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Sample records for bone preclinical studies

  1. Reproducibility of results in preclinical studies: a perspective from the bone field.

    Science.gov (United States)

    Manolagas, Stavros C; Kronenberg, Henry M

    2014-10-01

    The biomedical research enterprise-and the public support for it-is predicated on the belief that discoveries and the conclusions drawn from them can be trusted to build a body of knowledge which will be used to improve human health. As in all other areas of scientific inquiry, knowledge and understanding grow by layering new discoveries upon earlier ones. The process self-corrects and distills knowledge by discarding false ideas and unsubstantiated claims. Although self-correction is inexorable in the long-term, in recent years biomedical scientists and the public alike have become alarmed and deeply troubled by the fact that many published results cannot be reproduced. The chorus of concern reached a high pitch with a recent commentary from the NIH Director, Francis S. Collins, and Principal Deputy Director, Lawrence A. Tabak, and their announcement of specific plans to enhance reproducibility of preclinical research that relies on animal models. In this invited perspective, we highlight the magnitude of the problem across biomedical fields and address the relevance of these concerns to the field of bone and mineral metabolism. We also suggest how our specialty journals, our scientific organizations, and our community of bone and mineral researchers can help to overcome this troubling trend. PMID:24916175

  2. Preparation and preclinical pharmacological study on a novel bone imaging agent {sup 99m}Tc-EMIDP

    Energy Technology Data Exchange (ETDEWEB)

    Lin Jianguo [Key Laboratory of Nuclear Medicine, Ministry of Health and Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Luo Shineng, E-mail: shineng914@yahoo.com.c [Key Laboratory of Nuclear Medicine, Ministry of Health and Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Chen Chuanqing [Key Laboratory of Nuclear Medicine, Ministry of Health and Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122 (China); Qiu Ling, E-mail: qiulingwx@gmail.co [Key Laboratory of Nuclear Medicine, Ministry of Health and Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Wang Yan [Key Laboratory of Nuclear Medicine, Ministry of Health and Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122 (China); Cheng Wen; Ye Wanzhong [Key Laboratory of Nuclear Medicine, Ministry of Health and Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Xia Yongmei [School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122 (China)

    2010-09-15

    A novel zoledronic acid (ZL) derivative, 1-hydroxy-2-(2-ethyl-4-methyl-1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid (EMIDP), was prepared and labeled with {sup 99m}Tc successfully in a high labeling yield and good stability in vitro. The preclinical pharmacological properties of {sup 99m}Tc-EMIDP were investigated and compared with {sup 99m}Tc-MDP and {sup 99m}Tc-ZL. The studies of biodistribution in mice and SPECT bone imaging of the rabbit suggest that {sup 99m}Tc-EMIDP has highly selective uptake in the skeletal system and rapid clearance in the soft tissues. The present findings indicate that {sup 99m}Tc-EMIDP holds great potential for bone scintigraphy.

  3. Microrobotized blasting improves the bone-to-textured implant response. A preclinical in vivo biomechanical study.

    Science.gov (United States)

    Coelho, Paulo G; Gil, Luiz F; Neiva, Rodrigo; Jimbo, Ryo; Tovar, Nick; Lilin, Thomas; Bonfante, Estevam A

    2016-03-01

    This study evaluated the effect of microrobotized blasting of titanium endosteal implants relative to their manually blasted counterparts. Two different implant systems were utilized presenting two different implant surfaces. Control surfaces (Manual) were fabricated by manually grit blasting the implant surfaces while experimental surfaces (Microblasted) were fabricated through a microrobotized system that provided a one pass grit blasting routine. Both surfaces were created with the same ~50µm average particle size alumina powder at ~310KPa. Surfaces were then etched with 37% HCl for 20min, washed, and packaged through standard industry procedures. The surfaces were characterized through scanning electron microscopy (SEM) and optical interferometry, and were then placed in a beagle dog radius model remaining in vivo for 3 and 6 weeks. The implant removal torque was recorded and statistical analysis evaluated implant system and surface type torque levels as a function of time in vivo. Histologic sections were qualitatively evaluated for tissue response. Electron microscopy depicted textured surfaces for both manual and microblasted surfaces. Optical interferometry showed significantly higher Sa, Sq, values for the microblasted surface and no significant difference for Sds and Sdr values between surfaces. In vivo results depicted that statistically significant gains in biomechanical fixation were obtained for both implant systems tested at 6 weeks in vivo, while only one system presented significant biomechanical gain at 3 weeks. Histologic sections showed qualitative higher amounts of new bone forming around microblasted implants relative to the manually blasted group. Microrobotized blasting resulted in higher biomechanical fixation of endosteal dental implants and should be considered as an alternative for impant surface manufacturing. PMID:26703231

  4. Preclinical evaluation of strontium-containing bioactive bone cement

    International Nuclear Information System (INIS)

    Strontium (Sr) has become more attractive for orthopaedic applications as they can simultaneously stimulate bone formation and prevent bone loss. A Sr-containing bioactive bone cement (Sr-BC) has been designed to fix osteoporotic bone fracture. Sr is a trace element, so the safety of containing Sr is concerned when Sr-BC is implanted in human body. The preclinical assessment of biocompatibility of Sr-BC was conducted according to ISO 10993 standards. MTT assay showed that this bioactive bone cement was non-toxic to mouse fibroblasts, and it met the basic requirement for the orthopaedic implant. The three independent genetic toxicity studies including Ames, chromosome aberration and bone marrow micronucleus assays demonstrated absence of genotoxic components in Sr-BC, which reassured the safety concerns of this novel bone cement. The muscle implantation results in present study were also encouraging. The acute inflammation around the cement was observed at 1 week post-implantation; however, no significant difference was observed between control and Sr-BC groups. These responses may be attributed to the presence of the foreign body, but the tissue healed after 12 weeks implantation. In summary, the above preclinical results provide additional assurance for the safety of this implant. Sr-BC can be used as a potential alternative to the traditional bone cement. - Highlights: • Strontium-containing bioactive bone cement (Sr-BC) was designed. • The biocompatibility of Sr-BC was evaluated according ISO 10993 standards. • Preclinical results provide additional assurance for the safety of Sr-BC

  5. In-vivo efficacy of compliant 3D nano-composite in critical-size bone defect repair: a six month preclinical study in rabbit.

    Directory of Open Access Journals (Sweden)

    Nitin Sagar

    Full Text Available Bone defects above critical size do not heal completely by itself and thus represent major clinical challenge to reconstructive surgery. Numerous bone substitutes have already been used to promote bone regeneration, however their use, particularly for critical-sized bone defects along with their long term in vivo safety and efficacy remains a concern. The present study was designed to obtain a complete healing of critical-size defect made in the proximal tibia of New Zealand White rabbit, using nano-hydroxyapatite/gelatin and chemically carboxymethylated chitin (n-HA/gel/CMC scaffold construct. The bone-implant interfaces and defect site healing was evaluated for a period up to 25 weeks using radiography, micro-computed tomography, fluorescence labeling, and histology and compared with respective SHAM (empty contra lateral control. The viscoelastic porous scaffold construct allows easy surgical insertion and post-operatively facilitate oxygenation and angiogenesis. Radiography of defect treated with scaffold construct suggested expedited healing at defect edges and within the defect site, unlike confined healing at edges of the SHAM sites. The architecture indices analyzed by micro-computed tomography showed a significant increase in percentage of bone volume fraction, resulted in reconciled cortico-trabecular bone formation at n-HA/gel/CMC constructs treated site (15.2% to 52.7% when compared with respective SHAM (10.2% to 31.8%. Histological examination and fluorescence labeling revealed that the uniformly interconnected porous surface of scaffold construct enhanced osteoblasts' activity and mineralization. These preclinical data suggest that, n-HA/gel/CMC construct exhibit stimulation of bone's innate regenerative capacity, thus underscoring their use in guided bone regeneration.

  6. Effect of Stem Cell Therapy on Bone Mineral Density: A Meta-Analysis of Preclinical Studies in Animal Models of Osteoporosis

    Science.gov (United States)

    Li, Feng; Zhou, Changlin; Xu, Liang; Tao, Shuqing; Zhao, Jingyi; Gu, Qun

    2016-01-01

    Background Preclinical studies of the therapeutic role of stem cell based therapy in animal models of osteoporosis have largely yielded inconsistent results. We performed a meta-analysis to provide an overview of the currently available evidence. Methods Pubmed, Embase and Cochrane Library databases were systematically searched for relevant controlled studies. A random-effect model was used for pooled analysis of the effect of stem cell based therapy on bone mineral density (BMD). Stratified analyses were performed to explore the effect of study characteristics on the outcomes. Results Pooled results from 12 preclinical studies (110 animals in stem cell treatment groups, and 106 animals in control groups) indicated that stem cell based treatment was associated with significantly improved BMD (standardized mean difference [SMD] = 1.29, 95% Confidence Interval [CI]: 0.84–1.74, P 0.05). Egger’s test detected potential publication bias (P = 0.055); however, ‘trim and fill’ analysis yielded similar results after statistically incorporating the hypothetical studies in the analysis (SMD = 1.24, 95% CI: 0.32–2.16, P < 0.001). Conclusions Stem cell transplantation may improve BMD in animal models of osteoporosis. Our meta-analysis indicates a potential therapeutic role of stem cell based therapy for osteoporosis, and serves to augment the rationale for clinical studies. PMID:26882451

  7. Multimodal imaging of bone metastases: From preclinical to clinical applications

    Directory of Open Access Journals (Sweden)

    Stephan Ellmann

    2015-10-01

    Full Text Available Metastases to the skeletal system are commonly observed in cancer patients, highly affecting the patients' quality of life. Imaging plays a major role in detection, follow-up, and molecular characterisation of metastatic disease. Thus, imaging techniques have been optimised and combined in a multimodal and multiparametric manner for assessment of complementary aspects in osseous metastases. This review summarises both application of the most relevant imaging techniques for bone metastasis in preclinical models and the clinical setting.

  8. [Preclinical study of noopept toxicity].

    Science.gov (United States)

    Kovalenko, L P; Smol'nikova, N M; Alekseeva, S V; Nemova, E P; Sorokina, A V; Miramedova, M G; Kurapova, S P; Sidorina, E I; Kulakova, A V; Daugel'-Dauge, N O

    2002-01-01

    Within the framework of a preclinical investigation, the new nootrope drug noopept (N-phenyl-acetyl-L-propyl-glycine ethylate) was tested for chronic toxicity upon peroral administration in a dose of 10 or 100 mg/kg over 6 months in both male and female rabbits. The results of observations showed that noopept administered in this dose range induced no irreversible pathologic changes in the organs and systems studied and exhibited no allergenic, immunotoxic, and mutagen activity. The drug affected neither the generative function nor the antenatal or postnatal progeny development. Noopept produced a dose-dependent suppression of inflammation reaction to concanavalin A and stimulated the cellular and humoral immune response in mice. PMID:12025790

  9. Preclinical studies of concomitant chemoradiation

    International Nuclear Information System (INIS)

    Animal models are widely used in preclinical studies in order to explain the mechanisms of action of chemotherapy, radiotherapy and concomitant chemoradiation, to analyze pathophysiology of tumors and to evaluate the treatment of choice for malignant tumors. The choice of murine tumor or human tumor xenograft system is still debated. Xenografted human tumors have two main advantages: their human origin and wanted pathological type, which is necessary for future clinical studies. There are a lot of disadvantages of xenografted tumors: the stroma and vascular network of transplanted tumors have murine origin, the graft is mostly ectopic, the volume of transplanted tumors at the time of chemoradiotherapy is much smaller than that of the tumor in man; due to residual immunity it is difficult to determine response to cytotoxic treatment. It is still impossible to extrapolate the results obtained in a tumor model in animal to man. These investigations are useful for interpretation of clinical results and for proposing the less empirical method of chemoradiation for phase II clinical trials. (author)

  10. Nanocapsular forms of preparations in preclinical studies

    Directory of Open Access Journals (Sweden)

    Ekaterina Grinevich

    2010-07-01

    Full Text Available The paper examines preclinical study of nanocapsule deliverysystem, particularly the influence of nanocapsule with a vasodilatorin the process of programmed myocardial cells death. Isosorbidedinitrate was loaded in nanocapsules. To investigate the effectnanocapsule isosorbide dinitrate on the process of apoptosis incardiomyocytes, a series of experimental works wereperformed. For this purpose, a model of coronary insufficiency in 4groups of animals were elaborated. The experimental works onlaboratory animals were conducted in accordance withrequirements of the European Convention for the protection ofvertebrate animals. The first preclinical trials showed the presenceof specific activity of obtained drugs. The basis of nanocapsularsystem was phosphatidylinositol, and the active loading substanceswere alprostadil, interferon alpha.

  11. Quantification of osteolytic bone lesions in a preclinical rat trial

    Science.gov (United States)

    Fränzle, Andrea; Bretschi, Maren; Bäuerle, Tobias; Giske, Kristina; Hillengass, Jens; Bendl, Rolf

    2013-10-01

    In breast cancer, most of the patients who died, have developed bone metastasis as disease progression. Bone metastases in case of breast cancer are mainly bone destructive (osteolytic). To understand pathogenesis and to analyse response to different treatments, animal models, in our case rats, are examined. For assessment of treatment response to bone remodelling therapies exact segmentations of osteolytic lesions are needed. Manual segmentations are not only time-consuming but lack in reproducibility. Computerized segmentation tools are essential. In this paper we present an approach for the computerized quantification of osteolytic lesion volumes using a comparison to a healthy reference model. The presented qualitative and quantitative evaluation of the reconstructed bone volumes show, that the automatically segmented lesion volumes complete missing bone in a reasonable way.

  12. Preclinical studies of sex differences: a clinical perspective

    OpenAIRE

    Voskuhl, Rhonda

    2016-01-01

    The new policy from the National Institutes of Health to encourage grant applicants to consider studying both females and males in preclinical biological experiments has been met with support and opposition. Here, we will discuss implications of preclinical studies of sex differences on clinical research.

  13. Dissolution DNP for in vivo preclinical studies

    Science.gov (United States)

    Comment, Arnaud

    2016-03-01

    The tremendous polarization enhancement afforded by dissolution dynamic nuclear polarization (DNP) can be taken advantage of to perform preclinical in vivo molecular and metabolic imaging. Following the injection of molecules that are hyperpolarized via dissolution DNP, real-time measurements of their biodistribution and metabolic conversion can be recorded. This technology therefore provides a unique and invaluable tool for probing cellular metabolism in vivo in animal models in a noninvasive manner. It gives the opportunity to follow and evaluate disease progression and treatment response without requiring ex vivo destructive tissue assays. Although its considerable potential has now been widely recognized, hyperpolarized magnetic resonance by dissolution DNP remains a challenging method to implement for routine in vivo preclinical measurements. The aim of this article is to provide an overview of the current state-of-the-art technology for preclinical applications and the challenges that need to be addressed to promote it and allow its wider dissemination in the near future.

  14. Preclinical and clinical safety studies on DNA vaccines.

    OpenAIRE

    Schalk, Johanna A C; Mooi, Frits R.; Berbers, Guy A M; Aerts, Leon A G J M van; Ovelgönne, Hans; Kimman, Tjeerd G.

    2007-01-01

    DNA vaccines are based on the transfer of genetic material, encoding an antigen, to the cells of the vaccine recipient. Despite high expectations of DNA vaccines as a result of promising preclinical data their clinical utility remains unproven. However, much data is gathered in preclinical and clinical studies about the safety of DNA vaccines. Here we review current knowledge about the safety of DNA vaccines. Safety concerns of DNA vaccines relate to genetic, immunologic, toxic, and environme...

  15. Preclinical evaluation of Sunitinib as a single agent in the prophylactic setting in a mouse model of bone metastases

    International Nuclear Information System (INIS)

    A substantial number of breast cancer patients are identified as being at high risk of developing metastatic disease. With increasing number of targeted therapeutics entering clinical trials, chronic administration of these agents may be a feasible approach for the prevention of metastases within this subgroup of patients. In this preclinical study we examined whether Sunitinib, a multi-tyrosine kinase inhibitor which has anti-angiogenic and anti-resorptive activity, is effective in the prevention of bone metastases. Sunitinib was administered daily with the first dose commencing prior to tumor cell inoculation. Intracardiac injection was performed with MDA-MB23 bone-seeking cells, which were stably transfected with DsRed2. In vivo plain radiography and fluorescent imaging (Berthold NightOwl) was used in the analysis of bone metastases. Histomorphometry was used for the quantification of TRAP+ cells from bone sections and immunohistochemistry was performed using an antibody reactive to CD34 for quantification of microvessel density. Preventive dosing administration of Sunitinib does not inhibit colonization of tumor cells to bone or reduce the size of osteolytic lesions. There was a decrease in the number of TRAP+ cells with Sunitinib treatment but this did not reach significance. Sunitinib inhibited tumor growth as determined by imaging of fluorescent tumor area. Immunohistochemical analyses of microvessel density revealed a concomitant decrease in the number of tumor blood vessels. The findings suggest that Sunitinib can be used as a therapeutic agent for the treatment of bone metastases but as a single agent it is not effective in terms of prevention. Therefore a combination approach with other cytostatic drugs should be pursued

  16. Chemical and preclinical studies on Hedyotis diffusa with anticancer potential.

    Science.gov (United States)

    Niu, Yu; Meng, Qiu-Xia

    2013-01-01

    This paper presents the chemical and preclinical anticancer research on Hedyotis diffusa Willd. in detail, one of the most renowned herbs often prescribed in the polyherbal formulas for cancer treatment in traditional Chinese medicine. Anthraquinones, flavonoids, and terpenoids constitute the majority of the 69 compounds that have been isolated and identified from H. diffusa. The anticancer effects of the methanolic, ethanolic, and aqueous extracts in various preclinical cancer models have been described. This review also summarized the anticancer activity of constituents of the herb and the mechanisms of action. All the studies suggest that H. diffusa has enormous potential in the therapy of cancer and warrants further chemical and pharmacological investigation. PMID:23600735

  17. Preclinical models for in vitro mechanical loading of bone-derived cells.

    Science.gov (United States)

    Michael Delaine-Smith, Robin; Javaheri, Behzad; Helen Edwards, Jennifer; Vazquez, Marisol; Rumney, Robin Mark Howard

    2015-01-01

    It is well established that bone responds to mechanical stimuli whereby physical forces are translated into chemical signals between cells, via mechanotransduction. It is difficult however to study the precise cellular and molecular responses using in vivo systems. In vitro loading models, which aim to replicate forces found within the bone microenvironment, make the underlying processes of mechanotransduction accessible to the researcher. Direct measurements in vivo and predictive modeling have been used to define these forces in normal physiological and pathological states. The types of mechanical stimuli present in the bone include vibration, fluid shear, substrate deformation and compressive loading, which can all be applied in vitro to monolayer and three-dimensional (3D) cultures. In monolayer, vibration can be readily applied to cultures via a low-magnitude, high-frequency loading rig. Fluid shear can be applied to cultures in multiwell plates via a simple rocking platform to engender gravitational fluid movement or via a pump to cells attached to a slide within a parallel-plate flow chamber, which may be micropatterned for use with osteocytes. Substrate strain can be applied via the vacuum-driven FlexCell system or via a four-point loading jig. 3D cultures better replicate the bone microenvironment and can also be subjected to the same forms of mechanical stimuli as monolayer, including vibration, fluid shear via perfusion flow, strain or compression. 3D cocultures that more closely replicate the bone microenvironment can be used to study the collective response of several cell types to loading. This technical review summarizes the methods for applying mechanical stimuli to bone cells in vitro. PMID:26331007

  18. Using Micro-CT Derived Bone Microarchitecture to Analyze Bone Stiffness - A Case Study on Osteoporosis Rat Bone.

    Science.gov (United States)

    Wu, Yuchin; Adeeb, Samer; Doschak, Michael R

    2015-01-01

    Micro-computed tomography (Micro-CT) images can be used to quantitatively represent bone geometry through a range of computed attenuation-based parameters. Nonetheless, those parameters remain indirect indices of bone microarchitectural strength and require further computational tools to interpret bone structural stiffness and potential for mechanical failure. Finite element analysis (FEA) can be applied to measure trabecular bone stiffness and potentially predict the location of structural failure in preclinical animal models of osteoporosis, although that procedure from image segmentation of Micro-CT derived bone geometry to FEA is often challenging and computationally expensive, resulting in failure of the model to build. Notably, the selection of resolution and threshold for bone segmentation are key steps that greatly affect computational complexity and validity. In the following study, we evaluated an approach whereby Micro-CT derived grayscale attenuation and segmentation data guided the selection of trabecular bone for analysis by FEA. We further correlated those FEA results to both two- and three-dimensional bone microarchitecture from sham and ovariectomized (OVX) rats (n = 10/group). A virtual cylinder of vertebral trabecular bone 40% in length from the caudal side was selected for FEA, because Micro-CT based image analysis indicated the largest differences in microarchitecture between the two groups resided there. Bone stiffness was calculated using FEA and statistically correlated with the three-dimensional values of bone volume/tissue volume, bone mineral density, fractal dimension, trabecular separation, and trabecular bone pattern factor. Our method simplified the process for the assessment of trabecular bone stiffness by FEA from Micro-CT images and highlighted the importance of bone microarchitecture in conferring significantly increased bone quality capable of resisting failure due to increased mechanical loading. PMID:26042089

  19. Using Micro-CT Derived Bone Microarchitecture to Analyze Bone Stiffness - A Case Study on Osteoporosis Rat Bone

    Directory of Open Access Journals (Sweden)

    Yuchin eWu

    2015-05-01

    Full Text Available Micro-computed tomography images can be used to quantitatively represent bone geometry through a range of computed attenuation-based parameters. Nonetheless, those parameters remain indirect indices of bone micro-architectural strength and require further computational tools to interpret bone structural stiffness and potential for mechanical failure. Finite element analysis (FEA can be applied to measure trabecular bone stiffness and potentially predict the location of structural failure in preclinical animal models of osteoporosis, although that procedure from image segmentation of micro-CT derived bone geometry to FEA is often challenging and computationally expensive, resulting in failure of the model to build. Notably, the selection of resolution and threshold for bone segmentation are key steps that greatly affect computational complexity and validity. In the following study, we evaluated an approach whereby Micro-CT derived greyscale attenuation and segmentation data guided the selection of trabecular bone for analysis by FEA. We further correlated those FEA results to both two and three dimensional bone microarchitecture from sham and ovariectomized (OVX rats (n=10/group. A virtual cylinder of vertebral trabecular bone 40% in length from the caudal side was selected for FEA because micro-CT based image analysis indicated the largest differences in microarchitecture between the two groups resided there. Bone stiffness was calculated using FEA and statistically correlated with the three dimensional values of bone volume/tissue volume, bone mineral density, fractal dimension, trabecular separation and trabecular bone pattern factor. Our method simplified the process for the assessment of trabecular bone stiffness by FEA from Micro-CT images and highlighted the importance of bone microarchitecture in conferring significantly increased bone quality capable of resisting failure due to increased mechanical loading.

  20. Preclinical studies of [99mTc]DTPA-mannosyl-dextran

    International Nuclear Information System (INIS)

    We report the preclinical testing of a synthetic receptor-binding macromolecule, [99mTc]DTPA-mannosyl-dextran (36 kDa, 8 DTPA and 55 mannosyl units per dextran, KD = 0.12 nM), for sentinel node detection. Nonclinical safety studies included cardiac pharmacology safety studies, acute toxicology and pathology studies at 50 and 500 times the scaled human dose in both rats and rabbits after foot pad administration, and perivascular irritation studies in rabbits following intra-muscular administration at 100 and 1000 times the scaled human dose. Biodistribution studies in rabbits at 15 m, 1 h, and 3 h indicated that [99mTc]DTPA-mannosyl-dextran cleared the hind foot pad with a biological half-life of 2.21 ± 0.27 h. Other than mild hepatocyte hypertrophy in rabbits, no abnormalities in toxicology or pathology were found. Intravenous administration had no effect on survival, any clinical observations, electrocardiograms, or blood pressures. Intramuscular injection had no effect on survival, clinical observations, injection site observations, or injection site histopathology. The estimated absorbed radiation dose to the affected breast was 0.15 mGy/MBq and the effective dose was 1.06 x 10-2 mSv/MBq. This preclinical study demonstrates that [99mTc]DTPA-mannosyl-dextran has no toxicities and has an acceptable biodistribution and radiation dose

  1. Optimized design and analysis of preclinical intervention studies in vivo.

    Science.gov (United States)

    Laajala, Teemu D; Jumppanen, Mikael; Huhtaniemi, Riikka; Fey, Vidal; Kaur, Amanpreet; Knuuttila, Matias; Aho, Eija; Oksala, Riikka; Westermarck, Jukka; Mäkelä, Sari; Poutanen, Matti; Aittokallio, Tero

    2016-01-01

    Recent reports have called into question the reproducibility, validity and translatability of the preclinical animal studies due to limitations in their experimental design and statistical analysis. To this end, we implemented a matching-based modelling approach for optimal intervention group allocation, randomization and power calculations, which takes full account of the complex animal characteristics at baseline prior to interventions. In prostate cancer xenograft studies, the method effectively normalized the confounding baseline variability, and resulted in animal allocations which were supported by RNA-seq profiling of the individual tumours. The matching information increased the statistical power to detect true treatment effects at smaller sample sizes in two castration-resistant prostate cancer models, thereby leading to saving of both animal lives and research costs. The novel modelling approach and its open-source and web-based software implementations enable the researchers to conduct adequately-powered and fully-blinded preclinical intervention studies, with the aim to accelerate the discovery of new therapeutic interventions. PMID:27480578

  2. Resveratrol: A review of preclinical studies for human cancer prevention

    International Nuclear Information System (INIS)

    The search for novel and effective cancer chemopreventive agents has led to the identification of various naturally occurring compounds one of which is resveratrol (trans-3,4',5-trihydroxystilbene), a phytoalexin derived from the skin of grapes and other fruits. Resveratrol is known to have potent anti-inflammatory and antioxidant effects and to inhibit platelet aggregation and the growth of a variety of cancer cells. Its potential chemopreventive and chemotherapeutic activities have been demonstrated in all three stages of carcinogenesis (initiation, promotion, and progression), in both chemically and UVB-induced skin carcinogenesis in mice, as well as in various murine models of human cancers. Evidence from numerous in vitro and in vivo studies has confirmed its ability to modulate various targets and signaling pathways. This review discusses the current preclinical and mechanistic data available and assesses resveratrol's anticancer effects to support its potential as an anticancer agent in human populations

  3. Porcine Heterotopic Composite Tissue Allograft Transplantation using A Large Animal Model for Preclinical Studies

    Directory of Open Access Journals (Sweden)

    Yur-Ren Kuo

    2006-06-01

    Full Text Available Background: Composite tissue allograft (CTA transplantation is currently limited by therisks of side effects resulting from long-term high-dose immunosuppression.Therefore, preclinical animal models are essential to help CTA transplantationadvance into clinical reality. Evidence has shown that small-animalmodel (rodents immunotherapy protocols cannot be directly applied tohumans. This study investigated whether a miniature porcine model is reproduciblefor preclinical studies.Methods: Based on the concept of vascularized skeletal tissue allograft transplantation,limb heterotopic allograft tissue from a mismatched donor miniature pig consistingof the distal femur, knee joint, tibia, fibula, and surrounding musclewith a vascularized skin paddle model supplied by the superficial femoralvessels was transplanted into recipient pigs. Swine viability and rejectionsigns of the allograft were monitored postoperatively. Histopathologicalchanges in the allograft tissues were examined using hematoxylin and eosinstaining if the allo-skin flap was rejected.Results: The recipient pigs were ambulatory immediately following surgery. Theflaps showed no visible signs of rejection over the first 4 days of observation.The skin flaps appeared bluish-purple and edematous on postoperative days5~7, and progressed to tissue necrosis and rejection on postoperative days8~13. Histological examination revealed marked mononuclear cell infiltrationand necrotic changes in the all rejected tissues, especial in the allograftskin tissues (skin > muscle > bone > cartilage.Conclusions: The results showed this the porcine CTA model is reproducible and suitablefor preclinical training for human CTA transplantation. Monitoring of theallo-skin flap is a useful strategy to evaluate composite tissue allograft rejection.

  4. The impact of weakly bound 89Zr on preclinical studies: Non-specific accumulation in solid tumors and aspergillus infection

    DEFF Research Database (Denmark)

    Severin, Gregory; Jørgensen, Jesper T.; Wiehr, Stefan;

    2015-01-01

    Preclinical studies involving 89Zr often report significant bone accumulation, which is associated with dissociation of the radiometal from the tracer. However, experiments determining the uptake of unbound 89Zr in disease models are not performed as routine controls. The purpose of the present s...

  5. Pre-clinical in vivo models for the screening of bone biomaterials for oral/craniofacial indications: focus on small-animal models.

    Science.gov (United States)

    Stavropoulos, Andreas; Sculean, Anton; Bosshardt, Dieter D; Buser, Daniel; Klinge, Björn

    2015-06-01

    Preclinical in vivo experimental studies are performed for evaluating proof-of-principle concepts, safety and possible unwanted reactions of candidate bone biomaterials before proceeding to clinical testing. Specifically, models involving small animals have been developed for screening bone biomaterials for their potential to enhance bone formation. No single model can completely recreate the anatomic, physiologic, biomechanic and functional environment of the human mouth and jaws. Relevant aspects regarding physiology, anatomy, dimensions and handling are discussed in this paper to elucidate the advantages and disadvantages of small-animal models. Model selection should be based not on the 'expertise' or capacities of the team, but rather on a scientifically solid rationale, and the animal model selected should reflect the question for which an answer is sought. The rationale for using heterotopic or orthotopic testing sites, and intraosseous, periosseous or extraskeletal defect models, is discussed. The paper also discusses the relevance of critical size defect modeling, with focus on calvarial defects in rodents. In addition, the rabbit sinus model and the capsule model in the rat mandible are presented and discussed in detail. All animal experiments should be designed with care and include sample-size and study-power calculations, thus allowing generation of meaningful data. Moreover, animal experiments are subject to ethical approval by the relevant authority. All procedures and the postoperative handling and care, including postoperative analgesics, should follow best practice. PMID:25867979

  6. Feasibility study of pre-clinical Thiel embalmed human cadaver for MR-guided focused ultrasound of the spine.

    Science.gov (United States)

    Karakitsios, Ioannis; Mihcin, Senay; Saliev, Timur; Melzer, Andreas

    2016-06-01

    Background Magnetic Resonance-guided Focused Ultrasound Surgery (MRgFUS) is a non-invasive treatment option based on high acoustic absorption and minimal thermal conductivity of the bone to destroy nerves and reduce pain. There is lack of a preclinical validation tool with correct human anatomy. This work introduces usage of an ex-vivo Thiel embalmed human tissue model for preclinical verification of MRgFUS on intervertebral discs or bone metastases within the spinal body. Material and methods Thiel embalmed human cadaver was subjected to FUS sonication of the vertebra (with energies 250J, 420J, 600J) and the intervertebral disc (with energies 310J, 610J, 950J) of the lumbar spine for 20s of sonication under MR guidance. Results For the vertebra, maximum temperatures were recorded as 38 °C, 58.3 °C, 69 °C. The intervertebral disc reached maximum temperatures of 23.7 °C, 54 °C, 83 °C. The temperature measurements showed that the spinal canal and adjacent organs were not heated > 0.1 °C. Conclusions A heating pattern that can induce thermal ablation was achieved in the vertebral body and the intervertebral disc. Adjacent structures and nerves were not heated in lethal levels. Thus, the Thiel embalmed human cadaver can be a safe and efficient model for preclinical study of application of MRgFUS on the upper lumbar spine. PMID:26923220

  7. Preclinical Studies with Umbilical Cord Mesenchymal Stromal Cells in Different Animal Models for Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Eder Zucconi

    2011-01-01

    Full Text Available Umbilical cord mesenchymal stromal cells (MSC have been widely investigated for cell-based therapy studies as an alternative source to bone marrow transplantation. Umbilical cord tissue is a rich source of MSCs with potential to derivate at least muscle, cartilage, fat, and bone cells in vitro. The possibility to replace the defective muscle cells using cell therapy is a promising approach for the treatment of progressive muscular dystrophies (PMDs, independently of the specific gene mutation. Therefore, preclinical studies in different models of muscular dystrophies are of utmost importance. The main objective of the present study is to evaluate if umbilical cord MSCs have the potential to reach and differentiate into muscle cells in vivo in two animal models of PMDs. In order to address this question we injected (1 human umbilical cord tissue (hUCT MSCs into the caudal vein of SJL mice; (2 hUCT and canine umbilical cord vein (cUCV MSCs intra-arterially in GRMD dogs. Our results here reported support the safety of the procedure and indicate that the injected cells could engraft in the host muscle in both animal models but could not differentiate into muscle cells. These observations may provide important information aiming future therapy for muscular dystrophies.

  8. Preclinical Studies with Umbilical Cord Mesenchymal Stromal Cells in Different Animal Models for Muscular Dystrophy

    Science.gov (United States)

    Zucconi, Eder; Vieira, Natassia Moreira; Bueno, Carlos Roberto; Secco, Mariane; Jazedje, Tatiana; Costa Valadares, Marcos; Fussae Suzuki, Miriam; Bartolini, Paolo; Vainzof, Mariz; Zatz, Mayana

    2011-01-01

    Umbilical cord mesenchymal stromal cells (MSC) have been widely investigated for cell-based therapy studies as an alternative source to bone marrow transplantation. Umbilical cord tissue is a rich source of MSCs with potential to derivate at least muscle, cartilage, fat, and bone cells in vitro. The possibility to replace the defective muscle cells using cell therapy is a promising approach for the treatment of progressive muscular dystrophies (PMDs), independently of the specific gene mutation. Therefore, preclinical studies in different models of muscular dystrophies are of utmost importance. The main objective of the present study is to evaluate if umbilical cord MSCs have the potential to reach and differentiate into muscle cells in vivo in two animal models of PMDs. In order to address this question we injected (1) human umbilical cord tissue (hUCT) MSCs into the caudal vein of SJL mice; (2) hUCT and canine umbilical cord vein (cUCV) MSCs intra-arterially in GRMD dogs. Our results here reported support the safety of the procedure and indicate that the injected cells could engraft in the host muscle in both animal models but could not differentiate into muscle cells. These observations may provide important information aiming future therapy for muscular dystrophies. PMID:21785565

  9. Preclinical studies on new proteins as carrier for glycoconjugate vaccines.

    Science.gov (United States)

    Tontini, M; Romano, M R; Proietti, D; Balducci, E; Micoli, F; Balocchi, C; Santini, L; Masignani, V; Berti, F; Costantino, P

    2016-07-29

    Glycoconjugate vaccines are made of carbohydrate antigens covalently bound to a carrier protein to enhance their immunogenicity. Among the different carrier proteins tested in preclinical and clinical studies, five have been used so far for licensed vaccines: Diphtheria and Tetanus toxoids, the non-toxic mutant of diphtheria toxin CRM197, the outer membrane protein complex of Neisseria meningitidis serogroup B and the Protein D derived from non-typeable Haemophilus influenzae. Availability of novel carriers might help to overcome immune interference in multi-valent vaccines containing several polysaccharide-conjugate antigens, and also to develop vaccines which target both protein as well saccharide epitopes of the same pathogen. Accordingly we have conducted a study to identify new potential carrier proteins. Twenty-eight proteins, derived from different bacteria, were conjugated to the model polysaccharide Laminarin and tested in mice for their ability in inducing antibodies against the carbohydrate antigen and eight of them were subsequently tested as carrier for serogroup meningococcal C oligosaccharides. Four out of these eight were able to elicit in mice satisfactory anti meningococcal serogroup C titers. Based on immunological evaluation, the Streptococcus pneumoniae protein spr96/2021 was successfully evaluated as carrier for serogroups A, C, W, Y and X meningococcal capsular saccharides. PMID:27317455

  10. A crowdsourcing model for creating preclinical medical education study tools.

    Science.gov (United States)

    Bow, Hansen C; Dattilo, Jonathan R; Jonas, Andrea M; Lehmann, Christoph U

    2013-06-01

    During their preclinical course work, medical students must memorize and recall substantial amounts of information. Recent trends in medical education emphasize collaboration through team-based learning. In the technology world, the trend toward collaboration has been characterized by the crowdsourcing movement. In 2011, the authors developed an innovative approach to team-based learning that combined students' use of flashcards to master large volumes of content with a crowdsourcing model, using a simple informatics system to enable those students to share in the effort of generating concise, high-yield study materials. The authors used Google Drive and developed a simple Java software program that enabled students to simultaneously access and edit sets of questions and answers in the form of flashcards. Through this crowdsourcing model, medical students in the class of 2014 at the Johns Hopkins University School of Medicine created a database of over 16,000 questions that corresponded to the Genes to Society basic science curriculum. An analysis of exam scores revealed that students in the class of 2014 outperformed those in the class of 2013, who did not have access to the flashcard system, and a survey of students demonstrated that users were generally satisfied with the system and found it a valuable study tool. In this article, the authors describe the development and implementation of their crowdsourcing model for creating study materials, emphasize its simplicity and user-friendliness, describe its impact on students' exam performance, and discuss how students in any educational discipline could implement a similar model of collaborative learning. PMID:23619061

  11. Preclinical studies for increasing radiation response of malignant brain tumours

    International Nuclear Information System (INIS)

    Malignant gliomas are the most common among the CNS cancers. Standard treatment for these tumours - comprises of surgery, followed by Radiotherapy (RT). Combination of Temozolomide (TMZ) increases survival, but hematological toxicities are also increased as compared to RT alone. The median survival depends on grade and location of tumour, as well as the age of the patient. Grade IV gliomas (GSMs) are third leading cause of cancer induced death in the age group of 15 to 34 years. Therefore, it is important to carry out further preclinical studies to develop more effective treatment of malignant gliomas. The present studies were carried out on different established malignant glioma cell lines. (U373MG) as well as primary monolayer cultures derived from biopsies obtained from patients with malignant gliomas. Exponentially growing cells were exposed to TMZ, Lonidamine (LND) (in 0.1% DMSO), or 2-Deoxy-D-Glucose (2-DG, aqueous solution) - with or without 60Co-Gamma-rays (1- 2 Gy). The drugs were removed 4 hours after irradiation and the cultures were processed further for different assays of damage. Short term (4 h) treatments with TMZ 20 μM, LND 100 μM or their combination; did not induce micronuclei formation in the unirradiated cultures of U373MG cells. However, radiation (2 Gy) induced micronuclei was significantly increased by drug treatments. In primary cultures from different tumours, TMZ (≤ 10 μM) or 2-DG (1 mM), or gamma-irradiation (1-2 Gy) induced micronuclei and/ or apoptosis. The effects, however, varied in different tumours. These data show that clinically achievable, very low concentrations of these drugs could induce cellular damage and death; and increase radiosensitivity of malignant gliomas. Therefore, adjuvants like Lonidamine and 2-DG, with non-overlapping toxicities, could optimize treatment of malignant gliomas, by reducing the side effects of radio-chemotherapy. (author)

  12. The effect of learning styles and study behavior on success of preclinical students in pharmacology

    OpenAIRE

    Halil Asci; Esin Kulac; Mekin Sezik; F Nihan Cankara; Ekrem Cicek

    2016-01-01

    Objectives: To evaluate the effect of learning styles and study behaviors on preclinical medical students′ pharmacology exam scores in a non-Western setting. Materials and Methods: Grasha-Reichmann Student Learning Study Scale and a modified Study Behavior Inventory were used to assess learning styles and study behaviors of preclinical medical students (n = 87). Logistic regression models were used to evaluate the independent effect of gender, age, learning style, and study behavior on ph...

  13. Pomegranate Peel Extract Prevents Bone Loss in a Preclinical Model of Osteoporosis and Stimulates Osteoblastic Differentiation in Vitro

    Directory of Open Access Journals (Sweden)

    Mélanie Spilmont

    2015-11-01

    Full Text Available The nutritional benefits of pomegranate have attracted great scientific interest. The pomegranate, including the pomegranate peel, has been used worldwide for many years as a fruit with medicinal activity, mostly antioxidant properties. Among chronic diseases, osteoporosis, which is associated with bone remodelling impairment leading to progressive bone loss, could eventually benefit from antioxidant compounds because of the involvement of oxidative stress in the pathogenesis of osteopenia. In this study, with in vivo and ex vivo experiments, we investigated whether the consumption of pomegranate peel extract (PGPE could limit the process of osteopenia. We demonstrated that in ovariectomized (OVX C57BL/6J mice, PGPE consumption was able to significantly prevent the decrease in bone mineral density (−31.9%; p < 0.001 vs. OVX mice and bone microarchitecture impairment. Moreover, the exposure of RAW264.7 cells to serum harvested from mice that had been given a PGPE-enriched diet elicited reduced osteoclast differentiation and bone resorption, as shown by the inhibition of the major osteoclast markers. In addition, PGPE appeared to substantially stimulate osteoblastic MC3T3-E1 alkaline phosphatase (ALP activity at day 7, mineralization at day 21 and the transcription level of osteogenic markers. PGPE may be effective in preventing the bone loss associated with ovariectomy in mice, and offers a promising alternative for the nutritional management of this disease.

  14. Porcine adipose-derived stem cells from buccal fat pad and subcutaneous adipose tissue for future preclinical studies in oral surgery

    OpenAIRE

    Niada, S; L.M. Ferreira; Arrigoni, E.; Addis, A.; M. Campagnol; E. Broccaioli; Brini, A T

    2013-01-01

    Introduction Adipose-derived stem cells (ASCs) are progenitor cells used in bone tissue engineering and regenerative medicine. Despite subcutaneous adipose tissue being more abundant, the buccal fat pad (BFP) is easily accessible for dentists and maxillofacial surgeons. For this reason, considering the need for preclinical study and the swine as an optimal animal model in tissue engineering applications, we compared the features of porcine ASCs (pASCs) from both tissue-harvesting sites. Metho...

  15. Intravital microscopy as a tool to study drug delivery in preclinical studies

    OpenAIRE

    Amornphimoltham, Panomwat; Masedunskas, Andrius; Weigert, Roberto

    2010-01-01

    The technical developments in the field of non-linear microscopy have made intravital microscopy one of the most successful techniques for studying physiological and pathological processes in live animals. Intravital microscopy has been utilized to address many biological questions in basic research and is now a fundamental tool for preclinical studies, with an enormous potential for clinical applications. The ability to dynamically image cellular and subcellular structures combined with the ...

  16. Monte Carlo simulation on pre-clinical irradiation: A heterogeneous phantom study on monoenergetic kilovoltage photon beams

    Science.gov (United States)

    Chow, James C. L.

    2012-10-01

    This study investigated radiation dose variations in pre-clinical irradiation due to the photon beam energy and presence of tissue heterogeneity. Based on the same mouse computed tomography image dataset, three phantoms namely, heterogeneous, homogeneous and bone homogeneous were used. These phantoms were generated by overriding the relative electron density of no voxel (heterogeneous), all voxel (homogeneous) and the bone voxel (bone homogeneous) to one. 360° photon arcs with beam energies of 50 - 1250 keV were used in mouse irradiations. Doses in the above phantoms were calculated using the EGSnrc-based DOSXYZnrc code through the DOSCTP. Monte Carlo simulations were carried out in parallel using multiple nodes in a high-performance computing cluster. It was found that the dose conformity increased with the increase of the photon beam energy from the keV to MeV range. For the heterogeneous mouse phantom, increasing the photon beam energy from 50 keV to 1250 keV increased seven times the dose deposited at the isocenter. For the bone dose enhancement, the mean dose was 2.7 times higher when the bone heterogeneity was not neglected using the 50 keV photon beams in the mouse irradiation. Bone dose enhancement affecting the mean dose was found in the photon beams with energy range of 50 - 200 keV and the dose enhancement decreased with an increase of the beam energy. Moreover, the MeV photon beam had a higher dose at the isocenter, and a better dose conformity compared to the keV beam.

  17. Ethical challenges in preclinical Alzheimer's disease observational studies and trials: Results of the Barcelona summit.

    Science.gov (United States)

    Molinuevo, José L; Cami, Jordi; Carné, Xavier; Carrillo, Maria C; Georges, Jean; Isaac, Maria B; Khachaturian, Zaven; Kim, Scott Y H; Morris, John C; Pasquier, Florence; Ritchie, Craig; Sperling, Reisa; Karlawish, Jason

    2016-05-01

    Alzheimer's disease (AD) is among the most significant health care burdens. Disappointing results from clinical trials in late-stage AD persons combined with hopeful results from trials in persons with early-stage suggest that research in the preclinical stage of AD is necessary to define an optimal therapeutic success window. We review the justification for conducting trials in the preclinical stage and highlight novel ethical challenges that arise and are related to determining appropriate risk-benefit ratios and disclosing individuals' biomarker status. We propose that to conduct clinical trials with these participants, we need to improve public understanding of AD using unified vocabulary, resolve the acceptable risk-benefit ratio in asymptomatic participants, and disclose or not biomarker status with attention to study type (observational studies vs clinical trials). Overcoming these challenges will justify clinical trials in preclinical AD at the societal level and aid to the development of societal and legal support for trial participants. PMID:26988427

  18. A cross-laboratory preclinical study on the effectiveness of interleukin-1 receptor antagonist in stroke.

    Science.gov (United States)

    Maysami, Samaneh; Wong, Raymond; Pradillo, Jesus M; Denes, Adam; Dhungana, Hiramani; Malm, Tarja; Koistinaho, Jari; Orset, Cyrille; Rahman, Mahbubur; Rubio, Marina; Schwaninger, Markus; Vivien, Denis; Bath, Philip M; Rothwell, Nancy J; Allan, Stuart M

    2016-03-01

    Stroke represents a global challenge and is a leading cause of permanent disability worldwide. Despite much effort, translation of research findings to clinical benefit has not yet been successful. Failure of neuroprotection trials is considered, in part, due to the low quality of preclinical studies, low level of reproducibility across different laboratories and that stroke co-morbidities have not been fully considered in experimental models. More rigorous testing of new drug candidates in different experimental models of stroke and initiation of preclinical cross-laboratory studies have been suggested as ways to improve translation. However, to our knowledge, no drugs currently in clinical stroke trials have been investigated in preclinical cross-laboratory studies. The cytokine interleukin 1 is a key mediator of neuronal injury, and the naturally occurring interleukin 1 receptor antagonist has been reported as beneficial in experimental studies of stroke. In the present paper, we report on a preclinical cross-laboratory stroke trial designed to investigate the efficacy of interleukin 1 receptor antagonist in different research laboratories across Europe. Our results strongly support the therapeutic potential of interleukin 1 receptor antagonist in experimental stroke and provide further evidence that interleukin 1 receptor antagonist should be evaluated in more extensive clinical stroke trials. PMID:26661169

  19. The impact of weakly bound 89Zr on preclinical studies: Non-specific accumulation in solid tumors and aspergillus infection

    International Nuclear Information System (INIS)

    Preclinical studies involving 89Zr often report significant bone accumulation, which is associated with dissociation of the radiometal from the tracer. However, experiments determining the uptake of unbound 89Zr in disease models are not performed as routine controls. The purpose of the present study was to investigate the impact of free or weakly bound 89Zr on PET quantifications in disease models, in order to determine if such control experiments are warranted. Methods: Chemical studies were carried out to find a 89Zr compound that would solubilize the 89Zr as a weak chelate, thus mimicking free or weakly bound 89Zr released in circulation. 89Zr oxalate had the desired characteristics, and was injected into mice bearing FaDu and HT29 solid tumor xenografts, and mice infected in the lungs with the mold Aspergillus fumigatus, as well as in healthy controls (naïve). PET/CT or PET/MR imaging followed to quantify the distribution of the radionuclide in the disease models. Results: 89Zr oxalate was found to have a plasma half-life of 5.1 ± 2.3 h, accumulating mainly in the bones of all animals. Both tumor types accumulated 89Zr on the order of 2‐4 %ID/cm3, which is comparable to EPR-mediated accumulation of certain species. In the aspergillosis model, the concentration of 89Zr in lung tissue of the naïve animals was 6.0 ± 1.1 %ID/g. This was significantly different from that of the animals with advanced disease, showing 11.6 ± 1.8 %ID/g. Conclusions: Given the high levels of 89Zr accumulation in the disease sites in the present study, we recommend control experiments mapping the biodistribution of free 89Zr in any preclinical study employing 89Zr where bone uptake is observed. Aqueous 89Zr oxalate appears to be a suitable compound for such studies. This is especially relevant in studies where the tracer accumulation is based upon passive targeting, such as EPR

  20. Methodological quality of preclinical stroke studies is not required for publication in high-impact journals

    OpenAIRE

    Minnerup, Jens; Wersching, Heike; Diederich, Kai; Schilling, Matthias; Ringelstein, Erich Bernd; Wellmann, Jürgen; Schäbitz, Wolf-Rüdiger

    2010-01-01

    Omitting quality characteristics in animal stroke studies leads to an overestimation of the efficacy of candidate stroke drugs. Nevertheless, the methodological quality of preclinical stroke studies is often limited. As publishing of research results in high-impact journals is an important motivation for scientists, we analyzed whether study quality predicts high-impact publishing. Animal stroke studies of neuroprotective drugs that were recently investigated in clinical phase II/III trials w...

  1. Preclinical examination of clofarabine in pediatric ependymoma: Intratumoral concentrations insufficient to warrant further study

    OpenAIRE

    Patel, Yogesh T.; Jacus, Megan O.; Boulos, Nidal; Dapper, Jason D.; Davis, Abigail D.; Vuppala, Pradeep K.; Freeman, Burgess B.; Mohankumar, Kumarasamypet M.; Throm, Stacy L.; Gilbertson, Richard J.; Stewart, Clinton F.

    2015-01-01

    Clofarabine, a deoxyadenosine analog, was an active anticancer drug in our in vitro high-throughput screening against mouse ependymoma neurospheres. To characterize the clofarabine disposition in mice for further preclinical efficacy studies, we evaluated the plasma and central nervous system (CNS) disposition in a mouse model of ependymoma. A plasma pharmacokinetic study of clofarabine (45 mg/kg, IP) was performed in CD1 nude mice bearing ependymoma to obtain initial plasma pharmacokinetic p...

  2. Rag2-/-;gammac-/- immunodeficient mice, a new preclinical model to study antitumor approaches

    OpenAIRE

    Antognoli, Agnese

    2010-01-01

    Animal models have been relevant to study the molecular mechanisms of cancer and to develop new antitumor agents. Anyway, the huge divergence in mouse and human evolution made difficult the translation of the gained achievements in preclinical mouse based studies. The generation of clinically relevant murine models requires their humanization both concerning the creation of transgenic models and the generation of humanized mice in which to engraft a functional human immune system, and reprodu...

  3. A Comparative Study of Multimedia and Conventional Education Methods in Undergraduate Training in Preclinical Endodontics

    OpenAIRE

    A Khayat; A Keshtkar

    2004-01-01

    Background: There is little systematic research about the efficacy of multimedia-based system for learning in medical sciences. The purpose of this study was to evaluate the efficacy of an interactive multimedia courseware package to demonstrate access cavity preparation for undergraduate dental students in preclinical endodontics course and compare with tutorial method of education. Methods: This study was performed on 62 undergraduate dental students. The students were randomly assigned in ...

  4. Nefopam analgesia and its role in multimodal analgesia: A review of preclinical and clinical studies.

    Science.gov (United States)

    Girard, Philippe; Chauvin, Marcel; Verleye, Marc

    2016-01-01

    Nefopam is a non-opioid, non-steroidal, centrally acting analgesic drug used to prevent postoperative pain, primarily in the context of multimodal analgesia. This paper reviews preclinical and clinical studies in which nefopam has been combined with opioids, non-steroidal anti-inflammatory compounds, and paracetamol. This report focuses on the literature during the last decade and discusses the translational efforts between animal and clinical studies in the context of multimodal or balanced analgesia. In preclinical rodent models of acute and inflammatory pain, nefopam combinations including opioids revealed a synergistic interaction or enhanced morphine analgesia in six out of seven studies. Nefopam combinations including non-steroidal anti-inflammatory drugs (NSAIDs) (aspirin, ketoprofen or nimesulide) or paracetamol likewise showed enhanced analgesic effects for the associated compound in all instances. Clinical studies have been performed in various types of surgeries involving different pain intensities. Nefopam combinations including opioids resulted in a reduction in morphine consumption in 8 out of 10 studies of severe or moderate pain. Nefopam combinations including NSAIDs (ketoprofen or tenoxicam) or paracetamol also demonstrated a synergic interaction or an enhancement of the analgesic effect of the associated compound. In conclusion, this review of nefopam combinations including various analgesic drugs (opioids, NSAIDs and paracetamol) reveals that enhanced analgesia was demonstrated in most preclinical and clinical studies, suggesting a role for nefopam in multimodal analgesia based on its distinct characteristics as an analgesic. Further clinical studies are needed to evaluate the analgesic effects of nefopam combinations including NSAIDs or paracetamol. PMID:26475417

  5. Antidepressant mechanism of ketamine: perspective from preclinical studies

    OpenAIRE

    Scheuing, Lisa; Chiu, Chi-Tso; Liao, Hsiao-Mei; Chuang, De-Maw

    2015-01-01

    A debilitating mental disorder, major depressive disorder is a leading cause of global disease burden. Existing antidepressant drugs are not adequate for the majority of depressed patients, and large clinical studies have demonstrated their limited efficacy and slow response onset. Growing evidence of low-dose ketamine's rapid and potent antidepressant effects offers strong potential for future antidepressant agents. However, ketamine has considerable drawbacks such as its abuse potential, ps...

  6. Preclinical Study for Application of Fabricated High Activity Ir-192

    International Nuclear Information System (INIS)

    This study was performed to evaluate the feasibility and safety of high activity Ir-192 sources manufactured by KAERI(Korea Atomic Energy Research Institute) for application to present equipment such as various applicators inserted to patients and PLATO(Nucletron, Netherland) of treatment planning system and to evaluate safety and accuracy of Ir-192 as practical clinic use through in vitro dosimetry of Ir-192. We confirmed the physical and radiobiological safety of KAERI sources to use practical. KAERI sources are applicable to commercial high dose rate brachytherapy machine safely. Then those can be substituted for the imported sources such as sources made by Nucletron, Gammamed and exported to the foreign country

  7. Recent Developments in Instrumentation for Pre-Clinical Imaging Studies

    International Nuclear Information System (INIS)

    Full text: Recent advances in imaging instrumentation have led to a variety of tomograph designs for dedicated pre clinical imaging of laboratory animals. These advances make it possible to image and quantify the kinetics of radiolabelled pharmaceuticals in a wide range of animal models from rodents to non-human primates. Applications include evaluation of promising new radiopharmaceuticals, study of the molecular origins of human disease and evaluation of new forms of therapy. These applications and advances in instrumentation are equally applicable to positron emitters and single photon emitters. This paper provides an overview of recent advances which have led to the current state-of-the-art in pre clinical imaging. The common inorganic scintillators that have been used for SPECT and PET, including some of the promising materials recently studied. The current crystal of choice for SPECT imaging is NaI(Tl) because of its high light output and density which make it well suited to imaging photons in the 100-200 keV range. However, NaI(Tl) has the disadvantage that it must be hermetically sealed to prevent absorption of moisture from the environment. Therefore, investigators have explored a number of alternative inorganic crystals, including CsI(Tl) and cerium-doped yttrium aluminium perovskite (YAP), as well as solid state detectors such as cadmium zinc telluride (CZT). Many of the crystals used in SPECT have also been tried for PET, including NaI(Tl) and YAP. However these crystals have lower stopping power than BGO and NaI(Tl) is also relatively slow. A very promising scintillator for PET is cerium-doped lutetium oxyorthosilicate (LSO) (1) which has similar stopping power to BGO and relatively high light output and fast decay. The first PET scanner to use LSO was the UCLA animal scanner, microPET, which also makes use of a number of other new technologies and unique design features. Recently, improvements in multi-anode and crossed wire position sensitive

  8. Endpoint measures in the mdx mouse relevant for muscular dystrophy pre-clinical studies

    OpenAIRE

    Kobayashi, Yvonne M.; Rader, Erik P; Crawford, Robert W.; Campbell, Kevin P.

    2011-01-01

    Loss of mobility influences the quality of life for patients with neuromuscular diseases. Common measures of mobility and chronic muscle damage are the six-minute walk test and serum creatine kinase. Despite extensive pre-clinical studies of therapeutic approaches, characterization of these measures is incomplete. To address this, a six-minute ambulation assay, serum creatine kinase, and myoglobinuria were investigated for the mdx mouse, a dystrophinopathy mouse model commonly used in pre-cli...

  9. Targeting SRC in glioblastoma tumors and brain metastases: rationale and preclinical studies

    OpenAIRE

    Ahluwalia, Manmeet; de Groot, John; Liu, Wei; Gladson, Candece L.

    2010-01-01

    Glioblastoma (GBM) is an extremely aggressive, infiltrative tumor with a poor prognosis. The regulatory approval of bevacizumab for recurrent GBM has confirmed that molecularly targeted agents have potential for GBM treatment. Preclinical data showing that SRC and SRC-family kinases (SFKs) mediate intracellular signaling pathways controlling key biologic/oncogenic processes provide a strong rationale for investigating SRC/SFK inhibitors, eg, dasatinib, in GBM and clinical studies are underway...

  10. Scaling Pharmacodynamics from In Vitro and Preclinical Animal Studies to Humans

    OpenAIRE

    Mager, Donald E.; Woo, Sukyung; Jusko, William J.

    2009-01-01

    An important feature of mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) models is the identification of drug- and system-specific factors that determine the intensity and time-course of pharmacological effects. This provides an opportunity to integrate information obtained from in vitro bioassays and preclinical pharmacological studies in animals to anticipate the clinical and adverse responses to drugs in humans. The fact that contemporary PK/PD modeling continues to evolve and seeks...

  11. Accelerating drug discovery for Alzheimer's disease: best practices for preclinical animal studies

    OpenAIRE

    Shineman, Diana W; Basi, Guriqbal S.; Bizon, Jennifer L.; Colton, Carol A.; Greenberg, Barry D.; Hollister, Beth A; Lincecum, John; Leblanc, Gabrielle G.; Lee, Linda H; Luo, Feng; Morgan, Dave; Morse, Iva; Refolo, Lorenzo M; Riddell, David R; Scearce-Levie, Kimberly

    2011-01-01

    Animal models have contributed significantly to our understanding of the underlying biological mechanisms of Alzheimer's disease (AD). As a result, over 300 interventions have been investigated and reported to mitigate pathological phenotypes or improve behavior in AD animal models or both. To date, however, very few of these findings have resulted in target validation in humans or successful translation to disease-modifying therapies. Challenges in translating preclinical studies to clinical...

  12. Preclinical study evaluating a novel trocar site closure system

    Directory of Open Access Journals (Sweden)

    Walker PA

    2016-04-01

    times while improving closure safety. Initial animal studies have shown that the neoClose® device yields a durable fascial closure that is easy to adopt from a technical standpoint.Keywords: trocal closure, laparoscopy, trocar hernia, closure device

  13. Development of regional chemotherapies: feasibility, safety and efficacy in clinical use and preclinical studies.

    Science.gov (United States)

    Cai, Shuang; Bagby, Taryn R; Forrest, M Laird

    2011-11-01

    Conventional oral and intravenous chemotherapies permeate throughout the body, exposing healthy tissues to similar cytotoxic drug levels as tumors. This leads to significant dose-limiting toxicities that may prevent patients from receiving sufficient treatment to overcome cancers. Therefore, a number of locoregional drug-delivery strategies have been evaluated and implemented in preclinical studies, clinical trials and in practice, in the past decades to minimize systemic toxicities from chemotherapeutic agents and to improve treatment outcomes. Localized treatment is beneficial because many cancers, such as melanoma, peritoneal cancer and breast cancer, advance locally adjacent to the site of the primary tumors prior to their circulatory invasion. In this article, we will review the feasibility, safety and efficacy of multiple localized chemotherapies in clinical use and preclinical development. PMID:22229080

  14. Preclinical Studies with Umbilical Cord Mesenchymal Stromal Cells in Different Animal Models for Muscular Dystrophy

    OpenAIRE

    Eder Zucconi; Natassia Moreira Vieira; Carlos Roberto Bueno; Mariane Secco; Tatiana Jazedje; Marcos Costa Valadares; Miriam Fussae Suzuki; Paolo Bartolini; Mariz Vainzof; Mayana Zatz

    2011-01-01

    Umbilical cord mesenchymal stromal cells (MSC) have been widely investigated for cell-based therapy studies as an alternative source to bone marrow transplantation. Umbilical cord tissue is a rich source of MSCs with potential to derivate at least muscle, cartilage, fat, and bone cells in vitro. The possibility to replace the defective muscle cells using cell therapy is a promising approach for the treatment of progressive muscular dystrophies (PMDs), independently of the specific gene mutati...

  15. Preclinical studies of [{sup 99m}Tc]DTPA-mannosyl-dextran

    Energy Technology Data Exchange (ETDEWEB)

    Hoh, Carl K. E-mail: ckhoh@ucsd.edu; Wallace, Anne M.; Vera, David R

    2003-05-01

    We report the preclinical testing of a synthetic receptor-binding macromolecule, [{sup 99m}Tc]DTPA-mannosyl-dextran (36 kDa, 8 DTPA and 55 mannosyl units per dextran, K{sub D} = 0.12 nM), for sentinel node detection. Nonclinical safety studies included cardiac pharmacology safety studies, acute toxicology and pathology studies at 50 and 500 times the scaled human dose in both rats and rabbits after foot pad administration, and perivascular irritation studies in rabbits following intra-muscular administration at 100 and 1000 times the scaled human dose. Biodistribution studies in rabbits at 15 m, 1 h, and 3 h indicated that [{sup 99m}Tc]DTPA-mannosyl-dextran cleared the hind foot pad with a biological half-life of 2.21 {+-} 0.27 h. Other than mild hepatocyte hypertrophy in rabbits, no abnormalities in toxicology or pathology were found. Intravenous administration had no effect on survival, any clinical observations, electrocardiograms, or blood pressures. Intramuscular injection had no effect on survival, clinical observations, injection site observations, or injection site histopathology. The estimated absorbed radiation dose to the affected breast was 0.15 mGy/MBq and the effective dose was 1.06 x 10{sup -2} mSv/MBq. This preclinical study demonstrates that [{sup 99m}Tc]DTPA-mannosyl-dextran has no toxicities and has an acceptable biodistribution and radiation dose.

  16. Plant-based medicines for anxiety disorders, Part 1: a review of preclinical studies.

    Science.gov (United States)

    Sarris, Jerome; McIntyre, Erica; Camfield, David A

    2013-03-01

    Research in the area of herbal psychopharmacology has revealed a variety of promising medicines that may provide benefit in the treatment of general anxiety and specific anxiety disorders. However, a comprehensive review of plant-based anxiolytics has been absent to date. This article (part 1) reviews herbal medicines for which only preclinical investigations for anxiolytic activity have been performed. In part 2, we review herbal medicines for which there have been clinical investigations for anxiolytic activity. An open-ended, language-restricted (English) search of MEDLINE (PubMed), CINAHL, Scopus and the Cochrane Library databases was conducted (up to 28 October 2012) using specific search criteria to identify herbal medicines that have been investigated for anxiolytic activity. This search of the literature revealed 1,525 papers, from which 53 herbal medicines were included in the full review (having at least one study using the whole plant extract). Of these plants, 21 had human clinical trial evidence (reviewed in part 2), with another 32 having solely preclinical studies (reviewed here in part 1). Preclinical evidence of anxiolytic activity (without human clinical trials) was found for Albizia julibrissin, Sonchus oleraceus, Uncaria rhynchophylla, Stachys lavandulifolia, Cecropia glazioui, Magnolia spp., Eschscholzia californica, Erythrina spp., Annona spp., Rubus brasiliensis, Apocynum venetum, Nauclea latifolia, Equisetum arvense, Tilia spp., Securidaca longepedunculata, Achillea millefolium, Leea indica, Juncus effusus, Coriandrum sativum, Eurycoma longifolia, Turnera diffusa, Euphorbia hirta, Justicia spp., Crocus sativus, Aloysia polystachya, Albies pindrow, Casimiroa edulis, Davilla rugosa, Gastrodia elata, Sphaerathus indicus, Zizyphus jujuba and Panax ginseng. Common mechanisms of action for the majority of botanicals reviewed primarily involve GABA, either via direct receptor binding or ionic channel or cell membrane modulation; GABA transaminase

  17. Spectroscopic analysis of bones for forensic studies

    Energy Technology Data Exchange (ETDEWEB)

    Tofanelli, Mirko [Applied and Laser Spectroscopy Laboratory, Institute of Chemistry of Organometallic Compounds, Research Area of CNR, Via G. Moruzzi, 1, 56124 Pisa (Italy); Pardini, Lorenzo [Institut für Physik und IRIS Adlershof, Humboldt-Universität zu Berlin, Zum Großen Windkanal 6, 12489 Berlin (Germany); Borrini, Matteo [Research Centre in Evolutionary Anthropology and Palaeoecology, School of Natural Sciences and Psychology, Liverpool John Moores University, Byrom Street, Liverpool (United Kingdom); Bartoli, Fulvio; Bacci, Alessandra [Department of Biology, University of Pisa, Via A. Volta, 4, 56126 Pisa (Italy); D’Ulivo, Alessandro; Pitzalis, Emanuela; Mascherpa, Marco Carlo; Legnaioli, Stefano; Lorenzetti, Giulia; Pagnotta, Stefano [Applied and Laser Spectroscopy Laboratory, Institute of Chemistry of Organometallic Compounds, Research Area of CNR, Via G. Moruzzi, 1, 56124 Pisa (Italy); Holanda Cavalcanti, Gildo de [Instituto de Fìsica, Universidade Federal Fluminense, Av. Gal. Milton Tavares de Souza, s/no Campus da Praia Vermelha, CEP 24210-346, Niterói, Rio de Janeiro (Brazil); Lezzerini, Marco [Department of Earth Sciences, University of Pisa, Via Santa Maria, 53, 56126 Pisa (Italy); Palleschi, Vincenzo, E-mail: vincenzo.palleschi@cnr.it [Applied and Laser Spectroscopy Laboratory, Institute of Chemistry of Organometallic Compounds, Research Area of CNR, Via G. Moruzzi, 1, 56124 Pisa (Italy)

    2014-09-01

    The elemental analysis of human bones can give information about the dietary habits of the deceased, especially in the last years of their lives, which can be useful for forensic studies. The most important requirement that must be satisfied for this kind of analysis is that the concentrations of analyzed elements are the same as ante mortem. In this work, a set of bones was analyzed using Laser-Induced Breakdown Spectroscopy (LIBS) and validated using Inductively Coupled Plasma–Optical Emission Spectroscopy (ICP-OES), in order to compare those two techniques and to investigate the effect of possible alterations in the elemental concentrations' proportion resulting from the treatment usually applied for preparing the bones for traditional forensic analysis. The possibility that elemental concentrations' changes would occur after accidental or intentional burning of the bones was also studied. - Highlights: • The LIBS analysis of (animal) bones is presented, to establish its feasibility for forensic studies. • Untreated bones and bones subjected to high temperatures (boiled, burned) were analyzed. • A simple calibration, using a single reference sample, gave reasonable quantitative results. • The comparison of the results demonstrates that LIBS analysis can provide nutritional information. • The nutritional information obtained are the same on untreated, boiled and burned bones.

  18. Spectroscopic analysis of bones for forensic studies

    International Nuclear Information System (INIS)

    The elemental analysis of human bones can give information about the dietary habits of the deceased, especially in the last years of their lives, which can be useful for forensic studies. The most important requirement that must be satisfied for this kind of analysis is that the concentrations of analyzed elements are the same as ante mortem. In this work, a set of bones was analyzed using Laser-Induced Breakdown Spectroscopy (LIBS) and validated using Inductively Coupled Plasma–Optical Emission Spectroscopy (ICP-OES), in order to compare those two techniques and to investigate the effect of possible alterations in the elemental concentrations' proportion resulting from the treatment usually applied for preparing the bones for traditional forensic analysis. The possibility that elemental concentrations' changes would occur after accidental or intentional burning of the bones was also studied. - Highlights: • The LIBS analysis of (animal) bones is presented, to establish its feasibility for forensic studies. • Untreated bones and bones subjected to high temperatures (boiled, burned) were analyzed. • A simple calibration, using a single reference sample, gave reasonable quantitative results. • The comparison of the results demonstrates that LIBS analysis can provide nutritional information. • The nutritional information obtained are the same on untreated, boiled and burned bones

  19. Advanced Pre-clinical Research Approaches and Models to Studying Pediatric Anesthetic Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Cheng eWang

    2012-10-01

    Full Text Available Advances in pediatric and obstetric surgery have resulted in an increase in the duration and complexity of anesthetic procedures. A great deal of concern has recently arisen regarding the safety of anesthesia in infants and children. Because of obvious limitations, it is not possible to thoroughly explore the effects of anesthetic agents on neurons in vivo in human infants or children. However, the availability of some advanced pre-clinical research approaches and models, such as imaging technology both in vitro and in vivo, stem cell and nonhuman primate experimental models, have provided potentially invaluable tools for examining the developmental effects of anesthetic agents. This review discusses the potential application of some sophisticaled research approaches, e.g., calcium imaging, in stem cell-derived in vitro models, especially human embryonic neural stem cells, along with their capacity for proliferation and their potential for differentiation, to dissect relevant mechanisms underlying the etiology of the neurotoxicity associated with developmental exposures to anesthetic agents. Also, this review attempts to discuss several advantages for using the developing rhesus monkey models (in vivo, when combined with dynamic molecular imaging approaches, in addressing critical issues related to the topic of pediatric sedation/anesthesia. These include the relationships between anesthetic-induced neurotoxicity, dose response, time-course and developmental stage at time of exposure (in vivo studies, serving to provide the most expeditious platform toward decreasing the uncertainty in extrapolating pre-clinical data to the human condition.

  20. Preclinical examination of clofarabine in pediatric ependymoma: intratumoral concentrations insufficient to warrant further study.

    Science.gov (United States)

    Patel, Yogesh T; Jacus, Megan O; Boulos, Nidal; Dapper, Jason D; Davis, Abigail D; Vuppala, Pradeep K; Freeman, Burgess B; Mohankumar, Kumarasamypet M; Throm, Stacy L; Gilbertson, Richard J; Stewart, Clinton F

    2015-05-01

    Clofarabine, a deoxyadenosine analog, was an active anticancer drug in our in vitro high-throughput screening against mouse ependymoma neurospheres. To characterize the clofarabine disposition in mice for further preclinical efficacy studies, we evaluated the plasma and central nervous system disposition in a mouse model of ependymoma. A plasma pharmacokinetic study of clofarabine (45 mg/kg, IP) was performed in CD1 nude mice bearing ependymoma to obtain initial plasma pharmacokinetic parameters. These estimates were used to derive D-optimal plasma sampling time points for cerebral microdialysis studies. A simulation of clofarabine pharmacokinetics in mice and pediatric patients suggested that a dosage of 30 mg/kg IP in mice would give exposures comparable to that in children at a dosage of 148 mg/m(2). Cerebral microdialysis was performed to study the tumor extracellular fluid (ECF) disposition of clofarabine (30 mg/kg, IP) in the ependymoma cortical allografts. Plasma and tumor ECF concentration-time data were analyzed using a nonlinear mixed effects modeling approach. The median unbound fraction of clofarabine in mouse plasma was 0.79. The unbound tumor to plasma partition coefficient (K pt,uu: ratio of tumor to plasma AUCu,0-inf) of clofarabine was 0.12 ± 0.05. The model-predicted mean tumor ECF clofarabine concentrations were below the in vitro 1-h IC50 (407 ng/mL) for ependymoma neurospheres. Thus, our results show the clofarabine exposure reached in the tumor ECF was below that associated with an antitumor effect in our in vitro washout study. Therefore, clofarabine was de-prioritized as an agent to treat ependymoma, and further preclinical studies were not pursued. PMID:25724157

  1. Self-reported preclinical mobility limitation and fall history as predictors of future falls in older women: prospective cohort study

    DEFF Research Database (Denmark)

    Mänty, Minna Regina; Heinonen, A; Viljanen, A;

    2010-01-01

    We studied if self-reported preclinical mobility limitation, described as modification of task performance without perception of difficulty, predicts future falls in older women with and without fall history. Our results suggest that combined measure of self-reported preclinical mobility limitation...... and fall history may offer one possibility for inexpensive fall-risk evaluation in clinical practice. INTRODUCTION: We studied if self-reported preclinical mobility limitation predicts future falls in older women with and without fall history. METHODS: The study population consisted of 428 community...... mobility limitation. Fall history was recalled for previous 12 months and dichotomized. The incidence of future falls over 12 months was followed up with fall calendars. RESULTS: During the fall follow-up, a total of 440 falls were reported by 201 participants. Among those with fall history, women with...

  2. Study on 41Ca-AMS for diagnosis and assessment of cancer bone metastasis in rats

    Science.gov (United States)

    Shen, Hongtao; Pang, Fangfang; Jiang, Shan; He, Ming; Dong, Kejun; Dou, Liang; Pang, Yijun; Yang, Xianlin; Ruan, Xiangdong; Liu, Manjun; Xia, Chunbo

    2015-10-01

    The annual incidence of new cancer patients in China is about 2 million, 30-40% of which will end up with bone metastasis. Profound study on the preclinical model and early diagnosis of cancer bone metastasis in rats are very significant for the drug development, better understanding and treatment of bone metastases. In order to monitor the process of bone metabolism and early detection of bone metastasis of cancer cells, a technique of 41Ca isotope tracer combined with AMS has been developed and applied in the study on the bone metastasis of cancer cells by rat model. In this work, 3-month-old female Sprague-Dawley (SD) rats were randomly divided into different groups, and tumor cells injected respectively into the tail vein, femoral artery, femoral cavity and the thigh muscle to establish the rat models for bone metastases. The most appropriate model, i.e., the thigh muscle group, was finally adopted in our real metastases experiment. Each rat in this group was intramuscularly (i.m.) injected with 250 μl CaCl2 solution (containing 1.4 mg Ca and 5nCi 41Ca). About 40 days later, the rat mammary gland carcinoma cells (Walker 256) were injected into these rats following the established protocol. After bone metastasis, medicine interventions were performed. The sequential urine and blood samples were collected and analyzed for 41Ca (by AMS) and N-terminal telopeptide (Ntx), respectively. Bone Mineral Density (BMD) values in the femur and the tibia were measured by CT scan. The results of 41Ca/Ca in longitudinal urinary samples can sensitively reveal the skeletal perturbations caused by bone metastasis of rats, suggests that 41Ca might be similarly developed for human use and improve clinical management through the assessment of the curative effect and non-invasive detection of the earliest stages of cancer growth in bone.

  3. Preclinical animal acute toxicity studies of new developed MRI contrast agent based on gadolinium

    Science.gov (United States)

    Nam, I. F.; Zhuk, V. V.

    2015-04-01

    Acute toxicity test of new developed MRI contrast agent based on disodium salt of gadopentetic acid complex were carried out on Mus musculus and Sprague Dawley rats according to guidelines of preclinical studies [1]. Groups of six animals each were selected for experiment. Death and clinical symptoms of animals were recorded during 14 days. As a result the maximum tolerated dose (MTD) for female mice is 2.8 mM/kg of body weight, male mice - 1.4 mM/kg, female rats - 2.8 mM/kg, male rats - 5.6 mM/kg of body weight. No Observed Adverse Effect Dose (NOAEL) for female mice is 1.4 mM/kg, male mice - 0.7 mM/kg, male and female rats - 0.7 mM/kg. According to experimental data new developed MRI contrast agent based on Gd-DTPA complex is low-toxic.

  4. Preclinical Cancer Chemoprevention Studies Using Animal Model of Inflammation-Associated Colorectal Carcinogenesis

    International Nuclear Information System (INIS)

    Inflammation is involved in all stages of carcinogenesis. Inflammatory bowel disease, such as ulcerative colitis and Crohn’s disease is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer (CRC). Several molecular events involved in chronic inflammatory process are reported to contribute to multi-step carcinogenesis of CRC in the inflamed colon. They include over-production of free radicals, reactive oxygen and nitrogen species, up-regulation of inflammatory enzymes in arachidonic acid biosynthesis pathway, up-regulation of certain cytokines, and intestinal immune system dysfunction. In this article, firstly I briefly introduce our experimental animal models where colorectal neoplasms rapidly develop in the inflamed colorectum. Secondary, data on preclinical cancer chemoprevention studies of inflammation-associated colon carcinogenesis by morin, bezafibrate, and valproic acid, using this novel inflammation-related colorectal carcinogenesis model is described

  5. Contribution of Large Pig for Renal Ischemia-Reperfusion and Transplantation Studies: The Preclinical Model

    Directory of Open Access Journals (Sweden)

    S. Giraud

    2011-01-01

    Full Text Available Animal experimentation is necessary to characterize human diseases and design adequate therapeutic interventions. In renal transplantation research, the limited number of in vitro models involves a crucial role for in vivo models and particularly for the porcine model. Pig and human kidneys are anatomically similar (characterized by multilobular structure in contrast to rodent and dog kidneys unilobular. The human proximity of porcine physiology and immune systems provides a basic knowledge of graft recovery and inflammatory physiopathology through in vivo studies. In addition, pig large body size allows surgical procedures similar to humans, repeated collections of peripheral blood or renal biopsies making pigs ideal for medical training and for the assessment of preclinical technologies. However, its size is also its main drawback implying expensive housing. Nevertheless, pig models are relevant alternatives to primate models, offering promising perspectives with developments of transgenic modulation and marginal donor models facilitating data extrapolation to human conditions.

  6. Preclinical Cancer Chemoprevention Studies Using Animal Model of Inflammation-Associated Colorectal Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Takuji Tanaka

    2012-07-01

    Full Text Available Inflammation is involved in all stages of carcinogenesis. Inflammatory bowel disease, such as ulcerative colitis and Crohn’s disease is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer (CRC. Several molecular events involved in chronic inflammatory process are reported to contribute to multi-step carcinogenesis of CRC in the inflamed colon. They include over-production of free radicals, reactive oxygen and nitrogen species, up-regulation of inflammatory enzymes in arachidonic acid biosynthesis pathway, up-regulation of certain cytokines, and intestinal immune system dysfunction. In this article, firstly I briefly introduce our experimental animal models where colorectal neoplasms rapidly develop in the inflamed colorectum. Secondary, data on preclinical cancer chemoprevention studies of inflammation-associated colon carcinogenesis by morin, bezafibrate, and valproic acid, using this novel inflammation-related colorectal carcinogenesis model is described.

  7. Preclinical Cancer Chemoprevention Studies Using Animal Model of Inflammation-Associated Colorectal Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Takuji [Cytopatholgy Division, Tohkai Cytopathology Institute, Cancer Research and Prevention (TCI-CaRP), 5-1-2 Minami-uzura, Gifu 500-8285 (Japan); Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan)

    2012-07-16

    Inflammation is involved in all stages of carcinogenesis. Inflammatory bowel disease, such as ulcerative colitis and Crohn’s disease is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer (CRC). Several molecular events involved in chronic inflammatory process are reported to contribute to multi-step carcinogenesis of CRC in the inflamed colon. They include over-production of free radicals, reactive oxygen and nitrogen species, up-regulation of inflammatory enzymes in arachidonic acid biosynthesis pathway, up-regulation of certain cytokines, and intestinal immune system dysfunction. In this article, firstly I briefly introduce our experimental animal models where colorectal neoplasms rapidly develop in the inflamed colorectum. Secondary, data on preclinical cancer chemoprevention studies of inflammation-associated colon carcinogenesis by morin, bezafibrate, and valproic acid, using this novel inflammation-related colorectal carcinogenesis model is described.

  8. BMP6-Engineered MSCs Induce Vertebral Bone Repair in a Pig Model: A Pilot Study.

    Science.gov (United States)

    Pelled, Gadi; Sheyn, Dmitriy; Tawackoli, Wafa; Jun, Deuk Soo; Koh, Youngdo; Su, Susan; Cohn Yakubovich, Doron; Kallai, Ilan; Antebi, Ben; Da, Xiaoyu; Gazit, Zulma; Bae, Hyun; Gazit, Dan

    2016-01-01

    Osteoporotic patients, incapacitated due to vertebral compression fractures (VCF), suffer grave financial and clinical burden. Current clinical treatments focus on symptoms' management but do not combat the issue at the source. In this pilot study, allogeneic, porcine mesenchymal stem cells, overexpressing the BMP6 gene (MSC-BMP6), were suspended in fibrin gel and implanted into a vertebral defect to investigate their effect on bone regeneration in a clinically relevant, large animal pig model. To check the effect of the BMP6-modified cells on bone regeneration, a fibrin gel only construct was used for comparison. Bone healing was evaluated in vivo at 6 and 12 weeks and ex vivo at 6 months. In vivo CT showed bone regeneration within 6 weeks of implantation in the MSC-BMP6 group while only minor bone formation was seen in the defect site of the control group. After 6 months, ex vivo analysis demonstrated enhanced bone regeneration in the BMP6-MSC group, as compared to control. This preclinical study presents an innovative, potentially minimally invasive, technique that can be used to induce bone regeneration using allogeneic gene modified MSCs and therefore revolutionize current treatment of challenging conditions, such as osteoporosis-related VCFs. PMID:26770211

  9. Bone Forming Potential of An-Organic Bovine Bone Graft: A Cone Beam CT study

    OpenAIRE

    Uzbek, Usman Haider; Rahman, Shaifulizan Ab; Alam, Mohammad Khursheed; gillani, syed wasif

    2014-01-01

    Purpose: An-organic bovine bone graft is a xenograft with the potential of bone formation. The aim of this study was to evaluate the bone density using cone beam computed tomography scans around functional endosseous implant in the region of both augmented maxillary sinus with the an-organic bovine bone graft and the alveolar bone over which the graft was placed to provide space for the implants.

  10. Our evolving science: studying the influence of sex in preclinical research

    OpenAIRE

    Mazure, Carolyn M

    2016-01-01

    The policy announcement by the National Institutes of Health that sex should be considered as a relevant variable in preclinical research has sparked considerable debate. This debate has largely centered on specific concerns regarding how the policy will be implemented. However, others have reacted to the new policy by calling into question the capacity of preclinical science to generate data that can be useful to human health. This commentary examines the basis for this contention and mainta...

  11. Local treatment of a bone graft by soaking in zoledronic acid inhibits bone resorption and bone formation. A bone chamber study in rats.

    OpenAIRE

    Belfrage Ola; Isaksson Hanna; Tägil Magnus

    2012-01-01

    ABSTRACT: BACKGROUND: Bone grafts are frequently used in orthopaedic surgery. Graft remodelling is advantageous but can occur too quickly, and premature bone resorption might lead to decreased mechanical integrity of the graft. Bisphosphonates delay osteoclastic bone resorption but may also impair formation of new bone. We hypothesize that these effects are dose dependent. In the present study we evaluate different ways of applying bisphosphonates locally to the graft in a bone...

  12. A radiographic study of solitary bone cysts

    International Nuclear Information System (INIS)

    The aim of this study was to evaluate the clinical, radiographic and histopathologic features of 23 cases of solitary bone cyst by means of the analysis of radiographs and biopsy specimens in 23 persons visited the Department of Oral and Maxillofacial Radiology, School of Dentistry, Kyung Hee University and Chunbuk National University. The obtained results were as follows; 1. The incidence of solitary bone cyst was almost equal in males (52.2%) and in females(42.8%) and the prevalent age of the solitary bone cyst were the second decade (47.8%) and the third decade (21.7%). 2. In the signs and symptoms of solitary bone cyst, pain or tenderness revealed in 17.4%, swelling revealed in 13.0%, pain and swelling revealed in 21.7%, paresthesia revealed in 4.4% and 43.5% were a symptom and the tooth vitality involved in the solitary bone cyst, 76.5% were posterior and 23.5% were either positive or negative. 3. In the location of the solitary bone cyst, 47.8% present posterior region, 21.7% present anterior region, 21.6% present anterior and posterior region, 4.4% present condylar process area. 4. In the hyperostotic border of the solitary bone cyst, 47.8% were seen entirely, 21.8% were seen partially, and 30.4% were not seen. 5. In the change of tooth, 59.1% were loss of the alveolar lamina dura, 13.6% were root resorption 4.55% were tooth displacement, 4.55% were root resorption and tooth displacement. 6. In the change of cortical bone of the solitary bone cyst, 39.1% were intact and 60.9% were thinning and expansion of cortical bone. 7. In the histopathologic findings of 9 cases, 33.3% were thin connective tissue wall, 11.1% were thickened myxo-fibromatous wall, 55.6% were thickened myxofibromatous wall with dysplastic bone formation.

  13. Preliminary study using pulsating water jet for bone cement demolition

    OpenAIRE

    S. Hloch; Kloc, J.; Foldyna, J.; Pude, F.; Smolko, I.; M. Zeleňák; Sitek, L. (Libor); Hvizdoš, P.; Monka, P.; Monková, K.; Kozak, D.; A. Stoić; A. Sedmak; Milosevic, M; Lehocká, D.

    2015-01-01

    The paper deals with the study of using the selective property of ultrasonic pulsating water jet for the disintegration of bone cement which creates the interface between femoral stem and trabecular bone tissue. For investigation, commercial bone cements were used. Bone cements were tested by nanoindentation in order to review their mechanical properties. A representative sample Palacos R+G was selected for disintegration of bone cement. Bone cements samples fixed between two plexiglass...

  14. Noninferiority of Shanghai Cingular biotech’s bovine pericardial valve preclinical study in juvenile ovine model

    Science.gov (United States)

    Chen, Jin-Miao; Ding, Yu; Lu, Shu-Yang; Pan, Sun; Abudupataer, Mieradilijiang

    2016-01-01

    Background This study introduces a newly Chinese domestic-designed/manufactured bovine pericardial valve, the SCBC valve (Shanghai Cingular Biotech Corporation, Shanghai, China), and evaluates its hemodynamic performance and calcification potential compared with the Carpentier-Edwards (CE) PerimountTM valve (Edwards Lifesciences, Irvine, CA, USA) in juvenile sheep for preclinical study. Methods Five SCBC valves in study group and three CE PerimountTM valves (6900P with TFX) in control group were implanted in the mitral position of juvenile sheep and followed up for five months. Transthoracic echocardiography (TTE) for hemodynamic measurement was performed ten days, three months and five months postoperatively. Valve calcification was assessed by X-ray after euthanasia. Other collected data included macroscopic examination, blood analysis, microorganism culture and histological assessment. Results All sheep in two groups lived to sacrifice without evidence of valvular dysfunction. The SCBC valve had similar hemodynamic performance and susceptibility of calcification compared with the CE PerimountTM valve in juvenile ovine model. In all other parameters, the SCBC valve also exhibited no significant difference compared with the CE PerimountTM valve. Conclusions Our study demonstrated that the SCBC valve can exhibit similar mid-term satisfactory safety and efficacy compared with the CE PerimountTM valve in the mitral position of juvenile sheep model. PMID:27293835

  15. Videotaped Feedback Method to Enhance Learning in Preclinical Operative Dentistry: An Experimental Study.

    Science.gov (United States)

    Shah, Dipali Yogesh; Dadpe, Ashwini Manish; Kalra, Dheeraj Deepak; Garcha, Vikram P

    2015-12-01

    The aim of this study was to investigate if a videotaped feedback method enhanced teaching and learning outcomes in a preclinical operative laboratory setting for novice learners. In 2013, 60 dental students at a dental school in India were randomly assigned to two groups: control (n=30) and experimental (n=30). The control group prepared a Class II tooth preparation for amalgam after receiving a video demonstration of the exercise. The experimental group received the same video demonstration as the control group, but they also participated in a discussion and analysis of the control groups' videotaped performance and then performed the same exercise. The self-evaluation scores (SS) and examiner evaluation scores (ES) of the two groups were compared using the unpaired t-test. The experimental group also used a five-point Likert scale to rate each item on the feedback form. The means of SS (13.65±2.43) and ES (14.75±1.97) of the experimental group were statistically higher than the means of SS (11.55±2.09) and ES (11.60±1.82) of the control group. Most students in the experimental group perceived that this technique enhanced their learning experience. Within the limits of this study, the videotaped feedback using both ideal and non-ideal examples enhanced the students' performance. PMID:26632301

  16. Scaling pharmacodynamics from in vitro and preclinical animal studies to humans.

    Science.gov (United States)

    Mager, Donald E; Woo, Sukyung; Jusko, William J

    2009-01-01

    An important feature of mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) models is the identification of drug- and system-specific factors that determine the intensity and time-course of pharmacological effects. This provides an opportunity to integrate information obtained from in vitro bioassays and preclinical pharmacological studies in animals to anticipate the clinical and adverse responses to drugs in humans. The fact that contemporary PK/PD modeling continues to evolve and seeks to emulate systems level properties should provide enhanced capabilities to scale-up pharmacodynamic data. Critical steps in drug discovery and development, such as lead compound and first in human dose selection, may become more efficient with the implementation and further refinement of translational PK/PD modeling. In this review, we highlight fundamental principles in pharmacodynamics and the basic expectations for in vitro bioassays and traditional allometric scaling in PK/PD modeling. Discussion of PK/PD modeling efforts for recombinant human erythropoietin is also included as a case study showing the potential for advanced systems analysis to facilitate extrapolations and improve understanding of inter-species differences in drug responses. PMID:19252333

  17. Fixation of tibial plateau fractures with synthetic bone graft versus natural bone graft: a comparison study.

    LENUS (Irish Health Repository)

    Ong, J C Y

    2012-06-01

    The goal of this study was to determine differences in fracture stability and functional outcome between synthetic bone graft and natural bone graft with internal fixation of tibia plateau metaphyseal defects.

  18. Selection of unrelated donors for bone marrow transplantation studied in rhesus monkeys

    International Nuclear Information System (INIS)

    Graft versus Host disease (GvHD) remains to be a severe limitation to a more general application of bone marrow transplantation. Clinically acceptable results are restricted to those potential recipients for which a major histocompatibility complex (MHC) identical sibling donor is available. At an average family size of 2 to 3 siblings, the frequency of such donors is not more than approximately 30%. This pre-clinical study in rhesus monkeys is directed at the selection of donors for recipients which lack an MHC identical sibling. (Auth.)

  19. Reconstitution of immunodeficient SCID/beige mice with human cells: Applications in preclinical studies

    International Nuclear Information System (INIS)

    Experimental studies of the in vivo behaviour of human cells and tissues have become possible with the development of immunodeficient mice strains. Such mice accept readily allogeneic or xenogeneic grafts, including grafts of human cells or tissues, without rejection. In this review we describe different immunodeficient mouse strains that have been used for reconstitution by human immune cells. We subsequently go through the experience that we and others have had with reconstitution, and mention the adverse effects, in particular xenogeneic graft versus host reactions. The use of haematopoietic stem cells avoids such reactions but the immunological reconstitution may take several months. We then report the use of immunodeficient mice for the study of chronic vascular rejection of human mesenteric arteries due to cellular or humoral alloreaction. We have shown that SCID/beige mice grafted with a human artery at the place of the aorta developed a thickening of the intima of the human artery after 5-6 weeks, when they were reconstituted with spleen cells from another human donor. The thickening is mainly due to a proliferation of smooth muscle cells. The same type of lesion developed if they received injection of antibodies towards HLA class I antigens. The arteries of the mouse did not develop any lesion. The arterial lesions closely resembled those seen after clinical organ transplantation. Mice that received spleen cells from the same human donor developed little or no lesions. An important aspect of this experimental transplantation model is the possibility to test drugs that may be used in clinical transplantation. In recent experiments we have shown that novel immunosuppressive drugs can inhibit the hyperproliferation of smooth muscle cells in vitro. Preclinical testing in reconstituted SCID/beige mice grafted with human arteries will permit the evaluation of the potential use of these drugs to prevent chronic vascular rejection. The model also allows

  20. Miltefosine Lipid Nanocapsules for Single Dose Oral Treatment of Schistosomiasis Mansoni: A Preclinical Study.

    Directory of Open Access Journals (Sweden)

    Maha M Eissa

    Full Text Available Miltefosine (MFS is an alkylphosphocholine used for the local treatment of cutaneous metastases of breast cancer and oral therapy of visceral leishmaniasis. Recently, the drug was reported in in vitro and preclinical studies to exert significant activity against different developmental stages of schistosomiasis mansoni, a widespread chronic neglected tropical disease (NTD. This justified MFS repurposing as a potential antischistosomal drug. However, five consecutive daily 20 mg/kg doses were needed for the treatment of schistosomiasis mansoni in mice. The present study aims at enhancing MFS efficacy to allow for a single 20mg/kg oral dose therapy using a nanotechnological approach based on lipid nanocapsules (LNCs as oral nanovectors. MFS was incorporated in LNCs both as membrane-active structural alkylphospholipid component and active antischistosomal agent. MFS-LNC formulations showed high entrapment efficiency (EE%, good colloidal properties, sustained release pattern and physical stability. Further, LNCs generally decreased MFS-induced erythrocyte hemolytic activity used as surrogate indicator of membrane activity. While MFS-free LNCs exerted no antischistosomal effect, statistically significant enhancement was observed with all MFS-LNC formulations. A maximum effect was achieved with MFS-LNCs incorporating CTAB as positive charge imparting agent or oleic acid as membrane permeabilizer. Reduction of worm load, ameliorated liver pathology and extensive damage of the worm tegument provided evidence for formulation-related efficacy enhancement. Non-compartmental analysis of pharmacokinetic data obtained in rats indicated independence of antischistosomal activity on systemic drug exposure, suggesting possible gut uptake of the stable LNCs and targeting of the fluke tegument which was verified by SEM. The study findings put forward MFS-LNCs as unique oral nanovectors combining the bioactivity of MFS and biopharmaceutical advantages of LNCs

  1. Study of treating tibial large bone defect with migration of lengthened bone segment in goats

    Institute of Scientific and Technical Information of China (English)

    YANG liu; LI Qi-hong; ZHOU Zhong-an; TAN Zu-jian; PENG Yi-liang

    2001-01-01

    To study the effects of migration of lengthened bone segment (MLBS) on the blood circulation and repair remodeling process at the ends of large bone defect of a long bone. Methods: A total of 18 adult goats were used and more than 35% of the original length of their left tibia was resected. Upper metaphysiotomy to lengthen upper part of the tibia was done and the lengthened bone segment was migrated to repair the large bone defect. The results were observed with X-ray films, Chinese-ink permeated transparent sections and histological study. Results: After MLBS, the defect ends of the tibia were supplied with abundant blood circulation which resulted in rapid and solid long bone healing. Conclusion: Repair of large bone defect of long bones with MLBS provides a new method for clinical practice.

  2. Silver nanoparticle/chitosan oligosaccharide/poly(vinyl alcohol nanofibers as wound dressings: a preclinical study

    Directory of Open Access Journals (Sweden)

    Li CW

    2013-11-01

    Full Text Available Chenwen Li,1,* Ruoqiu Fu,1,* Caiping Yu,1 Zhuoheng Li,1 Haiyan Guan,1 Daqiang Hu,1 Dehua Zhao,2 Laichun Lu1 1Department of Pharmacy, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 2College of Pharmacy, Chongqing Medical University, Chongqing, People's Republic of China *These authors contributed equally to this work Abstract: In this study, a mixture of poly(vinyl alcohol (PVA and chitosan oligosaccharides (COS was electrospun with silver nanoparticles (AgNPs to produce fibrous mats for use in wound healing. The AgNPs were reduced by COS prior to electrospinning or Ag+ was reduced via ultraviolet irradiation in nanofibers. The morphologies of the PVA/COS/AgNO3 and PVA/COS-AgNP nanofibers were analyzed by scanning electron microscopy. Formation of the AgNPs was investigated by field emission transmission electron microscopy, ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. We also evaluated the biocompatibility of the nanofibers, particularly their cytotoxicity to human skin fibroblasts and potential to cause primary skin irritation. The in vitro antibacterial activity and in vivo wound healing capacity of the nanofibers were also investigated. The nanofibers had a smooth surface with an average diameter of 130–192 nm. The diameters of the AgNPs were in the range of 15–22 nm. The nanofibers significantly inhibited growth of Escherichia coli and Staphylococcus aureus bacteria. PVA/COS-AgNP nanofibers accelerated the rate of wound healing over that of the control (gauze. The results of our in vitro and in vivo animal experiments suggest that PVA/COS-AgNP nanofibers should be of greater interest than PVA/COS/AgNO3 nanofibers for clinical use as a bioactive wound dressing. Keywords: preclinical study, wound dressing, electrospinning, silver nanoparticles, poly(vinyl alcohol, chitosan oligosaccharides

  3. Gene therapy targeting cord blood-derived CD34+ cells from HIV-exposed infants: preclinical studies

    OpenAIRE

    Li, X.; Gervaix, Alain; Kang, D.; Law, P.; Spector, S. A.; Ho, A D; Wong-Staal, F

    1998-01-01

    Hematopoietic CD34+ cells from placental and umbilical cord blood (PUCB) can be valuable vehicles for gene therapy of immunodeficiencies and genetic disorders. We have conducted preclinical studies towards the treatment of HIV-1-infected infants with genetically 'immunized' CD34+ cells derived from PUCB using anti-HIV-1 hairpin ribozyme genes. PUCB was collected from 10 newborns of HIV-1-positive mothers. CD34+ cells were enriched with a modified procedure using Dynal immunomagnetic beads and...

  4. The effects of surgicel and bone wax hemostatic agents on bone healing: An experimental study

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    Nasser Nooh

    2014-01-01

    Full Text Available Background: The biological effects of hemostatic agends on the physiological healing process need to be tested. The aim of this study was to assess the effects of oxidized cellulose (surgicel and bone wax on bone healing in goats′ feet. Materials and Methods: Three congruent circular bone defects were created on the lateral aspects of the right and left metacarpal bones of ten goats. One defect was left unfilled and acted as a control; the remaining two defects were filled with bone wax and surgicel respectively. The 10 animals were divided into two groups of 5 animals each, to be sacrificed at the 3rd and 5th week postoperatively. Histological analysis assessing quality of bone formed and micro-computed tomography (MCT measuring the quantities of bone volume (BV and bone density (BD were performed. The results of MCT analysis pertaining to BV and BD were statistically analyzed using two-way analysis of variance (ANOVA and posthoc least significant difference tests. Results: Histological analysis at 3 weeks showed granulation tissue with new bone formation in the control defects, active bone formation only at the borders for surgicel filled defects and fibrous encapsulation with foreign body reaction in the bone wax filled defects. At 5 weeks, the control and surgicel filled defects showed greater bone formation; however the control defects had the greatest amount of new bone. Bone wax filled defects showed very little bone formation. The two-way ANOVA for MCT results showed significant differences for BV and BD between the different hemostatic agents during the two examination periods. Conclusion: Surgicel has superiority over bone wax in terms of osseous healing. Bone wax significantly hinders osteogenesis and induces inflammation.

  5. Radioiodination of central nerves system dopamine D2 receptor imaging agent. IBZM preparation and preclinical study

    International Nuclear Information System (INIS)

    To study preparation of central nerves system dopamine D2 imaging agent 131I-IBZM and its preclinical investigation, peracetic acid was used as the oxidant for preparing radioiodinated 125I-IBZM and 131I-IBZM, D2 binding properties of IBZM were examined by in vitro binding saturation analysis, rat whole body and regional brain biodistribution, rat brain autoradiography and rabbit SPECT static imaging, etc. The results are: 1. The radiolabelling yields of 125I-IBZM and 131I-IBZM were 84.18% +- 3.06% and 78.50% +- 3.47%. The radiochemical purity were over 95% after being isolated by HPLC; and were over 90% after being isolated by organic extraction. 2. Scatchard plot of D2 receptor saturation binding analysis showed: Kd = 0.53 +- 0.06 nmol/L, Bmax = 466.45 +- 45.88 fmol/mg protein. 3. The rat brain autoradiography and analysis showed that there was high 125I-IBZM uptake in striatal area 2 hr after injection, the striatal/cerebellum ratio was 6.22 +- 0.48; the high 125-IBZM uptake can be blocked by haloperidol--a special dopamine D2 receptor antagonist. 4. 131I-IBZM rat biodistribution and rabbit SPECT planar imaging showed good initial brain uptake and retention, the initial uptake of rat brain was 1.893 +- 0.147% ID/g at 2 min and 1.044 +- 0.135% ID/g at 60 min. The results showed that the radioiodinated IBZM had high affinity, saturation and specificity to rat's and rabbit's central nerves system dopamine D2 receptors

  6. A quantitative histological study of early clinical and preclinical Alzheimer's disease.

    Science.gov (United States)

    Hubbard, B M; Fenton, G W; Anderson, J M

    1990-04-01

    Brains from 70 unselected general hospital necropsy cases aged 60-95 years were surveyed histologically for changes of Alzheimer's disease using Congo Red-Gallocyanin preparations. Counts were made of neurofibrillary tangles in two areas of the neocortex, the hippocampal formation and the substantia innominata. Neurons were counted in the subiculum of the hippocampus, the substantia innominata and the locus coeruleus. In addition, a retrospective enquiry was made concerning the mental health of the patients in the study; cognitive performance was graded on the Global Deterioration Scale (GDS 1-7). Four cases (5.7%) had clinical and pathological changes amounting to early Alzheimer's disease. Tangles were very numerous in all areas and there was a 30% deficit or more of neurons in at least two of the structures counted. Although the diagnosis of Alzheimer's disease was not recorded during life, all had shown signs of early cognitive decline (GDS grades 3-6). A further six cases (8.6%) showed excessive tangle accumulation which may represent preclinical Alzheimer's disease. Tangles were present in the temporal neocortex (Brodmann area 22), whereas they were absent in the remainder of the survey. Tangle density in the hippocampal formation (greater than 50 tangles in a 10 microns section) was also above the baseline level of the majority of cases. However, neuron loss was not widespread in these cases and none had shown evidence of cognitive impairment. The findings confirm that the early stages of Alzheimer's disease commonly occur amongst general hospital necropsies. The emergence of clinical signs of dementia appears to be related to the loss of a critical volume of neurons and not to tangle accumulation alone. PMID:2345598

  7. Clinical study on postoperative steroid hormon replacement for preclinical Cushing's syndrome

    International Nuclear Information System (INIS)

    Diagnostic criteria for preclinical Cushing's syndrome (PCS) were reported in 1996. However, requirement of postoperative steroid hormone replacement is still controversial issue. In this study, we observed recent surgical cases retrospectively and evaluate the use of postoperative steroid hormone replacement. Eighteen patients with PCS underwent surgery from 1997 to 2007 in Jikei University Hospital. Thirteen of them received postoperative steroid hormone replacement. We investigated preoperative hormone activity by 131I-adosterol scintigraphy and suppression of adrenocorticotropic hormone (ACTH) and evaluated the requirement of postoperative steroid hormone replacement. Preoperative serum cortisol was normal range in all patients. Serum ACTH was suppressed in 10 of them (56%). In 131I-adosterol scintigraphy, accumulation in ipsilateral side was observed in all patients. Accumulation in contralateral side was observed in 13 patients whose serum ACTH had tendency to be suppressed. Mean period of steroid hormone replacement was 19.8 weeks. Patients with lower preoperative ACTH tended to require longer period until withdrawal of steroid hormone replacement. In addition, patients received steroid hormone replacement with higher starting dose significantly required longer period. Three of them had complications during tapering of steroid hormone. Postoperative adrenal insufficiency is important issue as postoperative management of PCS patients whose function of contralateral adrenal or pituitary gland is suppressed. 131I-adosterol scintigraphy and preoperative serum ACTH were important factors to evaluate the requirement of postoperative steroid hormone replacement. Especially, patients with low preoperative serum ACTH tended to require long duration of postoperative steroid hormone replacement. On the other hand, patients with accumulation of contralateral side in 131I-adosterol scintigraphy and without suppression of serum ACTH may not require steroid hormone

  8. Tissue damage in the canine normal esophagus by photoactivation with talaporfin sodium (laserphyrin: a preclinical study.

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    Takahiro Horimatsu

    Full Text Available BACKGROUND: Treatment failure at the primary site after chemoradiotherapy is a major problem in achieving a complete response. Photodynamic therapy (PDT with porfimer sodium (Photofrin® has some problems such as the requirement for shielding from light for several weeks and a high incidence of skin phototoxicity. PDT with talaporfin sodium (Laserphyrin is less toxic and is expected to have a better effect compared with Photofrin PDT. However, Laserphyrin PDT is not approved for use in the esophagus. In this preclinical study, we investigated tissue damage of the canine normal esophagus caused by photoactivation with Laserphyrin. METHODOLOGY/PRINCIPAL FINDINGS: Diode laser irradiation was performed at 60 min after administration. An area 5 cm oral to the esophagogastric junction was irradiated at 25 J/cm(2, 50 J/cm(2, and 100 J/cm(2 using a three-step escalation. The irradiated areas were evaluated endoscopically on postirradiation days 1 and 7, and were subjected to histological examination after autopsy. The areas injured by photoactivation were 52 mm(2, 498 mm(2, and 831 mm(2 after irradiation at 25 J/cm(2, 50 J/cm(2, and 100 J/cm(2, respectively. Tissue injury was observed in the muscle layer or even deeper at any irradiation level and became more severe as the irradiation dose increased. At 100 J/cm(2 both inflammatory changes and necrosis were seen histologically in extra-adventitial tissue. CONCLUSIONS/SIGNIFICANCE: To minimize injury of the normal esophagus by photoactivation with Laserphyrin, diode laser irradiation at 25 J/cm(2 appears to be safe. For human application, it would be desirable to investigate the optimal laser dose starting from this level.

  9. Longitudinal study on osteoarthritis and bone metabolism

    OpenAIRE

    L Postiglione; Savastano, S; A. Scognamiglio; G. Nutile; Carpinelli, A; Esposito, A.; del Puente, A; Padula, S.; Oriente, P

    2011-01-01

    Objective: The relationship between Osteoarthritis (OA) and Osteoporosis (OP) is not well defined due to lacking in longitudinal data, mainly regarding correlations between biochemical factors and OA incidence. Aim of this paper was to investigate the predictive value for OA incidence of bone mass variations and of selected biochemical markers in healthy women participating in a population-based longitudinal study carried out in Naples (Italy). Subjects and Methods: High completion rate (85.2...

  10. Bone Regeneration Using Bone Morphogenetic Proteins and Various Biomaterial Carriers

    Directory of Open Access Journals (Sweden)

    Zeeshan Sheikh

    2015-04-01

    Full Text Available Trauma and disease frequently result in fractures or critical sized bone defects and their management at times necessitates bone grafting. The process of bone healing or regeneration involves intricate network of molecules including bone morphogenetic proteins (BMPs. BMPs belong to a larger superfamily of proteins and are very promising and intensively studied for in the enhancement of bone healing. More than 20 types of BMPs have been identified but only a subset of BMPs can induce de novo bone formation. Many research groups have shown that BMPs can induce differentiation of mesenchymal stem cells and stem cells into osteogenic cells which are capable of producing bone. This review introduces BMPs and discusses current advances in preclinical and clinical application of utilizing various biomaterial carriers for local delivery of BMPs to enhance bone regeneration.

  11. Stimulation of bone marrow cells and bone formation by nacre: in vivo and in vitro studies.

    Science.gov (United States)

    Lamghari, M; Almeida, M J; Berland, S; Huet, H; Laurent, A; Milet, C; Lopez, E

    1999-08-01

    There is frequently a loss of vertebral bone due to disease or aging. Nacre (mother of pearl from the oyster Pinctada maxima) stimulates bone cell differentiation and bone formation in vitro and in vivo. Experimental bone defects were prepared in the vertebrae of sheep and used to test the suitability of nacre as an injectable osteogenic biomaterial for treating vertebral bone loss. Twenty-one cavities were prepared in the first four upper lumbar vertebrae of 11 sheep and filled with nacre powder. The lumbar vertebrae were removed after 1 to 12 weeks, embedded undecalcified in methacrylate, and processed for histological studies. The nacre slowly dissolved and the experimental cavities contained a large active cell population. By 12 weeks, the experimental cavity was occupied by newly matured bone trabeculae in contact with or adjacent to the dissolving nacre. The functional new bone trabeculae were covered with osteoid lined with osteoblasts, indicating continuing bone formation. The in vitro study on rat bone marrow explants cultured with a water-soluble extract of the nacre organic matrix also resulted in the stimulation of osteogenic bone marrow cells with enhanced alkaline phosphatase activity. Thus, both the in vivo and in vitro findings suggest that nacre contains one or more signal molecules capable of activating osteogenic bone marrow cells. PMID:10458284

  12. A Mouse Model for Studying Nutritional Programming: Effects of Early Life Exposure to Soy Isoflavones on Bone and Reproductive Health.

    Science.gov (United States)

    Ward, Wendy E; Kaludjerovic, Jovana; Dinsdale, Elsa C

    2016-01-01

    Over the past decade, our research group has characterized and used a mouse model to demonstrate that "nutritional programming" of bone development occurs when mice receive soy isoflavones (ISO) during the first days of life. Nutritional programming of bone development can be defined as the ability for diet during early life to set a trajectory for better or compromised bone health at adulthood. We have shown that CD-1 mice exposed to soy ISO during early neonatal life have higher bone mineral density (BMD) and greater trabecular inter-connectivity in long bones and lumbar spine at young adulthood. These skeletal sites also withstand greater forces before fracture. Because the chemical structure of ISO resembles that of 17-β-estradiol and can bind to estrogen receptors in reproductive tissues, it was prudent to expand analyses to include measures of reproductive health. This review highlights aspects of our studies in CD-1 mice to understand the early life programming effects of soy ISO on bone and reproductive health. Preclinical mouse models can provide useful data to help develop and guide the design of studies in human cohorts, which may, depending on findings and considerations of safety, lead to dietary interventions that optimize bone health. PMID:27187422

  13. A Mouse Model for Studying Nutritional Programming: Effects of Early Life Exposure to Soy Isoflavones on Bone and Reproductive Health

    Science.gov (United States)

    Ward, Wendy E.; Kaludjerovic, Jovana; Dinsdale, Elsa C.

    2016-01-01

    Over the past decade, our research group has characterized and used a mouse model to demonstrate that “nutritional programming” of bone development occurs when mice receive soy isoflavones (ISO) during the first days of life. Nutritional programming of bone development can be defined as the ability for diet during early life to set a trajectory for better or compromised bone health at adulthood. We have shown that CD-1 mice exposed to soy ISO during early neonatal life have higher bone mineral density (BMD) and greater trabecular inter-connectivity in long bones and lumbar spine at young adulthood. These skeletal sites also withstand greater forces before fracture. Because the chemical structure of ISO resembles that of 17-β-estradiol and can bind to estrogen receptors in reproductive tissues, it was prudent to expand analyses to include measures of reproductive health. This review highlights aspects of our studies in CD-1 mice to understand the early life programming effects of soy ISO on bone and reproductive health. Preclinical mouse models can provide useful data to help develop and guide the design of studies in human cohorts, which may, depending on findings and considerations of safety, lead to dietary interventions that optimize bone health. PMID:27187422

  14. Wound-Healing Potential of Cultured Epidermal Sheets Is Unaltered after Lyophilization: A Preclinical Study in Comparison to Cryopreserved CES

    OpenAIRE

    Jang, H.; Kim, Y. H.; Kim, M. K.; Lee, K H; Jeon, S.

    2013-01-01

    Lyophilized Cultured Epidermal Sheets (L-CES) have been reported to be as effective as the cryopreserved CES (F-CES) in treating skin ulcers. However, unlike F-CES, no preclinical study assessing wound-healing effects has been conducted for L-CES. The present study was set out to investigate the microstructure, cytokine profile, and wound-healing effects of L-CES in comparison to those of F-CES. Keratinocytes were cultured to prepare CES, followed by cryopreservation at −70°C and lyophilizati...

  15. Alveolar bone of BBMl rats: a morphometric and histochemical study

    OpenAIRE

    Johnson, R B; Carlson, E. C.

    1989-01-01

    The present study reported histochemical changes in alveolar bone glycosaminoglycans (GAG) (using Safranin 0 ) and in interdental bone height in three groups of BB/W rats: diabetic, diabetes prone, and diabetes resistant. Safranin O staining intensity suggested that total GAG levels were highest in diabetic bone (p

  16. Longitudinal study on osteoarthritis and bone metabolism

    Directory of Open Access Journals (Sweden)

    L. Postiglione

    2011-09-01

    Full Text Available Objective: The relationship between Osteoarthritis (OA and Osteoporosis (OP is not well defined due to lacking in longitudinal data, mainly regarding correlations between biochemical factors and OA incidence. Aim of this paper was to investigate the predictive value for OA incidence of bone mass variations and of selected biochemical markers in healthy women participating in a population-based longitudinal study carried out in Naples (Italy. Subjects and Methods: High completion rate (85.2% and statistically adequate sample size were obtained: 139 women (45 to 79 years of age were examined and follow up visit was performed after two years (24±2 months, following the same protocol. Patients underwent medical examination, questionnaire, anthropometric measurements, blood sampling and urine collection. Bone mineral density (BMD measurement was performed by dual energy X-ray absorptiometry (DEXA at the lumbar spine (L1-L4 and femoral neck. Radiographs of dorsal and lumbar spine in lateral view were performed at basal and at 24 months visits; a team of three experts scored radiographs using Kellegren and Lawrence grading. Results: The score was calculated for two individual radiographic features (narrowing of the joint space, presence of osteophytes and as a global score. Results show a relevant percentage, 23% up, of subjects presenting both OA and OP. In the cross-sectional study the presence of osteophytosis correlates with anthropometric variables and PTH levels. In the longitudinal study results show a correlation between serum vitamin D and delta score for osteophytosis (β=0.02 p<0.05. Conclusions: Data obtained outline the importance of further studies on the pathogenetic link between OA and bone metabolism.

  17. Threats to validity in the design and conduct of preclinical efficacy studies: a systematic review of guidelines for in vivo animal experiments.

    Directory of Open Access Journals (Sweden)

    Valerie C Henderson

    Full Text Available BACKGROUND: The vast majority of medical interventions introduced into clinical development prove unsafe or ineffective. One prominent explanation for the dismal success rate is flawed preclinical research. We conducted a systematic review of preclinical research guidelines and organized recommendations according to the type of validity threat (internal, construct, or external or programmatic research activity they primarily address. METHODS AND FINDINGS: We searched MEDLINE, Google Scholar, Google, and the EQUATOR Network website for all preclinical guideline documents published up to April 9, 2013 that addressed the design and conduct of in vivo animal experiments aimed at supporting clinical translation. To be eligible, documents had to provide guidance on the design or execution of preclinical animal experiments and represent the aggregated consensus of four or more investigators. Data from included guidelines were independently extracted by two individuals for discrete recommendations on the design and implementation of preclinical efficacy studies. These recommendations were then organized according to the type of validity threat they addressed. A total of 2,029 citations were identified through our search strategy. From these, we identified 26 guidelines that met our eligibility criteria--most of which were directed at neurological or cerebrovascular drug development. Together, these guidelines offered 55 different recommendations. Some of the most common recommendations included performance of a power calculation to determine sample size, randomized treatment allocation, and characterization of disease phenotype in the animal model prior to experimentation. CONCLUSIONS: By identifying the most recurrent recommendations among preclinical guidelines, we provide a starting point for developing preclinical guidelines in other disease domains. We also provide a basis for the study and evaluation of preclinical research practice. Please see

  18. Vindarnas Boning : En studie av monumentalistiskt historiebruk

    OpenAIRE

    Aronsson, Tobias

    2007-01-01

    Monuments are raised all over the world of several different reasons. A monument dosen´t only refer just to itself, it also tells something about the historical context they are risen into. The overall purpose of this study is to try to reveal how history is used through the process, and rising of the monument "Vindarnas Boning" in Karlstad, Sweden 16/6, 1967. The historical narrative around this monument is about to show the importance of the esthetics, the main forces around the monument an...

  19. Plant-based medicines for anxiety disorders, part 2: a review of clinical studies with supporting preclinical evidence.

    Science.gov (United States)

    Sarris, Jerome; McIntyre, Erica; Camfield, David A

    2013-04-01

    Research in the area of herbal psychopharmacology has revealed a variety of promising medicines that may provide benefit in the treatment of general anxiety and specific anxiety disorders. However, a comprehensive review of plant-based anxiolytics has been absent to date. Thus, our aim was to provide a comprehensive narrative review of plant-based medicines that have clinical and/or preclinical evidence of anxiolytic activity. We present the article in two parts. In part one, we reviewed herbal medicines for which only preclinical investigations for anxiolytic activity have been performed. In this current article (part two), we review herbal medicines for which there have been both preclinical and clinical investigations of anxiolytic activity. A search of MEDLINE (PubMed), CINAHL, Scopus and the Cochrane Library databases was conducted (up to 28 October 2012) for English language papers using the search terms 'anxiety' OR 'anxiety disorder' OR 'generalized anxiety disorder' OR 'social phobia' OR 'post-traumatic stress disorder' OR 'panic disorder' OR 'agoraphobia' OR 'obsessive compulsive disorder' in combination with the search terms 'Herb*' OR 'Medicinal Plants' OR 'Botanical Medicine' OR 'Chinese herb*', in addition to individual herbal medicines. This search of the literature revealed 1,525 papers, of which 53 plants were included in the review (having at least one study using the whole plant extract). Of these plants, 21 had human clinical trial evidence (reviewed here in part two), with the other 32 having solely preclinical evidence (reviewed in part one). Support for efficacy was found for chronic use (i.e. greater than one day) of the following herbs in treating a range of anxiety disorders in human clinical trials: Piper methysticum, Matricaria recutita, Ginkgo biloba, Scutellaria lateriflora, Silybum marianum, Passiflora incarnata, Withania somniferum, Galphimia glauca, Centella asiatica, Rhodiola rosea, Echinacea spp., Melissa officinalis and Echium

  20. Targeting Bone Marrow to Potentiate the Anti-Tumor Effect of Tyrosine Kinase Inhibitor in Preclinical Rat Model of Human Glioblastoma

    Science.gov (United States)

    Shaaban, S.; Alsulami, M.; Arbab, S.A.; Ara, R.; Shankar, A.; Iskander, A.; Angara, K.; Jain, M.; Bagher-Ebadian, H.; Achyut, B.R.; Arbab, A.S.

    2016-01-01

    Antiangiogenic agents caused paradoxical increase in pro-growth and pro-angiogenic factors and caused tumor growth in glioblastoma (GBM). It is hypothesized that paradoxical increase in pro-angiogenic factors would mobilize Bone Marrow Derived Cells (BMDCs) to the treated tumor and cause refractory tumor growth. The purposes of the studies were to determine whether whole body irradiation (WBIR) or a CXCR4 antagonist (AMD3100) will potentiate the effect of vatalanib (a VEGFR2 tyrosine kinase inhibitor) and prevent the refractory growth of GBM. Human GBM were grown orthotopically in three groups of rats (control, pretreated with WBIR and AMD3100) and randomly selected for vehicle or vatalanib treatments for 2 weeks. Then all animals underwent Magnetic Resonance Imaging (MRI) followed by euthanasia and histochemical analysis. Tumor volume and different vascular parameters (plasma volume (vp), forward transfer constant (Ktrans), back flow constant (kep), extravascular extracellular space volume (ve) were determined from MRI. In control group, vatalanib treatment increased the tumor growth significantly compared to that of vehicle treatment but by preventing the mobilization of BMDCs and interaction of CXCR4-SDF-1 using WBIR and ADM3100, respectively, paradoxical growth of tumor was controlled. Pretreatment with WBIR or AMD3100 also decreased tumor cell migration, despite the fact that ADM3100 increased the accumulation of M1 and M2 macrophages in the tumors. Vatalanib also increased Ktrans and ve in control animals but both of the vascular parameters were decreased when the animals were pretreated with WBIR and AMD3100. In conclusion, depleting bone marrow cells or CXCR4 interaction can potentiate the effect of vatalanib.

  1. A bioluminescent mouse model of proliferation to highlight early stages of pancreatic cancer: A suitable tool for preclinical studies.

    Science.gov (United States)

    de Latouliere, Luisa; Manni, Isabella; Iacobini, Carla; Pugliese, Giuseppe; Grazi, Gian Luca; Perri, Pasquale; Cappello, Paola; Novelli, Franco; Menini, Stefano; Piaggio, Giulia

    2016-09-01

    Transgenic mouse models designed to recapitulate genetic and pathologic aspects of cancer are useful to study early stages of disease as well as its progression. Among several, two of the most sophisticated models for pancreatic ductal adenocarcinoma (PDAC) are the LSL-Kras(G12D/+);Pdx-1-Cre (KC) and LSL-Kras(G12D/+);LSL-Trp53(R172H/+);Pdx-1-Cre (KPC) mice, in which the Cre-recombinase regulated by a pancreas-specific promoter activates the expression of oncogenic Kras alone or in combination with a mutant p53, respectively. Non-invasive in vivo imaging offers a novel approach to preclinical studies introducing the possibility to investigate biological events in the spatio/temporal dimension. We recently developed a mouse model, MITO-Luc, engineered to express the luciferase reporter gene in cells undergoing active proliferation. In this model, proliferation events can be visualized non-invasively by bioluminescence imaging (BLI) in every body district in vivo. Here, we describe the development and characterization of MITO-Luc-KC- and -KPC mice. In these mice we have now the opportunity to follow PDAC evolution in the living animal in a time frame process. Moreover, by relating in vivo and ex vivo BLI and histopathological data we provide evidence that these mice could represents a suitable tool for pancreatic cancer preclinical studies. Our data also suggest that aberrant proliferation events take place early in pancreatic carcinogenesis, before tumour appearance. PMID:26704357

  2. Therapeutic vaccination in chronic hepatitis B: preclinical studies in the woodchuck.

    Science.gov (United States)

    Kosinska, Anna D; Zhang, Ejuan; Lu, Mengji; Roggendorf, Michael

    2010-01-01

    Recommended treatment of chronic hepatitis B with interferon-α and/or nucleos(t)ide analogues does not lead to a satisfactory result. Induction of HBV-specific T cells by therapeutic vaccination or immunotherapies may be an innovative strategy to overcome virus persistence. Vaccination with commercially available HBV vaccines in patients did not result in effective control of HBV infection, suggesting that new formulations of therapeutic vaccines are needed. The woodchuck (Marmota monax) is a useful preclinical model for developing the new therapeutic approaches in chronic hepadnaviral infections. Several innovative approaches combining antiviral treatments with nucleos(t)ide analogues, DNA vaccines, and protein vaccines were tested in the woodchuck model. In this paper we summarize the available data concerning therapeutic immunization and gene therapy using recombinant viral vectors approaches in woodchucks, which show encouraging results. In addition, we present potential innovations in immunomodulatory strategies to be evaluated in this animal model. PMID:21188201

  3. Preclinical studies of potential amyloid binding PET/SPECT ligands in Alzheimer's disease

    International Nuclear Information System (INIS)

    Visualizing the neuropathological hallmarks amyloid plaques and neurofibrillary tangles of Alzheimer's disease in vivo using positron emission tomography (PET) or single photon emission computed tomography will be of great value in diagnosing the individual patient and will also help in our understanding of the disease. The successful introduction of [11C]PIB as a PET tracer for the amyloid plaques less than 10 years ago started an intensive research, and numerous new compounds for use in molecular imaging of the amyloid plaques have been developed. The candidates are based on dyes like thioflavin T, Congo red and chrysamine G, but also on other types such as benzoxazoles, curcumin and stilbenes. In the present review, we present methods of the radiochemistry and preclinical evaluation as well as the main properties of some of these compounds.

  4. Therapeutic Vaccination in Chronic Hepatitis B: Preclinical Studies in the Woodchuck

    Directory of Open Access Journals (Sweden)

    Anna D. Kosinska

    2010-01-01

    Full Text Available Recommended treatment of chronic hepatitis B with interferon-α and/or nucleos(tide analogues does not lead to a satisfactory result. Induction of HBV-specific T cells by therapeutic vaccination or immunotherapies may be an innovative strategy to overcome virus persistence. Vaccination with commercially available HBV vaccines in patients did not result in effective control of HBV infection, suggesting that new formulations of therapeutic vaccines are needed. The woodchuck (Marmota monax is a useful preclinical model for developing the new therapeutic approaches in chronic hepadnaviral infections. Several innovative approaches combining antiviral treatments with nucleos(tide analogues, DNA vaccines, and protein vaccines were tested in the woodchuck model. In this paper we summarize the available data concerning therapeutic immunization and gene therapy using recombinant viral vectors approaches in woodchucks, which show encouraging results. In addition, we present potential innovations in immunomodulatory strategies to be evaluated in this animal model.

  5. Pharmacokinetics and tolerability of NSC23925b, a novel P-glycoprotein inhibitor: preclinical study in mice and rats.

    Science.gov (United States)

    Gao, Yan; Shen, Jacson K; Choy, Edwin; Zhang, Zhan; Mankin, Henry J; Hornicek, Francis J; Duan, Zhenfeng

    2016-01-01

    Overexpression of P-glycoprotein (Pgp) increases multidrug resistance (MDR) in cancer, which greatly impedes satisfactory clinical treatment and outcomes of cancer patients. Due to unknown pharmacokinetics, the use of Pgp inhibitors to overcome MDR in the clinical setting remains elusive despite promising in vitro results. The purpose of our current preclinical study is to investigate the pharmacokinetics and tolerability of NSC23925b, a novel and potent P-glycoprotein inhibitor, in rodents. Plasma pharmacokinetic studies of single-dose NSC23925b alone or in combination with paclitaxel or doxorubicin were conducted in male BALB/c mice and Sprague-Dawley rats. Additionally, inhibition of human cytochrome P450 (CYP450) by NSC23925b was examined in vitro. Finally, the maximum tolerated dose (MTD) of NSC23925b was determined. NSC23925b displayed favorable pharmacokinetic profiles after intraperitoneal/intravenous (I.P./I.V.) injection alone or combined with chemotherapeutic drugs. The plasma pharmacokinetic characteristics of the chemotherapy drugs were not affected when co-administered with NSC23925b. All the animals tolerated the I.P./I.V. administration of NSC23925b. Moreover, the enzymatic activity of human CYP450 was not inhibited by NSC23925b. Our results demonstrated that Pgp inhibitor NSC23925b exhibits encouraging preclinical pharmacokinetic characteristics and limited toxicity in vivo. NSC23925b has the potential to treat cancer patients with MDR in the future. PMID:27157103

  6. Immunologic studies of canine bone marrow chimeras

    International Nuclear Information System (INIS)

    When prospective male or female recipients from the Cooperstown colony were exposed to supralethal total body irradiation and were reconstituted with bone marrow obtained from genotypically DL-A-identical littermate or nonlittermate donors such treatment resulted, in regularly reproducible fashion, in the establishment of a long-term state of chimerism with no evidence of graft-versus-host disease in any of the recipients. The resulting chimeras have survived thus far for 882-1466 days, with donor red cell antigen and leukocyte sex marker evidence of the persistence of chimerism. Subsequent challenge of the chimeras with renal and skin allografts obtained from the specific donor of marrow resulted in the long-term survival of such transplants without any evidence of rejection for 833--1402 days. Skin allografts obtained from other dogs were, however, accorded first-set rejection times. Recent studies indicate that the state of allogeneic unresponsiveness produced by supralethal total body irradiation and bone marrow transplantation also extends to other organs from the donor of marrow, including heart, liver, pancreas and duodenum, and lung

  7. Solid-state P-31 MR studies of bone mineral and calcium phosphate bone cements

    International Nuclear Information System (INIS)

    Calcium phosphate bone cements have recently been used to promote bone healing and remodeling, but little is known of their bioabsorption. The purpose of this paper to characterize and quantitate bone mineral and calcium phosphate bone cements with the use of solid-state P-31 NMR imaging to establish a model for bioabsorption studies. Pulverized cortical rabbit bone, octacalcium phosphate spherulites, and two synthetic apatite formulations (A and B, Norian, Mountain View, Calif) were evaluated in vitro. A 9.4-T Varian VXR-400S spectrometer operating at 161.9 MHz for P-31 was used to obtain NMR imaging spectra with the magic-angel spinning technique at a sample spin frequency of 6-7.5 kHz, utilizing an external 85% phosphoric acid reference. T1 was determined in a static 90 degrees τ 90 degrees experiment. Quantitation was attempted in mixed samples

  8. Preclinical profile of cabazitaxel.

    Science.gov (United States)

    Vrignaud, Patricia; Semiond, Dorothée; Benning, Veronique; Beys, Eric; Bouchard, Hervé; Gupta, Sunil

    2014-01-01

    First-generation taxanes have changed the treatment paradigm for a wide variety of cancers, but innate or acquired resistance frequently limits their use. Cabazitaxel is a novel second-generation taxane developed to overcome such resistance. In vitro, cabazitaxel showed similar antiproliferative activity to docetaxel in taxane-sensitive cell lines and markedly greater activity in cell lines resistant to taxanes. In vivo, cabazitaxel demonstrated excellent antitumor activity in a broad spectrum of docetaxel-sensitive tumor xenografts, including a castration-resistant prostate tumor xenograft, HID28, where cabazitaxel exhibited greater efficacy than docetaxel. Importantly, cabazitaxel was also active against tumors with innate or acquired resistance to docetaxel, suggesting therapeutic potential for patients progressing following taxane treatment and those with docetaxel-refractory tumors. In patients with tumors of the central nervous system (CNS), and in patients with pediatric tumors, therapeutic success with first-generation taxanes has been limited. Cabazitaxel demonstrated greater antitumor activity than docetaxel in xenograft models of CNS disease and pediatric tumors, suggesting potential clinical utility in these special patient populations. Based on therapeutic synergism observed in an in vivo tumor model, cabazitaxel is also being investigated clinically in combination with cisplatin. Nonclinical evaluation of the safety of cabazitaxel in a range of animal species showed largely reversible changes in the bone marrow, lymphoid system, gastrointestinal tract, and male reproductive system. Preclinical safety signals of cabazitaxel were consistent with the previously reported safety profiles of paclitaxel and docetaxel. Clinical observations with cabazitaxel were consistent with preclinical results, and cabazitaxel is indicated, in combination with prednisone, for the treatment of patients with hormone-refractory metastatic prostate cancer previously treated

  9. Preclinical studies on [{sup 11}C]MPDX for mapping adenosine A{sub 1} receptors by positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwata, Kiichi; Kimura, Yuichi; Oda, Keiichi; Kawamura, Kazunori; Ishii, Kenji; Senda, Michio [Tokyo Metropolitan Inst. of Gerontology (Japan). Positron Medical Center; Nariai, Tadashi; Wakabayashi, Shinichi [Tokyo Medical and Dental Univ. (Japan). School of Medicine; Shimada, Junichi [Kyowa Hakko Kogyo Co. Ltd., Tokyo (Japan). Pharmaceutical Research Inst.

    2002-09-01

    In previous in vivo studies with mice, rats and cats, we have demonstrated that [{sup 11}C]MPDX ([1-methyl-{sup 11}C]8-dicyclopropylmethyl-1-methyl-3-propylxanthine) is a potential radioligand for mapping adenosine A{sub 1} receptors of the brain by positron emission tomography (PET). In the present study, we performed a preclinical study. The radiation absorbed-dose by [{sup 11}C]MPDX in humans estimated from the tissue distribution in mice was low enough for clinical use, and the acute toxicity and mutagenicity of MPDX were not found. The monkey brain was clearly visualized by PET with [{sup 11}C]MPDX. We have concluded that [{sup 11}C]MPDX is suitable for mapping adenosine A{sub 1} receptors in the human brain by PET. (author)

  10. Therapeutic vaccination and immunomodulation in the treatment of chronic hepatitis B: preclinical studies in the woodchuck.

    Science.gov (United States)

    Kosinska, Anna D; Liu, Jia; Lu, Mengji; Roggendorf, Michael

    2015-02-01

    Infection with hepatitis B virus (HBV) may lead to subclinical, acute or chronic hepatitis. In the prevaccination era, HBV infections were endemic due to frequent mother to child transmission in large regions of the world. However, there are still estimated 240 million chronic HBV carriers today and ca. 620,000 patients die per year due to HBV-related liver diseases. Recommended treatment of chronic hepatitis B with interferon-α and/or nucleos(t)ide analogues does not lead to satisfactory results. Induction of HBV-specific T cells by therapeutic vaccination or immunomodulation may be an innovative strategy to overcome virus persistence. Vaccination with commercially available HBV vaccines in patients with or without therapeutic reduction of viral load did not result in effective immune control of HBV infection, suggesting that combination of antiviral treatment with new formulations of therapeutic vaccines is needed. The woodchuck (Marmota monax) and its HBV-like woodchuck hepatitis virus are a useful preclinical animal model for developing new therapeutic approaches in chronic hepadnaviral infections. Several innovative approaches combining antiviral treatments using nucleos(t)ide analogues, with prime-boost vaccination using DNA vaccines, new hepadnaviral antigens or recombinant adenoviral vectors were tested in the woodchuck model. In this review, we summarize these encouraging results obtained with these therapeutic vaccines. In addition, we present potential innovations in immunostimulatory strategies by blocking the interaction of the inhibitory programmed death receptor 1 with its ligand in this animal model. PMID:25535101

  11. Analysis of antigen specific T cells in diabetes - Lessons from pre-clinical studies and early clinical trials.

    Science.gov (United States)

    Krishnamurthy, Balasubramanian; Selck, Claudia; Chee, Jonathan; Jhala, Guarang; Kay, Thomas W H

    2016-07-01

    Antigen-specific immune tolerance promises to provide safe and effective therapies to prevent type 1 diabetes (T1D). Antigen-specific therapy requires two components: well-defined, clinically relevant autoantigens; and safe approaches to inducing tolerance in T cells specific for these antigens. Proinsulin is a critical autoantigen in both NOD mice, based on knockout mouse studies and induction of immune tolerance to proinsulin preventing disease whereas most antigens cannot, and also in human T1D based on proinsulin-specific T cells being found in the islets of affected individuals and the early appearance of insulin autoantibodies. Effective antigen-specific therapies that prevent T1D in humans have not yet been developed although doubt remains about the best molecular form of the antigen, the dose and the route of administration. Preclinical studies suggest that antigen specific therapy is most useful when administered before onset of autoimmunity but this time-window has not been tested in humans until the recent "pre-point" study. There may be a 'window of opportunity' during the neonatal period when 'vaccine' like administration of proinsulin for a short period may be sufficient to prevent diabetes. After the onset of autoimmunity, naive antigen-specific T cells have differentiated into antigen-experienced memory cells and the immune responses have spread to multiple antigens. Induction of tolerance at this stage becomes more difficult although recent studies have suggested generation of antigen-specific TR1 cells can inhibit memory T cells. Preclinical studies are required to identify additional 'help' that is required to induce tolerance to memory T cells and develop protocols for effective therapy in individuals with established autoimmunity. PMID:27083395

  12. Bone

    International Nuclear Information System (INIS)

    Bone scanning provides information on the extent of primary bone tumors, on possible metastatic disease, on the presence of osteomyelitis prior to observation of roentgenographic changes so that earlier therapy is possible, on the presence of collagen diseases, on the presence of fractures not disclosed by x-ray films, and on the evaluation of aseptic necrosis. However, the total effect and contribution of bone scanning to the diagnosis, treatment, and ultimate prognosis of pediatric skeletal diseases is, as yet, unknown. (auth)

  13. Local treatment of a bone graft by soaking in zoledronic acid inhibits bone resorption and bone formation. A bone chamber study in rats

    Directory of Open Access Journals (Sweden)

    Belfrage Ola

    2012-12-01

    Full Text Available Abstract Background Bone grafts are frequently used in orthopaedic surgery. Graft remodelling is advantageous but can occur too quickly, and premature bone resorption might lead to decreased mechanical integrity of the graft. Bisphosphonates delay osteoclastic bone resorption but may also impair formation of new bone. We hypothesize that these effects are dose dependent. In the present study we evaluate different ways of applying bisphosphonates locally to the graft in a bone chamber model, and compare that with systemic treatment. Methods Cancellous bone grafts were placed in titanium chambers and implanted in the tibia of 50 male rats, randomly divided into five groups. The first group served as negative control and the grafts were rinsed in saline before implantation. In the second and third groups, the grafts were soaked in a zoledronic acid solution (0.5 mg/ml for 5 seconds and 10 minutes respectively before being rinsed in saline. In the fourth group, 8 μL of zoledronic acid solution (0.5 mg/ml was pipetted onto the freeze-dried grafts without rinsing. The fifth group served as positive control and the rats were given zoledronic acid (0.1 mg/kg systemically as a single injection two weeks after surgery. The grafts were harvested at 6 weeks and analysed with histomorphometry, evaluating the ingrowth distance of new bone into the graft as an equivalent to the anabolic osteoblast effect and the amount (bone volume/total volume; BV/TV of remaining bone in the remodelled graft as equivalent to the catabolic osteoclast effect. Results In all chambers, almost the entire graft had been revascularized but only partly remodelled at harvest. The ingrowth distance of new bone into the graft was lower in grafts soaked in zoledronic acid for 10 minutes compared to control (p = 0.007. In all groups receiving zoledronic acid, the BV/TV was higher compared to control. Conclusions This study found a strong inhibitory effect on bone resorption by

  14. Advances in breast cancer treatment and prevention: preclinical studies on aromatase inhibitors and new selective estrogen receptor modulators (SERMs)

    International Nuclear Information System (INIS)

    Intensive basic and clinical research over the past 20 years has yielded crucial molecular understanding into how estrogen and the estrogen receptor act to regulate breast cancer and has led to the development of more effective, less toxic, and safer hormonal therapy agents for breast cancer management and prevention. Selective potent aromatase inhibitors are now challenging the hitherto gold standard of hormonal therapy, the selective estrogen-receptor modulator tamoxifen. Furthermore, new selective estrogen-receptor modulators such as arzoxifene, currently under clinical development, offer the possibility of selecting one with a more ideal pharmacological profile for treatment and prevention of breast cancer. Two recent studies in preclinical model systems that evaluate mechanisms of action of these new drugs and suggestions about their optimal clinical use are discussed

  15. X-Ray Exam: Bone Age Study (For Parents)

    Science.gov (United States)

    ... Your Child All About Food Allergies X-Ray Exam: Bone Age Study KidsHealth > For Parents > X-Ray Exam: Bone Age Study Print A A A Text ... MORE ON THIS TOPIC Precocious Puberty X-Ray Exam: Wrist What Is a Growth Disorder? Turner Syndrome ...

  16. Concise review: Preclinical studies on human cell-based therapy in rodent ischemic stroke models: where are we now after a decade?

    Science.gov (United States)

    Leong, Wai Khay; Lewis, Martin D; Koblar, Simon A

    2013-06-01

    Stroke, a debilitating brain insult, afflicts millions of individuals globally each year. In the last decade, researchers have investigated cell-based therapy as an alternative strategy to improve neurological outcome following stroke. This concise review critically examines preclinical reports using human adult and fetal stem/progenitor cells in rodent models of ischemic stroke. As we enter the second decade of study, we should aim to optimize our collective likelihood to translational success for stroke victims worldwide. We advocate international consensus recommendations be developed for future preclinical research. PMID:23390084

  17. A radiographic study of alveolar bone loss in Irish schoolchildren

    International Nuclear Information System (INIS)

    Bitewing radiographs were used to assess evidence of alveolar bone loss in 1492 children in the age range 7-12 years. According to the method used in this study, alveolar bone loss was shown to occur in 1.7% of the children, and maxillary teeth were affected twice as frequently as mandibular teeth. (Author)

  18. In vivo quantification of bone-fluorine by delayed neutron activation analysis: a pilot study of hand-bone-fluorine levels in a Canadian population

    International Nuclear Information System (INIS)

    Humans can be exposed to fluorine (F) through their diet, occupation, environment and oral dental care products. Fluorine, at proper dosages, is believed to have positive effects by reducing the incidence of dental caries, but fluorine toxicity can occur when people are exposed to excessive quantities of fluorine. In this paper we present the results of a small pilot in vivo study on 33 participants living in Southwestern Ontario, Canada. The mean age of participants was 45 ± 18 years with a range of 20–87 years. The observed calcium normalized hand-bone-fluorine concentrations in this small pilot study ranged from 1.1 to 8.8 mg F/g Ca. Every person measured in this study had levels of fluorine in bone above the detection limit of the system. The average fluorine concentration in bone was found to be 3.5 ± 0.4 mg F/g Ca. No difference was observed in average concentration for men and women. In addition, a significant correlation (r2 = 0.55, p < 0.001) was observed between hand-bone-fluorine content and age. The amount of fluorine was found to increase at a rate of 0.084 ± 0.014 mg F/g Ca per year. There was no significant difference observed in this small group of subjects between the accumulation rates in men and women. To the best of our knowledge, this is the first time data from in vivo measurement of fluorine content in humans by neutron activation analysis have been presented. The data determined by this technique were found to be consistent with results from ex vivo studies from other countries. We suggest that the data demonstrate that this low risk non-invasive diagnostic technique will permit the routine assessment of bone-fluorine content with potential application in the study of clinical bone-related diseases. This small study demonstrated that people in Southern Ontario are exposed to fluoride in measureable quantities, and that fluoride can be seen to accumulate in bone with age. However, all volunteers were found to have levels below those

  19. A MULTI-SITE SHEEP MODEL FOR CANCELLOUS BONE HEALING

    OpenAIRE

    MatthewhenryPelletier

    2014-01-01

    Appropriate, well characterized bone defect animal models remain essential for preclinical research. This pilot study demonstrates a relevant animal model for cancellous bone defect healing. Three different defect diameters (8, 11, 14mm) of fixed depth (25mm) were compared in both skeletally immature (18 month old) and aged sheep (5 year old). In each animal, four defects were surgically created and placed in the cancellous bone of the medial distal femoral and proximal tibial epiphyses bi...

  20. Combined analysis of pharmacokinetic and efficacy data of preclinical studies with statins markedly improves translation of drug efficacy to human trialss

    NARCIS (Netherlands)

    Steeg, E. van de; Kleemann, R.; Jansen, H.T.; Duyvenvoorde, W. van; Offerman, E.H.; Wortelboer, H.M.; DeGroot, J.

    2013-01-01

    Correct prediction of human pharmacokinetics (PK) and the safety and efficacy of novel compounds based on preclinical data, is essential but often fails. In the current study, we aimed to improve the predictive value of ApoE*3Leiden (E3L) trans-genic mice regarding the cholesterol-lowering efficacy

  1. Phospholipogenic Pharmaceuticals Are Associated with a Higher Incidence of Histological Findings than Nonphospholipogenic Pharmaceuticals in Preclinical Toxicology Studies

    OpenAIRE

    Barone, Linda R.; Scott Boyer; Damewood, James R.; James Fikes; Ciaccio, Paul J.

    2012-01-01

    While phospholipidosis is thought to be an adaptive response to chemical challenge, many phospholipogenic compounds are known to display adverse effects in preclinical species and humans. To investigate the link between phospholipogenic administration and incidence of preclinical histological signals, an internal AstraZeneca in vivo toxicology report database was searched to identify phospholipogenic and nonphospholipogenic compounds. The datasets assembled comprised 46 phospholipogenic and 6...

  2. Evaluation of bone response to various anorganic bovine bone xenografts: an experimental calvaria defect study.

    Science.gov (United States)

    Tovar, N; Jimbo, R; Gangolli, R; Perez, L; Manne, L; Yoo, D; Lorenzoni, F; Witek, L; Coelho, P G

    2014-02-01

    This in vivo study investigated the in vivo performance of two newly developed synthetic bone substitutes and compared them to commercially available xenografts (Bio-Oss, Geistlich Pharma AG, Switzerland; OsteoGraf, Dentsply, USA). The materials were tested in a rabbit calvaria model, and the bone forming properties were observed at 4 and 8 weeks after implantation by means of histomorphometry and micro computed tomography (micro-CT). Defects without any graft material were used as negative controls. Micro-CT showed that all materials tested presented new bone formation that filled the defects at both time points, whereas the negative control presented less bone formation, with soft tissue infiltration into the defects. Comparable bone fill percentages were observed for histomorphometric and micro-CT results. Even though no statistically significant difference was found quantitatively between all of the bone graft substitute groups, a higher mean decrease in graft material filling the defects, along with higher remodelling activity, was evident for the experimental materials compared to the commercially available xenografts at 8 weeks. The results indicate that the experimental materials possess high degradability, along with osteoconduction comparable to commercially available xenografts. PMID:23948358

  3. Studies on bone scintigraphy in renal osteodystrophy

    International Nuclear Information System (INIS)

    Bone scintigraphy was superior over roentgenography for detection of abnormal bone findings in chronic dialysis patients. According to the type of scintigraphic findings, an increase in the hot area in the cranium or the mandibule seemed to express fibrous osteitis due to secondary hyperparathyroidism. Multiple coin-shaped hot areas in ribs were thought to indicate advanced osteomalacia or osteomalacia in patients with aluminum poisoning. The 4 hr-B/St ratio of the cranium was thought to serve as a quantitative indicator of the status of fibrous osteitis due to secondary hyperparathyroidism to show the progress and therapeutic course of the disease. (Chiba, N.)

  4. A comparative study of calcium sulfate artificial bone graft versus allograft in the reconstruction of bone defect after tumor curettage

    Institute of Scientific and Technical Information of China (English)

    Yang Yongkun; Niu Xiaohui; Zhang Qing; Hao Lin; Ding Yi; Xu Hairong

    2014-01-01

    Background Cavity reconstruction after benign bone tumor removal is varied and controversial.AIIograft is widely used but is associated with complications.New bone substitutes,such as calcium sulfate artificial bone,have been introduced for bone tumor operation.However,the bone healing response of artificial bone has not been compared with allograft bone.We therefore compared calcium sulfate grafts (study group) with bone allografts (control group) for the treatment of benign bone tumors.Methods We retrospectively reviewed 50 patients who underwent calcium sulfate reconstruction and 50 patients who underwent allograft cancellous bone reconstruction.The two groups were well matched.The mean follow-up time of the study group was 19.9 (12-55) months.We investigated bone healing response,complications,and factors affecting bone healing.Results At the last follow-up,84% (42/50) of cases in the study group and 62% (31/50) of cases in the control group had achieved clinical healing (P=0.013).The initial healing rate showed no significant difference between the two groups (100% vs.96%,P=0.153).The mean healing times for calcium sulfate and allograft bone were 9.6 (3-42) months and 13.8 (3-36) months,respectively (P <0.01).Complications in the study group were minor and resolved.Implant volume was a significant factor affecting bone healing.Conclusion The calcium sulfate bone substitute showed a satisfactory healing outcome and safety profile in reconstruction of bone defects after benign bone tumor curettage,especially in smaller cavities.

  5. Preclinical profile of cabazitaxel

    Directory of Open Access Journals (Sweden)

    Vrignaud P

    2014-10-01

    Full Text Available Patricia Vrignaud,1 Dorothée Semiond,2 Veronique Benning,2 Eric Beys,2 Hervé Bouchard,3 Sunil Gupta4 1Sanofi Oncology, Vitry-sur-Seine, France; 2Sanofi DSAR, Alfortville, France; 3Sanofi LGCR, Vitry-sur-Seine, France; 4Sanofi Oncology, Cambridge, MA, USA Abstract: First-generation taxanes have changed the treatment paradigm for a wide variety of cancers, but innate or acquired resistance frequently limits their use. Cabazitaxel is a novel second-generation taxane developed to overcome such resistance. In vitro, cabazitaxel showed similar antiproliferative activity to docetaxel in taxane-sensitive cell lines and markedly greater activity in cell lines resistant to taxanes. In vivo, cabazitaxel demonstrated excellent antitumor activity in a broad spectrum of docetaxel-sensitive tumor xenografts, including a castration-resistant prostate tumor xenograft, HID28, where cabazitaxel exhibited greater efficacy than docetaxel. Importantly, cabazitaxel was also active against tumors with innate or acquired resistance to docetaxel, suggesting therapeutic potential for patients progressing following taxane treatment and those with docetaxel-refractory tumors. In patients with tumors of the central nervous system (CNS, and in patients with pediatric tumors, therapeutic success with first-generation taxanes has been limited. Cabazitaxel demonstrated greater antitumor activity than docetaxel in xenograft models of CNS disease and pediatric tumors, suggesting potential clinical utility in these special patient populations. Based on therapeutic synergism observed in an in vivo tumor model, cabazitaxel is also being investigated clinically in combination with cisplatin. Nonclinical evaluation of the safety of cabazitaxel in a range of animal species showed largely reversible changes in the bone marrow, lymphoid system, gastrointestinal tract, and male reproductive system. Preclinical safety signals of cabazitaxel were consistent with the previously reported

  6. Anti-tumor activity of calcitriol: pre-clinical and clinical studies.

    Science.gov (United States)

    Trump, Donald L; Hershberger, Pamela A; Bernardi, Ronald J; Ahmed, Sharmilla; Muindi, Josephia; Fakih, Marwan; Yu, Wei-Dong; Johnson, Candace S

    2004-05-01

    1,25-Dihydroxycholecalciferol (calcitriol) is recognized widely for its effects on bone and mineral metabolism. Epidemiological data suggest that low Vitamin D levels may play a role in the genesis of prostate cancer and perhaps other tumors. Calcitriol is a potent anti-proliferative agent in a wide variety of malignant cell types. In prostate, breast, colorectal, head/neck and lung cancer as well as lymphoma, leukemia and myeloma model systems calcitriol has significant anti-tumor activity in vitro and in vivo. Calcitriol effects are associated with an increase in G0/G1 arrest, induction of apoptosis and differentiation, modulation of expression of growth factor receptors. Glucocorticoids potentiate the anti-tumor effect of calcitriol and decrease calcitriol-induced hypercalcemia. Calcitriol potentiates the antitumor effects of many cytotoxic agents and inhibits motility and invasiveness of tumor cells and formation of new blood vessels. Phase I and II trials of calcitriol either alone or in combination with carboplatin, taxanes or dexamethasone have been initiated in patients with androgen dependent and independent prostate cancer and advanced cancer. Data indicate that high-dose calcitriol is feasible on an intermittent schedule, no dose-limiting toxicity has been encountered and optimal dose and schedule are being delineated. Clinical responses have been seen with the combination of high dose calcitriol+dexamethasone in androgen independent prostate cancer (AIPC) and apparent potentiation of the antitumor effects of docetaxel have been seen in AIPC. These results demonstrate that high intermittent doses of calcitriol can be administered to patients without toxicity, that the MTD is yet to be determined and that calcitriol has potential as an anti-cancer agent. PMID:15225831

  7. Scanning acoustic microscopy study of human cortical and trabecular bone.

    Science.gov (United States)

    Bumrerraj, S; Katz, J L

    2001-12-01

    Scanning acoustic microscopy (SAM) has been used in the burst mode to study the properties of human cortical and trabecular bone. An Olympus UH3 SAM (Olympus Co., Tokyo, Japan) was used with a 400 MHz burst mode lens (120 degrees aperture, nominal lateral resolution 2.5 microm). The human cortical bone was from the midshaft of a femur from a 60+ male cadaver; the trabecular bone specimens were obtained from the distal femoral condyles of another 60+ human male cadaver. Elastic moduli for both trabecular and cortical bone were obtained by means of a series of calibration curves correlating SAM gray levels of known materials with their elastic moduli; specimens included: polypropylene, PMMA, Teflon, aluminum, Pyrex glass, titanium, and stainless steel. Values obtained by this method are in good agreement with those obtained by nanoindentation techniques. The three critical findings earlier by Katz and Meunier were observed here as well in both the cortical and trabecular bone samples. PMID:11853252

  8. Morphological Study of Wormian Bones in Dried Human Skulls

    Directory of Open Access Journals (Sweden)

    Divyesh Patel

    2015-09-01

    Full Text Available Background: Wormian bones may be defined as a those accidental bones found in the cranium having no regular relation to their normal ossification centre. They are assocated with cranial and central nervous system abnormalities. Knowledge of these bones is important for anthropo-logists, forensic experts, radiologists, orthopedic and neurosurgeons to avoid misleading for multiple fractures of the skull. Materials and Methods: Adult dry human skulls (n= 27 of unknown age and sex availablein the Department of Anatomy, Govt. Medical College, Surat were included in the study. Result: Overall incidence of wormian bone was 44.4%. They occurred more frequently at lambdoid suture (48.14%.Wormian bones were also presentat asterion (18.5%, along the coronal suture (0.03%, along the parito-temporal suture (0.07%, along the occipito-mastoid suture (0.03%,andat pterion (0.03 %. Wormain bones were found 48.1% on left half of skull and 37.03% on right half of skull. Conclusion: The Wormian bones were more frequent at the lambdoid suture. The clinical importances of these variant bones were emphasized with relevant review of literature. [Natl J Med Res 2015; 5(3.000: 222-225

  9. Bone defect animal models for testing efficacy of bone substitute biomaterials

    Directory of Open Access Journals (Sweden)

    Ye Li

    2015-07-01

    Full Text Available Large bone defects are serious complications that are most commonly caused by extensive trauma, tumour, infection, or congenital musculoskeletal disorders. If nonunion occurs, implantation for repairing bone defects with biomaterials developed as a defect filler, which can promote bone regeneration, is essential. In order to evaluate biomaterials to be developed as bone substitutes for bone defect repair, it is essential to establish clinically relevant in vitro and in vivo testing models for investigating their biocompatibility, mechanical properties, degradation, and interactional with culture medium or host tissues. The results of the in vitro experiment contribute significantly to the evaluation of direct cell response to the substitute biomaterial, and the in vivo tests constitute a step midway between in vitro tests and human clinical trials. Therefore, it is essential to develop or adopt a suitable in vivo bone defect animal model for testing bone substitutes for defect repair. This review aimed at introducing and discussing the most available and commonly used bone defect animal models for testing specific substitute biomaterials. Additionally, we reviewed surgical protocols for establishing relevant preclinical bone defect models with various animal species and the evaluation methodologies of the bone regeneration process after the implantation of bone substitute biomaterials. This review provides an important reference for preclinical studies in translational orthopaedics.

  10. Photodynamic therapy with the phthalocyanine photosensitizer Pc 4: The case experience with preclinical mechanistic and early clinical-translational studies

    International Nuclear Information System (INIS)

    Photodynamic therapy (PDT) is emerging as a promising non-invasive treatment for cancers. PDT involves either local or systemic administration of a photosensitizing drug, which preferentially localizes within the tumor, followed by illumination of the involved organ with light, usually from a laser source. Here, we provide a selective overview of our experience with PDT at Case Western Reserve University, specifically with the silicon phthalocyanine photosensitizer Pc 4. We first review our in vitro studies evaluating the mechanism of cell killing by Pc 4-PDT. Then we briefly describe our clinical experience in a Phase I trial of Pc 4-PDT and our preliminary translational studies evaluating the mechanisms behind tumor responses. Preclinical work identified (a) cardiolipin and the anti-apoptotic proteins Bcl-2 and Bcl-xL as targets of Pc 4-PDT, (b) the intrinsic pathway of apoptosis, with the key participation of caspase-3, as a central response of many human cancer cells to Pc 4-PDT, (c) signaling pathways that could modify apoptosis, and (d) a formulation by which Pc 4 could be applied topically to human skin and penetrate at least through the basal layer of the epidermis. Clinical-translational studies enabled us to develop an immunohistochemical assay for caspase-3 activation, using biopsies from patients treated with topical Pc 4 in a Phase I PDT trial for cutaneous T-cell lymphoma. Results suggest that this assay may be used as an early biomarker of clinical response

  11. Preclinical studies on [11C]TMSX for mapping adenosine A2A receptors by positron emission tomography

    International Nuclear Information System (INIS)

    In previous in vivo studies with mice, rats and monkeys, we have demonstrated that [11C]TMSX ([7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)- 1,3,7-trimethylxanthine) is a potential radioligand for mapping adenosine A2A receptors of the brain by positron emission tomography (PET). In the present study, we performed a preclinical study. A suitable preparation method for [11C]TMSX injection was established. The radiation absorbed-dose by [11C]TMSX in humans estimated from the tissue distribution in mice was low enough for clinical use, and the acute toxicity and mutagenicity of TMSX were not found. The striatal uptake of [11C]TMSX in mice was reduced by pretreatment with theophylline at the dose of 10 and 100 mg/kg, suggesting that the [11C]TMSX PET should be carefully performed in the patients received with theophylline. We have concluded that [11C]TMSX is suitable for mapping adenosine A2A receptors in the human brain by PET. (author)

  12. Does Bacillus anthracis Lethal Toxin Directly Depress Myocardial Function? A Review of Clinical Cases and Preclinical Studies.

    Science.gov (United States)

    Suffredini, Dante A; Sampath-Kumar, Hanish; Li, Yan; Ohanjanian, Lernik; Remy, Kenneth E; Cui, Xizhong; Eichacker, Peter Q

    2015-12-01

    The US outbreak of B.anthracis infection in 2001 and subsequent cases in the US and Europe demonstrate that anthrax is a continuing risk for the developed world. While several bacterial components contribute to the pathogenesis of B. anthracis, production of lethal toxin (LT) is strongly associated with the development of hypotension and lethality. However, the mechanisms underlying the cardiovascular instability LT produces are unclear. Some evidence suggests that LT causes shock by impairing the peripheral vasculature, effects consistent with the substantial extravasation of fluid in patients dying with B. anthracis. Other data suggests that LT directly depresses myocardial function. However a clinical correlate for this latter possibility is less evident since functional studies and post-mortem examination in patients demonstrate absent or minimal cardiac changes. The purposes of this review were to first present clinical studies of cardiac functional and histologic pathology with B. anthracis infection and to then examine in vivo, in vitro, and ex vivo preclinical studies of LT's myocardial effects. Together, these data suggest that it is unclear whether that LT directly depresses cardiac function. This question is important for the clinical management and development of new therapies for anthrax and efforts should continue to be made to answer it. PMID:26703730

  13. Does Bacillus anthracis Lethal Toxin Directly Depress Myocardial Function? A Review of Clinical Cases and Preclinical Studies

    Directory of Open Access Journals (Sweden)

    Dante A. Suffredini

    2015-12-01

    Full Text Available The US outbreak of B.anthracis infection in 2001 and subsequent cases in the US and Europe demonstrate that anthrax is a continuing risk for the developed world. While several bacterial components contribute to the pathogenesis of B. anthracis, production of lethal toxin (LT is strongly associated with the development of hypotension and lethality. However, the mechanisms underlying the cardiovascular instability LT produces are unclear. Some evidence suggests that LT causes shock by impairing the peripheral vasculature, effects consistent with the substantial extravasation of fluid in patients dying with B. anthracis. Other data suggests that LT directly depresses myocardial function. However a clinical correlate for this latter possibility is less evident since functional studies and post-mortem examination in patients demonstrate absent or minimal cardiac changes. The purposes of this review were to first present clinical studies of cardiac functional and histologic pathology with B. anthracis infection and to then examine in vivo, in vitro, and ex vivo preclinical studies of LT’s myocardial effects. Together, these data suggest that it is unclear whether that LT directly depresses cardiac function. This question is important for the clinical management and development of new therapies for anthrax and efforts should continue to be made to answer it.

  14. A prospective study of alcohol consumption and bone mineral density.

    OpenAIRE

    Holbrook, T L; Barrett-Connor, E.

    1993-01-01

    OBJECTIVES--To study the effects of alcohol consumption on bone mineral density in a defined population. DESIGN--Prospective study of bone mineral density, measured during 1988-91, in a cohort who had given baseline data on alcohol intake in the previous week and in the previous 24 hours and other factors affecting bone mineral density during 1973-5. SETTING--Rancho Bernardo, California. SUBJECTS--182 men and 267 women aged 45 and over at baseline, half having been randomly selected and half ...

  15. Synchrotron Study of Strontium in Modern and Ancient Human Bones

    Science.gov (United States)

    Pingitore, N. E.; Cruz-Jimenez, G.

    2001-05-01

    Archaeologists use the strontium in human bone to reconstruct diet and migration in ancient populations. Because mammals discriminate against strontium relative to calcium, carnivores show lower bone Sr/Ca ratios than herbivores. Thus, in a single population, bone Sr/Ca ratios can discriminate a meat-rich from a vegetarian diet. Also, the ratio of 87-Sr to 86-Sr in soils varies with the underlying geology; incorporated into the food chain, this local signature becomes embedded in our bones. The Sr isotopic ratio in the bones of individuals or populations which migrate to a different geologic terrane will gradually change as bone remodels. In contrast, the isotopic ratio of tooth enamel is fixed at an early age and is not altered later in life. Addition of Sr to bone during post-mortem residence in moist soil or sediment compromises application of the Sr/Ca or Sr-isotope techniques. If this post-mortem Sr resides in a different atomic environment than the Sr deposited in vivo, x-ray absorption spectroscopy could allow us to distinguish pristine from contaminated, and thus unreliable, samples. Initial examination of a suite of modern and ancient human and animal bones by extended x-ray absorption fine structure (EXAFS) showed no obvious differences between the fresh and buried materials. We note, with obvious concern, that the actual location of Sr in modern bone is controversial: there is evidence both that Sr substitutes for Ca and that Sr is sorbed on the surfaces of bone crystallites. Additional material is being studied.

  16. Common handling procedures conducted in preclinical safety studies result in minimal hepatic gene expression changes in Sprague-Dawley rats.

    Directory of Open Access Journals (Sweden)

    Yudong D He

    Full Text Available Gene expression profiling is a tool to gain mechanistic understanding of adverse effects in response to compound exposure. However, little is known about how the common handling procedures of experimental animals during a preclinical study alter baseline gene expression. We report gene expression changes in the livers of female Sprague-Dawley rats following common handling procedures. Baseline gene expression changes identified in this study provide insight on how these changes may affect interpretation of gene expression profiles following compound exposure. Rats were divided into three groups. One group was not subjected to handling procedures and served as controls for both handled groups. Animals in the other two groups were weighed, subjected to restraint in Broome restrainers, and administered water via oral gavage daily for 1 or 4 days with tail vein blood collections at 1, 2, 4, and 8 hours postdose on days 1 and 4. Significantly altered genes were identified in livers of animals following 1 or 4 days of handling when compared to the unhandled animals. Gene changes in animals handled for 4 days were similar to those handled for 1 day, suggesting a lack of habituation. The altered genes were primarily immune function related genes. These findings, along with a correlating increase in corticosterone levels suggest that common handling procedures may cause a minor immune system perturbance.

  17. Reform in Teaching Preclinical Pathophysiology

    Science.gov (United States)

    Li, Yong-Yu; Li, Kun; Yao, Hong; Xu, Xiao-Juan; Cai, Qiao-Lin

    2015-01-01

    Pathophysiology is a scientific discipline that studies the onset and progression of pathological conditions and diseases, and pathophysiology is one of the core courses in most preclinical medical curricula. In China, most medical schools house a Department of Pathophysiology, in contrast to medical schools in many developed countries. The staff…

  18. A review of treatment planning for precision image-guided photon beam pre-clinical animal radiation studies

    Energy Technology Data Exchange (ETDEWEB)

    Verhaegen, Frank; Hoof, Stefan van; Granton, Patrick V.; Trani, Daniela [Maastricht University Medical Center (Netherlands). Dept. of Radiation Oncology (MAASTRO)

    2014-07-01

    Recently, precision irradiators integrated with a high-resolution CT imaging device became available for pre-clinical studies. These research platforms offer significant advantages over older generations of animal irradiators in terms of precision and accuracy of image-guided radiation targeting. These platforms are expected to play a significant role in defining experiments that will allow translation of research findings to the human clinical setting. In the field of radiotherapy, but also others such as neurology, the platforms create unique opportunities to explore e.g. the synergy between radiation and drugs or other agents. To fully exploit the advantages of this new technology, accurate methods are needed to plan the irradiation and to calculate the three-dimensional radiation dose distribution in the specimen. To this end, dedicated treatment planning systems are needed. In this review we will discuss specific issues for precision irradiation of small animals, we will describe the workflow of animal treatment planning, and we will examine several dose calculation algorithms (factorization, superposition-convolution, Monte Carlo simulation) used for animal irradiation with kilovolt photon beams. Issues such as dose reporting methods, photon scatter, tissue segmentation and motion will also be discussed briefly.

  19. Re-evaluate the effect of hyperbaric oxygen therapy in cancer - a preclinical therapeutic small animal model study.

    Directory of Open Access Journals (Sweden)

    Sneha Pande

    Full Text Available Tumor hypoxia is a known driver of angiogenesis that also facilitates tumor growth. Moreover, poorly oxygenated central tumor area remains relatively radio or chemo resistant. HBO therapy is known to elevate the levels of dissolved oxygen and eliminates tumor hypoxia. It has been one of the modalities in cancer treatment; therefore its optimization is important. In this experimental study, no cancer enhancing effect was seen during the course of HBO therapy; however, post therapy there was an accelerated growth and progression of tumor. HBO treated mice lived shorter and the response to therapy was dose & tumor volume dependent. HBO therapy probably exert its effect on the cancer proliferating cells through multiple pathways such as increased DNA damage, apoptosis & geno-toxicity leading to slow cancer progression while post therapy tumorigenic effect could be due to impaired DNA repair mechanism, mutagenic effect & aneuploidy as well as altered blood supply & nutrients. Tumor growth reached plateau with time and this finding validated theoretical model predicting tumor reaching an asymptotic limit. While, marked asymmetry observed in tumor volume progression or cancer cell proliferation rate in each of the experimental C3H mouse suggested a need for an alternate small animal pre-clinical cancer therapeutic model.

  20. A review of treatment planning for precision image-guided photon beam pre-clinical animal radiation studies

    International Nuclear Information System (INIS)

    Recently, precision irradiators integrated with a high-resolution CT imaging device became available for pre-clinical studies. These research platforms offer significant advantages over older generations of animal irradiators in terms of precision and accuracy of image-guided radiation targeting. These platforms are expected to play a significant role in defining experiments that will allow translation of research findings to the human clinical setting. In the field of radiotherapy, but also others such as neurology, the platforms create unique opportunities to explore e.g. the synergy between radiation and drugs or other agents. To fully exploit the advantages of this new technology, accurate methods are needed to plan the irradiation and to calculate the three-dimensional radiation dose distribution in the specimen. To this end, dedicated treatment planning systems are needed. In this review we will discuss specific issues for precision irradiation of small animals, we will describe the workflow of animal treatment planning, and we will examine several dose calculation algorithms (factorization, superposition-convolution, Monte Carlo simulation) used for animal irradiation with kilovolt photon beams. Issues such as dose reporting methods, photon scatter, tissue segmentation and motion will also be discussed briefly.

  1. A review of treatment planning for precision image-guided photon beam pre-clinical animal radiation studies.

    Science.gov (United States)

    Verhaegen, Frank; van Hoof, Stefan; Granton, Patrick V; Trani, Daniela

    2014-12-01

    Recently, precision irradiators integrated with a high-resolution CT imaging device became available for pre-clinical studies. These research platforms offer significant advantages over older generations of animal irradiators in terms of precision and accuracy of image-guided radiation targeting. These platforms are expected to play a significant role in defining experiments that will allow translation of research findings to the human clinical setting. In the field of radiotherapy, but also others such as neurology, the platforms create unique opportunities to explore e.g. the synergy between radiation and drugs or other agents. To fully exploit the advantages of this new technology, accurate methods are needed to plan the irradiation and to calculate the three-dimensional radiation dose distribution in the specimen. To this end, dedicated treatment planning systems are needed. In this review we will discuss specific issues for precision irradiation of small animals, we will describe the workflow of animal treatment planning, and we will examine several dose calculation algorithms (factorization, superposition-convolution, Monte Carlo simulation) used for animal irradiation with kilovolt photon beams. Issues such as dose reporting methods, photon scatter, tissue segmentation and motion will also be discussed briefly. PMID:24629309

  2. Preclinical pharmacology and toxicology study of Ad-hTERT-E1a-Apoptin, a novel dual cancer-specific oncolytic adenovirus

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Yanxin [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122 (China); Guo, Huanhuan [Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122 (China); Changchun Brother Biotech Co., Ltd., Changchun, 130000 (China); Hu, Ningning; He, Dongyun [Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122 (China); The Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130122 (China); Zhang, Shi [Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122 (China); School of Clinical Medicine, Jilin University, Changchun 130001 (China); Chu, Yunjie [Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun 130021 (China); Huang, Yubin [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Li, Xiao, E-mail: lixiao06@mails.jlu.edu.cn [Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122 (China); The Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130122 (China); Sun, LiLi, E-mail: linjiaxiaoya@163.com [Department of Head and Neck Surgery, Tumor Hospital of Jilin Province, Changchun 130012 (China); Jin, Ningyi, E-mail: ningyij@126.com [Institute of Military Veterinary, Academy of Military Medical Sciences of PLA, Changchun 130122 (China); The Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130122 (China)

    2014-10-15

    Clinical studies have demonstrated that conditionally replicating adenovirus is safe. We constructed an oncolytic adenovirus, Ad-hTERT-E1a-Apoptin, using a cancer-specific promoter (human telomerase reverse transcriptase promoter, hTERTp) and a cancer cell-selective apoptosis-inducing gene (Apoptin). Ad-hTERT-E1a-Apoptin was proven effective both in vitro and in vivo in our previous study. In this study, the preclinical safety profiles of Ad-hTERT-E1a-Apoptin in animal models were investigated. At doses of 5.0 × 10{sup 8}, 2.5 × 10{sup 9}, and 1.25 × 10{sup 10} viral particles (VP)/kg, Ad-hTERT-E1a-Apoptin had no adverse effects on mouse behavior, muscle cooperation, sedative effect, digestive system, and nervous systems, or on beagle cardiovascular and respiratory systems at 5.0 × 10{sup 8}, 2.5 × 10{sup 9}, and 1.25 × 10{sup 10} VP/kg doses. In acute toxicity tests in mice, the maximum tolerated dose > 5 × 10{sup 10} VP/kg. There was no inflammation or ulceration at the injection sites within two weeks. In repeat-dose toxicological studies, the no observable adverse effect levels of Ad-hTERT-E1a-Apoptin in rats (1.25 × 10{sup 10} VP/kg) and beagles (2.5 × 10{sup 9} VP/kg) were 62.5- and 12.5-fold of the proposed clinical dose, respectively. The anti-virus antibody was produced in animal sera. Bone marrow examination revealed no histopathological changes. Guinea pigs sensitized by three repeated intraperitoneal injections of 1.35 × 10{sup 10} VP/mL Ad-hTERT-E1a-Apoptin each and challenged by one intravenous injection of 1.67 × 10{sup 8} VP/kg Ad-hTERT-E1a-Apoptin did not exhibit any sign of systemic anaphylaxis. Our data from different animal models suggest that Ad-hTERT-E1a-Apoptin is a safe anti-tumor therapeutic agent. - Highlights: • We use the rodents and non-rodents animal models to evaluation Ad-hTERT-E1a-Apoptin. • Ad-hTERT-E1a-Apoptin is a safe anti-tumor therapeutic agent. • Demonstrate the safety and feasibility dose of injected Ad

  3. Preclinical pharmacology and toxicology study of Ad-hTERT-E1a-Apoptin, a novel dual cancer-specific oncolytic adenovirus

    International Nuclear Information System (INIS)

    Clinical studies have demonstrated that conditionally replicating adenovirus is safe. We constructed an oncolytic adenovirus, Ad-hTERT-E1a-Apoptin, using a cancer-specific promoter (human telomerase reverse transcriptase promoter, hTERTp) and a cancer cell-selective apoptosis-inducing gene (Apoptin). Ad-hTERT-E1a-Apoptin was proven effective both in vitro and in vivo in our previous study. In this study, the preclinical safety profiles of Ad-hTERT-E1a-Apoptin in animal models were investigated. At doses of 5.0 × 108, 2.5 × 109, and 1.25 × 1010 viral particles (VP)/kg, Ad-hTERT-E1a-Apoptin had no adverse effects on mouse behavior, muscle cooperation, sedative effect, digestive system, and nervous systems, or on beagle cardiovascular and respiratory systems at 5.0 × 108, 2.5 × 109, and 1.25 × 1010 VP/kg doses. In acute toxicity tests in mice, the maximum tolerated dose > 5 × 1010 VP/kg. There was no inflammation or ulceration at the injection sites within two weeks. In repeat-dose toxicological studies, the no observable adverse effect levels of Ad-hTERT-E1a-Apoptin in rats (1.25 × 1010 VP/kg) and beagles (2.5 × 109 VP/kg) were 62.5- and 12.5-fold of the proposed clinical dose, respectively. The anti-virus antibody was produced in animal sera. Bone marrow examination revealed no histopathological changes. Guinea pigs sensitized by three repeated intraperitoneal injections of 1.35 × 1010 VP/mL Ad-hTERT-E1a-Apoptin each and challenged by one intravenous injection of 1.67 × 108 VP/kg Ad-hTERT-E1a-Apoptin did not exhibit any sign of systemic anaphylaxis. Our data from different animal models suggest that Ad-hTERT-E1a-Apoptin is a safe anti-tumor therapeutic agent. - Highlights: • We use the rodents and non-rodents animal models to evaluation Ad-hTERT-E1a-Apoptin. • Ad-hTERT-E1a-Apoptin is a safe anti-tumor therapeutic agent. • Demonstrate the safety and feasibility dose of injected Ad-hTERT-E1a-Apoptin

  4. A study of bone uptake according to renal function in the whole body bone scan

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Yong In; Jang, Dong Gun [Dept. of Nuclear Medicine, Dongnam Institute of Radiological and Medical Sciences Cancer Center, Busan (Korea, Republic of); Park, Cheol Woo [Dept. of Radiological Technology Dong-Eui Institute of Technology, Busan (Korea, Republic of)

    2013-12-15

    Whole body bone scan has been used to confirm bone metastasis and follow-up study with radio isotope. However, if the factors related to 99mTc uptake and waiting time for study are inappropriate, it would be image of low quality. The purpose of present study was to investigate correlation between the evaluation index of renal function and uptake of radiopharmaceuticals. The population for this retrospective study consisted of 387 patients who underwent whole body bone scan between June 2012 and December 2012. As a result of quantitative and qualitative analysis, we were able to confirm that GFR of less than normal range and creatinine levels in blood of more than average are more likely to be under the mean uptake rate. As a result of analysis on the indicator affecting soft-tissue and bone uptake, the correlation of all elements was somewhat low. Also there are no statistically significances due to the other parameters we did not deal with. Therefore, further research on additional factors is needed for exact study and improvement of the image quality.

  5. Correlating preclinical animal studies and human clinical trials of a multifunctional, polymeric nanoparticle

    OpenAIRE

    Eliasof, Scott; Lazarus, Douglas; Peters, Christian G.; Case, Roy I.; Cole, Roderic O.; Hwang, Jungyeon; Schluep, Thomas; Chao, Joseph; Lin, James; Yen, Yun; Han, Han; Wiley, Devin T.; Zuckerman, Jonathan E.; Davis, Mark E.

    2013-01-01

    Nanoparticles are currently being investigated in a number of human clinical trials. As information on how nanoparticles function in humans is difficult to obtain, animal studies that can be correlative to human behavior are needed to provide guidance for human clinical trials. Here, we report correlative studies on animals and humans for CRLX101, a 20- to 30-nm-diameter, multifunctional, polymeric nanoparticle containing camptothecin (CPT). CRLX101 is currently in phase 2 clinical trials, an...

  6. The role of orbitofrontal cortex in drug addiction: a review of preclinical studies

    OpenAIRE

    Schoenbaum, Geoffrey; Shaham, Yavin

    2007-01-01

    Studies using brain imaging methods have shown that neuronal activity in the orbitofrontal cortex, a brain area thought to promote the ability to control behavior according to likely outcomes or consequences, is altered in drug addicts. These human imaging findings have led to the hypothesis that core features of addiction like compulsive drug use and drug relapse are mediated in part by drug-induced changes in orbitofrontal function. Here, we discuss results from laboratory studies using rat...

  7. Comparative Study of Mechanical Stresses in Human Limb Bones

    OpenAIRE

    Doina Drăgulescu; Lucian Rusu; Vlad Morcovescu; Cris Precup

    2004-01-01

    This research studies the upper and lower limb bones of elderly persons. The measurements of compressive, tensile and bending forces were performed on 147 specimens: 72 in a compression trial, 21 in a tensile trial and 54 in a bending trial. Bones were extracted from 38 cadavers (60–70-years-old at the time of death). Experimental protocols were developed to minimise the possible errors in obtaining the data. All results were statistically processed. There was a significant difference between...

  8. X-ray microscopy study of bone mineralization

    International Nuclear Information System (INIS)

    Transmission spectro-microscopy around the calcium K-edge and fluorescence microscopy were performed respectively on the Transmission X-ray Microscope (TXM) and Scanning X-ray Microscope (SXM) end-stations of ID21 beamline at ESRF, to map the calcium distribution and the Ca/P ratio in bone samples. Preliminary results are presented. The motivation for these experiments is the study of the genetic determinism of bone mineralisation parameters in two different strains of mice

  9. Wound-Healing Potential of Cultured Epidermal Sheets Is Unaltered after Lyophilization: A Preclinical Study in Comparison to Cryopreserved CES

    Directory of Open Access Journals (Sweden)

    H. Jang

    2013-01-01

    Full Text Available Lyophilized Cultured Epidermal Sheets (L-CES have been reported to be as effective as the cryopreserved CES (F-CES in treating skin ulcers. However, unlike F-CES, no preclinical study assessing wound-healing effects has been conducted for L-CES. The present study was set out to investigate the microstructure, cytokine profile, and wound-healing effects of L-CES in comparison to those of F-CES. Keratinocytes were cultured to prepare CES, followed by cryopreservation at −70°C and lyophilization. Under microscopic observation, intact cells with apparent intracellular junctions were observed in L-CES. The L-CES, like fresh CES, consisted of three to four well-maintained epidermal layers, as shown by the expression of keratins, involucrin, and p63. There were no differences in the epidermal layer or protein expression between L-CES and F-CES, and both CES were comparable to fresh CES. TGF-α, EGF, VEGF, IL-1α, and MMPs were detected in L-CES at levels similar to those in F-CES. In a mouse study, wounds treated with L-CES or F-CES completely healed at least 4 days faster than untreated wounds. CES-treated wounds completely healed by day 10, while the untreated wounds did not heal by day 14. Masson’s trichrome staining showed that collagen deposition in the CES-treated wounds was highly increased in the dermis of the wound center compared to that in the control wounds. Thus, this study demonstrates that L-CES is as clinically effective as F-CES for wound treatment.

  10. A study of the traumatic bone cyst

    International Nuclear Information System (INIS)

    Traumatic bone cyst is a pathologic cavity that is not lined with epithelium. It is, therefore, not a true cyst. It may be a normal variant rather than a disease process. The etiology of the condition is unknown. This condition is occurred widely ranging ages(2 to 75 years), however, most are found during the second decade of life. Radiographically, this condition is radiolucent lesion with well-defined outline, scalloping of superior margins. Cyst enucleation and curettage is the treatment of choice. The authors compared and analyzed the clinicoradiologic features of the five cases of traumatic bone cyst, diagnosed at the Dental college hospital in Chosun University, Kwangju, Korea. The five cases were shown the followed results; 1. 3 cases occurred in second decade of life and no significant sex differences (M:F, 2:3) All cases occurred in mandible. 2. Two patients complained symptoms, but three cases had no symptom with encountering during routine examination. 3. In 3 of 5 cases, teeth vitality existed except one tooth and no checking of teeth vitality in two cases. 4. All cases didn't have any accurate trauma history, but one case was in orthodontic treatment, another case was postextraction site area. 5. Radiologically, 'scalloping appearance' were evident in all cases; in 3 cases, multilocular tendency and only one case seen intact mandibular canal image. 6. Histologically, all section showed bone trabeculae with ballistic activity, 2 cases showed no epithelial lining, and other 2 cases were seen inflammatory cell infiltration in edematous tissue. 7. Surgical intervention (curettage) was that treatment of choice.

  11. The tyrosine kinase inhibitor sunitinib affects ovulation but not ovarian reserve in mouse: A preclinical study

    NARCIS (Netherlands)

    V. Bernard (Valérie); J. Bouilly (Justine); P. Kramer (Piet); N. Carré (Nadège); M. Schlumberger (Martin); J.A. Visser (Jenny A.); J. Young (Jacques); N.B. Binart (Nadine Binart)

    2016-01-01

    textabstractThe aim of the study was to evaluate ovarian toxicity of tyrosine kinase inhibitor (TKI) sunitinib, since only scarce data are available on gonadal function after this treatment. Six-weekold female mice received orally, once daily, vehicle or sunitinib (50 mg/kg/d) during 5 weeks. Fertil

  12. The Usefulness of Systematic Reviews of Animal Experiments for the Design of Preclinical and Clinical Studies

    OpenAIRE

    de Vries, Rob B. M.; Wever, Kimberley E; Avey, Marc T.; Stephens, Martin L.; Sena, Emily S.; Leenaars, Marlies

    2014-01-01

    The question of how animal studies should be designed, conducted, and analyzed remains underexposed in societal debates on animal experimentation. This is not only a scientific but also a moral question. After all, if animal experiments are not appropriately designed, conducted, and analyzed, the results produced are unlikely to be reliable and the animals have in effect been wasted. In this article, we focus on one particular method to address this moral question, namely systematic reviews o...

  13. Validation of the Filovirus Plaque Assay for Use in Preclinical Studies

    Directory of Open Access Journals (Sweden)

    Amy C. Shurtleff

    2016-04-01

    Full Text Available A plaque assay for quantitating filoviruses in virus stocks, prepared viral challenge inocula and samples from research animals has recently been fully characterized and standardized for use across multiple institutions performing Biosafety Level 4 (BSL-4 studies. After standardization studies were completed, Good Laboratory Practices (GLP-compliant plaque assay method validation studies to demonstrate suitability for reliable and reproducible measurement of the Marburg Virus Angola (MARV variant and Ebola Virus Kikwit (EBOV variant commenced at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID. The validation parameters tested included accuracy, precision, linearity, robustness, stability of the virus stocks and system suitability. The MARV and EBOV assays were confirmed to be accurate to ±0.5 log10 PFU/mL. Repeatability precision, intermediate precision and reproducibility precision were sufficient to return viral titers with a coefficient of variation (%CV of ≤30%, deemed acceptable variation for a cell-based bioassay. Intraclass correlation statistical techniques for the evaluation of the assay’s precision when the same plaques were quantitated by two analysts returned values passing the acceptance criteria, indicating high agreement between analysts. The assay was shown to be accurate and specific when run on Nonhuman Primates (NHP serum and plasma samples diluted in plaque assay medium, with negligible matrix effects. Virus stocks demonstrated stability for freeze-thaw cycles typical of normal usage during assay retests. The results demonstrated that the EBOV and MARV plaque assays are accurate, precise and robust for filovirus titration in samples associated with the performance of GLP animal model studies.

  14. Validation of the Filovirus Plaque Assay for Use in Preclinical Studies.

    Science.gov (United States)

    Shurtleff, Amy C; Bloomfield, Holly A; Mort, Shannon; Orr, Steven A; Audet, Brian; Whitaker, Thomas; Richards, Michelle J; Bavari, Sina

    2016-01-01

    A plaque assay for quantitating filoviruses in virus stocks, prepared viral challenge inocula and samples from research animals has recently been fully characterized and standardized for use across multiple institutions performing Biosafety Level 4 (BSL-4) studies. After standardization studies were completed, Good Laboratory Practices (GLP)-compliant plaque assay method validation studies to demonstrate suitability for reliable and reproducible measurement of the Marburg Virus Angola (MARV) variant and Ebola Virus Kikwit (EBOV) variant commenced at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). The validation parameters tested included accuracy, precision, linearity, robustness, stability of the virus stocks and system suitability. The MARV and EBOV assays were confirmed to be accurate to ±0.5 log10 PFU/mL. Repeatability precision, intermediate precision and reproducibility precision were sufficient to return viral titers with a coefficient of variation (%CV) of ≤30%, deemed acceptable variation for a cell-based bioassay. Intraclass correlation statistical techniques for the evaluation of the assay's precision when the same plaques were quantitated by two analysts returned values passing the acceptance criteria, indicating high agreement between analysts. The assay was shown to be accurate and specific when run on Nonhuman Primates (NHP) serum and plasma samples diluted in plaque assay medium, with negligible matrix effects. Virus stocks demonstrated stability for freeze-thaw cycles typical of normal usage during assay retests. The results demonstrated that the EBOV and MARV plaque assays are accurate, precise and robust for filovirus titration in samples associated with the performance of GLP animal model studies. PMID:27110807

  15. Mesenchymal stem cell therapy for salivary gland dysfunction and xerostomia: a systematic review of preclinical studies

    DEFF Research Database (Denmark)

    Jensen, David Hebbelstrup; Oliveri, Roberto Stefan; Trojahn-Kølle, Stig-Frederik;

    2014-01-01

    was to assess, through systematic review, the potential benefit of mesenchymal stem cell (MSC) therapy in radiation-induced and SS-related salivary gland dysfunction and xerostomia. We searched PubMed/MEDLINE, Embase, Web of Science, the Cochrane Database of Systematic Reviews, the World Health Organization...... gland dysfunction and xerostomia. Nonetheless, the preliminary studies identified in the present review were encouraging for further research....

  16. Masitinib Antagonizes ATP-Binding Cassette Subfamily C Member 10-Mediated Paclitaxel Resistance: A Preclinical Study

    OpenAIRE

    Kathawala, Rishil J; Sodani, Kamlesh; Chen, Kang; PATEL, ATISH; Abuznait, Alaa H.; Anreddy, Nagaraju; Sun, Yue-Li; Kaddoumi, Amal; Ashby, Charles R.; Chen, Zhe-Sheng

    2014-01-01

    Paclitaxel displays clinical activity against a wide variety of solid tumors. However, resistance to paclitaxel significantly attenuates the response to chemotherapy. The ABC transporter subfamily C member 10 (ABCC10), also known as multi-drug resistance protein 7 (MRP7) efflux transporter, is a major mediator of paclitaxel resistance. In this study, we show that masitinib, a small molecule stem-cell growth factor receptor (c-Kit) tyrosine kinase inhibitor, at non-toxic concentrations, signif...

  17. Choosing preclinical study models of diabetic retinopathy: key problems for consideration

    Directory of Open Access Journals (Sweden)

    Mi XS

    2014-11-01

    Full Text Available Xue-Song Mi,1,2 Ti-Fei Yuan,3,4 Yong Ding,1 Jing-Xiang Zhong,1 Kwok-Fai So4,5 1Department of Ophthalmology, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People’s Republic of China; 3School of Psychology, Nanjing Normal University, Nanjing, People’s Republic of China; 4Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong; 5Guangdong-Hongkong-Macau Institute of Central Nervous System, Jinan University, Guangzhou, People’s Republic of China Abstract: Diabetic retinopathy (DR is the most common complication of diabetes mellitus in the eye. Although the clinical treatment for DR has already developed to a relative high level, there are still many urgent problems that need to be investigated in clinical and basic science. Currently, many in vivo animal models and in vitro culture systems have been applied to solve these problems. Many approaches have also been used to establish different DR models. However, till now, there has not been a single study model that can clearly and exactly mimic the developmental process of the human DR. Choosing the suitable model is important, not only for achieving our research goals smoothly, but also, to better match with different experimental proposals in the study. In this review, key problems for consideration in choosing study models of DR are discussed. These problems relate to clinical relevance, different approaches for establishing models, and choice of different species of animals as well as of the specific in vitro culture systems. Attending to these considerations will deepen the understanding on current study models and optimize the experimental design for the final goal of preventing DR. Keywords: animal model, in vitro culture, ex vivo culture, neurovascular dysfunction

  18. Preclinical Magnetic Resonance Imaging and Spectroscopy Studies of Memory, Aging, and Cognitive Decline

    Science.gov (United States)

    Febo, Marcelo; Foster, Thomas C.

    2016-01-01

    Neuroimaging provides for non-invasive evaluation of brain structure and activity and has been employed to suggest possible mechanisms for cognitive aging in humans. However, these imaging procedures have limits in terms of defining cellular and molecular mechanisms. In contrast, investigations of cognitive aging in animal models have mostly utilized techniques that have offered insight on synaptic, cellular, genetic, and epigenetic mechanisms affecting memory. Studies employing magnetic resonance imaging and spectroscopy (MRI and MRS, respectively) in animal models have emerged as an integrative set of techniques bridging localized cellular/molecular phenomenon and broader in vivo neural network alterations. MRI methods are remarkably suited to longitudinal tracking of cognitive function over extended periods permitting examination of the trajectory of structural or activity related changes. Combined with molecular and electrophysiological tools to selectively drive activity within specific brain regions, recent studies have begun to unlock the meaning of fMRI signals in terms of the role of neural plasticity and types of neural activity that generate the signals. The techniques provide a unique opportunity to causally determine how memory-relevant synaptic activity is processed and how memories may be distributed or reconsolidated over time. The present review summarizes research employing animal MRI and MRS in the study of brain function, structure, and biochemistry, with a particular focus on age-related cognitive decline.

  19. Issues in pharmaceutical development of thymosin alpha1 from preclinical studies through marketing.

    Science.gov (United States)

    Tuthill, Cynthia

    2007-09-01

    SciClone Pharmaceuticals licensed the commercial and patent rights to thymosin alpha1, for geographical regions of the world excluding the United States and Europe, in the early 1990s. With this license, SciClone embarked on global drug development, and the issues encountered for thymosin alpha1 are reflective of the roller coaster of modern approval of pharmaceuticals. Most of the required toxicology studies had been completed prior to licensure, but some newer studies had to be conducted to obtain approvals in certain countries. The recent development of the "International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use" (ICH) guidelines allows for a clearer definition of the required battery of toxicology studies, although some countries still have not adopted these guidelines, and the local regulations have had to be understood and followed. Other hurdles include the complications that manufacturing requirements can differ between countries, and certain countries require local clinical experience trials in addition to SciClone's cumulative clinical data. A further obstacle was the pleiotropic nature of the mechanism of action of thymosin alpha1, with the resulting difficulty in the unraveling of its pharmacologic effects. With close attention to these regulatory details, SciClone has obtained approvals in more than 30 countries and has successfully begun commercial sales. PMID:17947591

  20. Radiosynthesis, evaluation and preclinical studies of a new 5HT2A radioligand

    International Nuclear Information System (INIS)

    123I-5-I-R91150, a radioiodinated analogue of R91150 (a ligand (antagonist) of Janssen Research Foundation), showing high affinity and selectivity for 5HT2A receptors, was developed as a potential in vivo 5HT2A receptor tracer for SPECT. The applied radiochemistry, whereby the radioiodine was substituted on the 5 - position of the benzamide ring, allowed to obtain the tracer with high specific activity and high purity. In vitro and in vivo rat studies revealed that the new tracer bound reversibly with the required high affinity (Kd=0.1 nM) and high selectivity (a factor ranging from 10000 to at least 50 vis a vis other receptors) to 5HT2A receptors. In young normal subjects the major part of the 123I-5-I-R91150 radioactivity in the brain is present in cortical areas. Cortical area to cerebellum activity ratio reaches an equilibrium value of about 1.8 around 90 min. till 4 hours p.i.. This binding was specific and reversible. The cortical activity reflects a distribution in the brain similar to that of the mapping of 5HT2A receptors from post mortem studies. These findings suggested that 123I-5-I-R91150 allows imaging and quantitative estimation with SPECT and could be used for further clinical studies. The radiobromine analogue was synthetised as a potential PET tracer. (author)

  1. Quality of Reporting and Adherence to ARRIVE Guidelines in Animal Studies for Chagas Disease Preclinical Drug Research: A Systematic Review.

    Science.gov (United States)

    Gulin, Julián Ernesto Nicolás; Rocco, Daniela Marisa; García-Bournissen, Facundo

    2015-11-01

    Publication of accurate and detailed descriptions of methods in research articles involving animals is essential for health scientists to accurately interpret published data, evaluate results and replicate findings. Inadequate reporting of key aspects of experimental design may reduce the impact of studies and could act as a barrier to translation of research findings. Reporting of animal use must be as comprehensive as possible in order to take advantage of every study and every animal used. Animal models are essential to understanding and assessing new chemotherapy candidates for Chagas disease pathology, a widespread parasitic disease with few treatment options currently available. A systematic review was carried out to compare ARRIVE guidelines recommendations with information provided in publications of preclinical studies for new anti-Trypanosoma cruzi compounds. A total of 83 publications were reviewed. Before ARRIVE guidelines, 69% of publications failed to report any macroenvironment information, compared to 57% after ARRIVE publication. Similar proportions were observed when evaluating reporting of microenvironmental information (56% vs. 61%). Also, before ARRIVE guidelines publication, only 13% of papers described animal gender, only 18% specified microbiological status and 13% reported randomized treatment assignment, among other essential information missing or incomplete. Unfortunately, publication of ARRIVE guidelines did not seem to enhance reporting quality, compared to papers appeared before ARRIVE publication. Our results suggest that there is a strong need for the scientific community to improve animal use description, animal models employed, transparent reporting and experiment design to facilitate its transfer and application to the affected human population. Full compliance with ARRIVE guidelines, or similar animal research reporting guidelines, would be an excellent start in this direction. PMID:26587586

  2. Quality of Reporting and Adherence to ARRIVE Guidelines in Animal Studies for Chagas Disease Preclinical Drug Research: A Systematic Review.

    Directory of Open Access Journals (Sweden)

    Julián Ernesto Nicolás Gulin

    2015-11-01

    Full Text Available Publication of accurate and detailed descriptions of methods in research articles involving animals is essential for health scientists to accurately interpret published data, evaluate results and replicate findings. Inadequate reporting of key aspects of experimental design may reduce the impact of studies and could act as a barrier to translation of research findings. Reporting of animal use must be as comprehensive as possible in order to take advantage of every study and every animal used. Animal models are essential to understanding and assessing new chemotherapy candidates for Chagas disease pathology, a widespread parasitic disease with few treatment options currently available. A systematic review was carried out to compare ARRIVE guidelines recommendations with information provided in publications of preclinical studies for new anti-Trypanosoma cruzi compounds. A total of 83 publications were reviewed. Before ARRIVE guidelines, 69% of publications failed to report any macroenvironment information, compared to 57% after ARRIVE publication. Similar proportions were observed when evaluating reporting of microenvironmental information (56% vs. 61%. Also, before ARRIVE guidelines publication, only 13% of papers described animal gender, only 18% specified microbiological status and 13% reported randomized treatment assignment, among other essential information missing or incomplete. Unfortunately, publication of ARRIVE guidelines did not seem to enhance reporting quality, compared to papers appeared before ARRIVE publication. Our results suggest that there is a strong need for the scientific community to improve animal use description, animal models employed, transparent reporting and experiment design to facilitate its transfer and application to the affected human population. Full compliance with ARRIVE guidelines, or similar animal research reporting guidelines, would be an excellent start in this direction.

  3. Efficient vitreolysis by combining plasmin and sulfur hexafluoride injection in a preclinical study in rabbit eyes

    OpenAIRE

    Wu, Wei-Chi; Liu, Chi-Hsien; Chen, Chih-Chun; Wang, Nan-Kai; Chen, Kwan-Jen; Chen, Tun-Lu; Hwang, Yih-Shiou; Li, Lien-Min; Lai, Chi-Chun

    2012-01-01

    Purpose To investigate the efficacy of plasmin and sulfur hexafluoride (SF6) on the vitreoretinal junction, as well as the long-term safety in the eye and effect on the recipient’s general health after application in the eye. Methods The study design included four groups of rabbits with three animals in each group. Group 1 received an intravitreal injection (IVI) of plasmin and SF6 in the right eye; group 2 received an IVI of plasmin in the right eye; group 3 received an IVI of SF6 in the rig...

  4. Isolated Liver and Limb Perfusion in Preclinical and Clinical Studies: gene therapy and biochemotherapeutic strategies

    OpenAIRE

    Etten, Boudewijn

    2004-01-01

    markdownabstract__Abstract__ The liver is the major site of metastatic spread of primary colorectal cancer, whereas 3% of all patients with colorectal cancer will develop resectable liver metastases. If a resection with curative intent is done, a five year survival rate of 25-30% has been demonstrated in a large number of studies. The natural history of untreated patients with comparable liver involvement shows a five year survival rate of 0-3% (8). As noted above, the majority of patients wi...

  5. A Preclinical Study of the Safety and Efficacy of Occlusin™ 500 Artificial Embolization Device in Sheep

    International Nuclear Information System (INIS)

    Introduction: This study evaluated the safety, effectiveness, and biodegradation of a new embolic agent, Occlusin™ 503 Artificial Embolization Device (OCL 503). The agent consists of biodegradable poly-lactic-co-glycolic acid microspheres (150–212 μm) coated with type I bovine collagen and was compared with Embosphere® Microspheres (300–500 μm) in this controlled study of uterine artery embolization (UAE) in sheep. Methods: Unilateral UAE was performed in 32 adult ewes randomly assigned. Vessels were embolized to effective stasis. The cohort was divided into four groups, which were sacrificed at 1, 3, 6, and 12 months. Results: Both agents were 100% effective in achieving stasis. At 6 months, all OCL 503-treated arteries were occluded, the microspheres degraded with time, and at 12 months all four animals examined demonstrated recanalization. OCL 503 was found in the untreated uterine artery in one animal with no other evidence of non target embolization. In the Embosphere-treated group, all vessels remained occluded and microspheres were detected in the contralateral uterine artery in 6 of 15 examined vessels and in 10 vaginal, 2 ovarian, and 1 vesical artery. No procedural-related complications were seen in either group. Conclusions: OCL 503 is as effective an embolic agent as Embosphere® Microspheres when embolizing ovine uterine arteries and resorbs with time, allowing recanalization of the treated arteries. No device-related issues or adverse events were observed.

  6. Preclinical study of dopamine D2 receptor imaging agent 131I-epidepride

    International Nuclear Information System (INIS)

    Objective: To study the radioactivity distribution and the characteristic of imaging with dopamine D2 receptor imaging agent-epidepride. Methods: 131I-epidepride was prepared using hydrogen peroxide as the oxidant. The authors chose SD rats to study the characteristics of 131I-epidepride distribution in vivo and in brain. Two rabbits were used in SPECT imaging. Dynamic acquisition was performed in one rabbit after rapid injection of 370 MBq 131I-epidepride, and time-activity curve was obtained with Region of Interesting (ROI) technique. The other rabbit had brain tomography imaging and whole body imaging according to the result of time-activity curve. Results: The radiolabeling yield (RLY) of 131I-epidepride with hydrogen peroxide was over 95%. In vivo, the uptake of heart and lung was the fastest, so was the clearance of the two organs. The clearance of 131I-epidepride from the body was mainly through liver, stomach and intestines. The striatum uptake was concentrated and stable, while the cerebellum clearance was rapid. Conclusion: The hydrogen peroxide method is simple and fast with high RLY. The striatum uptake is concentrated and stable. 131I-epidepride is an effective agent suitable for dopamine D2 receptor imaging and may be a promising agent for clinical application

  7. Modulation of radiation-induced oral mucositis by pentoxifylline: Preclinical studies

    International Nuclear Information System (INIS)

    Oral mucositis is a frequent early side effect of radio(chemo)therapy of head-and-neck malignancies. The epithelial radiation response is accompanied by inflammatory reactions; their interaction with epithelial processes remains unclear. The aim of the present study was to investigate the effect of pentoxifylline (PTX) on the oral mucosal radiation response in the mouse tongue model. Irradiation comprised fractionation (5 fractions of 3 Gy/week) over 1 (days 0-4) or 2 weeks (days 0-4, 7-11), followed by graded local top-up doses (day 7/14), in order to generate complete dose-effect curves. PTX (15 mg/kg subcutaneously) was applied once daily over varying time intervals. Ulceration of mouse tongue epithelium, corresponding to confluent mucositis, was analyzed as the clinically relevant endpoint. With fractionated irradiation over 1 week, PTX administration significantly reduced the incidence of mucosal reactions when initiated before (day - 5) the onset of fractionation; a trend was observed for start of PTX treatment on day 0. Similarly, PTX treatment combined with 2 weeks of fractionation had a significant effect on ulcer incidence in all but one experiment. This clearly illustrates the potential of PTX to ameliorate oral mucositis during daily fractionated irradiation. PTX resulted in a significant reduction of oral mucositis during fractionated irradiation, which may be attributed to stimulation of mucosal repopulation processes. The biological basis of this effect, however, needs to be clarified in further, detailed mechanistic studies. (orig.)

  8. Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis.

    Science.gov (United States)

    Cunha-Júnior, Edézio Ferreira; Martins, Thiago Martino; Canto-Cavalheiro, Marilene Marcuzzo; Marques, Paulo Roberto; Portari, Elyzabeth Avvad; Coelho, Marsen Garcia Pinto; Netto, Chaquip Daher; Costa, Paulo Roberto Ribeiro; Sabino, Katia Costa de Carvalho; Torres-Santos, Eduardo Caio

    2016-06-01

    Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and anti-leukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg/kg of body weight/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. An in vivo toxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis. PMID:27067332

  9. Curcumin nanoformulations : A review of pharmaceutical properties and preclinical studies and clinical data related to cancer treatment

    NARCIS (Netherlands)

    Naksuriya, Ornchuma; Okonogi, Siriporn; Schiffelers, Raymond M.; Hennink, Wim E.

    2014-01-01

    Curcumin, a natural yellow phenolic compound, is present in many kinds of herbs, particularly in Curcuma longa Linn. (turmeric). It is a natural antioxidant and has shown many pharmacological activities such as anti-inflammatory, anti-microbial, anti-cancer, and anti-Alzheimer in both preclinical an

  10. Quantitative bone scintigraphy. A study in patients with prostatic carcinoma

    International Nuclear Information System (INIS)

    Quantitative bone scintigraphy was performed in patients with prostatic carcinoma before orchiectomy as well as two weeks, two and six months after operation. The count rate was recorded as serial gamma camera images over the lower thoracic and all lumbar vertebrae from 1 to 240 min and at 24 h after injection of 99Tcm-MDP. In almost all abnormal vertebrae an increased count rate was observed within one hour after injection. Most of the vertebrae which were considered normal at 4 h after injection, but had an increased 24h/4h ratio developed into abnormal vertebrae later in the study. The patients with normal bone scintigrams showed no change in 99Tcm-MDP uptake during the study. The reproducibility of quantitative bone scintigraphy was found to be ± 7% (1 SD). In response to therapy, most of the patients with abnormal bone scintigrams showed an increase in count rate two weeks after operation followed by a decrease to the pre-operative level after two months and a further decrease after six months. This so called 'flare phenomenon' was found to indicate 99Tcm-MDP in the vascular phase as well as an active bone uptake. In some of the patients the whole-body retention of 99Tcm-MDP after 24 h and the bone mineral density in the vertebrae were determined and found to be valuable in the interpretation of skeletal metastases and the assessment of response to therapy. (71 refs.)

  11. Systematic Approach to Remediation in Basic Science Knowledge for Preclinical Students: A case study

    Science.gov (United States)

    Amara, Francis

    Remediation of pre-clerkship students for deficits in basic science knowledge should help them overcome their learning deficiencies prior to clerkship. However, very little is known about remediation in basic science knowledge during pre-clerkship. This study utilized the program theory framework to collect and organize mixed methods data of the remediation plan for pre-clerkship students who failed their basic science cognitive examinations in a Canadian medical school. This plan was analyzed using a logic model narrative approach and compared to literature on the learning theories. The analysis showed a remediation plan that was strong on governance and verification of scores, but lacked: clarity and transparency of communication, qualified remedial tutors, individualized diagnosis of learner's deficits, and student centered learning. Participants admitted uncertainty about the efficacy of the remediation process. A remediation framework is proposed that includes student-centered participation, individualized learning plan and activities, deliberate practice, feedback, reflection, and rigorous reassessment.

  12. Solitaire FR revascularization device 4×40: safety study and effectiveness in preclinical models.

    Science.gov (United States)

    Wainwright, John Michael; Jahan, Reza

    2016-07-01

    Recent randomized clinical trials have shown the benefit of stent retrievers for endovascular intervention in patients with acute ischemic stroke. The Solitaire 2 FR 4×40 device was developed to address longer clots as well as procedural difficulties. This study was undertaken to evaluate the safety of the new device in a swine model at 0, 30, and 90 days as well as its in vitro effectiveness. There were no significant differences in the overall animal health, tissue injury, hemorrhagic or thrombogenic events related to device usage. Based on the comparison at multiple time points, the Solitaire 2 4×40 device was similar in safety and usability to the Solitaire 2 4×20 device. Due to the additional length of the device, the Solitaire 2 4×40 device may in fact provide a number of additional technical benefits in the neurothrombectomy treatment of ischemic stroke. PMID:26101268

  13. Sensitization of prostate cancer to ionizing radiation by targeting poly(ADP-robose) polymerase: preclinical studies

    International Nuclear Information System (INIS)

    Poly(ADP-ribose) polymerase (PARP) is a DNA-binding enzyme which plays important roles in the maintenance of genome stability, immediate cellular responses to DNA damage, and apoptosis. A DNA-binding domain of PARP (PARP-DBD) acts as a dominant-negative mutant by binding to DNA strand breaks irreversibly and sensitizing mammalian cells to DNA-damaging agents (1, 2). To direct the expression of human PARP-DBD to prostate we developed recombinant plasmids expressing the PARP-DBD under the control of the 5'-flanking sequences of the human prostate-specific antigen (PSA) gene. In vitro studies revealed that PSA promoter driven expression of the PARP-DBD showed prostate tissue specificity and androgen responsiveness and sensitized LNCaP cells to DNA-damaging agents, such as ionizing radiation and etoposide (3). To assess the efficiency of this strategy in vivo, we developed a cationic liposome-mediated gene delivery of PARP-DBD plasmid in tumor xenografts of PSA producing and androgen sensitive prostate cancer cells (LNCaP and 22Rv1). Tumor bearing mice were treated with intratumoral liposome-complexed PARP-DBD (LE-PARP-DBD), ionizing radiation (IR) or a combination of LE-PARP-DBD and IR. Control groups received blank liposomes or were left untreated. Administration of LE-PARP-DBD resulted in expression of dominant-negative mutant of PARP in tumor cells and enhanced radiation-induced inhibition of tumor growth. These results provide a proof-of- principle for a novel therapeutic strategy to control prostate cancer. The study was supported in part by grants from the U.S. Army Medical Research and Development Command DAMD 17-00-1-0019 and DAMD 17-00-1-0276 (to V.S.). (1) J.Biol.Chem., 265:18721-18724, 1990; (2) Cancer Research, 58: 3495-3498, 1998; (3) Cancer Research, 62: 6879-6883, 2002

  14. Pre-clinical validation of a vaginal cream containing copaiba oil (reproductive toxicology study).

    Science.gov (United States)

    Lima, C S; de Medeiros, B J L; Favacho, H A S; dos Santos, K C; de Oliveira, B R; Taglialegna, J C; da Costa, E V M; de Campos, K J; Carvalho, J C T

    2011-09-15

    The aims of this study was to evaluate the effects of oil-resin of Copaiba (Copaifera duckei Dwyer), aired in vaginal cream on the reproductive performance of female rats (Rattus norvegicus). To determine the components of the C. duckei oleoresin, gas chromatography coupled with mass spectrometry (CG-MS) was used, and considering the trans-caryophyllene sesquiterpene as a phytochemical marker in the oleoresin. Due to the extensive use of copaiba oleoresin in the suppository form for gynecological infections, an evaluation was carried out on the effects of copaiba oleoresin (Copaifera duckei Dwyer), delivered in a vaginal cream, on the reproductive performance of female Wistar rats. For this purpose, three groups (n=5-6/group) of female rats were treated as follows: 1--vaginal cream of copaiba oleoresin (28.6 mg/kg), 2--base vaginal cream and 3--control (physiological saline 0.9%), administered intravaginally, for 30 days before pregnancy, and from day zero to day 20 during pregnancy. Laparotomy was performed on the 21st day of pregnancy, followed by the determination of reproductive variables: number of live and dead fetuses, mass of the fetuses and placentas, number of implantations and resorptions, number of corpora lutea, pre- and post-implantation loss, and analyses of the fetuses with regard to external and internal anomalies and/or malformations (skeletal and visceral). The trans-caryophyllene present in the sample is suggested as a phytochemical marker and the results of this study demonstrate an absence of maternal toxicity and foetotoxicity embryofoetotoxicity at the dose administered, corresponding to ten times the recommended dose for use in humans. Accordingly, no significant statistical difference was observed between the treated and control groups, for the variables analyzed. Thus, it is concluded that the vaginal cream containing 2.5% copaiba oleoresin is safe during gestation, in female rats (Rattus norvegicus) of the Wistar strain. PMID:21665449

  15. A Selective Nociceptin Receptor Antagonist to Treat Depression: Evidence from Preclinical and Clinical Studies.

    Science.gov (United States)

    Post, Anke; Smart, Trevor S; Krikke-Workel, Judith; Dawson, Gerard R; Harmer, Catherine J; Browning, Michael; Jackson, Kimberley; Kakar, Rishi; Mohs, Richard; Statnick, Michael; Wafford, Keith; McCarthy, Andrew; Barth, Vanessa; Witkin, Jeffrey M

    2016-06-01

    Nociceptin/Orphanin FQ (N/OFQ) is an endogenous ligand of the N/OFQ peptide (NOP) receptor, which is a G protein-coupled receptor in brain regions associated with mood disorders. We used a novel, potent, and selective orally bioavailable antagonist, LY2940094, to test the hypothesis that blockade of NOP receptors would induce antidepressant effects. In this study we demonstrate that targeting NOP receptors with LY2940094 translates to antidepressant-like effects in rodent models and, importantly, to antidepressant efficacy in patients with major depressive disorder (MDD). The proof-of-concept study (POC) was an 8-week, double-blind, placebo-controlled trial that evaluated LY2940094 as a novel oral medication for the treatment of patients with MDD. Once daily oral dosing of LY2940094 at 40 mg for 8 weeks vs placebo provided some evidence for an antidepressant effect based on the change from baseline to week 8 in the GRID-Hamilton Depression Rating Scale-17 item total score, although the predefined POC efficacy criterion (probability of LY2940094 being better than placebo⩾88%) was not met (82.9%). LY2940094 also had an early effect on the processing of emotional stimuli at Week 1 as shown by an increased recognition of positive relative to negative facial expressions in an emotional test battery. LY2940094 was safe and well tolerated. Overall, these are the first human data providing evidence that the blockade of NOP receptor signaling represents a promising strategy for the treatment of MDD. PMID:26585287

  16. The preclinical pharmacological study of dopamine transporter imaging agent 18F-FP-β-CIT

    Institute of Scientific and Technical Information of China (English)

    LI Xiaomin; CHEN Zhengping; WANG Songpei; TANG Jie; LIN Yansong; ZHU Zhaohui; FANG Ping

    2007-01-01

    The paper is to study pharmacologic characteristics of 18F-FP-β-CIT (18F-N-(3-fluoropropyl)-2β- carbomethoxy-3β- (4-iodophenyl)nortropane) as an imaging agent for dopamine transporter. The radiochemical purity of 18F-FP-β-CIT in aqueous solution was over 95% after standing at room temperature for 4h. Biodistribution displayed rapid uptake in rat brain (1.375 %ID/organ at 5min and 0.100 %ID/organ at 180 min) and the striatal uptake was 1.444,0.731, 0.397, 0.230 and 0.146 %ID/g at 5, 30, 60, 120 and 180 min, respectively. The values of striatum/cerebellum,striatum/frontal cortex and striatum / hippocampus in rat's brain at 30 min were 3.38, 2.17 and 2.40 respectively. The uptake in striatum can be blocked by β-CFT, suggesting that 18F-FP-β-CIT binds to DAT peculiarly. The compound was rapidly cleared from monkey's blood. The striatal uptake was bilaterally decreased in the left-sided lesioned PD rats, compared with normal control. Brain PET imaging studies in normal monkey showed that 18F-FP-β-CIT was concentrated in striatum. The test of undue toxicity showed that the dose received by mice was 1250 times as by human, which indicates that 18F-FP-β-CIT is very safe. So 18F-FP-β-CIT is a promising PET imaging agent for DAT with safety and validity.

  17. Virtual reality, augmented reality, and robotics applied to digestive operative procedures: from in vivo animal preclinical studies to clinical use

    Science.gov (United States)

    Soler, Luc; Marescaux, Jacques

    2006-04-01

    Technological innovations of the 20 th century provided medicine and surgery with new tools, among which virtual reality and robotics belong to the most revolutionary ones. Our work aims at setting up new techniques for detection, 3D delineation and 4D time follow-up of small abdominal lesions from standard mecial images (CT scsan, MRI). It also aims at developing innovative systems making tumor resection or treatment easier with the use of augmented reality and robotized systems, increasing gesture precision. It also permits a realtime great distance connection between practitioners so they can share a same 3D reconstructed patient and interact on a same patient, virtually before the intervention and for real during the surgical procedure thanks to a telesurgical robot. In preclinical studies, our first results obtained from a micro-CT scanner show that these technologies provide an efficient and precise 3D modeling of anatomical and pathological structures of rats and mice. In clinical studies, our first results show the possibility to improve the therapeutic choice thanks to a better detection and and representation of the patient before performing the surgical gesture. They also show the efficiency of augmented reality that provides virtual transparency of the patient in real time during the operative procedure. In the near future, through the exploitation of these systems, surgeons will program and check on the virtual patient clone an optimal procedure without errors, which will be replayed on the real patient by the robot under surgeon control. This medical dream is today about to become reality.

  18. Preclinical studies identify non-apoptotic low-level caspase-3 as therapeutic target in pemphigus vulgaris.

    Directory of Open Access Journals (Sweden)

    Camille Luyet

    Full Text Available The majority of pemphigus vulgaris (PV patients suffer from a live-threatening loss of intercellular adhesion between keratinocytes (acantholysis. The disease is caused by auto-antibodies that bind to desmosomal cadherins desmoglein (Dsg 3 or Dsg3 and Dsg1 in mucous membranes and skin. A currently unresolved controversy in PV is whether apoptosis is involved in the pathogenic process. The objective of this study was to perform preclinical studies to investigate apoptotic pathway activation in PV pathogenesis with the goal to assess its potential for clinical therapy. For this purpose, we investigated mouse and human skin keratinocyte cultures treated with PV antibodies (the experimental Dsg3 monospecific antibody AK23 or PV patients IgG, PV mouse models (passive transfer of AK23 or PVIgG into adult and neonatal mice as well as PV patients' biopsies (n=6. A combination of TUNEL assay, analyses of membrane integrity, early apoptotic markers such as cleaved poly-ADP-ribose polymerase (PARP and the collapse of actin cytoskeleton failed to provide evidence for apoptosis in PV pathogenesis. However, the in vitro and in vivo PV models, allowing to monitor progression of lesion formation, revealed an early, transient and low-level caspase-3 activation. Pharmacological inhibition confirmed the functional implication of caspase-3 in major events in PV such as shedding of Dsg3, keratin retraction, proliferation including c-Myc induction, p38MAPK activation and acantholysis. Together, these data identify low-level caspase-3 activation downstream of disrupted Dsg3 trans- or cis-adhesion as a major event in PV pathogenesis that is non-synonymous with apoptosis and represents, unlike apoptotic components, a promising target for clinical therapy. At a broader level, these results posit that an impairment of adhesive functions in concert with low-level, non-lethal caspase-3 activation can evoke profound cellular changes which may be of relevance for other

  19. The skeletal radiography vs bone scintigraphy in assessment of bone destruction in patients with multiple myeloma: a comparative study

    International Nuclear Information System (INIS)

    Objective: To evaluate the radiography and bone scintigraphy for bone destruction in patients with multiple myeloma. Methods: Skeletal radiographs and bone radionuclide images of 20 patients newly diagnosed as multiple myeloma were comparatively studied. Results: On radiograph, lytic bone destruction was seen in 90% cases, pathological fracture was revealed in 80% cases, and diffuse osteoporosis was shown in 80% cases. While the positive rate of the bone scintigraphy was 45%. Areas of increased uptake and filling defects were revealed on scintigraphic images. Conclusion: Radiography has higher sensitivity and specificity than radionuclide imaging in imaging bone destruction and pathological fracture in patients with multiple myeloma. Skeletal radiography is still the first choice of imaging modalities in assessing the bone destruction in patients with multiple myeloma

  20. The Tyrosine Kinase Inhibitor Sunitinib Affects Ovulation but Not Ovarian Reserve in Mouse: A Preclinical Study

    Science.gov (United States)

    Bernard, Valérie; Bouilly, Justine; Kramer, Piet; Carré, Nadège; Schlumberger, Martin; Visser, Jenny A.; Young, Jacques; Binart, Nadine

    2016-01-01

    The aim of the study was to evaluate ovarian toxicity of tyrosine kinase inhibitor (TKI) sunitinib, since only scarce data are available on gonadal function after this treatment. Six-week-old female mice received orally, once daily, vehicle or sunitinib (50 mg/kg/d) during 5 weeks. Fertility parameters were analyzed from ovulation to litter assessment. Sunitinib exposure significantly reduced (i) corpora lutea number per ovary (1.1 ± 0.38 in sunitinib group versus 4 ± 0.79 in control group, p<0.01) and (ii) serum Anti Müllerian hormone (AMH) levels in sunitinib treated mice (12.01 ± 1.16) compared to control mice (14.33 ± 0.87 ng/ml, p< 0.05). However, primordial and growing follicles numbers per ovary were not different in both groups. After treatment withdrawal, female mice in both groups were able to obtain litters. These data could be helpful to counsel clinicians and patients, when fertility preservation methods are discussed, before TKI treatment in girls and young women. PMID:27035144

  1. Effect of selective inhibitors of inflammation on oral mucositis: Preclinical studies

    International Nuclear Information System (INIS)

    Objective: Oral mucositis is a severe, dose-limiting side effect of radio(chemo)therapy for head and neck tumors. The epithelial radiation response (ulceration) is accompanied by inflammatory changes. Their interaction with the epithelial processes remains unclear. The present study was initiated to determine the effect of inhibition of TNF-α or COX-2 on the epithelial radiation response in the mouse tongue model. Methods: Daily fractionated irradiation was given with 5 x 3 Gy/week over one (days 0-4) or two weeks (days 0-4, 7-11). Each protocol was terminated by graded test doses (5 dose groups, 10 animals each) to a defined area of the lower tongue surface to generate full dose-effect curves for mucosal ulceration. A TNF-α inhibiting antibody (Infliximab) or a COX-2 inhibitor (Celecoxib) was administered. Results: No effect of Infliximab or Celecoxib was found in any of the protocols. Isoeffective doses for ulcer induction were unchanged. Also, the time course of the response was largely unaffected. Conclusions: Inhibition of TNF-α or COX-2, two dominating inflammatory pathways, did not result in modulation of the response of oral epithelium during fractionated irradiation. This suggests that the inflammatory changes mediated through TNF-α or COX-2 are not relevant for the epithelial radiation response of oral mucosa.

  2. The Tyrosine Kinase Inhibitor Sunitinib Affects Ovulation but Not Ovarian Reserve in Mouse: A Preclinical Study.

    Directory of Open Access Journals (Sweden)

    Valérie Bernard

    Full Text Available The aim of the study was to evaluate ovarian toxicity of tyrosine kinase inhibitor (TKI sunitinib, since only scarce data are available on gonadal function after this treatment. Six-week-old female mice received orally, once daily, vehicle or sunitinib (50 mg/kg/d during 5 weeks. Fertility parameters were analyzed from ovulation to litter assessment. Sunitinib exposure significantly reduced (i corpora lutea number per ovary (1.1 ± 0.38 in sunitinib group versus 4 ± 0.79 in control group, p<0.01 and (ii serum Anti Müllerian hormone (AMH levels in sunitinib treated mice (12.01 ± 1.16 compared to control mice (14.33 ± 0.87 ng/ml, p< 0.05. However, primordial and growing follicles numbers per ovary were not different in both groups. After treatment withdrawal, female mice in both groups were able to obtain litters. These data could be helpful to counsel clinicians and patients, when fertility preservation methods are discussed, before TKI treatment in girls and young women.

  3. The Tyrosine Kinase Inhibitor Sunitinib Affects Ovulation but Not Ovarian Reserve in Mouse: A Preclinical Study.

    Science.gov (United States)

    Bernard, Valérie; Bouilly, Justine; Kramer, Piet; Carré, Nadège; Schlumberger, Martin; Visser, Jenny A; Young, Jacques; Binart, Nadine

    2016-01-01

    The aim of the study was to evaluate ovarian toxicity of tyrosine kinase inhibitor (TKI) sunitinib, since only scarce data are available on gonadal function after this treatment. Six-week-old female mice received orally, once daily, vehicle or sunitinib (50 mg/kg/d) during 5 weeks. Fertility parameters were analyzed from ovulation to litter assessment. Sunitinib exposure significantly reduced (i) corpora lutea number per ovary (1.1 ± 0.38 in sunitinib group versus 4 ± 0.79 in control group, p<0.01) and (ii) serum Anti Müllerian hormone (AMH) levels in sunitinib treated mice (12.01 ± 1.16) compared to control mice (14.33 ± 0.87 ng/ml, p< 0.05). However, primordial and growing follicles numbers per ovary were not different in both groups. After treatment withdrawal, female mice in both groups were able to obtain litters. These data could be helpful to counsel clinicians and patients, when fertility preservation methods are discussed, before TKI treatment in girls and young women. PMID:27035144

  4. COMPARATIVE STUDY OF CYTOLOGIC AND COLPOSCOPIC FINDINGS IN PRECLINICAL CERVICAL CANCER

    Directory of Open Access Journals (Sweden)

    Penagaluru

    2015-11-01

    Full Text Available BACKGROUND The cytologic diagnosis of cervical smears has become a very important screening test for the detection of pre-invasive and invasive cervical epithelial abnormalities. MATERIALS AND METHODS It is a prospective study conducted for a period of 1 year in 100 women who fulfilled the inclusion criteria. Colposcopy, PAP smear and biopsy were done. RESULTS Majority 70.5% i.e., (12/17 of CIN occurred in the age group of 30-49 years. Among the 9 women who took OCP, 12% (2/17 had CIN. Incidence of CIN in the permanently sterilized group was 59% (10/17 and among IUCD user was 5.9% (1/17. Among women who were diagnosed to have CIN, 70.5% (12/17 complained of excessive vaginal discharge 11.7% (2/17 of women had post-coital bleeding. PAP smear had a sensitivity of 29% and a specificity of 88% which was attributed to the high number of false, negative smears. Colposcopy showed a sensitivity of 82% and a specificity of 81%. Sensitivity was more than pap smear but specificity was less than pap smear. Accuracy of Colposcopy was found to be 82% which was comparatively more accurate than pap smear (78%. CONCLUSIONS COLPOSCOPY offers an excellent tool in evaluating cervical lesions. It is an easy and perspective method and its importance lies in teaching, diagnosis and management of cervical lesions, both neoplastic and non-neoplastic.

  5. Khat (Catha edulis F.) and cannabinoids: Parallel and contrasting behavioral effects in preclinical and clinical studies.

    Science.gov (United States)

    Geresu, Berhanu

    2015-11-01

    After a brief outline of Catha edulis F. (khat) and the cannabinoid systems, the interactions between the pharmacological effects of khat and cannabinoids will be reviewed. Khat chewing is a widespread habit that has a deep-rooted sociocultural tradition in Africa and the Middle East. Experimental studies conducted to investigate khat's central and peripheral effects have revealed an amphetamine-like mechanism of action mediated through the dopaminergic system. The endocannabinoid system comprises the receptors, the endogenous agonists and the related biochemical machinery responsible for synthesizing these substances and terminating their actions. Endocannabinoids are synthesized "on demand" from membrane phospholipids and then rapidly cleared by cellular uptake and enzymatic degradation. Khat and cannabinoids produce a body of parallel and contrasting behavioral effects. Concurrent consumption of khat and cannabinoids may increase the risk of getting or precipitating psychosis, has rewarding and motivational effect, increases the threshold of pain perception and impairs learning and memory. On the other hand, the action of cannabis to enhance food intake is likely to reduce khat's appetite suppressant effects. PMID:26469212

  6. Modulation of radiation-induced oral mucositis by pentoxifylline: Preclinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Gruber, Sylvia; Bozsaky, Eva [Medical University/AKH Vienna, Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Comprehensive Cancer Center, Vienna (Austria); Schmidt, Margret [Technical University of Dresden, Dept. Radiotherapy and Radiation Oncology, OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden (Germany); German Cancer Center (DKFZ), Heidelberg (Germany). German Cancer Consortium (DKTK) partner site Dresden; Wolfram, Kathrin; Haagen, Julia; Habelt, Bettina; Puttrich, Martin [Technical University of Dresden, Dept. Radiotherapy and Radiation Oncology, OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden (Germany); Doerr, Wolfgang [Medical University/AKH Vienna, Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Comprehensive Cancer Center, Vienna (Austria); Technical University of Dresden, Dept. Radiotherapy and Radiation Oncology, OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden (Germany)

    2014-10-29

    Oral mucositis is a frequent early side effect of radio(chemo)therapy of head-and-neck malignancies. The epithelial radiation response is accompanied by inflammatory reactions; their interaction with epithelial processes remains unclear. The aim of the present study was to investigate the effect of pentoxifylline (PTX) on the oral mucosal radiation response in the mouse tongue model. Irradiation comprised fractionation (5 fractions of 3 Gy/week) over 1 (days 0-4) or 2 weeks (days 0-4, 7-11), followed by graded local top-up doses (day 7/14), in order to generate complete dose-effect curves. PTX (15 mg/kg subcutaneously) was applied once daily over varying time intervals. Ulceration of mouse tongue epithelium, corresponding to confluent mucositis, was analyzed as the clinically relevant endpoint. With fractionated irradiation over 1 week, PTX administration significantly reduced the incidence of mucosal reactions when initiated before (day - 5) the onset of fractionation; a trend was observed for start of PTX treatment on day 0. Similarly, PTX treatment combined with 2 weeks of fractionation had a significant effect on ulcer incidence in all but one experiment. This clearly illustrates the potential of PTX to ameliorate oral mucositis during daily fractionated irradiation. PTX resulted in a significant reduction of oral mucositis during fractionated irradiation, which may be attributed to stimulation of mucosal repopulation processes. The biological basis of this effect, however, needs to be clarified in further, detailed mechanistic studies. (orig.) [German] Die orale Mukositis ist eine haeufige fruehe Nebenwirkung der Radio(chemo)therapie von Kopf-Hals-Tumoren. Die epitheliale Strahlenreaktion wird von Entzuendungserscheinungen begleitet; deren Interaktion mit epithelialen Prozessen ist derzeit unklar. Ziel der vorliegenden Untersuchung war die quantitative Erfassung des Effekts einer Behandlung mit Pentoxifyllin (PTX) auf die Strahlenreaktion der Mundschleimhaut

  7. The preclinical pharmacological study of dopamine transporter imaging agent [99mTc]TRODAT-1

    International Nuclear Information System (INIS)

    Objective: To investigate the pharmacological characteristics of 99mTc-TRODAT-1 as an imaging agent for dopamine transporter. Methods: (1) The quality control of one-vial formulation produced in China. (2) Biodistribution in rats. (3) Imaging in normal and hemi-Parkinsonian model monkeys. Results: (1) The radiochemical purity of [99mTc]TRODAT-1 was about 79.9% evaluated by TLC. It was stable for 2.5 hours at room temperature. (2) The clearance of [99mTc]TRODAT-1 in the blood of rats was fast. The major portion of radioactivity was excreted by hepatobiliary system. (3) The brain uptake was moderate. But the agent had high-affinity binding to DAT which was highly concentrated in striatal area and there was no specific uptake in cerebellum. The ratio of ST/CB was high. (4) Pretreatment with haloperidol, a non-competing ligand, did not result in any significant change in the level of striatal uptake. (5) The distribution pattern as well as the brain regional uptake of [99mTc]TRODAT-1 did not display any significant difference between male and female rats at 60 min post-injection. (6) Monkeys' SPECT images clearly displayed the normal uptake and the pathologic changes in striatal area at 3 hours post-injection. The semi-quantitative analysis, ST/CB ratio, could reveal the specific uptake value for [99mTc]TRODAT-1 in reflecting the numeral and functional changes in DAT. Conclusion: [99mTc]TRODAT-1 labeled by one-vial formulation of China can be the imaging agent of DAT in clinical study. It proves to be effective and promising radiopharmaceuticals in vivo assessment of the loss of dopamine neurons in Parkinson's disease and other neurodegenerative disease

  8. Preclinical safety studies of 213BI labeled PA12 for targeted alpha therapy of cancer

    International Nuclear Information System (INIS)

    Full text: The urokinase plasminogen activator (uPA) system is involved in cancer growth and metastasis. The plasminogen activator inhibitor type 2 (PAI2) and uPA can form a stable complex, which is bound to the cell surface uPA receptor (uPAR). We labeled PAI2 with 213Bi to form the alpha conjugate. This conjugate targets uPA/uPAR and has been found to have promising therapeutic properties for breast, prostate and pancreatic cancer. This paper reports studies of the acute and delayed toxicity in mice; the effect of lysine renal protection; pharmacokinetics; a comparison of CHX-A-DTPA and cDTPA chelators, and in vivo 213Bi-PAI2 stability by Ca-DTPA challenge. Pharmacokinetics of 213Bi-PAI2 in nude mice demonstrated that the kidneys were the critical organs for retention of Bismuth in the chelate complex. The CHX-A-DTPA and cDTPA immunoconjugates were found to have similar percent I D/kg in the kidney, with no significant retention of Bi evident in other organs such as liver, heart, lung, and spleen. Ca-DTPA chelators significantly reduced the renal 213Bi accumulation at 15 minutes, not for 30 and 120 minutes, indicating high in vivo stability of 213Bi-PAI2 and the need for pre-injection purification of conjugates. The acute toxicity limit by weight loss was more than 450 MBq/kg. Mild to moderate, patchy tubular necrosis was observed accompanied by slight urea increase. Radiation nephritis was the source of lethal delayed toxicity arising at 20 - 30 weeks post-treatment, for which the maximum tolerance dose was 110 MBq/kg. Kidney uptake was not significantly decreased by lysine at 185 MBq/kg, nor was there any change in delayed toxicity

  9. Optimization and qualification of an 8-color intracellular cytokine staining assay for quantifying T cell responses in rhesus macaques for pre-clinical vaccine studies

    OpenAIRE

    Donaldson, Mitzi M.; Kao, Shing-Fen; Eslamizar, Leila; Gee, Connie; Koopman, Gerrit; Lifton, Michelle; Schmitz, Joern E.; Sylwester, Andrew W.; Wilson, Aaron; Hawkins, Natalie; Self, Steve G.; Roederer, Mario; Foulds, Kathryn E.

    2012-01-01

    Vaccination and SIV challenge of macaque species is the best animal model for evaluating candidate HIV vaccines in pre-clinical studies. As such, robust assays optimized for use in nonhuman primates are necessary for reliable ex vivo measurement of immune responses and identification of potential immune correlates of protection. We optimized and qualified an 8-color intracellular cytokine staining assay for the measurement of IFNγ, IL-2, and TNF from viable CD4 and CD8 T cells from cryopreser...

  10. Preclinical models for neuroblastoma: establishing a baseline for treatment.

    Directory of Open Access Journals (Sweden)

    Tal Teitz

    Full Text Available BACKGROUND: Preclinical models of pediatric cancers are essential for testing new chemotherapeutic combinations for clinical trials. The most widely used genetic model for preclinical testing of neuroblastoma is the TH-MYCN mouse. This neuroblastoma-prone mouse recapitulates many of the features of human neuroblastoma. Limitations of this model include the low frequency of bone marrow metastasis, the lack of information on whether the gene expression patterns in this system parallels human neuroblastomas, the relatively slow rate of tumor formation and variability in tumor penetrance on different genetic backgrounds. As an alternative, preclinical studies are frequently performed using human cell lines xenografted into immunocompromised mice, either as flank implant or orthtotopically. Drawbacks of this system include the use of cell lines that have been in culture for years, the inappropriate microenvironment of the flank or difficult, time consuming surgery for orthotopic transplants and the absence of an intact immune system. PRINCIPAL FINDINGS: Here we characterize and optimize both systems to increase their utility for preclinical studies. We show that TH-MYCN mice develop tumors in the paraspinal ganglia, but not in the adrenal, with cellular and gene expression patterns similar to human NB. In addition, we present a new ultrasound guided, minimally invasive orthotopic xenograft method. This injection technique is rapid, provides accurate targeting of the injected cells and leads to efficient engraftment. We also demonstrate that tumors can be detected, monitored and quantified prior to visualization using ultrasound, MRI and bioluminescence. Finally we develop and test a "standard of care" chemotherapy regimen. This protocol, which is based on current treatments for neuroblastoma, provides a baseline for comparison of new therapeutic agents. SIGNIFICANCE: The studies suggest that use of both the TH-NMYC model of neuroblastoma and the

  11. Allopregnanolone preclinical acute pharmacokinetic and pharmacodynamic studies to predict tolerability and efficacy for Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Ronald W Irwin

    /kg. The predicted MTD in human female is 0.37mg/kg. In male rats the NOAEL and MTD were less than those determined for female. Outcomes of these PK/PD studies predict a safe and efficacious dose range for initial clinical trials of allopregnanolone for Alzheimer's disease. These findings have translational relevance to multiple neurodegenerative conditions.

  12. Toxicity of novel anti-hepatitis drug bicyclol: A preclinical study

    Institute of Scientific and Technical Information of China (English)

    Geng-Tao Liu; Yan Li; Huai-Ling Wei; Hong Lu; Hui Zhang; Yu-Gui Gao; Ling-Zhi Wang

    2005-01-01

    AIM: To study the toxicity of bicyclol to animals.METHODS: Acute toxicity test was performed in Kunming strain mice that were orally given bicyclol at the doses of 3 and 5 g/kg body weight, respectively. Wistar rats were orally administered bicyclol at a dose of 5 g/kg body weight. Death and clinical symptoms of animals were recorded within 7 d. Sub-acute toxicity test was carried out in rats that were treated with various doses of bicyclol (150, 300, 600 mg/kg) once daily for 14 d.Animal behaviors, blood biochemical markers, blood and urine pictures were examined. Chronic toxicity test was conducted in 80 Wistar rats of both sexes. The animals were orally administered with various doses of bicyclol[150, 300, 600 mg/kg, 100-400 folds corresponding to for patients] once daily for 6 mo except for Sunday. The control group was given the same volume of 0.2%sodium carboxyl methylcellulose (Na-CMC). Twenty-one beagle dogs received bicyclol (25, 75, 225 mg/kg, 16.6,50, 150 folds corresponding to the proposed therapeutic dose of bicyclol for patients) once a day for 6 mo except for Sunday. The body weight, food intake, urine and feces, blood picture, blood biochemical markers, and pathological examination of main organs were determined. Mutagenicity and teratogenicity were determined. Mutagenicity assay included Ames's test, chromosome aberration test in CHL cells and micronucleus test in mice. For the teratogenicity assay, pregnant Wistar rats weighing 200-250 g were treated with 0.2, 1.0 g/kg bicyclol once daily from the 7th d of gestation for 10 d.RESULTS: The oral LD50 of bicyclol was over 5 g/kg in mice and rats. No noticeable alterations in subacute and chronic toxicity of rats and dogs were demonstrated. No mutagenicity and teratogenicity of bicyclol were found.CONCLUSION: Bicyclol has no detectable chronic toxicity as well as mutagenicity and teratogenicity in animals.

  13. The Experimental Study of Constructing Tissue Engineered Bone by Compounding Zinc-sintered Bovine Cancellous Bone with Marrow Stromal Cells

    Institute of Scientific and Technical Information of China (English)

    ZHENG Qi-xin; HAO Jie; GUO Xiao-dong; LIU Su-nan; Wu Yong-chao; YAN Yu-hua

    2004-01-01

    To study the osteogenic ability of tissue-engineered bone constructed by compounding zinc-sin-tered bovine cancellous bone with rabbit marrow stromal cells ( MSCs ) in vivo, the zinc- sintered bovine cancellousbone of beta-tricalcium phosphate (TCP) type was prepared by sintering the fresh calf cancellous bone twice andthen loading it with zinc-ion. The rabbit MSCs were cultured, induced and seeded onto the zinc- sintered bovine can-cellous bones. The tissue-engineered bones were then implanted into the rabbits' bock muscles. The newly formedbone tissues were observed by histological methods and the areas of new osseous tissues were measured at the end ofthe 4 th and 8 th week. The zinc-sintered bovine cancellous bones alone were implanted on the other side as control.The osteogenic activity of MSCs was identified by alkaline phosphatase (ALP) staining and calcification nod chi-nalizarin staining. At the end of 4th week, a small amount of new bone tissues was observed. At the end of 8thweek, there were many newly formed bone mature tissues. Moreover, the area of the latter was significantly largerthan that of the former( P<0.01), while in the control group there was no new bone formation. The tissue-engi-neered bone, which was constructed by combining zinc-sintered bovine cancellous bone with MSCs, has satisfactoryosteogenic capabilities in vivo.

  14. Preclinical Comparative Study of (68)Ga-Labeled DOTA, NOTA, and HBED-CC Chelated Radiotracers for Targeting PSMA.

    Science.gov (United States)

    Ray Banerjee, Sangeeta; Chen, Zhengping; Pullambhatla, Mrudula; Lisok, Ala; Chen, Jian; Mease, Ronnie C; Pomper, Martin G

    2016-06-15

    (68)Ga-labeled, low-molecular-weight imaging agents that target the prostate-specific membrane antigen (PSMA) are increasingly used clinically to detect prostate and other cancers with positron emission tomography (PET). The goal of this study was to compare the pharmacokinetics of three PSMA-targeted radiotracers: (68)Ga-1, using DOTA-monoamide as the chelating agent; (68)Ga-2, containing the macrocyclic chelating agent p-SCN-Bn-NOTA; and (68)Ga-DKFZ-PSMA-11, currently in clinical trials, which uses the acyclic chelating agent, HBED-CC. The PSMA-targeting scaffold for all three agents utilized a similar Glu-urea-Lys-linker construct. Each radiotracer enabled visualization of PSMA+ PC3 PIP tumor, kidney, and urinary bladder as early as 15 min post-injection using small animal PET/computed tomography (PET/CT). (68)Ga-2 demonstrated the fastest rate of clearance from all tissues in this series and displayed higher uptake in PSMA+ PC3 PIP tumor compared to (68)Ga-1 at 1 h post-injection. There was no significant difference in PSMA+ PC3 PIP tumor uptake for the three agents at 2 and 3 h post-injection. (68)Ga-DKFZ-PSMA-11 demonstrated the highest uptake and retention in normal tissues, including kidney, blood, spleen, and salivary glands and PSMA-negative PC3 flu tumors up to 3 h post-injection. In this preclinical evaluation (68)Ga-2 had the most advantageous characteristics for PSMA-targeted PET imaging. PMID:27076393

  15. Cardiovascular outcomes of sodium-glucose cotransporter 2 inhibitors: A comprehensive review of clinical and preclinical studies.

    Science.gov (United States)

    Ghosh, Raktim Kumar; Bandyopadhyay, Dhrubajyoti; Hajra, Adrija; Biswas, Monodeep; Gupta, Anjan

    2016-06-01

    Diabetes is a leading cause of morbidity and mortality worldwide. Management of diabetes is changing at a rapid pace. Three new classes of antidiabetic drugs including GLP-1 (Glucagon-like peptide 1), DPP-IV (Dipeptidyl peptidase IV) and SGLT2 (Sodium glucose cotransporter 2) inhibitors have been approved in the last few years. Treating diabetes with the antidiabetic drug does not always reduce the cardiovascular complications of diabetes. On the contrary, there was a huge controversy regarding the effect of rosiglitazone on cardiovascular risk reduction a few years ago. Since then, submission of postmarketing cardiovascular outcome study data has been mandated by US FDA and other drug regulatory agencies for newer antidiabetic medications. This is to avoid further premature claims regarding cardiovascular harm or safety of the newer classes. We already have some cardiovascular safety data available on DPP-IV and GLP-1 groups of medications. Dapagliflozin, canagliflozin, and empagliflozin are currently approved SGLT2 inhibitors. We do not have sufficient cardiovascular outcome data available for this novel class. However, this group of drugs, which act by increasing renal glucose excretion, have also shown some non-glycemic benefits including weight reduction, blood pressure control, diuretic action, renal protection, decrease in arterial stiffness and uric acid reduction. Empagliflozin, a new member of SGLT2 class, showed significant cardiovascular morbidity and mortality benefit in recently published EMPA-REG OUTCOME trial. The authors summarize all the published clinical and preclinical cardiovascular outcome data of SGLT2 inhibitors, including recently completed and ongoing major clinical trials in this comprehensive review. PMID:27017118

  16. The prevalence and correlations of medical student burnout in the pre-clinical years: a cross-sectional study.

    Science.gov (United States)

    Mazurkiewicz, Rebecca; Korenstein, Deborah; Fallar, Robert; Ripp, Jonathan

    2012-01-01

    Burnout is a psychological syndrome of emotional exhaustion, depersonalization, and impaired personal accomplishment induced by repeated workplace stressors. Current research suggests that physician burnout may have its origins in medical school. The consequences of medical student burnout include both personal and professional distress, loss of empathy, and poor health. We hypothesized that burnout occurs prior to the initiation of the clinical years of medical education. This was a cross-sectional survey administered to third-year medical students at the Mount Sinai School of Medicine (MSSM) in New York, New York (a traditional-style medical school with a marked division between pre-clinical and clinical training occurring at the beginning of the third year). Survey included an instrument used to measure job burnout, a sleep deprivation screen, and questions related to demographic information, current rotation, psychiatric history, time spent working/studying, participation in extracurricular activities, social support network, autonomy and isolation. Of the 86 medical students who participated, 71% met criteria for burnout. Burnt out students were significantly more likely to suffer from sleep deprivation (p = 0.0359). They were also more likely to disagree with the following statements: "I have control over my daily schedule" (p = 0.0286) and "I am confident that I will have the knowledge and skills necessary to become an intern when I graduate" (p = 0.0263). Our findings show that burnout is present at the beginning of the third year of medical school, prior to the initiation of the clinical years of medical training. Medical student burnout is quite common, and early efforts should be made to empower medical students to both build the knowledge and skills necessary to become capable physicians, as well as withstand the emotional, mental, and physical challenges inherent to medical school. PMID:21781020

  17. Embalmed and fresh frozen human bones in orthopedic cadaveric studies: which bone is authentic and feasible?

    OpenAIRE

    Topp, Tobias; Müller, Thorben; Huss, Sebastian; Kann, Peter Herbert; Weihe, Eberhard; Ruchholtz, Steffen; Zettl, Ralph Peter

    2012-01-01

    Background and purpose The most frequently used bones for mechanical testing of orthopedic and trauma devices are fresh frozen cadaveric bones, embalmed cadaveric bones, and artificial composite bones. Even today, the comparability of these different bone types has not been established. Methods We tested fresh frozen and embalmed cadaveric femora that were similar concerning age, sex, bone mineral density, and stiffness. Artificial composite femora were used as a reference group. Testing para...

  18. Can evaluation of a dental procedure at the outset of learning predict later performance at the preclinical level? A pilot study.

    LENUS (Irish Health Repository)

    Polyzois, Ioannis

    2011-05-01

    The purpose of this study was to examine the effectiveness of conventional pre-clinical training in dentistry and to determine if evaluation of a dental procedure at the beginning of dental training can be a predictor for future performance. A group of second year dental students with no previous experience in operative dentistry were asked to prepare a conventional class I cavity on a lower first molar typodont. Their first preparation was carried out after an introductory lecture and a demonstration and their second at the end of conventional training. The prepared typodonts were coded and blindly scored for the traditional assessment criteria of outline form, retention form, smoothness, cavity depth and cavity margin angulation. Once the codes were broken, a paired t-test was used to compare the difference between the means of before and after scores (P<0.0001) and a Pearson\\'s linear correlation to test the association (r=0.4). From the results of this study, we could conclude that conventional preclinical training results in a significant improvement in the manual skills of the dental students and that the dental procedure used had only a limited predictive value for later performance at the preclinical level.

  19. Celecoxib does not significantly delay bone healing in a rat femoral osteotomy model: a bone histomorphometry study

    Directory of Open Access Journals (Sweden)

    Iwamoto J

    2011-12-01

    Full Text Available Jun Iwamoto1, Azusa Seki2, Yoshihiro Sato3, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Hamri Co, Ltd, Tokyo, Japan; 3Department of Neurology, Mitate Hospital, Fukuoka, JapanBackground and objective: The objective of the present study was to determine whether celecoxib, a cyclo-oxygenase-2 inhibitor, would delay bone healing in a rat femoral osteotomy model by examining bone histomorphometry parameters.Methods: Twenty-one 6-week-old female Sprague-Dawley rats underwent a unilateral osteotomy of the femoral diaphysis followed by intramedullary wire fixation; the rats were then divided into three groups: the vehicle administration group (control, n = 8, the vitamin K2 administration (menatetrenone 30 mg/kg orally, five times a week group (positive control, n = 5, and the celecoxib administration (4 mg/kg orally, five times a week group (n = 8. After 6 weeks of treatment, the wires were removed, and a bone histomorphometric analysis was performed on the bone tissue inside the callus. The lamellar area relative to the bone area was significantly higher and the total area and woven area relative to the bone area were significantly lower in the vitamin K2 group than in the vehicle group. However, none of the structural parameters, such as the callus and bone area relative to the total area, lamellar and woven areas relative to the bone area, or the formative and resorptive parameters such as osteoclast surface, number of osteoclasts, osteoblast surface, osteoid surface, eroded surface, and bone formation rate per bone surface differed significantly between the vehicle and celecoxib groups.Conclusion: The present study implies that celecoxib may not significantly delay bone healing in a rat femoral osteotomy model based on the results of a bone histomorphometric analysis.Keywords: femoral osteotomy, bone healing, callus, rat, celecoxib

  20. Reducing Attrition via Improved Strategies for Pre-clinical Drug Discovery : SPR-biosensor Aided Interaction Studies

    OpenAIRE

    Winquist, Johan

    2012-01-01

    The efficacy of a drug is tightly intertwined with its interaction mechanism with the drug target. The mechanism is dependent on the physicochemical and structural characteristics of both target and drug molecule. Drug discovery is plagued by a high attrition rate, whereas in the clinic, a major issue is drug resistance. To improve the quality of the lead compounds in the pre-clinical phase of drug discovery, and thereby reducing the attrition, a deeper understanding of interaction mechanisms...

  1. Changes in Vertebral Bone Marrow Fat and Bone Mass After Gastric Bypass Surgery: A Pilot Study

    OpenAIRE

    Schafer, AL; Li, X; Schwartz, AV; Tufts, LS; Wheeler, AL; Grunfeld, C; Stewart, L; Rogers, SJ; Carter, JT; Posselt, AM; Black, DM; Shoback, DM

    2015-01-01

    Bone marrow fat may serve a metabolic role distinct from other fat depots, and it may be altered by metabolic conditions including diabetes. Caloric restriction paradoxically increases marrow fat in mice, and women with anorexia nervosa have high marrow fat. The longitudinal effect of weight loss on marrow fat in humans is unknown. We hypothesized that marrow fat increases after Roux-en-Y gastric bypass (RYGB) surgery, as total body fat decreases. In a pilot study of 11 morb...

  2. Future prospects for SPECT imaging using the radio-lanthanide terbium-155 production and preclinical studies in tumor bearing mice

    International Nuclear Information System (INIS)

    Full text of publication follows. Background: since SPECT continues to be the predominant technology in clinical oncology we propose the radio lanthanide 155Tb (t1/2 = 5.3 d, E = 87 keV (32%); 105 keV (25%) as a new isotope for SPECT imaging purposes [Ref. 1]. The aim of this study was the production and separation of 155Tb and its preclinical application in mice using different 155Tb-labeled tumor targeting agents. Methods: 155Tb was produced at ISOLDE (CERN, Switzerland) by high-energy (1.4 GeV) proton irradiation of a tantalum target followed by an on-line separation according to the mass-charge ratio of the ions [Ref.1]. Collected products of mass number 155 were shipped to PSI and separated from isobar and pseudo-isobar impurities by cation exchange chromatography similar to a previously reported procedure [Refs. 1,2]. Four different biomolecules, based on a peptide (DOTATATE), a folate (cm09 [Ref. 3]) and an antibody (chCE7) were radiolabeled with 155Tb. Imaging studies were performed in mice bearing somatostatin receptor positive AR42J tumors, folate receptor positive KB tumors or L1-CAM expressing SKOV-3 tumors. Results: the total yield of the two-step separation process of 155Tb was 85%. 155Tb was obtained in a physiological L-lactate solution suitable for direct labeling and in vivo application of the biomolecules. Radiolabeling was achieved in an excellent purity of > 98% at specific activities of ∼ 1.8 MBq/nmol (155Tb-DOTATATE) and ∼ 5.6 MBq/nmol (155Tb-folate). The radiolabeling of the antibody was achieved at a specific activity of ∼ 44 MBq/mg (155Tb-CHX-A''-DTPA-chCE7). SPECT/CT experiments revealed an excellent visualization of AR42J tumors in mice 1 h after injection of 155Tb-DOTATATE. The long-circulating 155Tb-cm09 allowed imaging of KB tumors even over several days. Conclusions. In this study we demonstrated the excellent features of 155Tb for SPECT imaging using fast-cleared and a long-circulating biomolecules. 155Tb may be of

  3. A new double bone-double bundle patellar tendon-bone graft model: A calf model study

    OpenAIRE

    Öztürk, Hayati; Öztemur, Zekeriya; Bulut, Okay; Tezeren, Seyfi Gündüz

    2011-01-01

    AbstractThe aim of this study is to improve a new graft model for anatomic double bundle Anterior Crucial Ligament reconstruction (ACL). The aim of ACL reconstruction is to reproduce the functions of the native ACL. An anatomic double bundle ACL reconstruction utilizes two separate grafts to replace the Anterior Medial (AM) and Posterior Lateral (PL) bundles of the ACL. Bone-Patellar Tendon-Bone (BPTB) Graft was harvested from calf knee. Patellar tendon and distal bone were split as longitudi...

  4. Study on temporomandibular joint disorders by bone scintigraphy and bone metabolic markers (ICTP, PICP) in synovial fluid

    International Nuclear Information System (INIS)

    The aim of this study was to evaluate bone metabolic condition in imaging findings of temporomandibular joint disorders (TMD) using bone scintigraphy, which has a high sensitivity to bone metabolism, and two bone metabolic markers: pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) and carboxy-terminal propeptide of type I procollagen (PICP) which influence both the formation and absorption of bone. The subjects were 92 patients (18 male, 74 female, mean age 40.3±18.2 years of age, 112 temporomandibular joints (TMJs)) with TMD who underwent bone scintigraphy using 99mTc-methylene diphosphonate sodium (MDP) and/or had their concentration of bone metabolic markers (ICTP and PICP) measured in synovial lavage fluid by a radioimmunoassay kit using competitive inhibition. Synovial lavage fluid was a mixture of synovial fluid and physiological saline, obtained by irrigation of the superior joint compartment of TMD patients. Sixteen female controls (mean age 42.7±15.7 years of age) with no symptoms of TMD, but who had other diseases and who underwent bone scintigraphy, were selected. The position and configuration of the articular disk of patients with TMD were diagnosed by MRI and/or double contrastarthrography. All patients were examined for morphological bone change of the TMJ by tomography and were evaluated using both a positive ratio and an accumulation ratio (radioactivity counts of TMJ region/radioactivity counts of neck soft tissue region) by bone scintigraphy. We obtained the following results and conclusions. All the temporomandibular joints with morphological bone change showed an increase in accumulation by bone scintigraphy. Some of the temporomandibular joints without morphological bone change also showed an increase in accumulation. There were no statistically significant differences between disk position, disk configuration and accumulation ratio. Most of the temporomandibular joints, which had an increase in accumulation

  5. Microenvironmental influence on pre-clinical activity of polo-like kinase inhibition in multiple myeloma: implications for clinical translation.

    Directory of Open Access Journals (Sweden)

    Douglas W McMillin

    Full Text Available Polo-like kinases (PLKs play an important role in cell cycle progression, checkpoint control and mitosis. The high mitotic index and chromosomal instability of advanced cancers suggest that PLK inhibitors may be an attractive therapeutic option for presently incurable advanced neoplasias with systemic involvement, such as multiple myeloma (MM. We studied the PLK 1, 2, 3 inhibitor BI 2536 and observed potent (IC50<40 nM and rapid (commitment to cell death <24 hrs in vitro activity against MM cells in isolation, as well as in vivo activity against a traditional subcutaneous xenograft mouse model. Tumor cells in MM patients, however, don't exist in isolation, but reside in and interact with the bone microenvironment. Therefore conventional in vitro and in vivo preclinical assays don't take into account how interactions between MM cells and the bone microenvironment can potentially confer drug resistance. To probe this question, we performed tumor cell compartment-specific bioluminescence imaging assays to compare the preclinical anti-MM activity of BI 2536 in vitro in the presence vs. absence of stromal cells or osteoclasts. We observed that the presence of these bone marrow non-malignant cells led to decreased anti-MM activity of BI 2536. We further validated these results in an orthotopic in vivo mouse model of diffuse MM bone lesions where tumor cells interact with non-malignant cells of the bone microenvironment. We again observed that BI 2536 had decreased activity in this in vivo model of tumor-bone microenvironment interactions highlighting that, despite BI 2536's promising activity in conventional assays, its lack of activity in microenvironmental models raises concerns for its clinical development for MM. More broadly, preclinical drug testing in the absence of relevant tumor microenvironment interactions may overestimate potential clinical activity, thus explaining at least in part the gap between preclinical vs. clinical efficacy in MM

  6. Study and rheological characterization of various bone ash porcelain formulations

    International Nuclear Information System (INIS)

    The bone ash porcelain is a widely accepted product on the market because their qualities such as high strength and whiteness, to differ from common table porcelains. Its traditional formulation comes from an English recipe, consisting of 25% of kaolin, 25% of feldspar and 50% of bovine bone ash. In some studies, this proportion is adapted to regional conditions, optimizing the formulation according to the raw materials available. In this study, the rheological behavior of bone porcelain suspensions, in which the flux feldspar is partially substituted by an alternative flux (espudomenio, wollastonite and glass). The results show that the rheological behavior of porcelain is affected by the size, shape, surface area and particle size distribution of particles in suspension

  7. Roentgen study of bone age in obese children

    International Nuclear Information System (INIS)

    The study included 100 children (50 boys and 50 girls) aged from 1 to 18 years with different degree of obesity, classified according to the scheme of Knyazev et al. The bone age was determined by a X-ray method including conventional X-ray study of the left hand at standard conditions. The H. Thiemann - I. Nittz Atlass (1986) was used as a test. It was established that the children with overweight had a change in the bone age which in most cases outstriped the calendar one. It was stated that the determination of the index 'bone age' remained to be a reliable method for studing the obesity effect on the growth and developing of the children' organism. 2 figs., 2 tabs., 12 refs

  8. Imaging bone infection using Tc-99m infecton: case studies

    International Nuclear Information System (INIS)

    Tc-99m infecton (ciprofloxacin) was introduced recently as an infection imaging agent which is specific for bacteria. If successful, this may prove superior to labelled leucocyte imaging, antibodies and other nonspecific agents in terms of logistics, cost and efficacy. We had recently acquired few kits for Tc-99m infecton preparation. Our preliminary experience suggests that it has high specificity for the infected bone and may be useful in bone tuberculosis. Three cases are presented where both Tc-99m MDP scanning and Tc-99m infecton study were undertaken to highlight the potential of this new agent. (author)

  9. Bone tissue engineering for spine fusion : An experimental study on ectopic and orthotopic implants in rats

    NARCIS (Netherlands)

    van Gaalen, SM; Dhert, WJA; van den Muysenberg, A; Oner, FC; van Blitterswijk, C; Verbout, AJ; de Bruijn, J.D.

    2004-01-01

    Alternatives to the use of autologous bone as a bone graft in spine surgery are needed. The purpose of this study was to examine tissue-engineered bone constructs in comparison with control scaffolds without cells in a posterior spinal implantation model in rats. Syngeneic bone marrow cells were cul

  10. Bone Repair on Fractures Treated with Osteosynthesis, ir Laser, Bone Graft and Guided Bone Regeneration: Histomorfometric Study

    Science.gov (United States)

    dos Santos Aciole, Jouber Mateus; dos Santos Aciole, Gilberth Tadeu; Soares, Luiz Guilherme Pinheiro; Barbosa, Artur Felipe Santos; Santos, Jean Nunes; Pinheiro, Antonio Luiz Barbosa

    2011-08-01

    The aim of this study was to evaluate, through the analysis of histomorfometric, the repair of complete tibial fracture in rabbits fixed with osteosynthesis, treated or not with infrared laser light (λ780 nm, 50 mW, CW) associated or not to the use of hydroxyapatite and guided bone regeneration (GBR). Surgical fractures were created, under general anesthesia (Ketamina 0,4 ml/Kg IP and Xilazina 0,2 ml/Kg IP), on the dorsum of 15 Oryctolagus rabbits that were divided into 5 groups and maintained on individual cages, at day/night cycle, fed with solid laboratory pelted diet and had water ad libidum. On groups II, III, IV and V the fracture was fixed with wire osteosynthesis. Animals of groups III and V were grafted with hydroxyapatite and GBR technique used. Animals of groups IV and V were irradiated at every other day during two weeks (16 J/cm2, 4×4 J/cm2). Observation time was that of 30 days. After animal death (overdose of general anesthetics) the specimes were routinely processed to wax and underwent histological analysis by light microscopy. The histomorfometric analysis showed an increased bone neoformation, increased collagen deposition, less reabsorption and inflammation when laser was associated to the HATCP. It is concluded that IR laser light was able to accelerate fracture healing and the association with HATCP and GBR resulted on increased deposition of CHA.

  11. Effects of liquid nitrogen cryotherapy and bone grafting on artificial bone defects in minipigs: a preliminary study.

    Science.gov (United States)

    Pogrel, M A; Regezi, J A; Fong, B; Hakim-Faal, Z; Rohrer, M; Tran, C; Schiff, T

    2002-06-01

    Liquid nitrogen cryotherapy has been advocated as an adjunct in the enucleation and curettage of locally aggressive lesions of the jaws. Simultaneous autogenous bone grafting has also been advocated to accelerate bone formation and reduce morbidity. There is, however, relatively little scientific basis for either of these hypotheses. In this study, nine Yucatan minipigs had artificial defects created in the mandible, which were treated with liquid nitrogen spray. Half of the defects were grafted with autogenous bone from the chin and half were closed primarily. Two animals were sacrificed 3 days postoperatively to measure the width of necrosis and the rest were sacrificed at 3 months to assess healing and new bone formation. It was found that drilling the artificial defects alone caused bone necrosis for a mean depth of 0.09 mm. Liquid nitrogen cryospray caused a mean depth of bone necrosis of 0.82 mm (range 0.51-1.52 mm). The defects that were bone grafted healed well clinically. Defects not bone grafted showed a 50% rate of wound breakdown and sequestrum formation with delayed healing. Vital staining showed a non-significantly greater rate of bone formation in the grafted defects. Digitally superimposed radiography showed a non-significantly greater bone density in the non-grafted defects at 3 months postoperatively. It appears that liquid nitrogen cryospray does devitalize an area of bone around defects in the mandible. The width of necrosis is usually less than 1 mm and subsequent healing is enhanced by autogenous bone grafting. This has clinical implications. PMID:12190137

  12. A Study of Bones = Un Estudio de Huesos.

    Science.gov (United States)

    Kogan, Yvonne

    Proving that project work can be done with young children who are schooled in a full-immersion program in a second language, this article describes a study of bones undertaken by 5-year-old children in a bilingual school in Mexico City. The article discusses the process and shows the results achieved by the children during the three phases of the…

  13. Preclinical in vivo Performance of Novel Biodegradable, Electrospun Poly(lactic acid and Poly(lactic-co-glycolic acid Nanocomposites: A Review

    Directory of Open Access Journals (Sweden)

    Claudia Holderegger

    2015-08-01

    Full Text Available Bone substitute materials have witnessed tremendous development over the past decades and autogenous bone may still be considered the gold standard for many clinicians and clinical approaches in order to rebuild and restore bone defects. However, a plethora of novel xenogenic and synthetic bone substitute materials have been introduced in recent years in the field of bone regeneration. As the development of bone is actually a calcification process within a collagen fiber arrangement, the use of scaffolds in the formation of fibers may offer some advantages, along with additional handling characteristics. This review focuses on material characteristics and degradation behavior of electrospun biodegradable polyester scaffolds. Furthermore, we concentrated on the preclinical in vivo performance with regard to bone regeneration in preclinical studies. The major findings are as follows: Scaffold composition and architecture determine its biological behavior and degradation characteristics; The incorporation of inorganic substances and/or organic substances within composite scaffolds enhances new bone formation; L-poly(lactic acid and poly(lactic-co-glycolic acid composite scaffolds, especially when combined with basic substances like hydroxyapatite, tricalcium phosphate or demineralized bone powder, seem not to induce inflammatory tissue reactions in vivo.

  14. A study of bone marrow failure syndrome in children

    Directory of Open Access Journals (Sweden)

    Gupta V

    2008-01-01

    Full Text Available Background: Bone marrow failure syndrome (BMFS, or aplastic anemia, includes peripheral blood single cytopenias, as well as pancytopenia due to inability of the marrow to effectively produce blood cells. Aim: To study the clinico-hematological profile and etiological factors of bone marrow failure syndrome in children. Setting and Design: This prospective study was carried out in the Department of Pediatrics of a university teaching hospital over 36 months. Materials and Methods: Children with pancytopenia (Hb < 10 g/dl, absolute neutrophil count < 1.5 x 10 9 /L, platelet count < 100 x 10 9 /L and bone marrow cellularity < 25% were included in the study. History of exposure to drugs, socioeconomic status, ethnicity and occupation of father were noted. Bone marrow aspiration; trephine biopsy; Ham test; viral studies for hepatitis A, B and C; and cytogenetic investigations were carried out. Statistical Analysis: Relative risk was estimated by odds ratio (OR with 95% confidence interval (CI in matched cases and controls. Results: Of the 53 children studied, 6 (11.3% were diagnosed as Fanconi anemia. Two cases had features of myelodysplastic syndrome. Forty-five children were labeled as acquired aplastic anemia, of whom one had evidence of hepatitis B infection and two patients (5.8% had paroxysmal nocturnal hemoglobinuria. Aplastic anemia was more common in children from family with lower socioeconomic status; in Muslims; and where the father′s occupation was weaving, dyeing and painting. However, the number was small to make statistically significant conclusions. No correlation could be established with exposure to drugs. Conclusion: Fanconi anemia was responsible for approximately one-tenth of the cases of bone marrow failure syndrome. Majority of the patients had acquired aplastic anemia. Hepatitis B infection was an uncommon cause of acquired aplastic anemia.

  15. Bone Enhancement with BMP-2 for Safe Clinical Translation

    OpenAIRE

    Kisiel, Marta

    2013-01-01

    Bone morphogenetic protein-2 (BMP-2) is considered a promising adjuvant for the treatment of bone regeneration. However, BMP-2 delivery in a conventional collagen scaffold needs a high dose to achieve an effective outcome. Moreover, such dosage may lead to serious side effects. The aim of the following thesis was to find clinically acceptable strategies reducing the required dose of BMP-2 by improving the delivery and optimizing the preclinical testing of the new approaches. In all the studie...

  16. Odanacatib Restores Trabecular Bone of Skeletally Mature Female Rabbits With Osteopenia but Induces Brittleness of Cortical Bone: A Comparative Study of the Investigational Drug With PTH, Estrogen, and Alendronate.

    Science.gov (United States)

    Khan, Mohd Parvez; Singh, Atul Kumar; Singh, Abhishek Kumar; Shrivastava, Pragya; Tiwari, Mahesh Chandra; Nagar, Geet Kumar; Bora, Himangshu Kousik; Parameswaran, Venkitanarayanan; Sanyal, Sabyasachi; Bellare, Jayesh R; Chattopadhyay, Naibedya

    2016-03-01

    Cathepsin K (CK), a lysosomal cysteine protease, is highly expressed in mature osteoclasts and degrades type 1 collagen. Odanacatib (ODN) is a selective and reversible CK inhibitor that inhibits bone loss in preclinical and clinical studies. Although an antiresorptive, ODN does not suppress bone formation, which led us to hypothesize that ODN may display restorative effect on the osteopenic bones. In a curative study, skeletally mature New Zealand rabbits were ovarectomized (OVX) and after induction of bone loss were given a steady-state exposure of ODN (9 mM/d) for 14 weeks. Sham-operated and OVX rabbits treated with alendronate (ALD), 17b-estradiol (E2), or parathyroid hormone (PTH) served as various controls. Efficacy was evaluated by assessing bone mineral density (BMD), bone microarchitecture (using micro-computed tomography), fluorescent labeling of bone, and biomechanical strength. Skeletal Ca/P ratio was measured by scanning electron microscopy (SEM) with X-ray microanalysis, crystallinity by X-ray diffraction, and bone mineral density distribution (tissue mineralization) by backscattered SEM. Between the sham and ODN-treated osteopenic groups, lumbar and femur metaphyseal BMD, Ca/P ratio, trabecular microstructure and geometric indices, vertebral compressive strength, trabecular lining cells, cortical parameters (femoral area and thickness and periosteal deposition), and serum P1NP were largely comparable. Skeletal improvements in ALD-treated or E2-treated groups fell significantly short of the sham/ODN/PTH group. However, the ODN group displayed reduced ductility and enhanced brittleness of central femur, which might have been contributed by higher crytallinity and tissue mineralization. Rabbit bone marrow stromal cells expressed CK and when treated with ODN displayed increased formation of mineralized nodules and decreased apoptosis in serum-deficient medium compared with control. In vivo, ODN did not suppress remodeling but inhibited osteoclast activity

  17. Manufacture of nanoparticles from bone: a preliminary study.

    Science.gov (United States)

    Florczyk, Stephen J; Saha, Subrata

    2009-01-01

    This study investigated a mechanical processing method using vibratory milling to reduce the particle size of bone ash to produce hydroxyapatite (HA) nanoparticles from bovine bone. Bovine femurs were cleaned of soft tissue, cut into small pieces, heated to 600 deg for 24 h, and ground into a coarse powder. A 50 wt% suspension was prepared, vibratory milled for 18 h, and then the milled suspension was filter pressed, dried, and ground into powder. The powder was analyzed with scanning electron microscopy and X-ray diffraction, which confirmed the particle size and the chemical composition of the powder-matched HA. The results of this study qualitatively showed that it is possible to produce HA nanoparticles from bone. This research explores a "green" manufacturing process that reuses a scrap material from the food industry and reduces the use of chemical precursors for synthetic nanoparticle synthesis. Such HA powder can potentially be used as a bone substitute and for coating orthopedic and dental implants. PMID:21083538

  18. Bone scintigraphy and osteo-articular tuberculosis in transplant patients: a study of 50 bone scans

    International Nuclear Information System (INIS)

    Bone scintigraphy with 99 m technecium labelled phosphorus compounds was achieved in 50 west Africans migrant workers in Paris. Bone and joint tuberculosis was assumed in 20 cases. In 5 of these 20 cases, bone scan, but not X-ray, showed abnormalities, and in 4, bone scan disclosed more localisations than X-rays. In 7 cases, yet, bone scan was normal, with major osteolytic X-rays lesions in 3 cases, minor in 2 cases, and isolated cold abcesses in two more cases: these means 7 false-negative results. Among the 30 other cases, 29 were considered as mechanical vertebral pathology, and 1 sacro-iliitis Brucellosis. Bone scan was normal in 28 cases the 2 others are unexplained false-positive. Although non-specific and not completely reliable, we think that bone-scanning is useful in bone-tuberculosis check-up, especially to obtain early diagnosis and detect multifocal localisations

  19. Bone scintigraphy and osteo-articular tuberculosis in transplant patients: a study of 50 bone scans

    Energy Technology Data Exchange (ETDEWEB)

    Coulaud, J.P.; Mechali, D.; Morau, G. (Hopital Claude-Bernard, Paris (France))

    1982-01-01

    Bone scintigraphy with 99 m technecium labelled phosphorus compounds was achieved in 50 west Africans migrant workers in Paris. Bone and joint tuberculosis was assumed in 20 cases. In 5 of these 20 cases, bone scan, but not X-ray, showed abnormalities, and in 4, bone scan disclosed more localisations than X-rays. In 7 cases, yet, bone scan was normal, with major osteolytic X-rays lesions in 3 cases, minor in 2 cases, and isolated cold abcesses in two more cases: these means 7 false-negative results. Among the 30 other cases, 29 were considered as mechanical vertebral pathology, and 1 sacro-iliitis Brucellosis. Bone scan was normal in 28 cases the 2 others are unexplained false-positive. Although non-specific and not completely reliable, we think that bone-scanning is useful in bone-tuberculosis check-up, especially to obtain early diagnosis and detect multifocal localisations.

  20. Spatial Navigation in Preclinical Alzheimer's Disease.

    Science.gov (United States)

    Allison, Samantha L; Fagan, Anne M; Morris, John C; Head, Denise

    2016-02-01

    Although several previous studies have demonstrated navigational deficits in early-stage symptomatic Alzheimer's disease (AD), navigational abilities in preclinical AD have not been examined. The present investigation examined the effects of preclinical AD and early-stage symptomatic AD on spatial navigation performance. Performance on tasks of wayfinding and route learning in a virtual reality environment were examined. Comparisons were made across the following three groups: Clinically normal without preclinical AD (n = 42), clinically normal with preclinical AD (n = 13), and early-stage symptomatic AD (n = 16) groups. Preclinical AD was defined based on cerebrospinal fluid Aβ42 levels below 500 pg/ml. Preclinical AD was associated with deficits in the use of a wayfinding strategy, but not a route learning strategy. Moreover, post-hoc analyses indicated that wayfinding performance had moderate sensitivity and specificity. Results also confirmed early-stage symptomatic AD-related deficits in the use of both wayfinding and route learning strategies. The results of this study suggest that aspects of spatial navigation may be particularly sensitive at detecting the earliest cognitive deficits of AD. PMID:26967209

  1. Bone loss in inflammatory Bowel disease: our multicentric study

    Directory of Open Access Journals (Sweden)

    Alessandro Geraci

    2011-05-01

    Full Text Available Patients with inflammatory bowel disease are at increased risk of developing disorder in bone and mineral metabolism The study was aimed to determine if inflammatory bowel disease (IBD is a risk factor for osteoporosis in 103 adult patients. We included 103 IBD patients, 67 patients with Crohn’s disease (CD and 36 with ulcerative colitis (UC. Bone mineral density was measured by dual-energy X-ray absorptiometry. We used T score to express bone loss (osteopenia: -2.5 SD <-1 SD, osteoporosis: T <-2.5 SD. Plain x-rays were examined to search for vertebral compression or spontaneous fractures before DEXA. Among the 103 patients, 47.7% exhibited osteopenia of the femoral neck and 62.3% of the lumbar spine, with no significant difference between CD and UC. The prevalence of osteoporosis of the lumbar spine was significantly higher in CD patients (41.2% versus 8.7%. Osteoporosis is frequent in IBD patients, especially in CD patients. Female gender, malnutrition (body mass index <20 kg/m2, disease course (>2 years and active disease would be risk factors of bone mineral loss in IBD.

  2. Cranial bone morphometric study among mouse strains

    OpenAIRE

    Yamamura Ken-ichi; Kawakami Minoru

    2008-01-01

    Abstract Background Little is known about the molecular mechanism which regulates how the whole cranium is shaped. Mouse models currently available for genetic research include several hundreds of unique inbred strains and genetically engineered mutants. By cross comparing their genomic structures, we can elucidate the cause of any differences in the phenotype between two strains. The craniometry of subspecies, or closely related species, of mice provide a good systemic model to study the rel...

  3. A clinical study on radiotherapy for metastatic bone tumor

    International Nuclear Information System (INIS)

    Seventy patients with 102 lesions of painful bone metastasis treated by radiation were studied. The conclusion is as follows; 1. Cumulative survival rate after irradiation to bone metastasis was very poor. Fifty percent survival term was very short, that was about 4 months in total cases, and 3 months in the cases of lung cancer. 2. It seemed that pain often occured in weight bearing bones. 3. In total cases, response rate was 85 % and complete response rate was 57 %. Concerning irradiated metastatic bone tumors, response rate was low in the thoracic and lumber spine, and concerning primary lesion it was low in cancer of the digestive organs. 4. It is important for pain relief to estimate the prognosis of a patient. ''A large dosage short term irradiation'' was more effective to the patient whom long survival term was not expected, because it was more effective and adequate for pain relief within short duration. 5. It needed TDF about 100 for pain relief without any correlation to primary lesion and histological type. It is equal to 40 Gy/8 fr./10 days and 60 Gy/30 fr./40 days. 6. An analysis of prognostic factor for pain relief was performed using multivariate analysis. Such factors were related to the prognosis of pain relief. Those were following; 1) treatment site, 2) histological type, 3) primary lesion, 4) total dose, 5) age, 6) one dose, 7) sex and 8) mode of metastasis. 7. There was no severe side effect that made it impossible to continue radiotherapy. 8. It seemed that the radiotherapy for painful bone metastasis was more effective and useful treatment. (author)

  4. Study of 201Tl uptake by bone and bone marrow on 201Tl scintigraphy

    International Nuclear Information System (INIS)

    Thallium-201 (Tl-201) uptake in the bone and bone marrow was examined in a total of 93 patients with various diseases. Sternal uptake of Tl-201 was observed when patients had bone marrow abnormality especially associated with hematopoietic disease. It was associated with proliferation of immature cells and of various types of bone marrow cells, especially erythroblastic and plasma cells. Whole-body Tl-201 scanning showed a high uptake (82%) in the sternum, chest, lumbar vertebrae, and pelvis. Thallium-201 was definitively taken up by the sternum in polycythemia (5/41), hemolytic anemia (2/2), iron deficiency anemia (2/2), and multiple myeloma (2/5). For leukemia, Tl-201 uptake was slight or negative. Thallium-201 scanning proved useful in visualizing bone marrow abnormality, although careful interpretation of bone and bone marrow uptake is required. (Namekawa, K)

  5. Performance characterization of a new CZT-based preclinical SPECT system: a comparative study of different collimators

    Science.gov (United States)

    Yu, A. R.; Park, S.-J.; Choi, Y. Y.; Kim, K. M.; Kim, H.-J.

    2015-09-01

    Triumph X-SPECT is a newly released CZT-based preclinical small-animal SPECT system with interchangeable collimators. The purpose of this work was to evaluate and systematically compare the imaging performances of three different collimators in the CZT-based preclinical small-animal system: a single-pinhole collimator (SPH), a multi-pinhole collimator (MPH) and a parallel-hole collimator. We measured the spatial resolutions and sensitivities of the three collimators with 99mTc sources, considering three distinct energy window widths (5, 10, and 20%), and used the NEMA NU4-2008 Image Quality phantom to test the imaging performance of the three collimators in terms of uniformity and spill-over ratio (SOR) for each energy window. With a 10% energy window width at a radius of rotation (ROR) of 30 mm, the system resolution of the SPH, MPH and parallel-hole collimators was 0.715, 0.855 and 3.270 mm FWHM, respectively. For the same energy window, the sensitivity of the system with SPH, MPH and parallel-hole collimators was 32.860, 152.514 and 49.205 counts/sec/MBq at a 100 mm source-to-detector distance and 6.790, 33.376 and 49.038 counts/sec/MBq at a 130 mm source-to-detector distance, respectively. The image noise and SORair for the three collimators were 20.137, 12.278 and 11.232 (%STDunif) and 0.106, 0.140 and 0.161, respectively. Overall, the results show that the SPH had better spatial resolution than the other collimators. The MPH had the highest sensitivity at 100 mm source-to-collimator distance, and the parallel-hole collimator had the highest sensitivity at 130 mm-source-to-detector distance. Therefore, the proper collimator for Triumph X-SPECT system must be determined by the task. These results provide valuable reference data and insight into the imaging performance of various collimators in CZT-based preclinical small-animal SPECT.

  6. Performance characterization of a new CZT-based preclinical SPECT system: a comparative study of different collimators

    International Nuclear Information System (INIS)

    Triumph X-SPECT is a newly released CZT-based preclinical small-animal SPECT system with interchangeable collimators. The purpose of this work was to evaluate and systematically compare the imaging performances of three different collimators in the CZT-based preclinical small-animal system: a single-pinhole collimator (SPH), a multi-pinhole collimator (MPH) and a parallel-hole collimator. We measured the spatial resolutions and sensitivities of the three collimators with 99mTc sources, considering three distinct energy window widths (5, 10, and 20%), and used the NEMA NU4-2008 Image Quality phantom to test the imaging performance of the three collimators in terms of uniformity and spill-over ratio (SOR) for each energy window. With a 10% energy window width at a radius of rotation (ROR) of 30 mm, the system resolution of the SPH, MPH and parallel-hole collimators was 0.715, 0.855 and 3.270 mm FWHM, respectively. For the same energy window, the sensitivity of the system with SPH, MPH and parallel-hole collimators was 32.860, 152.514 and 49.205 counts/sec/MBq at a 100 mm source-to-detector distance and 6.790, 33.376 and 49.038 counts/sec/MBq at a 130 mm source-to-detector distance, respectively. The image noise and SORair for the three collimators were 20.137, 12.278 and 11.232 (%STDunif) and 0.106, 0.140 and 0.161, respectively. Overall, the results show that the SPH had better spatial resolution than the other collimators. The MPH had the highest sensitivity at 100 mm source-to-collimator distance, and the parallel-hole collimator had the highest sensitivity at 130 mm-source-to-detector distance. Therefore, the proper collimator for Triumph X-SPECT system must be determined by the task. These results provide valuable reference data and insight into the imaging performance of various collimators in CZT-based preclinical small-animal SPECT

  7. Effects of Two Types of Anorganic Bovine Bone on Bone Regeneration: A Histological and Histomorphometric Study of Rabbit Calvaria

    OpenAIRE

    Mojgan Paknejad; Amir Reza Rokn; Siamak Yaghobee; Pantea Moradinejad; Mohadeseh Heidari; Ali Mehrfard

    2014-01-01

    Objective: The purpose of this study was to evaluate the efficacy of two types of bone substitutes, Bio-Oss and NuOss, for repair of bone defects. Materials and Methods: This study was performed on the calvaria of 14 New Zealand rabbits. The 6mm critical size defect (CSD) models of bone regeneration were used. Three CSDs were created in each surgical site. The first defect was filled with NuOss, the second one with Bio-Oss and the third one remained unfilled as the control. After healing peri...

  8. Nanomedicines for cancer therapy: state-of-the-art and limitations to pre-clinical studies that hinder future developments

    Science.gov (United States)

    Dawidczyk, Charlene; Russell, Luisa; Searson, Peter

    2014-08-01

    The ability to efficiently deliver a drug or gene to a tumor site is dependent on a wide range of factors including circulation time, interactions with the mononuclear phagocyte system, extravasation from circulation at the tumor site, targeting strategy, release from the delivery vehicle, and uptake in cancer cells. Nanotechnology provides the possibility of creating delivery systems where the design constraints are decoupled, allowing new approaches for reducing the unwanted side effects of systemic delivery, increasing tumor accumulation, and improving efficacy. The physico-chemical properties of nanoparticle-based delivery platforms introduce additional complexity associated with pharmacokinetics and tumor accumulation. To assess the impact of nanoparticle-based delivery systems, we first review the design strategies and pharmacokinetics of FDA-approved nanomedicines. Next we review nanomedicines under development, summarizing the range of nanoparticle platforms, strategies for targeting, and pharmacokinetics. We show how the lack of uniformity in preclinical trials prevents systematic comparison and hence limits advances in the field.

  9. ISO 12189 standard for the preclinical evaluation of posterior spinal stabilization devices--II: A parametric comparative study.

    Science.gov (United States)

    La Barbera, Luigi; Costa, Francesco; Villa, Tomaso

    2016-02-01

    The International Standardization Organization (ISO) 12189 standard was recently introduced to preclinically evaluate and compare the mechanical properties of posterior stabilization devices. This scenario presents some new significant steps ahead over the vertebrectomy model recommended by American Society for Testing and Materials (ASTM) F1717 standard: the modular anterior support allows for describing a closer scenario to the effective clinical use as well as to test very flexible and dynamic posterior stabilization devices. Despite these significant advantages, ISO 12189 received little attention in the literature. Anatomical parameters depending on the spinal level were compared to the published data or original measurements on biplanar stereoradiography on 13 patients. Other mechanical variables, describing the test set-up design, were considered and all parameters were investigated using a numerical parametric finite element model. Stress values were calculated by also considering their worst-case combination. The standard set-up represents quite well the anatomy of an instrumented average thoracolumbar segment. The parametric comparative analysis demonstrates a significant (even beyond +350%) maximum increase in the stress on the device, compared to the standard currently in use. The anterior support stiffness plays the most detrimental effect (maximum stress increases up to 396%). The initial precompression step has an important role in determining the final stress values achieved at peak load (up to +76%). Moreover, when combining these two contributions, an even higher stress increase may be achieved (up to 473%). Despite the other anatomical parameters playing a secondary role, their worst-case combination demonstrates that a device could potentially undergo higher stresses than those reached according to standard suggestions (maximum increase of 22.4% at L1). Any user/designer should be aware of these effects when using ISO 12189 standard for the

  10. Tracking the hyoid bone in videofluoroscopic swallowing studies

    Science.gov (United States)

    Kellen, Patrick M.; Becker, Darci; Reinhardt, Joseph M.; van Daele, Douglas

    2008-03-01

    Difficulty swallowing, or dysphagia, has become a growing problem. Swallowing complications can lead to malnutrition, dehydration, respiratory infection, and even death. The current gold standard for analyzing and diagnosing dysphagia is the videofluoroscopic barium swallow study. In these studies, a fluoroscope is used to image the patient ingesting barium solutions of different volumes and viscosities. The hyoid bone anchors many key muscles involved in swallowing and plays a key role in the process. Abnormal hyoid bone motion during a swallow can indicate swallowing dysfunction. Currently in clinical settings, hyoid bone motion is assessed qualitatively, which can be subject to intra-rater and inter-rater bias. This paper presents a semi-automatic method for tracking the hyoid bone that makes quantitative analysis feasible. The user defines a template of the hyoid on one frame, and this template is tracked across subsequent frames. The matching phase is optimized by predicting the position of the template based on kinematics. An expert speech pathologist marked the position of the hyoid on each frame of ten studies to serve as the gold standard. Results from performing Bland-Altman analysis at a 95% confidence interval showed a bias of 0.0+/-0.08 pixels in x and -0.08+/-0.09 pixels in y between the manually-defined gold standard and the proposed method. The average Pearson's correlation between the gold standard and the proposed method was 0.987 in x and 0.980 in y. This paper also presents a method for automatically establishing a patient-centric coordinate system for the interpretation of hyoid motion. This coordinate system corrects for upper body patient motion during the study and identifies superior-inferior and anterior-posterior motion components. These tools make the use of quantitative hyoid motion analysis feasible in clinical and research settings.

  11. Evaluation of the appropriateness of the preclinical phase (stage A and stage B) of heart failure Management in Outpatient clinics in Italy rationale and design of the 'VASTISSIMO' study.

    Science.gov (United States)

    Mureddu, Gian F; Nistri, Stefano; Faggiano, Pompilio; Fimiani, Biagio; Misuraca, Gianfranco; Maggi, Antonio; Gori, Anna M; Uguccioni, Massimo; Tavazzi, Luigi; Zito, Giovanni B

    2016-07-01

    Early detection of heart failure, when still preclinical, is fundamental. Therefore, it is important to assess whether preclinical heart failure management by cardiologists is adequate. The VASTISSIMO study ('EValuation of the AppropriateneSs of The preclInical phase (Stage A and Stage B) of heart failure Management in Outpatient clinics in Italy') is a prospective nationwide study aimed to evaluate the appropriateness of diagnosis and management of preclinical heart failure (stages A and B) by cardiologists working in outpatient clinics in Italy. Secondary goals are to verify if an online educational course for cardiologists can improve management of preclinical heart failure, and evaluate how well cardiologists are aware of patients' adherence to medications. The study involves 80 outpatient cardiology clinics distributed throughout Italy, affiliated either to the Hospital Cardiologists Association or to the Regional Association of Outpatient Cardiologists, and is designed with two phases of consecutive outpatient enrolment each lasting 1 month. In phase 1, physicians' awareness of the risk of heart failure and their decision-making process are recorded. Subsequently, half of the cardiologists are randomized to undergo an online educational course aimed to improve preclinical heart failure management through implementation of guideline recommendations. At the end of the course, all cardiologists are evaluated (phase 2) to see whether changes in clinical management have occurred in those who underwent the educational program versus those who did not. Patients' adherence to prescribed medications will be assessed through the Morisky Self-report Questionnaire. This study should provide valuable information about cardiologists' awareness of preclinical heart failure and the appropriateness of clinical practice in outpatient cardiology clinics in Italy. PMID:27028840

  12. Infant dietary patterns and bone mass in childhood: the Generation R Study

    OpenAIRE

    van den Hooven, E. H.; Heppe, D. H. M.; Kiefte-de Jong, J.C.; Medina-Gomez, C; Moll, H.A.; Hofman, A.; Jaddoe, V. W. V.; Rivadeneira, F.; Franco, O. H.

    2015-01-01

    Summary Early life nutrition affects peak bone mass attainment. In this prospective cohort study, children with high adherence to a “dairy and whole grains” pattern in infancy had higher bone mineral density at the age of 6 years. Although the observed effects are small, our study provides insight into mechanisms linking early nutrition to bone acquisition in childhood. Introduction Nutrition in early life may affect peak bone mass attainment. Previous studies on childhood nutrition and skele...

  13. Essentials for starting a pediatric clinical study (4): Clinical pediatric safety planning based on preclinical toxicity studies and pediatric pharmacovigilance guidance.

    Science.gov (United States)

    Sheth, Neha

    2009-01-01

    Juvenile toxicology studies in animals provide useful information to guide monitoring of potential adverse effects in children especially on growth and development. In order to continue to gain knowledge and build upon these preclinical studies, recent experience has suggested that additional approaches for monitoring of safety concerns in the pediatric population may be required. Recently, pediatric guidance has become available from the health authorities which provide pharmacovigilance concepts as they specifically relate to drugs being developed for pediatric indications. Clinical trials are typically not robust enough to detect rare or delayed safety effects as the pediatric trials are relatively short-term. Furthermore, such long term or rare effects may not be detected via standard voluntary postmarketing surveillance. Safety monitoring of children with Juvenile Inflammatory Arthritis (JIA) taking nonsteroid anti-inflammatory drug (NSAID)s will be used as an example to describe a post-marketing risk management and pharmacovigilance program that serves to better evaluate safety data from various sources. The intent of this program is to identify adverse events (AE), including events with longer latency, which may be associated with NSAID use in a pediatric population. In this presentation, the 4 major components of the program are to be addressed. Such a program may serve as a model to proactively generate and monitor safety data in order to identify AEs that may be associated with new therapeutics for a pediatric population. PMID:19571487

  14. Preclinical study of radioiodinated glucose-Tyr3-octreotate: Comparison with 111In-DOTA-Tyr3-octreotate

    International Nuclear Information System (INIS)

    Full text: Targeted radionuclide imaging and treatment are based upon the interaction of radioligands with receptors in the target tissue (namely high density receptor specific tumours). As receptors for somatostatin (mainly somatostatin receptor subtype-2 /sstr2/) are over-expressed in several human tumours of endocrine origin, a number of radiolabeled somatostatin analogs have been recently introduced as the vectors for targeted imaging and therapy; commercially available 111In-DTPA-octreotide being a gold standard in this field. Several publications demonstrate that a substitution of Tyr instead of Phe in the peptide position 3 and oxidation of carboxyl end of octreotide significantly increased the affinity of the peptide to sstr2. More recently it has been shown that NH2-terminal carbohydration leads to a further improvement of the peptide receptor affinity and its retention in the tumour. In this study we present preclinical analysis of distribution profile and elimination pathways of radioiodinated glucose-Tyr3-octreotate (125I-gluc-TOCA) in comparison with that of another promising targeted radiopharmaceutical, namely 111In-DOTA-Tyr3-octreotate (111In- DOTA-TOCA). Gluc-TOCA was radioiodinated using chloramine-T method. For radiolabeling of DOTA-TOCA with radiometal, to 200 μl of 0.4 M acetate buffer with 0.24 M gentisic acid pH 5, 10μl of peptide solution in 0.1% TFA (1mg/ml) were added together with 0.5-1 mCi of 111InCl3 in 0.04 M HCl. Reaction mixture was heated 25 minutes to 90-95 deg. C. Pharmacokinetic studies were performed on male Wistar rats. Results confirmed that specific internalization of 125I-gluc-TOCA by sstr2 - expressing AR423 rat pancreatic carcinoma cells in vitro was about twice of that for 111In-DOTA-TOCA. In rats, 125I-gluc-TOCA exhibited prolonged plasma clearance in comparison with the other peptide. Slower decrease of plasma radioactivity after 125I-gluc-TOCA was due to its higher lipophilicity and thus higher plasma protein binding

  15. Effects of two types of anorganic bovine bone on bone regeneration: a histological and histomorphometric study of rabbit calvaria.

    Directory of Open Access Journals (Sweden)

    Mojgan Paknejad

    2014-12-01

    Full Text Available The purpose of this study was to evaluate the efficacy of two types of bone substitutes, Bio-Oss and NuOss, for repair of bone defects.This study was performed on the calvaria of 14 New Zealand rabbits. The 6mm critical size defect (CSD models of bone regeneration were used. Three CSDs were created in each surgical site. The first defect was filled with NuOss, the second one with Bio-Oss and the third one remained unfilled as the control. After healing periods of one and two months (seven animal for each time point, histological and histomorphometric analyses were carried out to assess the amount of new bone formation, presence of inflammation, foreign body reaction and type of new bone. Qualitative variables were analyzed by multiple comparisons, Wilcoxon, Friedman and Mann Whitney tests. Quantitative variables were analyzed using the Mann-Whitney and Wilcoxon tests. Level of statistical significance was set at 0.05.The level of inflammation was not significantly different at four and eight weeks in the Bio-Oss (P=0.944, NuOss (P=1.000 and control groups (P=0.71. At four weeks, foreign body reaction was not observed in Bio-Oss, NuOss and control groups. There was no significant difference in the type of the newly formed bone at four and eight weeks in any group (P=0.141 for Bio-Oss, P=0.06 for NuOss and P=0.389 for the control group.Deproteinized bovine bone mineral can be used as a scaffold in bone defects to induce bone regeneration.

  16. Human B-cell cancer cell lines as a preclinical model for studies of drug effect in diffuse large B-cell lymphoma and multiple myeloma.

    Science.gov (United States)

    Laursen, Maria Bach; Falgreen, Steffen; Bødker, Julie Støve; Schmitz, Alexander; Kjeldsen, Malene Krag; Sørensen, Suzette; Madsen, Jakob; El-Galaly, Tarec Christoffer; Bøgsted, Martin; Dybkær, Karen; Johnsen, Hans Erik

    2014-11-01

    Drug resistance in cancer refers to recurrent or primary refractory disease following drug therapy. At the cellular level, it is a consequence of molecular functions that ultimately enable the cell to resist cell death-one of the classical hallmarks of cancer. Thus, drug resistance is a fundamental aspect of the cancer cell phenotype, in parallel with sustained proliferation, immortality, angiogenesis, invasion, and metastasis. Here we present a preclinical model of human B-cell cancer cell lines used to identify genes involved in specific drug resistance. This process includes a standardized technical setup for specific drug screening, analysis of global gene expression, and the statistical considerations required to develop resistance gene signatures. The state of the art is illustrated by the first-step classical drug screen (including the CD20 antibody rituximab, the DNA intercalating topoisomerase II inhibitor doxorubicin, the mitotic inhibitor vincristine, and the alkylating agents cyclophosphamide and melphalan) along with the generation of gene lists predicting the chemotherapeutic outcome as validated retrospectively in clinical trial datasets. This B-cell lineage-specific preclinical model will allow us to initiate a range of laboratory studies, with focus on specific gene functions involved in molecular resistance mechanisms. PMID:25072621

  17. Topography of Acoustical Properties of Long Bones: From Biomechanical Studies to Bone Health Assessment

    OpenAIRE

    Tatarinov, Alexey; Sarvazyan, Armen

    2008-01-01

    The article presents a retrospective view on the assessment of long bones condition using topographical patterns of the acoustic properties. The application of ultrasonic point-contact transducers with exponential waveguides on a short acoustic base for detailed measurements in human long bones by the surface transmission was initiated during the 1980s in Latvia. The guided wave velocity was mapped on the surface of the long bones and the topographical patterns reflected the biomechanical pec...

  18. Bone Geometry, Volumetric Bone Mineral Density, Microarchitecture and Estimated Bone Strength in Caucasian Females with Systemic Lupus Erythematosus. A Cross-Sectional Study Using HR-pQCT

    DEFF Research Database (Denmark)

    Hansen, Stinus; Gudex, Claire; Ahrberg, Fabian; Brixen, Kim; Voss, Anne

    2014-01-01

    Patients with systemic lupus erythematosus (SLE) have an increased risk of fracture. We used high resolution peripheral quantitative computed tomography (HR-pQCT) to measure bone geometry, volumetric bone mineral density (vBMD), cortical and trabecular microarchitecture and estimated bone strength...... by finite element analysis (FEA) at the distal radius and tibia to assess bone characteristics beyond BMD that may contribute to the increased risk of fracture. Thirty-three Caucasian women with SLE (median age 48, range 21-64 years) and 99 controls (median age 45, range 21-64 years) were studied....... Groups were comparable in radius regarding geometry and vBMD, but SLE patients had lower trabecular number (-7 %, p < 0.05), higher trabecular separation (13 %, p < 0.05) and lower FEA-estimated failure load compared to controls (-10 %, p < 0.05). In tibia, SLE patients had lower total vBMD (-11 %, p < 0...

  19. Prevalence and variation of sesamoid bones in the hand: a multi-center radiographic study

    OpenAIRE

    Chen, Wei; Cheng, Jiaxiang; Sun, Ran; Zhang, Zekun; Zhu, Yanbin; Ipaktchi, Kyros; Zhang, Yingze

    2015-01-01

    There is rare studies with regard to sesamoid bone variations of the hand in addition to its prevalence and distribution. This study aims to assess both the prevalence and variation of sesamoid bones of the hand. A retrospective review of posteroanterior (PA) and oblique radiographs of 436 left and 414 right hands of 850 adult patients obtained from four hospitals was performed. All X-ray films were examined independently for existing sesamoid bones. The presence of sesamoid bones was confirm...

  20. Effect of porous polycaprolactone beads on bone regeneration: preliminary in vitro and in vivo studies

    OpenAIRE

    Byun, June-Ho; Lee, Han A Reum; Kim, Tae Ho; Lee, Jin Ho; Oh, Se Heang

    2014-01-01

    Background For the effective bone regeneration with appropriate pathological/physiological properties, a variety of bone fillers have been adapted as a therapeutic treatment. However, the development of ideal bone fillers is still remained as a big challenge in clinical practice. The main aims of this study are i) fabrication of a highly porous PCL beads; and ii) the estimation of the potential use of the porous PCL beads as a bone filler through preliminary animal study. Results The porous P...

  1. Update of the Stroke Therapy Academic Industry Roundtable Preclinical Recommendations

    OpenAIRE

    Fisher, Marc; Feuerstein, Giora; Howells, David W.; Hurn, Patricia D.; Kent, Thomas A.; Savitz, Sean I.; Lo, Eng H

    2009-01-01

    The initial Stroke Therapy Academic Industry Roundtable (STAIR) recommendations published in 1999 were intended to improve the quality of preclinical studies of purported acute stroke therapies. Although recognized as reasonable, they have not been closely followed nor rigorously validated. Substantial advances have occurred regarding the appropriate quality and breadth of preclinical testing for candidate acute stroke therapies for better clinical translation. The updated STAIR preclinical r...

  2. The basics of preclinical drug development for neurodegenerative disease indications

    OpenAIRE

    Spack Edward G; Steinmetz Karen L

    2009-01-01

    Abstract Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have...

  3. Experimental study with domestic bone cement in the percutaneous vertebroplasty

    International Nuclear Information System (INIS)

    Objective: To study the feasibility of injecting domestic bone cement in the process of the percutaneous vertebroplasty. Methods: (1) Various types cement were disposed with domestic PMMA. The concretionary phases of cement were observed according to the stages and holding time. Then the most ideal ratio of the mixed cement was selected and ten cement columns were made with this ratio, which was taken as the trial group. The other ten referring to was taken as the contrast one. The biological mechanics was measured with a load and the data of the results were compared. (2) Twenty thoracic and lumbar adjacent bodies were removed intact from five human corpses. These bodies were divided into two groups, in one group PMMA were injected, the other was severed as the contrast one. Then in these twenty vertebral bodies the biological mechanics was measured and the treatment effect was evaluated. (3) In 12 healthy dogs PVP in lumber was tried so as to observe the operational difficulty during the process of injected this bone cement and CT was used to evaluate the result of PMMA, diffusion and the complications caused by it. Results: The most ideal ratio was 4:2.6:1 (g, ml, ml) between powder, monome and contrast. After injecting this kind of cement, the loading strength of these vertebral bodies was increased remarkably (P<0.01). Conclusion: Injecting domestic bone cement provides the theoretical foundations for the clinical application of PVP. (author)

  4. Clinical study and image diagnosis of nasal bone fracture

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Takenori; Suzuki, Naohiro; Okitsu, Takuji [Sendai City Hospital (Japan)

    2002-01-01

    In this study we reviewed the clinical features, diagnoses and treatments of 232 cases of nasal bone fracture cases treated at our department from January 1994 to June 2000. A marked predominance of males in the age range of 10-29 years was noted. Analysis of the causes of the nasal fractures were attributed to fighting (66 cases), traffic accidents (64 cases), sports (56 cases) and others (46 cases). The external appearance of nasal fractures were divided into 5 types, 85 cases of the displacement type, 27 cases of the depressed type, 32 of the mixed type, 56 of the non-deformation type and 32 of the unclassified type because of facial swelling. The sensitivity of conventional X-ray examination in identifying nasal fractures was 75.6%. Computed tomography scan (CT scan) was performed in 196 patients and showed that the middle and lower portions of nasal bones were fractured more easily than those of the upper portion. Nasal septum fracture occurred in 22 cases (11.2%). Other facial fractures combined with nasal fracture were found in 40 cases (20.4%). The type of combined fracture depended on the cause of the injury, for example, the combination of nasal and blow-out fracture was often caused by fighting, and many combined fractures of more than two facial bones resulted from traffic accidents. A total of 83 patients (35.8%) received reduction of the nasal bone fractures under general anaesthesia. The measurement of irradiation of each radiological examination revealed that the exposed dose of the newest model CT was similar to that of the conventional X-ray examination and tomography. (author)

  5. Meta-analysis of pre-clinical studies of early decompression in acute spinal cord injury: a battle of time and pressure.

    Directory of Open Access Journals (Sweden)

    Peter E Batchelor

    Full Text Available The use of early decompression in the management of acute spinal cord injury (SCI remains contentious despite many pre-clinical studies demonstrating benefits and a small number of supportive clinical studies. Although the pre-clinical literature favours the concept of early decompression, translation is hindered by uncertainties regarding overall treatment efficacy and timing of decompression.We performed meta-analysis to examine the pre-clinical literature on acute decompression of the injured spinal cord. Three databases were utilised; PubMed, ISI Web of Science and Embase. Our inclusion criteria consisted of (i the reporting of efficacy of decompression at various time intervals (ii number of animals and (iii the mean outcome and variance in each group. Random effects meta-analysis was used and the impact of study design characteristics assessed with meta-regression.Overall, decompression improved behavioural outcome by 35.1% (95%CI 27.4-42.8; I(2=94%, p<0.001. Measures to minimise bias were not routinely reported with blinding associated with a smaller but still significant benefit. Publication bias likely also contributed to an overestimation of efficacy. Meta-regression demonstrated a number of factors affecting outcome, notably compressive pressure and duration (adjusted r(2=0.204, p<0.002, with increased pressure and longer durations of compression associated with smaller treatment effects. Plotting the compressive pressure against the duration of compression resulting in paraplegia in individual studies revealed a power law relationship; high compressive forces quickly resulted in paraplegia, while low compressive forces accompanying canal narrowing resulted in paresis over many hours.These data suggest early decompression improves neurobehavioural deficits in animal models of SCI. Although much of the literature had limited internal validity, benefit was maintained across high quality studies. The close relationship of compressive

  6. [Studies of biologic activation associated with molecular receptor increase and tumor response in ChL6/L6 protocol patients; Studies in phantoms; Quantitative SPECT; Preclinical studies; and Clinical studies]. DOE annual report, 1994-95

    International Nuclear Information System (INIS)

    The authors describe results which have not yet been published from their associated studies listed in the title. For the first, they discuss Lym-1 single chain genetically engineered molecules, analysis of molecular genetic coded messages to enhance tumor response, and human dosimetry and therapeutic human use radiopharmaceuticals. Studies in phantoms includes a discussion of planar image quantitation, counts coincidence correction, organ studies, tumor studies, and 90Y quantitation with Bremsstrahlung imaging. The study on SPECT discusses attenuation correction and scatter correction. Preclinical studies investigated uptake of 90Y-BrE-3 in mice using autoradiography. Clinical studies discuss image quantitation verses counts from biopsy samples, S factors for radiation dose calculation, 67Cu imaging studies for lymphoma cancer, and 111In MoAb imaging studies for breast cancer to predict 90Y MoAb therapy

  7. Orthopantomographic study of the alveolar bone level on periodontal disease

    International Nuclear Information System (INIS)

    The author had measured the alveolar bone level of periodontal disease on 50 cases of orthopantomogram to detect the degree of alveolar bone resorption of both sexes of Korean. The results were obtained as follows; 1. Alveolar bone resorption of mesial and distal portion was similar in same patient. 2. The order of alveolar bone resorption was mandibular anterior region, posterior region, canine and premolar region of both jaws. 3. The degree of alveolar bone destruction was severe in shorter root length than longer one. 4. The degree of alveolar bone resorption was severe in fourth decades.

  8. Studying Light Propagation in Bone for Treatment of Bone Cancers with Photodynamic Therapy

    Science.gov (United States)

    Rossi, Vincent; Gustafson, Scott; Jacques, Steven

    2008-05-01

    Photodynamic therapy makes use of light, photosensitizing agents, and oxygen as a selective means of treating cancer. The work presented is aimed at applying photodynamic therapy towards treatment of osteosarcoma in small animal clinics. To best facilitate clinical treatments, we must first understand how light propagates and how best to deliver adequate light to achieve phototoxic effects within bone. This work aims at characterizing how light propagates through bone and then applying that knowledge towards predicting light distributions in bone. Reflectance spectroscopy using an optical fiber source-collector pair is used to determine the scattering properties of bone tissues, and the absorption due to water and oxygenated and deoxygenated hemoglobin---native absorbers at visible and near-IR wavelengths. Resulting optical characterizations are then applied to a cylindrically symmetric Monte Carlo model in order to predict and guide the delivery of light within bone in order to achieve the desired phototoxic effect.

  9. Bone density and hemoglobin levels in older persons: results from the InCHIANTI study.

    Science.gov (United States)

    Cesari, Matteo; Pahor, Marco; Lauretani, Fulvio; Penninx, Brenda W H J; Bartali, Benedetta; Russo, Roberto; Cherubini, Antonio; Woodman, Richard; Bandinelli, Stefania; Guralnik, Jack M; Ferrucci, Luigi

    2005-06-01

    Hypoxemia has been recognized as a risk factor for bone loss. The aim of the present study is to investigate the relationship of bone mass and density measures with anemia and hemoglobin levels in a large sample of older community-dwelling persons. The study is based on data from 950 participants enrolled in the "Invecchiare in Chianti" (Aging in the Chianti area, InCHIANTI) study. All the analyses were performed considering continuous hemoglobin levels as well as the dichotomous anemia variable (defined according to WHO criteria as hemoglobin < 12 g/dl in women and < 13 g/dl in men). A peripheral quantitative computerized tomography (pQCT) scan of the right calf was performed in all participants to evaluate total bone density, trabecular bone density, cortical bone density, and the ratio between cortical and total bone area. Linear regression analyses were used to assess the multivariate relationship of pQCT bone measures with anemia and hemoglobin levels after adjustment for demographics, chronic conditions, muscle strength and biological variables. Participants were 75.0 (SD 6.9) years old. In our sample, 101 participants (10.6%) were anemic. In women, coefficients from adjusted linear regression analyses evaluating the association between pQCT bone measures (per SD increase) and hemoglobin levels/anemia showed significant associations of anemia with total bone density (beta = -0.335, SE = 0.163; P = 0.04) and cortical bone density (beta = -0.428, SE = 0.160; P = 0.008). Relationships with borderline significance were found for the associations of anemia with trabecular bone density and the ratio between cortical and total bone area. Significant associations were found between hemoglobin levels and trabecular bone density (beta = 0.112, SE = 0.049; P = 0.02), total bone density (beta = 0.101, SE = 0.046; P = 0.03), cortical bone density (beta = 0.100, SE = 0.046; P = 0.03) and the ratio between cortical bone and total area (beta = 0.092, SE = 0.045; P = 0

  10. Bone densitometry in the Feminine Climacteric routine study or election?

    International Nuclear Information System (INIS)

    A descriptive and cross-sectional study was conducted, on the basis of a systematic review of the clinical histories of the database, between July 1999 and July 2001.Strategy consisted of reviewing at random clinical data up to obtaining a sample of 100 patients with bone densitometry by mains of dual energy X ray absorbtiometry (DEXA) device. The standard number was statistically significant and representative of the population under study.Results: It is emphasized that more of a hal of the patients studied presented loss of the bone mineral density and 11% with and altered morphometry of the column, similar to other national and international studies. the risk factors for osteoporosis were presented in 71% of the cases, having those patients older densitometric alterations.Conclusions:considering the results and the situation that generates risk of fracture with its high socioeconomic costs, the authors recommend the routine use of the densitometry in the Feminine Climateric or in its absence, a selective screening, reserving the study for patients with given risk factors.It is proposed a guideline to select patients in which conducting the study ia a priority

  11. The value of the UK Clinical Aptitude Test in predicting pre-clinical performance: a prospective cohort study at Nottingham Medical School

    Directory of Open Access Journals (Sweden)

    James David

    2010-07-01

    Full Text Available Abstract Background The UK Clinical Aptitude Test (UKCAT was introduced in 2006 as an additional tool for the selection of medical students. It tests mental ability in four distinct domains (Quantitative Reasoning, Verbal Reasoning, Abstract Reasoning, and Decision Analysis, and the results are available to students and admissions panels in advance of the selection process. As yet the predictive validity of the test against course performance is largely unknown. The study objective was to determine whether UKCAT scores predict performance during the first two years of the 5-year undergraduate medical course at Nottingham. Methods We studied a single cohort of students, who entered Nottingham Medical School in October 2007 and had taken the UKCAT. We used linear regression analysis to identify independent predictors of marks for different parts of the 2-year preclinical course. Results Data were available for 204/260 (78% of the entry cohort. The UKCAT total score had little predictive value. Quantitative Reasoning was a significant independent predictor of course marks in Theme A ('The Cell', (p = 0.005, and Verbal Reasoning predicted Theme C ('The Community' (p Conclusion This limited study from a single entry cohort at one medical school suggests that the predictive value of the UKCAT, particularly the total score, is low. Section scores may predict success in specific types of course assessment. The ultimate test of validity will not be available for some years, when current cohorts of students graduate. However, if this test of mental ability does not predict preclinical performance, it is arguably less likely to predict the outcome in the clinical years. Further research from medical schools with different types of curriculum and assessment is needed, with longitudinal studies throughout the course.

  12. Effects of bone morphogenetic protein-2 on bone cells in primary culture: immunohistochemical and electronmicroscopical studies

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, I.; Prochnow, N.; Mueller, K.M. [Berufsgenossenschaftliche Kliniken Bergmannsheil, Bochum (Germany). Inst. fuer Pathologie; Wiemann, M.; Schirrmacher, K.; Bingmann, D. [Essen Univ. (Germany). Inst. fuer Physiologie; Sebald, W. [Wuerzburg Univ. (Germany). Inst. fuer Physiologische Chemie II

    2001-02-01

    Bone morphogenetic protein 2 (BMP-2), among other morphogenetic effects on non osseous tissues, promotes bone formation in vivo. Therefore, BMP-2 may accelerate the integration of osseous implants. Although the effects of BMPs on cell proliferation have been studied extensively in vivo or in cell lines, little is published about effects on bone cells in primary cultures, especially on cell differentiation. As such information is a prerequisite to understand and to control effects of BMPs on cells at the surface of implant materials, the present experiments aimed to describe effects of BMP-2 on primary cultures derived from calvarial fragments of neonatal rats. The cells were stimulated with 50 nM BMP-2 added to the nutrient medium for 3 or 6 days. Light- and electronmicroscopical studies showed that cells in the sprouting zones were larger and more often spindle shaped. Stimulated cells had more nucleoli than control cells and the endoplasmic reticulum was widened. They retained properties of typical bone cells: An immunhistochemical analysis showed that stimulated cells increased the activity of alkaline phosphatase, they secreted collagen type I and to a minor extent collagen type III. In BMP-2 treated cells the pattern of cells stained for actin, desmin and vimentin hardly changed whereas extracellular fibronectin appeared to be less cross-linked in BMP-2 treated cultures. The distribution and labeling strength of osteocalcin, a specific marker protein of bone cells did not change markedly. After exposure to BMP-2 cells tended to detach from the cover slips. Electron microscopy showed a reduced number of cell processes possibly facilitating the detachment and/or mobility. Stimulated cells contained an increased number of lamellar bodies which may reflect an increased synthesis and/or membrane turnover. Staining of non-osseous cells with anti-CD68-or anti-myeloid antibodies revealed that the small percentage of these cells regularly occurring in primary cultures

  13. Effects of low-intensity pulsed ultrasound on new trabecular bone during bone-tendon junction healing in a rabbit model: a synchrotron radiation micro-CT study.

    Directory of Open Access Journals (Sweden)

    Hongbin Lu

    Full Text Available This study was designed to evaluate the effects of low-intensity pulsed ultrasound on bone regeneration during the bone-tendon junction healing process and to explore the application of synchrotron radiation micro computed tomography in three dimensional visualization of the bone-tendon junction to evaluate the microarchitecture of new trabecular bone. Twenty four mature New Zealand rabbits underwent partial patellectomy to establish a bone-tendon junction injury model at the patella-patellar tendon complex. Animals were then divided into low-intensity pulsed ultrasound treatment (20 min/day, 7 times/week and placebo control groups, and were euthanized at week 8 and 16 postoperatively (n = 6 for each group and time point. The patella-patellar tendon specimens were harvested for radiographic, histological and synchrotron radiation micro computed tomography detection. The area of the newly formed bone in the ultrasound group was significantly greater than that of control group at postoperative week 8 and 16. The high resolution three dimensional visualization images of the bone-tendon junction were acquired by synchrotron radiation micro computed tomography. Low-intensity pulsed ultrasound treatment promoted dense and irregular woven bone formation at week 8 with greater bone volume fraction, number and thickness of new trabecular bone but with lower separation. At week 16, ultrasound group specimens contained mature lamellar bone with higher bone volume fraction and thicker trabeculae than that of control group; however, there was no significant difference in separation and number of the new trabecular bone. This study confirms that low-intensity pulsed ultrasound treatment is able to promote bone formation and remodeling of new trabecular bone during the bone-tendon junction healing process in a rabbit model, and the synchrotron radiation micro computed tomography could be applied for three dimensional visualization to quantitatively evaluate

  14. Study of Interparietal (Inca) bone in dry human skulls

    OpenAIRE

    Janki Jadav; Vaishakhi Gonsai; Ashok Nirvan

    2015-01-01

    Introduction: Squamous part of occipital bone consists of two parts, supraoccipital and interparietal. Interparietal portion may remain separated from the supraoccipital by a suture, it is then called the interparietal bone. Inca population has common manifestation of Interparietal bones, that’s why it is also called ‘Os Inca’ which suggest their ethnic correlation and genetic inheritance. Presence of Inca bone in a skull is great importance to Neurosurgeons, Orthopedic surgeons, Radiologist...

  15. Bone fragility in postmenopausa women: a preliminar study

    OpenAIRE

    Fonseca, E.M.M.; Pereira, Ana I.; Rocha, D.F.S.; Noronha, J.K.

    2012-01-01

    The aim of this work is to identify the prevalence of risks factors for bone fragility in postmenopausal women with hormonal replacement therapy (HRT) within two groups (with bone fracture history and without bone fracture history) and to evaluate the effect of modifiable risk factors on bone mineral density (BMD). The overall prevalence of osteoporosis in postmenopausal Portuguese women is high. A pattern identification of occurrences, in a group of patients submitted to this analysis, will ...

  16. The role of metabotropic glutamate receptor 5 in the pathogenesis of mood disorders and addiction:Combining preclinical evidence with human Positron Emission Tomography (PET studies

    Directory of Open Access Journals (Sweden)

    Sylvia eTerbeck

    2015-03-01

    Full Text Available In the present review, we deliver an overview of the involvement of metabotropic glutamate receptor 5 (mGluR5 activity and density in pathological anxiety, mood disorders and addiction. Specifically, we will describe mGluR5 studies in humans that employed Positron Emission Tomography (PET and combined the findings with preclinical animal research. This combined view of different methodological approaches — from basic neurobiological approaches to human studies — might give a more comprehensive and clinically relevant view of mGluR5 function in mental health than the view on preclinical data alone. We will also review the current research data on mGluR5 along the Research Domain Criteria (RDoC. Firstly, we found evidence of abnormal glutamate activity related to the positive and negative valence systems, which would suggest that antagonistic mGluR5 intervention has prominent anti-addictive, anti-depressive and anxiolytic effects. Secondly, there is evidence that mGluR5 plays in important role in systems for social functioning and the response to social stress. Finally, mGluR5’s important role in sleep homeostasis suggests that this glutamate receptor may play an important role in RDoC’s arousal and modulatory systems domain. Glutamate was previously mostly investigate in non-human studies, however initial human clinical PET research now also supports the hypothesis that, by mediating brain excitability, neuroplasticity and social cognition, abnormal metabotropic glutamate activity might predispose individuals to a broad range of psychiatric problems.

  17. Pre-clinical studies of toxin-specific Nanobodies: Evidence of in vivo efficacy to prevent fatal disturbances provoked by scorpion envenoming

    International Nuclear Information System (INIS)

    Scorpions represent a significant threat to humans and animals in various countries throughout the world. Recently, we introduced Nanobodies (Nbs) to combat more efficiently scorpion envenoming and demonstrated the performance of NbAahIF12 and NbAahII10 to neutralize scorpion toxins of Androctonus australis hector venom. A bispecific Nb construct (NbF12-10) comprising these two Nbs is far more protective than the classic Fab′2 based therapy and is the most efficient antivenom therapy against scorpion sting in preclinical studies. Now we investigate the biodistribution and pharmacokinetics of 99mTc labeled Nbs by in vivo imaging in rodents and compared these data with those of the Fab′2 product (PAS). The pharmacodynamics of the Nbs was investigated in rats by in vivo echocardiography and it is shown that NbF12-10 prevents effectively the hemodynamic disturbances induced by a lethal dose of venom. Moreover, even a late injection of NbF12-10 restores the heart rate and brings the blood pressure to baseline values. Histology confirms that NbF12-10 prevents lung and heart lesions of treated mice after envenoming. In conjunction, in this preclinical study, we provide proof of concept that NbF12-10 prevents effectively the fatal disturbances induced by Androctonus venom, and that the Nanobody based therapeutic has a potential to substitute the classic Fab′2 based product as immunotherapeutic in scorpion envenoming. Further clinical study using larger cohorts of animals should be considered to confirm the full protecting potential of our NbF12-10. -- Highlights: ► Nanobody therapy prevents the hemodynamic disturbances induced by a lethal dose. ► Late injection of Nanobody restores hemodynamic parameters to baseline values. ► Nanobody therapy prevents lung and heart lesions of treated mice after envenoming. ► Labeled Nanobody and Fab’2 pharmacokinetics curves reach plateau in favour of Nanobody.

  18. Risk factors for low bone mass in healthy young adults from North India: studies on BMD and bone turnover markers

    Directory of Open Access Journals (Sweden)

    Anita Fotedar Verma

    2015-04-01

    Full Text Available Background: Despite availability of adequate sunshine, Indian population has the highest prevalence of low bone mass and Bone Mineral Content (BMC. Risk factors for osteoporosis have been extensively studied in the west but poorly investigated in India. We studied BMD and Bone Turnover Markers (BTMs among healthy young adults. Methods: Fifty one healthy young adults (28 Males, 23 Females in the age group of 20-35 years were studied. Morphometric, biochemical parameters and BMD (whole body, spine, hip and wrist were recorded. Anthropometric measurements included height, weight, BMI and Waist/Hip Ratio (WHR. BTMs studied included - serum Bone-Specific Alkaline Phosphatase (sBAP, serum Collagen cross-linked C-Terminal telopeptide (sCTx, serum Osteocalcin (OC and human intact parathyroid hormone (hPTH using standard ELISA kits. Results: Of 51 healthy volunteers 21.57% had normal BMD, 13.73% were frankly osteoporotic and 64.70% were osteopenic. Age, weight and BMI were the best predictors of total BMD and BMC at all sites. sCTX positively correlated with Total Bone Area (TBA, BMD at Hip and Forearm. Using multiple regressions - age, weight, and BMI were significant predictors of BMD in young adults. Percentage body fat had inverse correlation with BMC, BMD and TBA. Weight and height positively correlated with BMD at femoral neck, inter-trochanter and Ward's triangle. Body weight was best predictor of BMD at femoral neck, Ward's triangle, forearm UD, forearm MID and forearm1/3. Conclusion: Majority of healthy young Indians have poor bone health as evidenced by bone markers. [Int J Res Med Sci 2015; 3(4.000: 933-939

  19. “Over-inlay” block graft and differential morphometry: a novel block graft model to study bone regeneration and host-to-graft interfaces in rats

    Science.gov (United States)

    2016-01-01

    Purpose The aim of this study was to present new a model that allows the study of the bone healing process, with an emphasis on the biological behavior of different graft-to-host interfaces. A standardized “over-inlay” surgical technique combined with a differential histomorphometric analysis is presented in order to optimize the use of critical-size calvarial defects in pre-clinical testing. Methods Critical-size defects were created into the parietal bone of 8 male Wistar rats. Deproteinized bovine bone (DBBM) blocks were inserted into the defects, so that part of the block was included within the calvarial thickness and part exceeded the calvarial height (an “over-inlay” graft). All animals were sacrificed at 1 or 3 months. Histomorphometric and immunohistochemical evaluation was carried out within distinct regions of interest (ROIs): the areas adjacent to the native bone (BA), the periosteal area (PA) and the central area (CA). Results The animals healed without complications. Differential morphometry allowed the examination of the tissue composition within distinct regions: the BA presented consistent amounts of new bone formation (NB), which increased over time (24.53%±1.26% at 1 month; 37.73%±0.39% at 3 months), thus suggesting that this area makes a substantial contribution toward NB. The PA was mainly composed of fibrous tissue (71.16%±8.06% and 78.30%±2.67%, respectively), while the CA showed high amounts of DBBM at both time points (78.30%±2.67% and 74.68%±1.07%, respectively), demonstrating a slow remodeling process. Blood vessels revealed a progressive migration from the interface with native bone toward the central area of the graft. Osterix-positive cells observed at 1 month within the PA suggested that the periosteum was a source of osteoprogenitor elements. Alkaline phosphatase data on matrix deposition confirmed this observation. Conclusions The present model allowed for a standardized investigation of distinct graft

  20. Combination of Micro nutrients for Bone (COMB) Study: Bone Density after Micro nutrient Intervention

    International Nuclear Information System (INIS)

    Along with other investigations, patients presenting to an environmental health clinic with various chronic conditions were assessed for bone health status. Individuals with compromised bone strength were educated about skeletal health issues and provided with therapeutic options for potential amelioration of their bone health. Patients who declined pharmacotherapy or who previously experienced failure of drug treatment were offered other options including supplemental micro nutrients identified in the medical literature as sometimes having a positive impact on bone mineral density (BMD). After 12 months of consecutive supplemental micro nutrient therapy with a combination that included vitamin D3, vitamin K2, strontium, magnesium and docosahexaenoic acid (DHA), repeat bone densitometry was performed. The results were analyzed in a group of compliant patients and demonstrate improved BMD in patients classified with normal, osteopenic and osteoporotic bone density. According to the results, this combined micro nutrient supplementation regimen appears to be at least as effective as bis phosphonates or strontium ranelate in raising BMD levels in hip, spine, and femoral neck sites. No fractures occurred in the group taking the micro nutrient protocol. This micro nutrient regimen also appears to show efficacy in individuals where bis phosphonate therapy was previously unsuccessful in maintaining or raising BMD. Prospective clinical trials are required to confirm efficacy

  1. The Economics of Reproducibility in Preclinical Research.

    Directory of Open Access Journals (Sweden)

    Leonard P Freedman

    2015-06-01

    Full Text Available Low reproducibility rates within life science research undermine cumulative knowledge production and contribute to both delays and costs of therapeutic drug development. An analysis of past studies indicates that the cumulative (total prevalence of irreproducible preclinical research exceeds 50%, resulting in approximately US$28,000,000,000 (US$28B/year spent on preclinical research that is not reproducible-in the United States alone. We outline a framework for solutions and a plan for long-term improvements in reproducibility rates that will help to accelerate the discovery of life-saving therapies and cures.

  2. Efficacy of multiple exposure with low level He-Ne laser dose on acute wound healing: a pre-clinical study

    Science.gov (United States)

    Prabhu, Vijendra; Rao, Bola Sadashiva S.; Mahato, Krishna Kishore

    2014-02-01

    Investigations on the use of Low Level Laser Therapy (LLLT) for wound healing especially with the red laser light have demonstrated its pro-healing potential on a variety of pre-clinical and surgical wounds. However, until now, in LLLT the effect of multiple exposure of low dose laser irradiation on acute wound healing on well-designed pre-clinical model is not much explored. The present study aimed to investigate the effect of multiple exposure of low dose Helium Neon laser on healing progression of full thickness excision wounds in Swiss albino mice. Further, the efficacy of the multiple exposure of low dose laser irradiation was compared with the single exposure of optimum dose. Full thickness excision wounds (circular) of 15 mm diameter were created, and subsequently illuminated with the multiple exposures (1, 2, 3, 4 and 5 exposure/ week until healing) of He-Ne (632.8 nm, 4.02 mWcm-2) laser at 0.5 Jcm-2 along with single exposure of optimum laser dose (2 J/cm-2) and un-illuminated controls. Classical biophysical parameters such as contraction kinetics, area under the curve and the mean healing time were documented as the assessment parameters to examine the efficacy of multiple exposures with low level laser dose. Experimental findings substantiated that either single or multiple exposures of 0.5 J/cm2 failed to produce any detectable alterations on wound contraction, area under the curve and mean healing time compared to single exposure of optimum dose (2 Jcm-2) and un-illuminated controls. Single exposure of optimum, laser dose was found to be ideal for acute wound healing.

  3. Radiographic study of bone changes on TMJ arthrosis

    Energy Technology Data Exchange (ETDEWEB)

    You, Dong Soo [Dept. of Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1982-11-15

    The author analyzed the morphologic changes of bone structures from 1256 radiographs of 314 patients with temporomandibular joint arthrosis, which were obtained by the oblique-lateral projection and orthopantomography. The interrelations of the bone changes and clinical symptoms were examined. Also, the positional relationships of condylar head, articular fossa and articular eminence in the mouth open and closed state were observed in the patients with bone changes. The results were as follows; 1. The most frequent bone change in the TMJ arthrosis was eburnation of cortical bone (35.64%) of total cases. Then came bone surface erosion and localized radiolucency (26.18%), marginal proliferation (9.7%) and flattening of articular surface (9.58%) in that order. 2. The most frequent site of bone change was articular eminence (41.70%). The came condylar head (21.09%) and articular fossa (20.73%) in that order. 3. In the patients with bone changes, their clinical symptoms were pain (51.55%), clicking sound during mandibular movement (37.71%) and limited mandibular movement (10.73%). In the patients complaining pain, their radiographs showed eburnation of cortical bone (30.68%), bone surface erosion and localized radiolucency (27.45%) and flattening in the (30.68%), bone surface erosion and localized radiolucency (27.45%) and flattening of articular surface (10.68%). 4. The condylar positional changes in the TMJ arthrosis patients with bone changes were as follows: in the mouth closed state, there were the widening of joint space in 624 cases (50.00%), the narrowing of joint space in 543 cases (43.47%) and bone on bone relationships in 82 cases (6.57%). In the mouth open state, there were forward positioning of the condyle in 332 cases (28.55%), limitation of movement in 332 cases (28.55%), bone on bone relationships in 248 cases (21.31%) and downward positioning of condyle in 217 cases (18.66%). Bone on bone relationships in 248 cases (21.32%) and downward positioning of

  4. Radiographic study of bone changes on TMJ arthrosis

    International Nuclear Information System (INIS)

    The author analyzed the morphologic changes of bone structures from 1256 radiographs of 314 patients with temporomandibular joint arthrosis, which were obtained by the oblique-lateral projection and orthopantomography. The interrelations of the bone changes and clinical symptoms were examined. Also, the positional relationships of condylar head, articular fossa and articular eminence in the mouth open and closed state were observed in the patients with bone changes. The results were as follows; 1. The most frequent bone change in the TMJ arthrosis was eburnation of cortical bone (35.64%) of total cases. Then came bone surface erosion and localized radiolucency (26.18%), marginal proliferation (9.7%) and flattening of articular surface (9.58%) in that order. 2. The most frequent site of bone change was articular eminence (41.70%). The came condylar head (21.09%) and articular fossa (20.73%) in that order. 3. In the patients with bone changes, their clinical symptoms were pain (51.55%), clicking sound during mandibular movement (37.71%) and limited mandibular movement (10.73%). In the patients complaining pain, their radiographs showed eburnation of cortical bone (30.68%), bone surface erosion and localized radiolucency (27.45%) and flattening in the (30.68%), bone surface erosion and localized radiolucency (27.45%) and flattening of articular surface (10.68%). 4. The condylar positional changes in the TMJ arthrosis patients with bone changes were as follows: in the mouth closed state, there were the widening of joint space in 624 cases (50.00%), the narrowing of joint space in 543 cases (43.47%) and bone on bone relationships in 82 cases (6.57%). In the mouth open state, there were forward positioning of the condyle in 332 cases (28.55%), limitation of movement in 332 cases (28.55%), bone on bone relationships in 248 cases (21.31%) and downward positioning of condyle in 217 cases (18.66%). Bone on bone relationships in 248 cases (21.32%) and downward positioning of

  5. Preclinical in vitro and in vivo studies to examine the potential use of photodynamic therapy in the treatment of osteomyelitis

    Science.gov (United States)

    Bisland, Stuart K.; Chien, Claudia; Wilson, Brian C.; Burch, Shane

    2005-04-01

    Osteomyelitis can lead to severe morbidity and even death resulting from an acute or chronic inflammation of the bone and contiguous structures due to fungal or bacterial infection. Incidence approximates 1 in 1,000 neonates and 1 in 5,000 children in the United States annually and increases up to 0.36% and 16% in adults with diabetes or sickle cell anaemia, respectively. Current regiments of treatment include antibiotics and/or surgery. However, the increasing number of antibiotic resistant pathogens suggests that alternate strategies are required. We are investigating photodynamic therapy (PDT) as one such alternate treatment for osteomyelitis using a bioluminescent strain of biofilm-producing staphylococcus aureus (SA) grown onto kirschner wires (K-wire). SA-coated K-wires were exposed to methylene blue (MB) or 5-aminolevulinic acid (ALA)-mediated PDT either in vitro or following implant into the tibial medullary cavity of Sprague-Dawley rats. The progression of SA biofilm was monitored non-invasively using bioluminescence and expressed as a percentage of the signal for each sample immediately prior to treatment. SA infections were subject to PDT 10 days post inoculation. Treatment comprised administration of ALA (300 mg/Kg) intraperitoneally followed 4 hr later by light (635 +/- 10 nm; 38 or 75 J/cm2) delivered transcutaneously via an optical fiber placed onto the tibia. In vitro, MB and ALA displayed similar cell kill with >= 4log10 cell kill. In vivo, ALA-mediated PDT inhibited biofilm implants in bone. These results confirm that MB or ALA-mediated PDT have potential to treat SA cultures grown in vitro or in vivo using an animal model of osteomyelitis.

  6. The frequency of osteolytic bone metastasis is determined by conditions of the soil, not the number of seeds; evidence from in vivo models of breast and prostate cancer

    OpenAIRE

    Wang, N; Reeves, K.J.; Brown, H.K.; Fowles, A.C.M.; Docherty, F.E.; Ottewell, P.D.; Croucher, P.I.; Holen, I; Eaton, C.L.

    2015-01-01

    Background While both preclinical and clinical studies suggest that the frequency of growing skeletal metastases is elevated in individuals with higher bone turnover, it is unclear whether this is a result of increased numbers of tumour cells arriving in active sites or of higher numbers of tumour cells being induced to divide by the bone micro-environment. Here we have investigated how the differences in bone turnover affect seeding of tumour cells and/or development of overt osteolytic b...

  7. [The progress in application of parathyroid hormone in craniomaxillofacial bone regeneration study].

    Science.gov (United States)

    Chen, X Y; Tang, Z L

    2016-06-01

    Parathyroid hormone(PTH)is synthesized and secreted by chief cell of Gley's glands which possesses dual functions of catabolism and anabolism. It regulates the proliferation and differentiation of multiple cell lines including osteoblast, osteoclast and skeletal lining cells. Furthermore, PTH activates various signaling pathways which control calcium, phosphorous' metabolism and bone conversion, accelerating the bone regeneration and reconstruction. However, the study of PTH in craniomaxillofacial bone regeneration is relatively less and whether the role of parathyroid glands and the mechanism of ossification are consistent with the long bone or not needs further investigation. This review focuses on the progress of PTH in craniomaxillofacial bone regeneration in recent years. PMID:27256534

  8. Study of osteoporosis through the measurement of bone density, trace elements, biomechanical properties and immunocytochemicals

    International Nuclear Information System (INIS)

    Osteoporosis is defined as an absolute decrease in the amount of bone to a level below required for mechanical support. It is an important bone disease in elderly people in many countries. Unfortunately, there is no reliable statistical data in Turkey for the incidence of osteoporosis. A decrease in bone mass is the important cause in fractures in osteoporosis. Therefore, we intend to study both bone density and other variables such as trace elements, biomechanical properties and other immunocytochemicals in bone, all combined might give an information about the cause and prevention of osteoporosis. (author)

  9. Marrow uptake index (MUI): A quantitative scintigraphic study of bone marrow in aplastic anaemia

    International Nuclear Information System (INIS)

    Aplastic anaemia affects the entire bone marrow. This prospective study was undertaken to develop and standardise a new nuclear medicine technique called 'dynamic bone marrow imaging'. Eleven patients and ten controls were studied. Serial images of the pelvis were obtained in frame mode following intravenous injection of 185-370 mBq of 99mTc S. Colloid, and an index, called the bone marrow uptake index was calculated by taking into consideration the time activity curve obtained over the iliac crest. This was followed by static imaging of the entire bone marrow in all cases. It was possible to obtain excellent information regarding topographic distribution of bone marrow as well as detect early changes in bone marrow function following treatment. An attempt was also made to correlate bone marrow cellularity as obtained by bone marrow biopsy with results of dynamic bone marrow scintigraphy. On the basis of the encouraging results obtained in the present study, the authors feel that dynamic bone marrow imaging is an excellent technique for the objective evaluation of bone marrow in aplastic anaemia. 20 refs.; 4 figs.; 5 tabs

  10. Bones and oil reservoirs : bioengineers use oilpatch technology to study fluid flow in bones

    Energy Technology Data Exchange (ETDEWEB)

    Marsters, S.

    2003-06-01

    The fact that porosity and the presence of channels are qualities that are common to oil reservoirs and bones, led to the use of reservoir modelling technology in investigating bone disorders and to the discovery of dramatic changes in the structure and blood supply of osteoarthritic bones that lie under degenerating cartilage. CMG (Computer Modelling Group) Ltd., developers of reservoir simulation software claim that their software packages can help with the modelling of cellular responses to strains and deformations that occur as fluid flows through bone after a traumatic event such as a tear in the anterior cruciate ligament, a common sports-related injury. Researchers at the University of Calgary expect that by looking at the changes in blood and fluid flow within the bone, they can attain a better understanding of the chain of events that leads to osteoarthritis. Better understanding of the progression of the disease could eventually lead to more precise administration of drugs to deal with osteoarthritic pain, and even to the prevention of painful arthritic joints.

  11. Clinical Traumatic Brain Injury in the Preclinical Setting.

    Science.gov (United States)

    Berkner, Justin; Mannix, Rebekah; Qiu, Jianhua

    2016-01-01

    Traumatic brain injury (TBI) is the leading cause of death and disability for people under 45 years of age. Clinical TBI is often the result of disparate forces resulting in heterogeneous injuries. Preclinical modeling of TBI is a vital tool for studying the complex cascade of metabolic, cellular, and molecular post-TBI events collectively termed secondary injury. Preclinical models also provide an important platform for studying therapeutic interventions. However, modeling TBI in the preclinical setting is challenging, and most models replicate only certain aspects of clinical TBI. This chapter details the most widely used models of preclinical TBI, including the controlled cortical impact, fluid percussion, blast, and closed head models. Each of these models replicates particular critical aspects of clinical TBI. Prior to selecting a preclinical TBI model, it is important to address what aspect of human TBI is being sought to evaluate. PMID:27604710

  12. Confocal laser scanning microscopy in study of bone calcification

    International Nuclear Information System (INIS)

    Highlights: ► High-magnification images with depth selection, and thin sections were observed using CLSM. ► The direction and velocity of calcification of the bone was observed by administration of 2 fluorescent dyes. ► In dog femora grafted with coral blocks, newly-formed bone was observed in the coral block space with a rough surface. ► Twelve weeks after dental implant was grafted in dog femora, the space between screws was filled with newly-formed bones. - Abstract: Bone regeneration in mandible and maxillae after extraction of teeth or tumor resection and the use of rough surface implants in bone induction must be investigated to elucidate the mechanism of calcification. The calcified tissues are subjected to chemical decalcification or physical grinding to observe their microscopic features with light microscopy and transmission electron microscopy where the microscopic tissue morphology is significantly altered. We investigated the usefulness of confocal laser scanning microscopy (CLSM) for this purpose. After staggering the time of administration of calcein and alizarin red to experimental rats and dogs, rat alveolar bone and dog femur grafted with coral as scaffold or dental implants were observed with CLSM. In rat alveolar bone, the calcification of newly-formed bone and net-like canaliculi was observed at the mesial bone from the roots progressed at the rate of 15 μm/day. In dog femur grafted with coral, newly-formed bones along the space of coral were observed in an orderly manner. In dog femur with dental implants, after 8 weeks, newly-formed bone proceeded along the rough surface of the implants. CLSM produced high-magnification images of newly-formed bone and thin sections were not needed.

  13. Morphological Study of Wormian Bones in Dried Human Skulls

    OpenAIRE

    Divyesh Patel; Ketan Chauhan; Dhananjay Patil

    2015-01-01

    Background: Wormian bones may be defined as a those accidental bones found in the cranium having no regular relation to their normal ossification centre. They are assocated with cranial and central nervous system abnormalities. Knowledge of these bones is important for anthropo-logists, forensic experts, radiologists, orthopedic and neurosurgeons to avoid misleading for multiple fractures of the skull. Materials and Methods: Adult dry human skulls (n= 27) of unknown age and sex availablei...

  14. Proteomics approaches for the studies of bone metabolism

    OpenAIRE

    Lee, Ji-Hyun; Cho, Je-Yoel

    2014-01-01

    Bone is an active tissue, in which bone formation by osteoblast is followed by bone resorption by osteoclasts, in a repeating cycle. Proteomics approaches may allow the detection of changes in cell signal transduction, and the regulatory mechanism of cell differentiation. LC-MS/MS-based quantitative methods can be used with labeling strategies, such as SILAC, iTRAQ, TMT and enzymatic labeling. When used in combination with specific protein enrichment strategies, quantitative proteomics method...

  15. Infrared laser and bone metabolism; A pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Gordjestani, M.; Dermaut, L. (Department of Orthodontics, University of Ghent (Belgium)); Thierens, H. (Institute of Medical Physics, University of Ghent (Belgium))

    1994-01-01

    A circular defect in each parietal bone of six Wislander rats was created. The animals were divided into two three-unit subgroups. The experimental group received infrared laser radiation on the left defect. The control group was sham irradiated. After 28 days, the bone metabolism was evaluated by technetium-99m methylene diphosphonate scintigraphy. The obtained results revealed no differences in bone metabolic activity between the laser-treated and the control defects. (au) (18 refs.).

  16. Confocal laser scanning microscopy in study of bone calcification

    Energy Technology Data Exchange (ETDEWEB)

    Nishikawa, Tetsunari, E-mail: tetsu-n@cc.osaka-dent.ac.jp [Department of Oral Pathology, Osaka Dental University, Osaka (Japan); Kokubu, Mayu; Kato, Hirohito [Department of Oral Pathology, Osaka Dental University, Osaka (Japan); Imai, Koichi [Department of Biomaterials, Osaka Dental University, Osaka (Japan); Tanaka, Akio [Department of Oral Pathology, Osaka Dental University, Osaka (Japan)

    2012-12-01

    Highlights: Black-Right-Pointing-Pointer High-magnification images with depth selection, and thin sections were observed using CLSM. Black-Right-Pointing-Pointer The direction and velocity of calcification of the bone was observed by administration of 2 fluorescent dyes. Black-Right-Pointing-Pointer In dog femora grafted with coral blocks, newly-formed bone was observed in the coral block space with a rough surface. Black-Right-Pointing-Pointer Twelve weeks after dental implant was grafted in dog femora, the space between screws was filled with newly-formed bones. - Abstract: Bone regeneration in mandible and maxillae after extraction of teeth or tumor resection and the use of rough surface implants in bone induction must be investigated to elucidate the mechanism of calcification. The calcified tissues are subjected to chemical decalcification or physical grinding to observe their microscopic features with light microscopy and transmission electron microscopy where the microscopic tissue morphology is significantly altered. We investigated the usefulness of confocal laser scanning microscopy (CLSM) for this purpose. After staggering the time of administration of calcein and alizarin red to experimental rats and dogs, rat alveolar bone and dog femur grafted with coral as scaffold or dental implants were observed with CLSM. In rat alveolar bone, the calcification of newly-formed bone and net-like canaliculi was observed at the mesial bone from the roots progressed at the rate of 15 {mu}m/day. In dog femur grafted with coral, newly-formed bones along the space of coral were observed in an orderly manner. In dog femur with dental implants, after 8 weeks, newly-formed bone proceeded along the rough surface of the implants. CLSM produced high-magnification images of newly-formed bone and thin sections were not needed.

  17. Green Tea and Bone Health: Evidence from Laboratory Studies

    OpenAIRE

    Shen, Chwan-Li; Yeh, James K.; Cao, Jay J; Chyu, Ming-Chien; Wang, Jia-Sheng

    2011-01-01

    Osteoporosis is a major health problem in the elderly. Epidemiological evidence has shown an association between tea consumption and the prevention of bone loss in the elderly population. Ingestion of green tea and green tea bioactive compounds may be beneficial in mitigating bone loss of this population and decreasing their risk of osteoporotic fractures. This review describes the effect of green tea with its bioactive components on bone health with an emphasis on the following: (i) the etio...

  18. Case Studies for Practical Food Effect Assessments across BCS/BDDCS Class Compounds using In Silico, In Vitro, and Preclinical In Vivo Data

    OpenAIRE

    Heimbach, Tycho; Xia, Binfeng; Lin, Tsu-Han; He, Handan

    2012-01-01

    Practical food effect predictions and assessments were described using in silico, in vitro, and/or in vivo preclinical data to anticipate food effects and Biopharmaceutics Classification System (BCS)/Biopharmaceutics Drug Disposition Classification System (BDDCS) class across drug development stages depending on available data: (1) limited in silico and in vitro data in early discovery; (2) preclinical in vivo pharmacokinetic, absorption, and metabolism data at candidate selection; and (3) ph...

  19. The successes and limitations of preclinical studies in predicting the pharmacodynamics and safety of cell-surface-targeted biological agents in patients

    OpenAIRE

    Polson, Andrew G; Fuji, Reina N

    2012-01-01

    To improve drug development outcomes, it is important to review when preclinical pharmacodynamic and safety models have successfully predicted human responses and when they have not. In a recent issue of the BJP, Bugelski and Martin examined the concordance between preclinical and human data for biopharmaceuticals targeted to cell-surface proteins. The cases are interesting and several trends emerge. The pharmacodynamics of biopharmaceuticals in non-human primates is largely predictive; the u...

  20. THE STUDY OF OUTCOME OF CHRONIC PYOGEN IC LONG BONE OSTEOMYELITIS TREATED BY ANTIBIOTIC IMPREGNATED BONE CEMENT BEADS AND NAILS

    Directory of Open Access Journals (Sweden)

    Soumyajit

    2015-01-01

    Full Text Available OBJECTIVE: In developing country the incidence of chronic pyogenic infection of long bone is high among children and adults. This entity is difficult to be managed by conventional systemic antibiotics alone. Many treatment methods for long bone osteomyelitis were attempted but unfortunately the eradication of chronic osteomyelitis remains a problem. Local antibiotic therapy has been introduced by arthroplasty surgeons and subsequently this method has been tried for treating chronic osteomyelitis. Treatment of chronic osteomyelitis using antibiotic - impregnated bone cement beads or nail after thorough debride ment has become a good option of treatment. Therefore this prospective study has been designed to evaluate the effect of local antibiotic therapy in the form of bone cement beads or nail for eradication of chronic pyogenic long bone osteomyelitis. METHODS: Thirty patients with chronic osteomyelitis of metaphyseal and diaphyseal area of long bones were studied prospectively about outcome of treatment. The diagnosis of chronic osteomyelitis was made on the basis of clinical and radiological features and confirmed by deep aspiration, staining and culture sensitivity of the aspirate. Patients suffering from fungal or tubercular osteomyelitis were excluded. Also the patients with small bones osteomyelitis or open injury more than Gustilo type 2 were excluded. Antibiotic impregnated polymethylmethacrylate beads or nails were implanted after thorough debridement and wound closed primarily. Two dose of intervenous antibiotic were used, one before and another after operation. Beads or nails were removed at the end of six weeks. Patients were followed up for an average period of two years. RESULT: Out of thirty patients in this study, twenty eight patients were cured completely and two patients had persistent discharge till the last follow up visit. No organism found in six cases. No systemic adverse reactions were seen. CONCLUSION: The present study

  1. Changes in vertebral bone marrow fat and bone mass after gastric bypass surgery: A pilot study.

    Science.gov (United States)

    Schafer, A L; Li, X; Schwartz, A V; Tufts, L S; Wheeler, A L; Grunfeld, C; Stewart, L; Rogers, S J; Carter, J T; Posselt, A M; Black, D M; Shoback, D M

    2015-05-01

    Bone marrow fat may serve a metabolic role distinct from other fat depots, and it may be altered by metabolic conditions including diabetes. Caloric restriction paradoxically increases marrow fat in mice, and women with anorexia nervosa have high marrow fat. The longitudinal effect of weight loss on marrow fat in humans is unknown. We hypothesized that marrow fat increases after Roux-en-Y gastric bypass (RYGB) surgery, as total body fat decreases. In a pilot study of 11 morbidly obese women (6 diabetic, 5 nondiabetic), we measured vertebral marrow fat content (percentage fat fraction) before and 6 months after RYGB using magnetic resonance spectroscopy. Total body fat mass declined in all participants (mean ± SD decline 19.1 ± 6.1 kg or 36.5% ± 10.9%, pEffects of RYGB on marrow fat differed by diabetes status (adjusted p=0.04). There was little mean change in marrow fat in nondiabetic women (mean +0.9%, 95% CI -10.0 to +11.7%, p=0.84). In contrast, marrow fat decreased in diabetic women (-7.5%, 95% CI -15.2 to +0.1%, p=0.05). Changes in total body fat mass and marrow fat were inversely correlated among nondiabetic (r=-0.96, p=0.01) but not diabetic (r=0.52, p=0.29) participants. In conclusion, among those without diabetes, marrow fat is maintained on average after RYGB, despite dramatic declines in overall fat mass. Among those with diabetes, RYGB may reduce marrow fat. Thus, future studies of marrow fat should take diabetes status into account. Marrow fat may have unique metabolic behavior compared with other fat depots. PMID:25603463

  2. Bone Regeneration in Iliac Crestal Defects: An Experimental Study on Sheep

    Science.gov (United States)

    Lorusso, Felice; Ravera, Lorenzo; Mortellaro, Carmen; Piattelli, Adriano

    2016-01-01

    Background. Oral rehabilitation of partially fully edentulous patients with dental implants has become a routine procedure in clinical practice. In a site with a lack of bone GBR is a surgical procedure that provides an augmentation in terms of volume for the insertion of dental implants. Materials and Methods. In the iliac crest of six sheep 4 defects were created where an implant was inserted, three of them with different biomaterials and a control site. All animals were sacrificed after a 4-month healing period. All specimens were processed and analyzed with histomorphometry. Statistical evaluation was done to evaluate percentage of bone defect filled by new bone. Results. All experimental groups showed an increase of the new bone. Higher and highly statistically significant differences were found in the percentages of bone defect filled by new bone in group filled with corticocancellous 250–1000 microns particulate porcine bone mix. Conclusions. This study demonstrates that particulate porcine bone mix and porcine corticocancellous collagenate prehydrated bone mix when used as scaffold are able to induce bone regeneration. Moreover, these data suggest that these biomaterials have higher biocompatibility and are capable of inducing faster and greater bone formation. PMID:27413746

  3. Confocal laser scanning microscopy in study of bone calcification

    Science.gov (United States)

    Nishikawa, Tetsunari; Kokubu, Mayu; Kato, Hirohito; Imai, Koichi; Tanaka, Akio

    2012-12-01

    Bone regeneration in mandible and maxillae after extraction of teeth or tumor resection and the use of rough surface implants in bone induction must be investigated to elucidate the mechanism of calcification. The calcified tissues are subjected to chemical decalcification or physical grinding to observe their microscopic features with light microscopy and transmission electron microscopy where the microscopic tissue morphology is significantly altered. We investigated the usefulness of confocal laser scanning microscopy (CLSM) for this purpose. After staggering the time of administration of calcein and alizarin red to experimental rats and dogs, rat alveolar bone and dog femur grafted with coral as scaffold or dental implants were observed with CLSM. In rat alveolar bone, the calcification of newly-formed bone and net-like canaliculi was observed at the mesial bone from the roots progressed at the rate of 15 μm/day. In dog femur grafted with coral, newly-formed bones along the space of coral were observed in an orderly manner. In dog femur with dental implants, after 8 weeks, newly-formed bone proceeded along the rough surface of the implants. CLSM produced high-magnification images of newly-formed bone and thin sections were not needed.

  4. Changes in total body bone mineral density following a common bone health plan with two versions of a unique bone health supplement: a comparative effectiveness research study

    Directory of Open Access Journals (Sweden)

    Dapilmoto Monika

    2011-04-01

    Full Text Available Abstract Background The US Surgeon General's Report on Bone Health suggests America's bone-health is in jeopardy and issued a "call to action" to develop bone-health plans that: (1 improve nutrition, (2 increase health literacy and, (3 increase physical activity. This study is a response to this call to action. Methods After signing an informed consent, 158 adults agreed to follow an open-label bone-health plan for six months after taking a DXA test of bone density, a 43-chemistry blood test panel and a quality of life inventory (AlgaeCal 1. Two weeks after the last subject completed, a second group of 58 was enrolled and followed the identical plan, but with a different bone-health supplement (AlgaeCal 2. Results There were no significant differences between the two groups in baseline bone mineral density (BMD or in variables related to BMD (age, sex, weight, percent body fat, fat mass, or fat-free mass. In both groups, no significant differences in BMD or related variables were found between volunteers and non-volunteers or between those who completed per protocol and those who were lost to attrition. Both groups experienced a significant positive mean annualized percent change (MAPC in BMD compared to expectation [AlgaeCal 1: 1.15%, p = 0.001; AlgaeCal 2: 2.79%, p = 0.001]. Both groups experienced a positive MAPC compared to baseline, but only AlgaeCal 2 experienced a significant change [AlgaeCal 1: 0.48%, p = 0.14; AlgaeCal 2: 2.18%, p p = 0.005. The MAPC contrast between compliant and partially compliant subjects was significant for both plans (p = 0.001 and p = 0.003 respectively. No clinically significant changes in a 43-panel blood chemistry test were found nor were there any changes in self-reported quality of life in either group. Conclusions Following The Plan for six months with either version of the bone health supplement was associated with significant increases in BMD as compared to expected and, in AlgaeCal 2, the increase from

  5. Radiochemistry, pre-clinical studies and first clinical investigation of 90Y-labeled hydroxyapatite (HA) particles prepared utilizing 90Y produced by (n,γ) route

    International Nuclear Information System (INIS)

    Introduction: The scope of using no carrier added (NCA) 90Y [T1/2 = 64.1 h, Eβ(max) = 2.28 MeV] obtained from 90Sr/90Y generator in radiation synovectomy (RSV) is widely accepted. In the present study, the prospect of using 90Y produced by (n,γ) route in a medium flux research reactor for use in RSV was explored. Methods: Yttrium-90 was produced by thermal neutron irradiation of Y2O3 target at a neutron flux of ~ 1 × 1014 n/cm2.s for 14 d. The influence of various experimental parameters were systematically investigated and optimized to arrive at the most favorable conditions for the formulation of 90Y labeled hydroxyapatite (HA) using HA particles of 1–10 μm size range. An optimized kit formulation strategy was developed for convenient one-step compounding of 90Y-HA, which is easily adaptable at hospital radiopharmacy. The pre-clinical biological evaluation of 90Y-HA particles was studied by carrying out biodistribution and bioluminiscence imaging studies in Wistar rats. The first clinical investigation using the radiolabeled preparation was performed on a patient suffering from chronic arthritis in knee joint by administering 185 MBq 90Y-HA formulated at the hospital radiopharmacy deploying the proposed strategy. Results: Yttrium-90 was produced with a specific activity of 851 ± 111 MBq/mg and radionuclidic purity of 99.95 ± 0.02%. 90Y-labeled HA particles (185 ± 10 MBq doses) were formulated in high radiochemical purity (> 99%) and excellent in vitro stability. The preparation showed promising results in pre-clinical studies carried out in Wistar rats. The preliminary results of the first clinical investigation of 90Y-HA preparation in a patient with rheumatoid arthritis in knee joints demonstrated the effectiveness of the formulation prepared using 90Y produced via (n,γ) route in the management of the disease. Conclusion: The studies revealed that effective utilization of 90Y produced via (n,γ) route in a medium flux research reactor coupled with the

  6. 3D printed nanocomposite matrix for the study of breast cancer bone metastasis.

    Science.gov (United States)

    Zhu, Wei; Holmes, Benjamin; Glazer, Robert I; Zhang, Lijie Grace

    2016-01-01

    Bone is one of the most common metastatic sites of breast cancer, but the underlying mechanisms remain unclear, in part due to an absence of advanced platforms for cancer culture and study that mimic the bone microenvironment. In the present study, we integrated a novel stereolithography-based 3D printer and a unique 3D printed nano-ink consisting of hydroxyapatite nanoparticles suspended in hydrogel to create a biomimetic bone-specific environment for evaluating breast cancer bone invasion. Breast cancer cells cultured in a geometrically optimized matrix exhibited spheroid morphology and migratory characteristics. Co-culture of tumor cells with bone marrow mesenchymal stem cells increased the formation of spheroid clusters. The 3D matrix also allowed for higher drug resistance of breast cancer cells than 2D culture. These results validate that our 3D bone matrix can mimic tumor bone microenvironments, suggesting that it can serve as a tool for studying metastasis and assessing drug sensitivity. From the Clinical Editor: Cancer remains a major cause of mortality for patients in the clinical setting. For breast cancer, bone is one of the most common metastatic sites. In this intriguing article, the authors developed a bone-like environment using 3D printing technology to investigate the underlying biology of bone metastasis. Their results would also allow a new model for other researchers who work on cancer to use. PMID:26472048

  7. Effects of denosumab on bone histomorphometry: the FREEDOM and STAND studies.

    Science.gov (United States)

    Reid, Ian R; Miller, Paul D; Brown, Jacques P; Kendler, David L; Fahrleitner-Pammer, Astrid; Valter, Ivo; Maasalu, Katre; Bolognese, Michael A; Woodson, Grattan; Bone, Henry; Ding, Beiying; Wagman, Rachel B; San Martin, Javier; Ominsky, Michael S; Dempster, David W

    2010-10-01

    Denosumab, a human monoclonal antibody against RANKL, reversibly inhibits osteoclast-mediated bone resorption and has been developed for use in osteoporosis. Its effects on bone histomorphometry have not been described previously. Iliac crest bone biopsies were collected at 24 and/or 36 months from osteoporotic postmenopausal women in the FREEDOM study (45 women receiving placebo and 47 denosumab) and at 12 months from postmenopausal women previously treated with alendronate in the STAND study (21 continuing alendronate and 15 changed to denosumab at trial entry). Qualitative histologic evaluation of biopsies was unremarkable. In the FREEDOM study, median eroded surface was reduced by more than 80% and osteoclasts were absent from more than 50% of biopsies in the denosumab group. Double labeling in trabecular bone was observed in 94% of placebo bones and in 19% of those treated with denosumab. Median bone-formation rate was reduced by 97%. Among denosumab-treated subjects, those with double labels and those with absent labels had similar levels of biochemical markers of bone turnover. In the STAND trial, indices of bone turnover tended to be lower in the denosumab group than in the alendronate group. Double labeling in trabecular bone was seen in 20% of the denosumab biopsies and in 90% of the alendronate samples. Denosumab markedly reduces bone turnover and also reduces fracture numbers. Longer follow-up is necessary to determine how long such low turnover is safe. PMID:20533525

  8. Studies on the effect of low level laser therapy on bone repair

    International Nuclear Information System (INIS)

    The speed and quality of bone repair has direct clinical relevance. It has been suggested that Low Level Laser Therapy (LLLT) accelerates bone healing and that neuropeptides play a role in bone metabolism. This study investigated LLLT effects (using a GaAlAs semiconductor laser, 830 nm wavelength, 70 mW output power at an energy density of 4J/cm2) on the repair of pinned immobilised femoral osteotomies in male Sprague Dawley rats randomly assigned to 3 experimental groups: a control group, group A (osteotomised limb irradiated) and group B (non-osteotomised limb irradiated). Specimens were retrieved from 1-5 weeks post-trauma for histology, immunohistochemical investigation of neuropeptide expression (NPY, CGRP, SP, VIP), radioimmunoassay, bone mineral density (BMD) and biomechanical strength testing studies. Histology suggested accelerated bone repair in group B by 3 weeks, while by 5 weeks the control group was more advanced displaying bony union. Distinct differences were detected in the pattern and level of neuropeptide expression in repairing fractures between groups with several novel and discrete peptide localisations being reported for bone and cartilage cell types and bone marrow megakaryocytes. A role for neuropeptides in bone metabolism is supported. Bone densitometry showed no significant difference between groups for in vivo BMD data but did on more accurate in vitro assessment. Biomechanical studies demonstrated stronger osteotomies in the control group compared to irradiated groups at 5 weeks post-osteotomy suggesting that bone quality may be poorer after LLLT. The initial acceleration of bone repair after laser therapy indicates that it is biostimulatory to repair (a systemic effect was detected), however as the control group was more advanced by 5 weeks post-fracture further investigation of different treatment schedules is indicated. This research confirms that BMD is not the sole determinant of bone strength but that bone quality is clearly

  9. Infant milk feeding influences adult bone health: a prospective study from birth to 32 years.

    Directory of Open Access Journals (Sweden)

    Satu Pirilä

    Full Text Available BACKGROUND: Peak bone mass, attained by early adulthood, is influenced by genetic and life-style factors. Early infant feeding and duration of breastfeeding in particular, associate with several health-related parameters in childhood. The aim of this study was to examine whether the effects of early infant feeding extend to peak bone mass and other bone health characteristics at adult age. METHODS AND FINDINGS: A cohort of 158 adults (76 males born in Helsinki, Finland, 1975, prospectively followed up from birth, underwent physical examination and bone densitometry to study bone area, bone mineral content (BMC, and bone mineral density (BMD at 32 years of age. Life-style factors relevant for bone health were recorded. For data analysis the cohort was divided into three equal-size groups according to the total duration of breastfeeding (BF: Short (≤3 months, Intermediate and Prolonged (≥7 months BF groups. In males short BF is associated with higher bone area, BMC, and BMD compared to longer BF. Males in the Short BF group had on average 4.7% higher whole body BMD than males in the Prolonged BF group. In multivariate analysis, after controlling for multiple confounding factors, the influence of BF duration on adult bone characteristics persisted in males. Differences between the three feeding groups were observed in lumbar spine bone area and BMC, and whole body BMD (MANCOVA; p = 0.025, p = 0.013, and p = 0.048, respectively, favoring the Short BF group. In women no differences were observed. CONCLUSIONS: In men, early infant milk feeding may have a significant impact on adult bone health. A potential explanation is that the calcium and phosphate contents were strikingly higher in formula milk and commercial cow milk/cow milk dilutions as opposed to human milk. Our novel finding merits further studies to determine means to ensure optimal bone mass development in infants with prolonged breastfeeding.

  10. Pre-clinical studies of toxin-specific Nanobodies: Evidence of in vivo efficacy to prevent fatal disturbances provoked by scorpion envenoming

    Energy Technology Data Exchange (ETDEWEB)

    Hmila, Issam [Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 Place Pasteur, BP-74, 1002 Tunis (Tunisia); Cosyns, Bernard [Laboratory of In Vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel (Belgium); Tounsi, Hayfa [Service d' Anatomo-Pathologie, Institut Pasteur de Tunis, 13 Place Pasteur, BP-74, 1002 Tunis (Tunisia); Roosens, Bram; Caveliers, Vicky [Laboratory of In Vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel (Belgium); Abderrazek, Rahma Ben [Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 Place Pasteur, BP-74, 1002 Tunis (Tunisia); Boubaker, Samir [Service d' Anatomo-Pathologie, Institut Pasteur de Tunis, 13 Place Pasteur, BP-74, 1002 Tunis (Tunisia); Muyldermans, Serge [Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussel (Belgium); Department of Structural Biology, VIB, Brussels (Belgium); El Ayeb, Mohamed [Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 Place Pasteur, BP-74, 1002 Tunis (Tunisia); Bouhaouala-Zahar, Balkiss, E-mail: balkiss.bouhaouala@pasteur.rns.tn [Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 Place Pasteur, BP-74, 1002 Tunis (Tunisia); Faculté de Médecine de Tunis, Université de Tunis-El Manar (Tunisia); Lahoutte, Tony [Laboratory of In Vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel (Belgium)

    2012-10-15

    Scorpions represent a significant threat to humans and animals in various countries throughout the world. Recently, we introduced Nanobodies (Nbs) to combat more efficiently scorpion envenoming and demonstrated the performance of NbAahIF12 and NbAahII10 to neutralize scorpion toxins of Androctonus australis hector venom. A bispecific Nb construct (NbF12-10) comprising these two Nbs is far more protective than the classic Fab′{sub 2} based therapy and is the most efficient antivenom therapy against scorpion sting in preclinical studies. Now we investigate the biodistribution and pharmacokinetics of {sup 99m}Tc labeled Nbs by in vivo imaging in rodents and compared these data with those of the Fab′{sub 2} product (PAS). The pharmacodynamics of the Nbs was investigated in rats by in vivo echocardiography and it is shown that NbF12-10 prevents effectively the hemodynamic disturbances induced by a lethal dose of venom. Moreover, even a late injection of NbF12-10 restores the heart rate and brings the blood pressure to baseline values. Histology confirms that NbF12-10 prevents lung and heart lesions of treated mice after envenoming. In conjunction, in this preclinical study, we provide proof of concept that NbF12-10 prevents effectively the fatal disturbances induced by Androctonus venom, and that the Nanobody based therapeutic has a potential to substitute the classic Fab′{sub 2} based product as immunotherapeutic in scorpion envenoming. Further clinical study using larger cohorts of animals should be considered to confirm the full protecting potential of our NbF12-10. -- Highlights: ► Nanobody therapy prevents the hemodynamic disturbances induced by a lethal dose. ► Late injection of Nanobody restores hemodynamic parameters to baseline values. ► Nanobody therapy prevents lung and heart lesions of treated mice after envenoming. ► Labeled Nanobody and Fab’2 pharmacokinetics curves reach plateau in favour of Nanobody.

  11. Complete twelve month bone remodeling with a bi-phasic injectable bone substitute in benign bone tumors: a prospective pilot study

    OpenAIRE

    Kaczmarczyk, Jacek; Sowinski, Piotr; Goch, Maciej; Katulska, Katarzyna

    2015-01-01

    Background Benign primary bone tumors are commonly treated by surgery involving bone grafts or synthetic bone void fillers. Although synthetic bone grafts may provide early mechanical support while minimizing the risk of donor-site morbidity and disease transmission, difficult handling properties and less than optimal transformation to bone have limited their use. Methods In a prospective series, patients with benign bone tumors were treated by minimal invasive intervention with a bi-phasic a...

  12. Studies on {sup 177}Lu-labeled methylene diphosphonate as potential bone-seeking radiopharmaceutical for bone pain palliation

    Energy Technology Data Exchange (ETDEWEB)

    Abbasi, Imtiaz Ahmed, E-mail: imtiaz_abbasi@yahoo.co

    2011-04-15

    Objective: {sup 99m}Tc-MDP (technetium-99{sup m}-labeled methylene diphosphonate) has been widely used as a radiopharmaceutical for bone scintigraphy in cases of metastatic bone disease. {sup 177}Lu is presently considered as an excellent radionuclide for developing bone pain palliation agents. No study on preparing a complex of {sup 177}Lu with MDP has been reported yet. Based on these facts, it was hypothesized that a bone-seeking {sup 177}Lu-MDP (lutetium-177-labeled MDP) radiopharmaceutical could be developed as an agent for palliative radiotherapy of bone pain due to skeletal metastases. Biodistribution studies after intravenous injection of {sup 177}Lu-MDP complex in rats may yield important information to assess its potential for clinical use as a bone pain palliation agent for the treatment of bone metastases. Methods: {sup 177}Lu was produced by irradiating natural Lu{sub 2}O{sub 3} (10 mg) target at a thermal flux {approx}8.0x10{sup 13} n/cm{sup 2} per second for 12 h in the swimming pool-type reactor.{sup 177}Lu was labeled with MDP by adding nearly 37 MBq (1.0 mCi) of {sup 177}LuCl{sub 3} to a vial containing 10 mg MDP. The radiochemical purity and labeling efficiencies were determined by thin layer chromatography. Labeling of {sup 177}Lu with MDP was optimized, and one sample was subjected to high-performance liquid chromatography (HPLC) analysis. Twelve Sprague-Dawley rats were injected with 18.5 MBq (0.5 mCi). {sup 177}Lu-MDP in a volume of 0.1 ml was injected intravenously and then sacrificed at 2 min, 1 h, 2 h and 22 h (three rats at each time point) after injection. Samples of various organs were separated, weighed and measured for radioactivity and expressed as percent uptake of injected dose per gram. Bioevaluation studies with rats under gamma-camera were also performed to verify the results. Results: The quality control using thin layer chromatography has shown >99% radiochemical purity of {sup 177}Lu-MDP complex. Chromatography with Whatman 3

  13. Experimental study of damage and fracture of cancellous bone using a digital speckle correlation method.

    Science.gov (United States)

    Yao, Xuefeng; Wang, Peng; Dai, Ruchun

    2008-01-01

    Cancellous bone is a widespread structure in a creatural body, for instance, in the femoral head and spondyle. The damage evolution and crack growth of cattle cancellous bone were studied under three-point-bending load conditions. A series of speckle images with deformation information surrounding the crack tip were recorded, and the full-field displacement distributions were obtained at different loading levels by means of digital speckle correlation method (DSCM). Characterizations of the damage deformation and fracture of cancellous bone were analyzed. These results provide some useful information for studying the fracture behavior of cancellous bone. PMID:18601571

  14. Normal SUV Values Measured from NaF18- PET/CT Bone Scan Studies

    OpenAIRE

    Aung Zaw Win; Carina Mari Aparici

    2014-01-01

    Objectives Cancer and metabolic bone diseases can alter the SUV. SUV values have never been measured from healthy skeletons in NaF18-PET/CT bone scans. The primary aim of this study was to measure the SUV values from normal skeletons in NaF18-PET/CT bone scans. Methods A retrospective study was carried out involving NaF18- PET/CT bone scans that were done at our institution between January 2010 to May 2012. Our excluding criteria was patients with abnormal real function and patients with past...

  15. Experimental radionuclide studies on the replacement of extended damages of the long bones

    International Nuclear Information System (INIS)

    In dogs extended defects of the long bones were produced and then replaced by distraction osteosynthesis. The metabolic processes in the newly formed bone were studied possess a high significance as to the study of the course of bone formation. The osteosynthesis was characterized by an accelerated blood flow in the extremity and by an increased concentration of sup(99m)Tc-pyrophosphate pointing to an intensification of the metabolic processes. After the regeneration of the bone metabolic processes and blood flow were normalized. (author)

  16. Study on the Microstructure of Human Articular Cartilage/Bone Interface

    Institute of Scientific and Technical Information of China (English)

    Yaxiong Liu; Qin Lian; Jiankang He; Jinna Zhao; Zhongmin Jin; Dichen Li

    2011-01-01

    For improving the theory of gradient microstructure of cartilage/bone interface, human distal femurs were studied. Scanning Electron Microscope (SEM), histological sections and MicroCT were used to observe, measure and model the microstructure of cartilage/bone interface. The results showed that the cartilage/bone interface is in a hierarchical structure which is composed of four different tissue layers. The interlocking of hyaline cartilage and calcified cartilage and that of calcified cartilage and subchondral bone are in the manner of"protrusion-pore" with average diameter of 17.0 μm and 34.1 μm respectively. In addition, the cancellous bone under the cartilage is also formed by four layer hierarchical structure, and the adjacent layers are connected by bone trabecula in the shape of H, I and Y, forming a complex interwoven network structure. Finally, the simplified structure model of the cartilage/bone interface was proposed according to the natural articular cartilage/bone interface. The simplified model is a 4-layer gradient biomimetic structure, which corresponds to four different tissues of natural cartilage/bone interface. The results of this work would be beneficial to the design of bionic scaffold for the tissue engineering of articular cartilage/bone.

  17. The importance of assessing the rate of bone turnover and the balance between bone formation and bone resorption during daily teriparatide administration for osteoporosis: a pilot study.

    Science.gov (United States)

    Nakatoh, Shinichi

    2016-03-01

    This study aimed to examine the importance of simultaneously measuring bone formation and resorption markers during daily teriparatide administration. In 135 women with osteoporosis, bone mineral density (BMD) was measured at 0, 24, and 48 weeks after teriparatide administration. Bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b were measured at 0, 4, 12, 24, 36, and 48 weeks. Subanalyses were performed in groups divided according to the BMD change at 48 weeks (increased and decreased groups), history of fragility fracture (acute and chronic groups), and treatment prior to teriparatide administration (alendronate, raloxifene, and naïve groups). The scatter diagram of multiple of median formation (MoMf) and multiple of median resorption (MoMr) showed that the distribution gradually spread to a high turnover by week 24. A significant correlation was observed between the rate of change in BMD at week 48 and the turnover rate [√(MoMf(2) + MoMr(2))] at week 0. Significant differences were observed in the turnover rate between the acute and chronic groups at weeks 0 and 4 and between the groups divided according to prior treatment from week 0 to 24. Because the assessment of either bone formation markers or bone resorption markers may result in erroneous data, it is necessary to assess them together during teriparatide treatment. The turnover rate at treatment initiation is a useful indicator to predict changes in BMD. When evaluating the turnover rate and balance (MoMf/MoMr), one should consider patient characteristics, including history of fragility fracture and prior treatment. PMID:26031934

  18. Mechanical Quantification of Local Bone Quality in the Humeral Head: A Feasibility Study

    OpenAIRE

    Scola, Alexander; Gebhard, Florian; Weckbach, Sebastian; Dehner, Christoph; Schwyn, Ronald; Fliri, Ladina; Röderer, Götz

    2013-01-01

    Objectives: Surgical treatment of proximal humerus fractures can be challenging due to osteoporosis. The weak bone stock makes stable implant anchorage difficult, which can result in low primary stability. Accordingly, significant failure rates, even with modern locking plates, are reported in the literature. Intraoperative knowledge of local bone quality could be helpful in improving results. This study evaluates the feasibility of local bone quality quantification using breakaway torque mea...

  19. Growth in early life predicts bone strength in late adulthood: The Hertfordshire Cohort Study

    OpenAIRE

    Oliver, Helen; Jameson, Karen A.; Sayer, Avan Aihie; Cooper, Cyrus; Dennison, Elaine M; ,

    2007-01-01

    Infant growth is a determinant of adult bone mass, and poor childhood growth is a risk factor for adult hip fracture. Peripheral quantitative computed tomography (pQCT) allows non-invasive assessment of bone strength. We utilised this technology to examine relationships between growth in early life and bone strength. We studied 313 men and 318 women born in Hertfordshire between 1931 and 1939 who were still resident there in adult life, for whom detailed early life records were available. Lif...

  20. A radiological evaluation of marginal bone around dental implants: An in-vivo study

    OpenAIRE

    Nandal, Shikha; Ghalaut, Pankaj; Shekhawat, Himanshu

    2014-01-01

    Context: This article presents an original research conducted at Government Dental College, PGIDS, Rohtak. Aims: (1) To evaluate the marginal bone level changes around dental implants based on the radiological examination. (2) To evaluate the relationship of various parameters, i.e., gender, implant length, implant diameter and location of implants on the amount of bone loss around dental implants. Materials and Methods: An in-vivo study was undertaken to evaluate the crestal bone loss on mes...

  1. Bone T-Scores and Functional Status: A Cross-Sectional Study on German Elderly

    OpenAIRE

    Shoma Berkemeyer; Jochen Schumacher; Ulrich Thiem; Ludger Pientka

    2009-01-01

    BACKGROUND: We explore the association between bone T-scores, used in osteoporosis diagnosis, and functional status since we hypothesized that bone health can impact elderly functional status and indirectly independence. METHODS: In a cross-sectional study (2005-2006) on community dwelling elderly (> = 75 years) from Herne, Germany we measured bone T-scores with Dual-energy X-ray Absorptiometry, and functional status indexed by five geriatric tests: activities of daily living, instrumental ac...

  2. Frequency of bone-bruises in ankle sprains. Magnetic resonance imaging studies

    International Nuclear Information System (INIS)

    We retrospectively studied MRI on the frequency of bone-bruises in ankle sprains, especially those of the lateral collateral ligaments of the ankle joint. Bone-bruises occurred in 3.8% (4/106) of ruptures of anterior talofibular ligament (ATFL), and 6.3% (5/79) of ruptures of ATFL and calcaneofibular ligament (CFL). Bone-bruises were more likely to be seen in ATFL and CFL ruptures than in ATFL rupture alone. (author)

  3. Frequency of bone-bruises in ankle sprains. Magnetic resonance imaging studies

    Energy Technology Data Exchange (ETDEWEB)

    Uto, Yuji; Morooka, Masaaki [Morooka Orthopaedic Surgery Hospital, Fukuoka (Japan)

    2002-09-01

    We retrospectively studied MRI on the frequency of bone-bruises in ankle sprains, especially those of the lateral collateral ligaments of the ankle joint. Bone-bruises occurred in 3.8% (4/106) of ruptures of anterior talofibular ligament (ATFL), and 6.3% (5/79) of ruptures of ATFL and calcaneofibular ligament (CFL). Bone-bruises were more likely to be seen in ATFL and CFL ruptures than in ATFL rupture alone. (author)

  4. Incidence of pain flare following palliative radiotherapy for symptomatic bone metastases: multicenter prospective observational study

    OpenAIRE

    Gomez-Iturriaga, Alfonso; Cacicedo, Jon; Navarro, Arturo; Morillo, Virginia; Willisch, Patricia; Carvajal, Claudia; Hortelano, Eduardo; Lopez-Guerra, Jose Luis; Illescas, Ana; Casquero, Francisco; del Hoyo, Olga; Ciervide, Raquel; Irasarri, Ana; Pijoan, Jose Ignacio; Bilbao, Pedro

    2015-01-01

    Background Palliative radiotherapy (RT) is an effective treatment for symptomatic bone metastases. Pain flare, a transient worsening of the bone pain after RT, has been described in previous reports with different incidence rates. The aim of the study was to prospectively evaluate the incidence of pain flare following RT for painful bone metastases and evaluate its effects on pain control and functionality of the patients. Methods Between June 2010 and June 2014, 204 patients were enrolled in...

  5. Bone turnover and metabolism in patients with early multiple sclerosis and prevalent bone mass deficit: a population-based case-control study.

    Directory of Open Access Journals (Sweden)

    Stine Marit Moen

    Full Text Available BACKGROUND: Low bone mass is prevalent in ambulatory multiple sclerosis (MS patients even shortly after clinical onset. The mechanism is not known, but could involve shared etiological risk factors between MS and low bone mass such as hypovitaminosis D operating before disease onset, or increased bone loss after disease onset. The aim of this study was to explore the mechanism of the low bone mass in early-stage MS patients. METHODOLOGY/PRINCIPAL FINDINGS: We performed a population-based case-control study comparing bone turnover (cross-linked N-terminal telopeptide of type 1 collagen; NTX, bone alkaline phosphatase; bALP, metabolism (25-hydroxy- and 1, 25-dihydroxyvitamin D, calcium, phosphate, and parathyroid hormone, and relevant lifestyle factors in 99 patients newly diagnosed with clinically isolated syndrome (CIS or MS, and in 159 age, sex, and ethnicity matched controls. After adjustment for possible confounders, there were no significant differences in NTX (mean 3.3; 95% CI -6.9, 13.5; p = 0.519, bALP (mean 1.6; 95% CI -0.2, 3.5; p = 0.081, or in any of the parameters related to bone metabolism in patients compared to controls. The markers of bone turnover and metabolism were not significantly correlated with bone mass density, or associated with the presence of osteoporosis or osteopenia within or between the patient and control groups. Intake of vitamin D and calcium, reported UV exposure, and physical activity did not differ significantly. CONCLUSIONS/SIGNIFICANCE: Bone turnover and metabolism did not differ significantly in CIS and MS patients with prevalent low bone mass compared to controls. These findings indicate that the bone deficit in patients newly diagnosed with MS and CIS is not caused by recent acceleration of bone loss, and are compatible with shared etiological factors between MS and low bone mass.

  6. Comparative study on seeding methods of human bone marrow stromal cells in bone tissue engineering

    Institute of Scientific and Technical Information of China (English)

    齐欣; 刘建国; 常颖; 徐莘香

    2004-01-01

    Background In general the traditional static seeding method has its limitation while the dynamic seeding method reveals its advantages over traditional static method. We compared static and dynamic seeding method for human bone marrow stromal cells (hBMSCs) in bone tissue engineering.Methods DNA assay was used for detecting the maximal initial seeding concentration for static seeding. Dynamic and static seeding methods were compared, when scaffolds were loaded with hBMSCs at this maximal initial cell seeding concentration. Histology and scanning electron microscope (SEM) were examined to evaluate the distribution of cells inside the constructs. Markers encoding osteogenic genes were measured by fluorescent RT-PCR. The protocol for dynamic seeding of hBMSCs was also investigated.Results DNA assay showed that the static maximal initial seeding concentration was lower than that in dynamic seeding. Histology and SEM showed even distribution and spread of cells in the dynamically seeded constructs, while their statically seeded counterparts showed cell aggregation.Fluorescent RT-PCR again showed stronger osteogenic potential of dynamically seeded constructs.Conclusion dynamic seeding of hBMSCs is a promising technique in bone tissue engineering.

  7. Studies on apoptosis in bone tumor cells induced by 153Sm

    Institute of Scientific and Technical Information of China (English)

    ZHU Shou-Peng; XIAO Dong; HAN Xiao-Feng

    2004-01-01

    The apoptosis in human bone tumor cells induced by internal irradiation with 153Sm was studied. The morphological changes in bone tumor cells were observed by electronic and fluorescent microscopy, as well as DNA agarose gel eletrophoresis. DNA chain fragmentation, microautoradiographic tracing and the inhibition rate of proliferation in bone tumor cells exposed to 153Sm with different duration time were examined. It was demonstrated that the bone tumor cells exposed to 153Sm displayed nuclear fragmentation, pyknosis, margination of condensed chromatin, and formation of membrane bounded apoptotic bodies, whereas the percentage of DNA chain fragmentation of bone tumor cells increases in direct proportion to the duration of irradiation with 153Sm, as well as DNA ladder formation in apoptotic cells. Also a marked inhibition effect of proliferation in bone tumor cells after exposure with 153Sm was observed.

  8. Studies on apoptosis in bone tumor cells induced by 153Sm

    International Nuclear Information System (INIS)

    The apoptosis in human bone tumor cells induced by internal irradiation with 153Sm was studied. The morphological changes in bone tumor cells were observed by electronic and fluorescent microscopy, as well as DNA agarose gel electrophoresis. DNA chain fragmentation, microautoradiographic tracing and the inhibition rate of proliferation in bone tumor cells exposed to 153Sm with different duration time were examined. It was demonstrated that the bone tumor cells exposed to 153Sm displayed nuclear fragmentation, pyknosis, margination of condensed chromatin, and formation of membrane bounded apoptotic bodies, whereas the percentage of DNA chain fragmentation of bone tumor cells increases in direct proportion to the duration of irradiation with 153Sm, as well as DNA ladder formation in apoptotic cells. Also a marked inhibition effect of proliferation in bone tumor cells after exposure with 153Sm was observed. (authors)

  9. Preclinical Research Unit at CENTIS

    International Nuclear Information System (INIS)

    The description of the CENTIS Preclinical Research Unit. It has two purposes: Quality assurance system, and the Accreditation facing current national and international standards according with the competent authority

  10. Preclinical Evaluation of the Immunomodulatory Properties of Cardiac Adipose Tissue Progenitor Cells Using Umbilical Cord Blood Mesenchymal Stem Cells: A Direct Comparative Study

    Directory of Open Access Journals (Sweden)

    Isaac Perea-Gil

    2015-01-01

    Full Text Available Cell-based strategies to regenerate injured myocardial tissue have emerged over the past decade, but the optimum cell type is still under scrutiny. In this context, human adult epicardial fat surrounding the heart has been characterized as a reservoir of mesenchymal-like progenitor cells (cardiac ATDPCs with potential clinical benefits. However, additional data on the possibility that these cells could trigger a deleterious immune response following implantation are needed. Thus, in the presented study, we took advantage of the well-established low immunogenicity of umbilical cord blood-derived mesenchymal stem cells (UCBMSCs to comparatively assess the immunomodulatory properties of cardiac ATDPCs in an in vitro allostimulatory assay using allogeneic mature monocyte-derived dendritic cells (MDDCs. Similar to UCBMSCs, increasing amounts of seeded cardiac ATDPCs suppressed the alloproliferation of T cells in a dose-dependent manner. Secretion of proinflammatory cytokines (IL6, TNFα, and IFNγ was also specifically modulated by the different numbers of cardiac ATDPCs cocultured. In summary, we show that cardiac ATDPCs abrogate T cell alloproliferation upon stimulation with allogeneic mature MDDCs, suggesting that they could further regulate a possible harmful immune response in vivo. Additionally, UCBMSCs can be considered as valuable tools to preclinically predict the immunogenicity of prospective regenerative cells.

  11. Histopathologic ear findings of syphilis: a temporal bone study.

    Science.gov (United States)

    Hızlı, Ömer; Hızlı, Pelin; Kaya, Serdar; Monsanto, Rafael da Costa; Paparella, Michael M; Cureoglu, Sebahattin

    2016-09-01

    To the best of our knowledge, histopathologic studies of syphilitic ears have generally focused on hydropic changes; so far, no such studies have investigated peripheral vestibular otopathology using differential interference contrast microscopy, in patients with syphilis. For this study, we examined 13 human temporal bone samples from 8 patients with a history of syphilis. Using conventional light microscopy, we performed qualitative histopathologic assessment. In addition, using differential interference contrast microscopy, we performed type I and type II vestibular hair cell counts on each vestibular sense organ with minimal autolysis; in which the neuroepithelium was oriented perpendicular to the plane of section. We then compared vestibular hair cell densities (cells per 0.01 mm² surface area) in the syphilis group vs. the control group. In the syphilis group, we observed precipitate in the endolymphatic or perilymphatic spaces in 1 (7.7 %) of the samples and endolymphatic hydrops in eight (61.5 %) of the samples. Hydrops involved the cochlea (four samples) and/or saccule (four samples). In addition, the syphilis group experienced a significant loss of type II vestibular hair cells in the maculae of the utricle and saccule, and in the cristae of the lateral and posterior semicircular canals, as compared with the control group (P < 0.05). PMID:26573155

  12. Methotrexate Toxicity in Growing Long Bones of Young Rats: A Model for Studying Cancer Chemotherapy-Induced Bone Growth Defects in Children

    Directory of Open Access Journals (Sweden)

    Chiaming Fan

    2011-01-01

    Full Text Available The advancement and intensive use of chemotherapy in treating childhood cancers has led to a growing population of young cancer survivors who face increased bone health risks. However, the underlying mechanisms for chemotherapy-induced skeletal defects remain largely unclear. Methotrexate (MTX, the most commonly used antimetabolite in paediatric cancer treatment, is known to cause bone growth defects in children undergoing chemotherapy. Animal studies not only have confirmed the clinical observations but also have increased our understanding of the mechanisms underlying chemotherapy-induced skeletal damage. These models revealed that high-dose MTX can cause growth plate dysfunction, damage osteoprogenitor cells, suppress bone formation, and increase bone resorption and marrow adipogenesis, resulting in overall bone loss. While recent rat studies have shown that antidote folinic acid can reduce MTX damage in the growth plate and bone, future studies should investigate potential adjuvant treatments to reduce chemotherapy-induced skeletal toxicities.

  13. Study of the reaction of uranium and plutonium with bone char

    International Nuclear Information System (INIS)

    A study of the reaction of plutonium with a commercial bone char indicates that this bone char has a high capacity for removing plutonium from aqueous wastes. The adsorption of plutonium by bone char is pH dependent, and for plutonium(IV) polymer appears to be maximized near pH 7.3 for plutonium concentrations typical of some waste streams. Adsorption is affected by dissolved salts, especially calcium and phosphate salts. Freundlich isotherms representing the adsorption of uranium and plutonium have been prepared. The low potential imposed upon aqueous solutions by commercial bone char is adequate for reduction of hexavalent plutonium to a lower plutonium oxidation state

  14. Three-dimensional visualization and characterization of bone structure using reconstructed in-vitro μCT images: A pilot study for bone microarchitecture analysis

    International Nuclear Information System (INIS)

    Micro Computed Tomography (μCT) has been largely used to perform micrometer scale imaging of specimens, bone biopsies and small animals for the study of porous or cavity-containing objects. One of its favored applications is for assessing structural properties of bone. In this research, we perform a pilot study to visualize and characterize bone structure of a chicken bone thigh, as well as to delineate its cortical and trabecular bone regions. We utilize an In-Vitro μCT scanner Skyscan 1173 to acquire a three dimensional image data of a chicken bone thigh. The thigh was scanned using X-ray voltage of 45 kV and current of 150 μA. The reconstructed images have spatial resolution of 142.50 μm/pixel. Using image processing and analysis e.i segmentation by thresholding the gray values (which represent the pseudo density) and binarizing the images, we were able to visualize each part of the bone, i.e., the cortical and trabecular regions. Total volume of the bone is 4663.63 mm3, and the surface area of the bone is 7913.42 mm2. The volume of the cortical is approximately 1988.62 mm3 which is nearly 42.64% of the total bone volume. This pilot study has confirmed that the μCT is capable of quantifying 3D bone structural properties and defining its regions separately. For further development, these results can be improved for understanding the pathophysiology of bone abnormality, testing the efficacy of pharmaceutical intervention, or estimating bone biomechanical properties

  15. Three-dimensional visualization and characterization of bone structure using reconstructed in-vitro μCT images: A pilot study for bone microarchitecture analysis

    Energy Technology Data Exchange (ETDEWEB)

    Latief, Fourier Dzar Eljabbar, E-mail: fourier@fi.itb.ac.id [Physics of Earth and Complex Systems, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132 (Indonesia); Dewi, Dyah Ekashanti Octorina [2Biomedical Engineering Research Division, School of Electrical Engineering and Informatics, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132 (Indonesia); Shari, Mohd Aliff Bin Mohd [Faculty of Electrical Engineering, Universiti Teknologi MARA Malaysia, 40000 Shah Alam, Selangor (Malaysia)

    2014-03-24

    Micro Computed Tomography (μCT) has been largely used to perform micrometer scale imaging of specimens, bone biopsies and small animals for the study of porous or cavity-containing objects. One of its favored applications is for assessing structural properties of bone. In this research, we perform a pilot study to visualize and characterize bone structure of a chicken bone thigh, as well as to delineate its cortical and trabecular bone regions. We utilize an In-Vitro μCT scanner Skyscan 1173 to acquire a three dimensional image data of a chicken bone thigh. The thigh was scanned using X-ray voltage of 45 kV and current of 150 μA. The reconstructed images have spatial resolution of 142.50 μm/pixel. Using image processing and analysis e.i segmentation by thresholding the gray values (which represent the pseudo density) and binarizing the images, we were able to visualize each part of the bone, i.e., the cortical and trabecular regions. Total volume of the bone is 4663.63 mm{sup 3}, and the surface area of the bone is 7913.42 mm{sup 2}. The volume of the cortical is approximately 1988.62 mm{sup 3} which is nearly 42.64% of the total bone volume. This pilot study has confirmed that the μCT is capable of quantifying 3D bone structural properties and defining its regions separately. For further development, these results can be improved for understanding the pathophysiology of bone abnormality, testing the efficacy of pharmaceutical intervention, or estimating bone biomechanical properties.

  16. Biomechanical study of the bone tissue with dental implants interaction

    Directory of Open Access Journals (Sweden)

    Navrátil P.

    2011-12-01

    Full Text Available The article deals with the stress-strain analysis of human mandible in the physiological state and after the dental implant application. The evaluation is focused on assessing of the cancellous bone tissue modeling-level. Three cancellous bone model-types are assessed: Non-trabecular model with homogenous isotropic material, nontrabecular model with inhomogeneous material obtained from computer tomography data using CT Data Analysis software, and trabecular model built from mandible section image. Computational modeling was chosen as the most suitable solution method and the solution on two-dimensional level was carried out. The results show that strain is more preferable value than stress in case of evaluation of mechanical response in cancellous bone. The non-trabecular model with CT-obtained material model is not acceptable for stress-strain analysis of the cancellous bone for singularities occurring on interfaces of regions with different values of modulus of elasticity.

  17. Bone locations of systemic mastocytosis: radiological and scintigraphic study

    International Nuclear Information System (INIS)

    Bone radiological signs in six cases of systemic mastocytosis are described: lesions may be diffuse or circumscribed and of the condensation and/or rarefaction type. In most cases, however, the lesions are of the mixed type. Bone mastocytosis may occur without any cutaneous lesions and this emphasizes the value, from the diagnostic point of view, of radiological examinations of the skeleton. Diagnosis is defined and confirmed by three features: the association of condensing lesions and bone rarefactions in different regions of the skeleton; the presence of mastocytic proliferation in stained biopsy specimens from the posterior iliac bone which is not decalcified; fixation of sup(99m)Tc pyrophosphate in the axial skeleton on scintigraphy

  18. Microstructural and Photoacoustic Infrared Spectroscopic Studies of Human Cortical Bone with Osteogenesis Imperfecta

    Science.gov (United States)

    Gu, Chunju; Katti, Dinesh R.; Katti, Kalpana S.

    2016-04-01

    The molecular basis of bone disease osteogenesis imperfecta (OI) and the mineralization of hydroxyapatite in OI bone have been of significant research interest. To further investigate the mechanism of OI disease and bone mineralization, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy, and x-ray diffraction (XRD) are used in the present study to describe the structural and compositional differences between OI and healthy bone. OI bone exhibits more porous, fibrous features, abnormal collagen fibrils, and abnormal mineral deposits. Likewise, photoacoustic-FTIR experiments indicate an aberrant collagen structure and an altered mineral structure in OI. In contrast, there is neither significant difference in the non-collagenous proteins (NCPs) composition observed nor apparent change in the crystal structure between OI and healthy bone minerals as shown in XRD and energy-dispersive x-ray spectroscopy (EDS) results. This observation indicates that the biomineralization process is more controlled by the bone cells and non-collagenous phosphorylated proteins. The present study also confirms that there is an orientational influence on the stoichiometry of the mineral in OI bone. Also, a larger volume of the hydrated layer in the transverse plane than the longitudinal plane of the mineral crystal structure is proposed. The appearance of a new C-S band in the FTIR spectra in OI bone suggests the substitution of glycine by cysteine in collagen molecules or/and an increased amount of cysteine-rich osteonectin that relates to mineral nucleation and mineral crystal formation.

  19. A Comparative Study of Bioartificial Bone Tissue Poly-L-lactic Acid/Polycaprolactone and PLLA Scaffolds Applied in Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Weizong Weng

    2014-01-01

    Full Text Available Bioartificial bone tissue engineering is an increasingly popular technique to repair bone defect caused by injury or disease. This study aimed to investigate the feasibility of PLLA/PCL (poly-L-lactic acid/polycaprolactone by a comparison study of PLLA/PCL and PLLA scaffolds applied in bone regeneration. Thirty healthy mature New Zealand rabbits on which 15 mm distal ulna defect model had been established were selected and then were divided into three groups randomly: group A (repaired with PLLA scaffold, group B (repaired with PLLA/PCL scaffold, and group C (no scaffold to evaluate the bone-remodeling ability of the implants. Micro-CT examination revealed the prime bone regeneration ability of group B in three groups. Bone mineral density of surgical site in group B was higher than group A but lower than group C. Meanwhile, the bone regeneration in both groups A and B proceeded with signs of inflammation for the initial fast degradation of scaffolds. As a whole, PLLA/PCL scaffolds in vivo initially degrade fast and were better suited to repair bone defect than PLLA in New Zealand rabbits. Furthermore, for the low mineral density of new bone and rapid degradation of the scaffolds, more researches were necessary to optimize the composite for bone regeneration.

  20. Normal SUV values measured from NaF18- PET/CT bone scan studies.

    Directory of Open Access Journals (Sweden)

    Aung Zaw Win

    Full Text Available Cancer and metabolic bone diseases can alter the SUV. SUV values have never been measured from healthy skeletons in NaF18-PET/CT bone scans. The primary aim of this study was to measure the SUV values from normal skeletons in NaF18-PET/CT bone scans.A retrospective study was carried out involving NaF18- PET/CT bone scans that were done at our institution between January 2010 to May 2012. Our excluding criteria was patients with abnormal real function and patients with past history of cancer and metabolic bone diseases including but not limited to osteoporosis, osteopenia and Paget's disease. Eleven studies met all the criteria.The average normal SUVmax values from 11 patients were: cervical vertebrae 6.84 (range 4.38-8.64, thoracic vertebrae 7.36 (range 6.99-7.66, lumbar vertebrae 7.27 (range 7.04-7.72, femoral head 2.22 (range 1.1-4.3, humeral head 1.82 (range 1.2-2.9, mid sternum 5.51 (range 2.6-8.1, parietal bone 1.71 (range 1.3-2.4.According to our study, various skeletal sites have different normal SUV values. SUV values can be different between the normal bones and bones with tumor or metabolic bone disease. SUV can be used to quantify NaF-18 PET/CT studies. If the SUV values of the normal skeleton are known, they can be used in the characterization of bone lesions and in the assessment of treatment response to bone diseases.

  1. An in vivo study of bone response to implants topographically modified by laser micromachining.

    Science.gov (United States)

    Hallgren, Carin; Reimers, Henrik; Chakarov, Dinko; Gold, Julie; Wennerberg, Ann

    2003-02-01

    Dental implants topographically modified by laser ablation of periodic arrays of micron-sized craters, were studied in a two-part laboratory investigation. The patterned and control (turned) implants were inserted in rabbit femur and tibia. After 12 weeks the fixation in the bone was evaluated mechanically or by histomorphometry (all threads along the implant and the three best consecutive threads were analysed). In the pilot study no difference was found with respect to bone-to-implant contact and peak removal torque. Significantly more bone was found for the control implants when measuring the bone area inside the threads in the tibia. In the second part of the study, the pattern was improved and significantly more bone-to-implant contact was found for the laser-machined implants. The second part of the study also demonstrated significantly greater peak removal torque values in the tibia with the test implants than the control implants. PMID:12485789

  2. Adiponectin and peak bone mass in men: a cross-sectional, population-based study

    DEFF Research Database (Denmark)

    Frost, M; Abrahamsen, B; Nielsen, T L;

    2010-01-01

    Adiponectin, a protein classically known to be secreted by adipocytes, is also secreted by bone-forming cells. Results of previous studies have been contradictory as to whether serum adiponectin and bone mineral density (BMD) are associated. The aim of this study was to investigate a possible...... association between serum adiponectin and BMD in young, healthy men at a time of peak bone mass. BMD in the femoral neck, total hip, and lumbar spine were measured in this population-based cross-sectional study of 700 men aged 20-29 years participating in the Odense Androgen Study. Magnetic resonance imaging...... of femoral cortical thickness and bone marrow size was performed in a subsample of 363 participants. The associations between serum adiponectin and various bone measures were investigated by means of regression analyses with adjustment for potential confounding variables. An inverse association was...

  3. Quality of Reporting and Adherence to ARRIVE Guidelines in Animal Studies for Chagas Disease Preclinical Drug Research: A Systematic Review

    OpenAIRE

    Julián Ernesto Nicolás Gulin; Daniela Marisa Rocco; Facundo García-Bournissen

    2015-01-01

    Publication of accurate and detailed descriptions of methods in research articles involving animals is essential for health scientists to accurately interpret published data, evaluate results and replicate findings. Inadequate reporting of key aspects of experimental design may reduce the impact of studies and could act as a barrier to translation of research findings. Reporting of animal use must be as comprehensive as possible in order to take advantage of every study and every animal used....

  4. Combined micro computed tomography and histology study of bone augmentation and distraction osteogenesis

    Science.gov (United States)

    Ilgenstein, Bernd; Deyhle, Hans; Jaquiery, Claude; Kunz, Christoph; Stalder, Anja; Stübinger, Stefan; Jundt, Gernot; Beckmann, Felix; Müller, Bert; Hieber, Simone E.

    2012-10-01

    Bone augmentation is a vital part of surgical interventions of the oral and maxillofacial area including dental implantology. Prior to implant placement, sufficient bone volume is needed to reduce the risk of peri-implantitis. While augmentation using harvested autologous bone is still considered as gold standard, many surgeons prefer bone substitutes to reduce operation time and to avoid donor site morbidity. To assess the osteogenic efficacy of commercially available augmentation materials we analyzed drill cores extracted before implant insertion. In younger patients, distraction osteogenesis is successfully applied to correct craniofacial deformities through targeted bone formation. To study the influence of mesenchymal stem cells on bone regeneration during distraction osteogenesis, human mesenchymal stem cells were injected into the distraction gap of nude rat mandibles immediately after osteotomy. The distraction was performed over eleven days to reach a distraction gap of 6 mm. Both the rat mandibles and the drill cores were scanned using synchrotron radiation-based micro computed tomography. The three-dimensional data were manually registered and compared with corresponding two-dimensional histological sections to assess bone regeneration and its morphology. The analysis of the rat mandibles indicates that bone formation is enhanced by mesenchymal stem cells injected before distraction. The bone substitutes yielded a wide range of bone volume and degree of resorption. The volume fraction of the newly formed bone was determined to 34.4% in the computed tomography dataset for the augmentation material Geistlich Bio-Oss®. The combination of computed tomography and histology allowed a complementary assessment for both bone augmentation and distraction osteogenesis.

  5. Preclinical Safety Pharmacology Study of a Novel Protein-Based Cancer Vaccine CHP-NY-ESO-1

    OpenAIRE

    Harada, Naozumi; Hoshiai, Kiyotaka; Takahashi, Yoshiyasu; Sakaguchi, Yasue; Kuno, Takayoshi; Hishida, Tadashi; Shiku, Hiroshi

    2008-01-01

    CHP-NY-ESO-1 is a novel therapeutic cancer vaccine consisting of a recombinantprotein of cancer antigen NY-ESO-1 and a polysaccharide-based delivery system,cholesteryl pullulan. A pilot clinical study of CHP-NY-ESO-1 in cancer patients waspreviously conducted, and the adverse events related to this drug were observed to belimited to skin reactions at injection sites. To further establish the safety ofCHP-NY-ESO-1, we studied the effects of its subcutaneous injection on vital functionssuch as ...

  6. Research of bone metastases in prostate cancer: scintigraphy and radiological study

    International Nuclear Information System (INIS)

    This paper analyses the results of bone scan and radiologic study of the bones on the search of metastases of prostate cancer seen in the last two years. In 44 patients with prostatic cancer the diagnostic of metastatic disease was made by the 99m Tc scan in 52%, and by the metastatic radiologic survey in only 25%. (author)

  7. Cabozantinib Inhibits Growth of Androgen-Sensitive and Castration-Resistant Prostate Cancer and Affects Bone Remodeling

    OpenAIRE

    Nguyen, Holly M.; Nazanin Ruppender; Xiaotun Zhang; Lisha G. Brown; Gross, Ted S.; Colm Morrissey; Roman Gulati; Vessella, Robert L.; Frauke Schimmoller; Aftab, Dana T.; Eva Corey

    2013-01-01

    Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa), cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemis...

  8. Acceleration of tendon healing using US guided intratendinous injection of bevacizumab: First pre-clinical study on a murine model

    International Nuclear Information System (INIS)

    Purpose: Tendinopathy shows early disorganized collagen fibers with neo-angiogenesis on histology. Peri-tendinous injection of corticosteroid is the commonly accepted strategy despite the abscence of inflammation in tendinosis. The aim of our study was to assess the potential of intratendinous injection of an anti-angiogenic drug (bevacizumab, AA) to treat tendinopathy in a murine model of patellar and Achilles tendinopathy, and to evaluate its local toxicity. Materials and method: Forty rats (160 patellar and Achilles tendons) were used for this study. We induced tendinosis (T+) in 80 tendons by injecting under ultrasonography (US) guidance Collagenase 1® (day 0 = D0, patellar = 40 and Achilles = 40). Clinical examination and tendon US were performed at D3, immediately followed by either AA (AAT+, n = 40) or physiological serum (PST+, n = 40, control) US-guided intratendinous injection. Follow-up at D6 and D13 using clinical, US and histology, and comparison between the 2 groups were performed. To study AA toxicity we compared the 80 remaining normal tendons (T−) after injecting AA in 40 (AAT−). Results: All AAT+ showed a better joint mobilization compared to PST+ at D6 (p = 0.004) with thinner US tendon diameters (p < 0.004), and less disorganized collagen fibers and neovessels on histology (p < 0.05). There was no difference at D13 regarding clinical status, US tendon diameter and histology (p > 0.05). Comparison between AAT− and T− showed no AA toxicity on tendon (p = 0.18). Conclusion: Our study suggests that high dose mono-injection of AA in tendinosis, early after the beginning of the disease, accelerates tendon's healing, with no local toxicity

  9. Acceleration of tendon healing using US guided intratendinous injection of bevacizumab: First pre-clinical study on a murine model

    Energy Technology Data Exchange (ETDEWEB)

    Dallaudière, Benjamin, E-mail: bendallau64@hotmail.fr [Service de Radiologie, Hôpital universitaire Bichat, Paris (France); Inserm U698, Hôpital universitaire Bichat, Paris (France); Université de Médecine Paris Diderot (France); Lempicki, Marta [Service de Radiologie, Hôpital universitaire Bichat, Paris (France); Université de Médecine Paris Diderot (France); Pesquer, Lionel [Centre d’Imagerie Ostéo Articulaire, Clinique du Sport de Bordeaux-Mérignac (France); Louedec, Liliane [Inserm U698, Hôpital universitaire Bichat, Paris (France); Preux, Pierre Marie [Laboratoire de Biostatistiques, Faculté de médecine, Limoges (France); Meyer, Philippe [Centre d’Imagerie Ostéo Articulaire, Clinique du Sport de Bordeaux-Mérignac (France); Hess, Agathe [Service de Radiologie, Hôpital universitaire Bichat, Paris (France); Université de Médecine Paris Diderot (France); Durieux, Marie Hèlène Moreau [Centre d’Imagerie Ostéo Articulaire, Clinique du Sport de Bordeaux-Mérignac (France); Hummel, Vincent; Larbi, Ahmed [Service de Radiologie, Hôpital universitaire Bichat, Paris (France); Deschamps, Lydia [Service d’ Anatomopathologie, Hôpital universitaire Bichat, Paris (France); and others

    2013-12-01

    Purpose: Tendinopathy shows early disorganized collagen fibers with neo-angiogenesis on histology. Peri-tendinous injection of corticosteroid is the commonly accepted strategy despite the abscence of inflammation in tendinosis. The aim of our study was to assess the potential of intratendinous injection of an anti-angiogenic drug (bevacizumab, AA) to treat tendinopathy in a murine model of patellar and Achilles tendinopathy, and to evaluate its local toxicity. Materials and method: Forty rats (160 patellar and Achilles tendons) were used for this study. We induced tendinosis (T+) in 80 tendons by injecting under ultrasonography (US) guidance Collagenase 1{sup ®} (day 0 = D0, patellar = 40 and Achilles = 40). Clinical examination and tendon US were performed at D3, immediately followed by either AA (AAT+, n = 40) or physiological serum (PST+, n = 40, control) US-guided intratendinous injection. Follow-up at D6 and D13 using clinical, US and histology, and comparison between the 2 groups were performed. To study AA toxicity we compared the 80 remaining normal tendons (T−) after injecting AA in 40 (AAT−). Results: All AAT+ showed a better joint mobilization compared to PST+ at D6 (p = 0.004) with thinner US tendon diameters (p < 0.004), and less disorganized collagen fibers and neovessels on histology (p < 0.05). There was no difference at D13 regarding clinical status, US tendon diameter and histology (p > 0.05). Comparison between AAT− and T− showed no AA toxicity on tendon (p = 0.18). Conclusion: Our study suggests that high dose mono-injection of AA in tendinosis, early after the beginning of the disease, accelerates tendon's healing, with no local toxicity.

  10. ‘PROBIOTIC BACTERIA ADMINISTRATION AS AN IMMUNOMODULATORY APPROACH FOR FOOD ALLERGY TREATMENT: PRECLINICAL STUDIES IN MOUSE MODELS’

    OpenAIRE

    Schiavi, Elisa

    2013-01-01

    Studi clinici ed epidemiologici hanno messo in evidenza l’associazione tra l’aumentata prevalenza delle malattie allergiche nei Paesi occidentali e la ridotta esposizione ai germi e/o l’ alterazione delle comunità microbiche intestinali, il cui metabolismo e composizione risultano cruciali per lo sviluppo e il mantenimento delle funzioni immunitarie. Riportare all’equilibrio il microbioma intestinale potrebbe rappresentare una strategia preventiva e/o terapeutica per le allergie, in particola...

  11. A Novel Pre-Clinical Murine Model to Study the Life Cycle and Progression of Cervical and Anal Papillomavirus Infections

    OpenAIRE

    Cladel, Nancy M.; Budgeon, Lynn R.; Balogh, Karla K.; Timothy K Cooper; Jiafen Hu; Christensen, Neil D.

    2015-01-01

    Background Papillomavirus disease and associated cancers remain a significant health burden in much of the world. The current protective vaccines, Gardasil and Cervarix, are expensive and not readily available to the underprivileged. In addition, the vaccines have not gained wide acceptance in the United States nor do they provide therapeutic value. Papillomaviruses are strictly species specific and thus human viruses cannot be studied in an animal host. An appropriate model for mucosal disea...

  12. Effect of surgical experience on imageless computer-assisted femoral component positioning in hip resurfacing – a preclinical study

    OpenAIRE

    Stiehler, Maik; Goronzy, Jens; Kirschner, Stephan; Hartmann, Albrecht; Schäfer, Torsten; Günther, Klaus-Peter

    2015-01-01

    Background: The clinical outcome of hip resurfacing (HR) as a demanding surgical technique associated with a substantial learning curve depends on the position of the femoral component. The aim of the study was to investigate the effects of the level of surgical experience on computer-assisted imageless navigation concerning precision of femoral component positioning, notching, and oversizing rate, as well as operative time. Methods: Three surgeons with different levels of experienc...

  13. A preclinical study of boron neutron capture therapy (BNCT) of spontaneous tumors in cats at RA-6 in Argentina

    International Nuclear Information System (INIS)

    BNCT is a binary treatment modality that combines irradiation with a thermal or epithermal neutron beam with tumor-seeking, boron containing drugs to produce selective irradiation of tumor tissue. Having demonstrated that BNCT mediated by boronophenylalanine (BPA) induced control of experimental squamous cell carcinomas (SCC) of the hamster cheek pouch mucosa with no damage to normal tissue we explored the feasibility and safety of treating spontaneous head and neck tumors, with particular focus on SCC, of terminal feline patients with low dose BPA-BNCT employing the thermal beam of RA-1. Having demonstrated partial tumor control with no radio toxic effects, the aim of the present study was to evaluate the effect of BPA-BNCT on tumor and normal tissue in 3 cases of spontaneous SCC in feline patients employing a higher neutron fluence than in the previous study. The present study was performed at RA-6 with the thermalized epithermal neutron beam. All three irradiations were successful. Except for an initial, moderate and reversible mucositis, no significant radio toxic effects were observed in terms of clinical follow-up, histological examination, biochemical analysis and assessment of autopsy material. Partial tumor control was evidenced in terms of growth inhibition and partial necrosis and improvement in the quality of life during the survival period. Optimization of the therapeutic efficacy of BNCT would require improvement in boron tumor targeting and strategies to increase in-depth dose in large tumors. (author)

  14. Early reversal cells in adult human bone remodeling

    DEFF Research Database (Denmark)

    Abdelgawad, Mohamed Essameldin; Delaisse, Jean-Marie; Hinge, Maja;

    2016-01-01

    . Earlier preclinical studies indicate that reversal cells degrade the organic matrix left behind by the osteoclasts and that this degradation is crucial for the initiation of the subsequent bone formation. To our knowledge, this study is the first addressing these catabolic activities in adult human bone......The mechanism coupling bone resorption and formation is a burning question that remains incompletely answered through the current investigations on osteoclasts and osteoblasts. An attractive hypothesis is that the reversal cells are likely mediators of this coupling. Their nature is a big matter of...... debate. The present study performed on human cancellous bone is the first one combining in situ hybridization and immunohistochemistry to demonstrate their osteoblastic nature. It shows that the Runx2 and CD56 immunoreactive reversal cells appear to take up TRAcP released by neighboring osteoclasts...

  15. Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E-e4/4 homozygotes: a replication study.

    Science.gov (United States)

    Caselli, R J; Osborne, D; Reiman, E M; Hentz, J G; Barbieri, C J; Saunders, A M; Hardy, J; Graff-Radford, N R; Hall, G R; Alexander, G E

    2001-08-15

    In a previous cross-sectional study of 100 asymptomatic individuals aged 49-69, we reported age-related decline in immediate and delayed memory that was steeper in apolipoprotein E (apoE)-e4/4 homozygotes than in members of other genetic subgroups. These findings were preliminarily based upon the statistical problem of multiple comparisons. We therefore sought to replicate these findings in a new cohort. From 1998 to 2000, 80 asymptomatic residents of Maricopa County, AZ were recruited through newspaper ads. 20 apoE-e4/4 homozygotes, 20 e3/4 heterozygotes, and 40 e4 noncarriers were matched (1:1:2) by age, gender, and years of education. All had normal neurologic and psychiatric examinations, including Folstein minimental status exam (MMSE) and Hamilton depression scale, and underwent a battery of neuropsychological tests identical to those in our previous study. The groups were well-matched for age (55.9+/-5.9 years), gender (60% women), and education (15.9+/-2.2 years), and were demographically similar to our previous cohort. Complex figure test recall was lower in e3/4 heterozygotes than noncarriers, but there was no significant difference between e4/4 homozygotes and noncarriers. There were no other significant differences in mean test scores between groups, but Wechsler adult intelligence scale-revised (WAIS-R) digit span showed a significant negative correlation with age in the e4/4 homozygote group relative to e4 noncarriers (p=0.008) as we had found in our previous study. In conclusion, we found a significant negative correlation of WAIS-R digit span with age in apoE-e4/4 homozygotes relative to e4 noncarriers in two separate cohorts, possibly reflecting an age-related effect on frontal lobe function in this genetic subgroup. PMID:11535238

  16. Healing of the proximal bone clock in anterior cruciate ligament reconstruction with bone-patellar-tendon-bone graft - a CT-controlled study

    International Nuclear Information System (INIS)

    Anterior cruciate ligament (ACL) reconstruction with the middle third of the patellar ligament is a widely used method to re-establish knee function after ACL-injury. However, there is still considerable debate about the operative technique and graft fixation The goal of this study was to evaluate ACL-reconstruction with bone-patellar tendon-bone (BPTB) graft and femoral fixation with endobutton clinically as well as to evaluate bone tunnel placement and tunnel morphology with CT and x-ray. 51 patients, who had undergone ACL-reconstruction with BPTB-graft and fixation with Endobutton, were evaluated clinically. In 51 cases standard x-ray films - anterior-posterior (AP) and lateral - and in 50 cases computed tomography (CT) scans were obtained. Femoral tunnel placement was measured with a three-dimensional coordinate system on both x-ray films and CT scans. Tunnel widening and bone block healing where determined with CT on both the femoral and the tibial side. 40 patients had a normal or nearly normal knee function, 6 patients scored abnormal and none of the patients was rated severely abonormal according to the International Knee Documentation Committee (IKDC) form. Tunnel placement could not be determined on plain x-rays in 46 cases on the AP-films and in 8 cases on the lateral films. Average position: AP: 89,8 %, lateral: 38,5 %. On CT-scans the position could be measured in all 50 cases. Average position CT: AP: 90,5 %, lateral: 34,1 %. Tunnel widening on the femoral side was 40 % tunnel widening where obtained. Femoral bone block healing was complete in all cases. This operative technique shows good clinical results, which are comparable to other studies on ACL-reconstruction with BPTB-grafts. Suspensory femoral fixation with Endobutton does not cause any significant tunnel widening as it was reported when using the same fixation but hamstring grafts. Average tunnel position was comparable to other studies. However, CT scans are superior to plain radiographs

  17. A novel pre-clinical murine model to study the life cycle and progression of cervical and anal papillomavirus infections.

    Directory of Open Access Journals (Sweden)

    Nancy M Cladel

    Full Text Available Papillomavirus disease and associated cancers remain a significant health burden in much of the world. The current protective vaccines, Gardasil and Cervarix, are expensive and not readily available to the underprivileged. In addition, the vaccines have not gained wide acceptance in the United States nor do they provide therapeutic value. Papillomaviruses are strictly species specific and thus human viruses cannot be studied in an animal host. An appropriate model for mucosal disease has long been sought. We chose to investigate whether the newly discovered mouse papillomavirus, MmuPV1, could infect mucosal tissues in Foxn1nu/Foxn1nu mice.The vaginal and anal canals of Foxn1nu/Foxn1nu mice were gently abraded using Nonoxynol-9 and "Doctor's BrushPicks" and MmuPV1 was delivered into the vaginal tract or the anal canal.Productive vaginal, cervical and anal infections developed in all mice. Vaginal/cervical infections could be monitored by vaginal lavage. Dysplasias were evident in all animals.Anogenital tissues of a common laboratory mouse can be infected with a papillomavirus unique to that animal. This observation will pave the way for fundamental virological and immunological studies that have been challenging to carry out heretofore due to lack of a suitable model system.

  18. Fluorine-18-fluorodeoxygglucose-guided breast cancer surgery with a positron-sensitive probe: Validation in preclinical studies

    International Nuclear Information System (INIS)

    In this study, the feasibility of utilizing 2-deoxy-2-fluoro-d-glucose (FDG) in conjunction with a positron-sensitive intraoperative probe to guide breast tumor excision was investigated. The probe was constructed with a plastic scintillator tip coupled to a photomultiplier tube with fiber optic cable. Anticipated resolution degradation was evaluated by measurement of line spread functions in the presence of background radiation. Realistic photon background distributions were simulated with a human torso phantom and a cardiac insert. The relationship between resolution and energy threshold was measured to find the optimal discriminator settings. In addition, probe sensitivity as a function of energy threshold was determined for various size-simulated tumors. Finally, the ability to localize breast cancers in vivo was tested in a rodent model. Mammary rat tumors implanted in Lewis rats were examined after injection with FDG; these results were correlated with those of histologic analyses. Measurements of line spread functions indicated that resolution could be maximized in a realistic background photon environment by increasing the energy threshold to levels at or above the Compton continuum edge (340 keV). At this setting, the probe's sensitivity was determined to be 58 and 11 cps/μCi for 3.18- and 6.35-mm diameter simulated tumors, respectively. Probe readings correlated well with histologic results; the probe was generally able to discriminate between tumor and normal tissue. This study indicates that breast cancer surgery guided by a positron-sensitive probe warrants future evaluation in breast-conserving surgery of patients with breast cancer. 23 refs., 5 figs

  19. Preclinical Studies of 68Ga-DOTATOC: Biodistribution Assessment in Syrian Rats and Evaluation of Absorbed Dose in Human Organs

    Directory of Open Access Journals (Sweden)

    mojdeh naderi

    2016-01-01

    Full Text Available Objective(s: Gallium-68 DOTA-DPhe1-Tyr3-Octreotide (68Ga-DOTATOC has been applied by several European centers for the treatment of a variety of human malignancies. Nevertheless, definitive dosimetric data are yet unavailable. According to the Society of Nuclear Medicine and Molecular Imaging, researchers are investigating the safety and efficacy of this radiotracer to meet Food and Drug Administration requirements. The aim of this study was to introduce the optimized procedure for 68Ga-DOTATOC preparation, using a novel germanium-68 (68Ge/68Ga generator in Iran and evaluate the absorbed doses in numerous organs with high accuracy. Methods: The optimized conditions for preparing the radiolabeled complex were determined via several experiments by changing the ligand concentration, pH, temperature and incubation time. Radiochemical purity of the complex was assessed, using high-performance liquid chromatography and instant thin-layer chromatography. The absorbed dose of human organs was evaluated, based on biodistribution studies on Syrian rats via Radiation Absorbed Dose Assessment Resource Method. Results: 68Ga-DOTATOC was prepared with radiochemical purity of >98% and specific activity of 39.6 MBq/nmol. The complex demonstrated great stability at room temperature and in human serum at 37°C at least two hours after preparation. Significant uptake was observed in somatostatin receptor-positive tissues such as pancreatic and adrenal tissues (12.83 %ID/g and 0.91 %ID/g, respectively. Dose estimations in human organs showed that the pancreas, kidneys and adrenal glands received the maximum absorbed doses (0.105, 0.074 and 0.010 mGy/MBq, respectively. Also, the effective absorbed dose was estimated at 0.026 mSv/MBq for 68Ga-DOTATOC. Conclusion: The obtained results showed that 68Ga-DOTATOC can be considered as an effective agent for clinical PET imaging in Iran.

  20. Development and validation of a method for the analysis of hydroxyzine hydrochloride in extracellular solution used in in vitro preclinical safety studies.

    Science.gov (United States)

    Briône, Willy; Brekelmans, Mari; Eijndhoven, Freek van; Schenkel, Eric; Noij, Theo

    2015-11-10

    In the process of drug development, preclinical safety studies are to be performed that require the analysis of the compound at very low concentrations with high demands on the performance of the analytical methods. In the current study, a UPLC-MS/MS method was developed and validated to quantify hydroxyzine hydrochloride in an extracellular solution used in a hERG assay in concentrations ranging from 0.01 to 10μM (4.5ng/ml-4.5μg/ml). Chromatographic separation was achieved isocratically on an Acquity BEH C18 analytical column. The assay was validated at concentrations of 0.11-1.1ng/ml in end solution for hydroxyzine hydrochloride. Linearity was demonstrated over the range of concentrations of 0.06-0.17ng/ml and over the range of concentrations of 0.6-1.7ng/ml in end solution with the coefficient of correlation r>0.99. Accuracy of the achieved concentration, intra-run, and inter-run precision of the method were well within the acceptance criteria (being mean recovery of 80-120% and relative standard deviation ≤10.0%). The limit of quantification in extracellular solution was 0.09ng/ml. Hydroxyzine hydrochloride in extracellular solution proved to be stable when stored in the fridge at 4-8°C for at least 37 days, at room temperature for at least 16 days and at +35°C for at least 16 days. The analytical method was successfully applied in hERG assay. PMID:26163869

  1. Development of Immunoassays for the Quantitative Assessment of Amyloid-β in the Presence of Therapeutic Antibody: Application to Pre-Clinical Studies.

    Science.gov (United States)

    Bogstedt, Anna; Groves, Maria; Tan, Keith; Narwal, Rajesh; McFarlane, Mary; Höglund, Kina

    2015-01-01

    Utilizing decision making biomarkers in drug development requires thorough assay validation. Special considerations need to be taken into account when monitoring biomarkers using immunoassays in the presence of therapeutic antibodies. We have developed robust and sensitive assays to assess target engagement and proof of mechanism to support the clinical progression of a human monoclonal antibody against the neurotoxic amyloid-β (Aβ)42 peptide. Here we present the introduction of novel pre-treatment steps to ensure drug-tolerant immunoassays and describe the validation of the complete experimental procedures to measure total Aβ42 concentration (bound and unbound) in cerebrospinal fluid (CSF) and plasma, free Aβ42 concentration (unbound) in CSF, and Aβ40 concentration in CSF. The difference in composition of the matrices (CSF and plasma) and antigen levels therein, in combination with the hydrophobic properties of Aβ protein, adds to the complexity of validation. Monitoring pharmacodynamics of an Aβ42 specific monoclonal antibody in a non-human primate toxicology study using these assays, we demonstrated a 1500-fold and a 3000-fold increase in total Aβ42 in plasma, a 4-fold and 8-fold increase in total Aβ42 in CSF together with a 95% and 96% reduction of free Aβ42 in CSF following weekly intravenous injections of 10 mg/kg and 100 mg/kg, respectively. Levels of Aβ40 were unchanged. The accuracy of these data is supported by previous pre-clinical studies as well as predictive pharmacokinetic/pharmacodynamics modeling. In contrast, when analyzing the same non-human primate samples excluding the pre-treatment steps, we were not able to distinguish between free and total Aβ42. Our data clearly demonstrate the importance of thorough evaluation of antibody interference and appropriate validation to monitor different types of biomarkers in the presence of a therapeutic antibody. PMID:26402635

  2. In situ study of the impact of inter- and intra-reader variability on region of interest (ROI) analysis in preclinical molecular imaging.

    Science.gov (United States)

    Habte, Frezghi; Budhiraja, Shradha; Keren, Shay; Doyle, Timothy C; Levin, Craig S; Paik, David S

    2013-01-01

    We estimated reader-dependent variability of region of interest (ROI) analysis and evaluated its impact on preclinical quantitative molecular imaging. To estimate reader variability, we used five independent image datasets acquired each using microPET and multispectral fluorescence imaging (MSFI). We also selected ten experienced researchers who utilize molecular imaging in the same environment that they typically perform their own studies. Nine investigators blinded to the data type completed the ROI analysis by drawing ROIs manually that delineate the tumor regions to the best of their knowledge and repeated the measurements three times, non-consecutively. Extracted mean intensities of voxels within each ROI are used to compute the coefficient of variation (CV) and characterize the inter- and intra-reader variability. The impact of variability was assessed through random samples iterated from normal distributions for control and experimental groups on hypothesis testing and computing statistical power by varying subject size, measured difference between groups and CV. The results indicate that inter-reader variability was 22.5% for microPET and 72.2% for MSFI. Additionally, mean intra-reader variability was 10.1% for microPET and 26.4% for MSFI. Repeated statistical testing showed that a total variability of CV < 50% may be needed to detect differences < 50% between experimental and control groups when six subjects (n = 6) or more are used and statistical power is adequate (80%). Surprisingly high variability has been observed mainly due to differences in the ROI placement and geometry drawn between readers, which may adversely affect statistical power and erroneously lead to negative study outcomes. PMID:23526701

  3. Comparison of common platelet receptors between the chacma baboon (Papio ursinus) and human for use in pre-clinical human-targeted anti-platelet studies.

    Science.gov (United States)

    Janse van Rensburg, Walter J

    2016-06-01

    Anti-platelet agents play a central part in the treatment and prevention of acute thrombotic events. Discriminating animal models are needed for the development of novel agents. The chacma baboon has been extensively used as a model to evaluate anti-platelet agents. However, limited data exist to prove the translatability of this species to humans. We aimed to determine the suitability of the chacma baboon in preclinical human targeted GPIIb/IIIa, GPIbα and P2Y12 studies. Light-transmission platelet aggregometry (LTA), whole blood impedance aggregometry, receptor number quantification and genomic DNA sequencing were performed. Baboon ADP and arachidonic acid-induced LTA aggregation results differed significantly from human values, even at increased concentrations. LTA ristocetin-induced agglutination was comparable between species, but baboon platelets needed twice the concentration of ristocetin to elicit a similar response. Citrated baboon blood had significantly less aggregation than humans when evaluated with impedance aggregometry. However, hirudinised baboon whole blood gave similar aggregation as humans at the same agonist concentrations. GPIIb, GPIIIa and GPIbα numbers were significantly more on the baboon platelets. None of the amino acids deemed vital for receptor function, ligand binding or receptor inhibition, were radically different between the species. However, a conservative change in a calcium-binding region of GPIIb may render the baboon platelets more sensitive to calcium-binding agents. The chacma baboon may be used for the evaluation of human-targeted GPIIb/IIIa-, GPIbα- and P2Y12-inhibiting agents. However, the best anticoagulant, optimal agonist concentrations, increase in receptor number and sequence differences must be considered for any future studies. PMID:26559117

  4. Preclinical evaluation of NETA-based bifunctional ligand for radioimmunotherapy applications using 212Bi and 213Bi: Radiolabeling, serum stability, and biodistribution and tumor uptake studies

    International Nuclear Information System (INIS)

    Introduction: Despite the great potential of targeted α-radioimmunotherapy (RIT) as demonstrated by pre-clinical and clinical trials, limited progress has been made on the improvement of chelation chemistry for 212Bi and 213Bi. A new bifunctional ligand 3p-C-NETA was evaluated for targeted α RIT using 212Bi and 213Bi. Methods: Radiolabeling of 3p-C-NETA with 205/6Bi, a surrogate of 212Bi and 213Bi, was evaluated at pH 5.5 and room temperature. In vitro stability of the 205/6Bi-3p-C-NETA-trastuzumab conjugate was evaluated using human serum (pH 7, 37 °C). Immunoreactivity and specific activity of the 205/6Bi-3p-C-NETA-trastuzumab conjugate were measured. An in vivo biodistribution study was performed to evaluate the in vivo stability and tumor targeting properties of the 205/6Bi-3p-C-NETA-trastuzumab conjugate in athymic mice bearing subcutaneous LS174T tumor xenografts. Result: The 3p-C-NETA-trastuzumab conjugate was extremely rapid in complexing with 205/6Bi, and the corresponding 205/6Bi-3p-C-NETA-trastuzumab was stable in human serum. 205/6Bi-3p-C-NETA-trastuzumab was prepared with a high specific activity and retained immunoreactivity. 205/6Bi-3p-C-NETA-trastuzumab conjugate displayed excellent in vivo stability and targeting as evidenced by low normal organ and high tumor uptake. Conclusion: The results of the in vitro and in vivo studies indicate that 3p-C-NETA is a promising chelator for RIT applications using 212Bi and 213Bi. Further detailed in vivo evaluations of 3p-C-NETA for targeted α RIT are warranted

  5. Inhibition of DNA-repair genes Ercc1 and Mgmt enhances temozolomide efficacy in gliomas treatment: a pre-clinical study.

    Science.gov (United States)

    Boccard, Sandra G; Marand, Sandie V; Geraci, Sandra; Pycroft, Laurie; Berger, François R; Pelletier, Laurent A

    2015-10-01

    Gliomas are the most common primary brain tumors. To date, therapies do not allow curing patients, and glioblastomas (GBMs) are associated with remarkably poor prognosis. This situation is at least partly due to intrinsic or acquired resistance to treatment, especially to chemotherapy. In 2005, temozolomide (TMZ) has become the first chemotherapeutic drug validated for GBM. Nevertheless TMZ efficacy depends on Mgmt status. While the methylation of Mgmt promoter was considered so far as a prognostic marker, its targeting is becoming an effective therapeutic opportunity. Thus, arrival of both TMZ and Mgmt illustrated that considerable progress can still be realized by optimizing adjuvant chemotherapy. A part of this progress could be accomplished in the future by overcoming residual resistance. The aim of the present study was to investigate the involvement of a set of other DNA-repair genes in glioma resistance to temozolomide. We focused on DNA-repair genes located in the commonly deleted chromosomal region in oligodendroglioma (1p/19q) highly correlated with patient response to chemotherapy. We measured effects of inhibition of ten DNA-repair genes expression using siRNAs on astrocytoma cell response to cisplatin (CDDP) and TMZ. SiRNAs targeting ercc1, ercc2, mutyh, and pnkp significantly sensitized cells to chemotherapy, increasing cell death by up to 25%. In vivo we observed a decrease of subcutaneous glioma tumor growth after injection of siRNA in conjunction with absorption of TMZ. We demonstrated in this pre-clinical study that targeting of DNA-repair genes such as Ercc1 could be used as an adjuvant chemosensitization treatment, similarly to Mgmt inhibition. PMID:26336131

  6. Adiponectin and peak bone mass in men: a cross-sectional, population-based study

    DEFF Research Database (Denmark)

    Nielsen, Morten Frost; Abrahamsen, B; Nielsen, T L;

    2010-01-01

    Adiponectin, a protein classically known to be secreted by adipocytes, is also secreted by bone-forming cells. Results of previous studies have been contradictory as to whether serum adiponectin and bone mineral density (BMD) are associated. The aim of this study was to investigate a possible...... of femoral cortical thickness and bone marrow size was performed in a subsample of 363 participants. The associations between serum adiponectin and various bone measures were investigated by means of regression analyses with adjustment for potential confounding variables. An inverse association was...... found between serum adiponectin and total hip BMD and a direct between adiponectin and femoral bone marrow size (r = -0.092; P = 0.036 and r = 0.164; P = 0.003, respectively). Femoral muscle size may, at least in part, explain the association between adiponectin and total hip BMD. Serum adiponectin was...

  7. Challenges for Preclinical Investigations of Human Biofield Modalities

    OpenAIRE

    Gronowicz, Gloria; Bengston, William; Yount, Garret

    2015-01-01

    Preclinical models for studying the effects of the human biofield have great potential to advance our understanding of human biofield modalities, which include external qigong, Johrei, Reiki, therapeutic touch, healing touch, polarity therapy, pranic healing, and other practices. A short history of Western biofield studies using preclinical models is presented and demonstrates numerous and consistent examples of human biofields significantly affecting biological systems both in vitro and in v...

  8. Balance of the Sexes: Addressing Sex Differences in Preclinical Research

    Science.gov (United States)

    Zakiniaeiz, Yasmin; Cosgrove, Kelly P.; Potenza, Marc N.; Mazure, Carolyn M.

    2016-01-01

    Preclinical research is fundamental for the advancement of biomedical sciences and enhancing healthcare. Considering sex differences in all studies throughout the entire biomedical research pipeline is necessary to adequately inform clinical research and improve health outcomes. However, there is a paucity of information to date on sex differences in preclinical work. As of 2009, most (about 80 percent) rodent studies across 10 fields of biology were still conducted with only male animals. In 2016, the National Institutes of Health implemented a policy aimed to address this concern by requiring the consideration of sex as a biological variable in preclinical research grant applications. This perspective piece aims to (1) provide a brief history of female inclusion in biomedical research, (2) describe the importance of studying sex differences, (3) explain possible reasons for opposition of female inclusion, and (4) present potential additional solutions to reduce sex bias in preclinical research. PMID:27354851

  9. Influence of mineral phase in mineralization of a biocomposite containing chitosan, demineralized bone matrix and bone ash—in vitro study

    Indian Academy of Sciences (India)

    Krithiga Gunasekaran; Santhosh Kumar Baskar; Divya Sapphire Mohan; Thotapalli P Sastry

    2014-05-01

    A resorbable composite which acts as a active barrier in guided bone regeneration was fabricated using chitosan, demineralized bone matrix and bone ash. Its potential to form bone like apatite in simulated body fluid was assessed in this study. The mechanical strength of these composites was correlated with bone ash ratios and composites with better tensile strength were studied for their acellular bioactivity by incubating in simulated body fluid for 21 days. Composites without bone ash did not show acellular bioactivity which was confirmed by thermogravimetric analysis. In case of biocomposites with bone ash, there was an increase in residual weight indicating the mineralization of the composite. The composite containing bone ash has shown the peaks related to phosphate vibrations in its Fourier-transform infrared spectrum. Scanning micrographs revealed formation of apatite like crystals on its surface. Ca/P ratio was found to be 1.7 which is nearer to that of natural bone. Thus, prepared composites can be used as resorbable biocomposite in maxillofacial and oral defects.

  10. Study on the Algorithm of Multifunctional Bone External Fixator

    Directory of Open Access Journals (Sweden)

    Chen Jianwen

    2015-01-01

    Full Text Available This paper discussed the problem that parameters of bone external fixator are difficult to calculate in the practical application. Positive solution is described in detail. We used MATLAB software to make simulation experiment. The innovation lies the development idea of using inverse position to verify the accuracy of positive solution. Forward displacement analysis was mainly developed using analytical method, which has many advantages, such as small dependence to the inverse solution and the higher precision. With further software development, we will have the algorithms; research model and interface program connected and form high precision smart compliance multifunctional bone external fixator products, which will greatly enhance the overall level of bone external fixation technology and clinical application treatment.

  11. Isolated lung perfusion as an adjuvant treatment of colorectal cancer lung metastases: a preclinical study in a pig model.

    Directory of Open Access Journals (Sweden)

    Pierre-Benoit Pagès

    Full Text Available BACKGROUND: The lung is a frequent site of colorectal cancer (CRC metastases. After surgical resection, lung metastases recurrences have been related to the presence of micrometastases, potentially accessible to a high dose chemotherapy administered via adjuvant isolated lung perfusion (ILP. We sought to determine in vitro the most efficient drug when administered to CRC cell lines during a short exposure and in vivo its immediate and delayed tolerance when administered via ILP. METHODS: First, efficacy of various cytotoxic molecules against a panel of human CRC cell lines was tested in vitro using cytotoxic assay after a 30-minute exposure. Then, early (operative and delayed (1 month tolerance of two concentrations of the molecule administered via ILP was tested on 19 adult pigs using hemodynamic, biological and histological criteria. RESULTS: In vitro, gemcitabine (GEM was the most efficient drug against selected CRC cell lines. In vivo, GEM was administered via ILP at regular (20 µg/ml or high (100 µg/ml concentrations. GEM administration was associated with transient and dose-dependant pulmonary vasoconstriction, leading to a voluntary decrease in pump inflow in order to maintain a stable pulmonary artery pressure. After this modulation, ILP using GEM was not associated with any systemic leak, systemic damage, and acute or delayed histological pulmonary toxicity. Pharmacokinetics studies revealed dose-dependant uptake associated with heterogenous distribution of the molecule into the lung parenchyma, and persistent cytotoxicity of venous effluent. CONCLUSIONS: GEM is effective against CRC cells even after a short exposure. ILP with GEM is a safe and reproducible technique.

  12. Pain and depression comorbidity: a preclinical perspective

    OpenAIRE

    Li, Jun-Xu

    2014-01-01

    Pain and depression are two highly prevalent and deleterious disorders with significant socioeconomic impact to society. Clinical observations have long recognized the co-existence and interactions of pain and depression. However, the underlying mechanisms of pain-depression comorbidity and their dynamic interactions remain largely unknown. Preclinical animal studies may provide critical information for the understanding of this important comorbidity. This review analyzed the current preclini...

  13. SU-E-J-156: Preclinical Inverstigation of Dynamic Tumor Tracking Using Vero SBRT Linear Accelerator: Motion Phantom Dosimetry Study

    Energy Technology Data Exchange (ETDEWEB)

    Mamalui-Hunter, M; Wu, J; Li, Z; Su, Z [University of Florida/Radiation Oncology, Jacksonville, FL (United States)

    2014-06-01

    Purpose: Following the ‘end-to-end testing’ paradigm of Dynamic Target Tracking option in our Image-Guided dedicated SBRT VeroTM linac, we verify the capability of the system to deliver planned dose to moving targets in the heterogeneous thorax phantom (CIRSTM). The system includes gimbaled C-band linac head, robotic 6 degree of freedom couch and a tumor tracking method based on predictive modeling of target position using fluoroscopically tracked implanted markers and optically tracked infrared reflecting external markers. Methods: 4DCT scan of the motion phantom with the VisicoilTM implanted marker in the close vicinity of the target was acquired, the ‘exhale’=most prevalent phase was used for planning (iPlan by BrainLabTM). Typical 3D conformal SBRT treatment plans aimed to deliver 6-8Gy/fx to two types of targets: a)solid water-equivalent target 3cm in diameter; b)single VisicoilTM marker inserted within lung equivalent material. The planning GTV/CTV-to-PTV margins were 2mm, the block margins were 3 mm. The dose calculated by MonteCarlo algorithm with 1% variance using option Dose-to-water was compared to the ion chamber (CC01 by IBA Dosimetry) measurements in case (a) and GafchromicTM EBT3 film measurements in case (b). During delivery, the target 6 motion patterns available as a standard on CIRSTM motion phantom were investigated: in case (a), the target was moving along the designated sine or cosine4 3D trajectory; in case (b), the inserted marker was moving sinusoidally in 1D. Results: The ion chamber measurements have shown the agreement with the planned dose within 1% under all the studied motion conditions. The film measurements show 98.1% agreement with the planar calculated dose (gamma criteria: 3%/3mm). Conclusion: We successfully verified the capability of the SBRT VeroTM linac to perform real-time tumor tracking and accurate dose delivery to the target, based on predictive modeling of the correlation between implanted marker motion and

  14. Retrospective study of renal images on whole bone scanning

    International Nuclear Information System (INIS)

    One hundred and twenty-seven cases were surveyed by sup(99m)Tc-pyrophosphate at Jikei hospital. Renal images on whole-bone scanning were observed in all cases; 75% of all renal images were normal and 25% were abnormal. Thirteen percent of these abnormal images were symmetric and 87% were asymmetric. Four of the symmetric renal images were bilaterally bad. Three of the four bilaterally bad renal images involved prostate carcinomas with general metastases and the last involved serious bilateral hydronephrosis. The reason for the high percentage of asymmetric renal images was that the materials involved many urogenital cases. Asymmetric renal images other than the urogenital cases, were recognised in 8% of all cases. This percentage is consistent with Hattner's report. Unilateral abnormal renal images involved 8 hydronephrosis cases, 2 unilateral nonfunctioning kidneys and one malrotation kidney. Among the hydronephrosis cases, serious cases gave low uptake and mild cases gave high uptake. The reason for this phenomenon was, presumably, that there were differences in renal uptake, renal excretion and renal pelvic accumulation. In nine cases, one kidney was not visualized on whole-bone scanning, 8 of them involved nephrectomy and the remainining one unilateral nonfunctioning kidney. Six cases presented locally abnormal renal images on whole-bone scanning, three of them suffered renal cell carcinomas and the rest renal solitary cyst. Eighty-eight percent of the abnormal renal images agreed with IVP findings. The renal images of whole-bone scanning faithfully reflected the original renal lesion. Two cases of renal carcinoma and renal solitary cyst recognized on whole-bone scanning are presented, to indicate the usefulness of renal images on whole-bone scanning. (auth.)

  15. SU-D-304-04: Pre-Clinical Feasibility Study for Intensity Modulated Grid Proton Therapy (IMgPT) Using a Newly Developed Delivery System

    Energy Technology Data Exchange (ETDEWEB)

    Tsiamas, P; Moskvin, V; Shin, J; Axente, M; Pirlepesov, F; Krasin, M; Merchant, T; Farr, J [St. Jude Children’s Research Hospital, Memphis, TN (United States)

    2015-06-15

    Purpose: The purpose of the current study was to characterize and evaluate intensity-modulated proton grid therapy (IMgPT) using a clinical proton beam. Methods: A TOPAS MC model of a new developmental mode (pre-clinical) of the Hitachi proton therapy system (PROBEAT) was used for simulation and characterization of proton grid therapy. TOPAS simulations of different energy ranges, depths and spot separation distances were performed. LET spectra for various energies and depths were produced with FLUKA MC code for evaluation potential interplay between planning parameters and their effect on the characterization of areas (valley) between spots. IMgPT planning aspects (spot spacing, skin dose, peak-to-valley ratios, beam selection, etc.) were evaluated for different phantom and patient cases. Raysearch software (v4.51) was used to perform the evaluation. Results: Calculated beam peak-to-valley ratios scenarios showed strong energy and depth dependence with ratios to be larger for higher energies and shallower depths. Peak-to-valley ratios for R90 range and for spot spacing of 1cm varied from 30% (E = 221.3 MeV, depth 30.6 cm) to 80% (E = 70.3 MeV, depth 4 cm). LET spectra calculations showed spectral hardening with depth, which might potential increase, spot separation distance and improve peak-to-valley ratios. IMgPT optimization, using constant spot spacing, showed skin dose reduction between peak regions of dose due to the irradiation of less skin. Single beam for bulky shallower tumors might be a potential candidate for proton grid therapy. Conclusions: Proton grid therapy using a clinical beam is a promising technique that reduces skin dose between peak regions of dose and may be suitable for the treatment of shallow tumors. IMgPT may be considered for use when bystander effects in off peak regions would be appropriate.

  16. SU-D-304-04: Pre-Clinical Feasibility Study for Intensity Modulated Grid Proton Therapy (IMgPT) Using a Newly Developed Delivery System

    International Nuclear Information System (INIS)

    Purpose: The purpose of the current study was to characterize and evaluate intensity-modulated proton grid therapy (IMgPT) using a clinical proton beam. Methods: A TOPAS MC model of a new developmental mode (pre-clinical) of the Hitachi proton therapy system (PROBEAT) was used for simulation and characterization of proton grid therapy. TOPAS simulations of different energy ranges, depths and spot separation distances were performed. LET spectra for various energies and depths were produced with FLUKA MC code for evaluation potential interplay between planning parameters and their effect on the characterization of areas (valley) between spots. IMgPT planning aspects (spot spacing, skin dose, peak-to-valley ratios, beam selection, etc.) were evaluated for different phantom and patient cases. Raysearch software (v4.51) was used to perform the evaluation. Results: Calculated beam peak-to-valley ratios scenarios showed strong energy and depth dependence with ratios to be larger for higher energies and shallower depths. Peak-to-valley ratios for R90 range and for spot spacing of 1cm varied from 30% (E = 221.3 MeV, depth 30.6 cm) to 80% (E = 70.3 MeV, depth 4 cm). LET spectra calculations showed spectral hardening with depth, which might potential increase, spot separation distance and improve peak-to-valley ratios. IMgPT optimization, using constant spot spacing, showed skin dose reduction between peak regions of dose due to the irradiation of less skin. Single beam for bulky shallower tumors might be a potential candidate for proton grid therapy. Conclusions: Proton grid therapy using a clinical beam is a promising technique that reduces skin dose between peak regions of dose and may be suitable for the treatment of shallow tumors. IMgPT may be considered for use when bystander effects in off peak regions would be appropriate

  17. Effect of nicotine on bone healing in rats - A histological study

    Directory of Open Access Journals (Sweden)

    Dilip Kumar Rayapati

    2014-04-01

    Full Text Available Background & Objectives: Nicotine is the major alkaloid in tobacco products (Nicotiona tabacum and a psychoactive ingredient responsible for the Central Nervous System (CNS effects and tobacco addiction. It’s been reported to have effects directly on the small blood vessels in producing vasoconstriction and increased vascular resistance that exerts on the microvasculature inhibiting the angioblastic response during re-vascularization and limits the recruitment of cytokines, Bone Morphogenic Proteins (BMPs, Transforming Growth Factor – β (TGF – β, Platelet Derived Growth Factor (PDGF and the basic Fibroblast Growth Factor (FGF. This leads to inhibition of re-epithelialization, osteogenesis and cellular healing. This study intends to demonstrate histologically the effect of nicotine on bone healing and the healing of bone defects incorporated with autogenous bone graft in an animal model. Methods: 60 female Wistar rats were used in the study. Nicotine hemisulfate at a dose of 3mg/kg body weight of the animal given twice daily for 4 weeks prior to creation of a bone defect. The defect on the ramus of the mandible and the healing in the defect was evaluated at weekly intervals for four weeks for both the quality and quantity of new bone formation by histological and histomorphometric analysis. Results: Significant impairment of healing of bone both in the early and late stages due to the influence of Nicotine was seen. Conclusion: In our study, incorporation of autogenous bone did significantly improve the bone healing process in the end stages of healing while nicotine significantly impaired the healing of bone in early stages.

  18. Bone reactions adjacent to titanium implants subjected to static load. A study in the dog (I)

    DEFF Research Database (Denmark)

    Gotfredsen, K; Berglundh, T; Lindhe, J

    2001-01-01

    The aim of the study was to evaluate the effect of lateral static load induced by an expansion force on the bone/implant interface and adjacent peri-implant bone. In 3 beagle dogs, the 2nd, 3rd and 4th mandibular premolars were extracted bilaterally. Twelve weeks later 8 implants of the ITI Dental...... Implant System were placed in each dog. Crowns connected in pairs were screwed on the implants 12 weeks after implant installation. The connected crowns contained an orthodontic expansion screw yielding 4 loading units in each dog. Clinical registrations, standardized radiographs and fluorochrome labeling...... were carried out during the 24-week loading period. Biopsies were harvested and processed for ground sectioning. The sections were subjected to histological examination. No evident marginal bone loss was observed at either test or control sites. The bone density and the mineralized bone-to-implant...

  19. Study of paleodiet by means of the PIXE analysis of ancient human bones from Teotihuacan

    International Nuclear Information System (INIS)

    This work focuses on the study of the paleodiet of individuals from Teotihuacan corresponding to the end of the Classic period and Mazapa phase. The analysis lies on the chemical composition variability of major and trace elements, such as Ca, Fe, Zn, Sr, and Ba among others, of bone remains. Particle Induced X-ray Emission Spectrometry (PIXE) was used to analyze the individual bone remains and sediments associated to the burial context. The bone remains were stripped of their external layer by mechanical cleaning, then powdered to prepare pellets. The bone and sediment pellets were irradiated using a 3 MeV proton beam and an external beam setup. Elemental concentrations of Ca, Fe, Zn, Sr and Ba, among other elements, were measured in bones and sediments from the archaeological excavations. An evaluation of the sample preparation, the effects of the archaeological context, as well as the paleodiet results are presented. (Author) 20 refs., 10 figs

  20. Preliminary study on the basic pattern of bone marrow scintigraphy in acute leukemia

    International Nuclear Information System (INIS)

    98 cases of acute leukemia had been studied with technetium-99m sulfur colloid bone marrow scintigraphy. The basic pattern was: (1) The generalized depression of central bone marrow (CBM) is most striking and its extent and degree of the depression is closely related with clinical staging of the disease. It was also found that the activity of CBM gradually increased with prolongation of complete remission course. (2) 72.4% cases showed variable degrees of peripheral bone marrow cavity expansion. Most of the peripheral expansion foci are localized in epiphyses of the knee joint, or further extended to cavity of long bone in extremities. In conclusion, bone marrow imaging is helpful to: (1) the diagnosis and evaluation of the distribution of hemapoietic activity in acate leukemia; (2) evaluation of the effect of chemotherapy and judgement of the prognosis; (3) the activity of CBM can probably be also used as an index to judge the clinical situation of the patient

  1. Preclinical assessment of infant formula.

    Science.gov (United States)

    Lönnerdal, Bo

    2012-01-01

    Infant formulas are the sole or predominant source of nutrition for many infants and are fed during a sensitive period of development and may therefore have short- and long-term consequences for infant health. Preclinical safety assessment therefore needs to include both short-term and long-term studies in animals. It is recommended that procedures are instituted by which experts may serve as independent scientists for companies developing novel products, without having their integrity compromised, and later serve the legislative institutions. A two-level assessment approach to determine the potential toxicity of a novel ingredient, its metabolites, and their effects in the matrix on developing organ systems has been suggested by IOM. This appears reasonable, as novel ingredients can be of different levels of concern. The use of modern methods in genomics and proteomics should be considered in these evaluation processes as well as novel methods to evaluate outcomes, including metabolomics and molecular techniques to assess the microbiome. PMID:22699767

  2. Preclinical Studies for Cartilage Repair

    OpenAIRE

    Hurtig, Mark B.; Buschmann, Michael D; Fortier, Lisa A; Hoemann, Caroline D; Hunziker, Ernst B.; Jurvelin, Jukka S.; Mainil-Varlet, Pierre; McIlwraith, C. Wayne; Sah, Robert L.; Whiteside, Robert A.

    2011-01-01

    Investigational devices for articular cartilage repair or replacement are considered to be significant risk devices by regulatory bodies. Therefore animal models are needed to provide proof of efficacy and safety prior to clinical testing. The financial commitment and regulatory steps needed to bring a new technology to clinical use can be major obstacles, so the implementation of highly predictive animal models is a pressing issue. Until recently, a reductionist approach using acute chondral...

  3. Treatment delay of bone tumours, compilation of a sociodemographic risk profile: A retrospective study

    International Nuclear Information System (INIS)

    Bone tumours are comparatively rare tumours and delays in diagnosis and treatment are common. The purpose of this study was to analyse sociodemographic risk factors for bone tumour patients in order to identify those at risk of prolonged patients delay (time span from first symptoms to consultation), professional delay (from consultation to treatment) or symptom interval (from first symptoms to treatment). Understanding these relationships might enable us to shorten time to diagnosis and therapy. We carried out a retrospective analysis of 265 patients with bone tumours documenting sociodemographic factors, patient delay, professional delay and symptom interval. A multivariate explorative Cox model was performed for each delay. Female gender was associated with a prolonged patient delay. Age under 30 years and rural living predisposes to a prolonged professional delay and symptom interval. Early diagnosis and prompt treatment are required for successful management of most bone tumour patients. We succeeded in identifying the histology independent risk factors of age under 30 years and rural habitation for treatment delay in bone tumour patients. Knowing about the existence of these risk groups age under 30 years and female gender could help the physician to diagnose bone tumours earlier. The causes for the treatment delays of patients living in a rural area have to be investigated further. If the delay initiates in the lower education of rural general physicians, further training about bone tumours might advance early detection. Hence the outcome of patients with bone tumours could be improved

  4. Use of carboxymethyl cellulose and collagen carrier with equine bone lyophilisate suggests late onset bone regenerative effect in a humerus drill defect - a pilot study in six sheep

    DEFF Research Database (Denmark)

    Jensen, Jonas; Foldager, Casper Bindzus; Jakobsen, Thomas Vestergaard;

    2010-01-01

    We assessed the use of a filler compound together with the osteoinductive demineralized bone matrix (DBM), Colloss E. The filler was comprised of carboxymethyl-cellulose and collagen type 1. The purpose of the study was to see if the filler compound would enhance the bone formation and distribute...

  5. Uremic bone diseases - Clinical laboratorial, scintigraphic and radiological study

    International Nuclear Information System (INIS)

    This paper evaluated the uremic bone disease in 10 patients on peritoneal dialysis, 10 on hemodialysis and 10 submited to renal transplantation. According to biochemical evaluation we observed hypocalcemia in some patients on dialysis and hipercalcemia in a renal transplanted and in another on peritoneal dialysis. However, there was no significative difference in the serum calcium concentration between the groups and the control group. Hiperphosphatemia occured in 8 patients on peritoneal dialysis and in 9 on hemodialysis and slight hiperphosphatemia occured in 2 renal transplanted patient. The product calcium X phosphorus was elevated in 2 patients on peritoneal dialysis and in 2 on hemodialysis. The magnesium serum concentration were hight in all patients on dialysis and the alkaline phosphatase serum levels were hight in 3 patients dialysis peritoneal and 4 on hemodialysis. A skeleton curvey showed abnormalities in 3 patients on peritoneal dialysis, 5 on hemodialysis and of 5 renal transplanted patients. However there was no significant difference between these results. The bone scanning was abnormal in 6 patients on peritoneal dialysis, 9 patients on hemodialysis and in 8 renal transplanted. The positive results of bone scanning compared with X ray were statistically significative. Bone scanning was the most sensitive method used to detect early abnormalities. (author)

  6. Preclinical models in radiation oncology

    International Nuclear Information System (INIS)

    As the incidence of cancer continues to rise, the use of radiotherapy has emerged as a leading treatment modality. Preclinical models in radiation oncology are essential tools for cancer research and therapeutics. Various model systems have been used to test radiation therapy, including in vitro cell culture assays as well as in vivo ectopic and orthotopic xenograft models. This review aims to describe such models, their advantages and disadvantages, particularly as they have been employed in the discovery of molecular targets for tumor radiosensitization. Ultimately, any model system must be judged by its utility in developing more effective cancer therapies, which is in turn dependent on its ability to simulate the biology of tumors as they exist in situ. Although every model has its limitations, each has played a significant role in preclinical testing. Continued advances in preclinical models will allow for the identification and application of targets for radiation in the clinic

  7. A Dosimetric Study of Radionuclide Therapy for Bone Marrow Ablation.

    Science.gov (United States)

    Bayouth, John Ellis

    In a phase I clinical trial, six multiple myeloma patients, who were non-responsive to conventional therapy and were scheduled for bone marrow transplantation, received Holmium-166 (166Ho) labeled to a bone seeking agent, DOTMP (1,4,7,10-tetraazacyclododecane -1,4,7,10-tetramethylene-phosphonic acid), for the purpose of bone marrow ablation. The specific aims of my research within this protocol were to evaluate the toxicity and efficacy of 166Ho DOTMP by quantifying the in vivo pharmacokinetics and radiation dosimetry, and by correlating these results to the biologic response observed. The reproducibility of pharmacokinetics from multiple injections of 166 Ho DOTMP administered to these myeloma patients was demonstrated from both blood and whole body retention. The skeletal concentration of 166 Ho DOTMP was heterogenous in all six patients: high in the ribs, pelvis, and lumbar vertebrae regions, and relatively low in the femurs, arms, and head. A novel technique was developed to calculate the radiation dose to the bone marrow in each skeletal ROI, and was applied to all six 166 Ho DOTMP patients. Radiation dose estimates for the bone marrow calculated using the standard MIRD "S" factors were compared with the average values derived from the heterogenous distribution of activity in the skeleton (i.e., the regional technique). The results from the two techniques were significantly different; the average of the dose estimates from the regional technique were typically 30% greater. Furthermore, the regional technique provided a range of radiation doses for the entire marrow volume, while the MIRD "S" factors only provided a single value. Dose volume histogram analysis of data from the regional technique indicated a range of dose estimates that varied by a factor of 10 between the high dose and low dose regions. Finally, the observed clinical response of cells and abnormal proteins measured in bone marrow aspirates and peripheral blood samples were compared with

  8. Laser Microablative Tunnel Formation to Initiate Alveolar Bone Regeneration. Pilot ex vivo Study

    Directory of Open Access Journals (Sweden)

    Karabut М.М.

    2013-12-01

    Full Text Available In recent years there has been demonstrated the ability of Erbium (Er laser to cause effective ablation of bone tissue with minimum collateral damage. Non-surgical treatment of periodontitis using Er laser improves probing depth and clinical attachment level. However, periodontal anti-inflammatory therapy should not be limited to these parameters, but also should initiate tissue regeneration including bone tissue damaged by the disease. The aim of the investigation was to evaluate feasibility and characterize the process of laser microablative tunnel formation in gingiva and alveolar bone using a pulse-periodic, single mode Er laser, and determine laser parameters providing appropriate size of the tunnel and coagulation zone needed to initiate healing and regeneration of the alveolar bone. Materials and Methods. Ex vivo pig jaw was used as a model for the study. To create a through-gingiva microperformation of the alveolar bone, we used a laboratory prototype of Er laser and delivery system Alta PE-AT (Dental Photonics, Inc.. Results. We performed a microperforation of a 1 mm thick gingiva and created a microcrater (tunnel in the underlying bone using a single pulse with energy 5, 10 and 30 mJ. The laser tunnel characteristics in the gingiva, bone and dentine were characterized as a function of laser irradiation parameters. Optical microscopy and histology examination did not reveal carbonization or significant collateral damage of the bone tissue. Conclusion. Using a laboratory prototype of Alta PE-AT Er laser we demonstrated feasibility of through gingiva laser microperforation of alveolar bone that can serve as the first step towards further study of healing and initiation of the alveolar bone regeneration.

  9. The generalized bone phenotype in children with neurofibromatosis 1: a sibling matched case-control study.

    Science.gov (United States)

    Armstrong, Linlea; Jett, Kimberly; Birch, Patricia; Kendler, David L; McKay, Heather; Tsang, Erica; Stevenson, David A; Hanley, David A; Egeli, Deetria; Burrows, Melonie; Friedman, J M

    2013-07-01

    People with neurofibromatosis 1 (NF1) have low bone mineralization, but the natural history and pathogenesis are poorly understood. We performed a sibling-matched case-control study of bone mineral status, morphology, and metabolism. Eighteen children with NF1 without focal bony lesions were compared to unaffected siblings and local population controls. Bone mineral content at the lumbar spine and proximal femur (dual energy X-ray absorptiometry (DXA)) was lower in children with NF1; this difference persisted after adjusting for height and weight. Peripheral quantitative computed tomography (pQCT) of the distal tibia showed that trabecular density was more severely compromised than cortical. Peripheral QCT-derived estimates of bone strength and resistance to bending and stress were poorer among children with NF1 although there was no difference in fracture frequencies. There were no differences in the size or shape of bones after adjusting for height. Differences in markers of bone turnover between cases and controls were in the directions predicted by animal studies, but did not reach statistical significance. Average serum calcium concentration was higher (although within the normal range) in children with NF1; serum 25-OH vitamin D, and PTH levels did not differ significantly between cases and controls. Children with NF1 were less mature (assessed by pubertal stage) than unaffected siblings or population controls. Children with NF1 have a generalized difference of bone metabolism that predominantly affects trabecular bone. Effects of decreased neurofibromin on bone turnover, calcium homeostasis, and pubertal development may contribute to the differences in bone mineral content observed among people with NF1. PMID:23713011

  10. A vascular access system (VAS) for preclinical models

    OpenAIRE

    Berry-Pusey, Brittany Nan

    2012-01-01

    Preclinical Molecular Imaging technologies have an increasingly broader application base while they at the same time are becoming more user-friendly. Tail vein injections are a routine but critical step in most imaging applications, with poor injections greatly affectingthe experimental results. The high skills and experience required to perform successful tail vein injections leave many preclinical imaging scientists ill-suited to perform this task. In a recent study, we found that trained r...

  11. Complications related to bone augmentation procedures of localized defects in the alveolar ridge. A retrospective clinical study

    DEFF Research Database (Denmark)

    Jensen, Anders Torp; Jensen, Simon Storgård; Worsaae, Nils

    2016-01-01

    PURPOSE: This retrospective clinical study aims to evaluate complications after augmentation of localized bone defects of the alveolar ridge. METHODS: From standardized registrations, the following complications related to bone augmentation procedures were recorded: soft tissue dehiscence, infect...

  12. Experimental studies of bone mechanoadaptation: bridging in vitro and in vivo studies with multiscale systems.

    Science.gov (United States)

    Brown, Genevieve N; Sattler, Rachel L; Guo, X Edward

    2016-02-01

    Despite advancements in technology and science over the last century, the mechanisms underlying Wolff's law-bone structure adaptation in response to physical stimuli-remain poorly understood, limiting the ability to effectively treat and prevent skeletal diseases. A challenge to overcome in the study of the underlying mechanisms of this principle is the multiscale nature of mechanoadaptation. While there exist in silico systems that are capable of studying across these scales, experimental studies are typically limited to interpretation at a single dimension or time point. For instance, studies of single-cell responses to defined physical stimuli offer only a limited prediction of the whole bone response, while overlapping pathways or compensatory mechanisms complicate the ability to isolate critical targets in a whole animal model. Thus, there exists a need to develop experimental systems capable of bridging traditional experimental approaches and informing existing multiscale theoretical models. The purpose of this article is to review the process of mechanoadaptation and inherent challenges in studying its underlying mechanisms, discuss the limitations of traditional experimental systems in capturing the many facets of this process and highlight three multiscale experimental systems which bridge traditional approaches and cover relatively understudied time and length scales in bone adaptation. PMID:26855756

  13. A comparative study of whole body DWIBS MRI versus bone scan for evaluating skeletal metastases

    Directory of Open Access Journals (Sweden)

    SG Gandage

    2012-12-01

    Full Text Available BackgroundSkeletal metastases in oncology patients are identified by Bone scan and/Positron Emission Tomography (PET scan. But developing countries in the world still lack adequate numbers of these imaging facilities.AimsSince Magnetic Resonance Imaging (MRI is widely available as compared to bone scan or PET scan; a double blind study was undertaken to see if whole body imaging with MRI can give an idea of skeletal metastases.MethodDiffusion weighted whole body Magnetic Resonance Imaging with background body signal suppression (DWIBS was performed using 1.5 Tesla (T MRI on histopathologically proven cases of carcinoma of breast within two months of mastectomy and followed up after a year of surgery. Similarly bone scan was also performed in these patients.ResultsDWIBS MRI demonstrated the presence and extent of bone metastases in 10 out of a total 18 patients included in study while bone scan could demonstrate them in only three cases. A highly significant difference between proportions of the skeletal metastases detected by whole body DWIBS-MRI than that by bone scan at one year follow-up. (i.e. p<0.01, z=2.66 was seen.ConclusionDWIBS MRI scores high in demonstrating skeletal metastases. Further comparative studies are necessary to evaluate if DWIBS can replace bone scan or PET scan.

  14. Studying on process for labeling of EDTMP with 90Y using for bone pain palliation

    International Nuclear Information System (INIS)

    This Study describes the method for preparation of labelling compound Ethylene diamine tetramethylene phosphonic acid (EDTMP) with 90Y. Malignant cancer is one of the most important resulting in human death. Bone metastases in nearly 25% of all cancer patients; so it is useful to develop radiopharmaceuticals for the treatment of bone cancer. Yttrium-90 is high energy (2.3 MeV) beta emitter required with a physical haft life of 2.7 days which has limited bone-seeking properties. Its physical properties make it ideal for therapeutic application, the most energetic beta emission being able to penetrate to 1 cm from the site of deposition in soft tissue with an average range of approximately 4 mm. Theoretically, therefore, it can penetrate all marrow spaces in normal trabecular bone and conceivably even to the centre of large tumours where bone destruction may be extensive. Specific deposition of 90Y into the skeleton demands its delivery in a chemical form with affinity for bone mineral alone. Compounds with these properties are the phosphonate analogues of polyaminocarboxylic acids, and one in particular EDTMP (ethylen diamine tetra methylene phosphonate) has already been used to target 153Sm to bone mineral with success. Because of chemical similarities between 90Y and the rare earths, EDTMP should form stable complexes with 90Y and carry it specifically to the bone with comparable efficiency. Skeletal uptake of -emitting radionuclides may be used for bone pain palliation or myeloablation. The physical characteristics of the β- particles required for the two conditions are, however, different, that is, higher energies are favorable for destruction of bone marrow. (author)

  15. A study of the bone healing kinetics of plateau versus screw root design titanium dental implants.

    LENUS (Irish Health Repository)

    Leonard, Gary

    2009-03-01

    This study was designed to compare the bone healing process around plateau root from (PRF) and screw root from (SRF) titanium dental implants over the immediate 12 week healing period post implant placement.

  16. A study of the association between urinary aluminum concentration and pre-clinical findings among aluminum-handling and non-handling workers

    OpenAIRE

    OGAWA,Masanori; Kayama, Fujio

    2015-01-01

    Background Aluminum is considered to be a relatively safe metal for humans. However, there are some reports that aluminum can be toxic to humans and animals. In order to estimate the toxicity of aluminum with respect to humans, we measured the aluminum concentration in urine of aluminum-handling and non-handling workers and investigated the relationships between their urinary aluminum concentrations and pre-clinical findings. Methods Twenty-three healthy aluminum-handling workers and 10 healt...

  17. Threats to Validity in the Design and Conduct of Preclinical Efficacy Studies: A Systematic Review of Guidelines for In Vivo Animal Experiments

    OpenAIRE

    Henderson, Valerie C.; Jonathan Kimmelman; Dean Fergusson; Grimshaw, Jeremy M; Dan G Hackam

    2013-01-01

    Editors' Summary Background The development process for new drugs is lengthy and complex. It begins in the laboratory, where scientists investigate the causes of diseases and identify potential new treatments. Next, promising interventions undergo preclinical research in cells and in animals (in vivo animal experiments) to test whether the intervention has the expected effect and to support the generalization (extension) of this treatment–effect relationship to patients. Drugs that pass these...

  18. [GOOD PLANNING PRACTICE IN PRECLINICAL AND CLINICAL STUDIES OF UNFRACTIONATED AND FRACTIONATED HEPARINS IN RUSSIA AS THE BASIS OF SAFE AND EFFECTIVE ANTICOAGULATION THERAPY].

    Science.gov (United States)

    Gavrishina, E V; Dobrovolskii, A V; Niyazov, R R; Romodanovskii, D P; Vasil'ev, A N

    2015-01-01

    General principles of appropriate strategies for preclinical and clinical development of unfractionated and low-molecular-weight heparins and demonstration of their biosimilarity to corresponding reference medicinal products are provided. Demonstration of the biosimilarity of heparin-containing medicinal products constitutes the basis for their efficacy and safety during anticoagulation therapy. The main quality, safety, and efficacy characteristics of heparin products are described and the extent of non-clinical and clinical investigations necessary prior to drug marketing authorization are considered. PMID:27017700

  19. Timing of Decompressive Surgery of Spinal Cord after Traumatic Spinal Cord Injury: An Evidence-Based Examination of Pre-Clinical and Clinical Studies

    OpenAIRE

    Furlan, Julio C.; Noonan, Vanessa; Cadotte, David W.; Fehlings, Michael G.

    2011-01-01

    While the recommendations for spine surgery in specific cases of acute traumatic spinal cord injury (SCI) are well recognized, there is considerable uncertainty regarding the role of the timing of surgical decompression of the spinal cord in the management of patients with SCI. Given this, we sought to critically review the literature regarding the pre-clinical and clinical evidence on the potential impact of timing of surgical decompression of the spinal cord on outcomes after traumatic SCI....

  20. Preclinical and the first clinical studies on [11C]ITMM for mapping metabotropic glutamate receptor subtype 1 by positron emission tomography

    International Nuclear Information System (INIS)

    Introduction: Preclinical studies and first positron emission tomography (PET) imaging studies were performed using N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-[11C] methoxy-N-methylbenzamide ([11C]ITMM) to map metabotropic glutamate receptor type 1 (mGluR1) in the human brain. Methods: [11C]ITMM was synthesized by O-methylation of the desmethyl precursor with [11C]methyl triflate in the presence of NaOH at room temperature. In vitro selectivity and brain distributions of [11C]ITMM in mice were characterized. Radiation absorbed-dose by [11C]ITMM in humans was calculated from mouse distribution data. Acute toxicity of ITMM at 4.72 mg/kg body weight (> 74,000-fold clinical equivalent dose of [11C]ITMM) was evaluated. Mutagenicity of ITMM was studied by the Ames test. Clinical PET imaging of mGluR1 with [11C] ITMM was performed in a healthy volunteer. Results: ITMM had low activity for a 28-standard receptor binding profile. Regional brain uptake of [11C]ITMM in mice was heterogeneous and consistent with known mGluR1 distributions. The radiation absorbed-dose by [11C]ITMM in humans was sufficiently low for clinical use, and no acute toxicity or mutagenicity of ITMM occurred. A 90-min dynamic PET scan with [11C]ITMM in a healthy volunteer showed a gradual increase of radioactivity in the cerebellum. Total distribution volume of [11C]ITMM was highest in the cerebellum, followed by thalamus, cerebral cortex, and striatum; regional differences in brain radioactivity corresponded to the mGluR1 distribution in the brain. Peripherally, [11C]ITMM was stable in humans: 60% of the plasma radioactivity remained in the unchanged form for 60 min. Conclusions: [11C] ITMM is a suitable radioligand for imaging mGluR1 in the human brain providing acceptable dosimetry and pharmacological safety at the dose required for PET

  1. Bone tissue regeneration indento-alveolar surgery : clinical and experimental studies on biomaterials and bone graft substitutes

    OpenAIRE

    Sahlin-Platt, Annika

    2011-01-01

    Pathological processes in the alveolar and facial bones can lead to bone loss that may not heal with complete regeneration. Biomaterials can be used to facilitate the healing process and/or as a bone substitute, but the mechanisms are not fully understood. Persistent leakage of bacteria/bacterial toxins, after root canal treatment, may lead to a residual bone defect. The healing is dependent on a placed dental biomaterial providing a tight seal. The composition of the filling material may als...

  2. Autologous cell therapy as a new approach to treatment of radiation-induced bone marrow aplasia: preliminary study in a baboon model

    Energy Technology Data Exchange (ETDEWEB)

    Herodin, F.; Drouet, M. [Radiohematology Unit, Centre de Recherches du Service de Sante des Armees, La Tronche CEDEX (France)

    2002-07-01

    The sparing of viable hematopoietic stem and progenitor cells located in underexposed bone marrow territories associated with the relative radioresistance of certain stem cell populations is the rationale for autologous cell therapy consisting of ex vivo expansion of residual cells after collection postirradiation. The feasibility of this treatment mainly depends on time constraints and hematopoietic cell threshold. We showed in this study that in the absence of early-acting mobilizing agent administration, subliminar amounts of CD34{sup +} cells can be collected (1 x 10{sup 6} CD34{sup +} cells/100 mL bone marrow or for 1 L apheresis) from 6-Gy {gamma} globally irradiated baboons. Residual CD34{sup +} cells were successfully expanded in serum-free medium in the presence of antiapoptotic cytokine combination (stem cell factor + FLT-3 ligand + thrombopoietin + interleukin 3, 50 ng/mL each, i.e., 4F): K{sub CD34{sup +}} = x2.8 and x13.7 (n=2). Moreover, we demonstrated the short-term neutrophil engraftment potential of a low-size mixed expanded graft (1.5 x 10{sup 6} final CD34{sup +}cells/kg) issued from the coculture of unirradiated (20%) and 2.5-Gy in vitro irradiated (80%) CD34{sup +} cells on an allogeneic stromal cell layer in the presence of 4F. Further preclinical research needs to be performed to clearly establish this therapeutic approach that could be optimized by the early administration of antiapoptotic cytokines. (author)

  3. When is a bone scan study appropriate in asymptomatic men diagnosed with prostate cancer?

    Institute of Scientific and Technical Information of China (English)

    Raj P.Pal; Thivyaan Thiruudaian; Masood A.Khan

    2008-01-01

    Aims: To determine when a bone scan investigation is appropriate in asymptomatic men diagnosed with prostate cancer. Methods: Between November 2005 and July 2006, 317 men with prostate cancer underwent a bone scan study; 176 men fulfilled the inclusion criteria. Prostate-specific antigen (PSA) cut-offs as well as univariate and multivariate logistic regression analyses using digital rectal examination finding, biopsy Gleason scores and age were performed to determine when a bone scan study is likely to be of value. Results: Only 1/61 men (1.6%) with a serum PSA ≤ 20 ng/mL had a positive bone scan. However, 2/38 men (4.7%) with a serum PSA 20.1-40.0 ng/mL, 3/20 men (15%) with a serum PSA 40.1-60.0 ng/mL, 7/19 men (36.8%) with a serum PSA 60.1-100.0 ng/mL and 19/38 men (50%) with a serum PSA > 100.0 ng/mL had positive bone scans. Univariate and multivariate logistic regression analyses were uninformative in these groups. Conclusion: Based on our findings, a bone scan is of limited value in asymptomatic prostate cancer patients presenting PSA ≤ 20 ng/mL. Therefore, this investigation can be eliminated unless a curative treatment is contemplated. Furthermore, digital rectal examination finding, biopsy Gleason score and age are unhelpful in predicting those who might harbor bone metastasis.

  4. FUSION BETWEEN BODY AND GREATER CORNU: A RADIOLOGICAL STUDY OF DRY HYOID BONES

    OpenAIRE

    Bhavna; Rajan Kumar Singla; Ravi Kant Sharma

    2015-01-01

    Introduction: The study of fusion of body and greater cornua of hyoid bone is of tremendous clinical and forensic significance as it can be used to estimate the age of living or dead or skeletonized remains. It becomes all the more important as this fusion is relatively immune to some individual factors like life style, health and nutrition etc. Material method: The study comprised of 15 male and 15 female bones all collected from human cadavers with age >60 years. Digitalized radiogr...

  5. Current Studies of Acupuncture in Cancer-Induced Bone Pain Animal Models

    OpenAIRE

    Hee Kyoung Ryu; Yong-Hyeon Baek; Yeon-Cheol Park; Byung-Kwan Seo

    2014-01-01

    Acupuncture is generally accepted as a safe and harmless treatment option for alleviating pain. To explore the pain mechanism, numerous animal models have been developed to simulate specific human pain conditions, including cancer-induced bone pain (CIBP). In this study, we analyzed the current research methodology of acupuncture for the treatment of CIBP. We electronically searched the PubMed database for animal studies published from 2000 onward using these search terms: (bone cancer OR can...

  6. Bone Density in Chronic Schizophrenia with Long-Term Antipsychotic Treatment: Preliminary Study

    OpenAIRE

    Lee, Tae-Young; Chung, Moon-Yong; Chung, Hae-Kyung; Choi, Jin-Hee; Kim, Tae-Yong; So, Hyung-Seok

    2010-01-01

    Objective Decreased bone mineral density has been found in the chronic schizophrenic patients who have been given a long-term administration of antipsychotics. Hyperprolactinemia from the antipsychotics and the negative symptom of schizophrenia were considered as the causes for this finding. In this study, the effect of hyperprolactinemia and the negative symptom of schizophrenia on bone mineral density was investigated on male schizophrenic patients. Methods The cross-sectional study was car...

  7. Probabilistic Study of Bone Remodeling Using Finite Element Analysis

    Science.gov (United States)

    Werner, C.; Gorla, R. S. R.

    2013-08-01

    The dynamic bone remodeling process is a computationally challenging research area that struggles to understand the actual mechanisms. It has been observed that a mechanical stimulus in the bone greatly affects the remodeling process. A 3D finite element model of a femur is created and a probabilistic analysis is performed on the model. The probabilistic analysis measures the sensitivities of various parameters related to the material properties, geometric properties, and the three load cases defined as Single Leg Stance, Abduction, and Adduction. The sensitivity of each parameter is based on the calculated maximum mechanical stimulus and analyzed at various values of probabilities ranging from 0.001 to 0.999. The analysis showed that the parameters associated with the Single Leg Stance load case had the highest sensitivity with a probability of 0.99 and the angle of the force applied to the joint of the proximal femur had the overall highest sensitivity

  8. Study on the Algorithm of Multifunctional Bone External Fixator

    OpenAIRE

    Chen Jianwen; Shi Xuewei; Wei Mengting; Sun Hao

    2015-01-01

    This paper discussed the problem that parameters of bone external fixator are difficult to calculate in the practical application. Positive solution is described in detail. We used MATLAB software to make simulation experiment. The innovation lies the development idea of using inverse position to verify the accuracy of positive solution. Forward displacement analysis was mainly developed using analytical method, which has many advantages, such as small dependence to the inverse solution and t...

  9. Studies on three matrix molecules in bone and dentin

    OpenAIRE

    Petersson, Ulrika

    2003-01-01

    The biomineralization of bone and dentin is a complex and dynamic process, involving the formation of an organic framework in which mineral crystals are deposited. The noncollagenous proteins (NCPs) of the organic phase play a central role in the extracellular matrix (ECM) organization and mineralization regulation. To facilitate the understanding of the mechanisms of biomineralization, it is crucial to expand our knowledge regarding the functions of the NCPs in this process...

  10. Assessment of [18F]-fluoroacetate PET/CT as a tumor-imaging modality. Preclinical study in healthy volunteers and clinical evaluation in patients with liver tumor

    International Nuclear Information System (INIS)

    Although [18F]-FDG is a useful oncologic PET tracer, FDG uptake is known to be low in a certain type of hepatocellular carcinoma (HCC). [18F]-fluoroacetate (18F-FACE) is an [18F] fluorinated acetate, which is known to be converted into fatty acids, incorporated in membrane and is expected to be a promising oncologic PET tracer. The aim of this study was to evaluate the usefulness of 18F-FACE as an oncologic PET tracer in preclinical study in healthy volunteers and in patients with liver tumors. Twenty-four healthy volunteers (age 48.2 ± 12.9 years old; 15 male and 9 female) and ten patients with liver tumor (age 72.1 ± 7.0 years old; 6 male and 4 female) were included. We performed whole-body static PET/CT scan using 18F-FACE (n=34) and 18F-FDG (n=5 for volunteers, n=8 for patients) on each day, respectively. Qualitative analysis and quantitative analysis of tumors (5 HCCs, 1 cholangiocellular carcinoma, 4 metastatic tumors from colon cancer and P-NET) were performed using SUVmax and tumor-to-normal liver ratio (TNR). In healthy volunteers, 18F-FACE was metabolically stable in vivo and its biodistribution was almost similar to blood pool, basically uniformly independent of age and gender during PET scan time (up to 3 h). Normal physiological uptake of 18F-FACE at each organ including liver (SUVmean 1.8 ± 0.2) was lower than that of blood pool (SUVmean 2.3 ± 0.3) at 1 h after injection. Chronic inflammatory uptake around femur of post-operative state of femoral osteotomy and faint uptake of benign hemangioma were observed in a case of healthy volunteer. 18F-FACE (SUVmax 2.7 ± 0.6, TNR 1.5 ± 0.4) of liver tumors was significantly lower than those of 18F-FDG uptake (6.5 ± 4.2, 2.6 ± 1.7, respectively). In qualitative analysis, 18F-FDG was positive in 4 tumors (3 HCCs, 1 CCC) and negative in the other 6 tumors, while 18F-FACE was also positive in 4 tumors which were the same tumors with positive 18F-FDG uptake. Biodistribution of 18F-FACE was appropriate for

  11. Study on Z-H/BMP Toughened Compound Artificial Bone and Its Osteogenesis

    Institute of Scientific and Technical Information of China (English)

    XU Wei-guo; CHEN An-min; SUN Shu-zhen

    2003-01-01

    The purpose of this study was to find a kind of new artificial bone for anterior spinal fusion.ZrO2 stabilized by Y2O3 ( Y- PSZ), porous hydroxyapatite ( HA ) and bone morphogenetic protein (BMP) were used to make artificial compound bone ( Y2O3 ) ZrO2 -HA/ BMP( Z-H/ BMP ) , whose function was tested, microstructure and mineralogic composition constitution were analysised by SEM and XRD , and the corresponding animal tests were porformed. Osteogenesis of the material was observed by eyes, histology and SEM. Experimental results show that the component and ossific activity of Z-H/BMP were satisfactory.

  12. Study on the storage stability of Xeno-bone graft material by irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hak Jyung; Kim, Jae Hun; Lee, Ju Woon; Choi, Jong Il [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Kim, Tae Woon [R and D Center, Jeonbuk Technopark, Jeongeup (Korea, Republic of)

    2010-12-15

    In this study, the microbial safety and mechanical properties of xeno-bone graft material irradiated were investigated during the storage. Xeno-bone graft of the deminerlized bone matrix in carboxy-methyl-cellulose was gamma-irradiated and was cultured in PCA and PDA agar to check microbial contamination. Total aerobic bacteria and fungi were not detected in the irradiated and non-irradiated sample stored in accelerator at 30 .deg. C for 10 months. Viscosity of CMC treated gamma irradiation was also not changed by holding period.

  13. Does dermatitis herpetiformis result in bone loss as coeliac disease does?: a cross sectional study

    Directory of Open Access Journals (Sweden)

    Katalin Lorinczy

    2013-04-01

    Full Text Available Introduction and objectives: coeliac disease (CD and its cutaneous manifestation, dermatitis herpetiformis are both (DH gluten-sensitive diseases. Metabolic bone disease is common among patients with CD, even in asymptomatic forms. Data are scarce about bone density in patients with dermatitis herpetiformis. The aim of our study was to compare bone mineral density (BMD of celiac and dermatitis herpetiformis patients. Methods: 34 coeliac patients, 53 with dermatitis herpetiformis and 42 healthy controls were studied. The mean age was 38.0 ± 12.1, 32.18 ± 14.95, 35.33 ± 10.41 years in CD, dermatitis herpetiformis, and healthy controls, respectively. Bone mineral density of the lumbar spine, the left femoral neck and radius were measured by dual-energy X-ray absorptiometry. Low bone density, osteopenia and osteoporosis were defined as a body mass density (BMD T-score between 0 and -1, between -1 and -2.5, and under -2.5, respectively. Results: at lumbar region, consisting of dominantly trabecular compartment, a decreased BMD was detected in 49 % (n = 26 patients with dermatitis herpetiformis, 62 % (n = 21 of CD patients, and 29 % (n = 12 of healthy controls, respectively. Lower BMD were measured at the lumbar region in dermatitis herpetiformis and CD compared to healthy subjects (0.993 ± 0.136 g/cm² and 0.880 ± 0.155 g/cm² vs. 1.056 ± 0.126 g/cm²; p < 0.01. Density of bones consisting of dominantly cortical compartment (femoral neck did not differ in dermatitis herpetiformis and healthy subjects. Conclusions: our results show that a low bone mass is also frequent among patients with dermatitis herpetiformis. Bone mineral content in these patients is significantly lower in those parts of the skeleton which contain more trabecular than cortical bone.

  14. Biocompatibility Studies on Fibrin Glue Cultured with Bone Marrow Mesenchymal Stem Cells in Vitro

    Institute of Scientific and Technical Information of China (English)

    方煌; 彭松林; 陈安民; 黎逢峰; 任凯; 胡宁

    2004-01-01

    Summary: By culturing bone marrow mesenchymal stem cells of rabbits with fibrin glue in vitro,the biocompatibility of fibrin glue was investigated to study whether this material can be used as scaffolds in bone tissue engineering. After 2-months old New Zealand rabbits had been anesthetized, about 4-6 ml of bone marrow were aspirated from rabbit femoral trochanter. The monocytes suspension was aspirated after bone marrow was centrifuged with lymphocyte separating medium and cultured primarily. Then the cells were divided into two groups: one was cultured with complete medium and the other with induced medium. The cells of the two groups were collected and inoculated to the culture plate containing fibrin glue. In the control group, cells were inoculated without fibrin glue. The implanted cells and materials were observed at different stages under a phase-contrast microscope and scanning electron microscope. MTT and alkaline phosphatase (ALP) were measured. Bone marrow mesenchymal stem cells grew on the surface of fibrin glue and adhered to it gradually. Cells light absorption value (A value) and the ALP content showed no significant difference. Fibrin glue had no inhibitory effect on cell morphology, growth, proliferation and differentiation. It has good biocompatibility and can be used as scaffold materials for bone marrow mesenchymal stem cells in bone tissue engineering.

  15. A Comparative Study of Quantitative Assessment of Bone Mineral Density of Mandible

    International Nuclear Information System (INIS)

    This study was performed to compare the bone mineral densities measured at mandibular premolar area by copper-equivalent image and hydroxyapatite phantom with those measured at radius by dual energy absorptiometry and to evaluate the clinical usefulness of Digital system with slide scanner, copper-equivalent image, and hydroxyapatite phantom. For experiment, intraoral radiograms of 15 normal subjects ranged from 20 years old to 67 old were taken with copper-step wedge at mandibular premolar area and bone mineral densities calculated by conversion equation to bone mineral density of hydroxyapatite were compared with those measured at radius distal 1/3 area by Hologic QDR-1000. Obtained results as follows: 1) The conversion equation was Y=5.97X-0.25 and its determination coefficient was 0.9967. The coefficient of variation in the measurement of copper-equivalent value ranged from 4% to 8% and showed high reproducibility. 2) The coefficient of variation in the measurement of bone mineral density by the equation ranged from 7% to 8% and showed high reproducibility. 3) The bone mineral densities ranged from 0.35 to 0.79 g/cm2 at mandibular premolar area. 4) The correlation coefficient between bone mineral densities at mandibular premolar area and those at radius distal 1/3 area was 0.8965. As summary, digital image analyzing system using copper-equivalent image and hydroxyapatite phantom appeared to be clinically useful to measure the bone mineral density at dental area.

  16. [Transitory bone loss during substitution treatment for hypothyroidism. Results of a two year prospective study].

    Science.gov (United States)

    Trémollières, F; Pouillès, J M; Louvet, J P; Ribot, C

    1991-12-01

    The authors report the results of a prospective study designed to assess changes in vertebral and femoral bone density during the first two years of replacement therapy in 10 patients with hypothyroidism (4 men, 6 women). During the first year, bone density measured by dual photon absorptiometry fell significantly in the lumbar vertebrae (-5.4%), neck of the femur (-7%) and the trochanteric region (-7.3%). This bone loss was accompanied by an early increase in serum osteocalcin levels, urinary calcium/urinary creatinine ratio and in Sex Hormone Binding Globulin. During the second year, there was complete recovery of values of vertebral and trochanteric bone density, while density of the neck of the femur remained significantly lower than initial values. None of the patients showed any evidence of overdose during the period of monitoring of clinical and laboratory (free T4, total and free T3, ultra-sensitive TSH) parameters. This transitory bone loss could be indicative of a state of tissue hyperthyroidism and/or "hypersensitivity" of hypothyroid bone to the action of thyroid hormones. Its influence on the subsequent risk of fracture remains unclear. In the current state of knowledge, measurement of vertebral and femoral bone density appears to be indicated in patients given long term treatment which suppresses TSH, or requiring replacement therapy for severe hypothyroidism. Any demineralisation prior to treatment could justify the temporary prescription of an antiosteoclastic agent. PMID:1780668

  17. Study of caprine bones after moist and dry heat processes by X-ray diffraction

    International Nuclear Information System (INIS)

    Bone tissue is a biological material composed of hydroxyapatite (HAp) and collagen matrix. The bone X-ray diffraction (XRD) pattern presents characteristics of the hydroxyapatite crystallography planes. This paper presents the characterization by X-ray diffraction of caprine bone powder pattern and the comparison of this pattern with moist or dry heat cooked bone patterns. The parameters chosen to characterize the X-ray diffraction peaks were: angular position (2θ), full width at half maximumt (FWHM), and relative intensity (Irel). The X-ray diffraction patterns were obtained with a Shimadzu XRD-6000 diffractometer. The caprine bone XRD pattern revealed a significant correlation of several crystallographic parameters (lattice data) with hydroxyapatite. The profiles of the three bone types analyzed presented differences. The study showed as small angular displacement (decrease of the 2θ angle) of some peaks was observed after moist and dry heat cooking processes. The characterization of bone tissue aimed to contribute to future analysis in the field of archeology. (author)

  18. Histomorphological study of bone response to hydroxyapatite coating on stainless steel.

    Science.gov (United States)

    Merolli, A; Moroni, A; Faldini, C; Tranquilli Leali, P; Giannini, S

    2003-04-01

    Bone response to hydroxyapatite coating on stainless steel has not been so extensively tested in animals as it happened for other metallic substrate, like Ti6Al4V. For this reason, authors performed an in vivo histomorphological electron microscopic study of hydroxyapatite coating on duplex stainless steel cylinders, to gather further evidences on the characters of bone apposition at the interface. Sixteen HA-coated cylinders were implanted in the distal femur of New Zealand White rabbits. Comparison with uncoated controls was made. Retrieval steps were at: 4, 8, 26 and 34 weeks. Specimens were analyzed in a Jeol JSM 6301F scanning electron microscope. The response to HA-coated samples has a morphological character of tight apposition between bone and coating. Osteocytic lacunae may be found few microns close to the coating and newly formed bone is extremely interlocked with it so that even an higher magnification electron-microscopy cannot resolve any discontinuity in between. Pictures of physiological bone-turnover are distinguishable at the bone-coating interface; areas of well preserved coating may be present together with areas where local exfoliation or fragmentation has already completely exposed the metallic substrate. On the opposite in uncoated samples, despite a morphological picture of properly formed bone, the largest area of the metal has no direct apposition with it. PMID:15348457

  19. Study of caprine bones after moist and dry heat processes by X-ray diffraction

    Energy Technology Data Exchange (ETDEWEB)

    Barbosa, Caroline M., E-mail: carolmattosb@yahoo.com.br [Instituto de Arqueologia Brasileira (IAB), Belford Roxo, RJ (Brazil); Azeredo, Soraia R.; Lopes, Ricardo T., E-mail: soraia@lin.ufrj.br [Coordenacao dos Programas de Pos-Graduacao em Engenharia (COPPE/LIN/UFRJ), Rio de Janeiro, RJ (Brazil). Laboratorio de Instrumentacao Nuclear; Souza, Sheila M.F.M de, E-mail: sferraz@ensp.fiocruz.br [Fundacao Oswaldo Cruz (ENSP/FIOCRUZ), Rio de Janeiro, RJ (Brazil). Escola Nacional de Saude Publica Sergio Arouca

    2013-07-01

    Bone tissue is a biological material composed of hydroxyapatite (HAp) and collagen matrix. The bone X-ray diffraction (XRD) pattern presents characteristics of the hydroxyapatite crystallography planes. This paper presents the characterization by X-ray diffraction of caprine bone powder pattern and the comparison of this pattern with moist or dry heat cooked bone patterns. The parameters chosen to characterize the X-ray diffraction peaks were: angular position (2θ), full width at half maximumt (FWHM), and relative intensity (I{sub rel}). The X-ray diffraction patterns were obtained with a Shimadzu XRD-6000 diffractometer. The caprine bone XRD pattern revealed a significant correlation of several crystallographic parameters (lattice data) with hydroxyapatite. The profiles of the three bone types analyzed presented differences. The study showed as small angular displacement (decrease of the 2θ angle) of some peaks was observed after moist and dry heat cooking processes. The characterization of bone tissue aimed to contribute to future analysis in the field of archeology. (author)

  20. In vitro study of osteoclastogenesis under simulated bone augmentation: The effects of bone-conditioned medium and saliva on osteoclastogenesis

    OpenAIRE

    Caballé Serrano, Jordi

    2015-01-01

    The present PhD thesis is a compendium of four publications broadening the knowledge on osteoclastogenesis under simulated bone augmentation, more especially about the effects of saliva and bone-conditioned medium on osteoclastogenesis. Resorption of bone grafts and host bone, can be a challenge especially when a bonny defect has to be regenerated or there is a lack of host bone due to a trauma, pathology, aging or tooth extraction among others. In the oral cavity, saliva is present and can r...

  1. Association between Anthropometric Measures and Bone Mineral Density: Population-Based Study

    Directory of Open Access Journals (Sweden)

    HR Aghaei Meybodi

    2011-06-01

    Full Text Available "nBackground: Osteoporosis is a major public health concern around the world. It has been shown that bone mineral den­sity is correlated to anthropometric measures like height and weight, but this association may vary depending on ethnic and environmental factors. The aim of this study was to identify probable relations between anthropometric measures and bone mineral density."nMethods: In this population-based study, we compiled the data collected from Iranian Multicenter Osteoporosis Study to assess the possible associations between different anthropometric indices and bone mineral density at femur and lumbar spine. The gathered data was analyzed using t-test and one way ANOVA."nResults: Data was available for 4445 subjects, consisting 1900 males (42.7% and 2545 females (57.3%. We observed statistically significant correlations between bone mineral density and height, weight, waist circumference, hip circumfer­ence, waist to hip ratio and body mass index (BMI. Based on the result of linear regression modeling studies, BMI could be considered an independent predictor of bone mineral density."nConclusion: Iranian population shows similar measures compared to analogous studies in other populations. Lower weight should be carefully considered as a predisposing factor for bone loss and osteoporosis.

  2. Vitamin D, parathyroid hormone levels and bone mineral density in community-dwelling older women: The Rancho Bernardo Study

    OpenAIRE

    von Mühlen, Denise G; Greendale, Gail A.; Cedric F Garland; Wan, Lori; Barrett-Connor, Elizabeth

    2005-01-01

    Vitamin D (25(OH)D) increases the efficiency of intestinal calcium absorption. Low levels of serum calcium stimulate the secretion of parathyroid hormone (PTH), which maintains serum calcium levels at the expense of increased bone turnover, bone loss and increased risk of fractures. We studied the association between 25(OH)D and PTH levels, and their associations with bone mineral density (BMD), bone loss, and prevalence of hip fractures in 615 community-dwelling postmenopausal aged 50 - 97 y...

  3. Growth patterns of fossil vertebrates as deduced from bone microstructure: case studies from India

    Indian Academy of Sciences (India)

    S Ray; D Mukherjee; S Bandyopadhyay

    2009-11-01

    Bone microstructure is affected by ontogeny, phylogeny, biomechanics and environments. These aspects of life history of an extinct animal, especially its growth patterns, may be assessed as fossil bone generally maintains its histological integrity. Recent studies on the bone histology of fossil vertebrates from India encompass different types of temnospondyls and dicynodonts from different Permian and Triassic horizons. The examined taxa show that they had distinct bone histology and varied growth patterns. The Early Triassic trematosaurids had an overall fast growth, which contrasts with that of the Middle and Late Triassic temnospondyl taxa examined. The dicynodonts on the other hand, were characterized by an overall fast growth with periodic interruptions, variable growth rates dependent on ontogeny and indeterminate growth strategy. A comparative study encompassing several neotherapsid genera including the dicynodonts shows significant evolutionary trends towards determinate growth strategy and reduced developmental plasticity.

  4. A Comparative Study of Bioartificial Bone Tissue Poly-L-lactic Acid/Polycaprolactone and PLLA Scaffolds Applied in Bone Regeneration

    OpenAIRE

    Weizong Weng; Shaojun Song; Liehu Cao; Xiao Chen; Yuanqi Cai; Haihang Li; Qirong Zhou; Jun Zhang; Jiacan Su

    2014-01-01

    Bioartificial bone tissue engineering is an increasingly popular technique to repair bone defect caused by injury or disease. This study aimed to investigate the feasibility of PLLA/PCL (poly-L-lactic acid/polycaprolactone) by a comparison study of PLLA/PCL and PLLA scaffolds applied in bone regeneration. Thirty healthy mature New Zealand rabbits on which 15 mm distal ulna defect model had been established were selected and then were divided into three groups randomly: group A (repaired with ...

  5. Impact of dental implant insertion method on the peri-implant bone tissue: Experimental study

    Directory of Open Access Journals (Sweden)

    Stamatović Novak

    2013-01-01

    Full Text Available Background/Aim. The function of dental implants depends on their stability in bone tissue over extended period of time, i.e. on osseointegration. The process through which osseointegration is achieved depends on several factors, surgical insertion method being one of them. The aim of this study was to histopathologically compare the impact of the surgical method of implant insertion on the peri-implant bone tissue. Methods. The experiment was performed on 9 dogs. Eight weeks following the extraction of lower premolars implants were inserted using the one-stage method on the right mandibular side and two-stage method on the left side. Three months after implantation the animals were sacrificed. Three distinct regions of bone tissue were histopathologically analyzed, the results were scored and compared. Results. In the specimens of one-stage implants increased amount of collagen fibers was found in 5 specimens where tissue necrosis was also observed. Only moderate osteoblastic activity was found in 3 sections. The analysis of bone-to-implant contact region revealed statistically significantly better results regarding the amount of collagen tissue fibers for the implants inserted in the two-stage method (Wa = 59 105, α = 0.05. No necrosis and osteoblastic activity were observed. Conclusion. Better results were achieved by the two-stage method in bone-to-implant contact region regarding the amount of collagen tissue, while the results were identical regarding the osteoblastic activity and bone tissue necrosis. There was no difference between the methods in the bone-implant interface region. In the bone tissue adjacent to the implant the results were identical regarding the amount of collagen tissue, osteoblastic reaction and bone tissue necrosis, while better results were achieved by the two-stage method regarding the number of osteocytes.

  6. THE EFFECT OF STRAIN RATE ON FRACTURE TOUGHNESS OF HUMAN CORTICAL BONE: A FINITE ELEMENT STUDY

    OpenAIRE

    Ural, Ani; Zioupos, Peter; Buchanan, Drew; Vashishth, Deepak

    2011-01-01

    Evaluating the mechanical response of bone under high loading rates is crucial to understanding fractures in traumatic accidents or falls. In the current study, a computational approach based on cohesive finite element modeling was employed to evaluate the effect of strain rate on fracture toughness of human cortical bone. Two-dimensional compact tension specimen models were simulated to evaluate the change in initiation and propagation fracture toughness with increasing strain rate (range: 0...

  7. A new bone-ligament-bone autograft from the plantar plates of the toes and its potential use in scapholunate reconstruction: an anatomical study.

    Science.gov (United States)

    Müller, Miriam; Reik, Milena; Sauerbier, Michael; Germann, Günter

    2008-10-01

    The study was performed to investigate a new bone-ligament-bone autograft from the plantar plate of the toes. The anatomic properties of the plantar ligaments and the technical feasibility to harvest a bone-ligament-bone graft were examined to evaluate the potential use of this graft for a suitable reconstruction of the scapholunate (SL) interosseous ligament. The plantar plate of the metatarsophalangeal joints of the second to fifth toe and the proximal interphalangeal joints of the second to fourth toe were examined in 20 cadaver feet (15 fresh and 5 embalmed cadavers) and measurements such as length, thickness, and width were taken. The average length of the plantar ligaments of the proximal interphalangeal joint was 0.63 cm (D3) and 0.62 cm (D4). The length of the plantar plates of the proximal interphalangeal joint of the third and fourth toe was found to be similar to that of the SL ligament. In addition to the measurements, a bone-ligament-bone autograft of the plantar plates of the metatarsophalangeal joint was designed as an SL-ligament substitute and successfully transplanted into cadaveric wrists. This new autograft is intercalated between the scaphoid and lunate and, contrary to all previous methods, not simply superimposed upon them. Length of the plantar plates was considered by the authors as the main criteria for selection of the new bone-ligament-bone graft. The plantar plate of the proximal interphalangeal joint of the third and fourth toe showed a similar length compared with the SL ligament. Therefore, it can be concluded from the data that this bone-ligament-bone graft can be a suitable replacement for the SL ligament. PMID:18812722

  8. SYNCHROTRON RADIATION XRF MICROPROBE STUDY OF HUMAN BONE TUMOR SLICE

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The experimental apparatus of X-ray fluorescence (XRF) microprobe analysis at Beijing Synchrotron Radiation Facility (BSRF) is described Using the bovine liver as the standard reference.the minimum detection limit(MDL) of trace element was measured to determine the capability of biological sample analysis by synchrotron radiation XRF microprobe.The relative change of the content of the major or trace element in the normal and tumor part of human bone tissue slice was investigated The experimental result relation to the clinical medicine was also discussed.

  9. Preliminary study using pulsating water jet for bone cement demolition

    Czech Academy of Sciences Publication Activity Database

    Hloch, Sergej; Kloc, J.; Foldyna, Josef; Pude, F.; Smolko, I.; Zeleňák, Michal; Sitek, Libor; Hvizdoš, P.; Monka, P.; Monková, K.; Kozak, D.; Stoić, A.; Sedmak, A.; Milosevic, M.; Lehocká, D.; Mihalčinová, E.

    Ostrava : Ústav geoniky AV ČR, v.v.i, 2015 - (Sitek, L.; Klichová, D.), s. 37-54 ISBN 978-80-86407-56-2. [Vodní paprsek 2015 - výzkum, vývoj, aplikace. Velké Losiny (CZ), 06.10.2015-08.10.2015] R&D Projects: GA MŠk ED2.1.00/03.0082; GA MŠk(CZ) LO1406 Institutional support: RVO:68145535 Keywords : bone cement * ultrasonic pulsating water jet * revision arthroplasty Subject RIV: JQ - Machines ; Tools

  10. FUSION BETWEEN BODY AND GREATER CORNU: A RADIOLOGICAL STUDY OF DRY HYOID BONES

    Directory of Open Access Journals (Sweden)

    Bhavna

    2015-09-01

    Full Text Available Introduction: The study of fusion of body and greater cornua of hyoid bone is of tremendous clinical and forensic significance as it can be used to estimate the age of living or dead or skeletonized remains. It becomes all the more important as this fusion is relatively immune to some individual factors like life style, health and nutrition etc. Material method: The study comprised of 15 male and 15 female bones all collected from human cadavers with age >60 years. Digitalized radiographs of these bones were taken and fusion between body and greater cornua was studied. Results: A bilateral fusion was seen in 43.3% bones with another 33% showing unilateral fusion .The bilateral fusion did not depict any sex difference but unilateral fusion was more common on left side in males and right side in females. Conclusion: Fusion of body and greater cornua of hyoid bone after age of 60 years is not always seen so one should be cautious in interpreting fracture of this bone in persons with age >60years and look for other local pathological features like haematoma formation at the site of fracture.

  11. The contribution of bone scintigraphy in occupational health or medical insurance claims: a retrospective study

    International Nuclear Information System (INIS)

    Patients with a suspicion of bone damage following an industrial or traffic accident are often referred for bone scintigraphy as part of an occupational health or medical insurance investigation. The aim of this study was to assess the contribution and the potential role of bone scintigraphy compared with X-ray investigations in the aforementioned situation. To this end we evaluated 70 consecutive patients referred for bone scintigraphy during 1996 and 1997 by occupational health or medical insurance physicians. The most common reasons for referral were the exclusion of occult fractures of hands and feet, whiplash injuries, reflex sympathetic dystrophy or avascular necrosis, or the differentiation between an old and a recent vertebral fracture. X-rays were only available for comparative review of 53 patients, so only those were analysed. The results of bone scintigraphy were compared with X-rays, and their contribution and potential role in occupational health or medical insurance investigations assessed. In 31 out of the 53 patients investigated, bone scintigraphy findings concurred with X-rays as to the number and location of abnormalities. For 19 of the 53 patients, bone scintigraphy showed clinically relevant additional foci when compared with X-rays, predominantly involving lesions to hands/wrists and feet/ankles. Among these 19 patients, scintigraphic diagnoses were subsequently confirmed in ten cases by means of X-ray or computed tomography. In four patients, supplementary radiological investigations revealed no abnormalities, and in five patients no further investigations were undertaken. Finally, in three of the 53 patients, X-rays revealed bone damage (burst fractures) whilst the corresponding bone scintigraphy was negative, thus excluding recent injury. In conclusion, in 22 patients, representing 42% of the cases analysed, bone scintigraphy was conclusive compared with X-ray imaging in the final diagnosis and in this way in detecting occult or excluding

  12. In vitro incorporation studies of 99mTc-alendronate sodium at different bone cell lines

    International Nuclear Information System (INIS)

    Bisphosphonates can be labeled with Technetium-99m (99mTc) and are used for bone imaging because of their good localization in the skeleton and rapid clearance from soft tissues. Over the last decades bone scintigraphy has been used extensively in the evaluation of oncological patients to provide information about the sites of bone lesions, their prognosis and the effectiveness of therapy by showing the sequential changes in tracer uptake. Since the lesion visualization and lesion/bone ratio are important utilities for a bone scanning radiopharmaceutic; in this study incorporation of 99mTc labeled alendronate sodium (99mTc-ALD) was evaluated in U2OS (human bone osteosarcoma) and NCI-H209 (human bone carcinoma) cell lines. ALD was directly labeled by 99mTc, radiochemical purity and stability of the complex were analyzed by radioactive thin layer chromatography and radioactive high performance liquid chromatography studies. For cell incorporation study, NCI-H209 and U2OS cell lines were used with standard cell culture methods. The six well plates were used for all experiments and the integrity of each cell monolayer was checked by measuring its transepithelial electrical resistance (TEER) with an epithelial voltammeter. Results confirmed that ALD was successfully radiolabeled with 99mTc. 99mTc-ALD incorporated with NCI-H209 and U2OS cells. The uptake percentages of 99mTc-ALD in NCI-H209 and U2OS cell lines were found significantly different. Since 99mTc-ALD highly uptake in cancer cell line, the results demonstrated that radiolabeled ALD may be a promising agent for bone cancer diagnosis. (author)

  13. Histologic and histomorphometric study of bone repair around short dental implants inserted in rabbit tibia, associated with tricalcium phosphate graft bone

    OpenAIRE

    Marlice Azoia Lukiantchuki Barbosa; Liogi Iwaki Filho; Lilian Cristina Vessoni Iwaki; Maria Raquel Marçal Natali; Wilton Mitsunari Takeshita; Sérgio Sábio

    2014-01-01

    The use of short dental implants represents one way to overcome this limitation, in association with bone grafting procedures. Tricalcium phosphate-based grafts are among those widely used. The purpose of this study was to assess the biocompatibility of this biomaterial in the coverage of bone defects around short dental implants. Ten New Zealandrabbits were used in this study, each animal received 4 implants, two were placed in the right tibia region (control group) and two in the left tibia...

  14. Demineralized Bone Matrix Add-On for Acceleration of Bone Healing in Atypical Subtrochanteric Femoral Fracture: A Consecutive Case-Control Study

    OpenAIRE

    Noratep Kulachote; Paphon Sa-ngasoongsong; Norachart Sirisreetreerux; Pongsthorn Chanplakorn; Praman Fuangfa; Chanyut Suphachatwong; Wiwat Wajanavisit

    2016-01-01

    Background. Delayed union and nonunion are common complications in atypical femoral fractures (AFFs) despite having good fracture fixation. Demineralized bone matrix (DBM) is a successfully proven method for enhancing fracture healing of the long bone fracture and nonunion and should be used in AFFs. This study aimed to compare the outcome after subtrochanteric AFFs (ST-AFFs) fixation with and without DBM. Materials and Methods. A prospective study was conducted on 9 ST-AFFs patients using DB...

  15. Unilateral Pedicle Screw Fixation with Bone Graft vs. Bilateral Pedicle Screw Fixation with Bone Graft or Cage: A Comparative Study.

    Science.gov (United States)

    Yang, Si-Dong; Chen, Qian; Ding, Wen-Yuan; Zhao, Jian-Qiang; Zhang, Ying-Ze; Shen, Yong; Yang, Da-Long

    2016-01-01

    BACKGROUND The aim of this study was to explore the clinical efficacy of unilateral pedicle screw fixation with bone graft (UPSFB) in treating single-segment lumbar degenerative diseases (LDD), as compared to bilateral pedicle screw fixation with bone graft (BPSFB) or with cage (BPSFC). MATERIAL AND METHODS Medical records were retrospectively collected between 01/2010 and 02/2015 in Longyao County Hospital. According to surgical methods used, all patients were divided into 3 groups: UPSFB group, BPSFB group, and BPSFC group. Clinical outcomes were evaluated by blood loss, blood transfusion, duration of operation, hospital stay, postoperative complications, interbody fusion rate, reoperation rate, medical expenses, patient satisfaction survey, and JOA score. RESULTS Ninety-five patients were included and underwent 2.5-year follow-up, with 7 patients lost to regular follow-up. As compared to the BPSFB group and BPSFC group, the UPSFB group had less blood loss and less blood transfusion, as well as shorter hospital stay (pfusion rate, reoperation rate, JOA score, and patient satisfaction (all p>0.05). CONCLUSIONS As compared to BPSFB and BPSFC, UPSFB has the same reliability and effectiveness in treating single-segment LDD with unilateral radicular symptoms in a single lower extremity, with the additional advantage being less expensive. PMID:26988532

  16. Unilateral Pedicle Screw Fixation with Bone Graft vs. Bilateral Pedicle Screw Fixation with Bone Graft or Cage: A Comparative Study

    Science.gov (United States)

    Yang, Si-Dong; Chen, Qian; Ding, Wen-Yuan; Zhao, Jian-Qiang; Zhang, Ying-Ze; Shen, Yong; Yang, Da-Long

    2016-01-01

    Background The aim of this study was to explore the clinical efficacy of unilateral pedicle screw fixation with bone graft (UPSFB) in treating single-segment lumbar degenerative diseases (LDD), as compared to bilateral pedicle screw fixation with bone graft (BPSFB) or with cage (BPSFC). Material/Methods Medical records were retrospectively collected between 01/2010 and 02/2015 in Longyao County Hospital. According to surgical methods used, all patients were divided into 3 groups: UPSFB group, BPSFB group, and BPSFC group. Clinical outcomes were evaluated by blood loss, blood transfusion, duration of operation, hospital stay, postoperative complications, interbody fusion rate, reoperation rate, medical expenses, patient satisfaction survey, and JOA score. Results Ninety-five patients were included and underwent 2.5-year follow-up, with 7 patients lost to regular follow-up. As compared to the BPSFB group and BPSFC group, the UPSFB group had less blood loss and less blood transfusion, as well as shorter hospital stay (p0.05). Conclusions As compared to BPSFB and BPSFC, UPSFB has the same reliability and effectiveness in treating single-segment LDD with unilateral radicular symptoms in a single lower extremity, with the additional advantage being less expensive. PMID:26988532

  17. Elemental and structural studies at the bone-cartilage interface

    International Nuclear Information System (INIS)

    Micro-Proton Induced X-ray Emission (μ-PIXE) and Proton Induced Gamma-ray Emission (PIGE) techniques were employed in the investigation of trace and essential elements distribution in normal and diseased human femoral head sections affected by osteoarthritis (OA). PIGE was exploited in the determination of elements of low atomic number z15 viz Ca, Z, P and S were determined by PIXE. Accumulations of key elements in the bone and cartilage sections were observed, significant S and Na concentrations being found in the cartilage region particularly in normal tissues. Zn showed enhanced concentrations at the bone-cartilage interface. At a synchrotron facility, small angle X-ray scattering (SAXS) was utilized on a decalcified human femoral head section affected by OA, direct measurements being made of spatial alterations of collagen fibres. The SAXS results showed a slight decrease in the axial periodicity between normal collagen type I and that in diseased tissue in various sites, in contrast with the findings of others.

  18. Elemental and structural studies at the bone-cartilage interface

    Science.gov (United States)

    Kaabar, W.; Daar, E.; Bunk, O.; Farquharson, M. J.; Laklouk, A.; Bailey, M.; Jeynes, C.; Gundogdu, O.; Bradley, D. A.

    2011-10-01

    Micro-Proton Induced X-ray Emission (μ-PIXE) and Proton Induced Gamma-ray Emission (PIGE) techniques were employed in the investigation of trace and essential elements distribution in normal and diseased human femoral head sections affected by osteoarthritis (OA). PIGE was exploited in the determination of elements of low atomic number z15 viz Ca, Z, P and S were determined by PIXE. Accumulations of key elements in the bone and cartilage sections were observed, significant S and Na concentrations being found in the cartilage region particularly in normal tissues. Zn showed enhanced concentrations at the bone-cartilage interface. At a synchrotron facility, small angle X-ray scattering (SAXS) was utilized on a decalcified human femoral head section affected by OA, direct measurements being made of spatial alterations of collagen fibres. The SAXS results showed a slight decrease in the axial periodicity between normal collagen type I and that in diseased tissue in various sites, in contrast with the findings of others.

  19. Elemental and structural studies at the bone-cartilage interface

    Energy Technology Data Exchange (ETDEWEB)

    Kaabar, W., E-mail: w.kaabar@surrey.ac.uk [Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom); Daar, E. [Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom); Bunk, O. [Swiss Light Source, Paul Scherrer Institute, 5232 Villigen (Switzerland); Farquharson, M.J. [Department of Medical Physics and Applied Radiation Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1 (Canada); Laklouk, A. [Al-Fateh University, Tripoli (Libya); Bailey, M.; Jeynes, C. [Surrey Ion Beam Centre, University of Surrey, Guildford GU2 7XH (United Kingdom); Gundogdu, O. [Umuttepe Campus, University of Kocaeli, 41380 Kocaeli (Turkey); Bradley, D.A. [Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom)

    2011-10-01

    Micro-Proton Induced X-ray Emission ({mu}-PIXE) and Proton Induced Gamma-ray Emission (PIGE) techniques were employed in the investigation of trace and essential elements distribution in normal and diseased human femoral head sections affected by osteoarthritis (OA). PIGE was exploited in the determination of elements of low atomic number z<15 such as Na and F whereas elements with z>15 viz Ca, Z, P and S were determined by PIXE. Accumulations of key elements in the bone and cartilage sections were observed, significant S and Na concentrations being found in the cartilage region particularly in normal tissues. Zn showed enhanced concentrations at the bone-cartilage interface. At a synchrotron facility, small angle X-ray scattering (SAXS) was utilized on a decalcified human femoral head section affected by OA, direct measurements being made of spatial alterations of collagen fibres. The SAXS results showed a slight decrease in the axial periodicity between normal collagen type I and that in diseased tissue in various sites, in contrast with the findings of others.

  20. Experimental design and reporting standards for improving the internal validity of pre-clinical studies in the field of pain: Consensus of the IMI-Europain consortium

    DEFF Research Database (Denmark)

    Knopp, K.L.; Stenfors, C.; Baastrup, Cathrine Søndergaard;

    2015-01-01

    and conduct, and data analysis and interpretation. Key principles such as sample size calculation, a priori definition of a primary efficacy measure, randomization, allocation concealments, and blinding are discussed. In addition, considerations of how stress and normal rodent physiology impact...... activity and, where possible, on-target confirmation of that activity. It has, however, been suggested that at least 50% of all pre-clinical data, independent of discipline, cannot be replicated. Additionally, the paucity of “negative” data in the public domain indicates a publication bias, and...

  1. A comparative study of the 90Sr/Ca ratio in human diet and bone tissue

    International Nuclear Information System (INIS)

    A comparative study of both the evolution of strontium-90 content in the bones of individuals of different ages for the period 1962-1967 as related to calcium, and the corresponding diets allowed to establish the relationship between food contribution and the resulting bone burden. The study is mainly devoted to the group of adults for which a mathematical expression is proposed which allows for the exchangeable form of a skeletal calcium fraction turned over in less than a year from the dietary calcium, and the stabilized form constituting the larger part of bone tissue characterized by a slow turnover. Both the amount of the exchangeable fraction and the turnover rate of the stabilized fraction are determined for vertebrae and ribs. At birth, bone levels indicate that the calcium used for skeleton modelling during foetal life originates from both maternal diet and bone tissue and a value is given, to their relative significance. There appears a good relationship between bone levels in infants from 6 months to 1 year of age and their diets. The physiological parameters particular to this age are quantified. (authors

  2. A zooarchaeological study of bone assemblages from the Ma’anshan Paleolithic site

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Ten thousands of bone fragments were recovered from the Ma’anshan Paleolithic site, of which 4358 pieces can be identified to skeletal elements or species. In this research, the bone assemblages are quantified based on elements of MNI, MNE, and MAU. Then bone surface modifications and skeletal element profiles of the bone assemblages are studied to understand shlepping behaviors and reveal the technique of disarticulating and defleshing the animals’ bodies, etc. Based on the analyses of bone assemblages and the comparative study with the ethnoarchaeological as well as experimental data, it is assumed that later hominids at the site made fuller use of the game animals than the earlier hominids. Incorporating the lines of evidence from chronological dating, paleoenvironment, and polished bone tools between the two cultural layers, here we propose three hypotheses suggesting that the changes of environment, the migrations of the hominids from the North, or the demographic pulses may cause such a behavioral difference. However, it is yet to be determined which hypothesis can better explain the changes.

  3. Study on osteopotential activity of Terminalia arjuna bark extract incorporated bone substitute

    Indian Academy of Sciences (India)

    G Krithiga; T Hemalatha; R Deepachitra; Kausik Ghosh; T P Sastry

    2014-10-01

    Bark extract of Terminalia arjuna (TA) possesses potent medical properties and therefore, holds a reputed position in both Ayurvedic and Unani systems of medicine. Bone substitutes play an inevitable role in traumatic bone damages. Growth factors induce osteoinductivity, but suffer from limitations such as high cost and side effects. This study aims to evaluate the osteoinductive potential of bark extract of TA in bone substitutes. Bone substitutes prepared with TA bark extract were characterized for their physicochemical properties. In vitro biomineralization study was carried out using simulated body fluid. Cytotoxicity, alkaline phosphatase activity and mineralization potential were assessed using MG-63 cell lines. Scanning electron microscope revealed apatite formation on the surface after biomineralization. Thermogravimetric analysis showed 15% increase in residual weight by deposition of calcium and phosphate and their presence was identified by energy dispersive analysis. Increased alkaline phosphatase and calcium release was observed in bone substitutes prepared with TA extract compared with control. The functional groups of TA bark extract help in in vitro biomineralization. In MG-63 cells, it showed potential influence in cell differentiation. TA extract may be used as low-cost alternative for growth factors for treatment of fractured bones.

  4. Noninvasive optical measurement of bone marrow lesions: a Monte Carlo study on visible human dataset

    Science.gov (United States)

    Su, Yu; Li, Ting

    2016-03-01

    Bone marrow is both the main hematopoietic and important immune organ. Bone marrow lesions (BMLs) may cause a series of severe complications and even myeloma. The traditional diagnosis of BMLs rely on mostly bone marrow biopsy/ puncture, and sometimes MRI, X-ray, and etc., which are either invasive and dangerous, or ionizing and costly. A diagnosis technology with advantages in noninvasive, safe, real-time continuous detection, and low cost is requested. Here we reported our preliminary exploration of feasibility verification of using near-infrared spectroscopy (NIRS) in clinical diagnosis of BMLs by Monte Carlo simulation study. We simulated and visualized the light propagation in the bone marrow quantitatively with a Monte Carlo simulation software for 3D voxelized media and Visible Chinese Human data set, which faithfully represents human anatomy. The results indicate that bone marrow actually has significant effects on light propagation. According to a sequence of simulation and data analysis, the optimal source-detector separation was suggested to be narrowed down to 2.8-3.2cm, at which separation the spatial sensitivity distribution of NIRS cover the most region of bone marrow with high signal-to-noise ratio. The display of the sources and detectors were optimized as well. This study investigated the light transport in spine addressing to the BMLs detection issue and reported the feasibility of NIRS detection of BMLs noninvasively in theory. The optimized probe design of the coming NIRS-based BMLs detector is also provided.

  5. Assessment of trabecular bone changes around endosseous implants using image analysis techniques: A preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Zuki, Mervet El [Dept. of Oral Medicine and Radiology, Benghazi University College of Dentistry, Benghazi (Libya); Omami, Galal [Oral Diagnosis and Polyclinics, Faculty of Dentistry, The University of Hong Kong (Hong Kong); Horner, Keith [Dept. of Oral Radiology, University Dental Hospital of Manchester, Manchester (United Kingdom)

    2014-06-15

    The objective of this study was to assess the trabecular bone changes that occurred around functional endosseous dental implants by means of radiographic image analysis techniques. Immediate preoperative and postoperative periapical radiographs of de-identified implant patients at the University Dental Hospital of Manchester were retrieved, screened for specific inclusion criteria, digitized, and quantified for structural elements of the trabecular bone around the endosseous implants, by using image analysis techniques. Data were analyzed using SPSS version 11.5. P values of less than 0.05 were considered statistically significant. A total of 12 implants from 11 patients were selected for the study, and 26 regions of interest were obtained. There was a significant increase in the bone area in terms of the mean distance between nodes (p=0.006) and a significant decrease in the marrow area in terms of the bone area (p=0.006) and the length of marrow spaces (p=0.032). It appeared that the bone around the implant underwent remodeling that resulted in a net increase in bone after implant placement.

  6. Prospective study of bone marrow infiltration in aggressive lymphoma by three independent methods: Whole-body MRI, PET/CT and bone marrow biopsy

    International Nuclear Information System (INIS)

    Purpose: Initial lymphoma staging requires bone marrow assessment in aggressive lymphomas. Bone marrow lymphoma infiltration is routinely assessed by bone marrow biopsy (BMB), considered as the 'gold standard'. The aim of this study was to compare the performance of BMB, whole-body MRI and PET/CT for evaluation of BM infiltration. Methods: Patients with newly diagnosed aggressive lymphoma were evaluated by BMB, MRI and PET/CT. Two radiologists, two nuclear medicine physicians and one pathologist independently assessed the results of the three modalities. Bone was considered as involved if BM was positive or if PET/CT or MRI was positive and if there was a resolution of the abnormal image shown on PET/CT or MRI halfway or at the end of therapy. Results: Both MRI and PET/CT detected bone marrow lesions in the 9/43 patients, but two patients with multiple lesions had more lesions detected by PET/CT compared to MRI. Among these nine patients, two with an iliac crest lesion detected by both MRI and PET/CT had bone marrow involvement with large-cell lymphoma on histological examination. The other seven patients had focal MRI and PET/CT lesions in areas other than the iliac crest, where the blind BMB was done. The other patients had bone marrow without large-cell lymphoma involvement. In all cases, after lymphoma therapy bone marrow involvement regressed on histological examination, PET and MRI. Conclusion: These preliminary results suggest that non-invasive morphological procedures could be superior to BMB for bone marrow assessment in aggressive lymphomas. Ongoing study is underway to validate these results

  7. Effects of multi-deficiencies-diet on bone parameters of peripheral bone in ovariectomized mature rat.

    Directory of Open Access Journals (Sweden)

    Thaqif El Khassawna

    Full Text Available Many postmenopausal women have vitamin D and calcium deficiency. Therefore, vitamin D and calcium supplementation is recommended for all patients with osteopenia and osteoporosis. We used an experimental rat model to test the hypothesis that induction of osteoporosis is more efficiently achieved in peripheral bone through combining ovariectomy with a unique multi-deficiencies diet (vitamin D depletion and deficient calcium, vitamin K and phosphorus. 14-week-old Sprague-Dawley rats served as controls to examine the initial bone status. 11 rats were bilaterally ovariectomized (OVX and fed with multi-deficiencies diet. Three months later the treated group and the Sham group (n = 8 were euthanized. Bone biomechanical competence of the diaphyseal bone was examined on both, tibia and femur. Image analysis was performed on tibia via µCT, and on femur via histological analysis. Lower torsional stiffness indicated inferior mechanical competence of the tibia in 3 month OVX+Diet. Proximal metaphyseal region of the tibia showed a diminished bone tissue portion to total tissue in the µCT despite the increased total area as evaluated in both µCT and histology. Cortical bone showed higher porosity and smaller cross sectional thickness of the tibial diaphysis in the OVX+Diet rats. A lower ALP positive area and elevated serum level of RANKL exhibited the unbalanced cellular interaction in bone remodeling in the OVX+Diet rat after 3 month of treatment. Interestingly, more adipose tissue area in bone marrow indicated an effect of bone loss similar to that observed in osteoporotic patients. Nonetheless, the presence of osteoid and elevated serum level of PTH, BGP and Opn suggest the development of osteomalacia rather than an osteoporosis. As the treatment and fracture management of both osteoporotic and osteomalacia patients are clinically overlapping, this study provides a preclinical animal model to be utilized in local supplementation of minerals, drugs

  8. Lessons from the Bone Chapter of the Malaysian Aging Men Study

    Directory of Open Access Journals (Sweden)

    Kok-Yong Chin

    2016-05-01

    Full Text Available Male osteoporosis in Malaysia is a largely neglected problem. Therefore, a bone health study in men using quantitative ultrasonometry was launched as part of the Malaysian Aging Men Study in 2009–2012. This review aimed to summarize the findings of the aforementioned bone health study. The study examined the bone health of Chinese and Malaysian men aged 20 years and above living in Kuala Lumpur using a quantitative ultrasound device. Participants answered a questionnaire on their demographic details and physical activity status. Body anthropometry of the participants was measured and their blood collected for biochemical analysis. Results showed that a significant proportion of the Malaysian Chinese and Malay men had suboptimal bone health indicated by calcaneal speed of sound and vitamin D status. Age-related decline of the calcaneal speed of sound in these men was gradual and biphasic without ethnic difference. Body anthropometry such as height, weight, body mass index, and body fat percentage contributed to the variation of the calcaneal speed of sound in Malaysian men. Age-related changes in testosterone, insulin-like growth factor 1, and thyroid stimulating hormone also influenced the calcaneal speed of sound in these men. This study serves as a reminder that male osteoporosis in Malaysia should be an issue of concern. It is also a basis for a more comprehensive study on bone health in men in the future.

  9. Lessons from the Bone Chapter of the Malaysian Aging Men Study

    Science.gov (United States)

    Chin, Kok-Yong; Wan Ngah, Wan Zurinah; Ima-Nirwana, Soelaiman

    2016-01-01

    Male osteoporosis in Malaysia is a largely neglected problem. Therefore, a bone health study in men using quantitative ultrasonometry was launched as part of the Malaysian Aging Men Study in 2009–2012. This review aimed to summarize the findings of the aforementioned bone health study. The study examined the bone health of Chinese and Malaysian men aged 20 years and above living in Kuala Lumpur using a quantitative ultrasound device. Participants answered a questionnaire on their demographic details and physical activity status. Body anthropometry of the participants was measured and their blood collected for biochemical analysis. Results showed that a significant proportion of the Malaysian Chinese and Malay men had suboptimal bone health indicated by calcaneal speed of sound and vitamin D status. Age-related decline of the calcaneal speed of sound in these men was gradual and biphasic without ethnic difference. Body anthropometry such as height, weight, body mass index, and body fat percentage contributed to the variation of the calcaneal speed of sound in Malaysian men. Age-related changes in testosterone, insulin-like growth factor 1, and thyroid stimulating hormone also influenced the calcaneal speed of sound in these men. This study serves as a reminder that male osteoporosis in Malaysia should be an issue of concern. It is also a basis for a more comprehensive study on bone health in men in the future. PMID:27231930

  10. Studies on 99Tcm-sulfur colloid bone marrow scintigraphy in myeloproliferative disorders

    International Nuclear Information System (INIS)

    Objective: To discuss the imaging features and changing patterns of bone marrow scintigraphy in myeloproliferative disorders (MPD) as well as its clinical significance. Methods: Bone marrow scintigraphy using 99Tcm-sulfur colloid 370-550 MBq was performed on 85 MPD patients, including 40 cases of idiopathic myelofibrosis (IMF), 15 of polycythemia vera (PV), 5 of essential thrombocythaemia (ET), 30 of chronic granulocytic leukemia. Also, 40 cases of myelodysplastic syndromes (MDS) were observed in this study. Results: Abnormal bone marrow imaging was found in 88.2% of the 85 patients. The suppression rate of central bone marrow (CBM) and expansion rate of peripheral bone marrow (PBM) in these MPD patients were 61.2% and 56.5%, respectively. The imaging patterns was classified into three types according to the distribution and activity of bone marrow. 1) reduced imaging (31.8%); 2) increased and expanded imaging (27.1%); 3) depressed and expanded imaging (29.4%). Splenomegaly with minimal residual marrow activity was typical for late stages of MPD. Expansion of PBM was the further feature, but of no major importance for improving hematopoiesis of MPD, and it tended to retract during clinical recovery in chronic granulocytic leukemia (CGL). With expanding PBM, unmatched peripheral blood decreasing was found in MDS. The expansion pattern of PBM in different MPD was of relatively definite features. Conclusions: The imaging pattern of bone marrow was correlated with blood work-up data and clinical course or stages of MPD. Bone marrow scintigraphy may be proven useful in differential diagnosis and evaluation of clinical staging and prognosis of MPD

  11. Preclinical evaluation of natural antioxidants for development of radioprotector

    International Nuclear Information System (INIS)

    Whole body gamma ray exposure is harmful to all organs and systems. Various health effects depend on the radiation dose and dose rate and nature of exposure. Natural antioxidants have desired properties for development of radioprotector. However poor bioavailability and relatively low efficacy require high dose for intended applications. Selection of appropriate antioxidant is an important step for undertaking detailed preclinical evaluation in recommended animal models. Our focus is on natural antioxidants for development of radioprotector. We have performed extensive studies on selection of antioxidants using standard assay methods and during the course of these studies we have modified a number of assays. A number of antioxidants were considered for screening of potential radioprotectors. The antioxidants studied are available commercially as chemically pure compound. The outcome was selection of sesamol, component of sesame oil. Toxicity studies were carried out using OECD 423 toxicity guideline and undertaken efficacy studies in C57BL/6 mice and compared with another antioxidant melatonin. Sesamol (250 mg/kg body weight) has shown survival about 76% which was comparable to 86% with melatonin at lethal radiation dose. Further evaluation studies have been performed using radiation doses at LD50/30 and sub lethal range and the antioxidant dose was also lowered. Sesamol has increased antioxidant level in mice, lowered radiation induced damages in radiosensitive organs, facilitated recovery of haematopoietic and gastrointestinal systems. Sesamol also provided protection in germs cells. Bacterial translocation from GI in irradiated mice was also inhibited in the presence of sesamol. Chromosomal aberrations and micronuclei formation were lowered in bone marrow of mice and in human peripheral blood lymphocytes. Interestingly, both the antioxidants are from different origin but demonstrated similar trend in all measured parameters. Pharmacokinetic studies are in

  12. Further studies on the intermediary metabolism of bone in vitro and a monoclonal cell line (MMB-1) derived from bone: effects of parathyroid hormone and acetazolamide

    International Nuclear Information System (INIS)

    The mechanism/mechanisms by which PTH affects Ca homeostasis between blood and bone have not been clearly established. Most studies of metabolic acid production in bone took place during the late 1950s and early 1960s. Since that time, assay techniques for metabolic acid production have been improved for greater sensitivity, more has been learned as to how PTH mediates its cellular responses, and techniques for cell isolation and culture have dramatically improved. These improvements have made possible new approaches to the study of short term effects of PTH on metabolic acid production in bone. Chapter 1 explores the potential of bone to utilize substrates other than glucose for metabolic energy transfer. Chapter 2 characterizes glucose metabolism in mouse calvaria in vitro and explores effects of PTH, acetazolamide, and C1 13,850 on calvaria oxidative metabolism. Chapter 3 describes PTH effects on glucose metabolism of MMB-1 cells, a monoclonal cell line reported to possess osteoblast-like characteristics

  13. New method of fixation of in-bone implanted prosthesis

    Directory of Open Access Journals (Sweden)

    Mark Pitkin, PhD

    2013-08-01

    Full Text Available This article presents results on the effectiveness of a new version of the titanium porous composite skin and bone integrated pylon (SBIP. The SBIP is designed for direct skeletal attachment of limb prostheses and was evaluated in a preclinical study with three rabbits. In accordance with the study protocol, a new version of the pylon (SBIP-3 was implanted into the hind leg residuum of three rabbits. The SBIP-3 has side fins that are designed to improve the bond between the bone and pylon. The fins are positioned inside two slots precut in the bone walls; their length can be adjusted to match the thickness of the bone walls. After 13 (animal 1 or 26 (animals 2 and 3 wk, the animals were sacrificed and samples collected for histopathological analysis. The space between the fins and the bone into which they were fit was filled with fibrovascular tissue and woven bone. No substantial inflammation was found. We suggest that if further studies substantiate the present results, the proposed method can become an alternative to the established technique of implanting prostheses into the medullary canal of the hosting bone.

  14. Improving Bone Microarchitecture in Aging with Diosgenin Treatment: A Study in Senescence-Accelerated OXYS Rats.

    Science.gov (United States)

    Tikhonova, Maria A; Ting, Che-Hao; Kolosova, Nataliya G; Hsu, Chao-Yu; Chen, Jian-Horng; Huang, Chi-Wen; Tseng, Ging-Ting; Hung, Ching-Sui; Kao, Pan-Fu; Amstislavskaya, Tamara G; Ho, Ying-Jui

    2015-10-31

    Osteoporosis is a major disease associated with aging. We have previously demonstrated that diosgenin prevents osteoporosis in both menopause and D-galactose-induced aging rats. OXYS rats reveal an accelerated senescence and are used as a suitable model of osteoporosis. The aim of the present study was to analyze microarchitecture and morphological changes in femur of OXYS rats using morphological tests and microcomputed tomography scanning, and to evaluate the effects of oral administration of diosgenin at 10 and 50 mg/kg/day on femur in OXYS rats. The result showed that, compared with age-matched Wistar rats, the femur of OXYS rats revealed lower bone length, bone weight, bone volume, frame volume, frame density, void volume, porosity, external and internal diameters, cortical bone area, BV/TV, Tb.N, and Tb.Th, but higher Tb.Sp. Eight weeks of diosgenin treatment decreased porosity and Tb.Sp, but increased BV/TV, cortical bone area, Tb.N and bone mineral density, compared with OXYS rats treated with vehicle. These data reveal that microarchitecture and morphological changes in femur of OXYS rats showed osteoporotic aging features and suggest that diosgenin may have beneficial effects on aging-induced osteoporosis. PMID:26387656

  15. Bone healing in titanium and zirconia implants surface: a pilot study on the rabbit tibia

    Directory of Open Access Journals (Sweden)

    Mariza Akemi Matsumoto

    2013-06-01

    Full Text Available Introduction: Zirconia has been considered an alternative material to titanium for implant manufacturing, however the mechanisms regarding to bone healing in presence of zirconia implants remains poorly known. Objective: The objective of the investigation was to evaluate the bone healing surrounding titanium and zirconia implants in rabbits after 7, 14, 30, 45 and 60 days of implant placement through histological evaluation. Material and methods: Fifteen rabbits were used in this study and randomly subdivided into 5 groups, according to experimental periods. Titanium and zirconia implants were inserted into the right and left tibia, respectively. After healing periods of 7, 14, 30, 45 and 60 days, animals were euthanatized, the implants were removed and the samples were submitted to histological procedures. Results: Our histological results demonstrated similar bone healing surrounding titanium and zirconia implants after 7, 14 and 30 days after implant placement. After 45 days, a trend towards to earlier bone maturation was detected, remaining after 60 days. Inflammatory infiltrate, bone resorption and foreign body reaction were not observed in any periods and groups evaluated. Conclusion: Our findings demonstrated that zirconia and titanium presented a similar pattern of bone healing.

  16. Scanning electron microscope studies of bone samples: Influence of simulated microgravity

    Science.gov (United States)

    Mehta, Rahul; Chowdhury, Parimal; Ali, Nawab

    2007-08-01

    A scanning electron microscope (SEM) with backscatter and secondary electron emission detectors plus a Si(Li) detector for photon yield measurements was used to study bone samples from skull and leg of mice and rats. These animals were either suspended by their tail to induce simulated microgravity, characterized as hind-limb suspension (HLS) or not suspended (control). Analyses of the SEM images and energy dispersive spectrometer (EDS) spectra using Si(Li) detector indicate variation in the lattice structures, and in intensities of the characteristics X-rays, produced from the exposed bone surface due to its interaction with the electron beam. Using Flame software, the X-ray spectra were analyzed and normalized ratios of the elements determined. The elemental analysis indicated a variation in the density of calcium, potassium, and oxygen near the knee joints and near the sutures in the skull bones. The comparison of simulated microgravity subjected samples of the rat skull bones with that of the control samples revealed that in the suture region there was a large increase in the ratio of calcium, and to some degree for phosphorus, suggesting simulated microgravity affects distribution of these elements. Elemental composition for control samples with depth (within the cross section of the leg bones) revealed decrease of oxygen and increase of calcium in the first millimeter of the bone depth after which the relative percentage of elements stayed constant.

  17. Clinical study of bone changes after parathyroidectomy among patients maintained by hemodialysis

    International Nuclear Information System (INIS)

    Thirteen patients maintained by hemodialysis with secondary hyperparathyroidism were mainly studied using Tc 99m-MDP bone scintigraphy and lamina dura index (LDI) which was judged by dental films. After parathyroidectomy (PTX), the most prominent change appeared on the calvaria, maxilla, and mandible in scintigrams. Intensity of Tc 99m-MDP accumulation was represented by using a quantitative method of bone-to-soft tissue uptake ratio (4 hr-B/St ratio). 4 hr-B/St ratio gradually decreased and became normal within one and a half years after PTX. The accumulation of Tc 99m-MDP on the calvaria may reveal the status of bone metabolism in the patients with secondary hyperparathyroidism. Also, LDIes gradually decreased during 4 through 6 months after PTX. However it was considered that these indexes might need a long term to return to normal range. We couldn't differenciate which method was superior in the diagnostic value for detecting early skeletal changes between roentogenograms and bone scintigraphy as a indicator of post-PTX bone improvement. However, bone scintigraphy should be added to conventional examinations for following the courses of patients that underwent PTX because this procedure has many other advantages. (author)

  18. Age-related contrast enhancement study of normal bone marrow in lumbar spinal MR imaging

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the degree of contrast enhancement of normal bone marrow in L-spine relating to aging and to determine the range of contrast enhancement in normal bone marrow. We analyzed a total of 120 patients (20 per decade) who had undergone lumbar spinal MRI and who ranged in age from the 2nd decade to more than the 7th. Bone marrow revealed no abnormal pathology. Sagittal T1-weighted spin echo sequences were obtained before and after gadolinium administration. For each sequence, a region of interest was drawn within the L1 vertebral body from the midsagittal slice. Signal intensity (SI) values of each sequence were ascertained and the percentage increase in SI was calculated. After contrast enhancement, lumbar MRI revealed no statistically significant in the percentage increase in SI of normal bone marrow in relation to aging. Most patients (99%) however showed an SI increase of between 10% and 49%. In only four, none of whom were aged over 40, was this increase above 50%. Lumbar MRI, revealed no statistically significant difference in percentage increase in SI in normal bone marrow relating to aging, but when the increase is above 50% in a patient aged over 40, bone marrow pathology should be further investigated

  19. Infrared Spectroscopic Study on the Modified Mechanism of Aluminum-Impregnated Bone Charcoal

    Directory of Open Access Journals (Sweden)

    Hao Li

    2014-01-01

    Full Text Available Fluoride contamination in drinking water is a prominent and widespread problem in many parts of the world. Excessive ingestion of fluoride through water can lead to the high risk of fluorosis in human body. Bone charcoal, with the principal active component of hydroxyapatite, is a frequently used adsorbent for fluoride removal. Many laboratory experiments suggest that the aluminum-impregnated bone charcoal is an effective adsorbent in defluoridation. However, the mechanisms underlying this modification process are still not well understood, which in turn greatly impedes the further studies on other different modified adsorbents. To address this issue, we used the infrared spectroscopy to examine the bone charcoal and the aluminum-impregnated bone charcoal, respectively. The comparative results show that the −OH peak of infrared spectroscopy has been intensified after modification. This significant change helped speculate the modified mechanism of the aluminum-impregnated bone charcoal. In addition, it is found that the hydroxide ion dissociates from hydroxyapatite in the modification process. Such finding implies that the tetrahydroxoaluminate can be combined with the hydroxyapatite and the aluminum ion can be impregnated onto the bone char surface.

  20. Challenges for Preclinical Investigations of Human Biofield Modalities.

    Science.gov (United States)

    Gronowicz, Gloria; Bengston, William; Yount, Garret

    2015-11-01

    Preclinical models for studying the effects of the human biofield have great potential to advance our understanding of human biofield modalities, which include external qigong, Johrei, Reiki, therapeutic touch, healing touch, polarity therapy, pranic healing, and other practices. A short history of Western biofield studies using preclinical models is presented and demonstrates numerous and consistent examples of human biofields significantly affecting biological systems both in vitro and in vivo. Methodological issues arising from these studies and practical solutions in experimental design are presented. Important questions still left unanswered with preclinical models include variable reproducibility, dosing, intentionality of the practitioner, best preclinical systems, and mechanisms. Input from the biofield practitioners in the experimental design is critical to improving experimental outcomes; however, the development of standard criteria for uniformity of practice and for inclusion of multiple practitioners is needed. Research in human biofield studies involving preclinical models promises a better understanding of the mechanisms underlying the efficacy of biofield therapies and will be important in guiding clinical protocols and integrating treatments with conventional medical therapies. PMID:26665042

  1. Study of new sheep bone and Zn/Ca ratio around TiAlV screw: PIXE-RBS analysis

    International Nuclear Information System (INIS)

    This study reports on in vivo particle induced X-ray emission (PIXE) measurements combined with Rutherford backscattering spectroscopy (RBS) analyses of new remodeled sheep bone formed around TiAlV screws. The implants (screws) were anodized by a modified TiMaxTM process. The interface between the implant and the bone was carefully investigated. [Zn]/[Ca] in-depth composition profiles as well as Ca, Fe elemental maps were recorded. The thickness of new bone formed around the screw reached 300-400 μm. Osteon and Osteoid phases were identified in the new bone. A higher [Zn]/[Ca] ratio was observed in the new bone as compared to the mature bone. Blood vessels were observed in the bone in close contact with the screw. This study shows the potential of ion beam analysis for biological and biomedical characterization

  2. Pre-clinical testing of a phased array ultrasound system for MRI-guided noninvasive surgery of the brain-A primate study

    International Nuclear Information System (INIS)

    MRI-guided and monitored focused ultrasound thermal surgery of brain through intact skull was tested in three rhesus monkeys. The aim of this study was to determine the amount of skull heating in an animal model with a head shape similar to that of a human. The ultrasound beam was generated by a 512 channel phased array system (Exablate[reg] 3000, InSightec, Haifa, Israel) that was integrated within a 1.5-T MR-scanner. The skin was pre-cooled by degassed temperature controlled water circulating between the array surface and the skin. Skull surface temperature was measured with invasive thermocouple probes. The results showed that by applying surface cooling the skin and skull surface can be protected, and that the brain surface temperature becomes the limiting factor. The MRI thermometry was shown to be useful in detecting the tissue temperature distribution next to the bone, and it should be used to monitor the brain surface temperature. The acoustic intensity values during the 20 s sonications were adequate for thermal ablation in the human brain provided that surface cooling is used

  3. Pre-clinical testing of a phased array ultrasound system for MRI-guided noninvasive surgery of the brain-A primate study

    Energy Technology Data Exchange (ETDEWEB)

    Hynynen, Kullervo [Department of Radiology, Brigham and Women' s Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115 (United States)]. E-mail: kullervo@bwh.harvard.edu; McDannold, Nathan [Department of Radiology, Brigham and Women' s Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115 (United States); Clement, Greg [Department of Radiology, Brigham and Women' s Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115 (United States); Jolesz, Ferenc A. [Department of Radiology, Brigham and Women' s Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115 (United States); Zadicario, Eyal [InSightec, Inc., Haifa (Israel); Killiany, Ron [Boston University, Boston, MA (United States); Moore, Tara [Boston University, Boston, MA (United States); Rosen, Douglas [Boston University, Boston, MA (United States)

    2006-08-15

    MRI-guided and monitored focused ultrasound thermal surgery of brain through intact skull was tested in three rhesus monkeys. The aim of this study was to determine the amount of skull heating in an animal model with a head shape similar to that of a human. The ultrasound beam was generated by a 512 channel phased array system (Exablate[reg] 3000, InSightec, Haifa, Israel) that was integrated within a 1.5-T MR-scanner. The skin was pre-cooled by degassed temperature controlled water circulating between the array surface and the skin. Skull surface temperature was measured with invasive thermocouple probes. The results showed that by applying surface cooling the skin and skull surface can be protected, and that the brain surface temperature becomes the limiting factor. The MRI thermometry was shown to be useful in detecting the tissue temperature distribution next to the bone, and it should be used to monitor the brain surface temperature. The acoustic intensity values during the 20 s sonications were adequate for thermal ablation in the human brain provided that surface cooling is used.

  4. Clinical study of the alveolar bone height for the dental implant using preoperative computed tomographic examination

    International Nuclear Information System (INIS)

    CT examination is useful for preoperative dental implant, and many studies of concerning clinical studies using CT images have been reported. However, there are few reports comparing alveolar bone heights among age groups of many cases. The purpose of this study was to evaluate the clinical studies of preoperative CT examinations for alveolar bone heights and patient ages at our department of radiology using 64 multi-detector row CT. The subjects consisted of 5174 regions in 1312 (425 males and 887 females, mean age 55.5 yrs, 16-86 yrs) cases of preoperative CT examinations, between April 2006 and December 2007. CT machine used was the Aquilion TM64 (Toshiba Medical Systems, Japan), and the workstation used was the ZIOSTATION (ZIOSOFT, Japan). All of CT examinations were performed the position of implant placement and disease examined from CT findings. Alveolar bone heights for dental implants were examined from the CT images. For the maxilla, the alveolar bone height was the distance from the alveolar crest to the base of the nasal cavity, or the base of the maxillary sinus. For the mandible, the alveolar bone height is the distance from the alveolar crest and the upper wall of the mandibular canal, or the distance between the alveolar crest and inferior border of mandible. The numbers of the implant position were 955 site for the first molar of the mandible (the average alveolar bone height is 13.9 mm), 652 site for the second molar of the mandible (12.8 mm), and 567 site for the first molar of the maxilla (6.8 mm). In conclusion, the position where implant were to placed the most was the first molar of the mandible, and it's alveolar bone height got lower with age for women. It is over 60% of the maxillary molar area were lower 8 mm, so some kind of osteogenetic treatment was required in many cases, and hence we reassured the importance of CT. (author)

  5. The application of selective reaction monitoring confirms dysregulation of glycolysis in a preclinical model of schizophrenia

    OpenAIRE

    Martins-de-Souza Daniel; Alsaif Murtada; Ernst Agnes; Harris Laura W; Aerts Nancy; Lenaerts Ilse; Peeters Pieter J; Amess Bob; Rahmoune Hassan; Bahn Sabine; Guest Paul C

    2012-01-01

    Abstract Background Establishing preclinical models is essential for novel drug discovery in schizophrenia. Most existing models are characterized by abnormalities in behavioral readouts, which are informative, but do not necessarily translate to the symptoms of the human disease. Therefore, there is a necessity of characterizing the preclinical models from a molecular point of view. Selective reaction monitoring (SRM) has already shown promise in preclinical and clinical studies for multiple...

  6. Periodontitis and bone mineral density among pre and post menopausal women: A comparative study

    Directory of Open Access Journals (Sweden)

    Suresh Snophia

    2010-01-01

    Full Text Available Aim: The aim of the study was to assess the relationship between bone mineral density and periodontitis in premenopausal and postmenopausal women. Materials and Methods: Twenty women between the age group of 45-55 years were selected for this study. Ten premenopausal women with healthy periodontium constituted the control group and 10 postmenopausal women with ≥2mm of clinical attachment loss in> 30% of sites constituted the study group. All patients were assessed for plaque index, probing depth and clinical attachment loss. Radiographs (six IOPA and two posterior bitewing were taken and assessed for interproximal alveolar bone loss. The patients were scanned to assess the bone mineral density of lumbar spine (L2 and femur using dual energy X-ray absorptiometry (DEXA. Results: The bone mineral densities of lumbar spine (L2 and femur were significantly lower in the study group than the control group. Osteopenia of the lumbar spine and femur was observed in 60% whereas osteoporosis of lumbar spine was observed in 30% of cases in study group. Conclusion: Increased proportion of osteopenia and osteoporosis cases of lumbar spine and femur in postmenopausal women with periodontitis suggests that there is association between bone mineral density and periodontitis.

  7. Use of Bone Marrow derived Stem Cells in patients with Cardiovascular Disorders

    OpenAIRE

    Abraham S; Naveen AT; Kirtivasan V; Prasad GN; Karthik Vaidyanathan; Rajesh V.; Madhusankar N; Cherian KM

    2007-01-01

    Patients with end stage heart failure have very few treatment options. The long waiting times for transplant and the complications associated with immunosuppression has led to the search for alternatives. Subsequent to the isolation and characterization of stem cells, tremendous advances have been made and the safety and feasibility of autologous bone marrow derived stem cells has been proven in preclinical studies. Clinical studies have also shown mobilized cells repair the infracted heart, ...

  8. Assessment of bone marrow inflammation in patients with myelofibrosis: an {sup 18}F-fluorodeoxyglucose PET/CT study

    Energy Technology Data Exchange (ETDEWEB)

    Derlin, Thorsten [Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany); University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Alchalby, Haefaa; Triviai, Ioanna; Kroeger, Nicolaus [University Medical Center Hamburg-Eppendorf, Clinic for Stem Cell Transplantation, Hamburg (Germany); Bannas, Peter [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Veldhoen, Simon [University Medical Center Wuerzburg, Department of Diagnostic and Interventional Radiology, Wuerzburg (Germany); Apostolova, Ivayla [Otto-von-Guericke University, Department of Radiology and Nuclear Medicine, Magdeburg (Germany); Bengel, Frank M. [Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany)

    2015-04-01

    Myelofibrosis is a haematopoietic stem cell neoplasm characterized by bone marrow inflammation, reactive marrow fibrosis and extramedullary haematopoiesis. The aim of this study was to determine if {sup 18}F-FDG PET/CT can be used to noninvasively visualize and quantify the extent and activity of bone marrow involvement. In 30 patients, the biodistribution of {sup 18}F-FDG was analysed by measuring the standardized uptake value in the bone marrow compartment and spleen. Imaging findings were compared with laboratory, cytogenetic and histopathological data. Retention of {sup 18}F-FDG was observed in bone marrow and spleen. Bone marrow involvement varied, ranging from mildly increased uptake in the central skeleton to extensive uptake in most parts of the skeleton. The extent of bone marrow involvement decreased over time from initial diagnosis (r{sub s} = -0.43, p = 0.019). Metabolic activity of the bone marrow decreased as the histopathological grade of fibrosis increased (r{sub s} = -0.37, p = 0.04). There was a significant positive correlation between the metabolic activity of the bone marrow and that of the spleen (p = 0.04). {sup 18}F-FDG PET/CT is as a promising technique for the quantitation of bone marrow inflammation in myelofibrosis. Our data indicate that the intensity of bone marrow {sup 18}F-FDG uptake decreases as bone marrow fibrosis increases. Further evaluation in prospective studies is required to determine the potential clinical impact and prognostic significance of PET. (orig.)

  9. FUNCTIONAL OUTCOME OF ACCELERATED REHABILITATION IN ARTHROSCOPIC ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION WITH BONE PATELLAR TENDON BONE GRAFT A PROSPECTIVE STUDY

    Directory of Open Access Journals (Sweden)

    Hiranyakumar

    2016-03-01

    Full Text Available INTRODUCTION An ideal rehabilitation program post anterior cruciate ligament reconstruction enables an individual to return to pre injury levels at a faster rate with minimal to no risk of reinjury to the graft. Rehabilitation protocols have changed considerably over time in the past. It has become “aggressive”, meaning an intensive rehabilitation which includes greater variety of exercises and sports related training. AIM OF THE STUDY The aim of our study is to assess the outcome of accelerated rehabilitation post anterior cruciate ligament (ACL reconstruction. METHODOLOGY 106 patients were operated by a single surgeon underwent arthroscopic anterior cruciate ligament reconstruction using bone patella tendon bone graft and partial meniscectomy for associated meniscal tear. Patients were put on an accelerated rehabilitation protocol designed in our institute on first post-operative day, under the guidance of a physical therapist in consultation with the operated surgeon. Patients were followed up at 3 weeks, 6 months and 9 months, post onset of rehabilitation, patients were assessed using KT1000 Arthrometer and Lysholm knee scoring system. RESULTS Out of 106 patients, who were selected, 96(91% were males and 10(9% were females. The mean pre-operative Lysholm score was 55.09. Post operatively, while on accelerated rehabilitation program the Lysholm scores were 69.73 at 3 weeks, 89.13 at 6 months and 89.19 at 9 months. In our pre-operative evaluation mean KT 1000 arthrometer score was 10.53 and post-operative at six months was 3.49. At nine months 105 patients had excellent results whereas 1 patient had good result. CONCLUSION Accelerated rehabilitation protocol enables the patient to functionally recover faster to pre injury levels. A rehabilitation protocol for 6 months is sufficient in enabling a patient to get back to pre-injury levels. Functional outcome is the same with or without associated meniscal injuries.

  10. Forearm bone mineral density in familial hypocalciuric hypercalcemia and primary hyperparathyroidism: a comparative study.

    Science.gov (United States)

    Isaksen, Troels; Nielsen, Christian Stoltz; Christensen, Signe Engkjær; Nissen, Peter H; Heickendorff, Lene; Mosekilde, Leif

    2011-10-01

    Studies have shown that cancellous bone is relatively preserved in primary hyperparathyroidism (PHPT), whereas bone loss is seen in cortical bone. Familial hypocalciuric hypercalcemia (FHH) patients seem to preserve bone mineral in spite of hypercalcemia and often elevated plasma parathyroid hormone (PTH). The objective of this study was to compare total and regional forearm bone mineral density (BMD) in patients with PHPT and FHH and to examine if differences can be used to separate the two disorders. We included 63 FHH, and 121 PHPT patients in a cross-sectional study. We performed dual-energy X-ray absorptiometry scans of the forearm, hip and lumbar spine and measured a number of biochemical variables. PTH patients had significantly lower Z-scores in all parts of the forearm compared to FHH. This was also the case after adjustment for body mass index. When stratifying for age, gender and PTH, T-scores were still significantly lower in PHPT patients than in FHH patients at the total, the mid and the ultradistal forearm, but not at the proximal 1/3 forearm. In a multiple regression analysis BMD Z-score was lower in PHPT compared to FHH at the total forearm, the mid forearm and the ultradistal forearm but not the proximal forearm when adjusting for biochemical variables including PTH, 1,25(OH)(2)D and Ca(2+). These observations support that inactivating mutations in the CASR gene in bone cells in FHH may protect against forearm bone loss. Differences between the two groups in total or regional forearm BMD were inferior to the calcium/creatinine clearance ratio as a diagnostic tool to separate FHH from PHPT. PMID:21785908

  11. Nutritive orifice and nutritive channel in the long bones of the extremities of newborn children - roentgenanatomical and roentgenometric study

    International Nuclear Information System (INIS)

    A roentgenoanatomic and roentgenometric study was performed on 1239 bones from the limbs of dead newborn children from both sexes. Frontally made roentgenographies were used of the following kinds of bones: shoulder bones (210), cubit (222), radius (223), thigh bone (201), big tibia (192), and small tibia (191). The characteristics of the gastrointestinal tract for those bones are described, and measure the distance of its opening from the proximal and distal end along the bone, according to Pyle's method. The author offers the usage of the results as a norm for characterising the newborn children in the People's Republic of Bulgaria. The establishment of deviations in the characteristics of the gastrointestinal tract and its opening in the long bones, will enable the early diagnostic of congenital systematic diseases of the skeleton, as well as in forensic medicine in view of identification. (author)

  12. Discontinuous release of bone morphogenetic protein-2 loaded within interconnected pores of honeycomb-like polycaprolactone scaffold promotes bone healing in a large bone defect of rabbit ulna.

    Science.gov (United States)

    Bae, Ji-Hoon; Song, Hae-Ryong; Kim, Hak-Jun; Lim, Hong-Chul; Park, Jung-Ho; Liu, Yuchun; Teoh, Swee-Hin

    2011-10-01

    The choice of an appropriate carrier and its microarchitectural design is integral in directing bone ingrowth into the defect site and determining its subsequent rate of bone formation and remodeling. We have selected a three-dimensional polycaprolactone (PCL) scaffold with an interconnected honeycomb-like porous structure to provide a conduit for vasculature ingrowth as well as an osteoconductive pathway to guide recruited cells responding to a unique triphasic release of osteoinductive bone morphogenetic proteins (BMP) from these PCL scaffolds. We hypothesize that the use of recombinant human bone morphogenetic protein 2 (rhBMP2)-PCL constructs promotes rapid union and bone regeneration of a large defect. Results of our pilot study on a unilateral 15 mm mid-diaphyseal segmental rabbit ulna defect demonstrated enhanced bone healing with greater amount of bone formation and bridging under plain radiography and microcomputed tomography imaging when compared with an empty PCL and untreated group after 8 weeks postimplantation. Quantitative measurements showed significantly higher bone volume fraction and trabecular thickness, with lower trabecular separation in the rhBMP2-treated groups. Histology evaluation also revealed greater mature bone formation spanning across the entire scaffold region compared with other groups, which showed no bone regeneration within the central defect zone. We highlight that it is the uniqueness of the scaffold having a highly porous network of channels that promoted vascular integration and allowed for cellular infiltration, leading to a discontinuous triphasic BMP2 release profile that mimicked the release profile during natural repair mechanisms in vivo. This study serves as preclinical evidence demonstrating the potential of combining osteoinductive rhBMP2 with our PCL constructs for the repair of large defects in a large animal model. PMID:21682591

  13. A comparative study of zirconium and titanium implants in rat: osseointegration and bone material quality.

    Science.gov (United States)

    Hoerth, Rebecca M; Katunar, María R; Gomez Sanchez, Andrea; Orellano, Juan C; Ceré, Silvia M; Wagermaier, Wolfgang; Ballarre, Josefina

    2014-02-01

    Permanent metal implants are widely used in human medical treatments and orthopedics, for example as hip joint replacements. They are commonly made of titanium alloys and beyond the optimization of this established material, it is also essential to explore alternative implant materials in view of improved osseointegration. The aim of our study was to characterize the implant performance of zirconium in comparison to titanium implants. Zirconium implants have been characterized in a previous study concerning material properties and surface characteristics in vitro, such as oxide layer thickness and surface roughness. In the present study, we compare bone material quality around zirconium and titanium implants in terms of osseointegration and therefore characterized bone material properties in a rat model using a multi-method approach. We used light and electron microscopy, micro Raman spectroscopy, micro X-ray fluorescence and X-ray scattering techniques to investigate the osseointegration in terms of compositional and structural properties of the newly formed bone. Regarding the mineralization level, the mineral composition, and the alignment and order of the mineral particles, our results show that the maturity of the newly formed bone after 8 weeks of implantation is already very high. In conclusion, the bone material quality obtained for zirconium implants is at least as good as for titanium. It seems that the zirconium implants can be a good candidate for using as permanent metal prosthesis for orthopedic treatments. PMID:24170339

  14. STUDY OF AN ASSESSMENT OF THE FATE OF CALCIUM HYDROXY APATITE BLOCK WITH CORTICO CANCELLOUS BONE GRAFT USED IN COMMUNITED FRACTURES OF LONG BONE OF LOWER LIMB

    Directory of Open Access Journals (Sweden)

    Ahmad

    2015-03-01

    Full Text Available INTRODUCTION: In recent years there has been an increasing interest in biologically active calcium phosphate ceramic materials for orthopaedic application. A number of materials from human, animal or non - biological sources have been used to fill defects with or without additional autogenus bone. It would be ideal to have bone substitute w hich is easily fabricated and preserved, is biocompatible with bone, and is biodegradable. The calcium phosphate system, and in particular hydroxyappatite (HA, has long been the subject of intensive investigation. MATERIAL AND METHODS: This observational two year study was undertaken at S.N. Medical College and Hospital, Agra (U.P.. The patients having the comminuted fracture of the long bone of lower limbs were treated with autogenus bone graft and calcium hydroxy Apatite bone block. Functional results w ere presented according to Klemm and Borner (1986 criteria. RESULTS: The total cases studied were 25 out of which 21 cases had fracture of both bones of leg and 4 were of fracture femur. The patients were aged between 15 to 70 years. Most of the patients were males and the common mode of injury was road traffic accident. An excellent result were seen in the majority 9(36% of patients while 8(32% patients showed a good result and 6(24% showed a fair result. 17(68% patients had compound fracture while 8( 32% patients were having closed fracture. CONCLUSION: Calcium Hydroxy Apatite is a suitable alternative to bone graft. There was no evidence of any foreign body reaction and infection at the Calcium Hydroxy Apatite implanted site. There was satisfactory h ealing of all the comminuted fractures. The movement of adjacent joints was nearly normal. No refracture was observed on follow up.

  15. Evaluation Of Microdosing Strategies For Studies In Preclinical Drug Development: Demonstration Of Linear Pharmacokinetics In Dogs Of A Nucleoside Analogue Over A 50-Fold Dose Range

    Energy Technology Data Exchange (ETDEWEB)

    Sandhu, P; Vogel, J S; Rose, M J; Ubick, E A; Brunner, J E; Wallace, M A; Adelsberger, J K; Baker, M P; Henderson, P T; Pearson, P G; Baillie, T A

    2004-04-22

    The technique of accelerator mass spectrometry (AMS) was validated successfully and utilized to study the pharmacokinetics and disposition in dogs of a preclinical drug candidate (Compound A), after oral and intravenous administration. The primary objective of this study was to examine whether Compound A displayed linear kinetics across sub-pharmacological (microdose) and pharmacological dose ranges in an animal model, prior to initiation of a human microdose study. The AMS-derived disposition properties of Compound A were comparable to data obtained via conventional techniques such as LC-MS/MS and liquid scintillation counting analyses. Thus, Compound A displayed multiphasic kinetics and possessed low plasma clearance (4.4 mL/min/kg), a long terminal elimination half-life (19.4 hr) and high oral bioavailability (82%). Currently there are no published comparisons of the kinetics of a pharmaceutical compound at pharmacological versus sub-pharmacological doses employing microdosing strategies. The present study thus provides the first description of the pharmacokinetics of a drug candidate assessed under these two dosing regimens. The data demonstrated that the pharmacokinetic properties of Compound A were similar following dosing at 0.02 mg/kg as at 1 mg/kg, indicating that in the case of Compound A, the kinetics of absorption, distribution and elimination in the dog appear to be linear across this 50-fold dose range. Moreover, the exceptional sensitivity of AMS provided a pharmacokinetic profile of Compound A, even following a microdose, which revealed aspects of the disposition of this agent that were inaccessible by conventional techniques. The applications of accelerator mass spectrometry (AMS) are broad ranging and vary from studying environmental and ecological issues such as the isotopic composition of the atmosphere, soil and water (Hughen et al., 2000; Beck et al., 2001; Keith-Roach et al., 2001; Mironov et al., 2002), to archaeology and volcanology

  16. Study on de novo collagen biosynthesis and degradation markers of bone

    International Nuclear Information System (INIS)

    This investigation was carried out to study the performance of de novo biochemical markers of serum pro collagen type-1 amino terminal extension (PINP), as a marker of collagen biosynthesis, and urinary collagen crosslink free deoxypyridinoline (DPD) as a marker of collagen degradation. Moreover, urinary calcium C Ca) and inorganic phosphorus (P), as markers of bone demineralization, in addition to urinary creatinine (Cr), to reflect status of renal function, were also studied in order to assess the activity of bone turnover in osteoporotic (OST), postmenopausal (POST), peri menopausal(PERI), premenopausal (PRE) women and also in young adult (YON) ones. The obtained results showed that urinary creatinine levels were within the normal ranges in all women even in the elderly osteoporotic and postmenopausal women. Serum PINP did not reflect osteoblastic activity. Urinary DPD proved to be a good marker in monitoring the postmenopausal bone resorption and urinary Ca was a reliable marker for bone loss in osteoporosis and bone turnover in the postmenopausal status

  17. Pilot study of bone mineral density in breast cancer patients treated with adjuvant chemotherapy

    Science.gov (United States)

    Headley, J. A.; Theriault, R. L.; LeBlanc, A. D.; Vassilopoulou-Sellin, R.; Hortobagyi, G. N.

    1998-01-01

    The objective of this cross-sectional study was to determine lumbar spine bone mineral density (BMD) in breast cancer patients previously treated with adjuvant chemotherapy. Sixteen of 27 patients who received adjuvant chemotherapy became permanently amenorrheic as a result of chemotherapy. BMD was measured at the lumbar spine using dual energy X-ray absorptiometry (DEXA). Chemotherapy drugs and dosages along with a history of risk factors for reduced bone density including activity level, tobacco and/or alcohol use, metabolic bone disease, family history, and hormone exposure were identified. Results showed that women who became permanently amenorrheic as a result of chemotherapy had BMD 14% lower than women who maintained menses after chemotherapy. Chemotherapy-treated women who maintained ovarian function had normal BMD. This study suggests that women who have premature menopause as a result of chemotherapy for breast cancer are at increased risk of bone loss and may be at risk for early development of osteoporosis. Women who maintain menses do not appear to be at risk for accelerated trabecular bone loss.

  18. Mechanics of bone/PMMA composite structures: an in vitro study of human vertebrae.

    Science.gov (United States)

    Race, Amos; Mann, Kenneth A; Edidin, Avram A

    2007-01-01

    The goal of this study was to provide material property data for the cement/bone composite resulting from the introduction of PMMA bone cement into human vertebral bodies. A series of quasistatic tensile and compressive mechanical tests were conducted using cement/bone composite structures machined from cement-infiltrated vertebral bodies. Experiments were performed both at room temperature and at body temperature. We found that the modulus of the composite structures was lower than bulk cement (p<0.0001). For compression at 37( composite function)C: composite =2.3+/-0.5GPa, cement =3.1+/-0.2GPa; at 23( composite function)C: composite =3.0+/-0.3GPa, cement =3.4+/-0.2GPa. Specimens tested at room temperature were stiffer than those tested at body temperature (p=0.0004). Yield and ultimate strength factors for the composite were all diminished (55-87%) when compared to cement properties. In general, computational models have assumed that cement/bone composite had the same modulus as cement. The results of this study suggest that computational models of cement infiltrated vertebrae and cemented arthroplasties could be improved by specifying different material properties for cement and cement/bone composite. PMID:16797554

  19. Retrospective study on bone-level and soft-tissue-level cylindrical implants.

    Science.gov (United States)

    Lopez, M A; Andreasi Bassi, M; Confalone, L; Gaudio, R M; Lombardo, L; Lauritano, D

    2016-01-01

    The purpose of this prospective clinical study was to evaluate the survival rate (SVR - i.e. fixtures still in place at the end of the observation period) and success rate (SCR - i.e. bone resorption around implant neck) of two cylindrical implant systems. Both systems were equipped with a tapered connection, one requiring a bone-level (BL) placement, while the other a soft-tissue-level (STL) placement. In the period between January 1996 and October 2011, a total of 150 implants (76 in females and 74 in males, mean age 60±11 years) were inserted. The mean post-surgical follow-up was 84±47 months. Several parameters were evaluated as potential outcome conditioners: age, gender, diabetes, smoking, periodontitis, type of edentulism, replaced tooth, jaw location (i.e. maxilla or mandible), bone graft, immediate loading, post-extractive, type of prosthesis, implant diameter and length. An SPSS program was used for statistical analysis. Only two fixtures were lost, therefore SVR was 98.7%. SCR, expressed through the mean marginal bone loss, was 92%. The mean peri-implant bone loss was 0.121.47 mm for BL implants and 0.041.3 mm for STL implants. None of the studied variables had a statistical significant impact on SVR or SCR. Cylindrical implants are reliable for oral rehabilitation. PMID:27469547

  20. Study on peripheral expansion of bone marrow in hematologic patients and its clinical application

    International Nuclear Information System (INIS)

    It is found previously that the changing patterns of bone marrow scintigraphy resulting from hematologic disorders were various. This study focused on discussing the imaging features and regularity of expanded peripheral bone marrow (PBM) in some blood diseases as well as their clinical usefulness. Bone marrow scintigraphy with 99mTc-sulfur colloid 370∼550 MBq was performed in 130 cases with different types of blood diseases (iron-deficiency anemia 17 cases, chronic hemolytic 13 cases, aplastic 41 cases; leukemia 37 cases, marrow dyshyperplasia syndrome 22 cases) and various stages of the disease (19 cases). The aspiration in PBM comparing with central bone marrow (CBM) was made in 12 aplastic anemia and 10 leukemia patients. The expansion rate of PBM was 58.5% and the various blood diseases had different expansion regions. Repeated imaging showed that the expanded PBM tended to retract during clinical recovery. Aspiration from the expanding PBM defined more active hematopoiesis and higher count of leukemia blast cells than that from iliac crest. The results indicated the presence of 'focal residual leukemia' (FRL) in PBM of complete remission leukemia patient. The result of this study suggested that the expansion patterns of PBM in various hematologic disorders have definite features, which are helpful for the differential diagnosis, valuable for evaluation of the reserved capability of active marrow and prognosis of the patients according to the further analysis of the PBM state. The bone marrow imaging is also an indispensable technique for finding FRL

  1. FDG PET/CT dataset for navigation on femoral bone: a feasibility study.

    Science.gov (United States)

    Militz, Matthias; Uhde, Jörg; Christian, Georg; Linke, Rainer; Morgenstern, Mario; Hungerer, Sven

    2015-12-01

    FDG PET/CT has become a valuable tool in the diagnosis of the activity of chronic osteomyelitis. The surgical strategy in the treatment of chronic osteomyelitis is the identification of the bone focus and radical debridement of sequesters. The aim of the current study was the registration and use of the FDG PET/CT imaging datasets on a navigation system to provide diagnostic imaging based feedback during surgical procedures. For the present study, FDG PET/CT scans were acquired from artificial bones and cadaver bones with a local focus of activity. The DICOM data sets were merged using a navigation system. The referenced regions of interest were matched with fluoroscopic pictures to register the PET/CT DICOM datasets to the bone and direct visual control. Navigated targeting led to accurate results when verified with fluoroscopic images by targeting previously inserted reference points in artificial and cadaver bone. FDG PET/CT datasets are suitable for navigation and compatible with conventional planning and navigation software. The combination of diagnostic FDG PET/CT imaging with surgical navigation techniques could be a valuable tool for the accurate treatment of chronic osteomyelitis. PMID:26035105

  2. Histological and biomechanical studies of two bone colonizable cements in rabbits.

    Science.gov (United States)

    Lu, J X; About, I; Stephan, G; Van Landuyt, P; Dejou, J; Fiocchi, M; Lemaître, J; Proust, J P

    1999-08-01

    We have developed two colonizable bone cements: the first is a partially resorbable bisphenol-alpha-glycidyl methacrylate (Bis-GMA)-based cement (PRC) and the second is a calcium phosphate cement (CPC). PRC is composed of aluminous silanized ceramic and particles of a bioresorbable polymer embedded in a matrix of Bis-GMA. CPC consisted of tricalcium phosphate, monocalcium phosphate monohydrate, dicalcium phosphate dihydrate, and xanthane. Both cements were implanted into cavities drilled in rabbit femoral and tibial condyles. After 2, 4, 12, and 24 weeks of implantation, histological observations and biomechanical tests were performed. With CPC, a progressive osteointegration with a concomitant biodegradation in the presence of macrophages were observed. The mechanical study revealed a decrease of the compressive strength until the 4th week, followed by a slight increase. There was a general decrease in the elastic modulus with time. Moreover, by week 4, the histological study showed that the new bone was in direct contact with CPC margins. No inflammation was observed during the observation period. With PRC, the osteointegration as well as the biodegradation were slight, but its compressive strength was higher than that of cancellous bone and CPC (p < 0.05) at all observation periods. Its elastic modulus was greater than that of cancellous bone and CPC until the 4th week, then fell under the values of the cancellous bone. PMID:10458273

  3. Autologous cranial particulate bone graft: an experimental study of onlay cranioplasty.

    Science.gov (United States)

    Clune, James E; Mulliken, John B; Glowacki, Julie; Arany, Praveen R; Kulungowski, Ann M; Rogers, Gary F; Greene, Arin K

    2011-01-01

    The purpose of this study was to determine whether particulate bone graft maintains its volume when used for onlay cranioplasty. Twenty-five adult, male, New Zealand white rabbits were divided into 5 groups (n = 5/group). Groups 1 to 3 were controls: group 1, untreated; group 2, sham procedure; and group 3, burring the cortical surface. Group s 4 and 5 had augmentation of the parietal bones with particulate graft harvested from the frontal bone with a brace and bit. The particulate graft was placed on native parietal bone (group 4) or on parietal bone that had been abraded to punctuate bleeding with an electric burr (group 5). Volume maintenance and osseointegration of the grafts were determined by micro-computed tomography and histology. At 16 weeks postoperatively, the mean (SD) volumes of the parietal bones in control groups 1, 2, and 3 were 555.8 (29.2), 550.8 (36.8), and 539.0 (39.0) mm, respectively. Immediately after cranioplasty, the mean (SD) volumes of augmented parietal bone were 846.0 (10.8) mm for group 4 and 831.8 (11.8) mm for group 5. Sixteen weeks postoperatively, 100% of the group 4 grafts had resorbed (551.8 [SD, 24.0] mm), and parietal volume was no different from controls (P = 0.89). Group 5 maintained 54.2% of volume (695.6 [SD, 22.0] mm), which was greater than those of the controls (P < 0.0001). Particulate graft may be used for onlay cranioplasty if the recipient site is burred. Approximately one half of the onlay graft is resorbed, and its original shape is not maintained. PMID:21239926

  4. The Hounsfield value for cortical bone geometry in the proximal humerus - an in vitro study

    International Nuclear Information System (INIS)

    Fractures of the proximal humerus represent a major osteoporotic burden. Recent developments in CT imaging have emphasized the importance of cortical bone thickness distribution in the prevention and management of fragility fractures. We aimed to experimentally define the CT density of cortical bone in the proximal humerus for building cortical geometry maps. With ethical approval, we used ten fresh-frozen human proximal humeri. These were stripped of all soft tissue and high-resolution CT images were then taken. The humeral heads were then subsequently resected to allow access to the metaphyseal area. Using curettes, cancellous bone was removed down to hard cortical bone. Another set of CT images of the reamed specimen was then taken. Using CT imaging software and a CAD interface, we then compared cortical contours at different CT density thresholds to the reference inner cortical contour of our reamed specimens. Working with 3D model representations of these cortical maps, we were able to accurately make distance comparison analyses based on different CT thresholds. We could compute a single closest value at 700 HU. No difference was found in the HU-based contours generated along the 500-900 HU pixels (p = 1.000). The contours were significantly different from those generated at 300, 400, 1,000, and 1,100 HU. A Hounsfield range of 500-900 HU can accurately depict cortical bone geometry in the proximal humerus. Thresholding outside this range leads to statistically significant inaccuracies. Our results concur with a similar range reported in the literature for the proximal femur. Knowledge of regional variations in cortical bone thickness has direct implications for basic science studies on osteoporosis and its treatment, but is also important for the orthopedic surgeon since our decision for treatment options is often guided by local bone quality. (orig.)

  5. The Hounsfield value for cortical bone geometry in the proximal humerus - an in vitro study

    Energy Technology Data Exchange (ETDEWEB)

    Lim Fat, Daren; Kennedy, Jim; Galvin, Rose; O' Brien, Fergal; Mc Grath, Frank; Mullett, Hannan [Royal College of Surgeons in Ireland, Investigations Carried Out at Anatomy Lab, Dublin (Ireland)

    2012-05-15

    Fractures of the proximal humerus represent a major osteoporotic burden. Recent developments in CT imaging have emphasized the importance of cortical bone thickness distribution in the prevention and management of fragility fractures. We aimed to experimentally define the CT density of cortical bone in the proximal humerus for building cortical geometry maps. With ethical approval, we used ten fresh-frozen human proximal humeri. These were stripped of all soft tissue and high-resolution CT images were then taken. The humeral heads were then subsequently resected to allow access to the metaphyseal area. Using curettes, cancellous bone was removed down to hard cortical bone. Another set of CT images of the reamed specimen was then taken. Using CT imaging software and a CAD interface, we then compared cortical contours at different CT density thresholds to the reference inner cortical contour of our reamed specimens. Working with 3D model representations of these cortical maps, we were able to accurately make distance comparison analyses based on different CT thresholds. We could compute a single closest value at 700 HU. No difference was found in the HU-based contours generated along the 500-900 HU pixels (p = 1.000). The contours were significantly different from those generated at 300, 400, 1,000, and 1,100 HU. A Hounsfield range of 500-900 HU can accurately depict cortical bone geometry in the proximal humerus. Thresholding outside this range leads to statistically significant inaccuracies. Our results concur with a similar range reported in the literature for the proximal femur. Knowledge of regional variations in cortical bone thickness has direct implications for basic science studies on osteoporosis and its treatment, but is also important for the orthopedic surgeon since our decision for treatment options is often guided by local bone quality. (orig.)

  6. A Bivariate Whole Genome Linkage Study Identified Genomic Regions Influencing Both BMD and Bone Structure

    OpenAIRE

    Liu, Xiao-Gang; Liu, Yong-Jun; Liu, Jianfeng; Pei, Yufang; Xiong, Dong-Hai; Shen, Hui; Deng, Hong-Yi; Papasian, Christopher J.; Drees, Betty M.; Hamilton, James J.; Recker, Robert R.; Deng, Hong-Wen

    2008-01-01

    Areal BMD (aBMD) and areal bone size (ABS) are biologically correlated traits and are each important determinants of bone strength and risk of fractures. Studies showed that aBMD and ABS are genetically correlated, indicating that they may share some common genetic factors, which, however, are largely unknown. To study the genetic factors influencing both aBMD and ABS, bivariate whole genome linkage analyses were conducted for aBMD-ABS at the femoral neck (FN), lumbar spine (LS), and ultradis...

  7. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  8. Bone Grafts

    Science.gov (United States)

    A bone graft transplants bone tissue. Surgeons use bone grafts to repair and rebuild diseased bones in your hips, knees, spine, and sometimes other bones and joints. Grafts can also repair bone loss caused by some ...

  9. Ramucirumab: preclinical research and clinical development

    Directory of Open Access Journals (Sweden)

    Aprile G

    2014-10-01

    Full Text Available Giuseppe Aprile,1 Erika Rijavec,2 Caterina Fontanella,1 Karim Rihawi,1 Francesco Grossi21Department of Oncology, University Hospital of Udine, Udine, Italy; 2Lung Cancer Unit, National Cancer Institut “San Martino”, Genoa, ItalyAbstract: Ramucirumab (IMC-1121B, LY3009806, a fully humanized monoclonal antibody directed against the extracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2, is a new therapeutic option that selectively inhibits the human VEGFR-2 with a much greater affinity than its natural ligands. Based on the promising results of both preclinical and early clinical studies, ramucirumab has been tested in different tumor types either alone or in combination with chemotherapy. While it has recently been granted its first US Food and Drug Administration approval for use as a single agent in patients with advanced or metastatic gastric cancer or gastroesophageal junction carcinoma, its role for metastatic breast cancer or advanced non-small-cell lung cancer is still debated. The aims of this review are to recall and discuss the most significant preclinical and clinical studies that led to the development of ramucirumab and to present the results of the randomized clinical trials that have tested its efficacy in different malignancies, including gastric and lung cancer. Keywords: ramucirumab, gastric cancer, lung cancer, breast cancer, antiangiogenic

  10. Study of osteoporosis through the measurement of bone mineral density and trace elements

    International Nuclear Information System (INIS)

    The main purpose of this study was to establish a relation, if any, between bone mineral density, BMD, of the healthy Turkish population of the ages between 15 and 50 with social and demographic information, family history of fractures, personal and inherited characteristic, smoking and alcohol habit, history of fertility, level of physical activity, food consumption especially trace elements and other variables. Most of these relations were discussed in the last RCM in San Diego, CA, October 7-10,1996. Since then we have concentrated our work on more BMD and trace element measurements in bone. To this end, bone mineral density measurements, trace element studies, neutron activation analysis, fluoride analysis and atomic absorption analysis were undertaken and resulting data were analysed

  11. Single fraction versus multiple fraction radiotherapy for palliation of painful vertebral bone metastases: A prospective study

    Directory of Open Access Journals (Sweden)

    Dipanjan Majumder

    2012-01-01

    Conclusions: Different fractionation of radiation has same response and toxicity in treatment of vertebral bone metastasis. Single fraction RT may be safely used to treat these cases as this is more cost effective and less time consuming. Studies may be conducted to find out particular subgroup of patients to be benefitted more by either fractionation schedule; however, our study cannot comment on that issue.

  12. Hyperinsulinemia and bone mineral density in an elderly population : The Rotterdam study

    NARCIS (Netherlands)

    Stolk, RP; VanDaele, PLA; Pols, HAP; Burger, H; Hofman, A; Birkenhager, JC; Lamberts, SWJ; Grobbee, DE

    1996-01-01

    We studied the association between insulin and glucose levels and bone mineral density (BMD) in a population based study of 5931 elderly men and women, Serum insulin was measured 2 h after a nonfasting oral glucose load in subjects not using antidiabetes medication, BMD was measured by dual-energy X

  13. A short-term clinical study of marginal bone level change around microthreaded and platform-switched implants

    OpenAIRE

    Yun, Hee-Jung; Park, Jung-Chul; Yun, Jeong-Ho; Jung, Ui-Won; Kim, Chang-Sung; Choi, Seong-Ho; Cho, Kyoo-Sung

    2011-01-01

    Purpose The marginal bone levels around implants following restoration are used as a reference for evaluating implant success and survival. Two design concepts that can reduce crestal bone resorption are the microthread and platform-switching concepts. The aims of this study were to analyze the placement of microthreaded and platform-switched implants and their short-term survival rate, as well as the level of bone around the implants. Methods The subjects of this study were 27 patients (79 i...

  14. Navicular bone position determined by positional MRI: a reproducibility study

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Philip; Nybing, Janus D. [Copenhagen University Hospital Frederiksberg and Bispebjerg, Department of Radiology, Frederiksberg (Denmark); Johannsen, Finn E.; Stallknecht, Sandra E. [Copenhagen University Hospital Bispebjerg, Institute of Sports Medicine Copenhagen, Copenhagen, NV (Denmark); Hangaard, Stine; Hansen, Bjarke B. [Copenhagen University Hospital Frederiksberg, Parker Institute, Department of Rheumatology, Frederiksberg (Denmark); Boesen, Mikael [Copenhagen University Hospital Frederiksberg and Bispebjerg, Department of Radiology, Frederiksberg (Denmark); Copenhagen University Hospital Frederiksberg, Parker Institute, Department of Rheumatology, Frederiksberg (Denmark)

    2016-02-15

    To examine intraobserver, interobserver and between-day reproducibility of positional MRI for evaluation of navicular bone height (NVH) and medial navicular position (MNP). Positional MRI (pMRI) of the foot was performed on ten healthy participants (0.25 T G-scanner). Scanning was performed in supine and standing position, respectively. Two radiologists evaluated the images in a blinded manner. Reliability and agreement were assessed by calculation of intraclass correlation coefficient (ICC) and 95 % limits of agreement as a percentage of the mean (LOA%). Intraobserver and interobserver reliability was ''substantial'' in both supine and standing position (ICC 0.86-0.98) and showed good agreement (LOA% 4.9-14.7 %). Between-day reliability of navicular height and medial navicular position in standing position remained substantial (ICC 0.85-0.92) with adequate agreement (LOA% 8.3-19.8 %). In supine position between-day reliability was ''moderate'' for NVH (ICC 0.72) and ''slight'' for MNP (ICC 0.39). Agreement remained adequate between-days for MNP in supine position (LOA% 17.7 %), but it was less than adequate for NVH in supine position (LOA% 24.2 %). Navicular height and medial navicular position can be measured by pMRI in a very reproducible manner within and between observers. Increased measurement variation is observed between-days in supine position, which may be due to small positional differences or other unknown biomechanical factors. (orig.)

  15. Navicular bone position determined by positional MRI: a reproducibility study

    International Nuclear Information System (INIS)

    To examine intraobserver, interobserver and between-day reproducibility of positional MRI for evaluation of navicular bone height (NVH) and medial navicular position (MNP). Positional MRI (pMRI) of the foot was performed on ten healthy participants (0.25 T G-scanner). Scanning was performed in supine and standing position, respectively. Two radiologists evaluated the images in a blinded manner. Reliability and agreement were assessed by calculation of intraclass correlation coefficient (ICC) and 95 % limits of agreement as a percentage of the mean (LOA%). Intraobserver and interobserver reliability was ''substantial'' in both supine and standing position (ICC 0.86-0.98) and showed good agreement (LOA% 4.9-14.7 %). Between-day reliability of navicular height and medial navicular position in standing position remained substantial (ICC 0.85-0.92) with adequate agreement (LOA% 8.3-19.8 %). In supine position between-day reliability was ''moderate'' for NVH (ICC 0.72) and ''slight'' for MNP (ICC 0.39). Agreement remained adequate between-days for MNP in supine position (LOA% 17.7 %), but it was less than adequate for NVH in supine position (LOA% 24.2 %). Navicular height and medial navicular position can be measured by pMRI in a very reproducible manner within and between observers. Increased measurement variation is observed between-days in supine position, which may be due to small positional differences or other unknown biomechanical factors. (orig.)

  16. Experimental study of natural hydroxyapatite/chitosan composite on reconstructing bone defects

    Institute of Scientific and Technical Information of China (English)

    Hua Yuan; Ning Chen; XiaoyingLü; Buzhong Zheng

    2008-01-01

    Objective:To study the possibility of natural hydroxyapatite/chitosan composite on repairing bone defects. Methods:We developed a natural hydroxyapatite/chitosan composite that could be molded into any desired shape. The powder component consists of natural hydroxyapatite, which is epurated from bone of pigs. The liquid component consists of malic acid and chitosan. Operations were performed on the left tibias of 15 white rabbits to create two square bone defects. One of the defects was reconstructed with the composite, while the other was not repaired and used as a blank control. Three of the animals were killed at the end of 2 weeks, 4 weeks, 8 weeks, 12 weeks and 16 weeks respectively and implants were evaluated anatomically and histologically. Results:No apparent rejection reaction was found, except for a mild inflammatory infiltration observed 2 weeks after surgery. Fibrous tissue became thinner 2 -8 weeks after surgery and bony connections were detected 12 weeks after surgery. The new bone was the same as the recipient bone by the 16th postoperative week. Conclusion:The hydroxyapatite/chitosan composite has good biocompatibility and osteoconduction. It is a potential repairing material for clinical application.

  17. A new Fe-Mn-Si alloplastic biomaterial as bone grafting material: In vivo study

    Science.gov (United States)

    Fântânariu, Mircea; Trincă, Lucia Carmen; Solcan, Carmen; Trofin, Alina; Strungaru, Ştefan; Şindilar, Eusebiu Viorel; Plăvan, Gabriel; Stanciu, Sergiu

    2015-10-01

    Designing substrates having suitable mechanical properties and targeted degradation behavior is the key's development of bio-materials for medical application. In orthopedics, graft material may be used to fill bony defects or to promote bone formation in osseous defects created by trauma or surgical intervention. Incorporation of Si may increase the bioactivity of implant locally, both by enhancing interactions at the graft-host interface and by having a potential endocrine like effect on osteoblasts. A Fe-Mn-Si alloy was obtained as alloplastic graft materials for bone implants that need long recovery time period. The surface morphology of the resulted specimens was investigated using scanning electrons microscopy (VegaTescan LMH II, SE detector, 30 kV), X-ray diffractions (X'Pert equipment) or X-ray dispersive energy analyze (Bruker EDS equipment). This study objective was to evaluate in vivo the mechanisms of degradation and the effects of its implantation over the main metabolic organs. Biochemical, histological, plain X radiography and computed tomography investigations showed good compatibility of the subcutaneous implants in the rat organism. The implantation of the Fe-Mn-Si alloy, in critical size bone (tibiae) defect rat model, did not induced adverse biological reactions and provided temporary mechanical support to the affected bone area. The biodegradation products were hydroxides layers which adhered to the substrate surface. Fe-Mn-Si alloy assured the mechanical integrity in rat tibiae defects during bone regeneration.

  18. Study of strontium ranelate bone issues by X-ray microtomography

    International Nuclear Information System (INIS)

    The X-ray microtomography is a non-destructive image technique that allows evaluation of inner structure of several kinds of materials, such as trabecular bone. The microarchitecture of osteoporosis bone becomes more fragile and susceptible to fractures. Strontium ranelate (Protos) is a current oral medication used in the treatment of osteoporosis diseases, which promises to act stimulating the proliferation of osteoblasts, as well as inhibiting the proliferation of osteoclasts. In the present work, two ways to administer strontium ranelate are studied in experiments with rats and mice: via oral and via intra-peritoneal injections. Intra-peritoneal injections are easier and not susceptible to gastrointestinal tract issues such as diarrhoea and absorption variations. However, the only method to administrate the strontium ranelate described in literature is still the gavage. In order to establish the best technique for future experiments, structural bone changes in rats were evaluated. The results show that bone porosity parameter at the femoral head decreased after 23 days of treatment when both oral and intraperitoneal routes of strontium ranelate administration were applied, suggesting an improved bone microarchitecture.

  19. Analysis of facial bone fractures: An 11-year study of 2,094 patients

    Directory of Open Access Journals (Sweden)

    Hwang Kun

    2010-01-01

    Full Text Available Purpose: The medical records of these patients were reviewed and analysed to determine the clinical characteristics and treatment of facial bone fractures. Patients and Methods: This is a retrospective study of 2,094 patients with facial bone fractures from various accidents that were treated at the Inha University Hospital from 1996 to 2007. Results: The most common age group was the third decade of life (29%. Males were more common than females (3.98:1. The most common aetiology was violent assault or nonviolent traumatic injury (49.4%. The most common isolated fracture site was the nasal bone (37.7%, followed by the mandible (30%, orbital bones (7.6%, zygoma (5.7%, maxilla (1.3% and the frontal bone (0.3%. The largest group with complex fractures included the inferior region of the orbital floor and zygomaticomaxilla (14%. Closed reduction was performed in 46.3% of the cases while 39.7% of the cases required open reduction. For open reductions, the most commonly used soft-tissue approach was the intraoral approach (32.3%. The complication rate was 6.4% and the most common complication was hypoesthesia (68.4% followed by diplopia (25.6%. Conclusion: Long-term collection of epidemiological data regarding facial fractures and concomitant injuries is important for the evaluation of existing preventive measures and useful in the development of new methods of injury prevention and treatment.

  20. High Protein Intake Improves Insulin Sensitivity but Exacerbates Bone Resorption in Immobility (WISE Study)

    Science.gov (United States)

    Heer, Martina; Smith, Scott M.; Frings-Meuthen, Petra; Zwart, Sara R.; Baecker, Natalie

    2012-01-01

    Inactivity, like bed rest (BR), causes insulin resistance (IR) and bone loss even in healthy subjects. High protein intake seems to mitigate this IR but might exacerbate bone loss. We hypothesized that high protein intake (animal:vegetable protein ratio: 60:40), isocaloric, compared to the control group plus high potassium intake would prevent IR without affecting bone turnover. After a 20-day ambulatory adaptation to controlled confinement and diet, 16 women participated in a 60-day, 6 deg head-down-tilt BR and were assigned randomly to one of the two groups. Control subjects (CON, n=8) received 1g/kg body mass/d dietary protein. Nutrition subjects (NUT, n=8) received 1.45g/kg body mass/d dietary protein plus 7.2g branched chain amino acids per day during BR. All subjects received 1670 kcal/d. Bed rest decreased glucose disposal by 35% (pprotein intake prevented insulin resistance, but exacerbated bed rest induced increase in bone resorption markers C-telopeptide (> 30%) and Ntelopeptide (>20%) (both: pprotein intake. We conclude from these results that high protein intake might positively affect glucose tolerance, but might also foster bone loss. Further long-duration studies are mandatory before high protein intake for diabetic patients, who have an increased fracture risk, might be recommended.

  1. Skeletal-related events in urological cancer patients with bone metastasis. A multicenter study in Japan

    International Nuclear Information System (INIS)

    The objective of this study was to investigate the incidence of skeletal-related events (SRE) in urological cancer patients with bone metastases in Japan. Five hundred eleven patients with urological cancer and documented bone metastases treated from January 2003 to April 2008 in ten Japanese institutions were included in a retrospective analysis. Type and incidence of SRE (fracture, radiotherapy, spinal cord compression, surgery, hypercalcemia, and bone pain) were determined from patient medical records. The overall incidence of SRE, including 'pain', was 61%. The most common event was radiotherapy for bone metastases, with an incidence of 31%. The overall incidence of events seemed to be similar among Japanese and Western patients with prostate cancer and renal cell carcinoma when comparing data with previously published reports. Nevertheless, a much lower incidence of fracture (19.1%) was observed in Japanese renal cell carcinoma patients. The overall incidence of SRE in Japanese urological cancer patients with bone metastasis was similar to that in Western patients, but the incidence of fracture was lower in Japanese renal cancer patients. (author)

  2. Radionuclide bone scan, radiographic bone survey, and alkaline phosphatase: studies of limited value in asymptomatic patients with ovarian carcinoma

    International Nuclear Information System (INIS)

    Bone scans or skeletal surveys were obtained in 104 patients with ovarian carcinoma. No metastases were identified at staging in the 43 patients with Stage I or II disease. Four patients in the entire series had osseous metastases. Three of the 40 patients with Stage III epithelian ovarian carcinoma has osseous metastases at the time of staging. All of these were Grade III lesions. One Stage I, Grade III patient demonstrated osseous metastases two years after initial diagnosis. None of the four patients with osseous metastases had an elevated alkaline phosphatase; three of the four had bone pain. Based on these results, it is suggested that radiographic bone survey and radionuclide bone scans are not indicated as screening procedures in asymptomatic patients with ovarian carcinoma

  3. Radiological study of the temporal bone in chronic otitis media: Prospective study of 50 cases

    Directory of Open Access Journals (Sweden)

    Thripthi Rai

    2014-01-01

    Full Text Available Aim: To assess radiological findings in Chronic otitis media (COM, its involvement in middle ear and adjacent structure and to compare with similar published data. The ability of the radiological investigations to detect the various pathological and anatomical variations were evaluated and compared with intraoperative findings. COM is a long standing inflammation of the middle ear cleft without reference to etiology or pathogenesis. Due to the strategic location of the tympanomastoid compartment, separated from the middle and posterior cranial fossa by the thinnest of bony partitions, otitis media has the potential for intracranial extension. Hence, it becomes very important to know the location and extent of the disease before proceeding to surgical treatment. Radiological examination of the temporal bone helps us to achieve this objective. The present work has been undertaken to study the role of radiological imaging of the temporal bone as a diagnostic modality in COM and its use in determining the lines of management as in the type of surgical intervention required. Materials and Methods: This is a prospective study in which total of 50 cases with COM were studied. Results: HRCT is reliable for all the parameters like scutum erosion, ossicular erosion, mastoid pneumatisation, low lying dura, anterior lying sigmoid, Korner′s septum, cholesteatoma extension in the middle ear and mastoid, and presence of complications such as mastoiditis and mastoid abscess, mastoid cortex dehiscence, sigmoid sinus plate erosion, facial canal dehiscence, tegmen mastoideum erosion and labyrinthine fistula and intracranial complications with a P < 0.05 but not reliable for tegmen tympani erosion and posterior fossa dural plate erosion. Conclusion: HRCT is highly reliable and findings are in par with intraoperative findings in this study.

  4. A functional assessment of adolescents who were recipients of bone marrow transplantation: a prospective study

    OpenAIRE

    Dóro Maribel P.; Pasquini Ricardo; Löhr Suzane S.

    2003-01-01

    The aim of this study was to assess the physical performance (Karnofsky or Lansky's Performance Scale), as well as the social/familial, emotional, functional and cancer treatment by bone marrow transplant (FACT-BMT battery). Subjects were all adolescents (13 to 20 years of age) who underwent a transplant at the Bone Marrow Transplant Unit (Serviço de Transplante de Medula Óssea) of the University Hospital (Hospital de Clínicas) of Universidade Federal do Paraná, (STMO-HC-UFPR) in the calendar...

  5. Study of osteoporosis through the measurement of bone mineral density and trace elements

    International Nuclear Information System (INIS)

    The main purpose of this study was to establish a relation, if any, between bone mineral density (BMD) of the healthy Turkish population of the ages between 15 and 50 with social and demographic information, family history of fractures, personal and inherited characteristic, smoking and alcohol habit, history of fertility, level of physical activity, food consumption especially trace elements and other variables. Most of these relations were discussed in the last two Research Coordinated Meetings, in San Diego, CA, October 1996 and Sao Paulo, Brazil, August 1998. Since then we have concentrated our work on more BMD and trace element measurements in bone

  6. Chronic obstructive pulmonary disease and low bone mass: A case-control study

    Directory of Open Access Journals (Sweden)

    Rakesh K Gupta

    2014-01-01

    Full Text Available Background and Objective: Low bone mass (osteopenia and osteoporosis is one of the effects associated with chronic obstructive pulmonary disease (COPD. There is very little data from Saudi Arabia on COPD and low bone mass. This retrospective study was done to assess the prevalence of osteoporosis and osteopenia in COPD patients attending King Fahd Hospital of the University (KFHU, Alkhobar. Patients and Methods: After obtaining the ethical approval from the research committee, all patients seen between at the King Fahd Hospital of the University between January 2010 and December 2012 were included. The inclusion criteria included a follow up of a minimum 2 years, and the Medical Records should have the details of forced expiratory volume in one second (FEV 1 , blood bone profile and bone biomarkers and dual-energy X-ray absorptiometry (DEXA scan. Patients were labeled as osteopenia if the T score was -<1 to <-2.5 and osteoporosis of <-2.5 as per the WHO definition of osteopenia and osteoporosis. Results: Seventy-three patients were being followed in the clinics and 49 patients satisfied the inclusion criteria. The average age was 60.6 ± 10.47 years; males were 43 and females 6. Three (6.1% were normal and the remaining 46 (93.9% were with low bone mass. Thirty-two (65.3% were osteoporotic and 14 (28.57% were osteopenic. The average duration of COPD was 4.5 ± 6.2 years. Majority (n = 36, 73.4% of patients were in the Global Initiative for COPD (GOLD class II and III. FEV 1 was significantly lower in the patients with low bone mass 1.66 ± 0.60 versus 3.61 ± 0.58 (P < 0.001. Conclusions: Our study shows that over 90% of Saudi Arabian patients with COPD suffer from osteopenia and osteoporosis and unfortunately they remain under-diagnosed and undertreated.

  7. Cyclosporine-a and bone density around titanium implants: a histometric study in rabbits

    Directory of Open Access Journals (Sweden)

    Celso Eduardo Sakakura

    2011-06-01

    Full Text Available Aim: Cyclosporine A (CsA is an immunosuppressive agent commonly used to prevent organ transplantation rejection. It has been demonstrated that CsA may negatively affect osseointegration around dental implants. Therefore, the aim of this study was to evaluate the effect of CsA administration on bone density around titanium dental implants. Materials and Methods: Fourteen New Zealand rabbits were randomly divided into 2 groups with seven animals each. The test group (CsA received daily subcutaneous injection of CsA (10mg/kg body weight and the control group (CTL received saline solution by the same route of administration. Three days after the beginning of immunosuppressive therapy, one machined dental implant (7.00 mm in lenght and 3.75 mm in diameter was inserted bilaterally at the region of the tibial methaphysis. After 4 and 8 weeks the animals were sacrificed and the histometrical procedures were performed to analyse the bone density around the first four threads of the coronal part of the implant. Results: A significant increase in the bone density was observed from the 4- to the 8 week-period in the control group (37.41% + 14.85 versus 58.23% + 16.38 – p < 0.01. In contrast, bone density consistently decreased in the test group overtime (46.31% + 17.38 versus 16.28 + 5.08 – p <0.05. In the 8-week period, there was a significant difference in bone density between the control and the test groups (58.23 + 16.38 eand16.28 + 5.08 – p= 0.001. Conclusion: Within the limits of this study, long-term CsA administration may reduce bone density around titanium dental implants during the osseointegration process.

  8. Analysis of fracture healing in osteopenic bone caused by disuse: experimental study

    Directory of Open Access Journals (Sweden)

    A.G. Paiva

    2016-03-01

    Full Text Available Osteoporosis has become a serious global public health issue. Hence, osteoporotic fracture healing has been investigated in several previous studies because there is still controversy over the effect osteoporosis has on the healing process. The current study aimed to analyze two different periods of bone healing in normal and osteopenic rats. Sixty, 7-week-old female Wistar rats were randomly divided into four groups: unrestricted and immobilized for 2 weeks after osteotomy (OU2, suspended and immobilized for 2 weeks after osteotomy (OS2, unrestricted and immobilized for 6 weeks after osteotomy (OU6, and suspended and immobilized for 6 weeks after osteotomy (OS6. Osteotomy was performed in the middle third of the right tibia 21 days after tail suspension, when the osteopenic condition was already set. The fractured limb was then immobilized by orthosis. Tibias were collected 2 and 6 weeks after osteotomy, and were analyzed by bone densitometry, mechanical testing, and histomorphometry. Bone mineral density values from bony calluses were significantly lower in the 2-week post-osteotomy groups compared with the 6-week post-osteotomy groups (multivariate general linear model analysis, P<0.000. Similarly, the mechanical properties showed that animals had stronger bones 6 weeks after osteotomy compared with 2 weeks after osteotomy (multivariate general linear model analysis, P<0.000. Histomorphometry indicated gradual bone healing. Results showed that osteopenia did not influence the bone healing process, and that time was an independent determinant factor regardless of whether the fracture was osteopenic. This suggests that the body is able to compensate for the negative effects of suspension.

  9. A Study of the Effects of Desmotomy of the Navicular Bone Suspensory Ligament on Radio-Morphometric Features of the Navicular Bone in Normal Donkeys (Equus asinus)

    OpenAIRE

    M. Daradka; Z. Bani; Ismail, A.; A. Almomany

    2015-01-01

    This study was performed to investigate the effects of desmotomy of the Navicular Bone Suspensory Ligament (NBSL) on navicular bone radio-morphometric features and on navicular bone remodeling in normal donkeys (Equus asinus). Twenty normal healthy, adult, local breed donkeys, between 5 and 7 years of age and weighing 120-150 kg were used. Three radiographic views (lateromedial, dorsopalmar and palmaroproximal- palmarodistal oblique) of navicular bones of the forelimbs were taken of experimen...

  10. [Cathepsin K antagonists: preclinical and clinical data].

    Science.gov (United States)

    Gamsjäger, Marion; Resch, Heinrich

    2015-02-01

    Cathepsin K, a cysteine protease, is an essential enzyme in degradation of collagen type I. Since cathepsin K is relatively specific to osteoclasts, it represents a promising candidate for drug development. In the past decades, efforts have been made in developing highly potent, selective and orally applicable cathepsin K inhibitors. In contrast to balicatib and relacatib, whose drug development programmes were stopped due to cutaneous side-effects related to limited drug specificity, the more specific cathepsin K inhibitors odanacatib (ODN) and ONO-5334 have entered clinical trials. Odanacatib progressively increases bone mineral density (BMD) and decreases bone resorption markers in postmenopausal women with low BMD. Its clinical efficacy and safety was confirmed by several clinical studies but indicates that odanacatib is characterized by a resolution-of-effect with increases in bone resorption and rapid decreases in BMD following treatment discontinuation. A phase III fracture prevention study in postmenopausal women with osteoporosis is currently in the final phase. PMID:25572547

  11. A New Method for Xenogeneic Bone Graft Deproteinization: Comparative Study of Radius Defects in a Rabbit Model

    OpenAIRE

    Lei, Pengfei; Sun, Rongxin; Wang, Long; Zhou, Jialin; Wan, Lifei; Zhou, Tianjian; Hu, Yihe

    2015-01-01

    Background and Objectives Deproteinization is an indispensable process for the elimination of antigenicity in xenograft bones. However, the hydrogen peroxide (H2O2) deproteinized xenograft, which is commonly used to repair bone defect, exhibits limited osteoinduction activity. The present study was designed to develop a new method for deproteinization and compare the osteogenic capacities of new pepsin deproteinized xenograft bones with those of conventional H2O2 deproteinized ones. Methods B...

  12. Long-term adverse outcomes in survivors of childhood bone sarcoma: the British Childhood Cancer Survivor Study

    OpenAIRE

    Fidler, M M; Frobisher, C; Guha, J; K. Wong; Kelly, J; Winter, D. L.; Sugden, E; Duncan, R.; Whelan, J; Reulen, R C; Hawkins, M. M.

    2015-01-01

    Background: With improved survival, more bone sarcoma survivors are approaching middle age making it crucial to investigate the late effects of their cancer and its treatment. We investigated the long-term risks of adverse outcomes among 5-year bone sarcoma survivors within the British Childhood Cancer Survivor Study. Methods: Cause-specific mortality and risk of subsequent primary neoplasms (SPNs) were investigated for 664 bone sarcoma survivors. Use of health services, health and marital st...

  13. Assessment of Corticotomy Facilitated Tooth Movement and Changes in Alveolar Bone Thickness - A CT Scan Study

    OpenAIRE

    Bhattacharya, Preeti; Bhattacharya, Hirak; Anjum, Arbab; Bhandari, Ravi; Agarwal, D. K.; Gupta, Ankur; Ansar, Juhi

    2014-01-01

    Introduction: Corticotomy is an effective method of accelerating the orthodontic treatment. The aim of this study was to compare the treatment time for the extraction space closure, between corticotomy assisted and conventional orthodontic tooth movement and to check the alveolar bone thickness before and after corticotomy procedure in the corticotomy group.

  14. Utility of bone scintigraphy in the study of hereditary disorders of the connective tissues (HDCT)

    International Nuclear Information System (INIS)

    Introduction: Collagen fiber genetic alterations predispose to pain and instability of joints, with a tendency to osteoarthritis, and may also cause fragility of other tissues. Objective: To demonstrate that Bone Scintigraphy is useful in the diagnosis of Heritable Disorders of Connective Tissues (HDCT). Material and methods: We studied the scintigraphic changes of wrists, carpal bones and hands of 22 adult patients with HDCT who were diagnosed clinically using both the Brighton Criteria(1), as well as own criteria**. We compared them to 22 controls with similar age and sex, who had a bone scintigram done for other purposes. Results: Statistically significant scintigraphic positivity was found in the areas studied in the patients as compared to controls (p ≤ 0.05), with a sensitivity of 95% and specificity of 73%. There was no correlation of the degree of positivity with age, sex or type of HDCT studied. A scintigraphic positivity was seen both in patients with lax joints, as well as in those with a lesser degree of joint mobility. Conclusions: We concluded that bone scintigraphic studies are useful in the diagnosis of adult HDCT patients (including Benign Joint Hyper mobility Syndrome (BJHS) and other forms of Ehlers-Danlos). We suggest that not only hypermobility of joints, but also cartilage fragility are important pathogenic factors in the genesis of these alterations. We formulate a new hypothesis of the importance of low folic acid intake during pregnancy, as a cause for mutations that would give rise to HDCT (Au)

  15. Preclinical Toxicology Studies of Recombinant Human Platelet-Derived Growth Factor-BB Either Alone or in Combination with Beta-Tricalcium Phosphate and Type I Collagen

    OpenAIRE

    Young, Conan S.; Gino Bradica; Hart, Charlie E.; Anuradha Karunanidhi; Reva M. Street; Lyndsey Schutte; Hollinger, Jeffrey O.

    2011-01-01

    Human platelet-derived growth factor-BB (hPDGF-BB) is a basic polypeptide growth factor released from platelets at the injury site. It is a multifunctional molecule that regulates DNA synthesis and cell division and induces biological effects that are implicated in tissue repair, atherosclerosis, inflammatory responses, and neoplastic diseases. This paper is an overview of the toxicology data generated from a broad testing platform to determine bone, soft tissue, and systemic responses follow...

  16. The basics of preclinical drug development for neurodegenerative disease indications.

    Science.gov (United States)

    Steinmetz, Karen L; Spack, Edward G

    2009-01-01

    Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties. For drugs intended to treat Alzheimer's disease or other brain-targeted diseases, the ability of a drug to cross the blood brain barrier may be a key issue. Toxicology and safety studies identify potential target organs for adverse effects and define the Therapeutic Index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA) Good Laboratory Practices and international guidelines, including the International Conference on Harmonization. Concurrent preclinical development activities include developing the Clinical Plan and preparing the new drug product, including the associated documentation to meet stringent FDA Good Manufacturing Practices regulatory guidelines. A wide range of commercial and government contract options are available for investigators seeking to advance their candidate(s). Government programs such as the Small Business Innovative Research and Small Business Technology Transfer grants and the National Institutes of Health Rapid Access to Interventional Development Pilot Program provide funding and

  17. The basics of preclinical drug development for neurodegenerative disease indications

    Directory of Open Access Journals (Sweden)

    Spack Edward G

    2009-06-01

    Full Text Available Abstract Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties. For drugs intended to treat Alzheimer's disease or other brain-targeted diseases, the ability of a drug to cross the blood brain barrier may be a key issue. Toxicology and safety studies identify potential target organs for adverse effects and define the Therapeutic Index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA Good Laboratory Practices and international guidelines, including the International Conference on Harmonisation. Concurrent preclinical development activities include developing the Clinical Plan and preparing the new drug product, including the associated documentation to meet stringent FDA Good Manufacturing Practices regulatory guidelines. A wide range of commercial and government contract options are available for investigators seeking to advance their candidate(s. Government programs such as the Small Business Innovative Research and Small Business Technology Transfer grants and the National Institutes of Health Rapid Access to Interventional Development Pilot

  18. Wnt signaling control of bone cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    Peter V N Bodine

    2008-01-01

    Wnts are a large family of growth factors that mediate essential biological processes like embryogenesis, morphogenesis and organogenesis. These proteins also play a role in oncogenesis, and they regulate apopt