers uNTx and sCTx compared to VEH. There was no additional efficacy with these markers achieved with H-ODN. Conversely, ODN displayed inversely dose-dependent reduction of bone formation markers, sP1NP and sBSAP, and L-ODN reduced formation to a lesser degree than ALN. At month 18 post-OVX, L-ODN showed robust increases in lumbar spine aBMD (11.4%, pmonkeys in prevention mode. Taken together, the results from this study have demonstrated that administration of ODN at levels which approximate clinical exposure in OVX-monkeys had comparable efficacy to ALN in DXA-based aBMD and QCT-based vBMD. However, FN cortical mineral content clearly demonstrated superior efficacy of ODN versus ALN in this model of estrogen-deficient non-human primates. © 2013 Elsevier Inc. All rights reserved.

  2. A biomechanical comparison of 3.5 locking compression plate fixation to 3.5 limited contact dynamic compression plate fixation in a canine cadaveric distal humeral metaphyseal gap model.

    Science.gov (United States)

    Filipowicz, D; Lanz, O; McLaughlin, R; Elder, S; Werre, S

    2009-01-01

    3.5 locking compression plate (LCP) fixation was compared to 3.5 limited contact dynamic compression plate (LC-DCP) fixation in a canine cadaveric, distal humeral metaphyseal gap model. Thirty paired humeri from adult, large breed dogs were separated into equal groups based on testing: static compression, cyclic compression, and cyclic torsion. Humeral constructs stabilised with LCP were significantly stiffer than those plated with LC-DCP when loaded in static axial compression (P = 0.0004). When cyclically loaded in axial compression, the LCP constructs were significantly less stiff than the LC-DCP constructs (P = 0.0029). Constructs plated with LCP were significantly less resistant to torsion over 500 cycles than those plated with LC-DCP (Plocking plates may be attributed to the stability afforded by the plate-screw interface of locking plates. The LCP constructs demonstrated less stiffness in dynamic testing in this model, likely due to plate-bone offset secondary to non-anatomic contouring and occasional incomplete seating of the locking screws when using the torque-limiting screw driver. Resolution of these aspects of LCP application may help improve the stiffness of fixation in fractures modeled by the experimental set-up of this investigation.

  3. The role of galenic innovation in improving treatment compliance and persistence: three case studies

    Directory of Open Access Journals (Sweden)

    Gili Marco A

    2011-08-01

    Full Text Available York Zoellner1, Maria-Magdalena Balp2, Andrea Gili Marco21Hamburg University of Applied Sciences, Hamburg, Germany; 2Novartis Pharma AG, Basel, SwitzerlandBackground: The purpose of this study was to explore whether newer galenic formulations with lower treatment burdens are associated with better patient compliance and persistence compared with older more burdensome modalities.Methods: Data from the IMS Disease Analyzer database were analyzed retrospectively for two pairs of analogs (alendronate sodium once daily vs once weekly and immediate-release vs extended-release methylphenidate and one pair of drugs with similar indications but important differences in convenience and dosing instructions (desferrioxamine vs deferasirox. Compliance was calculated as the sum of prescription durations for all prescriptions for each patient over 1 year. Persistence was calculated as the time between first and last prescriptions over 2 years (1 year for deferasirox and desferrioxamine. Data from Germany and the UK were available and used for analysis.Results: Incremental improvements in compliance were +30% in the UK and +26% in Germany for alendronate once weekly vs once daily, +14% in the UK and +19% in Germany for extended-release vs immediate-release methylphenidate, and +15% in Germany for desferrioxamine vs deferasirox. Incremental improvements in persistence were +9 months in the UK and +8 months in Germany for alendronate once weekly vs once daily, +4 months in the UK and +3 months in Germany for extended-release vs immediate-release methylphenidate, and +2 months in Germany for deferasirox vs desferrioxamine.Conclusion: The new formulations that we evaluated were associated with better compliance and persistence compared with older formulations. Despite the fact that some sources of bias could not be excluded, it is likely that these improvements can be attributed to the lower treatment burdens of the galenic formulations of the drugs considered

  4. Characterization of alendronic- and undecylenic acid coated magnetic nanoparticles for the targeted delivery of rosiglitazone to subcutaneous adipose tissue.

    Science.gov (United States)

    Saatchi, Katayoun; Tod, Sarah E; Leung, Donna; Nicholson, Kenton E; Andreu, Irene; Buchwalder, Christian; Schmitt, Veronika; Häfeli, Urs O; Gray, Sarah L

    2017-02-01

    Obesity is a state of positive energy balance where excess white adipose tissue accumulates to the detriment of metabolic health. Improving adipocyte function with systemic administration of thiazolidinediones (TZDs) improves metabolic outcomes in obesity, however TZD use is limited clinically due to undesirable side effects. Here we evaluate magnetic nanoparticles (MNPs) as a tool to target rosiglitazone (Rosi) specifically to adipose tissue. Results show Rosi can be adsorbed to MNPs (Rosi-MNPs) with hydrophobic coatings for which we present binding and release kinetics. Rosi adsorbed to MNPs retained the ability to induce PPARγ target gene expression in cells. Biodistribution analysis of radiolabeled Rosi-MNPs revealed a fat-implanted magnet significantly enhanced localization of Rosi to the targeted adipose tissue when administered by subcutaneous injection to obese mice. We propose MNPs for targeted delivery of anti-diabetic agents to superficially located subcutaneous adipose tissue. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Treatment of two-part fractures of the surgical neck of the humerus using a locked metaphyseal intramedullary nail proximally with angular stability

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    Leandro Viecili

    2015-02-01

    Full Text Available OBJECTIVES: To evaluate the functional results from patients with surgical neck fractures treated with a locked metaphyseal intramedullary nail and angular stability.METHODS: Twenty-two patients between the ages of 21 and 69 years were evaluated prospectively between January 2010 and January 2011. Their time taken for consolidation, age, sex, complications and functional results were correlated using the modified protocol of the University of California at Los Angeles (UCLA.RESULTS: The mean time taken for consolidation was 9.26 weeks ± confidence interval (CI of 0.40 weeks. One case (4.5% did not become consolidated. There were no cases of infection. There was one case (4.5% of adhesive capsulitis with good evolution through clinical treatment. Five patients (22.7% presented occasional mild pain and one case (4.5% reported medium-intensity pain associated with the subacromial impact of the implant. The mean score on the modified UCLA scale was 30.4 ± CI 1.6 points, obtained at the end of 12 weeks of evaluation: 18 cases (81.8% with "excellent" and "good" scores, three cases (13.6% with "fair" scores and one case (4.5% with a "poor" score.CONCLUSION: In the group of patients evaluated, treatment of two-part surgical neck fractures by means of a locked metaphyseal intramedullary nail and angular stability demonstrated satisfactory functional results and a low complication rate, similar to what is seen in the literature.

  6. The Metaphysics of Time

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    m a

    2012-03-01

    Events and moments, he thinks, can occur in time in two forms and thus there are two series of time: 1 A series in which two events and moments are ordered as past, present and future, 2 B series in which the events and moments are ordered as a priori and a posterior. The A series is necessary for time because without A series time does not exist. At the same time, A series leads to contradiction and time cannot exist as a real thing. Only one real and non-temporal series, he believes, exists but it appears as time series to us by our perception.

  7. Metaphysics after Aquinas

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    Moses Aaron T. Angeles

    2007-12-01

    Full Text Available It is interesting to note that after the death of St. Thomas his mentor, St. Albert the Great, remarked that his student put up an end to everybody's labor, not only in their own time, but even right up to the end of time. This was reported to us by a certain Bartholomew of Capua, protonotary from the Kingdom of Sicily, who was a witness of St. Thomas' canonization process. After the sudden demise of Thomas, Albert, already advanced in age, has assumed the task of defending the integrity of his student as a theologian and philosopher. On his return to Cologne, he wanted that all the works of Thomas read to him in set order, and he concluded his encomia saying that "Brother Thomas had in his writings put an end to everybody's labors right up to the end of the world, and that from now on all further work would be without purpose." Certainly modern readers would question such an assertion. Now that every ideology and systems of thought are under the suspicious eyes of postmodern thinkers, care must be exercised in proclaiming something as final and definite. No wonder such a statement was rarely uttered even within the ranks of the Dominican Friars.

  8. Marionette, Mechanics, Metaphysics, Modernity

    DEFF Research Database (Denmark)

    Holm, Bent

    scientific analyses of the marionette as a historical and a thematical phenomenon from the tradistional via the avant-garde to the electronis version......scientific analyses of the marionette as a historical and a thematical phenomenon from the tradistional via the avant-garde to the electronis version...

  9. Teriparatide vs. alendronate as a treatment for osteoporosis: changes in biochemical markers of bone turnover, BMD and quality of life.

    Science.gov (United States)

    Panico, Annalisa; Lupoli, Gelsy Arianna; Marciello, Francesca; Lupoli, Roberta; Cacciapuoti, Marianna; Martinelli, Addolorata; Granieri, Luciana; Iacono, Daniela; Lupoli, Giovanni

    2011-08-01

    We studied the use of teriparatide in postmenopausal women with severe osteoporosis. Two groups (A and B) of patients affected by severe osteoporosis (T-score ≤-2.5 at bone mineral density were analyzed and 2 vertebral fractures on radiograph). Group A was treated for 18 months with 20 µg/day of teriparatide. Group B was treated with bisphosphonates 70 mg/week. Every woman assumed 1 g of calcium and 800 IU of vitamin D3 daily. We evaluated the effects of therapy after 18 months (T18) from the beginning with bone turnover markers (alkaline phosphatase, procollagen type 1 N-terminal propeptide, and N-telopeptide cross-links) and dual-energy X-ray absorptiometry. Group A, at T18 procollagen type 1 N-terminal propeptide levels, increased 127%; bone alkaline phosphatase levels increased to 65%; N-telopeptide cross-links levels increased to 110%. Group B, at T18 procollagen type 1 N-terminal propeptide levels, decreased to 74%; bone alkaline phosphatase levels decreased to 41%; N-telopeptide cross-links levels decreased to 72%. After 18 months, lumbar bone mineral density increased to 12.4% and femoral bone mineral density increased to 5.2% in group A. Group B lumbar bone mineral density increased to 3.85% and femoral bone mineral density increased to 1.99%. Only a new vertebral fracture occurred in group A (2.4%), whereas 6 fractures occurred in group B (15.7%). The quality of life questionnaire of the European Foundation for Osteoporosis (QUALEFFO) revealed a significant improvement in daily living, performed domestic jobs, and locomotor function in groups A and B. The use of rhPTH in patients with severe osteoporosis offers more protection against fractures and improves the QoL more than bisphosphonates.

  10. Bioequivalence of generic alendronate sodium tablets (70 mg to Fosamax® tablets (70 mg in fasting, healthy volunteers: a randomized, open-label, three-way, reference-replicated crossover study

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    Zhang Y

    2017-07-01

    Full Text Available Yifan Zhang,1 Xiaoyan Chen,1 Yunbiao Tang,2 Youming Lu,1 Lixia Guo,1 Dafang Zhong1 1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 2Department of Pharmacy, The General Hospital of Shenyang Military Region, Shenyang, People’s Republic of China Purpose: The aim of this study was to evaluate the bioequivalence of a generic product 70 mg alendronate sodium tablets with the reference product Fosamax® 70 mg tablet. Materials and methods: A single-center, open-label, randomized, three-period, three-sequence, reference-replicated crossover study was performed in 36 healthy Chinese male volunteers under fasting conditions. In each study period, the volunteers received a single oral dose of the generic or reference product (70 mg. Blood samples were collected at pre-dose and up to 8 h after administration. The bioequivalence of the generic product to the reference product was assessed using the US Food and Drug Administration (FDA and European Medicines Agency (EMA reference-scaled average bioequivalence (RSABE methods. Results: The average maximum concentrations (Cmax of alendronic acid were 64.78±43.76, 56.62±31.95, and 60.15±37.12 ng/mL after the single dose of the generic product and the first and second doses of the reference product, respectively. The areas under the plasma concentration–time curves from time 0 to the last timepoint (AUC0–t were 150.36±82.90, 148.15±85.97, and 167.11±110.87 h·ng/mL, respectively. Reference scaling was used because the within-subject standard deviations of the reference product (sWR for Cmax and AUC0–t were all higher than the cutoff value of 0.294. The 95% upper confidence bounds were -0.16 and -0.17 for Cmax and AUC0–t, respectively, and the point estimates for the generic/reference product ratio were 1.08 and 1.00, which satisfied the RSABE acceptance criteria of the FDA. The 90% CIs for Cmax and AUC0–t were 90.35%–129

  11. A new metaphyseal bone defect model in osteoporotic rats to study biomaterials for the enhancement of bone healing in osteoporotic fractures.

    Science.gov (United States)

    Alt, Volker; Thormann, Ulrich; Ray, Seemun; Zahner, Daniel; Dürselen, Lutz; Lips, Katrin; El Khassawna, Thaqif; Heiss, Christian; Riedrich, Alina; Schlewitz, Gudrun; Ignatius, Anita; Kampschulte, Marian; von Dewitz, Helena; Heinemann, Sascha; Schnettler, Reinhard; Langheinrich, Alexander

    2013-06-01

    The intention of this study was to establish a new critical size animal model that represents clinically relevant situations with osteoporotic bone status and internally fixated metaphyseal defect fractures in which biomaterials for the enhancement of fracture healing in osteoporotic fracture defects can be studied. Twenty-eight rats were ovariectomized (OVX) and treated with a calcium-, phosphorus-, vitamin D3-, soy- and phytoestrogen-free diet. After 3months Dual-energy X-ray absorptiometry measurements showed statistically significant reductions in bone mineral density of the spine of -25.9% and of the femur of -21.3% of the OVX rats compared with controls, confirming osteoporosis in the OVX rats. The OVX rats then underwent either 3 or 5mm wedge-shaped osteotomy of the distal metaphyseal area of the femur that was internally stabilized with a T-shaped mini-plate. After 42days biomechanical testing yielded completely unstable conditions in the 5mm defect femora (bending stiffness 0Nmm(-2)) and a bending stiffness of 12,500Nmm(-2) in the 3mm defects, which showed the beginning of fracture consolidation. Micro-computed tomography showed statistically significant more new bone formation in the 3mm defects (4.83±0.37mm(2)), with bridging of the initial fracture defect area, compared with the 5mm defects (2.68±0.34mm(2)), in which no bridging of the initial defect was found. These results were confirmed by histology. In conclusion, the 5mm defect can be considered as a critical size defect model in which biomaterials can be tested. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  12. Necessidade, objetividade e o paradoxo metafísico do conhecimento científico Necessity, objectivity, and the metaphysical paradox of scientific knowledge

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    José Ricardo de C. M. Ayres

    1995-06-01

    Full Text Available A racionalidade científica moderna, buscando superar a fundamentação metafísica do conhecimento objetivo, toma a experiência do fato particular como a atualização de leis dadas a priori na mente humana ou na natureza, constituindo, paradoxalmente, uma nova e 'intransparente' metafísica. Entre as críticas contemporâneas a esta forma de pensar e fazer ciência, delineia-se uma compreensão construtivista, segundo a qual o fato particular e seu conhecimento objetivo resultam de relações circunstanciais entre o homem e seu mundo. Revisitando alguns dos principais fundadores da ciência ocidental, como Aristóteles, Bacon, Descartes, Leibniz, Kant, Newton e Stuart Mill, este ensaio hermenêutico procura explorar a participação do metaconceito de 'necessidade' nessa dialética do conhecimento, interpretando, em termos epistemológicos, seu papel na construção e hipóstase da racionalidade científica moderna.Modern scientific rationality, seeking to move beyond the metaphysical foundations of objective knowledge, takes the experience of a particular fact to be the actual expression of prior laws of the human mind or of nature, thereby paradoxically constituting a new, 'invisible' metaphysics. Among contemporary critiques of this way of 'thinking and doing science', a constructivist understanding is gaining outline; according to this conception, a particular fact and objective knowledge thereof derive from circumstantial relations between human beings and their world. Revisiting some of the main founders of Western science, such as Aristotle, Bacon, Descartes, Leibniz, Kant, Newton, and Stuart Mill, this hermeneutic essay explores the participation of the meta-concept of 'necessity' within this dialectic of knowledge and, in epistemological terms, interprets its role in the construction and hypostatization of modern scientific rationality.

  13. A prospective, randomised trial comparing closed intramedullary nailing with percutaneous plating in the treatment of distal metaphyseal fractures of the tibia.

    Science.gov (United States)

    Guo, J J; Tang, N; Yang, H L; Tang, T S

    2010-07-01

    We compared the outcome of closed intramedullary nailing with minimally invasive plate osteosynthesis using a percutaneous locked compression plate in patients with a distal metaphyseal fracture in a prospective study. A total of 85 patients were randomised to operative stabilisation either by a closed intramedullary nail (44) or by minimally invasive osteosynthesis with a compression plate (41). Pre-operative variables included the patients' age and the side and pattern of the fracture. Peri-operative variables were the operating time and the radiation time. Postoperative variables were wound problems, the time to union of the fracture, the functional American Orthopaedic Foot and Ankle surgery score and removal of hardware. We found no significant difference in the pre-operative variables or in the time to union in the two groups. However, the mean radiation time and operating time were significantly longer in the locked compression plate group (3.0 vs 2.12 minutes, p Foot and Ankle surgery scores, although the differences were not statistically significant (p = 0.234, p = 0.157, p = 0.897, p = 0.177 respectively). Three (6.8%) patients in the intramedullary nailing group and six (14.6%) in the locked compression plate group showed delayed wound healing, and 37 (84.1%) in the former group and 38 (92.7%) in the latter group expressed a wish to have the implant removed. We conclude that both closed intramedullary nailing and a percutaneous locked compression plate can be used safely to treat Orthopaedic Trauma Association type-43A distal metaphyseal fractures of the tibia. However, closed intramedullary nailing has the advantage of a shorter operating and radiation time and easier removal of the implant. We therefore prefer closed intramedullary nailing for patients with these fractures.

  14. Heidegger leitor de Nietzsche: a metafísica da vontade de potência como consumação da metafísica ocidental Heidegger reader of Nietzsche: a metaphysics of the will power as a consummation of Western metaphysics

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    Wanderley J. Ferreira Jr

    2013-04-01

    Full Text Available Aspectos básicos da leitura heideggeriana de Nietzsche. As possibilidades e as possíveis distorções operadas por tal interpretação em alguns conceitos fundamentais do pensamento nietzschiano. Num primeiro momento, explicitam-se as duas atitudes de Heidegger diante da história da filosofia e de seus principais pensadores, em momentos diferentes de seu pensamento. Em seguida, analisa-se, com um certo distanciamento crítico, em que sentido, conforme Heidegger, ocorre a consumação da metafísica do sujeito pensante [Descartes] na metafísica da vontade de potência e na ideia de além do homem, em Nietzsche.This article presents the basic aspects of Heidegger's reading of Nietzsche and the possibilities and possible distortions of this interpretation with regard to some basic concepts of Nietzschean thought. First, we make explicit two different attitudes of Heidegger toward the history of philosophy and its leading thinkers, as found in different periods of Heidegger's thought. Secondly we analyze, with a certain critical distance, in what sense, according to Heidegger, metaphysics is the consummation of the thinking subject (Descartes in the metaphysics of the will to power and the idea of beyond man in Nietzsche.

  15. Metaphyseal Distal Tibia Fractures: A Cohort, Single-Surgeon Study Comparing Outcomes of Patients Treated With Minimally Invasive Plating Versus Intramedullary Nailing.

    Science.gov (United States)

    Barcak, Eric; Collinge, Cory A

    2016-05-01

    The purpose of this study was to compare clinical and functional outcomes of patients with distal tibia fractures treated with minimally invasive plating (MIPO) or intramedullary nailing (IMN). Cohort study. Level II regional trauma center. Overall, 86 patients with metaphyseal distal fractures (within 5 cm of joint) with simple or no articular involvement treated by a single, fellowship trained, orthopedic trauma surgeon from 2002 to 2013. Intramedullary nailing or minimally invasive plate osteosynthesis. Clinical and radiographic results were evaluated at a minimum of 1-year follow-up. Limb-specific outcomes (American Orthopedic Foot and Ankle Surgeons' ankle-hindfoot instrument) and whole-person measures [Short Form 36 (SF-36) instrument] were assessed at the final follow-up. We studied 86 patients with distal tibia fractures treated with MIPO (43 patients) and IMN (43 patients). Thirty-seven patients in the MIPO group and 27 in the IMN group met inclusion criteria. All patients ultimately healed, with the average time to union of 23 weeks in both the groups. Complications were similar between the 2 groups (MIPO vs. IMN, respectively), including nonunion (8% vs. 7%), malalignment (3.6% vs. 3%), wound complications (3.6% vs. 3%), and infection (0% vs. 3.6%). The need for secondary procedures for the removal of implants was 25.9% in the IMN group (distal locking screws only in 6/7) versus 8.3% in the MIPO group (P = 0.05). Additionally, the American Orthopedic Foot and Ankle Surgeons and all SF-36 version 2 domain scores were quantitatively higher for the IMN group, although only Role Emotional reached a level of statistical superiority between the groups. Similar clinical results and marginally enhanced functional outcomes were seen when treating nonarticular or minimally articular metaphyseal distal tibia fractures with IMN compared with MIPO. However, patients treated with IMN required more frequent secondary surgeries for the removal of painful distal locking

  16. A Biomechanical Comparison of 3.5 Locking Compression Plate Fixation to 3.5 Limited Contact Dynamic Compression Plate Fixation in a Canine Cadaveric Distal Humeral Metaphyseal Gap Model

    OpenAIRE

    Filipowicz, Dean

    2008-01-01

    Objective- To compare the biomechanical properties of 3.5 locking compression plate (LCP) fixation to 3.5 limited contact dynamic compression plate (LC-DCP) fixation in a canine cadaveric, distal humeral metaphyseal gap model in static axial compression and cyclic axial compression and torsion. Study Design- Biomechanical in vitro study. Sample Population- 30 paired humeri from adult, medium to large breed dogs. Methods- Testing was performed monotonically to failure in axial compres...

  17. Esophageal transit and in vivo disintegration of branded risedronate sodium tablets and two generic formulations of alendronic acid tablets: a single-center, single-blind, six-period crossover study in healthy female subjects.

    Science.gov (United States)

    Perkins, Alan C; Blackshaw, P Elaine; Hay, Peter D; Lawes, Simon C; Atherton, Clare T; Dansereau, Richard J; Wagner, Leigh K; Schnell, Dan J; Spiller, Robin C

    2008-05-01

    Delayed esophageal transit or disintegration of oral bisphosphonate tablets before they enter the stomach may be of concern with respect to iatrogenic complications among patients receiving longterm treatment. Different formulations of generic bisphosphonate tablets meeting regulatory requirements may have substantial differences in pharmaceutical attributes from the branded product that may result in different characteristics during esophageal transit. The primary objective of this study was to evaluate and compare esophageal transit times and in vivo disintegration of 3 bisphosphonate formulations, one branded and the others generic, that are commercially available in Canada and the United Kingdom. This was a single-center, randomized, singleblind, 6-period crossover study in healthy postmenopausal women aged >50 years. Each subject received a single oral dose of a branded risedronate sodium 35-mg tablet and 2 generic formulations of alendronic acid 70-mg tablets (Novopharm Limited, Toronto, Canada, and Teva UK Limited, Morley, United Kingdom) in both the erect and semisupine (45 degrees ) positions. Although the products are labeled to be taken in the erect position, the semisupine position was included to simulate dosing in bedridden patients. Subjects took tablets with 30 mL of water in the morning after an overnight fast. The tablets were radiolabeled with technetium-99m ion-exchange resins to enable visualization and measurement of esophageal transit time and disintegration using a gamma camera. Dynamic scintigraphic images were obtained for a total of 10 minutes: 2 images per second for the first 30 seconds and 1 image every 15 seconds for 9.5 minutes. This was a mechanistic study and tolerability was not assessed. The study was conducted in 20 healthy white female subjects with a mean age of 62 years (range, 51-77 years). The effect of body position was statistically significant (P = 0.043), with the estimated hazard ratio (HR) of 0.74 indicating longer

  18. The fate of the hip in spondylo-epi-metaphyseal dysplasia: clinical and radiological evaluation of adults with SEMD Handigodu type

    International Nuclear Information System (INIS)

    Siddesh, N.D.; Shah, Hitesh; Joseph, Benjamin

    2012-01-01

    This study was undertaken to document the fate of the hip with reference to its structure and function in patients with spondylo-epi-metaphyseal dysplasia tarda Handigodu type (SEMD HG ). Radiographs of 271 adult patients with SEMD HG were studied to identify the pattern of long-term sequelae in the hips. Several measurements of the proximal femur and acetabulum were made to quantify morphological alterations in the hip. Fifty-four adult patients were examined and administered a questionnaire to evaluate the extent of disability attributable to the hips. Three patterns of changes in the hips were noted: 35% had acetabular protrusio, 33% had subluxation of the hip, and 32% had no protrusio or subluxation. Distinctly different anthropometric measurements and dimensional alterations around the hip were noted in these three patterns. Patients with protrusio were relatively tall while those with subluxation were the shortest. All the patients had developed degenerative arthritis of the hips by the fourth decade of life irrespective of the pattern of hip involvement. The reduction in the range of hip motion and fixed deformities were most severe in patients with protrusio. All the patients had significant disability and very low functional hip scores. Degenerative arthritis of the hip develops in the majority of patients with SEMD HG ; the symptoms are severe enough to warrant reconstructive surgery by the fourth decade of life. Protrusio or subluxation develops in a third of the patients each; both these complications will influence the surgical approach if total hip arthroplasty is planned. (orig.)

  19. From the "metaphysics of the individual" to the critique of society: on the practical significance of Michel Henry's phenomenology of life.

    Science.gov (United States)

    Staudigl, Michael

    This essay explores the practical significance of Michel Henry's "material phenomenology." Commencing with an exposition of his most basic philosophical intuition, i.e., his insight that transcendental affectivity is the primordial mode of revelation of our selfhood, the essay then brings to light how this intuition also establishes our relation to both the world and others. Animated by a radical form of the phenomenological reduction, Henry's material phenomenology brackets the exterior world in a bid to reach the concrete interior transcendental experience at the base of all exteriority. The essay argues that this "counter reduction," designed as a practical orientation to the world, suspends all traditional parameters of onto(theo)logical individuation in order to rethink subjectivity in terms of its transcendental corporeality, i.e., in terms of the invisible display of "affective flesh." The development of this "metaphysics of the individual" anchors his "practical philosophy" as he developed it-under shifting accents-throughout his oeuvre. In particular, the essay brings into focus Henry's reflections on modernity, the industry of mass culture and their "barbaric" movements. The essay briefly puts these cultural and political areas of Henry's of thinking into contact with his late "theological turn," i.e., his Christological account of Life and the (inter)subjective self-realization to which it gives rise.

  20. LAS CRÍTICAS DE ARISTÓTELES A PLATÓN EN METAFÍSICA I, 9 ARISTOTLE’S CRITICISMS OF PLATO IN METAPHYSICS I, 9

    Directory of Open Access Journals (Sweden)

    Silvana Gabriela Di Camillo

    2011-03-01

    Full Text Available

    O recurso à exposição crítica das doutrinas anteriores é um procedimento metodológico usual em Aristóteles. Mas a característica distintiva do Livro I da Metafísica é que, ao invés de estabelecer uma nova doutrina, o exame dos predecessores serve para confirmar os próprios conceitos aristotélicos, os quais ele usa para avaliar os êxitos e os erros das doutrinas analisadas. Essa imposição de conceitos próprios lhe valeu a acusação de ter uma compreensão histórica distorcida. Com a análise detalhada das críticas da teoria platônica das Idéias na Metafísica I, 9, pretendemos mostrar: a que as críticas de manipulação e distorção das opiniões dos seus antecessores ofuscam o grau em que as suas próprias posições emergem de uma análise crítica do pensamento anterior; e b que a imposição de conceitos próprios não é uma distorção, mas uma proposta de solução para os problemas que as teorias anteriores deixaram sem solução.

    The use of critical exposition of previous doctrines is a methodological procedure usual in Aristotle. But the distinctive characteristic of Book I of the Metaphysics is that, rather than to establish a new doctrine, a review of  predecessors serves to confirm the own concepts to be used in the evaluation of the doctrines examined. This imposition of own terms has cost him the charge of distorting historical understanding. With the detailed analysis of the criticisms of Plato's theory of Ideas in Metaphysics I, 9, we intend to show a that the criticism of manipulation and distortion of his predecessors' views overshadow the degree to which Aristotle's own positions emerge from a critical review of previous thought and b that the

  1. Absolute becoming, relational becoming and the arrow of time: Some non-conventional remarks on the relationship between physics and metaphysics

    Science.gov (United States)

    Dorato, Mauro

    The literature on the compatibility between the time of our experience-characterized by passage or becoming-and time as is represented within spacetime theories has been affected by a persistent failure to get a clear grasp of the notion of becoming, both in its relation to an ontology of events "spread" in a four-dimensional manifold, and in relation to temporally asymmetric physical processes. In the first part of my paper I try to remedy this situation by offering what I consider a clear and faithful explication of becoming, valid independently of the particular spacetime setting in which we operate. Along the way, I will show why the metaphysical debate between the so-called "presentists" and "eternalists" is completely irrelevant to the question of becoming, as the debate itself is generated by a failure to distinguish between a tensed and a tenseless sense of "existence". After a much needed distinction between absolute and relational becoming, I then show in what sense classical (non-quantum) spacetime physics presupposes both types of becoming, for the simple reason that spacetime physics presupposes an ontology of (timelike-separated) events. As a consequence, not only does it turn out that using physics to try to provide empirical evidence for the existence of becoming amounts to putting the cart before the horses, but also that the order imposed by "the arrow of becoming" is more fundamental than any other physical arrow of time, despite the fact that becoming cannot be used to explain why entropy grows, or retarded electromagnetic radiation prevails versus advanced radiation.

  2. The fate of the hip in spondylo-epi-metaphyseal dysplasia: clinical and radiological evaluation of adults with SEMD Handigodu type

    Energy Technology Data Exchange (ETDEWEB)

    Siddesh, N.D.; Shah, Hitesh; Joseph, Benjamin [Kasturba Medical College, Paediatric Orthopaedic Service, Manipal, Karnataka State (India)

    2012-08-15

    This study was undertaken to document the fate of the hip with reference to its structure and function in patients with spondylo-epi-metaphyseal dysplasia tarda Handigodu type (SEMD{sub HG}). Radiographs of 271 adult patients with SEMD{sub HG} were studied to identify the pattern of long-term sequelae in the hips. Several measurements of the proximal femur and acetabulum were made to quantify morphological alterations in the hip. Fifty-four adult patients were examined and administered a questionnaire to evaluate the extent of disability attributable to the hips. Three patterns of changes in the hips were noted: 35% had acetabular protrusio, 33% had subluxation of the hip, and 32% had no protrusio or subluxation. Distinctly different anthropometric measurements and dimensional alterations around the hip were noted in these three patterns. Patients with protrusio were relatively tall while those with subluxation were the shortest. All the patients had developed degenerative arthritis of the hips by the fourth decade of life irrespective of the pattern of hip involvement. The reduction in the range of hip motion and fixed deformities were most severe in patients with protrusio. All the patients had significant disability and very low functional hip scores. Degenerative arthritis of the hip develops in the majority of patients with SEMD{sub HG}; the symptoms are severe enough to warrant reconstructive surgery by the fourth decade of life. Protrusio or subluxation develops in a third of the patients each; both these complications will influence the surgical approach if total hip arthroplasty is planned. (orig.)

  3. Metaphysics of the tea ceremony: a randomized trial investigating the roles of intention and belief on mood while drinking tea.

    Science.gov (United States)

    Shiah, Yung-Jong; Radin, Dean

    2013-01-01

    This study explored whether drinking tea "treated" with good intentions would enhance mood more than drinking ordinary tea, under double-blind, randomized conditions. Each evening, for seven days in a row, volunteers recorded their mood using the Profile of Mood States (POMS) questionnaire. On days three, four, and five of the test, each participant drank 600 mL of oolong tea in the morning and again in the afternoon. One randomly assigned group blindly received tea that had been intentionally treated by three Buddhist monks; the other group blindly received untreated tea from the same source. On the last day of the test, each person indicated what type of tea he/she believed he/she had been drinking. Stratified, random sampling was used to assign 189 adults into two groups matched by age, gender, the psychological trait of neuroticism, and the amount of tea consumed on average per day. All participants were Taiwanese and lived in Kaohsiung, Taiwan, and the test was conducted over the course of one week to reduce mood fluctuations due to changes in local weather and other common influences. Those who drank treated tea showed a greater increase in mood than those who drank untreated tea (Cohen's d = 0.65, P = .02, two-tailed). Change in mood in those who believed that they were drinking treated tea was much better than those who did not believe (Cohen's d = 1.45, P = .00002, two-tailed). Tea treated with good intentions improved mood more than ordinary tea derived from the same source. Belief that one was drinking treated tea produced a large improvement in mood, but only if one was actually drinking the treated tea, indicating that belief and intentional enhancement interact. This also suggests that the esthetic and intentional qualities associated with the traditional tea ceremony may have subtle influences that extend beyond the ritual itself. © 2013 Elsevier Inc. All rights reserved.

  4. Influence of treatment with alendronate on the speed of sound, an ultrasound parameter, of the calcaneus in postmenopausal Japanese women with osteoporosis: a clinical practice-based observational study

    Directory of Open Access Journals (Sweden)

    Iwamoto J

    2012-06-01

    Full Text Available Jun Iwamoto,1 Tetsuya Takada,2 Yoshihiro Sato,3 Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, 2Department of Internal Medicine, Hiyoshi Medical Clinic, Kanagawa, 3Department of Neurology, Mitate Hospital, Fukuoka, JapanPurpose: The influence of alendronate (ALN treatment on the quantitative ultrasound parameters of the calcaneus remains to be established in Japanese patients. The aim of the present clinical practice-based observational study was to examine the influence of ALN treatment for 1 year on the speed of sound (SOS of the calcaneus and bone turnover markers in postmenopausal Japanese women with osteoporosis.Patients and methods: Forty-five postmenopausal Japanese women with osteoporosis who had received treatment with ALN for more than 1 year were enrolled in the study. The SOS and bone turnover markers were monitored over 1 year of ALN treatment.Results: The urinary levels of cross-linked N-terminal telopeptides of type I collagen and serum levels of alkaline phosphatase decreased significantly from the baseline values (–44.9% at 3 months and –22.2% at 12 months, respectively. The SOS increased modestly, but significantly, from the baseline value (0.6% at both 6 and 12 months. The percentage decrease in the urinary levels of cross-linked N-terminal telopeptides of type I collagen at 3 months was significantly correlated with the percentage increase in the SOS only at 6 months (correlation coefficient, 0.299.Conclusion: The present study confirmed that ALN treatment suppressed bone turnover, producing a clinically significant increase in the SOS of the calcaneus in postmenopausal Japanese women with osteoporosis.Keywords: postmenopausal osteoporosis, quantitative ultrasound (QUS, SOS, bone turnover, biochemical markers

  5. Open, Prospective, Multi-Center, Two-Part Study of Patient Preference with Monthly Ibandronate Therapy in Women with Postmenopausal Osteoporosis Switched From Daily or Weekly Alendronate or Risendronate-BONCURE: Results of Turkish Sub-Study

    Directory of Open Access Journals (Sweden)

    Nurten Eskiyurt

    2012-04-01

    Full Text Available Aim: BONCURE (Bonviva for Current Bisphosphonate Users Regional European Trial, aimed to evaluate patient preference with monthly ibandronate in women with postmenopausal osteoporosis who previously received daily or weekly alendronate or risendronate. Materials and Methods: This prospective, open-label study consisted of two sequential stages, Part A (screening and Part B (treatment. Patients enrolled into Part A completed the Candidate Identification Questionnaire (CIQ. In Part B, after completing the Osteoporosis Patient Satisfaction Questionnaire (OPSATQ, patients received monthly oral ibandronate 150 mg for 6 months. Following treatment, patients completed the OPSAT-Q and Preference Questionnaire. Results: A total of 223 patients (mean age, 63.7±9.51 years were enrolled in Part A from Turkey. Among them, 103 (46.2% answered “YES” to at least one CIQ question. The mean composite OPSAT-Q domain scores increased for convenience (mean change, 15.3±17.7 points, quality of life (10.4±20.4 points, overall satisfaction (11.9±22.7 points, and side effects (3.3±18.8 points. At month 6, 177 subjects (92.7% preferred once-monthly dosing schedule and 99.0% were compliant (≥80% with study treatment. Thirty (15.6% subjects experienced mild to moderate adverse events, mostly gastrointestinal. Conclusion: Postmenopausal women with osteoporosis prefer and are more satisfied and compliant with monthly dosing of ibandronate than daily or weekly bisphosphonate treatment. (Turkish Journal of Osteoporosis 2012;18:1-7

  6. Interzones of Law and Metaphysics

    DEFF Research Database (Denmark)

    Mossin, Christiane

    The dissertation analyzes a contemporary battlefield of law, the field of EU social rights, from a political-philosophical point of view. It is the conviction of the dissertation that law is deeply and inescapably conceptually connected with fundamental features of social order. The interrelations...... between the two do not merely concern the rights and obligations explicitly laid down in the law, but fundamental presumptions regarding the nature of human beings, overall purposes of social order, hierarchical and dynamic features of society and the possibility at all of regulation, its logics......, the dissertation reveals that EU social rights imply the contours of a particular social order. The essential features in question are derived through detailed analyses of EU social rights - through critical investigations of definitions of rightholders, material scope, legal core concepts, exclusions...

  7. The Metaphysics of Economic Exchanges

    Directory of Open Access Journals (Sweden)

    Massin Olivier

    2017-05-01

    Full Text Available What are economic exchanges? The received view has it that exchanges are mutual transfers of goods motivated by inverse valuations thereof. As a corollary, the standard approach treats exchanges of services as a subspecies of exchanges of goods. We raise two objections against this standard approach. First, it is incomplete, as it fails to take into account, among other things, the offers and acceptances that lie at the core of even the simplest cases of exchanges. Second, it ultimately fails to generalize to exchanges of services, in which neither inverse preferences nor mutual transfers hold true. We propose an alternative definition of exchanges, which treats exchanges of goods as a special case of exchanges of services and which builds in offers and acceptances. According to this theory: (i The valuations motivating exchanges are propositional and convergent rather than objectual and inverse; (ii All exchanges of goods involve exchanges of services/actions, but not the reverse; (iii Offers and acceptances, together with the contractual obligations and claims they bring about, lie at the heart of all cases of exchange.

  8. Energy: Between Physics and Metaphysics.

    Science.gov (United States)

    Bunge, Mario

    2000-01-01

    The general concept of energy is somewhat unclear as long as it is confined to physics since every chapter of it defines its own particular concept of energy. The general concept can be elucidated in terms of the hypergeneral concepts of concrete things and changeability. Concludes that physicists and philosophers can learn from one another.…

  9. Osteoporosis grave con aplastamientos vertebrales en dermatomiositis juvenil: Efecto del tratamiento con alendronato oral Severe osteoporosis with vertebral crushes in juvenile dermatomyositis: Effect of oral alendronate therapy

    Directory of Open Access Journals (Sweden)

    Cristina Tau

    2007-02-01

    Full Text Available Los glucocorticoides son usados comúnmente para el tratamiento de enfermedades inflamatorias, autoinmunes, enfermedades malignas, y en la prevención de rechazo de órganos trasplantados. Un efecto secundario frecuente del tratamiento prolongado es la pérdida de masa ósea que se produce por varios mecanismos y es causa de osteoporosis y fracturas vertebrales. El tratamiento con disfosfonatos ha sido propuesto para esta situación. Presentamos un caso clínico de osteoporosis grave en una niña con dermatomiositis juvenil, que respondió favorablemente al tratamiento con disfosfonatos orales.Glucocorticoids are used for the treatment of inflammatory and autoimmune diseases, cancer, and in prevention of organ rejects. A frequent secondary effect of longterm treatment with corticoids is the loss of bone mass, caused by several mechanisms: decrease in the intestinal calcium absorption, increase of the renal calcium excretion at the distal renal tubule, suppressive effect on the osteoblast and also in apoptosis of osteoclasts, inhibition in local production of IGF I (Insulin-like growth factor and IGFBPs (binding IGF I proteins necessary for bone metabolism, and decrease on osteocalcin production. Longterm treatment with corticoids is associated with osteoporosis and vertebral fractures. To improve this condition, treatment with bisphosphonates has been proposed. We present here a clinical case of a girl with dermatomyositis and severe osteoporosis with vertebral crushes, who responded well to oral bisphophonate treatment.

  10. Histomorphometric Assessment of Cancellous and Cortical Bone Material Distribution in the Proximal Humerus of Normal and Osteoporotic Individuals: Significantly Reduced Bone Stock in the Metaphyseal and Subcapital Regions of Osteoporotic Individuals.

    Science.gov (United States)

    Sprecher, Christoph M; Schmidutz, Florian; Helfen, Tobias; Richards, R Geoff; Blauth, Michael; Milz, Stefan

    2015-12-01

    Osteoporosis is a systemic disorder predominantly affecting postmenopausal women but also men at an advanced age. Both genders may suffer from low-energy fractures of, for example, the proximal humerus when reduction of the bone stock or/and quality has occurred.The aim of the current study was to compare the amount of bone in typical fracture zones of the proximal humerus in osteoporotic and non-osteoporotic individuals.The amount of bone in the proximal humerus was determined histomorphometrically in frontal plane sections. The donor bones were allocated to normal and osteoporotic groups using the T-score from distal radius DXA measurements of the same extremities. The T-score evaluation was done according to WHO criteria. Regional thickness of the subchondral plate and the metaphyseal cortical bone were measured using interactive image analysis.At all measured locations the amount of cancellous bone was significantly lower in individuals from the osteoporotic group compared to the non-osteoporotic one. The osteoporotic group showed more significant differences between regions of the same bone than the non-osteoporotic group. In both groups the subchondral cancellous bone and the subchondral plate were least affected by bone loss. In contrast, the medial metaphyseal region in the osteoporotic group exhibited higher bone loss in comparison to the lateral side.This observation may explain prevailing fracture patterns, which frequently involve compression fractures and certainly has an influence on the stability of implants placed in this medial region. It should be considered when planning the anchoring of osteosynthesis materials in osteoporotic patients with fractures of the proximal humerus.

  11. Notions directrices et architectonique de la métaphysique. La critique kantienne de Wolff en 1763 Main notions and architectonics of metaphysics. Kant’s criticism of Wolff in 1763

    Directory of Open Access Journals (Sweden)

    Stefanie Buchenau

    2011-12-01

    éthode wolffienne qu’il n’est supposé communément, et leur débat gagne en profondeur.This paper presents Christian Wolff’s argument on the evidence of metaphysical principles as expounded in his article Directive notions and the true use of the first science (1729. This article was a central and yet forgotten reference for those who responded to the 1762/1763 academy questions such as Kant. Wolff here asserts that metaphysics has a kind of certainty that is equal or even superior to mathematics and that it communicates such certainty to the remaining sciences. It is this Wolffian thesis that Kant attacked in 1763. A closer reading allows to acknowledge more philosophical premises of Wolff’s argument. Wolff’s thesis on the mathematical certainty of metaphysics inverts the former order of priorities between metaphysics (ontology and mathematics. According to Wolff (who here seemed to be influenced by Euclides’ geometry, metaphysical notions are at the foundation of mathematical and logical rules. Notions such as “identity”, “thing”, “possibility” etc. have a “directive” or methodical status : they direct the mind searching the truth. Together, these notions constitute a modern and “architectonic” ontology. This framework shows the methodological continuity between Wolff and Kant. Even though Kant contested the form of Wolff’s system, his response still formed part of the general program sketched by Wolff. Kant still attempted to found some kind of architectonic metaphysics containing a table of directive concepts. From this viewpoint, Kant owes more to Wolff than what has been commonly assumed, and the deep and complex debate between the two thinkers calls for more attention.

  12. Efeitos do treinamento resistido sobre variáveis relacionadas com a baixa densidade óssea de mulheres menopausadas tratadas com alendronato Effects of resistance training on low bone density-related variables in menopausal women taking alendronate

    Directory of Open Access Journals (Sweden)

    Cláudio Joaquim Borba-Pinheiro

    2010-04-01

    Full Text Available A osteoporose é uma doença crônica que atinge o esqueleto humano. OBJETIVO: Verificar os efeitos do treinamento resistido sobre a densidade mineral óssea (DMO, força muscular, equilíbrio e qualidade de vida em mulheres menopausadas em tratamento com alendronato. MÉTODOS: Participaram do estudo 16 voluntárias. Elas foram separadas em dois grupos: que praticaram o treino resistido (n = 9, 49,7 ± 4,2 idade e que constituíram o grupo controle (n = 7, 53,8 ± 4,4 idade. Os instrumentos de avaliação seguintes foram usados: a absorciometria de dupla energia por raios X -DXA (que mediu a coluna lombar L2-L4, colo do fêmur, triângulo de Wards e trocanter maior, o Osteoporosis Assessment Questionnaire (OPAQ e um teste de equilíbrio. O treinamento foi periodizado em 12 meses, divididos em seis ciclos com intensidade de 70-90% da carga máxima (10RM. Testes paramétricos (t ou Wilcoxon, para análise intragrupo e (Anova para intergrupos, foram usados. RESULTADOS: Foram encontradas diferenças significativas favoráveis ao grupo que treinou nos sítios da lombar L2-L4 (6,8%, p = 0,001, colo do fêmur (4,8%, p = 0,005 e trocanter (0,76%, p = 0,005. Além de diferenças significativas também para o equilíbrio corporal (21,4%, p = 0,001, qualidade de vida (9,1%, p = 0,001 e todas as medidas de força como na pressão de pernas 45° (49,3%, p Osteoporosis is a chronic disease of the human skeleton. OBJECTIVE: To verify the effects of resistance training on bone mineral density (BMD, muscular strength, balance and quality of life in menopausal women taking Alendronate. MATERIALS AND METHODS: Sixteen female volunteers participated in the study. The volunteers were separated into two groups: resistance training participants (n=9; 49.7±4.2 years and control group (n=7; 53.8±4.4 years. The following evaluation instruments were used: absorptiometry-DXA (which measured the lumbar spine L2-L4, neck femur, Wards triangle and major trochanter, the

  13. Oral Bisphosphonates and Improved Survival of Breast Cancer.

    Science.gov (United States)

    Rennert, Gad; Pinchev, Mila; Gronich, Naomi; Saliba, Walid; Flugelman, Anath; Lavi, Idit; Goldberg, Hadassah; Fried, Georgeta; Steiner, Mariana; Bitterman, Arie; Landsman, Keren; Rennert, Hedy S

    2017-04-01

    Purpose: Bisphosphonates are used for treatment or prevention of osteoporosis and of bone metastases. The use of oral bisphosphonates was suggested to be associated with reduced risk of developing breast cancer, and their positive influence on breast cancer survival was only demonstrated with third-generation bisphosphonates. We studied the association of use of oral bisphosphonates after breast cancer diagnosis on overall and breast cancer survival. Experimental Design: A nested case-control analysis was performed using data from the population-based Breast Cancer in Northern Israel Study (BCINIS). Participants were postmenopausal women with newly diagnosed breast cancer insured by Clalit. Use of second-generation bisphosphonates (alendronate and/or risedronate) was identified using computerized prescription records. The analysis was restricted to women who did not use bisphosphonates prior to diagnosis. Results: In a cohort of 3,731 postmenopausal women with breast cancer, followed up for an average of 70 months, there were 799 cases of death which were matched to 15,915 control periods of living breast cancer cases. Use of bisphosphonates after diagnosis for at least 18 months was significantly more common among survivors than among their matched controls who died, adjusted for tumor stage/grade (overall survival: OR = 0.63, 0.41-0.96, P = 0.03; breast cancer-specific survival: OR = 0.28, 0.09-0.91, P = 0.035). A similar advantageous effect, but statistically underpowered, was found in estrogen receptor (ER)-positive, ER-negative, and HER2neu-positive tumors. Conclusions: The use of oral bisphosphonates, by postmenopausal, probably osteoporotic, women initiated after diagnosis of breast cancer was associated with a significant improvement in overall and breast-specific odds of survival. Clin Cancer Res; 23(7); 1684-9. ©2016 AACR . ©2016 American Association for Cancer Research.

  14. Efeitos de tratamento combinado de alendronato de sódio, atorvastatina cálcica e ipriflavona na osteoporose induzida com dexametasona em ratas Effects of combined treatment of alendronate of sodium, calcic atorvastatin and ipriflavone in osteoporosis induced with dexamethasone in female rats

    Directory of Open Access Journals (Sweden)

    Aloísio da Silva Pinto

    2006-03-01

    Full Text Available O objetivo deste trabalho foi estudar a influência das combinações: bifosfonato (alendronato de sódio + estatina (atorvastatina cálcica, bifosfonato (alendronato de sódio + flavonóide (ipriflavona e estatina (atorvastatina cálcica + flavonóide (ipriflavona em ratas com osteoporose induzida pelo glicocorticóide dexametasona. As influências das associações dessas substâncias foram pesquisadas pela análise de testes dos marcadores bioquímicos de remodelação óssea, tais como, cálcio e fósforo sérico, fosfatase alcalina óssea e por exames histomorfométricos, caracterizando a densidade trabecular óssea. Através da avaliação da densidade trabecular óssea foi possível verificar o aumento da mesma em todos os tratamentos efetuados. Ressaltando-se, ainda, que as associações contendo alendronato de sódio apresentaram elevadas taxas de restauração tecidual óssea, alcançando valores superiores aos do grupo dos animais normais. Os marcadores bioquímicos não apresentaram resultados estatisticamente significativos, não fornecendo subsídios para o diagnóstico e acompanhamento da osteoporose. No entanto, a avaliação histomorfométrica permitiu a análise estática e dinâmica, bem como detecção de alterações teciduais na unidade metabólica óssea, particularmente, no osso trabecular.The objective of this work was to study the influence of the combinations: biphosphonate (alendronate of sodium + statin (calcic atorvastatin, biphosphonate (sodium alendronate + flavonoid (ipriflavone and statin (calcic atorvastatin + flavonoid (ipriflavone in female rats with osteoporosis induced by the glucocorticoid dexamethasone. The influence of the combinations of those drugs was observed through tests of the biochemical markers of bone remodeling, such as, levels of serum calcium and phosphorus and bone alkaline phosphatase and through histomorphometric exam, visualizing the bone trabecular density. Through the evaluation of the

  15. The Market Order as Metaphysical Loot

    DEFF Research Database (Denmark)

    Schwarzkopf, Stefan

    2012-01-01

    The mechanism through which the ideology of market capitalism emerged has mostly been interpreted as part of an incremental, inevitable, and thus legitimate ousting of theological concepts from a public sphere that became organized around the principles of the Enlightenment as a secular project. ...... for the mobilization of individual choice as a principle of social organization. The same process was responsible for underpinning the often unjust and illiberal market order with the vision of the world as an ordered and benign kosmos that emerged spontaneously from chaos.......The mechanism through which the ideology of market capitalism emerged has mostly been interpreted as part of an incremental, inevitable, and thus legitimate ousting of theological concepts from a public sphere that became organized around the principles of the Enlightenment as a secular project...

  16. Infants' metaphysics: the case of numerical identity.

    Science.gov (United States)

    Xu, F; Carey, S

    1996-04-01

    Adults conceptualize the world in terms of enduring physical objects. Sortal concepts provide conditions of individuation (establishing the boundaries of objects) and numerical identity (establishing whether an object is the same one as one encountered at some other time). In the adult conceptual system, there are two roughly hierarchical levels of object sortals. Most general is the sortal bounded physical object itself, for which spatiotemporal properties provide the criteria for individuation and identity. More specific sortals, such as dog or car, rely on additional types of properties to provide criteria for individuation and identity. We conjecture that young infants might represent only the general sortal, object, and construct more specific sortals later (the Object-first Hypothesis). This is closely related to Bower's (1974) conjecture that infants use spatiotemporal information to trace identity before they use property information. Five studies using the visual habituation paradigm were conducted to address the Object-first Hypothesis. In these studies, 10-month-old infants were able to use spatiotemporal information but failed to use property/kind information to set up representations of numerically distinct individuals, thus providing empirical evidence for the Object-first Hypothesis. Finally, infants succeed at object individuation in terms of more specific sortals by 12 months. The relation between success at our task and early noun comprehension is discussed.

  17. The physics and metaphysics of time

    NARCIS (Netherlands)

    Dieks, D.G.B.J.

    2012-01-01

    We review the current situation in the philosophy of time, partly to investigate Michael Dummett’s complaint that the philosophy of physics has become too specialized and technical to be able to communicate with mainstream philosophy. We conclude that the situation in this case is different: there

  18. "Humanitas", Metaphysics and Modern Liberal Arts

    Science.gov (United States)

    Tubbs, Nigel

    2014-01-01

    There is a new myth of the heterogeneous that is reducing the concept of humanity to a sinful enlightenment. In this article I investigate the contribution that a renewed understanding of liberal arts education might offer for the idea of a humanist education and for the concept of humanity; and this at a time when not only the concept of humanity…

  19. THE METAPHYSICS MARKET 1 MERCHANDIZING LANGUAGE AS ...

    African Journals Online (AJOL)

    Dealers have tried to possess purchasers by means of their. Products extracting, on oath, the buyers' linguistics .... On the materialist conception of language, then, language and languages have no aspect that is not ultimately ...... the truth-value of such a statement? (5) Is the principle itself either analytic or empirically.

  20. Mental Illness, Metaphysics, Facts and Values | Megone ...

    African Journals Online (AJOL)

    A number of prominent writers on the concept of mental illness/disease are committed to accounts which involve rejecting certain plausible widely held beliefs, namely: that it is part of the meaning of illness that it is bad for its possessor, so the concept of illness is essentially evaluative; that if a person has a mental illness, ...

  1. Metaphysics and mathematics: Perspectives on reality

    Directory of Open Access Journals (Sweden)

    Gideon J. Kühn

    2017-08-01

    Full Text Available The essence of number was regarded by the ancient Greeks as the root cause of the existence of the universe, but it was only towards the end of the 19th century that mathematicians initiated an in-depth study of the nature of numbers. The resulting unavoidable actuality of infinities in the number system led mathematicians to rigorously investigate the foundations of mathematics. The formalist approach to establish mathematical proof was found to be inconclusive: Gödel showed that there existed true propositions that could not be proved to be true within the natural number universe. This result weighed heavily on proposals in the mid-20th century for digital models of the universe, inspired by the emergence of the programmable digital computer, giving rise to the branch of philosophy recognised as digital philosophy. In this article, the models of the universe presented by physicists, mathematicians and theoretical computer scientists are reviewed and their relation to the natural numbers is investigated. A quantum theory view that at the deepest level time and space may be discrete suggests a profound relation between natural numbers and reality of the cosmos. The conclusion is that our perception of reality may ultimately be traced to the ontology and epistemology of the natural numbers.

  2. The metaphysics market - Merchandising language as matter ...

    African Journals Online (AJOL)

    AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of Use · Contact AJOL · News. OTHER RESOURCES... for Researchers · for Journals · for Authors · for Policy Makers · about Open Access · Journal Quality.

  3. Measurement of Workload: Physics, Psychophysics, and Metaphysics

    Science.gov (United States)

    Gopher, D.

    1984-01-01

    The present paper reviews the results of two experiments in which workload analysis was conducted based upon performance measures, brain evoked potentials and magnitude estimations of subjective load. The three types of measures were jointly applied to the description of the behavior of subjects in a wide battery of experimental tasks. Data analysis shows both instances of association and dissociation between types of measures. A general conceptual framework and methodological guidelines are proposed to account for these findings.

  4. Ape metaphysics: object individuation without language.

    Science.gov (United States)

    Mendes, Natacha; Rakoczy, Hannes; Call, Josep

    2008-02-01

    Developmental research suggests that whereas very young infants individuate objects purely on spatiotemporal grounds, from (at latest) around 1 year of age children are capable of individuating objects according to the kind they belong to and the properties they instantiate. As the latter ability has been found to correlate with language, some have speculated whether it might be essentially language dependent and therefore uniquely human. Existing studies with non-human primates seem to speak against this hypothesis, but fail to present conclusive evidence due to methodological shortcomings. In the present experiments we set out to test non-linguistic object individuation in three great ape species with a refined manual search methodology. Experiment 1 tested for spatiotemporal object individuation: Subjects saw 1 or 2 objects simultaneously being placed inside a box in which they could reach, and then in both conditions only found 1 object. After retrieval of the 1 object, subjects reached again significantly more often when they had seen 2 than when they had seen 1 object. Experiment 2 tested for object individuation according to property/kind information only: Subjects saw 1 object being placed inside the box, and then either found that object (expected) or an object of a different kind (unexpected). Analogously to Experiment 1, after retrieval of the 1 object, subjects reached again significantly more often in the unexpected than in the expected condition. These results thus confirm previous findings suggesting that individuating objects according to their property/kind is neither uniquely human nor essentially language dependent. It remains to be seen, however, whether this kind of object individuation requires sortal concepts as human linguistic thinkers use them, or whether some simpler form of tracking properties is sufficient.

  5. The Metaphysics of Crackle: Afrofuturism and Hauntology

    Directory of Open Access Journals (Sweden)

    Mark Fisher

    2013-11-01

    Full Text Available There has always been an intrinsically “hauntological” dimension to recorded music. But Derrida’s concept of hauntology has gained a new currency in the 21st century, when music has lost its sense of futurism, and succumbed to the pastiche- and retro-time of postmodernity. The emergence of a 21st century sonic hauntology is a sign that “white” culture can no longer escape the temporal disjunctions that have been constitutive of the Afrodiasporic experience since Africans were first abducted by slavers and projected from their own lifeworld into the abstract space-time of Capital. Time was always-already out of joint for the slave, and Afrofuturism and hauntology can now be heard as two versions of the same condition.

  6. Conceptual Relativity Meets Realism in Metaphysics

    Czech Academy of Sciences Publication Activity Database

    Marvan, Tomáš

    2016-01-01

    Roč. 12, č. 2 (2016), s. 23-37 E-ISSN 1849-0514 Institutional support: RVO:67985955 Keywords : Hilary Putnam * conceptual relativity * realism * optional languages Subject RIV: AA - Philosophy ; Religion OBOR OECD: Philosophy, History and Philosophy of science and technology https://www.ffri.hr/phil/casopis/content.html

  7. Improved intestinal absorption of water-soluble drugs by acetylation of G2 PAMAM dendrimer nanocomplexes in rat.

    Science.gov (United States)

    Yan, Chengyun; Gu, Jiwei; Lv, Yuguang; Shi, Weiguo; Jing, Hongying

    2017-06-01

    In search of an effective and less toxic absorption enhancer, we synthesized primary amine acetylation of generation 2 polyamidoamine (G2 PAMAM) dendrimer (Ac-G2) by the reaction of G2 PAMAM dendrimer with acetic anhydride, and evaluated the effects of Ac-G2 on the intestinal absorption of poorly absorbable water-soluble drugs using an in situ closed-loop method in rats. The results indicated that Ac50-G2 had a greatest absorption enhancing effect for 5(6)-carboxyfluorescein (CF) in various acetylation levels of G2 PAMAM dendrimers. Ac50-G2 with various concentrations (0.1-1.0%, w/v) could significantly improve the intestinal absorption of alendronate, CF, and fluorescein isothiocyanate-labeled dextrans (FD4), although they did not enhance the absorption of macromolecular drug of FD10, and the absorption enhancement effect of Ac50-G2 was concentration-dependent. Furthermore, we examined the intestinal membrane damage with or without Ac50-G2. The results displayed Ac50-G2 at lower concentrations (0.1-0.5%, w/v) did not cause any observed toxic effect to the intestinal membranes. These findings suggested Ac50-G2 at lower concentrations (below 0.5%, w/v) might be promising as an effective and safe absorption enhancers to promote the intestinal absorption of poorly absorbable drugs.

  8. The metaphysical foundation of morality in the Twelver's Shiite الأسس الميتافيزيقية للأخلاق لدى الشيعة الامامية

    Directory of Open Access Journals (Sweden)

    Mohammed Ali Mohammed Reza Al - Hakim محمد علي محمد رضا الحكيم

    2018-04-01

    Full Text Available The research revolves around the moral values in the Twelver's Shiite Islamic thought , which we can touch a tendency to rational thinking imprinted in this thought in general , and for the subject of ethics in particular, when acknowledge that deeds have their self-values, despite of the Islamic view, and that the mind can grasp them, and can judge on the deed whether its good , which it will be praised , or bad, which it will be condemn. Since the research focuses on the metaphysical foundations of ethics for a religious thought, we must go back to the origins of belief which it is based on, and they are five: monotheism, justice, prophethood, imamate, resurrection day, and the disclosure of their contents and ethical implications.

  9. METAPHYSICS OF WILL, METAPHYSICS OF IMPOSSIBLE: THE PULSIONAL DIMENSION AS EXCLUDED MIDDLE

    OpenAIRE

    DIOGO BARROS BOGEA

    2016-01-01

    Nietzsche e Heidegger delineiam os caminhos que se entrecortam dando origem ao nosso horizonte de questões: É ainda possível um pensamento que resista ao mesmo tempo à tentação de uma fundamentação absoluta, mas também ao furor desenfreado da maquinação calculadora? É ainda possível um pensamento que se coloque em condições de compreender e também de se posicionar criticamente tanto em relação aos fundamentalismos nostálgicos, quanto em relação à pura efetividade e produtivi...

  10. Proton Pump Inhibitor Use and the Antifracture Efficacy of Alendronate

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Eiken, Pia Agnete; Eastell, Richard

    2011-01-01

    BACKGROUND: Proton pump inhibitors (PPIs) are widely used in elderly patients and are frequently coadministered in users of oral bisphosphonates. Biologically, PPIs could affect the absorption of calcium, vitamin B(12), and bisphosphonates and could affect the osteoclast proton pump, thus...

  11. Development of docetaxel and alendronate-loaded chitosan ...

    African Journals Online (AJOL)

    differential scanning calorimetry as well as by in vitro drug release and cell culture studies. Results: NP size was within the tumour targeting range (~200 nm) with an effective positive charge (20. mV), thus increasing cellular uptake efficiency. Morphological analysis revealed clear spherical particles with uniform dispersion.

  12. O darwinismo e o sagrado na segunda metade do século XIX: alguns aspectos ideológicos e metafísicos do debate Darwinism and "the sacred" during the second half of the 19 th century: some ideological and metaphysical features of the debate

    Directory of Open Access Journals (Sweden)

    Juanma Sánchez Arteaga

    2008-01-01

    Full Text Available O artigo analisa alguns aspectos ideológicos e metafísicos da transformação do imaginário ocidental sobre a origem da espécie humana - a velha questão, "quem somos?", respondida de formas diversas pelo cristianismo e pela biologia evolutiva - na segunda metade do século XIX. Nesse período passa-se do predomínio da antropogênese cristã ao das explicações evolucionistas. Analisa-se a confrontação histórica que teve lugar, nesse período, entre alguns dos principais defensores científicos do evolucionismo materialista - Haeckel, Clémence Royer e Huxley - e os defensores de uma antropologia anti-evolucionista e cristã. Analisam-se brevemente os pontos principais da crítica de Darwin à religião e algumas similitudes e discrepâncias de sua crítica ao pensamento religioso com relação à realizada por Marx no mesmo período. Determinados aspectos ideológico-metafísicos foram componentes essenciais do discurso darwinista na sua luta para se impor às narrativas do cristianismo sobre a origem do ser humano.This paper analyzes some of the ideological and metaphysical features of the historical transformation of Western imaginary on human origins, during the second half of 19th Century. In this period, predominance of the Christian Natural Theology accounts about anthropogenesis gave place to a new paradigm, based on evolutionary biological explanations. We thus analyze the historical confrontation that took place between prominent materialistic scientists - Haeckel, Royer, Huxley - defending evolutionary theories, on one hand, and advocates of a non-evolutionist anthropology linked to Christian believe in Creation, on the other. This paper analyzes the main features of Darwin's criticism of religious thought, based on naturalistic basis, and presents some similarities and differences with the critique of religion made by Marx in the same period. Darwinism included some metaphysical and ideological elements as essential parts of

  13. Collaborative Improvement

    DEFF Research Database (Denmark)

    Kaltoft, Rasmus

    (Denmark, Italy and The Netherlands) each with three to five suppliers were involved. The CO-IMPROVE project and the thesis is based on “action research” and “action learning”. The main aim of the whole project is through actual involvement and actions make the researchers, companies and selected suppliers......The thesis data have been collected in the EU-sponsored project: Collaborative Improvement Tool for the Extended Manufacturing Enterprise, CO-IMPROVE. In this project four universities (Denmark, Ireland, Italy, and The Netherlands), two software vendors (Greece and Sweden) and three companies...

  14. Collaborative Improvement

    DEFF Research Database (Denmark)

    Kaltoft, Rasmus

    -organisational continuous improvement of their performance, relative to that of other EMEs. Developing a collaborative improvement relationship between companies is a protracted and complex process and, according to some surveys, the failure rate is as low as one to three. This failure rate is affected by a whole range...... of factors. The research presented in this thesis was aimed at identifying these factors and investigating their interplay and influence on the progress and success of the development of the collaborative improvement. This thesis presents our findings regarding the factors found, their interplay...

  15. Improving photosynthesis.

    Science.gov (United States)

    Evans, John R

    2013-08-01

    Photosynthesis is the basis of plant growth, and improving photosynthesis can contribute toward greater food security in the coming decades as world population increases. Multiple targets have been identified that could be manipulated to increase crop photosynthesis. The most important target is Rubisco because it catalyses both carboxylation and oxygenation reactions and the majority of responses of photosynthesis to light, CO₂, and temperature are reflected in its kinetic properties. Oxygenase activity can be reduced either by concentrating CO₂ around Rubisco or by modifying the kinetic properties of Rubisco. The C₄ photosynthetic pathway is a CO₂-concentrating mechanism that generally enables C₄ plants to achieve greater efficiency in their use of light, nitrogen, and water than C₃ plants. To capitalize on these advantages, attempts have been made to engineer the C₄ pathway into C₃ rice (Oryza sativa). A simpler approach is to transfer bicarbonate transporters from cyanobacteria into chloroplasts and prevent CO₂ leakage. Recent technological breakthroughs now allow higher plant Rubisco to be engineered and assembled successfully in planta. Novel amino acid sequences can be introduced that have been impossible to reach via normal evolution, potentially enlarging the range of kinetic properties and breaking free from the constraints associated with covariation that have been observed between certain kinetic parameters. Capturing the promise of improved photosynthesis in greater yield potential will require continued efforts to improve carbon allocation within the plant as well as to maintain grain quality and resistance to disease and lodging.

  16. Improving Photosynthesis

    Science.gov (United States)

    Evans, John R.

    2013-01-01

    Photosynthesis is the basis of plant growth, and improving photosynthesis can contribute toward greater food security in the coming decades as world population increases. Multiple targets have been identified that could be manipulated to increase crop photosynthesis. The most important target is Rubisco because it catalyses both carboxylation and oxygenation reactions and the majority of responses of photosynthesis to light, CO2, and temperature are reflected in its kinetic properties. Oxygenase activity can be reduced either by concentrating CO2 around Rubisco or by modifying the kinetic properties of Rubisco. The C4 photosynthetic pathway is a CO2-concentrating mechanism that generally enables C4 plants to achieve greater efficiency in their use of light, nitrogen, and water than C3 plants. To capitalize on these advantages, attempts have been made to engineer the C4 pathway into C3 rice (Oryza sativa). A simpler approach is to transfer bicarbonate transporters from cyanobacteria into chloroplasts and prevent CO2 leakage. Recent technological breakthroughs now allow higher plant Rubisco to be engineered and assembled successfully in planta. Novel amino acid sequences can be introduced that have been impossible to reach via normal evolution, potentially enlarging the range of kinetic properties and breaking free from the constraints associated with covariation that have been observed between certain kinetic parameters. Capturing the promise of improved photosynthesis in greater yield potential will require continued efforts to improve carbon allocation within the plant as well as to maintain grain quality and resistance to disease and lodging. PMID:23812345

  17. Metaphysics and knowledge in Popper: the propensitive emergence of world.

    OpenAIRE

    Alexandre Klock Ernzen

    2013-01-01

    A dissertaÃÃo tem por objeto de estudo o programa metafÃsico de Karl Popper expresso em sua tese das propensÃes como uma possÃvel soluÃÃo ao cisma da fÃsica moderna. Segundo o autor, os grandes cientistas possuÃam um programa de investigaÃÃo, em grande medida metafÃsico, que orientava metodologicamente suas decisÃes e descobertas acerca da realidade. Nossa dissertaÃÃo investigou como Popper argumenta a relaÃÃo entre filosofia e ciÃncia, simbiose necessÃria para procurar uma possÃvel soluÃÃo a...

  18. Metaphysical and value underpinnings of traditional medicine in West Africa.

    Science.gov (United States)

    Omonzejele, Peter F; Maduka, Chukwugozie

    2011-02-01

    This study investigated the extent to which recourse to traditional healers depended on biometric variables; ways of knowing in good time what ailments were more likely to be better handled by traditional healers; rationale behind traditional healing methodologies. On the whole, four research questions were engaged. The sample for the study included residents in urban (Benin City) and rural (Ehime Mbano) communities in Nigeria. The instruments comprised of two questionnaires. The traditional healers were also interviewed in addition. The findings of the research included the following: in both rural and urban areas, women and more elderly persons had more recourse than other groups to traditional medicine; Christians, less educated persons, self-employed persons and women affirmed most strongly to the efficacy of traditional medicine over Western medicine with respect to certain ailments; ways for averting spiritual illnesses included obeying instructions from ancestors and offering regular sacrifices to the gods; methods used by traditional healers to determine whether an ailment was "spiritual" or as a result of home problems included diagnosis linked to divination, interpretation of dreams particularly those involving visits by ancestors, interpretation of nightmares and omens such as the appearance of owls; methods for curing patients included use of herbs particularly those believed to have magical powers, offering of sacrifices, use of incantations and wearing of protective medicine.

  19. Metaphysics of colliding self-gravitating plane waves

    Energy Technology Data Exchange (ETDEWEB)

    Matzner, R.A.; Tipler, F.J.

    1984-04-15

    We discuss certain global features of colliding plane-wave solutions to Einstein's equations. In particular, we show that the apparently local curvature singularities both in the Khan-Penrose solution and in the Bell-Szekeres solution are actually global. These global singularities are associated with the breakdown of nondegenerate planar symmetry in the characteristic initial data sets.

  20. Heidegger and Levinas: Metaphysics, Ontology and the Horizon of ...

    African Journals Online (AJOL)

    Already in his earlier works Levinas proposes a distinct phenomenological project which takes into consideration the radicality of the other and otherness by questioning intentionality and the validity of intersubjectivity within intentional consciousness. His move “towards Heidegger and against Husserl” was due primarily to ...

  1. Humanities’ Metaphysical Underpinnings of Late Frontier Scientific Research

    Directory of Open Access Journals (Sweden)

    Alcibiades Malapi-Nelson

    2014-12-01

    Full Text Available The behavior/structure methodological dichotomy as locus of scientific inquiry is closely related to the issue of modeling and theory change in scientific explanation. Given that the traditional tension between structure and behavior in scientific modeling is likely here to stay, considering the relevant precedents in the history of ideas could help us better understand this theoretical struggle. This better understanding might open up unforeseen possibilities and new instantiations, particularly in what concerns the proposed technological modification of the human condition. The sequential structure of this paper is twofold. The contribution of three philosophers better known in the humanities than in the study of science proper are laid out. The key theoretical notions interweaving the whole narrative are those of mechanization, constructability and simulation. They shall provide the conceptual bridge between these classical thinkers and the following section. Here, a panoramic view of three significant experimental approaches in contemporary scientific research is displayed, suggesting that their undisclosed ontological premises have deep roots in the Western tradition of the humanities. This ontological lock between core humanist ideals and late research in biology and nanoscience is ultimately suggested as responsible for pervasively altering what is canonically understood as “human”.

  2. Rosmini's metaphysical evidence for the existence of God | Swartz ...

    African Journals Online (AJOL)

    Rosmini is of the opinion that the soul consists of both a bodily (natural) and a godly component. Both components unite in humankind. In Rosmini's cosmology, humankind is viewed in relation to God and the world (cosmos). Cosmology cannot be comprehensively explained without linking ontology and theology, ...

  3. Mirror neurons: Enigma of the metaphysical modular brain.

    Science.gov (United States)

    Acharya, Sourya; Shukla, Samarth

    2012-07-01

    Mirror neurons are one of the most important discoveries in the last decade of neuroscience. These are a variety of visuospatial neurons which indicate fundamentally about human social interaction. Essentially, mirror neurons respond to actions that we observe in others. The interesting part is that mirror neurons fire in the same way when we actually recreate that action ourselves. Apart from imitation, they are responsible for myriad of other sophisticated human behavior and thought processes. Defects in the mirror neuron system are being linked to disorders like autism. This review is a brief introduction to the neurons that shaped our civilization.

  4. Morals, Metaphysics and The Method of Cases | Beck | South ...

    African Journals Online (AJOL)

    South African Journal of Philosophy. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 29, No 4 (2010) >. Log in or Register to get access to full text downloads.

  5. analyzing Immanuel Kant's grounding for a metaphysics of morals

    OpenAIRE

    Bordum, Anders

    2002-01-01

    In this article I first argue that Immanuel Kant’s conception of the categorical imperative is important to his philosophy. I systematically, though indirectly, interconnect the cognitive and moral aspects of his thinking. Second, I present an interpretation of the Kantian ethics, taking as my point of departure, the concept of the categorical imperative. Finally, I show how the categorical imperative is given a dialogical interpretation by Jürgen Habermas in his approach, usually referred to...

  6. rosmini's metaphysical evidence for the existence of god

    African Journals Online (AJOL)

    VENTER, E.A.. 1970. Wysgerige temas. Tweede druk. Bloemfontein: Sacum Beperk. WINTERTON, F. 1888. Review. Papal condemnation of Rosmini. Notes. Mind 13(52):622626. Keywords. Trefwoorde. Rosmini. Rosmini. God. God. Soul. Siel. Natural theology. Natuurlike teologie. Existence. Bestaan. Ontology. Ontologie.

  7. Particle metaphysics. A critical account of subatomic reality

    International Nuclear Information System (INIS)

    Falkenburg, B.

    2007-01-01

    The empirical successes of atomic, nuclear, and particle physics have not reduced -- and may never fully resolve -- the philosophical controversies about the inner constitution of matter. This book examines these debates by exploring the particle concept in physics. Are the particles of modern physics ''real'' or are they fictitious entities, their existence deduced merely by the careless application of abstract theories? Or are the philosophers involved in the debate about ''scientific realism'' dedicating themselves to a problem that has long been solved by physicists? Studies of the experimental basis and theoretical relevance of the particle concept reveal that these questions are far from easy to answer, because, since the introduction of quantum theory, physical science no longer possesses a single unambiguous particle concept. All those interested in the ''true meaning'' of such physical concepts will find this book informative and thought provoking. It is written at a level accessible to scholars, students and teachers of science and philosophy. (orig.)

  8. The Metaphysical and Ontological Symbolism of Total Gravitational ...

    African Journals Online (AJOL)

    Having laid a firm foundation in SPACETIME for a detailed analysis of total gravitational collapse, by linking Einstein's Special Theory of Relativity (STR) to the General Theory (GTR) in the context of the Quantum Principle and within the all-embracing framework of GUT (the Grande Unification Theory), we proceed with an ...

  9. Doodling: The artistry of the roving metaphysical mind

    Directory of Open Access Journals (Sweden)

    Sharat Gupta

    2016-01-01

    Full Text Available A doodle is a simple drawing that is usually made to pass the time during a boring meeting, classroom lecture, or a prolonged telephonic conversation. Almost everyone has seen a doodle somewhere and many people have made such drawings. Doodling may not be of much interest to the general public as it is perceived to be a sign of disinterest, inattentiveness, or reverie. However, the act of doodling is of enduring interest to scientists as they believe that doodling research might actually reveal significant insights about the functioning of the subconscious mind. The widely held misconception about doodling as being just a way to ease one's boredom is all set to change since the findings of some recent researchers have shown that doodling might actually aid one's memory and recall performance. We hope that this review will instigate further research into this hitherto uncharted domain so that the real connotation of this seemingly mundane act can be decisively established.

  10. The search for a metaphysical entity in modern drama

    Directory of Open Access Journals (Sweden)

    Deborha Roos

    1981-03-01

    Full Text Available This is a thirst which all the fountains of the earth cannot quench. Each of these mysterious needs is one side of aperimeter whose complete figure, when we finally perceive it, has one name: GOD" (Bogardt, 1965. In the twentieth cen­ tury man finally murdered God and found himself ‘ left to live in a world hopeless, forlorn, desperate, frustrated, full of agony .... without an answer to the basic human questions”. When did this modern malaise start? In how far is this devastating new truth of nothingness reflected in the arts?

  11. THE CONCEPT OF SENCE IN THE WORLD, METAPHYSICS AND SCIENCE

    Directory of Open Access Journals (Sweden)

    Michal Sicinski

    2007-01-01

    Full Text Available The notion of objective sense is commonly used in various contexts, and is also frequently misused. It has been often criticised in the context of natural sciences during the last 200 years - the period of positivistically oriented science. In the ancient Greek philosophy the problem of Nature possessing its own sense was stressed, and from the problem the first germs of science started in the Ionic and Pythagorean schools. Contrary to that, Aristotelean approach initiated the positivist tradition which banned from science the question of Nature as possessing an internal sense, and the scholastics introduced a concept of Nature's sense being not intrinsic but granted to it by the divine action. The mathematisation of physics caused that the the divine action started to be interpreted as "mathematical", and in consequence, the sense of Nature was seen as expressed by mathematics. Later on, this mathematically expressed sense of Nature, as seen in physical theories, started to be perceived as independent from God and having not much to as supernatural: inside the mathematical science there was no place for any anthropomorphic Creators.Recently, however when in the newest physics the mathematical structures have already been perceived not only as a language but also as a kind of ultimate reality, a place for quasi-religious feeling of mystery hidden in these structures has been welcome. It means that within the field of modern physical theories there is no place for the traditional religious concepts, but there is a place for a kind of mystics of objective mathematics in the Pythagorean style, related to the modern "new spirituality" mysticism.The situation is completely different in the area of less mathematised branches like biology. The tensions between science and religion are strong there, and the alternative is as follows: traditional religiousness versus traditional atheism, but not a neutral science separated from religion versus a non-traditional mysticism of the mathematics beings united with nature, as it is in the case of newest physics. So, the biologist who are not ready to accept the popular tradition notion of God directly interfering with nature, e.g. creating the phenomenon of life or man, are ready to accept the old-fashioned "scientific" atheism. That is why the dialogue science and religion is rather difficult in relation to biology, despite being so fruitful in relation to physics and cosmology.

  12. What is a gene? From molecules to metaphysics.

    Science.gov (United States)

    Rolston, Holmes

    2006-01-01

    Mendelian genes have become molecular genes, with increasing puzzlement about locating them, due to increasing complexity in genomic webworks. Genome science finds modular and conserved units of inheritance, identified as homologous genes. Such genes are cybernetic, transmitting information over generations; this too requires multi-leveled analysis, from DNA transcription to development and reproduction of the whole organism. Genes are conserved; genes are also dynamic and creative in evolutionary speciation-most remarkably producing humans capable of wondering about what genes are.

  13. Metaphysics, science and the asphaltene phase behavior problem

    Energy Technology Data Exchange (ETDEWEB)

    Lockhart, T.P. [Eniricerche SpA, Milanese (Italy)

    1996-12-31

    Spontaneous phase separation and deposition of the asphaltenic component of crude oils is the source of costly problems in the petroleum industry. Over the past several decades so-called {open_quotes}colloid stabilization{close_quotes} model has dominated attempts to account for the phase behavior of the asphaltene fraction of the crude oil. We will argue that this model is not {open_quotes}scientific{close_quotes} in the sense that is has been applied only for the post-hoc rationalization of experimental results; absent have been serious attempts to experimentally test specific predictions deduced from the model. A critical examination of the colloid stabilization model brings to light several fundamental shortcomings. An alternative thermodynamic, or {open_quotes}solvation{close_quotes} model is shown to make predictions in far better agreement with experiment, and has been the key to developing an analytical model that accurately predicts the conditions under which crude oils become unstable to asphaltene deposition. This example will be used to argue that the defining elements of (good) scientific research - the formulation of explicit hypotheses of high predictive content and their critical evaluation, above all by experimental attempts at falsification - are also effective, indeed necessary, for analyzing the complex problems offered by the {open_quotes}real{close_quotes} world and for achieving technological advancement.

  14. Strawson and Schaumann on the Metaphysics of Transcendental ...

    African Journals Online (AJOL)

    The paper is a limited defence of one of P. F. Strawson's least popular declarations about the nature of Kant's transcendental idealism. An attempt is made to relate Strawson's reading to an interpretative controversy that emerged in the years immediately following the publication of the first edition of the Critique of Pure ...

  15. Particle metaphysics. A critical account of subatomic reality

    Energy Technology Data Exchange (ETDEWEB)

    Falkenburg, B. [Dortmund Univ. (Germany). Inst. fuer Philosophie

    2007-07-01

    The empirical successes of atomic, nuclear, and particle physics have not reduced -- and may never fully resolve -- the philosophical controversies about the inner constitution of matter. This book examines these debates by exploring the particle concept in physics. Are the particles of modern physics ''real'' or are they fictitious entities, their existence deduced merely by the careless application of abstract theories? Or are the philosophers involved in the debate about ''scientific realism'' dedicating themselves to a problem that has long been solved by physicists? Studies of the experimental basis and theoretical relevance of the particle concept reveal that these questions are far from easy to answer, because, since the introduction of quantum theory, physical science no longer possesses a single unambiguous particle concept. All those interested in the ''true meaning'' of such physical concepts will find this book informative and thought provoking. It is written at a level accessible to scholars, students and teachers of science and philosophy. (orig.)

  16. Cognitive Metaphor Theory and the Metaphysics of Immediacy

    Science.gov (United States)

    Madsen, Mathias W.

    2016-01-01

    One of the core tenets of cognitive metaphor theory is the claim that metaphors ground abstract knowledge in concrete, first-hand experience. In this paper, I argue that this grounding hypothesis contains some problematic conceptual ambiguities and, under many reasonable interpretations, empirical difficulties. I present evidence that there are…

  17. Neuroscientific Prediction and the Intrusion of Intuitive Metaphysics.

    Science.gov (United States)

    Rose, David; Buckwalter, Wesley; Nichols, Shaun

    2017-03-01

    How might advanced neuroscience-in which perfect neuro-predictions are possible-interact with ordinary judgments of free will? We propose that peoples' intuitive ideas about indeterminist free will are both imported into and intrude into their representation of neuroscientific scenarios and present six experiments demonstrating intrusion and importing effects in the context of scenarios depicting perfect neuro-prediction. In light of our findings, we suggest that the intuitive commitment to indeterminist free will may be resilient in the face of scientific evidence against such free will. Copyright © 2015 Cognitive Science Society, Inc.

  18. Can metaphysical values protect mountain wildlands from development damage?

    Science.gov (United States)

    Lawrence S. Hamilton; Jeneda Benally

    2015-01-01

    This paper addresses the question of whether spiritual, religious or cultural values held by humans for some wild mountain areas can protect these special places from developments that impair both these values and wild nature. The answer is sometimes yes, sometimes no, and sometimes a minimization of damage. Examples of each of these scenarios are briefly given, along...

  19. Kierkegaard, Levinas and the Question of Escaping Metaphysics ...

    African Journals Online (AJOL)

    To the ex tent that they offer philosophical alternatives that accommodate the temporal, both have had highly significant contributions to make to a postmodern style of thinking that has implications not limited to religion or ethics. A study of the philosophical strategies of these two thinkers, where they seem to succeed or fall ...

  20. Reincarnation As A Metaphysical Principle Of Explanation In African ...

    African Journals Online (AJOL)

    Reincarnation is a belief taught by many of the World's religions. It is the doctrine of second birth to earthly life. It is held that though the physical body decays at death, the life-force, or soul or spirit reincarnates in another body on earth. It is as if our physical bodies are like a suit of clothes that has to be discarded for a new ...

  1. Sports Activity Following Cementless Metaphyseal Hip Joint Arthroplasty

    Directory of Open Access Journals (Sweden)

    Czech Szymon

    2017-12-01

    Full Text Available An adequate level of physical activity has a substantial effect on both mental and physical human health. Physical activity is largely dependent on the function of the musculoskeletal and articular system. One of the most frequent diseases of this system is degenerative joint disease. Due to the changing and more demanding lifestyles and patients’ willingness to be involved in sports activity, the expectations of hip joint arthroplasty are becoming increasingly high. Alleviating pain ceases to be the only reason for which patients choose surgical interventions, while the expectations often include involvement in various sports. Only few studies contain recommendations concerning the frequency, type and intensity of sports activity which are acceptable after hip joint arthroplasty. The aim of the study was to evaluate function and physical activity of people following cementless short-stem hip joint arthroplasty in the observation of at least five years. The study group comprised 106 patients who underwent total hip arthroplasty due to degenerative joint diseases, chosen according to inclusion criteria. Patients underwent routine physical examinations following the Harris Hip Score protocol, responded to the UCLA scale and questionnaires concerning pre-surgical and current physical activity. Our results demonstrated that hip joint arthroplasty in people suffering from degenerative joint diseases has a beneficial effect on their level of functioning and physical activity. Although physical activity and the level of functioning obviously reduced as a person aged, the level of physical activity continued to be very high in both groups, with function of the hip joint evaluated as very good.

  2. Sports Activity Following Cementless Metaphyseal Hip Joint Arthroplasty.

    Science.gov (United States)

    Czech, Szymon; Hermanson, Jacek; Rodak, Piotr; Stołtny, Tomasz; Rodak, Łukasz; Kasperczyk, Sławomir; Koczy, Bogdan; Mielnik, Michał

    2017-12-01

    An adequate level of physical activity has a substantial effect on both mental and physical human health. Physical activity is largely dependent on the function of the musculoskeletal and articular system. One of the most frequent diseases of this system is degenerative joint disease. Due to the changing and more demanding lifestyles and patients' willingness to be involved in sports activity, the expectations of hip joint arthroplasty are becoming increasingly high. Alleviating pain ceases to be the only reason for which patients choose surgical interventions, while the expectations often include involvement in various sports. Only few studies contain recommendations concerning the frequency, type and intensity of sports activity which are acceptable after hip joint arthroplasty. The aim of the study was to evaluate function and physical activity of people following cementless short-stem hip joint arthroplasty in the observation of at least five years. The study group comprised 106 patients who underwent total hip arthroplasty due to degenerative joint diseases, chosen according to inclusion criteria. Patients underwent routine physical examinations following the Harris Hip Score protocol, responded to the UCLA scale and questionnaires concerning pre-surgical and current physical activity. Our results demonstrated that hip joint arthroplasty in people suffering from degenerative joint diseases has a beneficial effect on their level of functioning and physical activity. Although physical activity and the level of functioning obviously reduced as a person aged, the level of physical activity continued to be very high in both groups, with function of the hip joint evaluated as very good.

  3. Heidegger and Levinas: Metaphysics, Ontology and the Horizon of ...

    African Journals Online (AJOL)

    denise

    on reading intersubjective relations with the Other which strongly contrasts with the. Heideggerian concept of intersubjectivity. ... The main questions for both Levinas and Heidegger are the meaning of being, the mode of its ..... the question designates exactly the comprehension of being. The next step is to make clear how ...

  4. Between physics and metaphysics: structure as a boundary concept.

    Science.gov (United States)

    Tau, Ramiro

    2015-03-01

    The notion of structure is found to be used in a great number of theories, scientific research programs and world views. However, its uses and definitions are as diverse as the objects of the scientific disciplines where it can be found. Without trying to recreate the structuralist aspiration from the mid XX century, which believed to have found in this notion a common transdisciplinary language, I discuss a specific aspect of this concept that could be considered a constant in different perspectives. This aspect refers to the location of the notions of structure as boundaries in the different scientific theories. With this, I try to argue that the definition or presentation of a structure configures in itself the frontier for scientific knowledge, defining at the same time implied ontological assumptions. In order to discuss this hypothesis, and taking into consideration the double origin of contemporary notions of structure -the mathematical and linguistic line-, I revise several theoretical perspectives which made explicit the relation between structures and knowledge, and their relation with the real: the arguments on physical knowledge by Eddington, structural anthropology, structural linguistics, Lacanian psychoanalysis and Piaget's genetic psychology.

  5. Energeia vs Entelecheia: Schelling vs Hegel on Metaphysics Lambda

    Directory of Open Access Journals (Sweden)

    Marcela García Romero

    2016-07-01

    Full Text Available In what follows, I will take Schelling’s perspective into account regarding what he considers to be a partial or mistaken reading of Aristotle. There are several indications that this criticism is directed at Hegel, although Schelling does not mention Hegel by name in the particular work on which I concentrate, the Darstellung der reinrationalen Philosophie [DRP]. I will look at the differences between both interpretations but will do so from Schelling’s perspective. Then I will address two problems that Schelling’s use of the Aristotelian “pure actuality”: in what sense the pure actuality can be said to be individual, and what exactly is the role of Schelling’s notion of pure actuality in the transition from “purely rational” to “positive” philosophy which, as he says, depends on the will.

  6. Antjie Krog, Stephen Watson and the Metaphysics of Presence ...

    African Journals Online (AJOL)

    In this paper I explore some of the questions that follow from Stephen Watson's assertions that Antjie Krog's the stars say 'tsau' exhibits elements of plagiarism. In particular, I examine different conceptions of originality that can be identified in Watson and Krog's statements concerning the reworking of the /Xam materials into ...

  7. Cognitive Metaphor Theory and the Metaphysics of Immediacy.

    Science.gov (United States)

    Madsen, Mathias W

    2016-05-01

    One of the core tenets of cognitive metaphor theory is the claim that metaphors ground abstract knowledge in concrete, first-hand experience. In this paper, I argue that this grounding hypothesis contains some problematic conceptual ambiguities and, under many reasonable interpretations, empirical difficulties. I present evidence that there are foundational obstacles to defining a coherent and cognitively valid concept of "metaphor" and "concrete meaning," and some general problems with singling out certain domains of experience as more immediate than others. I conclude from these considerations that whatever the facts are about the comprehension of individual metaphors, the available evidence is incompatible with the notion of an underlying conceptual structure organized according to the immediacy of experience. Copyright © 2015 Cognitive Science Society, Inc.

  8. Fidelity to western metaphysics: A challenge to authentic African ...

    African Journals Online (AJOL)

    Filosofia Theoretica: Journal of African Philosophy, Culture and Religions. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 5, No 1 (2016) >. Log in or Register to get access to full text downloads.

  9. Metaphysics of Kola Nut: Towards an Authentic African Igbo ...

    African Journals Online (AJOL)

    Filosofia Theoretica: Journal of African Philosophy, Culture and Religions. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 2, No 2 (2013) >. Log in or Register to get access to full text downloads.

  10. Using Organizational Systems Theory to Improve Defense Acquisition and Warfighter Requirements

    Science.gov (United States)

    2007-12-01

    apparent from this metaphysical explanation is how improbable it is to perfectly characterize open, organizational systems—or even precisely parse out and...warrants additional explanation regarding how to cope with the complexity of system boundaries. Cope is the key word because there is no magic formula

  11. CDBG Public Improvements Activity

    Data.gov (United States)

    Department of Housing and Urban Development — CDBG activity related to public improvements, including senior centers, youth centers, parks, street improvements, water/sewer improvements, child care centers, fire...

  12. Improving Skiing: A Metaphor for Improving Leadership

    Science.gov (United States)

    Zimmerman, Judith A.

    2006-01-01

    Metaphors are powerful in describing organizations (Morgan, 1986; 1998) and stories reveal the meaning of experiences (Kouzes & Posner, 1993). As an avid skier and school change leader, the author has drawn on her personal experiences and the literature to develop the idea of improving skiing as a metaphor for improving leadership, particularly…

  13. How Lacan's Ethics Might Improve Our Understanding of Nietzsche's Critique of Platonism: The Neurosis and Nihilism of a ‘Life’ Against Life

    Directory of Open Access Journals (Sweden)

    Tim Themi

    2008-10-01

    Full Text Available his paper sets to answering the question of how Lacanrsquo;s 1959-60 Seminar on emThe Ethics of Psychoanalysis/em, with its recurring critique of the Platonic idea of a moral Sovereign Good, might contribute to and improve our understanding of the Nietzschean project to diagnose the moral metaphysics instigated by Plato in philosophy, and by Christianity in religion, as a history of untruth and nihilismndash;ndash;emopposed to life/emndash;ndash;in preparation for its overcoming. I explore the possibility that Lacanrsquo;s emEthics/em might make such a contribution by i its tripartite ontology of the real, the symbolic and the imaginary serving as an additional frame of reference for examining the nature of the Good and our configurations of desire beneath it; and ii by its more detailed elaboration of the archaic, polymorphous perversity at the instinctual base of the drives, what Lacan in his emEthics/em will call emdas Ding/em, the somewhat diabolical Freudian Thing. I also attempt to indicate how Nietzschersquo;s own ethics might make a contribution to those of the Lacanian, for the purposes of further combating what I will take to be the contemporary neurosis and nihilism of a lsquo;lifersquo; emagainst/em lifendash;ndash;as indicated today for instance by such phenomena as the physical destruction of the environment, along with us as amongst its earthly inhabitants.

  14. Making process improvement 'stick'.

    Science.gov (United States)

    Studer, Quint

    2014-06-01

    To sustain gains from a process improvement initiative, healthcare organizations should: Explain to staff why a process improvement initiative is needed. Encourage leaders within the organization to champion the process improvement, and tie their evaluations to its outcomes. Ensure that both leaders and employees have the skills to help sustain the sought-after process improvements.

  15. Accelerate Water Quality Improvement

    Science.gov (United States)

    EPA is committed to accelerating water quality improvement and minimizing negative impacts to aquatic life from contaminants and other stressors in the Bay Delta Estuary by working with California Water Boards to strengthen water quality improvement plans.

  16. Improving fleet performance

    Energy Technology Data Exchange (ETDEWEB)

    Ramjist, S. [Ontario Power Generation, Toronto, ON (Canada)

    2015-07-01

    Use Fleet Initiatives to Improve Overall Fleet Performance . Tightly Integrated with Business Planning (Cause & Effect) . Leverage Strength of Broader Organization - Converge on Standard Business Practices . Ancillary Benefit of Improved Agility.

  17. Collaborative quality improvement.

    Science.gov (United States)

    Luckenbaugh, Amy N; Miller, David C; Ghani, Khurshid R

    2017-07-01

    Quality improvement collaboratives were developed in many medical and surgical disciplines with the goal of measuring and improving the quality of care provided to patients. The aim of this review is to provide an overview of surgical quality improvement collaboratives, and in particular those aimed at improving urological care. Quality improvement collaboratives collect high-quality data using standardized methodologies, and use the data to provide feedback to physicians and practices, and then implement processes to improve patient outcomes. The largest regional collaborative in urology is the Michigan Urological Surgery Improvement Collaborative (MUSIC). Recent efforts by this group have been focused at understanding variation in care, improving patient selection for treatment, reducing treatment morbidity and measuring and optimizing technical skill. The American Urological Association has also recently launched a national quality registry (AQUA), with an initial focus on prostate cancer care. By understanding factors that result in exemplary performance, quality improvement collaboratives are able to develop best practices around areas of care with high variation that have the potential to improve outcomes and reduce costs. These developments have been made possible by the unique model offered by the collaborative structure with the goal of improving patient care at a population level.

  18. Improve Math Teaching with Incremental Improvements

    Science.gov (United States)

    Star, Jon R.

    2016-01-01

    Past educational reforms have failed because they didn't meet teachers where they were. They expected major changes in practices that may have been unrealistic for many teachers even under ideal professional learning conditions. Instead of promoting broad scale changes, improvement may be more likely if they are composed of small yet powerful…

  19. Continual improvement plan

    Science.gov (United States)

    1994-01-01

    NASA's approach to continual improvement (CI) is a systems-oriented, agency-wide approach that builds on the past accomplishments of NASA Headquarters and its field installations and helps achieve NASA's vision, mission, and values. The NASA of the future will fully use the principles of continual improvement in every aspect of its operations. This NASA CI plan defines a systematic approach and a model for continual improvement throughout NASA, stressing systems integration and optimization. It demonstrates NASA's constancy of purpose for improvement - a consistent vision of NASA as a worldwide leader in top-quality science, technology, and management practices. The CI plan provides the rationale, structures, methods, and steps, and it defines NASA's short term (1-year) objectives for improvement. The CI plan presents the deployment strategies necessary for cascading the goals and objectives throughout the agency. It also provides guidance on implementing continual improvement with participation from top leadership and all levels of employees.

  20. Socially Improving Tax Reforms

    OpenAIRE

    Duclos, Jean-Yves; Makdissi, Paul; Wodon, Quentin

    2008-01-01

    This paper proposes graphical methods to determine whether commodity-tax changes are "socially improving", in the sense of improving social welfare or decreasing poverty for large classes of social welfare and poverty indices. It also derives estimators of critical poverty lines and economic efficiency ratios which can be used to characterize socially-improving tax reforms. The statistical properties of the various estimators are derived in order to make the method implementable using survey ...

  1. Ergonomic Improvements for Foundries

    Energy Technology Data Exchange (ETDEWEB)

    Frank Peters; Patrick Patterson

    2002-06-18

    The goal of this project was to make improvements to the production systems of the steel casting industry through ergonomic improvements. Because of the wide variety of products, the wide range of product sizes, and the relatively small quantities of any particular product, manual operations remain a vital part of the production systems of the steel casting companies. Ergonomic improvements will assist the operators to more efficiently and consistently produce quality products.

  2. Software Process Improvement Defined

    DEFF Research Database (Denmark)

    Aaen, Ivan

    2002-01-01

    This paper argues in favor of the development of explanatory theory on software process improvement. The last one or two decades commitment to prescriptive approaches in software process improvement theory may contribute to the emergence of a gulf dividing theorists and practitioners....... It is proposed that this divide be met by the development of theory evaluating prescriptive approaches and informing practice with a focus on the software process policymaking and process control aspects of improvement efforts...

  3. Tree Improvement Glossary

    DEFF Research Database (Denmark)

    Schmidt, Lars Holger

    Forest tree improvement encompasses a number of scientific and technical areas like floral-, reproductive- and micro-biology, genetics breeding methods and strategies, propagation, gene conservation, data analysis and statistics, each area with a comprehensive terminology. The terms selected...... for definition here are those most frequently used in tree improvement literature. Clonal propagation is included in the view of the great expansion of that field as a means of mass multiplication of improved material....

  4. Process Improvement Essentials

    CERN Document Server

    Persse, James R

    2006-01-01

    Process Improvement Essentials combines the foundation needed to understand process improvement theory with the best practices to help individuals implement process improvement initiatives in their organization. The three leading programs: ISO 9001:2000, CMMI, and Six Sigma--amidst the buzz and hype--tend to get lumped together under a common label. This book delivers a combined guide to all three programs, compares their applicability, and then sets the foundation for further exploration.

  5. Georgia - Improved Learning Environment

    Data.gov (United States)

    Millennium Challenge Corporation — The school rehabilitation activity seeks to decrease student and teacher absenteeism, increase students’ time on task, and, ultimately, improve learning and labor...

  6. Improving palliative care.

    LENUS (Irish Health Repository)

    Moran, Sue

    2009-05-01

    Any service improvement project requires planning, action and evaluation. Using a recognised quality improvement framework can offer a structured approach to implementing and assessing changes to patient care. This article describes how use of the Deming Cycle has helped to identify nurses\\' learning needs.

  7. Improving Precision of Types

    DEFF Research Database (Denmark)

    Winther, Johnni

    mixing of unrelated types. Secondly, we present an improvement of the type checking algorithm in Java which enables the compiler to detect and ease the use of a common programming idiom called guarded casts. Thirdly, we present an improvement of the precision with which classes generated by a parser...

  8. Continuous Personal Improvement.

    Science.gov (United States)

    Emiliani, M. L.

    1998-01-01

    Suggests that continuous improvement tools used in the workplace can be applied to self-improvement. Explains the use of such techniques as one-piece flow, kanban, visual controls, and total productive maintenance. Points out misapplications of these tools and describes the use of fishbone diagrams to diagnose problems. (SK)

  9. Improving Listening Skills.

    Science.gov (United States)

    Geiss, Patricia A.; Mayer, Rose

    This report describes a program for improving listening skills, lack of which interferes with second language acquisition. The targeted population was first- and second-year Spanish students in one middle school and one high school. Intervention over 15 weeks included changes in the classroom environment (desk arrangement, improved lighting,…

  10. Improving Loop Dependence Analysis

    DEFF Research Database (Denmark)

    Jensen, Nicklas Bo; Karlsson, Sven

    2017-01-01

    Programmers can no longer depend on new processors to have significantly improved single-thread performance. Instead, gains have to come from other sources such as the compiler and its optimization passes. Advanced passes make use of information on the dependencies related to loops. We improve th...

  11. Continuous quality improvement

    International Nuclear Information System (INIS)

    Bourne, P.B.

    1985-01-01

    This paper describes the various statistical tools used at the Hanford Engineering Development Laboratory to achieve continuous quality improvement in the development of Breeder Reactor Technology and in reactor operations. The role of the quality assurance professionals in this process, including quantifiable measurements using actual examples, is provided. The commitment to quality improvement through top management involvement is dramatically illustrated

  12. Genetic improvement of vegetables

    International Nuclear Information System (INIS)

    Jaramillo Vasquez, J.G.

    2001-01-01

    Some genetic bases of the improvement of vegetables are given. The objectives of the genetic improvement and the fundamental stages of this process are done. The sources of genetic variation are indicated and they are related the reproduction systems of the main horticultural species. It is analyzed the concept of genetic inheritance like base to determine the procedures more appropriate of improvement. The approaches are discussed, has more than enough phenotypic value, genetic action and genotypic variance; Equally the heredability concepts and value of improvement. The conventional methods of improvement are described, like they are: the introduction of species or varieties, the selection, the pure line, the pedigree method, the selection for families, the recurrent selection, the selection for unique seed, the haploids method, the selection for heterosis and the synthetic varieties

  13. Documentation of Improvement Competences

    DEFF Research Database (Denmark)

    Johansen, Jørn; Back, Karsten Kristensen; Korsaa, Morten

    2017-01-01

    competences, which should or could be brought into play during the project – and therefor also in one way or another addresses the quality of the activated competences in the improvement project – a kind of qualification. The clue is that the structure of the report follows the units and element in the SPI......This paper demonstrates how a report used in a Master in Project management and Process improvement training at Roskilde University Denmark can be used to evaluate if a student can pass the ECQA SPI Manager exam. It also demonstrates how the structure of the report addresses all necessary...... Manager job role, which is based on the SPI Manifesto and the ImprovAbilityTM model (part of ISO/IEC 33014 Guideline for Process Improvement) among other types of knowledge and research....

  14. IMPROVING CONCEPTUAL DESIGN QUALITY

    DEFF Research Database (Denmark)

    Bush, Stuart; Robotham, Antony John

    1999-01-01

    This paper will consider how Quality Function Deployment (QFD) and Design for Manufacture and Assembly (DFMA) processes can be used to improve the design quality of products at the concept stage. We appreciate that both QFD and DFMA are techniques that have been used for some time by mature product...... quality is maintained in design project work. The projects described have been carried out with products manufactured by small to medium sized enterprises (SME's), where we have found significant opportunities for product improvement. The quantitative nature of DFMA analysis results allows the novice...... for continuous improvement of their products. However, we consider that if novice designers are able to successfully utilise design tools like QFD and DFMA and achieve improvements in design quality, then SME’s have no excuses for ignoring the benefits they could bring to their own product development activity....

  15. Improved Mass Spectrometer Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Improved Mass Spectrometer project will develop system requirements and analyze the path to space qualification.   The results of this project...

  16. Home Improvements Prevent Falls

    Science.gov (United States)

    ... turn JavaScript on. Feature: Falls and Older Adults Home Improvements Prevent Falls Past Issues / Winter 2014 Table ... and ensure your safety. "Safe-ty-fy" Your Home Some Questions for Your Provider Will my medicines ...

  17. Observatory Improvements for SOFIA

    Science.gov (United States)

    Peralta, Robert A.; Jensen, Stephen C.

    2012-01-01

    The Stratospheric Observatory for Infrared Astronomy (SOFIA) is a joint project between NASA and Deutsches Zentrum fuer Luft- und Raumfahrt (DLR), the German Space Agency. SOFIA is based in a Boeing 747 SP and flown in the stratosphere to observe infrared wavelengths unobservable from the ground. In 2007 Dryden Flight Research Center (DFRC) inherited and began work on improving the plane and its telescope. The improvements continue today with upgrading the plane and improving the telescope. The Observatory Verification and Validation (V&V) process is to ensure that the observatory is where the program says it is. The Telescope Status Display (TSD) will provide any information from the on board network to monitors that will display the requested information. In order to assess risks to the program, one must work through the various threats associate with that risk. Once all the risks are closed the program can work towards improving the observatory.

  18. Improving Healthcare Logistics Processes

    DEFF Research Database (Denmark)

    Feibert, Diana Cordes

    provision whilst providing high quality care. Logistics activities in hospitals provide a significant opportunity for cost containment in healthcare through the implementation of best practices. Literature provides little guidance on how to improve healthcare logistics processes. This study investigates...... logistics processes in hospitals and aims to provide theoretically and empirically based evidence for improving these processes to both expand the knowledge base of healthcare logistics and provide a decision tool for hospital logistics managers to improve their processes. Case studies were conducted...... at hospitals in Denmark and the US investigating three different types of processes: bed logistics, hospital cleaning, and pharmaceutical distribution. Based on an analysis and comparison of the case studies, a set of factors were identified influencing the decision on how to improve healthcare logistics...

  19. Improving Family Communications

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Listen Español Text Size Email Print Share Improving Family Communications Page Content Article Body How can I ...

  20. Maintenance improvement program

    International Nuclear Information System (INIS)

    Derbonne, D.R.; Plunkett, T.F.; Simpson, J.R.

    1989-01-01

    During fuel cycle 1 at River Bend station, considerable effort was expended to reduce corrective maintenance work orders (MWOs) to <1,000. This was done by complementing the plant staff with costly contract personnel. Coming out of the first refueling outage, most contract personnel were released. The change in MWO backlog started a steady rise. It became readily apparent that to avoid costly contract staff time, a maintenance improvement program (MIP) was necessary. The MIP Was primarily directed at two areas: crew efficiency improvements and improved preplanned MWO packages. The overall effect of the MIP was to achieve significant productivity improvements with reduced operation and maintenance cost by providing frequent accountability to all levels of maintenance supervision. The MIP also produced a feeling of pride among the maintenance department employees that had not really existed before. This was the best benefit of all