A brief review on experimental fluorosis.

PubMed

Perumal, Ekambaram; Paul, Vanaja; Govindarajan, Vimal; Panneerselvam, Lakshmikanthan

2013-11-25

Fluoride (F) is a naturally occurring contaminant in the water. F is essential for normal maintenance of teeth and bones. However, prolonged exposure to high concentration of F is found to be deleterious to teeth, bones and other organs. Besides drinking water, F can enter the body through food, dental products, drugs and industrial emission. People living in areas where F contamination is much higher than the expected level, are found to suffer from not only teeth and bone problem but also other systems, including brain and its functions. Since animals respond to the toxic effects of F like human beings, the deleterious effects of F have been produced experimentally in animals in order to determine the mechanism involved in the action of F. The reports indicating the chronic harmful effects of F in teeth, bones, heart, liver, kidneys, gastrointestinal tract, lungs, brain, blood, hormones and biochemical parameters of experimental animals and in in vitro studies have been reviewed in this article. The neurotoxic action of F that produces chiefly learning and memory impairment has also been included. The review also points out the harmful effects of F on reproduction, its teratogenic action and in inducing premature ageing. Finally, the reports indicating a reversal of certain toxicities of F in experimental animals after withdrawal of its exposure has been included. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The skull roof tracks the brain during the evolution and development of reptiles including birds.

PubMed

Fabbri, Matteo; Mongiardino Koch, Nicolás; Pritchard, Adam C; Hanson, Michael; Hoffman, Eva; Bever, Gabriel S; Balanoff, Amy M; Morris, Zachary S; Field, Daniel J; Camacho, Jasmin; Rowe, Timothy B; Norell, Mark A; Smith, Roger M; Abzhanov, Arhat; Bhullar, Bhart-Anjan S

2017-10-01

Major transformations in brain size and proportions, such as the enlargement of the brain during the evolution of birds, are accompanied by profound modifications to the skull roof. However, the hypothesis of concerted evolution of shape between brain and skull roof over major phylogenetic transitions, and in particular of an ontogenetic relationship between specific regions of the brain and the skull roof, has never been formally tested. We performed 3D morphometric analyses to examine the deep history of brain and skull-roof morphology in Reptilia, focusing on changes during the well-documented transition from early reptiles through archosauromorphs, including nonavian dinosaurs, to birds. Non-avialan taxa cluster tightly together in morphospace, whereas Archaeopteryx and crown birds occupy a separate region. There is a one-to-one correspondence between the forebrain and frontal bone and the midbrain and parietal bone. Furthermore, the position of the forebrain-midbrain boundary correlates significantly with the position of the frontoparietal suture across the phylogenetic breadth of Reptilia and during the ontogeny of individual taxa. Conservation of position and identity in the skull roof is apparent, and there is no support for previous hypotheses that the avian parietal is a transformed postparietal. The correlation and apparent developmental link between regions of the brain and bony skull elements are likely to be ancestral to Tetrapoda and may be fundamental to all of Osteichthyes, coeval with the origin of the dermatocranium.

Quantitative Evaluation of Atlas-based Attenuation Correction for Brain PET in an Integrated Time-of-Flight PET/MR Imaging System.

PubMed

Yang, Jaewon; Jian, Yiqiang; Jenkins, Nathaniel; Behr, Spencer C; Hope, Thomas A; Larson, Peder E Z; Vigneron, Daniel; Seo, Youngho

2017-07-01

Purpose To assess the patient-dependent accuracy of atlas-based attenuation correction (ATAC) for brain positron emission tomography (PET) in an integrated time-of-flight (TOF) PET/magnetic resonance (MR) imaging system. Materials and Methods Thirty recruited patients provided informed consent in this institutional review board-approved study. All patients underwent whole-body fluorodeoxyglucose PET/computed tomography (CT) followed by TOF PET/MR imaging. With use of TOF PET data, PET images were reconstructed with four different attenuation correction (AC) methods: PET with patient CT-based AC (CTAC), PET with ATAC (air and bone from an atlas), PET with ATAC patientBone (air and tissue from the atlas with patient bone), and PET with ATAC boneless (air and tissue from the atlas without bone). For quantitative evaluation, PET mean activity concentration values were measured in 14 1-mL volumes of interest (VOIs) distributed throughout the brain and statistical significance was tested with a paired t test. Results The mean overall difference (±standard deviation) of PET with ATAC compared with PET with CTAC was -0.69 kBq/mL ± 0.60 (-4.0% ± 3.2) (P < .001). The results were patient dependent (range, -9.3% to 0.57%) and VOI dependent (range, -5.9 to -2.2). In addition, when bone was not included for AC, the overall difference of PET with ATAC boneless (-9.4% ± 3.7) was significantly worse than that of PET with ATAC (-4.0% ± 3.2) (P < .001). Finally, when patient bone was used for AC instead of atlas bone, the overall difference of PET with ATAC patientBone (-1.5% ± 1.5) improved over that of PET with ATAC (-4.0% ± 3.2) (P < .001). Conclusion ATAC in PET/MR imaging achieves similar quantification accuracy to that from CTAC by means of atlas-based bone compensation. However, patient-specific anatomic differences from the atlas causes bone attenuation differences and misclassified sinuses, which result in patient-dependent performance variation of ATAC. © RSNA, 2017 Online supplemental material is available for this article.

The Application of Lean Thinking to the Care of Patients With Bone and Brain Metastasis With Radiation Therapy

PubMed Central

Kim, Christopher S.; Hayman, James A.; Billi, John E.; Lash, Kathy; Lawrence, Theodore S.

2007-01-01

Purpose Patients with bone and brain metastases are among the most symptomatic nonemergency patients treated by radiation oncologists. Treatment should begin as soon as possible after the request is generated. We tested the hypothesis that the operational improvement method based on lean thinking could help streamline the treatment of our patients referred for bone and brain metastases. Methods University of Michigan Health System has adopted lean thinking as a consistent approach to quality and process improvement. We applied the principles and tools of lean thinking, especially value as defined by the customer, value stream mapping processes, and one piece flow, to improve the process of delivering care to patients referred for bone or brain metastases. Results and Conclusion The initial evaluation of the process revealed that it was rather chaotic and highly variable. Implementation of the lean thinking principles permitted us to improve the process by cutting the number of individual steps to begin treatment from 27 to 16 and minimize variability by applying standardization. After an initial learning period, the percentage of new patients with brain or bone metastases receiving consultation, simulation, and treatment within the same day rose from 43% to nearly 95%. By implementing the ideas of lean thinking, we improved the delivery of clinical care for our patients with bone or brain metastases. We believe these principles can be applied to much of the care administered throughout our and other health care delivery areas. PMID:20859409

The application of lean thinking to the care of patients with bone and brain metastasis with radiation therapy.

PubMed

Kim, Christopher S; Hayman, James A; Billi, John E; Lash, Kathy; Lawrence, Theodore S

2007-07-01

Patients with bone and brain metastases are among the most symptomatic nonemergency patients treated by radiation oncologists. Treatment should begin as soon as possible after the request is generated. We tested the hypothesis that the operational improvement method based on lean thinking could help streamline the treatment of our patients referred for bone and brain metastases. University of Michigan Health System has adopted lean thinking as a consistent approach to quality and process improvement. We applied the principles and tools of lean thinking, especially value as defined by the customer, value stream mapping processes, and one piece flow, to improve the process of delivering care to patients referred for bone or brain metastases. The initial evaluation of the process revealed that it was rather chaotic and highly variable. Implementation of the lean thinking principles permitted us to improve the process by cutting the number of individual steps to begin treatment from 27 to 16 and minimize variability by applying standardization. After an initial learning period, the percentage of new patients with brain or bone metastases receiving consultation, simulation, and treatment within the same day rose from 43% to nearly 95%. By implementing the ideas of lean thinking, we improved the delivery of clinical care for our patients with bone or brain metastases. We believe these principles can be applied to much of the care administered throughout our and other health care delivery areas.

A COMPUTATIONAL ANALYSIS OF BONE FORMATION IN THE CRANIAL VAULT USING A COUPLED REACTION-DIFFUSION-STRAIN MODEL

PubMed Central

LEE, CHANYOUNG; RICHTSMEIER, JOAN T.; KRAFT, REUBEN H.

2017-01-01

Bones of the murine cranial vault are formed by differentiation of mesenchymal cells into osteoblasts, a process that is primarily understood to be controlled by a cascade of reactions between extracellular molecules and cells. We assume that the process can be modeled using Turing’s reaction-diffusion equations, a mathematical model describing the pattern formation controlled by two interacting molecules (activator and inhibitor). In addition to the processes modeled by reaction-diffusion equations, we hypothesize that mechanical stimuli of the cells due to growth of the underlying brain contribute significantly to the process of cell differentiation in cranial vault development. Structural analysis of the surface of the brain was conducted to explore the effects of the mechanical strain on bone formation. We propose a mechanobiological model for the formation of cranial vault bones by coupling the reaction-diffusion model with structural mechanics. The mathematical formulation was solved using the finite volume method. The computational domain and model parameters are determined using a large collection of experimental data that provide precise three dimensional (3D) measures of murine cranial geometry and cranial vault bone formation for specific embryonic time points. The results of this study suggest that mechanical strain contributes information to specific aspects of bone formation. Our mechanobiological model predicts some key features of cranial vault bone formation that were verified by experimental observations including the relative location of ossification centers of individual vault bones, the pattern of cranial vault bone growth over time, and the position of cranial vault sutures. PMID:29225392

Keratin 13 expression reprograms bone and brain metastases of human prostate cancer cells.

PubMed

Li, Qinlong; Yin, Lijuan; Jones, Lawrence W; Chu, Gina C-Y; Wu, Jason B-Y; Huang, Jen-Ming; Li, Quanlin; You, Sungyong; Kim, Jayoung; Lu, Yi-Tsung; Mrdenovic, Stefan; Wang, Ruoxiang; Freeman, Michael R; Garraway, Isla; Lewis, Michael S; Chung, Leland W K; Zhau, Haiyen E

2016-12-20

Lethal progression of prostate cancer metastasis can be improved by developing animal models that recapitulate the clinical conditions. We report here that cytokeratin 13 (KRT13), an intermediate filament protein, plays a directive role in prostate cancer bone, brain, and soft tissue metastases. KRT13 expression was elevated in bone, brain, and soft tissue metastatic prostate cancer cell lines and in primary and metastatic clinical prostate, lung, and breast cancer specimens. When KRT13 expression was determined at a single cell level in primary tumor tissues of 44 prostate cancer cases, KRT13 level predicted bone metastasis and the overall survival of prostate cancer patients. Genetically enforced KRT13 expression in human prostate cancer cell lines drove metastases toward mouse bone, brain and soft tissues through a RANKL-independent mechanism, as KRT13 altered the expression of genes associated with EMT, stemness, neuroendocrine/neuromimicry, osteomimicry, development, and extracellular matrices, but not receptor activator NF-κB ligand (RANKL) signaling networks in prostate cancer cells. Our results suggest new inhibitors targeting RANKL-independent pathways should be developed for the treatment of prostate cancer bone and soft tissue metastases.

Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential.

PubMed

Lojewski, Xenia; Srimasorn, Sumitra; Rauh, Juliane; Francke, Silvan; Wobus, Manja; Taylor, Verdon; Araúzo-Bravo, Marcos J; Hallmeyer-Elgner, Susanne; Kirsch, Matthias; Schwarz, Sigrid; Schwarz, Johannes; Storch, Alexander; Hermann, Andreas

2015-10-01

Brain perivascular cells have recently been identified as a novel mesodermal cell type in the human brain. These cells reside in the perivascular niche and were shown to have mesodermal and, to a lesser extent, tissue-specific differentiation potential. Mesenchymal stem cells (MSCs) are widely proposed for use in cell therapy in many neurological disorders; therefore, it is of importance to better understand the "intrinsic" MSC population of the human brain. We systematically characterized adult human brain-derived pericytes during in vitro expansion and differentiation and compared these cells with fetal and adult human brain-derived neural stem cells (NSCs) and adult human bone marrow-derived MSCs. We found that adult human brain pericytes, which can be isolated from the hippocampus and from subcortical white matter, are-in contrast to adult human NSCs-easily expandable in monolayer cultures and show many similarities to human bone marrow-derived MSCs both regarding both surface marker expression and after whole transcriptome profile. Human brain pericytes showed a negligible propensity for neuroectodermal differentiation under various differentiation conditions but efficiently generated mesodermal progeny. Consequently, human brain pericytes resemble bone marrow-derived MSCs and might be very interesting for possible autologous and endogenous stem cell-based treatment strategies and cell therapeutic approaches for treating neurological diseases. Perivascular mesenchymal stem cells (MSCs) recently gained significant interest because of their appearance in many tissues including the human brain. MSCs were often reported as being beneficial after transplantation in the central nervous system in different neurological diseases; therefore, adult brain perivascular cells derived from human neural tissue were systematically characterized concerning neural stem cell and MSC marker expression, transcriptomics, and mesodermal and inherent neuroectodermal differentiation potential in vitro and in vivo after in utero transplantation. This study showed the lack of an innate neuronal but high mesodermal differentiation potential. Because of their relationship to mesenchymal stem cells, these adult brain perivascular mesodermal cells are of great interest for possible autologous therapeutic use. ©AlphaMed Press.

The Morphogenesis of Cranial Sutures in Zebrafish

PubMed Central

Topczewska, Jolanta M.; Shoela, Ramy A.; Tomaszewski, Joanna P.; Mirmira, Rupa B.; Gosain, Arun K.

2016-01-01

Using morphological, histological, and TEM analyses of the cranium, we provide a detailed description of bone and suture growth in zebrafish. Based on expression patterns and localization, we identified osteoblasts at different degrees of maturation. Our data confirm that, unlike in humans, zebrafish cranial sutures maintain lifelong patency to sustain skull growth. The cranial vault develops in a coordinated manner resulting in a structure that protects the brain. The zebrafish cranial roof parallels that of higher vertebrates and contains five major bones: one pair of frontal bones, one pair of parietal bones, and the supraoccipital bone. Parietal and frontal bones are formed by intramembranous ossification within a layer of mesenchyme positioned between the dermal mesenchyme and meninges surrounding the brain. The supraoccipital bone has an endochondral origin. Cranial bones are separated by connective tissue with a distinctive architecture of osteogenic cells and collagen fibrils. Here we show RNA in situ hybridization for col1a1a, col2a1a, col10a1, bglap/osteocalcin, fgfr1a, fgfr1b, fgfr2, fgfr3, foxq1, twist2, twist3, runx2a, runx2b, sp7/osterix, and spp1/ osteopontin, indicating that the expression of genes involved in suture development in mammals is preserved in zebrafish. We also present methods for examining the cranium and its sutures, which permit the study of the mechanisms involved in suture patency as well as their pathological obliteration. The model we develop has implications for the study of human disorders, including craniosynostosis, which affects 1 in 2,500 live births. PMID:27829009

Regulation of Bone Metabolism by Serotonin.

PubMed

Lavoie, Brigitte; Lian, Jane B; Mawe, Gary M

2017-01-01

The processes of bone growth and turnover are tightly regulated by the actions of various signaling molecules, including hormones, growth factors, and cytokines. Imbalances in these processes can lead to skeletal disorders such as osteoporosis or high bone mass disease. It is becoming increasingly clear that serotonin can act through a number of mechanisms, and at different locations in the body, to influence the balance between bone formation and resorption. Its actions on bone metabolism can vary, based on its site of synthesis (central or peripheral) as well as the cells and subtypes of receptors that are activated. Within the central nervous system, serotonergic neurons act via the hypothalamus to suppress sympathetic input to the bone. Since sympathetic input inhibits bone formation, brain serotonin has a net positive effect on bone growth. Gut-derived serotonin is thought to inhibit bone growth by attenuating osteoblast proliferation via activation of receptors on pre-osteoblasts. There is also evidence that serotonin can be synthesized within the bone and act to modulate bone metabolism. Osteoblasts, osteoclasts, and osteocytes all have the machinery to synthesize serotonin, and they also express the serotonin-reuptake transporter (SERT). Understanding the roles of serotonin in the tightly balanced system of bone modeling and remodeling is a clinically relevant goal. This knowledge can clarify bone-related side effects of drugs that affect serotonin signaling, including serotonin-specific reuptake inhibitors (SSRIs) and receptor agonists and antagonists, and it can potentially lead to therapeutic approaches for alleviating bone pathologies.

Suppression of the motor deficit in a mucolipidosis type IV mouse model by bone marrow transplantation

PubMed Central

Walker, Marquis T.; Montell, Craig

2016-01-01

Mucolipidosis IV (MLIV) is a severe lysosomal storage disorder, which results from loss of the TRPML1 channel. MLIV causes multiple impairments in young children, including severe motor deficits. Currently, there is no effective treatment. Using a Drosophila MLIV model, we showed previously that introduction of trpml+ in phagocytic glia rescued the locomotor deficit by removing early dying neurons, thereby preventing amplification of neuronal death from cytotoxicity. Because microglia, which are phagocytic cells in the mammalian brain, are bone marrow derived, and cross the blood–brain barrier, we used a mouse MLIV model to test the efficacy of bone marrow transplantation (BMT). We found that BMT suppressed the reduced myelination and the increased caspase-3 activity due to loss of TRPML1. Using a rotarod test, we demonstrated that early BMT greatly delayed the motor impairment in the mutant mice. These data offer the possibility that BMT might provide the first therapy for MLIV. PMID:27270598

Role of Regulators of G Protein Signaling Proteins in Bone Physiology and Pathophysiology

PubMed Central

Jules, Joel; Yang, Shuying; Chen, Wei; Li, Yi-Ping

2016-01-01

Regulators of G protein signaling (RGS) proteins enhance the intrinsic GTPase activity of α subunits of the heterotrimeric G protein complex of G protein-coupled receptors (GPCRs) and thereby inactivate signal transduction initiated by GPCRs. The RGS family consists of nearly 37 members with a conserved RGS homology domain which is critical for their GTPase accelerating activity. RGS proteins are expressed in most tissues, including heart, lung, brain, kidney, and bone and play essential roles in many physiological and pathological processes. In skeletal development and bone homeostasis as well as in many bone disorders, RGS proteins control the functions of various GPCRs, including the parathyroid hormone receptor type 1 and calcium-sensing receptor and also regulate various critical signaling pathways, such as Wnt and calcium oscillations. This chapter will discuss the current findings on the roles of RGS proteins in regulating signaling of key GPCRs in skeletal development and bone homeostasis. We also will examine the current updates of RGS proteins’ regulation of calcium oscillations in bone physiology and highlight the roles of RGS proteins in selected bone pathological disorders. Despite the recent advances in bone and mineral research, RGS proteins remain understudied in the skeletal system. Further understanding of the roles of RGS proteins in bone should not only provide great insights into the molecular basis of various bone diseases but also generate great therapeutic drug targets for many bone diseases. PMID:26123302

[Clinical and pathological significance of carotid siphon calcification observed on bone condition of brain CT].

PubMed

Matsumoto, Hideyuki; Hamaguchi, Hirotoshi; Nakayama, Takahiro; Oda, Tetsuya; Ikagawa, Takashi; Imafuku, Ichiro

2008-02-01

On plain brain computed tomography (CT), it is difficult to evaluate stenosis of internal carotid artery (ICA) because ICA is surrounded by structures, even though we can observe calcification of carotid siphon in some patients by using bone condition. However the pathologic significance has not been well known. We studied the pathologic significance of carotid siphon calcification observed on bone condition of brain CT. A total of 112 patients who were diagnosed or suspected as cerebrovascular diseases were registered. We classified the calcification into four levels (none, mild, moderate, severe) based on the degree of calcification. Then we compared it with the degree of stenosis of carotid siphon seen on brain magnetic resonance angiography (MRA) and with max intima-medial thickness (IMT) from common carotid artery (CCA) to ICA on carotid ultrasonography. The mean +/- standard deviation of max IMT to none, mild, moderate and severe in the degree of calcification were 1.03 +/- 0.64 (0.4-2.8), 1.65 +/- 0.83 (0.5-4.1), 2.03 +/- 0.83 (0.8-4.1) and 2.81 +/- 1.15 (0.7-6.5) mm, respectively. The calcification on brain CT significantly correlated with the degree of stenosis on brain MRA and with max IMT on carotid ultrasonography. The calcification of carotid siphon on bone condition of brain CT correlated with stenosis of the same portion and atherosclerosis of CCA bifurcation. Recently, on DICOM viewer, clinicians can convert plain condition into bone condition on brain CT due to popularization of PACS. We should pay attention to calcification of carotid siphon in patients with ischemic cerebrovascular diseases because we can estimate the atherosclerosis of both carotid siphon and CCA bifurcation easily and immediately.

Pseudotumor cerebri following traumatic brain injury in a 29-year-old man

PubMed Central

Rahman, Mohammed Izad; Raveendran, Savitha; Kaliaperumal, Chandrasekaran; Marks, Charles

2012-01-01

We describe a case of pseudotumor cerebri in a young man developing 4 years post-traumatic brain injury (TBI). A 29-year-old man was admitted after sustaining a fall with headache, and no clinical deficits were noted on examination. CT brain demonstrated an extradural hematoma. This was successfully evacuated after his symptomatic worsening. Following this, he developed bone flap infection and had the infected bone flap removed. He developed chronic mild-to-moderate headache following these procedures, which failed to respond to medical treatment. Pseudotumor cerebri was diagnosed. A lumboperitoneal (LP) shunt, ventriculo-peritoneal (VP) shunt, and bitemporal craniectomy were performed as a part of management at different stages. Post-TBI patients may present with chronic headache and in such circumstances, a possibility of pseudotumor cerebri must be considered. Investigations should include neuroimaging in the form of MRI/MRV and fundoscopy to look for papilledema. Management in the form of CSF flow diversion techniques (VP and LP shunt) with medical management results in good clinical outcomes PMID:22690064

Detection and characterization of naturally acquired West Nile virus infection in a female wild turkey.

PubMed

Zhang, Z; Wilson, F; Read, R; Pace, L; Zhang, S

2006-03-01

An adult female wild turkey exhibiting disorientation and failure to flee when approached was submitted to the Mississippi Veterinary Research and Diagnostic Laboratory. Gross pathologic examination revealed evidence of dehydration and the presence of modest numbers of adult nematodes in the small intestine. Histologic examination revealed extensive multifocal perivascular lymphocytic infiltration in brain, marked heterophilic hyperplasia in bone marrow, and multifocal interstitial lymphocytic infiltration in heart, pancreas, ventriculus, and skeletal muscles. West Nile virus (WNV) was isolated from the brain, lung, and kidney tissues using cultured Vero cells. Higher copies of viral RNA were detected from brain, lung, and kidney than from heart, liver, or spleen by quantitative real-time reverse transcription-polymerase chain reaction (RRT-PCR) analysis. Immunohistochemical (IHC) analysis detected WNV antigen in various tissues including neurons, kidney, respiratory tract epithelium, heart, and bone marrow. On the basis of the data from this investigation, it is concluded that WNV caused encephalitis along with many other pathologic changes in the affected wild turkey.

TREATMENT OF STROKE WITH DETA-NONOATE AND BONE MARROW STROMAL CELLS UPREGULATES ANGIOPOIETIN-1/TIE2 AND ENHANCES NEOVASCULARIZATION

PubMed Central

CUI, X.; CHEN, J.; ZACHAREK, A.; ROBERTS, C.; SAVANT-BHONSALE, S.; CHOPP, M.

2008-01-01

Neovascularization may contribute to functional recovery after neural injury. Combination treatment of stroke with a nitric oxide donor, DETA-NONOate and bone marrow stromal cells promote functional recovery. However, the mechanisms underlying functional improvement have not been elucidated. In this study, we tested the hypothesis that combination treatment upregulates Angiopoietin1 and its receptor Tie2 in the ischemic brain and bone marrow stromal cells, thereby enhances cerebral neovascularization after stroke. Adult wild type male C57BL/6 mice were intravenously administered PBS, bone marrow stromal cells 5×105, DETA-NONOate 0.4 mg/kg or combination DETA-NONOate with bone marrow stromal cells (n=12/group) after middle cerebral artery occlusion. Combination treatment significantly upregulated Angiopoietin-1/Tie2 and tight junction protein (occludin) expression, and increased the number, diameter and perimeter of blood vessels in the ischemic brain compared with vehicle control (mean ± SE, p<0.05). In vitro, DETA-NONOate significantly increased Angiopoietin-1/Tie2 protein (n=6/group) and Tie2 mRNA (n=3/group) expression in bone marrow stromal cells. DETA-NONOate also significantly increased Angiopoietin-1 protein (n=6/group) and mRNA (n=3/group) expression in mouse brain endothelial cells (p<0.05). Angiopoietin-1 mRNA (n=3/group) was significantly increased in mouse brain endothelial cells treated with DETA-NONOate in combination with bone marrow stromal cells conditioned medium compared with cells treated with bone marrow stromal cells conditioned medium or DETA-NONOate alone. Mouse brain endothelial cell capillary tube-like formation assays (n=6/group) showed that Angiopoietin-1 peptide, the supernatant of bone marrow stromal cells and DETA-NONOate significantly increased capillary tube formation compared to vehicle control. Combination treatment significantly increased capillary tube formation compared with DETA-NONOate treatment alone. Inhibition of Angiopoietin-1 significantly attenuated combination treatment-induced tube formation. Our data indicated that combination treatment of stroke with DETA-NONOate and bone marrow stromal cells promotes neovascularization, which is at least partially mediated by upregulation of the Angiopoietin-1/Tie2 axis. PMID:18691637

Central Depletion of Brain-Derived Neurotrophic Factor in Mice Results in High Bone Mass and Metabolic Phenotype

PubMed Central

Zayzafoon, M.; Rymaszewski, M.; Heiny, J.; Rios, M.; Hauschka, P. V.

2012-01-01

Brain-derived neurotrophic factor (BDNF) plays important roles in neuronal differentiation/survival, the regulation of food intake, and the pathobiology of obesity and type 2 diabetes mellitus. BDNF and its receptor are expressed in osteoblasts and chondrocyte. BDNF in vitro has a positive effect on bone; whether central BDNF affects bone mass in vivo is not known. We therefore examined bone mass and energy use in brain-targeted BDNF conditional knockout mice (Bdnf2lox/2lox/93). The deletion of BDNF in the brain led to a metabolic phenotype characterized by hyperphagia, obesity, and increased abdominal white adipose tissue. Central BDNF deletion produces a marked skeletal phenotype characterized by increased femur length, elevated whole bone mineral density, and bone mineral content. The skeletal changes are developmentally regulated and appear concurrently with the metabolic phenotype, suggesting that the metabolic and skeletal actions of BDNF are linked. The increased bone development is evident in both the cortical and trabecular regions. Compared with control, Bdnf2lox/2lox/93 mice show greater trabecular bone volume (+50% for distal femur, P < 0.001; +35% for vertebral body, P < 0.001) and midfemoral cortical thickness (+11 to 17%, P < 0.05), measured at 3 and 6 months of age. The skeletal and metabolic phenotypes were gender dependent, with female being more affected than male mice. However, uncoupling protein-1 expression in brown fat, a marker of sympathetic tone, was not different between genotypes. We show that deletion of central BDNF expression in mice results in increased bone mass and white adipose tissue, with no significant changes in sympathetic signaling or peripheral serotonin, associated with hyperphagia, obesity, and leptin resistance. PMID:23011922

Injectable Reactive Biocomposites For Bone Healing In Critical-Size Rabbit Calvarial Defects

DTIC Science & Technology

2012-03-29

defects (i.e. be conformable), provide temporary protection to the brain until the bone heals, and enhance tissue regeneration with the delivery of...temporary protection to the brain until the bone heals, and enhance tissue regeneration with the delivery of biologics. In this study, we evaluated the...complex defects (i.e. be conformable), harden to provide temporary protection until tissue remodels (i.e. be settable), and enhance tissue regeneration

Central Nervous System Fibrosis Is Associated with Fibrocyte-Like Infiltrates

PubMed Central

Aldrich, Amy; Kielian, Tammy

2011-01-01

Fibrotic wall formation is essential for limiting pathogen dissemination during brain abscess development. However, little is known about the regulation of fibrotic processes in the central nervous system (CNS). Most CNS injury responses are associated with hypertrophy of resident astrocytes, a process termed reactive gliosis. Studies of fibrosis outside the CNS have identified two bone marrow–derived cell types, fibrocytes and alternatively activated M2 macrophages, as key mediators of fibrosis. The current study used bone marrow chimeras generated from green fluorescent protein transgenic mice to evaluate the appearance of these cell types and whether bone marrow–derived cells were capable of acquiring fibrotic characteristics during brain abscess development. Immunofluorescence staining revealed partial overlap between green fluorescent protein, α-smooth muscle actin, and procollagen, suggesting that a population of cells forming the brain abscess capsule originate from a bone marrow precursor. In addition, the influx of fibrocyte-like cells into brain abscesses immediately preceded the onset of fibrotic encapsulation. Fibrotic wall formation was also associated with increased numbers of alternatively activated M2 microglia and macrophages. To our knowledge, this is the first study demonstrating that bone marrow–derived infiltrates are capable of expressing fibrotic molecules during CNS inflammation. PMID:22015460

A link between central kynurenine metabolism and bone strength in rats with chronic kidney disease

PubMed Central

Pawlak, Krystyna; Oksztulska-Kolanek, Ewa; Domaniewski, Tomasz; Znorko, Beata; Karbowska, Malgorzata; Citkowska, Aleksandra; Rogalska, Joanna; Roszczenko, Alicja; Brzoska, Malgorzata M.; Pawlak, Dariusz

2017-01-01

Background Disturbances in mineral and bone metabolism represent one of the most complex complications of chronic kidney disease (CKD). Serotonin, a monoamine synthesized from tryptophan, may play a potential role in bone metabolism. Brain-derived serotonin exerts a positive effect on the bone structure by limiting bone resorption and enhancing bone formation. Tryptophan is the precursor not only to the serotonin but also and primarily to kynurenine metabolites. The ultimate aim of the present study was to determine the association between central kynurenine metabolism and biomechanical as well as geometrical properties of bone in the experimental model of the early stage of CKD. Methods Thirty-three Wistar rats were randomly divided into two groups (sham-operated and subtotal nephrectomized animals). Three months after surgery, serum samples were obtained for the determination of biochemical parameters, bone turnover biomarkers, and kynurenine pathway metabolites; tibias were collected for bone biomechanical, bone geometrical, and bone mass density analysis; brains were removed and divided into five regions for the determination of kynurenine pathway metabolites. Results Subtotal nephrectomized rats presented higher serum concentrations of creatinine, urea nitrogen, and parathyroid hormone, and developed hypocalcemia. Several biomechanical and geometrical parameters were significantly elevated in rats with experimentally induced CKD. Subtotal nephrectomized rats presented significantly higher kynurenine concentrations and kynurenine/tryptophan ratio and significantly lower tryptophan levels in all studied parts of the brain. Kynurenine in the frontal cortex and tryptophan in the hypothalamus and striatum correlated positively with the main parameters of bone biomechanics and bone geometry. Discussion In addition to the complex mineral, hormone, and metabolite changes, intensified central kynurenine turnover may play an important role in the development of bone changes in the course of CKD. PMID:28439468

Brainstem auditory-evoked potentials as an objective tool for evaluating hearing dysfunction in traumatic brain injury.

PubMed

Lew, Henry L; Lee, Eun Ha; Miyoshi, Yasushi; Chang, Douglas G; Date, Elaine S; Jerger, James F

2004-03-01

Because of the violent nature of traumatic brain injury, traumatic brain injury patients are susceptible to various types of trauma involving the auditory system. We report a case of a 55-yr-old man who presented with communication problems after traumatic brain injury. Initial results from behavioral audiometry and Weber/Rinne tests were not reliable because of poor cooperation. He was transferred to our service for inpatient rehabilitation, where review of the initial head computed tomographic scan showed only left temporal bone fracture. Brainstem auditory-evoked potential was then performed to evaluate his hearing function. The results showed bilateral absence of auditory-evoked responses, which strongly suggested bilateral deafness. This finding led to a follow-up computed tomographic scan, with focus on bilateral temporal bones. A subtle transverse fracture of the right temporal bone was then detected, in addition to the left temporal bone fracture previously identified. Like children with hearing impairment, traumatic brain injury patients may not be able to verbalize their auditory deficits in a timely manner. If hearing loss is suspected in a patient who is unable to participate in traditional behavioral audiometric testing, brainstem auditory-evoked potential may be an option for evaluating hearing dysfunction.

Role of Regulators of G Protein Signaling Proteins in Bone Physiology and Pathophysiology.

PubMed

Jules, Joel; Yang, Shuying; Chen, Wei; Li, Yi-Ping

2015-01-01

Regulators of G protein signaling (RGS) proteins enhance the intrinsic GTPase activity of α subunits of the heterotrimeric G protein complex of G protein-coupled receptors (GPCRs) and thereby inactivate signal transduction initiated by GPCRs. The RGS family consists of nearly 37 members with a conserved RGS homology domain which is critical for their GTPase accelerating activity. RGS proteins are expressed in most tissues, including heart, lung, brain, kidney, and bone and play essential roles in many physiological and pathological processes. In skeletal development and bone homeostasis as well as in many bone disorders, RGS proteins control the functions of various GPCRs, including the parathyroid hormone receptor type 1 and calcium-sensing receptor and also regulate various critical signaling pathways, such as Wnt and calcium oscillations. This chapter will discuss the current findings on the roles of RGS proteins in regulating signaling of key GPCRs in skeletal development and bone homeostasis. We also will examine the current updates of RGS proteins' regulation of calcium oscillations in bone physiology and highlight the roles of RGS proteins in selected bone pathological disorders. Despite the recent advances in bone and mineral research, RGS proteins remain understudied in the skeletal system. Further understanding of the roles of RGS proteins in bone should not only provide great insights into the molecular basis of various bone diseases but also generate great therapeutic drug targets for many bone diseases. © 2015 Elsevier Inc. All rights reserved.

Cell fusion in the brain: two cells forward, one cell back.

PubMed

Kemp, Kevin; Wilkins, Alastair; Scolding, Neil

2014-11-01

Adult stem cell populations, notably those which reside in the bone marrow, have been shown to contribute to several neuronal cell types in the rodent and human brain. The observation that circulating bone marrow cells can migrate into the central nervous system and fuse with, in particular, cerebellar Purkinje cells has suggested, at least in part, a potential mechanism behind this process. Experimentally, the incidence of cell fusion in the brain is enhanced with age, radiation exposure, inflammation, chemotherapeutic drugs and even selective damage to the neurons themselves. The presence of cell fusion, shown by detection of increased bi-nucleated neurons, has also been described in a variety of human central nervous system diseases, including both multiple sclerosis and Alzheimer's disease. Accumulating evidence is therefore raising new questions into the biological significance of cell fusion, with the possibility that it represents an important means of cell-mediated neuroprotection or rescue of highly complex neurons that cannot be replaced in adult life. Here, we discuss the evidence behind this phenomenon in the rodent and human brain, with a focus on the subsequent research investigating the physiological mechanisms of cell fusion underlying this process. We also highlight how these studies offer new insights into endogenous neuronal repair, opening new exciting avenues for potential therapeutic interventions against neurodegeneration and brain injury.

Bone and bone turnover.

PubMed

Crofton, Patricia M

2009-01-01

Children with cancer are exposed to multiple influences that may adversely affect bone health. Some treatments have direct deleterious effects on bone whilst others may have indirect effects mediated through various endocrine abnormalities. Most clinical outcome studies have concentrated on survivors of acute lymphoblastic leukaemia (ALL). There is now good evidence that earlier treatment protocols that included cranial irradiation with doses of 24 Gy or greater may result in growth hormone deficiency and low bone mineral density (BMD) in the lumbar spine and femoral neck. Under current protocols, BMD decreases during intensive chemotherapy and fracture risk increases. Although total body BMD may eventually return to normal after completion of chemotherapy, lumbar spine trabecular BMD may remain low for many years. The implications for long-term fracture risk are unknown. Risk factors for low BMD include high dose methotrexate, higher cumulative doses of glucocorticoids, male gender and low physical activity. BMD outcome in non-ALL childhood cancers has been less well studied but there is evidence that survivors of childhood brain or bone tumours, and survivors of bone marrow transplants for childhood malignancy, all have a high risk of long-term osteopenia. Long-term follow-up is required, with appropriate treatment of any endocrine abnormalities identified. Copyright (c) 2009 S. Karger AG, Basel.

Esophageal squamous cell carcinoma with dural and bone marrow metastases.

PubMed

Chen, Yen-Hao; Huang, Cheng-Hua

2014-09-21

Patients with esophageal squamous cell carcinoma generally present at an advanced stage at the time of diagnosis. The most common sites of visceral metastasis are the lung, liver and bone, but brain and bone marrow involvement is exceedingly rare. Herein, we report a 62-year-old man with a 4-wk history of progressive low back pain with radiation to bilateral lower legs, dysphagia and body weight loss. Esophageal squamous cell carcinoma with regional lymph node, liver and bone metastases was diagnosed. He underwent concurrent chemoradiotherapy and got a partial response. Four months later, he complained of headache, diplopia and severe hearing impairment in the left ear. There was no evidence for bacterial, fungal, tuberculous infection or neoplastic infiltration. Magnetic resonance imaging of the brain demonstrated thickening and enhancement of bilateral pachymeninges and multiple enhancing masses in bilateral skull. Dural metastasis was diagnosed and he received whole brain irradiation. In addition, laboratory examination revealed severe thrombocytopenia and leucopenia, and bone marrow study confirmed the diagnosis of metastatic squamous cell carcinoma. This is the first described case of esophageal squamous cell carcinoma with dural and bone marrow metastases. We also discuss the pathogenesis of unusual metastatic diseases and differential diagnosis of pachymeningeal thickening.

Treatment of stroke with (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate and bone marrow stromal cells upregulates angiopoietin-1/Tie2 and enhances neovascularization.

PubMed

Cui, X; Chen, J; Zacharek, A; Roberts, C; Savant-Bhonsale, S; Chopp, M

2008-09-22

Neovascularization may contribute to functional recovery after neural injury. Combination treatment of stroke with a nitric oxide donor, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate (DETA-NONOate) and bone marrow stromal cells promotes functional recovery. However, the mechanisms underlying functional improvement have not been elucidated. In this study, we tested the hypothesis that combination treatment upregulates angiopoietin-1 and its receptor Tie2 in the ischemic brain and bone marrow stromal cells, thereby enhancing cerebral neovascularization after stroke. Adult wild type male C57BL/6 mice were i.v. administered PBS, bone marrow stromal cells 5x10(5), DETA-NONOate 0.4 mg/kg or combination DETA-NONOate with bone marrow stromal cells (n=12/group) after middle cerebral artery occlusion. Combination treatment significantly upregulated angiopoietin-1/Tie2 and tight junction protein (occludin) expression, and increased the number, diameter and perimeter of blood vessels in the ischemic brain compared with vehicle control (mean+ or -S.E., P<0.05). In vitro, DETA-NONOate significantly increased angiopoietin-1/Tie2 protein (n=6/group) and Tie2 mRNA (n=3/group) expression in bone marrow stromal cells. DETA-NONOate also significantly increased angiopoietin-1 protein (n=6/group) and mRNA (n=3/group) expression in mouse brain endothelial cells (P<0.05). Angiopoietin-1 mRNA (n=3/group) was significantly increased in mouse brain endothelial cells treated with DETA-NONOate in combination with bone marrow stromal cell-conditioned medium compared with cells treated with bone marrow stromal cell-conditioned medium or DETA-NONOate alone. Mouse brain endothelial cell capillary tube-like formation assays (n=6/group) showed that angiopoietin-1 peptide, the supernatant of bone marrow stromal cells and DETA-NONOate significantly increased capillary tube formation compared with vehicle control. Combination treatment significantly increased capillary tube formation compared with DETA-NONOate treatment alone. Inhibition of angiopoietin-1 significantly attenuated combination treatment-induced tube formation. Our data indicated that combination treatment of stroke with DETA-NONOate and bone marrow stromal cells promotes neovascularization, which is at least partially mediated by upregulation of the angiopoietin-1/Tie2 axis.

Alpha-7 nicotinic acetylcholine receptor agonist treatment reduces neuroinflammation, oxidative stress, and brain injury in mice with ischemic stroke and bone fracture.

PubMed

Han, Zhenying; Li, Li; Wang, Liang; Degos, Vincent; Maze, Mervyn; Su, Hua

2014-11-01

Bone fracture at the acute stage of stroke exacerbates stroke injury by increasing neuroinflammation. We hypothesize that activation of α-7 nicotinic acetylcholine receptor (α-7 nAchR) attenuates neuroinflammation and oxidative stress, and reduces brain injury in mice with bone fracture and stroke. Permanent middle cerebral artery occlusion (pMCAO) was performed in C57BL/6J mice followed by tibia fracture 1 day later. Mice were treated with 0.8 mg/kg PHA 568487 (PHA, α-7 nAchR-specific agonist), 6 mg/kg methyllycaconitine (α-7 nAchR antagonist), or saline 1 and 2 days after pMCAO. Behavior was tested 3 days after pMCAO. Neuronal injury, CD68(+) , M1 (pro-inflammatory) and M2 (anti-inflammatory) microglia/macrophages, phosphorylated p65 component of nuclear factor kappa b in microglia/macrophages, oxidative and anti-oxidant gene expression were quantified. Compared to saline-treated mice, PHA-treated mice performed better in behavioral tests, had fewer apoptotic neurons (NeuN(+) TUNEL(+) ), fewer CD68(+) and M1 macrophages, and more M2 macrophages. PHA increased anti-oxidant gene expression and decreased oxidative stress and phosphorylation of nuclear factor kappa b p65. Methyllycaconitine had the opposite effects. Our data indicate that α-7 nAchR agonist treatment reduces neuroinflammation and oxidative stress, which are associated with reduced brain injury in mice with ischemic stroke plus tibia fracture. Bone fracture at the acute stage of stroke exacerbates neuroinflammation, oxidative stress, and brain injury, and our study has shown that the α-7 nAchR agonist, PHA (PHA 568487), attenuates neuroinflammation, oxidative stress, and brain injury in mice with stroke and bone fracture. Hence, PHA could provide an opportunity to develop a new strategy to reduce brain injury in patients suffering from stroke and bone fracture. © 2014 International Society for Neurochemistry.

Wild Type Bone Marrow Transplant Partially Reverses Neuroinflammation in Progranulin-Deficient Mice

PubMed Central

Yang, Yue; Aloi, Macarena S.; Cudaback, Eiron; Josephsen, Samuel R.; Rice, Samantha J.; Jorstad, Nikolas L.; Keene, C. Dirk; Montine, Thomas J.

2014-01-01

Frontotemporal dementia (FTD) is a neurodegenerative disease with devastating changes in behavioral performance and social function. Mutations in the progranulin gene (GRN) are one of the most common causes of inherited FTD due to reduced progranulin expression or activity, including in brain where it is expressed primarily by neurons and microglia. Thus, efforts aimed at enhancing progranulin levels might be a promising therapeutic strategy. Bone marrow-derived cells are able to engraft in the brain and adopt a microglial phenotype under myeloablative irradiation conditioning. This ability makes bone marrow (BM)-derived cells a potential cellular vehicle for transferring therapeutic molecules to the central nervous system. Here, we utilized BM cells from Grn+/+ (wild type or wt) mice labeled with green fluorescence protein for delivery of progranulin to progranulin deficient (Grn−/−) mice. Our results showed that wt bone marrow transplantation (BMT) partially reconstituted progranulin in the periphery and in cerebral cortex of Grn−/− mice. We demonstrated a pro-inflammatory effect in vivo and in ex vivo preparations of cerebral cortex of Grn−/− mice that was partially to fully reversed five months after BMT. Our findings suggest that BMT can be administered as a stem cell-based approach to prevent or to treat neurodegenerative diseases. PMID:25199051

A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury

DTIC Science & Technology

2011-09-01

parietal bones, and a threaded rod was implanted into the interparietal bone. These were affixed to the skull with dental acrylic. A hybrid, 16...then sealed with a silicone polymer (Kwik-Cast, WPI). The base of the probe connector was lowered onto the dental acrylic and fixed into place. An...the skull using a dental drill with a trephine bit over the cortex contralateral to the dominant forelimb. A total of 14 animals received CCI in the

Lomustine Nanoparticles Enable Both Bone Marrow Sparing and High Brain Drug Levels - A Strategy for Brain Cancer Treatments.

PubMed

Fisusi, Funmilola A; Siew, Adeline; Chooi, Kar Wai; Okubanjo, Omotunde; Garrett, Natalie; Lalatsa, Katerina; Serrano, Dolores; Summers, Ian; Moger, Julian; Stapleton, Paul; Satchi-Fainaro, Ronit; Schätzlein, Andreas G; Uchegbu, Ijeoma F

2016-05-01

The blood brain barrier compromises glioblastoma chemotherapy. However high blood concentrations of lipophilic, alkylating drugs result in brain uptake, but cause myelosuppression. We hypothesised that nanoparticles could achieve therapeutic brain concentrations without dose-limiting myelosuppression. Mice were dosed with either intravenous lomustine Molecular Envelope Technology (MET) nanoparticles (13 mg kg(-1)) or ethanolic lomustine (6.5 mg kg(-1)) and tissues analysed. Efficacy was assessed in an orthotopic U-87 MG glioblastoma model, following intravenous MET lomustine (daily 13 mg kg(-1)) or ethanolic lomustine (daily 1.2 mg kg(-1) - the highest repeated dose possible). Myelosuppression and MET particle macrophage uptake were also investigated. The MET formulation resulted in modest brain targeting (brain/ bone AUC0-4h ratios for MET and ethanolic lomustine = 0.90 and 0.53 respectively and brain/ liver AUC0-4h ratios for MET and ethanolic lomustine = 0.24 and 0.15 respectively). The MET formulation significantly increased mice (U-87 MG tumours) survival times; with MET lomustine, ethanolic lomustine and untreated mean survival times of 33.2, 22.5 and 21.3 days respectively and there were no material treatment-related differences in blood and femoral cell counts. Macrophage uptake is slower for MET nanoparticles than for liposomes. Particulate drug formulations improved brain tumour therapy without major bone marrow toxicity.

The impact of peripheral serotonin on leptin-brain serotonin axis, bone metabolism and strength in growing rats with experimental chronic kidney disease.

PubMed

Pawlak, Dariusz; Domaniewski, Tomasz; Znorko, Beata; Oksztulska-Kolanek, Ewa; Lipowicz, Paweł; Doroszko, Michał; Karbowska, Malgorzata; Pawlak, Krystyna

2017-12-01

Chronic kidney disease (CKD) results in decreased bone strength. Serotonin (5-HT) is one of the critical regulators of bone health, fulfilling distinct functions depending on its synthesis site: brain-derived serotonin (BDS) favors osteoblast proliferation, whereas gut-derived serotonin (GDS) inhibits it. We assessed the role of BDS and peripheral leptin in the regulation of bone metabolism and strength in young rats with 5/6 nephrectomy. BDS synthesis was accelerated during CKD progression. Decreased peripheral leptin in CKD rats was inversely related to BDS content in the hypothalamus, brainstem and frontal cortex. Serotonin in these brain regions affected bone strength and metabolism in the studied animals. The direct effect of circulating leptin on bone was not shown in uremia. At the molecular level, there was an inverse association between elevated GDS and the expression of cAMP responsive element-binding protein (Creb) gene in bone of CKD animals. In contrast, increased expression of activating transcription factor 4 (Atf4) was shown, which was associated with GDS-dependent transcription factor 1 (Foxo1), clock gene - Cry-1, cell cycle genes: c-Myc, cyclins, and osteoblast differentiation genes. These results identified a previously unknown molecular pathway, by which elevated GDS can shift in Foxo1 target genes from Creb to Atf4-dependent response, disrupting the leptin-BDS - dependent gene pathway in the bone of uremic rats. Thus, in the condition of CKD the effect of BDS and GDS on bone metabolism and strength can't be distinguished. Copyright © 2017 Elsevier Inc. All rights reserved.

The prophylactic reduction of aluminium intake.

PubMed

Lione, A

1983-02-01

The use of modern analytical methods has demonstrated that aluminium salts can be absorbed from the gut and concentrated in various human tissues, including bone, the parathyroids and brain. The neurotoxicity of aluminium has been extensively characterized in rabbits and cats, and high concentrations of aluminium have been detected in the brain tissue of patients with Alzheimer's disease. Various reports have suggested that high aluminium intakes may be harmful to some patients with bone disease or renal impairment. Fatal aluminium-induced neuropathies have been reported in patients on renal dialysis. Since there are no demonstrable consequences of aluminium deprivation, the prophylactic reduction of aluminium intake by many patients would appear prudent. In this report, the major sources of aluminium in foods and non-prescription drugs are summarized and alternative products are described. The most common foods that contain substantial amounts of aluminium-containing additives include some processed cheeses, baking powders, cake mixes, frozen doughs, pancake mixes, self-raising flours and pickled vegetables. The aluminium-containing non-prescription drugs include some antacids, buffered aspirins, antidiarrhoeal products, douches and haemorrhoidal medications. The advisability of recommending a low aluminium diet for geriatric patients is discussed in detail.

Brains, Bones, and Aging: Psychotropic medications and bone health among older adults

PubMed Central

Brown, Monique J.; Mezuk, Briana

2012-01-01

Psychotropic drugs are a crucial element of treatment for psychiatric disorders; however there is an established association between many classes of psychotropic medications and fracture risk among older adults, and growing evidence that some classes of medications may also impact bone mineral density (BMD). In this paper we review recent epidemiologic research on the association between psychotropic medications and osteoporosis, and discuss current controversies and unresolved issues surrounding this relationship. Key areas in need of focused inquiry include resolving whether the apparent association between psychotropic medications and BMD is due to confounding by indication, whether this relationship differs for men and women, and whether the implications of these medications for bone health vary over the life course. Clinical research to delineate the risk/benefit ratio of psychotropic medications for older adults, particularly those who are at high risk for fracture, is also needed to facilitate prescribing decisions between patients and physicians. PMID:23001917

Small Vessel Disease/White Matter Disease of the Brain and Its Association With Osteoporosis

PubMed Central

Alagiakrishnan, Kannayiram; Hsueh, Jenny; Zhang, Edwin; Khan, Khurshid; Senthilselvan, Ambikaipakan

2015-01-01

Background Evidence now suggests the role of neural effect on bone mass control. The effect of small vessel disease of the brain on osteoporosis has not been studied. The aim of this study was to investigate the association of white matter disease (WMD) of the brain with osteoporosis in the elderly. Methods In this retrospective cross-sectional study, 780 consecutive patient charts between 2010 and 2011 were reviewed in the Senior’s Outpatient Clinic at the University of Alberta Hospital. Subjects with brain computerized tomography (CT) were included in the study. Subjects with incomplete information, intracranial hemorrhage, acute stroke, cerebral edema, and/or normal pressure hydrocephalus on the CT were excluded. WMD was quantified on CT using Wahlund’s scoring protocol. Osteoporosis information was obtained from the chart, which has been diagnosed based on bone mineral density (BMD) information. Logistic regression analysis was done to determine the association of WMD severity with osteoporosis after controlling for confounding vascular risk factors. Results Of the 505 subjects who were included in the study, 188 (37%) had osteoporosis and 171 (91%) of these osteoporotic subjects were females. The mean age was 79.8 ± 7.04 years. The prevalence of WMD in osteoporosis subjects was 73%. In the unadjusted logistic regression analysis, there was a significant association between WMD severity and osteoporosis (odds ratio (OR): 1.10; 95% confidence interval (CI): 1.05 - 1.14; P < 0.001) and the significance remained in the adjusted model, after correcting for age, sex and all vascular risk factors (OR: 1.11; 95% CI: 1.05 - 1.18; P < 0.001). Conclusion WMD severity of the brain was associated with osteoporosis in the elderly. PMID:25780476

Cancer pain physiology

PubMed Central

Falk, Sarah; Bannister, Kirsty

2014-01-01

Mechanisms of inflammatory and neuropathic pains have been elucidated and translated to patient care by the use of animal models of these pain states. Cancer pain has lagged behind since early animal models of cancer-induced bone pain were based on the systemic injection of carcinoma cells. This precluded systematic investigation of specific neuronal and pharmacological alterations that occur in cancer-induced bone pain. In 1999, Schwei et al. described a murine model of cancer-induced bone pain that paralleled the clinical condition in terms of pain development and bone destruction, confined to the mouse femur. This model prompted related approaches, and we can now state that cancer pain may include elements of inflammatory and neuropathic pains but also unique changes in sensory processing. Cancer-induced bone pain results in progressive bone destruction, elevated osteoclast activity and distinctive nocifensive behaviours (indicating the triad of ongoing, spontaneous and movement-induced hyperalgesia). In addition, cancer cells induce an inflammatory infiltrate and release growth factors, cytokines, interleukins, chemokines, prostanoids and endothelins, resulting in a reduction of pH to below 5 and direct deformation of primary afferents within bone. These peripheral changes, in turn, drive hypersensitivity of spinal cord sensory neurons, many of which project to the parts of the brain involved in the emotional response to pain. Within the spinal cord, a unique neuronal function reorganization within segments of the dorsal horn of the spinal cord receiving nociceptive input from the bone are discussed. Changes in certain neurotransmitters implicated in brain modulation of spinal function are also altered with implications for the affective components of cancer pain. Treatments are described in terms of mechanistic insights and in the case of opioids, which modulate pain transmission at spinal and supraspinal sites, their use can be compromised by opioid-induced hyperalgesia. We discuss evidence for how this comes about and how it may be treated. PMID:26516549

Concepts on the pathogenesis of adolescent idiopathic scoliosis. Bone growth and mass, vertebral column, spinal cord, brain, skull, extra-spinal left-right skeletal length asymmetries, disproportions and molecular pathogenesis.

PubMed

Burwell, R Geoffrey; Dangerfield, Peter H; Freeman, Brian J C

2008-01-01

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). Encouraging advances thought to be related to AIS pathogenesis have recently been made in several fields including anthropometry of bone growth, bone mass, spinal growth modulation, extra-spinal left-right skeletal length asymmetries and disproportions, magnetic resonance imaging of vertebral column, spinal cord, brain, skull, and molecular pathogenesis. These advances are leading to the evaluation of new treatments including attempts at minimally invasive surgery on the spine and peri-apical ribs. Several concepts of AIS are outlined indicating their clinical applications but not their research potential. The concepts, by derivation morphological, molecular and mathematical, are addressed in 15 sections: 1) initiating and progressive factors; 2) relative anterior spinal overgrowth; 3) dorsal shear forces that create axial rotational instability; 4) rotational preconstraint; 5) uncoupled, or asynchronous, spinal neuro-osseous growth; 6) brain, nervous system and skull; 7) a novel neuro-osseous escalator concept based on a putative abnormality of two normal polarized processes namely, a) increasing skeletal dimensions, and b) the CNS body schema - both contained within a neuro-osseous timing of maturation (NOTOM) concept; 8) transverse plane pelvic rotation, skeletal asymmetries and developmental theory; 9) thoraco-spinal concept; 10) origin in contracture at the hips; 11) osteopenia; 12) melatonin deficiency; 13) systemic melatonin-signaling pathway dysfunction; 14) platelet calmodulin dysfunction; and 15) biomechanical spinal growth modulation. From these concepts, a collective model for AIS pathogenesis is formulated. The central concept of this model includes the body schema of the neural systems, widely-studied in adults, that control normal posture and coordinated movements with frames of reference in the posterior parietal cortex. The escalator concept has implications for the normal development of upright posture, and the evolution in humans of neural control, the trunk and unique bipedal gait.

Multiple bone metastases from glioblastoma multiforme without local brain relapse: a case report and review of the literature.

PubMed

Takanen, Silvia; Bangrazi, Caterina; Caiazzo, Rossella; Raffetto, Nicola; Tombolini, Vincenzo

2013-01-01

Extracranial metastases from glioblastoma multiforme (GBM) are a very rare event, even if an increasing incidence has been documented. We report the case of a young woman with primary GBM who developed bone metastases without local brain relapse. Because of persistent headache and visual disturbances, in March 2011 the patient underwent magnetic resonance imaging (MRI) evidencing a temporoparietal mass, which was surgically resected. Histology revealed GBM. She was given concomitant chemoradiotherapy according to the Stupp regimen. After a 4-week break, the patient received 6 cycles of adjuvant temozolomide according to the standard 5-day schedule every 28 days. In December 2011 she complained of progressive low back pain, and MRI showed multiple bone metastases from primary GBM, confirmed by histology. Cases of metastatic GBM in concurrence with a primary brain tumor or local relapse are more common in the literature; only a few cases have been reported where extracranial metastases from GBM occurred without any relapse in the brain. Here we report our experience.

Neurosurgical treatment of breast cancer metastases to the neurocranium.

PubMed

Stark, Andreas M

2010-12-16

Breast cancer metastases to the neurocranium might involve the bone, the dura, or the brain parenchyma. The latter location is the far most common. The annual incidence of brain metastases in patients with breast cancer is in the range of 4-11 per 100.000 persons per year. Symptoms and findings mainly result from the location of the lesion. The diagnostic method of choice is magnetic resonance imaging before and after administration of contrast material. Breast cancer brain metastases present as solid, cystic, or partially cystic lesions with marked contrast enhancement and perilesional edema. The therapeutic option of choice is microsurgical resection whenever possible. Adjuvant treatment includes radiotherapy, radiosurgery, and/or chemotherapy.

Neurosurgical Treatment of Breast Cancer Metastases to the Neurocranium

PubMed Central

Stark, Andreas M.

2011-01-01

Breast cancer metastases to the neurocranium might involve the bone, the dura, or the brain parenchyma. The latter location is the far most common. The annual incidence of brain metastases in patients with breast cancer is in the range of 4–11 per 100.000 persons per year. Symptoms and findings mainly result from the location of the lesion. The diagnostic method of choice is magnetic resonance imaging before and after administration of contrast material. Breast cancer brain metastases present as solid, cystic, or partially cystic lesions with marked contrast enhancement and perilesional edema. The therapeutic option of choice is microsurgical resection whenever possible. Adjuvant treatment includes radiotherapy, radiosurgery, and/or chemotherapy. PMID:21209717

Wild-type bone marrow transplant partially reverses neuroinflammation in progranulin-deficient mice.

PubMed

Yang, Yue; Aloi, Macarena S; Cudaback, Eiron; Josephsen, Samuel R; Rice, Samantha J; Jorstad, Nikolas L; Keene, C Dirk; Montine, Thomas J

2014-11-01

Frontotemporal dementia (FTD) is a neurodegenerative disease with devastating changes in behavioral performance and social function. Mutations in the progranulin gene (GRN) are one of the most common causes of inherited FTD due to reduced progranulin expression or activity, including in brain where it is expressed primarily by neurons and microglia. Thus, efforts aimed at enhancing progranulin levels might be a promising therapeutic strategy. Bone marrow (BM)-derived cells are able to engraft in the brain and adopt a microglial phenotype under myeloablative irradiation conditioning. This ability makes BM-derived cells a potential cellular vehicle for transferring therapeutic molecules to the central nervous system. Here, we utilized BM cells from Grn(+/+) (wild type or wt) mice labeled with green fluorescence protein for delivery of progranulin to progranulin-deficient (Grn(-/-)) mice. Our results showed that wt bone marrow transplantation (BMT) partially reconstituted progranulin in the periphery and in cerebral cortex of Grn(-/-) mice. We demonstrated a pro-inflammatory effect in vivo and in ex vivo preparations of cerebral cortex of Grn(-/-) mice that was partially to fully reversed 5 months after BMT. Our findings suggest that BMT can be administered as a stem cell-based approach to prevent or to treat neurodegenerative diseases.

Impact of the material composition on proton range variation - A Monte Carlo study

NASA Astrophysics Data System (ADS)

Wu, S. W.; Tung, C. J.; Lee, C. C.; Fan, K. H.; Huang, H. C.; Chao, T. C.

2015-11-01

In this study, we used the Geant4 toolkit to demonstrate the impacts of the material composition of tissues on proton range variation. Bragg curves of different materials subjected to a 250 MeV mono-energy proton beam were simulated and compared. These simulated materials included adipose, heart, brain, cartilage, cortical bone and water. The results showed that there was significant proton range deviation between Bragg curves, especially for cortical bone. The R50 values for a 250 MeV proton beam were approximately 39.55 cm, 35.52 cm, 37.00 cm, 36.51 cm, 36.72 cm, 22.53 cm, and 38.52 cm in the phantoms that were composed completely of adipose, cartilage, tissue, heart, brain, cortical bone, and water, respectively. Mass density and electron density were used to scale the proton range for each material; electron density provided better range scaling. In addition, a similar comparison was performed by artificially setting all material density to 1.0 g/cm3 to evaluate the range deviation due to chemical components alone. Tissue heterogeneity effects due to density variation were more significant, and less significant for chemical composition variation unless the Z/A was very different.

Effects of diquat, an aquatic herbicide, on the development of mallard embryos

USGS Publications Warehouse

Sewalk, C.J.; Brewer, G.L.; Hoffman, D.J.

2001-01-01

Bipyridylium herbicides produce embryotoxic and teratogenic effects in dipteran, amphibian, avian, and mammalian organisms. Diquat dibromide, a bipyridylium compound, is commonly used as an aquatic herbicide. Mallard (Anas platyrhynchos) eggs were exposed to diquat by immersing the eggs for 10s in solutions of 0.88, 3.5, 7, 14, or 56 g/L on either the fourth or twenty-first day of incubation. Application of diquat on day 4 yielded an estimated LC50 of 19.5 g/L through 18 days of incubation, and 9.6 g/L through hatching. Body and organ weights, and bone lengths of hatchlings did not differ between control and treatment groups with the exception of a slight increase in brain weight in the 14 g/L group. Malformations in diquat-treated embryos included defects of the brain, eye, bill, limb, and pelvis; skeletal scoliosis; and incomplete ossification. Subcutaneous edema was also present. Significant manifestations of oxidative stress were apparent in hatchlings and included increased hepatic thiobarbituric acid reactive substances (TBARS) (lipid peroxidation) and decreased brain reduced glutathione (GSH). Brain protein-bound sulfhydryls (PBSH) increased. Diquat applied on day 21 of incubation yielded an estimated LC50 of 12.6 g/L through hatching. Exposure at this late stage of development did not produce deformities. Body and organ weights, and, bone lengths of hatchlings did not differ between control and treatment groups. Significant manifestations of oxidative stress in hatchlings included decreased brain GSH, increased oxidized glutathione (GSSG) and ratio of GSSG:GSH. This study suggests that concentrations of diquat commonly used for aquatic weed control, when based upon the expected dilution effect of average water depth of the application area, would probably have little impact on mallard embryos. However, concentrations applied above ground to weeds and cattails along the edge of waters and ditches could adversely affect the survival and development of mallard embryos, and presumably other avian species nesting in such habitats.

Developmental abnormalities of the occipital bone in human chondrodystrophies (achondroplasia and thanatophoric dwarfism).

PubMed

Marin-Padilla, M; Marin-Padilla, T M

1977-01-01

Specific developmental malformations have been demonstrated in the occipital bone of two chondrodysplastic disorders (achondroplasia and thanatophoric dwarfism). Analysis of these malformations indicates that the occipital bone is primary affected in these disorders. In both cases, the endochondral-derived components of the occipital bone (the basioccipital, the two lateral parts, and the planum nuchale of the squama occipitalis) have failed to grow properly and are smaller and shorter than normal. On the other hand, the planum occipitalis of the squama, which derives from intramembranous ossification, is unaffected. In addition, the nature of these abnormalities indicates that the occipital synchondroses, together with the epiphyseal plates of other bones, are primarily affected in these two chondrodysplasias. The components of the occipital bone formed between the affected synchondroses failed to grow normally. The resulting malformation of the occipital bone is undoubtedly the cause of the shortening of the posterior cerebral fossa and of the considerable narrowing of the foramen magnum often described in these chondrodysplasias. It is postulated that growth disturbances between the affected occipital bone and the unaffected central nervous system results in the inadequacy of the posterior cerebral fossa and the foramen magnum to accommodate the growing brain. Consequently, compression of the brain at the posterior cerebral fossa or the foramen magnum levels could occur and thus lead to neurologic complications such as hydrocephalus and compression of the brain stem. It is suggested that the surgical removal of the fused posterior border of the lateral parts of the occipital bone (partial nuchalectomy) for the purpose of enlarging the narrow foramen magnum may be indicated in those chondrodysplastic children who develop these types of neurologic complications.

Analysis of tumor- and stroma-supplied proteolytic networks reveals a brain metastasis-promoting role for cathepsin S

PubMed Central

Sevenich, Lisa; Bowman, Robert L.; Mason, Steven D.; Quail, Daniela F.; Rapaport, Franck; Elie, Benelita T.; Brogi, Edi; Brastianos, Priscilla K.; Hahn, William C.; Holsinger, Leslie J.; Massagué, Joan; Leslie, Christina S.; Joyce, Johanna A.

2014-01-01

Metastasis remains the most common cause of death in most cancers, with limited therapies for combating disseminated disease. While the primary tumor microenvironment is an important regulator of cancer progression, it is less well understood how different tissue environments influence metastasis. We analyzed tumor-stroma interactions that modulate organ tropism of brain, bone and lung metastasis in xenograft models. We identified a number of potential modulators of site-specific metastasis, including cathepsin S as a regulator of breast-to-brain metastasis. High cathepsin S expression at the primary site correlated with decreased brain metastasis-free survival in breast cancer patients. Both macrophages and tumor cells produce cathepsin S, and only the combined depletion significantly reduced brain metastasis in vivo. Cathepsin S specifically mediates blood-brain barrier transmigration via proteolytic processing of the junctional adhesion molecule (JAM)-B. Pharmacological inhibition of cathepsin S significantly reduced experimental brain metastasis, supporting its consideration as a therapeutic target for this disease. PMID:25086747

Brain and Bone Damage in KARAP/DAP12 Loss-of-Function Mice Correlate with Alterations in Microglia and Osteoclast Lineages

PubMed Central

Nataf, Serge; Anginot, Adrienne; Vuaillat, Carine; Malaval, Luc; Fodil, Nassima; Chereul¶, Emmanuel; Langlois¶, Jean-Baptiste; Dumontel, Christiane; Cavillon, Gaelle; Confavreux, Christian; Mazzorana, Marlène; Vico, Laurence; Belin, Marie-Franaçoise; Vivier, Eric; Tomasello, Elena; Jurdic, Pierre

2005-01-01

Human polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy, also known as Nasu-Hakola disease, has been described to be associated with mutations affecting the immunoreceptor tyrosine-based activation motif-bearing KARAP/DAP12 immunoreceptor gene. Patients present bone fragilities and severe neurological alterations leading to presenile dementia. Here we investigated whether the absence of KARAP/DAP12-mediated signals in loss-of-function (KΔ75) mice also leads to bone and central nervous system pathological features. Histological analysis of adult KΔ75 mice brains revealed a diffuse hypomyelination predominating in anterior brain regions. As this was not accompanied by oligodendrocyte degeneration or microglial cell activation it suggests a developmental defect of myelin formation. Interestingly, in postnatal KΔ75 mice, we observed a dramatic reduction in microglial cell numbers similar to in vitro microglial cell differentiation impairment. Our results raise the intriguing possibility that defective microglial cell differentiation might be responsible for abnormal myelin development. Histomorphometry revealed that bone remodeling is also altered, because of a resorption defect, associated with a severe block of in vitro osteoclast differentiation. In addition, we show that, among monocytic lineages, KARAP/DAP12 specifically controls microglial and osteoclast differentiation. Our results confirm that KARAP/DAP12-mediated signals play an important role in the regulation of both brain and bone homeostasis. Yet, important differences exist between the symptoms observed in Nasu-Hakola patients and KΔ75 mice. PMID:15632019

Methods for intraoperative, sterile pose-setting of patient-specific microstereotactic frames

NASA Astrophysics Data System (ADS)

Vollmann, Benjamin; Müller, Samuel; Kundrat, Dennis; Ortmaier, Tobias; Kahrs, Lüder A.

2015-03-01

This work proposes new methods for a microstereotactic frame based on bone cement fixation. Microstereotactic frames are under investigation for minimal invasive temporal bone surgery, e.g. cochlear implantation, or for deep brain stimulation, where products are already on the market. The correct pose of the microstereotactic frame is either adjusted outside or inside the operating room and the frame is used for e.g. drill or electrode guidance. We present a patientspecific, disposable frame that allows intraoperative, sterile pose-setting. Key idea of our approach is bone cement between two plates that cures while the plates are positioned with a mechatronics system in the desired pose. This paper includes new designs of microstereotactic frames, a system for alignment and first measurements to analyze accuracy and applicable load.

Window classification of brain CT images in biomedical articles.

PubMed

Xue, Zhiyun; Antani, Sameer; Long, L Rodney; Demner-Fushman, Dina; Thoma, George R

2012-01-01

Effective capability to search biomedical articles based on visual properties of article images may significantly augment information retrieval in the future. In this paper, we present a new method to classify the window setting types of brain CT images. Windowing is a technique frequently used in the evaluation of CT scans, and is used to enhance contrast for the particular tissue or abnormality type being evaluated. In particular, it provides radiologists with an enhanced view of certain types of cranial abnormalities, such as the skull lesions and bone dysplasia which are usually examined using the " bone window" setting and illustrated in biomedical articles using "bone window images". Due to the inherent large variations of images among articles, it is important that the proposed method is robust. Our algorithm attained 90% accuracy in classifying images as bone window or non-bone window in a 210 image data set.

Brain mesenchymal stem cells: The other stem cells of the brain?

PubMed

Appaix, Florence; Nissou, Marie-France; van der Sanden, Boudewijn; Dreyfus, Matthieu; Berger, François; Issartel, Jean-Paul; Wion, Didier

2014-04-26

Multipotent mesenchymal stromal cells (MSC), have the potential to differentiate into cells of the mesenchymal lineage and have non-progenitor functions including immunomodulation. The demonstration that MSCs are perivascular cells found in almost all adult tissues raises fascinating perspectives on their role in tissue maintenance and repair. However, some controversies about the physiological role of the perivascular MSCs residing outside the bone marrow and on their therapeutic potential in regenerative medicine exist. In brain, perivascular MSCs like pericytes and adventitial cells, could constitute another stem cell population distinct to the neural stem cell pool. The demonstration of the neuronal potential of MSCs requires stringent criteria including morphological changes, the demonstration of neural biomarkers expression, electrophysiological recordings, and the absence of cell fusion. The recent finding that brain cancer stem cells can transdifferentiate into pericytes is another facet of the plasticity of these cells. It suggests that the perversion of the stem cell potential of pericytes might play an even unsuspected role in cancer formation and tumor progression.

Brain mesenchymal stem cells: The other stem cells of the brain?

PubMed Central

Appaix, Florence; Nissou, Marie-France; van der Sanden, Boudewijn; Dreyfus, Matthieu; Berger, François; Issartel, Jean-Paul; Wion, Didier

2014-01-01

Multipotent mesenchymal stromal cells (MSC), have the potential to differentiate into cells of the mesenchymal lineage and have non-progenitor functions including immunomodulation. The demonstration that MSCs are perivascular cells found in almost all adult tissues raises fascinating perspectives on their role in tissue maintenance and repair. However, some controversies about the physiological role of the perivascular MSCs residing outside the bone marrow and on their therapeutic potential in regenerative medicine exist. In brain, perivascular MSCs like pericytes and adventitial cells, could constitute another stem cell population distinct to the neural stem cell pool. The demonstration of the neuronal potential of MSCs requires stringent criteria including morphological changes, the demonstration of neural biomarkers expression, electrophysiological recordings, and the absence of cell fusion. The recent finding that brain cancer stem cells can transdifferentiate into pericytes is another facet of the plasticity of these cells. It suggests that the perversion of the stem cell potential of pericytes might play an even unsuspected role in cancer formation and tumor progression. PMID:24772240

Gut metastasis from breast carcinoma.

PubMed

Al-Qahtani, Mohammed S

2007-10-01

Breast cancer is the second most common malignancy in women. Common sites of metastases include the liver, lung, bone, and the brain. Metastases to the gastrointestinal tract are rare with patients presenting with small-bowel perforation, intestinal obstruction, and gastrointestinal bleeding. Here we report a case of a Saudi female presenting with invasive lobular carcinoma and ileo-cecal junction metastasis.

Treatment and care of patients with metastatic breast cancer.

PubMed

Beaumont, T; Leadbeater, M

This article provides an overview of the treatment options available for patients diagnosed with metastatic breast cancer. The article focuses on the four common organ sites affected by metastatic breast cancer, including the bone, lungs, liver and brain. The implications for nursing care are addressed, highlighting common side effects of treatment and frequent areas of concern for patients.

Meninges harbor cells expressing neural precursor markers during development and adulthood.

PubMed

Bifari, Francesco; Berton, Valeria; Pino, Annachiara; Kusalo, Marijana; Malpeli, Giorgio; Di Chio, Marzia; Bersan, Emanuela; Amato, Eliana; Scarpa, Aldo; Krampera, Mauro; Fumagalli, Guido; Decimo, Ilaria

2015-01-01

Brain and skull developments are tightly synchronized, allowing the cranial bones to dynamically adapt to the brain shape. At the brain-skull interface, meninges produce the trophic signals necessary for normal corticogenesis and bone development. Meninges harbor different cell populations, including cells forming the endosteum of the cranial vault. Recently, we and other groups have described the presence in meninges of a cell population endowed with neural differentiation potential in vitro and, after transplantation, in vivo. However, whether meninges may be a niche for neural progenitor cells during embryonic development and in adulthood remains to be determined. In this work we provide the first description of the distribution of neural precursor markers in rat meninges during development up to adulthood. We conclude that meninges share common properties with the classical neural stem cell niche, as they: (i) are a highly proliferating tissue; (ii) host cells expressing neural precursor markers such as nestin, vimentin, Sox2 and doublecortin; and (iii) are enriched in extracellular matrix components (e.g., fractones) known to bind and concentrate growth factors. This study underlines the importance of meninges as a potential niche for endogenous precursor cells during development and in adulthood.

Meninges harbor cells expressing neural precursor markers during development and adulthood

PubMed Central

Bifari, Francesco; Berton, Valeria; Pino, Annachiara; Kusalo, Marijana; Malpeli, Giorgio; Di Chio, Marzia; Bersan, Emanuela; Amato, Eliana; Scarpa, Aldo; Krampera, Mauro; Fumagalli, Guido; Decimo, Ilaria

2015-01-01

Brain and skull developments are tightly synchronized, allowing the cranial bones to dynamically adapt to the brain shape. At the brain-skull interface, meninges produce the trophic signals necessary for normal corticogenesis and bone development. Meninges harbor different cell populations, including cells forming the endosteum of the cranial vault. Recently, we and other groups have described the presence in meninges of a cell population endowed with neural differentiation potential in vitro and, after transplantation, in vivo. However, whether meninges may be a niche for neural progenitor cells during embryonic development and in adulthood remains to be determined. In this work we provide the first description of the distribution of neural precursor markers in rat meninges during development up to adulthood. We conclude that meninges share common properties with the classical neural stem cell niche, as they: (i) are a highly proliferating tissue; (ii) host cells expressing neural precursor markers such as nestin, vimentin, Sox2 and doublecortin; and (iii) are enriched in extracellular matrix components (e.g., fractones) known to bind and concentrate growth factors. This study underlines the importance of meninges as a potential niche for endogenous precursor cells during development and in adulthood. PMID:26483637

Multimodal Approaches for Regenerative Stroke Therapies: Combination of Granulocyte Colony-Stimulating Factor with Bone Marrow Mesenchymal Stem Cells is Not Superior to G-CSF Alone

PubMed Central

Balseanu, Adrian Tudor; Buga, Ana-Maria; Catalin, Bogdan; Wagner, Daniel-Christoph; Boltze, Johannes; Zagrean, Ana-Maria; Reymann, Klaus; Schaebitz, Wolf; Popa-Wagner, Aurel

2014-01-01

Attractive therapeutic strategies to enhance post-stroke recovery of aged brains include methods of cellular therapy that can enhance the endogenous restorative mechanisms of the injured brain. Since stroke afflicts mostly the elderly, it is highly desirable to test the efficacy of cell therapy in the microenvironment of aged brains that is generally refractory to regeneration. In particular, stem cells from the bone marrow allow an autologous transplantation approach that can be translated in the near future to the clinical practice. Such a bone marrow-derived therapy includes the grafting of stem cells as well as the delayed induction of endogenous stem cell mobilization and homing by the stem cell mobilizer granulocyte colony-stimulating factor (G-CSF). We tested the hypothesis that grafting of bone marrow-derived pre-differentiated mesenchymal cells (BM-MSCs) in G-CSF-treated animals improves the long-term functional outcome in aged rodents. To this end, G-CSF alone (50 μg/kg) or in combination with a single dose (106 cells) of rat BM MSCs was administered intravenously to Sprague-Dawley rats at 6 h after transient occlusion (90 min) of the middle cerebral artery. Infarct volume was measured by magnetic resonance imaging at 3 and 48 days post-stroke and additionally by immunhistochemistry at day 56. Functional recovery was tested during the entire post-stroke survival period of 56 days. Daily treatment for post-stroke aged rats with G-CSF led to a robust and consistent improvement of neurological function after 28 days. The combination therapy also led to robust angiogenesis in the formerly infarct core and beyond in the “islet of regeneration.” However, G-CSF + BM MSCs may not impact at all on the spatial reference-memory task or infarct volume and therefore did not further improve the post-stroke recovery. We suggest that in a real clinical practice involving older post-stroke patients, successful regenerative therapies would have to be carried out for a much longer time. PMID:25002846

Gaucher Disease

MedlinePlus

... the most common form, causes liver and spleen enlargement, bone pain and broken bones, and, sometimes, lung ... type 3, there may be liver and spleen enlargement. The brain is gradually affected. It usually starts ...

Image quality improvement in three-dimensional time-of-flight magnetic resonance angiography using the subtraction method for brain and temporal bone diseases.

PubMed

Peng, Shu-Hui; Shen, Chao-Yu; Wu, Ming-Chi; Lin, Yue-Der; Huang, Chun-Huang; Kang, Ruei-Jin; Tyan, Yeu-Sheng; Tsao, Teng-Fu

2013-08-01

Time-of-flight (TOF) magnetic resonance (MR) angiography is based on flow-related enhancement using the T1-weighted spoiled gradient echo, or the fast low-angle shot gradient echo sequence. However, materials with short T1 relaxation times may show hyperintensity signals and contaminate the TOF images. The objective of our study was to determine whether subtraction three-dimensional (3D) TOF MR angiography improves image quality in brain and temporal bone diseases with unwanted contaminations with short T1 relaxation times. During the 12-month study period, patients who had masses with short T1 relaxation times noted on precontrast T1-weighted brain MR images and 24 healthy volunteers were scanned using conventional and subtraction 3D TOF MR angiography. The qualitative evaluation of each MR angiogram was based on signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and scores in three categories, namely, (1) presence of misregistration artifacts, (2) ability to display arterial anatomy selectively (without contamination by materials with short T1 relaxation times), and (3) arterial flow-related enhancement. We included 12 patients with intracranial hematomas, brain tumors, or middle-ear cholesterol granulomas. Subtraction 3D TOF MR angiography yielded higher CNRs between the area of the basilar artery (BA) and normal-appearing parenchyma of the brain and lower SNRs in the area of the BA compared with the conventional technique (147.7 ± 77.6 vs. 130.6 ± 54.2, p < 0.003 and 162.5 ± 79.9 vs. 194.3 ± 62.3, p < 0.001, respectively) in all 36 cases. The 3D subtraction angiography did not deteriorate image quality with misregistration artifacts and showed a better selective display of arteries (p < 0.0001) and arterial flow-related enhancement (p < 0.044) than the conventional method. Subtraction 3D TOF MR angiography is more appropriate than the conventional method in improving the image quality in brain and temporal bone diseases with unwanted contaminations with short T1 relaxation times. Copyright © 2013. Published by Elsevier B.V.

Sodium selenate treatment mitigates reduction of bone volume following traumatic brain injury in rats.

PubMed

Brady, R D; Grills, B L; Romano, T; Wark, J D; O'Brien, T J; Shultz, S R; McDonald, S J

2016-12-14

Administration of sodium selenate to rats given traumatic brain injury (TBI) attenuates brain damage and improves long-term behavioural outcomes. We have previously provided evidence that TBI causes bone loss in rats, however the effect of sodium selenate treatment on bone quantity following TBI is unknown. Rats were randomly assigned into sham injury or fluid percussion injury (FPI) groups and administered saline or sodium selenate for 12 weeks post-injury. Femora were analysed using histomorphometry, peripheral quantitative computed tomography (pQCT) and biomechanical testing. Distal metaphyseal trabecular bone volume fraction of FPI-selenate rats was higher than FPI-vehicle rats (41.8%; p<0.01), however, femora from selenate-treated groups were shorter in length (4.3%; p<0.01) and had increased growth plate width (22.1%; p<0.01), indicating that selenate impaired long bone growth. pQCT analysis demonstrated that distal metaphyseal cortical thickness was decreased in TBI rats compared to shams (11.7%; p<0.05), however selenate treatment to TBI animals offset this reduction (p<0.05). At the midshaft we observed no differences in biomechanical measures. These are the first findings to indicate that mitigating TBI-induced neuropathology may have the added benefit of preventing osteoporosis and associated fracture risk following TBI.

Image-guided neurosurgery for secondary operative removal of projectiles after missile injury of the brain.

PubMed

Schulz, Chris; Woerner, Ulrich; Luelsdorf, Peter

2008-04-01

The primary treatment of penetrating missile injuries of the brain includes debridement of the scalp, fractured skull, and necrotic brain parenchyma. It is acceptable to remove all bony and metallic fragments that are accessible without additional trauma to nondamaged brain regions. Therefore, bone chips and bullets are often initially retained in the brain and are supposedly responsible for delayed cerebral infections and posttraumatic seizures. We successfully operated on 3 patients electively to remove bony and metallic fragments secondarily after penetrating brain trauma. We used an electromagnetic neuronavigation system for preoperative planning and chose a less invasive approach for the exact intraoperative localization of the fragments. All fragments were extracted without any problems. No patients had any additional neurologic deficits, and no signs of cerebral infections or seizures occurred between 4 and 8 weeks after the operative revision. We recommend the implementation of neuronavigation techniques into the surgical strategy for secondary removal of retained missile fragments.

Potential for thermal damage to the blood–brain barrier during craniotomy: implications for intracortical recording microelectrodes

NASA Astrophysics Data System (ADS)

Shoffstall, Andrew J.; Paiz, Jen E.; Miller, David M.; Rial, Griffin M.; Willis, Mitchell T.; Menendez, Dhariyat M.; Hostler, Stephen R.; Capadona, Jeffrey R.

2018-06-01

Objective. Our objective was to determine how readily disruption of the blood–brain barrier (BBB) occurred as a result of bone drilling during a craniotomy to implant microelectrodes in rat cortex. While the phenomenon of heat production during bone drilling is well known, practices to evade damage to the underlying brain tissue are inconsistently practiced and reported in the literature. Approach. We conducted a review of the intracortical microelectrode literature to summarize typical approaches to mitigate drill heating during rodent craniotomies. Post mortem skull-surface and transient brain-surface temperatures were experimentally recorded using an infrared camera and thermocouple, respectively. A number of drilling conditions were tested, including varying drill speed and continuous versus intermittent contact. In vivo BBB permeability was assayed 1 h after the craniotomy procedure using Evans blue dye. Main results. Of the reviewed papers that mentioned methods to mitigate thermal damage during craniotomy, saline irrigation was the most frequently cited (in six of seven papers). In post mortem tissues, we observed increases in skull-surface temperature ranging from  +3 °C to  +21 °C, dependent on drill speed. In vivo, pulsed-drilling (2 s-on/2 s-off) and slow-drilling speeds (1000 r.p.m.) were the most effective methods we studied to mitigate heating effects from drilling, while inconclusive results were obtained with saline irrigation. Significance. Neuroinflammation, initiated by damage to the BBB and perpetuated by the foreign body response, is thought to play a key role in premature failure of intracortical recording microelectrodes. This study demonstrates the extreme sensitivity of the BBB to overheating caused by bone drilling. To avoid damage to the BBB, the authors recommend that craniotomies be drilled with slow speeds and/or with intermittent drilling with complete removal of the drill from the skull during ‘off’ periods. While saline alone was ineffective at preventing overheating, its use is still recommended to remove bone dust from the surgical site and to augment other cooling methods.

Evaluation of Short and Long Term Cold Stress Challenge of Nerve Grow Factor, Brain-Derived Neurotrophic Factor, Osteocalcin and Oxytocin mRNA Expression in BAT, Brain, Bone and Reproductive Tissue of Male Mice Using Real-Time PCR and Linear Correlation Analysis.

PubMed

Camerino, Claudia; Conte, Elena; Caloiero, Roberta; Fonzino, Adriano; Carratù, Mariarosaria; Lograno, Marcello D; Tricarico, Domenico

2017-01-01

The correlation between the Ngf/p75ntr-Ntrk1 and Bdnf , Osteocalcin- Ost / Gprc6a and Oxytocin- Oxt/Oxtr genes, was challenged investigating their mRNA levels in 3 months-old mice after cold-stress (CS). Uncoupling protein-1 ( Ucp-1) was used as positive control. Control mice were maintained at room temperature T = 25°C, CS mice were maintained at T = 4°C for 6 h and 5-days ( N = 15 mice). RT-PCR experiments showed that Ucp-1 and Ngf genes were up-regulated after 6 h CS in brown adipose tissues (BAT), respectively, by 2 and 1.5-folds; Ucp-1 was upregulated also after 5-days, while Ngfr (p75ntr) and Ntrk1 genes were downregulated after 6 h and 5-days CS in BAT. NGF and P75NTR were upregulated in bone and testis following 5-days, and P75NTR in testis after 6 h CS. Bdnf was instead up-regulated in bone following 5-days CS and down-regulated in testis. OST was upregulated by 16 and 3-fold in bone and BAT, respectively, following 5-days CS. Gprc6a was upregulated after 6 h in brain, while Bglap ( Ost) gene was downregulated. Oxt gene was upregulated by 5-fold following 5-days CS in bone. Oxtr was upregulated by 0.5 and 0.3-fold, respectively, following 6 h and 5-days CS in brain. Oxtr and Oxt were downregulated in testis and in BAT. The changes in the expression levels of control genes vs. genes following 6 h and 5-days CS were correlated in all tissues, but not in BAT. Correlation in BAT was improved eliminating Ngfr (p75ntr) data. The correlation in brain was lost eliminating Oxtr data. In sum, Ucp-1 potentiation in BAT after cold stress is associated with early Ngf -response in the same tissue and trophic action in bone and testis. In contrast, BDNF exerts bone and neuroprotective effects. Similarly to Ucp-1, Bglap ( Ost) signaling is enhanced in bone and BAT while it may exert local neuroprotective effects thought its receptor. Ngfr (p75ntr) regulates the adaptation to CS through a feed-back loop in BAT. Oxtr regulates the gene-response to CS through a feed-forward loop in brain. Overall these results expand the understanding of the physiology of these molecules under metabolic thermogenesis.

Typical and atypical metastatic sites of recurrent endometrial carcinoma

PubMed Central

Krajewski, Katherine M.; Jagannathan, Jyothi; Giardino, Angela; Berlin, Suzanne; Ramaiya, Nikhil

2013-01-01

Abstract The purpose of this article is to illustrate the imaging findings of typical and atypical metastatic sites of recurrent endometrial carcinoma. Typical sites include local pelvic recurrence, pelvic and para-aortic nodes, peritoneum, and lungs. Atypical sites include extra-abdominal lymph nodes, liver, adrenals, brain, bones and soft tissue. It is important for radiologists to recognize the typical and atypical sites of metastases in patients with recurrent endometrial carcinoma to facilitate earlier diagnosis and treatment. PMID:23545091

Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Brain Damage in Experimental Traumatic Brain Injury Model

PubMed Central

Lau, Tsz; Kaneko, Yuji; van Loveren, Harry; Borlongan, Cesario V.

2012-01-01

Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI. PMID:22438975

TH-EF-207A-06: High-Resolution Optical-CT/ECT Imaging of Unstained Mice Femur, Brain, Spleen, and Tumor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, S; Dewhirst, M; Oldham, M

2016-06-15

Purpose: Optical transmission and emission computed tomography (optical-CT/ECT) provides high-resolution 3D attenuation and emission maps in unsectioned large (∼1cm{sup 3}) ex vivo tissue samples at a resolution of 12.9µm{sup 3} per voxel. Here we apply optical-CT/ECT to investigate high-resolution structure and auto-fluorescence in a range of optically cleared mice organs, including, for the first time, mouse bone (femur), opening the potential for study of bone metastasis and bone-mediated immune response. Methods: Three BALBc mice containing 4T1 flank tumors were sacrificed to obtain spleen, brain, tumor, and femur. Tissues were washed in 4% PFA, fixed in EtOH solution (for 5, 10,more » 10, and 2 days respectively), and then optically cleared for 3 days in BABBs. The femur was also placed in 0.25M aqueous EDTA for 15–30 days to remove calcium. Optical-CT/ECT attenuation and emission maps at 633nm (the latter using 530nm excitation light) were obtained for all samples. Bi-telecentric optical-CT was compared side-by-side with conventional optical projection tomography (OPT) imaging to evaluate imaging capability of these two rival techniques. Results: Auto-fluorescence mapping of femurs reveals vasculatures and fluorescence heterogeneity. High signals (A.U.=10) are reported in the medullary cavity but not in the cortical bone (A.U.=1). The brain strongly and uniform auto-fluoresces (A.U.=5). Thick, optically dense organs such as the spleen and the tumor (0.12, 0.46OD/mm) are reconstructed at depth without significant loss of resolution, which we attribute to the bi-telecentric optics of optical-CT. The attenuation map of tumor reveals vasculature, attenuation heterogeneity, and possibly necrotic tissue. Conclusion: We demonstrate the feasibility of optical-CT/ECT imaging of un-sectioned mice bones (femurs) and spleen with high resolution. This result, and the characterization of unstained organs, are important steps enabling future studies involving optical-CT/ECT applied to study metastasis and immunologic responses via fluorescence staining.« less

SU-F-J-213: Feasibility Study of Using a Dual-Energy Cone Beam CT (DECBCT) in Proton Therapy Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, H; Xing, L; Kanehira, T

2016-06-15

Purpose: The aim of this study is to evaluate the feasibility of using a dual-energy CBCT (DECBCT) in proton therapy treatment planning to allow for accurate electron density estimation. Methods: For direct comparison, two scenarios were selected: a dual-energy fan-beam CT (high: 140 kVp, low: 80 kVp) and a DECBCT (high: 125 kVp, low: 80 kVp). A Gammex 467 tissue characterization phantom was used, including the rods of air, water, bone (B2–30% mineral), cortical bone (SB3), lung (LN-300), brain, liver and adipose. For the CBCT, Hounsfield Unit (HU) numbers were first obtained from the reconstructed images after a calibration wasmore » made based on water (=0) and air materials (=−1000). For each tissue surrogate, region-of-interest (ROI) analyses were made to derive high-energy and low-energy HU values (HUhigh and HUlow), which were subsequently used to estimate electron density based on the algorithm as previously described by Hunemohr N., et al. Parameters k1 and k2 are energy dependent and can be derived from calibration materials. Results: While for the dual-energy FBCT, the electron density is found be within +/−3% error relative to the values provided by the phantom vendor: −1.8% (water), 0.03% (lung), 1.1% (brain), −2.82% (adipose), −0.49% (liver) and −1.89% (cortical bones). While for the DECBCT, the estimation of electron density exhibits a relatively larger variation: −1.76% (water), −36.7% (lung), −1.92% (brain), −3.43% (adipose), 8.1% (liver) and 9.5% (cortical bones). Conclusion: For DECBCT, the accuracy of electron density estimation is inferior to that of a FBCT, especially for materials of either low-density (lung) or high density (cortical bone) compared to water. Such limitation arises from inaccurate HU number derivation in a CBCT. Advanced scatter-correction and HU calibration routines, as well as the deployment of photon counting CT detectors need be investigated to minimize the difference between FBCT and CBCT.« less

SU-E-J-90: MRI-Based Treatment Simulation and Patient Setup for Radiation Therapy of Brain Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Y; Cao, M; Han, F

2014-06-01

Purpose: Traditional radiation therapy of cancer is heavily dependent on CT. CT provides excellent depiction of the bones but lacks good soft tissue contrast, which makes contouring difficult. Often, MRIs are fused with CT to take advantage of its superior soft tissue contrast. Such an approach has drawbacks. It is desirable to perform treatment simulation entirely based on MRI. To achieve MR-based simulation for radiation therapy, bone imaging is an important challenge because of the low MR signal intensity from bone due to its ultra-short T2 and T1, which presents difficulty for both dose calculation and patient setup in termsmore » of digitally reconstructed radiograph (DRR) generation. Current solutions will either require manual bone contouring or multiple MR scans. We present a technique to generate DRR using MRI with an Ultra Short Echo Time (UTE) sequence which is applicable to both OBI and ExacTrac 2D patient setup. Methods: Seven brain cancer patients were scanned at 1.5 Tesla using a radial UTE sequence. The sequence acquires two images at two different echo times. The two images were processed using in-house software. The resultant bone images were subsequently loaded into commercial systems to generate DRRs. Simulation and patient clinical on-board images were used to evaluate 2D patient setup with MRI-DRRs. Results: The majority bones are well visualized in all patients. The fused image of patient CT with the MR bone image demonstrates the accuracy of automatic bone identification using our technique. The generated DRR is of good quality. Accuracy of 2D patient setup by using MRI-DRR is comparable to CT-based 2D patient setup. Conclusion: This study shows the potential of DRR generation with single MR sequence. Further work will be needed on MR sequence development and post-processing procedure to achieve robust MR bone imaging for other human sites in addition to brain.« less

Glioblastoma-synthesized G-CSF and GM-CSF contribute to growth and immunosuppression: Potential therapeutic benefit from dapsone, fenofibrate, and ribavirin.

PubMed

Kast, Richard E; Hill, Quentin A; Wion, Didier; Mellstedt, Håkan; Focosi, Daniele; Karpel-Massler, Georg; Heiland, Tim; Halatsch, Marc-Eric

2017-05-01

Increased ratio of circulating neutrophils to lymphocytes is a common finding in glioblastoma and other cancers. Data reviewed establish that any damage to brain tissue tends to cause an increase in G-CSF and/or GM-CSF (G(M)-CSF) synthesized by the brain. Glioblastoma cells themselves also synthesize G(M)-CSF. G(M)-CSF synthesized by brain due to damage by a growing tumor and by the tumor itself stimulates bone marrow to shift hematopoiesis toward granulocytic lineages away from lymphocytic lineages. This shift is immunosuppressive and generates the relative lymphopenia characteristic of glioblastoma. Any trauma to brain-be it blunt, sharp, ischemic, infectious, cytotoxic, tumor encroachment, or radiation-increases brain synthesis of G(M)-CSF. G(M)-CSF are growth and motility enhancing factors for glioblastomas. High levels of G(M)-CSF contribute to the characteristic neutrophilia and lymphopenia of glioblastoma. Hematopoietic bone marrow becomes entrained with, directed by, and contributes to glioblastoma pathology. The antibiotic dapsone, the lipid-lowering agent fenofibrate, and the antiviral drug ribavirin are Food and Drug Administration- and European Medicines Agency-approved medicines that have potential to lower synthesis or effects of G(M)-CSF and thus deprive a glioblastoma of some of the growth promoting contributions of bone marrow and G(M)-CSF.

SDF-1 promotes endochondral bone repair during fracture healing at the traumatic brain injury condition.

PubMed

Liu, Xiaoqi; Zhou, Changlong; Li, Yanjing; Ji, Ye; Xu, Gongping; Wang, Xintao; Yan, Jinglong

2013-01-01

The objective of this study was to investigate the role of stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, on bone healing and whether SDF-1 contributes to accelerating bone repair in traumatic brain injury (TBI)/fracture model. Real-time polymerase chain reaction and immunohistochemical analysis were used to detect the expression of SDF-1 during the repair of femoral bone in TBI/fracture model. The TBI/fracture model was treated with anti-SDF-1 neutralizing antibody or AMD3100, an antagonist for CXCR4, and evaluated by histomorphometry. In vitro and in vivo migration assays were used to evaluate the functional effect of SDF-1 on primary mesenchymal stem cells. The expression of SDF1 and CXCR4 messenger RNA was increased during the bone healing in TBI/fracture model but was less increased in fracture only model. High expression of SDF-1 protein was observed in the surrounding tissue of the damaged bone. Treated with anti-SDF-1 antibody or AMD3100 could inhibit new bone formation. SDF-1 increased mesenchymal stem cell chemotaxis in vitro in a dose-dependent manner. The in vivo migration study demonstrated that mesenchymal stem cells recruited by SDF-1 participate in endochondral bone repair. The SDF-1/CXCR4 axis plays a crucial role in the accelerating fracture healing under the condition of TBI and contributes to endochondral bone repair.

Aging alters the immunological response to ischemic stroke.

PubMed

Ritzel, Rodney M; Lai, Yun-Ju; Crapser, Joshua D; Patel, Anita R; Schrecengost, Anna; Grenier, Jeremy M; Mancini, Nickolas S; Patrizz, Anthony; Jellison, Evan R; Morales-Scheihing, Diego; Venna, Venugopal R; Kofler, Julia K; Liu, Fudong; Verma, Rajkumar; McCullough, Louise D

2018-05-11

The peripheral immune system plays a critical role in aging and in the response to brain injury. Emerging data suggest inflammatory responses are exacerbated in older animals following ischemic stroke; however, our understanding of these age-related changes is poor. In this work, we demonstrate marked differences in the composition of circulating and infiltrating leukocytes recruited to the ischemic brain of old male mice after stroke compared to young male mice. Blood neutrophilia and neutrophil invasion into the brain were increased in aged animals. Relative to infiltrating monocyte populations, brain-invading neutrophils had reduced phagocytic potential, and produced higher levels of reactive oxygen species and extracellular matrix-degrading enzymes (i.e., MMP-9), which were further exacerbated with age. Hemorrhagic transformation was more pronounced in aged versus young mice relative to infarct size. High numbers of myeloperoxidase-positive neutrophils were found in postmortem human brain samples of old (> 71 years) acute ischemic stroke subjects compared to non-ischemic controls. Many of these neutrophils were found in the brain parenchyma. A large proportion of these neutrophils expressed MMP-9 and positively correlated with hemorrhage and hyperemia. MMP-9 expression and hemorrhagic transformation after stroke increased with age. These changes in the myeloid response to stroke with age led us to hypothesize that the bone marrow response to stroke is altered with age, which could be important for the development of effective therapies targeting the immune response. We generated heterochronic bone marrow chimeras as a tool to determine the contribution of peripheral immune senescence to age- and stroke-induced inflammation. Old hosts that received young bone marrow (i.e., Young → Old) had attenuation of age-related reductions in bFGF and VEGF and showed improved locomotor activity and gait dynamics compared to isochronic (Old → Old) controls. Microglia in young heterochronic mice (Old → Young) developed a senescent-like phenotype. After stroke, aged animals reconstituted with young marrow had reduced behavioral deficits compared to isochronic controls, and had significantly fewer brain-infiltrating neutrophils. Increased rates of hemorrhagic transformation were seen in young mice reconstituted with aged bone marrow. This work suggests that age alters the immunological response to stroke, and that this can be reversed by manipulation of the peripheral immune cells in the bone marrow.

Hematopoietic progenitors express neural genes

PubMed Central

Goolsby, James; Marty, Marie C.; Heletz, Dafna; Chiappelli, Joshua; Tashko, Gerti; Yarnell, Deborah; Fishman, Paul S.; Dhib-Jalbut, Suhayl; Bever, Christopher T.; Pessac, Bernard; Trisler, David

2003-01-01

Bone marrow, or cells selected from bone marrow, were reported recently to give rise to cells with a neural phenotype after in vitro treatment with neural-inducing factors or after delivery into the brain. However, we showed previously that untreated bone marrow cells express products of the neural myelin basic protein gene, and we demonstrate here that a subset of ex vivo bone marrow cells expresses the neurogenic transcription factor Pax-6 as well as neuronal genes encoding neurofilament H, NeuN (neuronal nuclear protein), HuC/HuD (Hu-antigen C/Hu-antigen D), and GAD65 (glutamic acid decarboxylase 65), as well as the oligodendroglial gene encoding CNPase (2′,3′ cyclic nucleotide 3′-phosphohydrolase). In contrast, astroglial glial fibrillary acidic protein (GFAP) was not detected. These cells also were CD34+, a marker of hematopoietic stem cells. Cultures of these highly proliferative CD34+ cells, derived from adult mouse bone marrow, uniformly displayed a phenotype comparable with that of hematopoietic progenitor cells (CD45+, CD34+, Sca-1+, AA4.1+, cKit+, GATA-2+, and LMO-2+). The neuronal and oligodendroglial genes expressed in ex vivo bone marrow also were expressed in all cultured CD34+ cells, and GFAP was not observed. After CD34+ cell transplantation into adult brain, neuronal or oligodendroglial markers segregated into distinct nonoverlapping cell populations, whereas astroglial GFAP appeared, in the absence of other neural markers, in a separate set of implanted cells. Thus, neuronal and oligodendroglial gene products are present in a subset of bone marrow cells, and the expression of these genes can be regulated in brain. The fact that these CD34+ cells also express transcription factors (Rex-1 and Oct-4) that are found in early development elicits the hypothesis that they may be pluripotent embryonic-like stem cells. PMID:14634211

Research Advances: Onions Battle Osteoporosis; New Weapon in War on TB; Smokers Beware: Study Shows Increased Cadmium Levels in the Brain May Cause Severe Neurological Disorders

NASA Astrophysics Data System (ADS)

King, Angela G.

2005-08-01

This Report from Other Journals surveys articles of interest to chemists that have been recently published in other science journals. Topics surveyed include reports that a compound in onions reduces bone loss; a new diarylquinone inhibits tuberculosis in vitro; and cadium in tobacco influences amphetamine effects.

Anaesthetic management for awake craniotomy in brain glioma resection: initial experience in Military Hospital Mohamed V of Rabat.

PubMed

Meziane, Mohammed; Elkoundi, Abdelghafour; Ahtil, Redouane; Guazaz, Miloudi; Mustapha, Bensghir; Haimeur, Charki

2017-01-01

The awake brain surgery is an innovative approach in the treatment of tumors in the functional areas of the brain. There are various anesthetic techniques for awake craniotomy (AC), including asleep-awake-asleep technique, monitored anesthesia care, and the recent introduced awake-awake-awake method. We describe our first experience with anesthetic management for awake craniotomy, which was a combination of these techniques with scalp nerve block, and propofol/rémifentanil target controlled infusion. A 28-year-oldmale underwent an awake craniotomy for brain glioma resection. The scalp nerve block was performed and a low sedative state was maintained until removal of bone flap. During brain glioma resection, the patient awake state was maintained without any complications. Once, the tumorectomy was completed, the level of anesthesia was deepened and a laryngeal mask airway was inserted. A well psychological preparation, a reasonable choice of anesthetic techniques and agents, and continuous team communication were some of the key challenges for successful outcome in our patient.

Brain Metastasis in Bone and Soft Tissue Cancers: A Review of Incidence, Interventions, and Outcomes

PubMed Central

Shweikeh, Faris; Bukavina, Laura; Saeed, Kashif; Sarkis, Reem; Suneja, Aarushi; Sweiss, Fadi; Drazin, Doniel

2014-01-01

Bone and soft tissue malignancies account for a small portion of brain metastases. In this review, we characterize their incidence, treatments, and prognosis. Most of the data in the literature is based on case reports and small case series. Less than 5% of brain metastases are from bone and soft tissue sarcomas, occurring most commonly in Ewing's sarcoma, malignant fibrous tumors, and osteosarcoma. Mean interval from initial cancer diagnosis to brain metastasis is in the range of 20–30 months, with most being detected before 24 months (osteosarcoma, Ewing sarcoma, chordoma, angiosarcoma, and rhabdomyosarcoma), some at 24–36 months (malignant fibrous tumors, malignant peripheral nerve sheath tumors, and alveolar soft part sarcoma), and a few after 36 months (chondrosarcoma and liposarcoma). Overall mean survival ranges between 7 and 16 months, with the majority surviving < 12 months (Ewing's sarcoma, liposarcoma, malignant fibrous tumors, malignant peripheral nerve sheath tumors, angiosarcoma and chordomas). Management is heterogeneous involving surgery, radiosurgery, radiotherapy, and chemotherapy. While a survival advantage may exist for those given aggressive treatment involving surgical resection, such patients tended to have a favorable preoperative performance status and minimal systemic disease. PMID:24757391

Clinicopathological factors associated with survival in patients with breast cancer brain metastasis.

PubMed

Li, Rong; Zhang, Kui; Siegal, Gene P; Wei, Shi

2017-06-01

Brain metastasis from breast cancer generally represents a catastrophic event yet demonstrates substantial biological heterogeneity. There have been limited studies solely focusing on the prognosis of patients with such metastasis. In this study, we carried out a comprehensive analysis in 108 consecutive patients with breast cancer brain metastases between 1997 and 2012 to further define clinicopathological factors associated with early onset of brain metastasis and survival outcomes after development of them. We found that lobular carcinoma, higher clinical stages at diagnosis, and lack of coexisting bone metastasis were significantly associated with a worse brain relapse-free survival when compared with brain-only metastasis. High histologic grade, triple-negative breast cancer, and absence of visceral involvement were unfavorable prognostic factors after brain metastasis. Furthermore, high histologic grade, advanced tumor stages, and lack of coexisting bone involvement indicated a worse overall survival. Thus, the previously established prognostic factors in early stage or advanced breast cancers may not entirely apply to patients with brain metastases. Furthermore, the prognostic significance of the clinicopathological factors differed before and after a patient develops brain metastasis. This knowledge might help in establishing an algorithm to further stratify patients with breast cancer into prognostically significant categories for optimal prevention, screening, and treatment of their brain metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

Estrogen synthesis and signaling pathways during ageing: from periphery to brain

PubMed Central

Cui, Jie; Shen, Yong; Li, Rena

2012-01-01

Estrogens are the primary female sex hormones and play important roles in both reproductive and non-reproductive systems. Estrogens can be synthesized in non-reproductive tissue as liver, heart, muscle, bone and brain. The tissue-specific estrogen synthesis is consistent with a diversity of estrogen actions. Here, we will focus on tissue and cell-specific estrogen synthesis and estrogen receptor signaling. This review will include three parts: (I) tissue and cell-specific estrogen synthesis and metabolism, (II) tissue and cell-specific distribution of estrogen receptors and signaling and (III) tissue-specific estrogen function and related disorders, including cardiovascular diseases, osteoporosis, Alzheimer's disease and Parkinson disease. This comprehensive review provides new insights into estrogens by giving a better understanding of the tissue-specific estrogen effects and their roles in various diseases. PMID:23348042

Mobilization of Endogenous Bone Marrow Derived Endothelial Progenitor Cells and Therapeutic Potential of Parathyroid Hormone after Ischemic Stroke in Mice

PubMed Central

Wang, Li-Li; Chen, Dongdong; Lee, Jinhwan; Gu, Xiaohuan; Alaaeddine, Ghina; Li, Jimei; Wei, Ling; Yu, Shan Ping

2014-01-01

Stroke is a major neurovascular disorder threatening human life and health. Very limited clinical treatments are currently available for stroke patients. Stem cell transplantation has shown promising potential as a regenerative treatment after ischemic stroke. The present investigation explores a new concept of mobilizing endogenous stem cells/progenitor cells from the bone marrow using a parathyroid hormone (PTH) therapy after ischemic stroke in adult mice. PTH 1-34 (80 µg/kg, i.p.) was administered 1 hour after focal ischemia and then daily for 6 consecutive days. After 6 days of PTH treatment, there was a significant increase in bone marrow derived CD-34/Fetal liver kinase-1 (Flk-1) positive endothelial progenitor cells (EPCs) in the peripheral blood. PTH treatment significantly increased the expression of trophic/regenerative factors including VEGF, SDF-1, BDNF and Tie-1 in the brain peri-infarct region. Angiogenesis, assessed by co-labeled Glut-1 and BrdU vessels, was significantly increased in PTH-treated ischemic brain compared to vehicle controls. PTH treatment also promoted neuroblast migration from the subventricular zone (SVZ) and increased the number of newly formed neurons in the peri-infarct cortex. PTH-treated mice showed significantly better sensorimotor functional recovery compared to stroke controls. Our data suggests that PTH therapy improves endogenous repair mechanisms after ischemic stroke with functional benefits. Mobilizing endogenous bone marrow-derived stem cells/progenitor cells using PTH and other mobilizers appears an effective and feasible regenerative treatment after ischemic stroke. PMID:24503654

Bone Morphogenetic Protein (BMP)-3b Gene Depletion Causes High Mortality in a Mouse Model of Neonatal Hypoxic-Ischemic Encephalopathy.

PubMed

Ogawa, Yuko; Tsuji, Masahiro; Tanaka, Emi; Miyazato, Mikiya; Hino, Jun

2018-01-01

Bone morphogenetic proteins (BMPs) are a group of proteins that induce the formation of bone and the development of the nervous system. BMP-3b, also known as growth and differentiation factor 10, is a member of the BMPs that is highly expressed in the developing and adult brain. BMP-3b is therefore thought to play an important role in the brain even after physiological neurogenesis has completed. BMP-3b is induced in peri-infarct neurons in aged brains and is one of the most highly upregulated genes during the initiation of axonal sprouting. However, little is known about the role of BMP-3b in neonatal brain injury. In the present study, we aimed to describe the effects of BMP-3b gene depletion on neonatal hypoxic-ischemic encephalopathy, which frequently results in death or lifelong neurological disabilities, such as cerebral palsy and mental retardation. BMP-3b knockout and wild type mice were prepared at postnatal day 12. Mice of each genotype were divided into sham-surgery, mild hypoxia-ischemia (HI), and severe HI groups ( n = 12-45). Mice in the HI groups were subjected to left common carotid artery ligation followed by 30 min (mild HI) or 50 min (severe HI) of systemic hypoxic insult. A battery of tests, including behavioral tests, was performed, and the brain was then removed and evaluated at 14 days after insult. Compared with wild type pups, BMP-3b knockout pups demonstrated the following characteristics. (1) The males exposed to severe HI had a strikingly higher mortality rate, and as many as 70% of the knockout pups but none of the wild type pups died; (2) significantly more hyperactive locomotion was observed in males exposed to severe HI; and (3) significantly more hyperactive rearing was observed in both males and females exposed to mild HI. However, BMP-3b gene depletion did not affect other parameters, such as cerebral blood flow, cylinder test and rotarod test performance, body weight gain, brain weight, spleen weight, and neuroanatomical injury. The results of this study suggest that BMP-3b may play a crucial role to survive in severe neonatal hypoxic-ischemic insult.

Transcranial Red and Near Infrared Light Transmission in a Cadaveric Model

PubMed Central

Jagdeo, Jared R.; Adams, Lauren E.; Brody, Neil I.; Siegel, Daniel M.

2012-01-01

Background and Objective Low level light therapy has garnered significant interest within the past decade. The exact molecular mechanisms of how red and near infrared light result in physiologic modulation are not fully understood. Heme moieties and copper within cells are red and near infrared light photoreceptors that induce the mitochondrial respiratory chain component cytochrome C oxidase, resulting in a cascade linked to cytoprotection and cellular metabolism. The copper centers in cytochrome C oxidase have a broad absorption range that peaks around 830 nm. Several in vitro and in vivo animal and human models exist that have demonstrated the benefits of red light and near infrared light for various conditions. Clinical applications for low level light therapy are varied. One study in particular demonstrated improved durable functional outcomes status post-stroke in patients treated with near infrared low level light therapy compared to sham treatment [1]. Despite previous data suggesting the beneficial effect in treating multiple conditions, including stroke, with low level light therapy, limited data exists that measures transmission in a human model. Study Design/Materials and Methods To investigate this idea, we measured the transmission of near infrared light energy, using red light for purposes of comparison, through intact cadaver soft tissue, skull bones, and brain using a commercially available LED device at 830 nm and 633 nm. Results Our results demonstrate that near infrared measurably penetrates soft tissue, bone and brain parenchyma in the formalin preserved cadaveric model, in comparison to negligible red light transmission in the same conditions. Conclusion These findings indicate that near infrared light can penetrate formalin fixed soft tissue, bone and brain and implicate that benefits observed in clinical studies are potentially related to direct action of near infrared light on neural tissue. PMID:23077622

Experimental Traumatic Brain Injury Induces Bone Loss in Rats.

PubMed

Brady, Rhys D; Shultz, Sandy R; Sun, Mujun; Romano, Tania; van der Poel, Chris; Wright, David K; Wark, John D; O'Brien, Terence J; Grills, Brian L; McDonald, Stuart J

2016-12-01

Few studies have investigated the influence of traumatic brain injury (TBI) on bone homeostasis; however, pathophysiological mechanisms involved in TBI have potential to be detrimental to bone. The current study assessed the effect of experimental TBI in rats on the quantity and quality of two different weight-bearing bones, the femur and humerus. Rats were randomly assigned into either sham or lateral fluid percussion injury (FPI) groups. Open-field testing to assess locomotion was conducted at 1, 4, and 12 weeks post-injury, with the rats killed at 1 and 12 weeks post-injury. Bones were analyzed using peripheral quantitative computed tomography (pQCT), histomorphometric analysis, and three-point bending. pQCT analysis revealed that at 1 and 12 weeks post-injury, the distal metaphyseal region of femora from FPI rats had reduced cortical content (10% decrease at 1 week, 8% decrease at 12 weeks; p < 0.01) and cortical thickness (10% decrease at 1 week, 11% decrease at 12 weeks p < 0.001). There was also a 23% reduction in trabecular bone volume ratio at 1 week post-injury and a 27% reduction at 12 weeks post-injury in FPI rats compared to sham (p < 0.001). There were no differences in bone quantity and mechanical properties of the femoral midshaft between sham and TBI animals. There were no differences in locomotor outcomes, which suggested that post-TBI changes in bone were not attributed to immobility. Taken together, these findings indicate that this rat model of TBI was detrimental to bone and suggests a link between TBI and altered bone remodeling.

Cerebral fat embolism syndrome causing brain death after long-bone fractures and acetazolamide therapy.

PubMed

Walshe, Criona M; Cooper, James D; Kossmann, Thomas; Hayes, Ivan; Iles, Linda

2007-06-01

A 19-year-old woman with multiple fractures and mild brain injury developed severe cerebral fat embolism syndrome after "damage control" orthopaedic surgery. Acetazolamide therapy to manage ocular trauma, in association with hyperchloraemia, caused a profound metabolic acidosis with appropriate compensatory hypocapnia. During ventilator weaning, unexpected brainstem coning followed increased sedation and brief normalisation of arterial carbon dioxide concentration. Autopsy found severe cerebral fat embolism and brain oedema. In patients with multiple trauma, cerebral fat embolism syndrome is difficult to diagnose, and may be more common after delayed fixation of long-bone fractures. Acetazolamide should be used with caution, as sudden restoration of normocapnia during compensated metabolic acidosis in patients with raised intracranial pressure may precipitate coning.

Guiding bone formation in a critical-sized defect and assessments.

PubMed

Jannetty, Joseph; Kolb, Eric; Boxberger, John; Deslauriers, Richard; Ganey, Timothy

2010-11-01

Development of alternatives to autologous bone has been served by many hypotheses and developments. Favorable properties of synthetic materials used currently in bone grafting support tissue differentiation without shielding capacity for integrated modeling. Ideally, new materials provide tissue compatibility and minimize patient morbidity and are attractive because of potential for in situ delivery, isothermal polymerization, porous structure, and nontoxic chemistry. For application in cranial bone, ability for materials to be laid adjacent to brain and offer postsurgical protection without neural risk is a critical asset. Kryptonite Bone Cement (KBC) meets the property criteria for cranial bone repair with regard to adhesive, conductive, and biologic transparency and US Food and Drug Administration approval for cranial bone void repair. To better delineate the morphology effective in cranial bone repair, a comparison was made between KBC and BoneSource, another material approved for the same indication. After Institutional Animal Care and Use Committee approval, the study assessed 24 rabbits, each with 2 separate cranial implants, to evaluate integration and absorption of the biomaterial at defined time points of 12, 18, 24, and 36 weeks. The 36-week assessment demonstrated near-complete resorption/integration of the BoneSource graft material. Bone was present within the biomaterial as well as independent of contact. The KBC was similarly integrated throughout the mass of the material, and new bone was in contact with the grafting material and also seen as separate islands of new bone. The bone demonstrated lamellar bone architecture with clear trabecular morphology. At higher magnification, the bone architecture can be clearly delineated, and comparison between the graft fillers is not obvious relative to the bone that has formed. Despite microscopic similarities, the most striking difference was maintenance of scaffold anatomy during bone regeneration. Kryptonite Bone Cement meets the criteria described in the introduction; properties of biologic transparency, osteoconductivity, and ergonomic utility offer other potential uses in bone repair. Key tenets of bone tissue regeneration observed in this analysis included adequate cell differentiation and tissue support. Bone that formed demonstrated lamellar rather than woven bone to suggest response to loading strain rather than merely biochemical precipitation. Over the 36-week study, the graft showed progressive bioabsorbable potential with calibrated replacement.

miR-7 suppresses brain metastasis of breast cancer stem-like cells by modulating KLF4

PubMed Central

Okuda, Hiroshi; Xing, Fei; Pandey, Puspa R; Sharma, Sambad; Watabe, Misako; Pai, Sudha K.; Mo, Yin-Yuan; Iiizumi-Gairani, Megumi; Hirota, Shigeru; Liu, Yin; Wu, Kerui; Pochampally, Radhika; Watabe, Kounosuke

2012-01-01

Despite significant improvement in survival rates of breast cancer patients, prognosis of metastatic disease is still dismal. Cancer stem-like cells (CSCs) are considered to play a role in metastatic progression of breast cancer; however, the exact pathological role of CSCs is yet to be elucidated. In this report, we found that CSCs (CD24−/CD44+/ESA+) isolated from metastatic breast cell lines are significantly more metastatic than non-CSC populations in an organ specific manner. The results of our microRNA profile analysis for these cells revealed that CSCs that are highly metastatic to bone and brain expressed significantly lower level of miR-7 and that this microRNA was capable of modulating one of the essential genes for induced pluripotent stem cell, KLF4. Interestingly, high expression of KLF4 was significantly and inversely correlated to brain- but not bone-metastasis free survival of breast cancer patients, and we indeed found that the expression of miR-7 significantly suppressed the ability of CSCs to metastasize to brain but not to bone in our animal model. We also examined the expression of miR-7 and KLF4 in brain-metastatic lesions and found that these genes were significantly down- or up-regulated, respectively, in the tumor cells in brain. Furthermore, the results of our in vitro experiments indicate that miR-7 attenuates the abilities of invasion and self-renewal of CSCs by modulating KLF4 expression. These results suggest that miR-7 and KLF4 may serve as biomarkers or therapeutic targets for brain metastasis of breast cancer. PMID:23384942

Evidence of bone marrow downregulation in brain-dead rats.

PubMed

Menegat, Laura; Simas, Rafael; Caliman, Julia M; Zanoni, Fernando L; Jacysyn, Jacqueline F; da Silva, Luiz Fernando F; Borelli, Primavera; Moreira, Luiz Felipe P; Sannomiya, Paulina

2017-06-01

Experimental findings support the evidence of a persistent leucopenia triggered by brain death (BD). This study aimed to investigate leucocyte behaviour in bone marrow and blood after BD in rats. BD was induced using intracranial balloon catheter inflation. Sham-operated (SH) rats were trepanned only. Thereafter bone marrow cells were harvested every six hours from the femoral cavity and used for total and differential counts. They were analysed further by flow cytometry to characterize lymphocyte subsets, granulocyte adhesion molecules expression and apoptosis/necrosis [annexin V/propidium iodide (PI) protocol]. BD rats exhibited a reduction in bone marrow cells due to a reduction in lymphocytes (40%) and segmented cells (45%). Bone marrow lymphocyte subsets were similar in BD and SH rats (CD3, P = 0.1; CD4, P = 0.4; CD3/CD4, P = 0.4; CD5, P = 0.4, CD3/CD5, P = 0.2; CD8, P = 0.8). Expression of L-selectin and beta 2 -integrins on granulocytes did not differ (CD11a, P = 0.9; CD11b/c, P = 0.7; CD62L, P = 0.1). There were no differences in the percentage of apoptosis and necrosis (Annexin V, P = 0.73; PI, P = 0.21; Annexin V/PI, P = 0.29). In conclusion, data presented suggest that the downregulation of the bone marrow is triggered by brain death itself, and it is not related to changes in lymphocyte subsets, granulocyte adhesion molecules expression or apoptosis and necrosis. © 2017 The Authors. International Journal of Experimental Pathology © 2017 International Journal of Experimental Pathology.

Intrinsic qualities of primate bones as predictors of skeletal element representation in modern and fossil carnivore feeding assemblages.

PubMed

Carlson, Kristian J; Pickering, Travis Rayne

2003-04-01

Plio-Pleistocene faunal assemblages from Swartkrans Cave (South Africa) preserve large numbers of primate remains. Brain, C.K., 1981. The Hunters or the Hunted? An Introduction to African Cave Taphonomy. University of Chicago Press, Chicago suggested that these primate subassemblages might have resulted from a focus by carnivores on primate predation and bone accumulation. Brain's hypothesis prompted us to investigate, in a previous study, this taphonomic issue as it relates to density-mediated destruction of primate bones (J. Archaeol. Sci. 29, 2002, 883). Here we extend our investigation of Brain's hypothesis by examining additional intrinsic qualities of baboon bones and their role as mediators of skeletal element representation in carnivore-created assemblages. Using three modern adult baboon skeletons, we collected data on four intrinsic bone qualities (bulk bone mineral density, maximum length, volume, and cross-sectional area) for approximately 81 bones per baboon skeleton. We investigated the relationship between these intrinsic bone qualities and a measure of skeletal part representation (the percentage minimum animal unit) for baboon bones in carnivore refuse and scat assemblages. Refuse assemblages consist of baboon bones not ingested during ten separate experimental feeding episodes in which individual baboon carcasses were fed to individual captive leopards and a spotted hyena. Scat assemblages consist of those baboon bones recovered in carnivore regurgitations and feces resulting from the feeding episodes. In refuse assemblages, volume (i.e., size) was consistently the best predictor of element representation, while cross-sectional area was the poorest predictor in the leopard refuse assemblage and bulk bone mineral density (i.e., a measure of the proportion of cortical to trabecular bone) was the poorest predictor in the hyena refuse assemblage. In light of previous documentation of carnivore-induced density-mediated destruction to bone assemblages, we interpret the current findings as suggestive of the secondary importance of bulk bone mineral density to other intrinsic qualities of skeletal elements (e.g., size, maximum dimension, and average cross-sectional area). It is only when skeletal elements are too large for consumption (e.g., many long bones) that they are fragmented following intra-element patterns of density-mediated carnivore destruction. There appears to be a size threshold beneath which bulk bone mineral density contributes little to mediating carnivore destruction of carcasses. Thus, depending on body size of the predator, body size of the prey, and specific size of the element, bulk bone mineral density may play little or no role of primary importance in mediating the destruction of skeletal elements. We compare patterns in modern comparative assemblages to patterns in primate fossil assemblages from Swartkrans. One of the fossil assemblages, Swartkrans Member 1, Hanging Remnant, most closely approximates a hyena (possibly refuse) assemblage pattern, while the Swartkrans Member 2 assemblage most closely approximates a leopard (possibly scat) assemblage pattern. The Swartkrans Member 1, Lower Bank, assemblage does not closely approximate any of our modern comparative assemblage patterns.

Tactile and bone-conduction auditory brain computer interface for vision and hearing impaired users.

PubMed

Rutkowski, Tomasz M; Mori, Hiromu

2015-04-15

The paper presents a report on the recently developed BCI alternative for users suffering from impaired vision (lack of focus or eye-movements) or from the so-called "ear-blocking-syndrome" (limited hearing). We report on our recent studies of the extents to which vibrotactile stimuli delivered to the head of a user can serve as a platform for a brain computer interface (BCI) paradigm. In the proposed tactile and bone-conduction auditory BCI novel multiple head positions are used to evoke combined somatosensory and auditory (via the bone conduction effect) P300 brain responses, in order to define a multimodal tactile and bone-conduction auditory brain computer interface (tbcaBCI). In order to further remove EEG interferences and to improve P300 response classification synchrosqueezing transform (SST) is applied. SST outperforms the classical time-frequency analysis methods of the non-linear and non-stationary signals such as EEG. The proposed method is also computationally more effective comparing to the empirical mode decomposition. The SST filtering allows for online EEG preprocessing application which is essential in the case of BCI. Experimental results with healthy BCI-naive users performing online tbcaBCI, validate the paradigm, while the feasibility of the concept is illuminated through information transfer rate case studies. We present a comparison of the proposed SST-based preprocessing method, combined with a logistic regression (LR) classifier, together with classical preprocessing and LDA-based classification BCI techniques. The proposed tbcaBCI paradigm together with data-driven preprocessing methods are a step forward in robust BCI applications research. Copyright © 2014 Elsevier B.V. All rights reserved.

MicroRNA-101a regulates microglial morphology and inflammation.

PubMed

Saika, Reiko; Sakuma, Hiroshi; Noto, Daisuke; Yamaguchi, Shuhei; Yamamura, Takashi; Miyake, Sachiko

2017-05-30

Microglia, as well as other tissue-resident macrophages, arise from yolk sac progenitors. Thus, it is likely that the central nervous system environment is critical for the acquisition of a distinct microglial phenotype. Several microRNAs that are enriched in the brain play crucial roles in brain development and may also play a role in the differentiation of microglia. To track the differentiation of hematopoietic cells into microglia, lineage-negative bone marrow cells were co-cultured with astrocytes in the absence or presence of microRNAs or their inhibitors. Microglia-like cells were identified as small, round cells that were immunopositive for CD11b, Iba1, CX3CR1, and triggering receptor expressed on myeloid cells (TREM)-2. Five microRNAs (miR-101a, miR-139-3p, miR-214 * , miR-218, and miR-1186) were identified as modifiers of the differentiation of bone marrow-derived microglia-like cells. Among them, miR-101a facilitated the differentiation of bone marrow cells into microglia-like cells most potently. Small, round cells expressing CD11b, Iba1, CX3CR1, and TREM-2 were predominant in cells treated by miR-101a. miR-101a was abundantly expressed in non-microglial brain cells. Transfection of miR-101a into microglia significantly increased the production of IL-6 in response to LPS. Finally, miR-101a downregulated the expression of MAPK phosphatase-1. miR-101a, which is enriched in the brain, promotes the differentiation of bone marrow cells into microglia-like cells.

Brain-targeted stem cell gene therapy corrects mucopolysaccharidosis type II via multiple mechanisms.

PubMed

Gleitz, Hélène Fe; Liao, Ai Yin; Cook, James R; Rowlston, Samuel F; Forte, Gabriella Ma; D'Souza, Zelpha; O'Leary, Claire; Holley, Rebecca J; Bigger, Brian W

2018-06-08

The pediatric lysosomal storage disorder mucopolysaccharidosis type II is caused by mutations in IDS, resulting in accumulation of heparan and dermatan sulfate, causing severe neurodegeneration, skeletal disease, and cardiorespiratory disease. Most patients manifest with cognitive symptoms, which cannot be treated with enzyme replacement therapy, as native IDS does not cross the blood-brain barrier. We tested a brain-targeted hematopoietic stem cell gene therapy approach using lentiviral IDS fused to ApoEII (IDS.ApoEII) compared to a lentivirus expressing normal IDS or a normal bone marrow transplant. In mucopolysaccharidosis II mice, all treatments corrected peripheral disease, but only IDS.ApoEII mediated complete normalization of brain pathology and behavior, providing significantly enhanced correction compared to IDS. A normal bone marrow transplant achieved no brain correction. Whilst corrected macrophages traffic to the brain, secreting IDS/IDS.ApoEII enzyme for cross-correction, IDS.ApoEII was additionally more active in plasma and was taken up and transcytosed across brain endothelia significantly better than IDS via both heparan sulfate/ApoE-dependent receptors and mannose-6-phosphate receptors. Brain-targeted hematopoietic stem cell gene therapy provides a promising therapy for MPS II patients. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Clinical Application of High-intensity Focused Ultrasound in Cancer Therapy

PubMed Central

Hsiao, Yi-Hsuan; Kuo, Shou-Jen; Tsai, Horng-Der; Chou, Ming-Chih; Yeh, Guang-Perng

2016-01-01

The treatment of cancer is an important issue in both developing and developed countries. Clinical use of ultrasound in cancer is not only for the diagnosis but also for the treatment. Focused ultrasound surgery (FUS) is a noninvasive technique. By using the combination of high-intensity focused ultrasound (HIFU) and imaging method, FUS has the potential to ablate tumor lesions precisely. The main mechanisms of HIFU ablation involve mechanical and thermal effects. Recent advances in HIFU have increased its popularity. Some promising results were achieved in managing various malignancies, including pancreas, prostate, liver, kidney, breast and bone. Other applications include brain tumor ablation and disruption of the blood-brain barrier. We aim at briefly outlining the clinical utility of FUS as a noninvasive technique for a variety of types of cancer treatment. PMID:26918034

Extracranial bone metastases from recurrent anaplastic astrocytoma on FDG PET/CT

PubMed Central

Li, Zu-Gui; Mu, Hai-Yu

2017-01-01

Abstract Objective: Extracranial bone metastases from astrocytoma are rare and frequently detected as part of multiorgan metastases. It is extremely rare for astrocytoma to have extracranial bone metastases alone. The importance of whole-body fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging in evaluating extracranial metastasis (ECMs) has not been described effectively due to the rarity of this event. The purpose of our case report is to emphasize the role of FDG PET/CT in the assessment of tumor recurrence and extracranial bone metastases from anaplastic astrocytoma. Methods and materials: A 25-year-old woman was firstly admitted with a 4-month history of progressive blurred vision, and 2-month history of intermittent headache. Presurgical MRI imaging revealed a large mass in the left trigone of lateral ventricle. Subsequently, she underwent tumor resection, radiotherapy and chemotherapy. A final pathological diagnosis of anaplastic astrocytoma (WHO III) was made. Nearly 12 months after the surgery, the follow-up brain MR imaging revealed a contrast-enhanced lesion in the site of operative region. Whole-body FDG PET/CT imaging was performed to evaluate the situation. Results: Postoperative brain FDG PET/CT showed an abnormal focal FDG uptake corresponding to the contrast-enhanced lesion in the operative area, suggesting a tumor recurrence. Whole-body FDG PET/CT also showed multiple FDG-avid osteosclerotic lesions in the body. It was highly suggestive of extracranial bone metastases. A subsequent open bone biopsy of FDG-avid lesion in right iliac crest was performed. Histopathological and immunohistochemical findings indicated characteristic of glioma. The patient died 1 month later, nearly 13 months after the initial diagnosis. Conclusions: ECMs from anaplastic astrocytoma are extremely rare but they do occur. Whole-body FDG PET/CT imaging with inclusion of brain was valuable in differentiating tumor recurrence from radiation necrosis and in detecting uncommon extracranial bone metastases from anaplastic astrocytoma, which were closely related to prognosis of this disease. PMID:28591062

Response of Woodpecker's Head during Pecking Process Simulated by Material Point Method.

PubMed

Liu, Yuzhe; Qiu, Xinming; Zhang, Xiong; Yu, T X

2015-01-01

Prevention of brain injury in woodpeckers under high deceleration during the pecking process has been an intriguing biomechanical problem for a long time. Several studies have provided different explanations, but the function of the hyoid bone, one of the more interesting skeletal features of a woodpecker, still has not been fully explored. This paper studies the relationship between a woodpecker head's response to impact and the hyoid bone. Based on micro-CT scanning images, the material point method (MPM) is employed to simulate woodpecker's pecking process. The maximum shear stress in the brainstem (SSS) is adopted as an indicator of brain injury. The motion and deformation of the first cervical vertebra is found to be the main reason of the shear stress of the brain. Our study found that the existence of the hyoid bone reduces the SSS level, enhances the rigidity of the head, and suppresses the oscillation of the endoskeleton after impact. The mechanism is explained by a brief mechanical analysis while the influence of the material properties of the muscle is also discussed.

Creatine supplementation in the aging population: effects on skeletal muscle, bone and brain.

PubMed

Gualano, Bruno; Rawson, Eric S; Candow, Darren G; Chilibeck, Philip D

2016-08-01

This narrative review aims to summarize the recent findings on the adjuvant application of creatine supplementation in the management of age-related deficits in skeletal muscle, bone and brain metabolism in older individuals. Most studies suggest that creatine supplementation can improve lean mass and muscle function in older populations. Importantly, creatine in conjunction with resistance training can result in greater adaptations in skeletal muscle than training alone. The beneficial effect of creatine upon lean mass and muscle function appears to be applicable to older individuals regardless of sex, fitness or health status, although studies with very old (>90 years old) and severely frail individuals remain scarce. Furthermore, there is evidence that creatine may affect the bone remodeling process; however, the effects of creatine on bone accretion are inconsistent. Additional human clinical trials are needed using larger sample sizes, longer durations of resistance training (>52 weeks), and further evaluation of bone mineral, bone geometry and microarchitecture properties. Finally, a number of studies suggest that creatine supplementation improves cognitive processing under resting and various stressed conditions. However, few data are available on older adults, and the findings are discordant. Future studies should focus on older adults and possibly frail elders or those who have already experienced an age-associated cognitive decline.

Anaesthetic management for awake craniotomy in brain glioma resection: initial experience in Military Hospital Mohamed V of Rabat

PubMed Central

Meziane, Mohammed; Elkoundi, Abdelghafour; Ahtil, Redouane; Guazaz, Miloudi; Mustapha, Bensghir; Haimeur, Charki

2017-01-01

The awake brain surgery is an innovative approach in the treatment of tumors in the functional areas of the brain. There are various anesthetic techniques for awake craniotomy (AC), including asleep-awake-asleep technique, monitored anesthesia care, and the recent introduced awake-awake-awake method. We describe our first experience with anesthetic management for awake craniotomy, which was a combination of these techniques with scalp nerve block, and propofol/rémifentanil target controlled infusion. A 28-year-oldmale underwent an awake craniotomy for brain glioma resection. The scalp nerve block was performed and a low sedative state was maintained until removal of bone flap. During brain glioma resection, the patient awake state was maintained without any complications. Once, the tumorectomy was completed, the level of anesthesia was deepened and a laryngeal mask airway was inserted. A well psychological preparation, a reasonable choice of anesthetic techniques and agents, and continuous team communication were some of the key challenges for successful outcome in our patient. PMID:28904684

Subject-specific bone attenuation correction for brain PET/MR: can ZTE-MRI substitute CT scan accurately?

PubMed

Khalifé, Maya; Fernandez, Brice; Jaubert, Olivier; Soussan, Michael; Brulon, Vincent; Buvat, Irène; Comtat, Claude

2017-09-21

In brain PET/MR applications, accurate attenuation maps are required for accurate PET image quantification. An implemented attenuation correction (AC) method for brain imaging is the single-atlas approach that estimates an AC map from an averaged CT template. As an alternative, we propose to use a zero echo time (ZTE) pulse sequence to segment bone, air and soft tissue. A linear relationship between histogram normalized ZTE intensity and measured CT density in Hounsfield units ([Formula: see text]) in bone has been established thanks to a CT-MR database of 16 patients. Continuous AC maps were computed based on the segmented ZTE by setting a fixed linear attenuation coefficient (LAC) to air and soft tissue and by using the linear relationship to generate continuous μ values for the bone. Additionally, for the purpose of comparison, four other AC maps were generated: a ZTE derived AC map with a fixed LAC for the bone, an AC map based on the single-atlas approach as provided by the PET/MR manufacturer, a soft-tissue only AC map and, finally, the CT derived attenuation map used as the gold standard (CTAC). All these AC maps were used with different levels of smoothing for PET image reconstruction with and without time-of-flight (TOF). The subject-specific AC map generated by combining ZTE-based segmentation and linear scaling of the normalized ZTE signal into [Formula: see text] was found to be a good substitute for the measured CTAC map in brain PET/MR when used with a Gaussian smoothing kernel of [Formula: see text] corresponding to the PET scanner intrinsic resolution. As expected TOF reduces AC error regardless of the AC method. The continuous ZTE-AC performed better than the other alternative MR derived AC methods, reducing the quantification error between the MRAC corrected PET image and the reference CTAC corrected PET image.

Subject-specific bone attenuation correction for brain PET/MR: can ZTE-MRI substitute CT scan accurately?

NASA Astrophysics Data System (ADS)

Khalifé, Maya; Fernandez, Brice; Jaubert, Olivier; Soussan, Michael; Brulon, Vincent; Buvat, Irène; Comtat, Claude

2017-10-01

In brain PET/MR applications, accurate attenuation maps are required for accurate PET image quantification. An implemented attenuation correction (AC) method for brain imaging is the single-atlas approach that estimates an AC map from an averaged CT template. As an alternative, we propose to use a zero echo time (ZTE) pulse sequence to segment bone, air and soft tissue. A linear relationship between histogram normalized ZTE intensity and measured CT density in Hounsfield units (HU ) in bone has been established thanks to a CT-MR database of 16 patients. Continuous AC maps were computed based on the segmented ZTE by setting a fixed linear attenuation coefficient (LAC) to air and soft tissue and by using the linear relationship to generate continuous μ values for the bone. Additionally, for the purpose of comparison, four other AC maps were generated: a ZTE derived AC map with a fixed LAC for the bone, an AC map based on the single-atlas approach as provided by the PET/MR manufacturer, a soft-tissue only AC map and, finally, the CT derived attenuation map used as the gold standard (CTAC). All these AC maps were used with different levels of smoothing for PET image reconstruction with and without time-of-flight (TOF). The subject-specific AC map generated by combining ZTE-based segmentation and linear scaling of the normalized ZTE signal into HU was found to be a good substitute for the measured CTAC map in brain PET/MR when used with a Gaussian smoothing kernel of 4~mm corresponding to the PET scanner intrinsic resolution. As expected TOF reduces AC error regardless of the AC method. The continuous ZTE-AC performed better than the other alternative MR derived AC methods, reducing the quantification error between the MRAC corrected PET image and the reference CTAC corrected PET image.

Comparison of transplantation of bone marrow stromal cells (BMSC) and stem cell mobilization by granulocyte colony stimulating factor after traumatic brain injury in rat.

PubMed

Bakhtiary, Mehrdad; Marzban, Mohsen; Mehdizadeh, Mehdi; Joghataei, Mohammad Taghi; Khoei, Samideh; Pirhajati Mahabadi, Vahid; Laribi, Bahareh; Tondar, Mahdi; Moshkforoush, Arash

2010-10-01

Recent clinical studies of treating traumatic brain injury (TBI) with autologous adult stem cells led us to compare effect of intravenous injection of bone marrow mesenchymal stem cells (BMSC) and bone marrow hematopoietic stem cell mobilization, induced by granulocyte colony stimulating factor (G-CSF), in rats with a cortical compact device. Forty adult male Wistar rats were injured with controlled cortical impact device and divided randomly into four groups. The treatment groups were injected with 2 × 106 intravenous bone marrow stromal stem cell (n = 10) and also with subcutaneous G-CSF (n = 10) and sham-operation group (n = 10) received PBS and "bromodeoxyuridine (Brdu)" alone, i.p. All injections were performed 1 day after injury into the tail veins of rats. All cells were labeled with Brdu before injection into the tail veins of rats. Functional neurological evaluation of animals was performed before and after injury using modified neurological severity scores (mNSS). Animals were sacrificed 42 days after TBI and brain sections were stained by Brdu immunohistochemistry. Statistically, significant improvement in functional outcome was observed in treatment groups compared with control group (P<0.01). mNSS showed no significant difference between the BMSC and G-CSF-treated groups during the study period (end of the trial). Histological analyses showed that Brdu-labeled (MSC) were present in the lesion boundary zone at 42nd day in all injected animals. In our study, we found that administration of a bone marrow-stimulating factor (G-CSF) and BMSC in a TBI model provides functional benefits.

SU-E-P-49: Evaluation of Image Quality and Radiation Dose of Various Unenhanced Head CT Protocols

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, L; Khan, M; Alapati, K

2015-06-15

Purpose: To evaluate the diagnostic value of various unenhanced head CT protocols and predicate acceptable radiation dose level for head CT exam. Methods: Our retrospective analysis included 3 groups, 20 patients per group, who underwent clinical routine unenhanced adult head CT examination. All exams were performed axially with 120 kVp. Three protocols, 380 mAs without iterative reconstruction and automAs, 340 mAs with iterative reconstruction without automAs, 340 mAs with iterative reconstruction and automAs, were applied on each group patients respectively. The images were reconstructed with H30, J30 for brain window and H60, J70 for bone window. Images acquired with threemore » protocols were randomized and blindly reviewed by three radiologists. A 5 point scale was used to rate each exam The percentage of exam score above 3 and average scores of each protocol were calculated for each reviewer and tissue types. Results: For protocols without automAs, the average scores of bone window with iterative reconstruction were higher than those without iterative reconstruction for each reviewer although the radiation dose was 10 percentage lower. 100 percentage exams were scored 3 or higher and the average scores were above 4 for both brain and bone reconstructions. The CTDIvols are 64.4 and 57.8 mGy of 380 and 340 mAs, respectively. With automAs, the radiation dose varied with head size, resulting in 47.5 mGy average CTDIvol between 39.5 and 56.5 mGy. 93 and 98 percentage exams were scored great than 3 for brain and bone windows, respectively. The diagnostic confidence level and image quality of exams with AutomAs were less than those without AutomAs for each reviewer. Conclusion: According to these results, the mAs was reduced to 300 with automAs OFF for head CT exam. The radiation dose was 20 percentage lower than the original protocol and the CTDIvol was reduced to 51.2 mGy.« less

Reduced limbic and hypothalamic volumes correlate with bone density in early Alzheimer's disease.

PubMed

Loskutova, Natalia; Honea, Robyn A; Brooks, William M; Burns, Jeffrey M

2010-01-01

Accelerated bone loss is associated with Alzheimer's disease (AD). Although the central nervous system plays a direct role in regulating bone mass, primarily through the actions of the hypothalamus, there is little work investigating the possible role of neurodegeneration in bone loss. In this cross-sectional study, we examined the association between bone mineral density (BMD) and neuroimaging markers of neurodegeneration (i.e., global and regional measures of brain volume) in early AD and non-demented aging. Fifty-five non-demented and 63 early AD participants underwent standard neurological and neuropsychological assessment, structural MRI scanning, and dual energy x-ray absorptiometry. In early AD, voxel-based morphometry analyses demonstrated that low BMD was associated with low volume in limbic grey matter (GM) including the hypothalamus, cingulate, and parahippocampal gyri and in the left superior temporal gyrus and left inferior parietal cortex. No relationship between BMD and regional GM volume was found in non-demented controls. The hypothesis-driven region of interest analysis further isolating the hypothalamus demonstrated a positive relationship between BMD and hypothalamic volume after controlling for age and gender in the early AD group but not in non-demented controls. These results demonstrate that lower BMD is associated with lower hypothalamic volume in early AD, suggesting that central mechanisms of bone remodeling may be disrupted by neurodegeneration.

The Central Nervous System and Bone Metabolism: An Evolving Story.

PubMed

Dimitri, Paul; Rosen, Cliff

2017-05-01

Our understanding of the control of skeletal metabolism has undergone a dynamic shift in the last two decades, primarily driven by our understanding of energy metabolism. Evidence demonstrating that leptin not only influences bone cells directly, but that it also plays a pivotal role in controlling bone mass centrally, opened up an investigative process that has changed the way in which skeletal metabolism is now perceived. Other central regulators of bone metabolism have since been identified including neuropeptide Y (NPY), serotonin, endocannabinoids, cocaine- and amphetamine-regulated transcript (CART), adiponectin, melatonin and neuromedin U, controlling osteoblast and osteoclast differentiation, proliferation and function. The sympathetic nervous system was originally identified as the predominant efferent pathway mediating central signalling to control skeleton metabolism, in part regulated through circadian genes. More recent evidence points to a role of the parasympathetic nervous system in the control of skeletal metabolism either through muscarinic influence of sympathetic nerves in the brain or directly via nicotinic receptors on osteoclasts, thus providing evidence for broader autonomic skeletal regulation. Sensory innervation of bone has also received focus again widening our understanding of the complex neuronal regulation of bone mass. Whilst scientific advance in this field of bone metabolism has been rapid, progress is still required to understand how these model systems work in relation to the multiple confounders influencing skeletal metabolism, and the relative balance in these neuronal systems required for skeletal growth and development in childhood and maintaining skeletal integrity in adulthood.

Effect of maternal obesity on fetal bone development in the rat

USDA-ARS?s Scientific Manuscript database

Epidemiological studies show that quality of nutrition during intrauterine and postnatal early life impact the risk of low bone mass and fracture later in life. Maternal consumption of high-fat diets has been demonstrated to affect health outcomes, such as: brain development; obesity; insulin resist...

Epigenetic control of fetal bone development through HoxA10 in the rat

USDA-ARS?s Scientific Manuscript database

Epidemiological studies show that quality of nutrition during intrauterine and early postnatal life impact the risk of low bone mass and fracture later in life. Maternal consumption of high-fat diets has been demonstrated to affect health outcomes, such as: brain development; obesity; insulin resist...

The distribution of lithium and its effects on the distribution and excretion of other ions in the rat

PubMed Central

Birch, N. J.; Jenner, F. A.

1973-01-01

1. In rats, lithium (ca 1 mEquiv/kg body weight) decreased brain sodium and magnesium, bone sodium and calcium and increased muscle calcium, plasma magnesium, urinary calcium and urine volume. 2. Lithium was particularly concentrated in bone. PMID:4730833

Anorexia nervosa and bulimia nervosa: brains, bones and breeding.

PubMed

Starr, Taylor B; Kreipe, Richard E

2014-05-01

Recent research has modified both the conceptualization and treatment of eating disorders. New diagnostic criteria reducing the "not otherwise specified" category should facilitate the early recognition and treatment of anorexia nervosa (AN) and bulimia nervosa (BN). Technology-based studies identify AN and BN as "brain circuit" disorders; epidemiologic studies reveal that the narrow racial, ethnic and income profile of individuals no longer holds true for AN. The major organs affected long term-the brain and skeletal system-both respond to improved nutrition, with maintenance of body weight the best predictor of recovery. Twin studies have revealed gene x environment interactions, including both the external (social) and internal (pubertal) environments of boys and of girls. Family-based treatment has the best evidence base for effectiveness for younger patients. Medication plays a limited role in AN, but a major role in BN. Across diagnoses, the most important medicine is food.

Investigation of the relationship between facial injuries and traumatic brain injuries using a realistic subject-specific finite element head model.

PubMed

Tse, Kwong Ming; Tan, Long Bin; Lee, Shu Jin; Lim, Siak Piang; Lee, Heow Pueh

2015-06-01

In spite of anatomic proximity of the facial skeleton and cranium, there is lack of information in the literature regarding the relationship between facial and brain injuries. This study aims to correlate brain injuries with facial injuries using finite element method (FEM). Nine common impact scenarios of facial injuries are simulated with their individual stress wave propagation paths in the facial skeleton and the intracranial brain. Fractures of cranio-facial bones and intracranial injuries are evaluated based on the tolerance limits of the biomechanical parameters. General trend of maximum intracranial biomechanical parameters found in nasal bone and zygomaticomaxillary impacts indicates that severity of brain injury is highly associated with the proximity of location of impact to the brain. It is hypothesized that the midface is capable of absorbing considerable energy and protecting the brain from impact. The nasal cartilages dissipate the impact energy in the form of large scale deformation and fracture, with the vomer-ethmoid diverging stress to the "crumpling zone" of air-filled sphenoid and ethmoidal sinuses; in its most natural manner, the face protects the brain. This numerical study hopes to provide surgeons some insight in what possible brain injuries to be expected in various scenarios of facial trauma and to help in better diagnosis of unsuspected brain injury, thereby resulting in decreasing the morbidity and mortality associated with facial trauma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Of Brain and Bone: The Unusual Case of Dr. A

PubMed Central

Narvid, J; Gorno-Tempini, ML; Slavotinek, A; DeArmond, SJ; Cha, YH; Miller, BL; Rankin, K.P

2009-01-01

Frontotemporal dementia (FTD) is a clinical syndrome characterized by progressive decline in social conduct and a focal pattern of frontal and temporal lobe damage. Its biological basis is still poorly understood but the focality of the brain degeneration provides a powerful model to study the cognitive and anatomical basis of social cognition. Here, we present Dr. A, a patient with a rare hereditary bone disease (hereditary multiple exostoses) and FTD (pathologically characterized as Pick’s disease), who presented with a profound behavioral disturbance characterized by acquired sociopathy. We conducted a detailed genetic, pathological, neuroimaging and cognitive study, including a battery of tests designed to investigate Dr. A’s abilities to understand emotional cues and to infer mental states and intentions to others (theory of mind). Dr. A’s genetic profile suggests the possibility that a mutation causing hereditary multiple exostoses, Ext2, may play a role in the pattern of neurodegeneration in frontotemporal dementia since knockout mice deficient in the Ext gene family member, Ext1, show severe CNS defects including loss of olfactory bulbs and abnormally small cerebral cortex. Dr. A showed significant impairment in emotion comprehension, second order theory of mind, attribution of intentions, and empathy despite preserved general cognitive abilities. Voxel-based morphometry on structural MRI images showed significant atrophy in the medial and right orbital frontal and anterior temporal regions with sparing of dorsolateral frontal cortex. This case demonstrates that social and emotional dysfunction in FTD can dissociate from preserved performance on classic executive functioning tasks. The specific pattern of anatomical damage shown by VBM emphasizes the importance of the network including the superior medial frontal gyrus as well as temporal polar areas, in regulation of social cognition and theory of mind. This case provides new evidence regarding the neural basis of social cognition and suggests a possible genetic link between bone disease and FTD. PMID:20183548

Cerebral, facial, and orbital involvement in Erdheim-Chester disease: CT and MR imaging findings.

PubMed

Drier, Aurélie; Haroche, Julien; Savatovsky, Julien; Godenèche, Gaelle; Dormont, Didier; Chiras, Jacques; Amoura, Zahir; Bonneville, Fabrice

2010-05-01

To retrospectively review the brain magnetic resonance (MR) imaging and computed tomographic (CT) findings in patients with Erdheim-Chester disease (ECD). The ethics committee required neither institutional review board approval nor informed patient consent for retrospective analyses of the patients' medical records and imaging data. The patients' medical files were retrospectively reviewed in accordance with human subject research protocols. Three neuroradiologists in consensus analyzed the signal intensity, location, size, number, and gadolinium uptake of lesions detected on brain MR images obtained in 33 patients with biopsy-proved ECD. Thirty patients had intracranial, facial bone, and/or orbital involvement, and three had normal neurologic imaging findings. The hypothalamic-pituitary axis was involved in 16 (53%) of the 30 patients, with six (20%) cases of micronodular or nodular masses of the infundibular stalk. Meningeal lesions were observed in seven (23%) patients. Three (10%) patients had bilateral symmetric T2 high signal intensity in the dentate nucleus areas, and five (17%) had multiple intraaxial enhancing masses. Striking intracranial periarterial infiltration was observed in three (10%) patients. Another patient (3%) had a lesion in the lumen of the superior sagittal sinus. Nine (30%) patients had orbital involvement. Twenty-four (80%) patients had osteosclerosis of the facial and/or skull bones. At least two anatomic sites were involved in two-thirds (n = 20) of the patients. Osteosclerosis of the facial bones associated with orbital masses and either meningeal or infundibular stalk masses was seen in eight (27%) patients. Lesions of the brain, meninges, facial bones, and orbits are frequently observed and should be systematically sought on the brain MR and CT images obtained in patients with ECD, even if these patients are asymptomatic. Careful attention should be directed to the periarterial environment.

Transcranial Doppler detection of cerebral fat emboli and relation to paradoxical embolism: a pilot study.

PubMed

Forteza, Alejandro M; Koch, Sebastian; Campo-Bustillo, Iszet; Gutierrez, Jose; Haussen, Diogo C; Rabinstein, Alejandro A; Romano, Jose; Zych, Gregory A; Duncan, Robert

2011-05-10

The fat embolism syndrome is clinically characterized by dyspnea, skin petechiae, and neurological dysfunction. It is associated mainly with long bone fracture and bone marrow fat passage to the systemic circulation. An intracardiac right-to-left shunt (RLS) could allow larger fat particles to reach the systemic circulation. Transcranial Doppler can be a useful tool to detect both RLS and the fat particles reaching the brain. We prospectively studied patients with femur shaft fracture with RLS evaluation, daily transcranial Doppler with embolus detection studies, and neurological examinations to evaluate the relation of RLS and microembolic signals to the development of fat embolism syndrome. Forty-two patients were included; 14 had an RLS detected. Seven patients developed neurological symptoms; all of them had a positive RLS (P=<0.001). The patients with an RLS showed higher counts and higher intensities of microembolic signals (P=<0.05 and P=<0.01, respectively) compared with those who did not have an RLS identified. The presence of high microembolic signal counts and intensities in patients with RLS was strongly predictive of the occurrence of neurological symptoms (odds ratio, 204; 95% confidence interval, 11 to 3724; P<0.001) with a positive predictive value of 86% and negative predictive value of 97%. In patients with long bone fractures, the presence of an RLS is associated with larger and more frequent microembolic signals to the brain detected by transcranial Doppler study and can predict the development of neurological symptoms.

The "Skull Flap" a new conceived device for decompressive craniectomy experimental study on dogs to evaluate the safety and efficacy in reducing intracranial pressure and subsequent impact on brain perfusion.

PubMed

Salvatore, Chibbaro; Fabrice, Vallee; Marco, Marsella; Leonardo, Tigan; Thomas, Lilin; Benoit, Lecuelle; Bernard, George; Pierre, Kehrli; Eric, Vicaut; Paolo, Diemidio

2013-10-01

Decompressive craniectomy (DC) is a procedure performed increasingly often in current neurosurgical practice. Significant perioperative morbidity may be associated to this procedure because of the large skull defect; also, later closure of the skull defect (cranioplasty) may be associated to post-operative morbidity as much as any other reconstructive operation. The authors present a newly conceived/developed device: The "Skull Flap" (SF). This system, placed at the time of the craniectomy, offers the possibility to provide cranial reconstruction sparing patients a second operation. In other words, DC and cranioplasty essentially take place at the same time and in addition, patients retain their own bone flap. The current study conducted on animal models, represents the logical continuation of a prior recent study, realized on cadaver specimens, to assess the efficacy and safety of this recently developed device. This is an experimental pilot study on dogs to assess both safety and efficacy of the SF device. Two groups of experimental raised intracranial pressure animal models underwent DC; in the first group of dogs, the bone flap was left in raised position above the skull defect using the SF device; on the second group the flap was discarded. All dogs underwent transcranial Doppler (TCD) to assess brain perfusion. Head computed tomography (CT) scan to determine flap position was also obtained in the group in which the SF device was placed. SF has proved to be a strong fixation device that allows satisfactory brain decompression by keeping the bone flap elevated from the swollen brain; later on, the SF allows cranial reconstruction in a simple way without requiring a second staged operation. In addition, it is relevant to note that brain perfusion was measured and found to be better in the group receiving the SF (while the flap being in a raised as well as in its natural position) comparing to the other group. The SF device has proved to be very easy to place, well-adaptable to a different type of flaps and ultimately very effective in maintaining satisfactory brain decompression and later on, making easy bone flap repositioning after brain swelling has subsided.

MO-F-CAMPUS-J-04: Tissue Segmentation-Based MR Electron Density Mapping Method for MR-Only Radiation Treatment Planning of Brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, H; Lee, Y; Ruschin, M

2015-06-15

Purpose: Automatically derive electron density of tissues using MR images and generate a pseudo-CT for MR-only treatment planning of brain tumours. Methods: 20 stereotactic radiosurgery (SRS) patients’ T1-weighted MR images and CT images were retrospectively acquired. First, a semi-automated tissue segmentation algorithm was developed to differentiate tissues with similar MR intensities and large differences in electron densities. The method started with approximately 12 slices of manually contoured spatial regions containing sinuses and airways, then air, bone, brain, cerebrospinal fluid (CSF) and eyes were automatically segmented using edge detection and anatomical information including location, shape, tissue uniformity and relative intensity distribution.more » Next, soft tissues - muscle and fat were segmented based on their relative intensity histogram. Finally, intensities of voxels in each segmented tissue were mapped into their electron density range to generate pseudo-CT by linearly fitting their relative intensity histograms. Co-registered CT was used as a ground truth. The bone segmentations of pseudo-CT were compared with those of co-registered CT obtained by using a 300HU threshold. The average distances between voxels on external edges of the skull of pseudo-CT and CT in three axial, coronal and sagittal slices with the largest width of skull were calculated. The mean absolute electron density (in Hounsfield unit) difference of voxels in each segmented tissues was calculated. Results: The average of distances between voxels on external skull from pseudo-CT and CT were 0.6±1.1mm (mean±1SD). The mean absolute electron density differences for bone, brain, CSF, muscle and fat are 78±114 HU, and 21±8 HU, 14±29 HU, 57±37 HU, and 31±63 HU, respectively. Conclusion: The semi-automated MR electron density mapping technique was developed using T1-weighted MR images. The generated pseudo-CT is comparable to that of CT in terms of anatomical position of tissues and similarity of electron density assignment. This method can allow MR-only treatment planning.« less

[Study of migration and distribution of bone marrow cells transplanted animals with B16 melanoma ].

PubMed

Poveshchenko, A F; Solovieva, A O; Zubareva, K E; Strunkin, D N; Gricyk, O B; Poveshchenko, O V; Shurlygina, A V; Konenkov, V I

2017-01-01

Purpose. Reveal features migration and distribution of syngeneic bone marrow cells (BMC) and subpopulations (MSC) after transplantation into the recipient carrier B16 melanoma bodies. Methods. We used mouse male and female C57BL/6 mice. Induction of Tumor Growth: B16 melanoma cells implanted subcutaneously into right hind paw of female C57BL/6 mice at a dose of 2.5 x 105 cells / mouse. migration study in vivo distribution and BMC and MSC was performed using genetic markers - Y-chromosome specific sequence line male C57Bl/6 syngeneic intravenous transplantation in females using the polymerase chain reaction (PCR) in real time on Authorized Termal Cycler - Light Cycler 480 II / 96 (Roche). Introduction suspension of unseparated bone marrow cells, mesenchymal stem cells from donor to recipient male mice (syngeneic recipient female C57BL/6), followed by isolation of recipients of organs was performed at regular intervals, then of organ recipients isolated DNA. Results. It was shown that bone marrow cells positive for Y-chromosome in migrate lymphoid (lymph nodes, spleen, bone marrow) or in non-lymphoid organs (liver, heart, brain, skin) syngeneic recipients. In addition to the migration of cells from the bone marrow to other organs, there is a way back migration of cells from the circulation to the bone marrow. B16 melanoma stimulates the migration of transplanted MSCs and BMC in bone marrow. It is found that tumor growth enhanced migration of transplanted bone marrow cells, including populations of MSCs in the bone marrow. In the early stages of tumor formation MSC migration activity higher than the BMC. In the later stages of tumor formation undivided population of bone marrow cells migrate to the intense swelling compared with a population of MSCs. Conclusion. The possibility of using bone marrow MSCs for targeted therapy of tumor diseases, because migration of MSCs in tumor tissue can be used to effectively deliver anticancer drugs.

[Immune dysfunction and cognitive deficit in stress and physiological aging. Part II: New approaches to cognitive disorder prevention and treatment ].

PubMed

Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

2014-01-01

Long-term stress as well as physiological aging result in similar immunological and hormonal disturbances including hypothalamic-pituitary-adrenal) axis depletion, aberrant immune response (regulatory T-cells, Tregs, and T(h17)-lymphocyte accumulation) and decreased dehydroepian-drosterone synthesis both in the brain and in the adrenal glands. Since the main mechanisms of inflammation control, "prompt" (stress hormones) and "delayed" (Tregs), are broken, serum cytokine levels increase and become sufficient for blood-brain-barrier disruption. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Structural and functional alterations of blood-brain-barrier as well as stress- (or age-) induced neuroinflammation promote influx of bone marrow derived dendritic cells and lymphocyte effectors into the brain parenchyma. Thereafter, mass intrusion ofpro-inflammatory mediators and immune cells having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets: 1) reduction of excessive Treg accumulation; 2) supporting hypothalamic-pituitary-adrenal axis and inflammatory reaction attenuation; 3) recovery of dehydroepiandrosterone level; 4) improvement of blood-brain-barrier function.

The Role of Peripheral Nerve Function in Age-Related Bone Loss and Changes in Bone Adaptation

DTIC Science & Technology

2015-12-01

scratch response in development of spontaneous dermatitis in NC/Nga mice. Br J Dermatol 2004;151:335-45. 32. Nakano T, Andoh T, Sasaki A, Nojima H, Kuraishi... contact a stripe of brain derived neurotrophic factor becomes the axon [16]. During neuron growth, mitochondria, membrane vesicles, proteins involved in...epiphyseal bone marrow [27]. The CGRP containing neurons in rat femurs near the growth plate come in contact with osteoclasts [21]. Neuropeptide

Functional photoacoustic tomography for neonatal brain imaging: developments and challenges

NASA Astrophysics Data System (ADS)

Hariri, Ali; Tavakoli, Emytis; Adabi, Saba; Gelovani, Juri; Avanaki, Mohammad R. N.

2017-03-01

Transfontanelle ultrasound imaging (TFUSI) is a routine diagnostic brain imaging method in infants who are born prematurely, whose skull bones have not completely fused together and have openings between them, so-called fontanelles. Open fontanelles in neonates provide acoustic windows, allowing the ultrasound beam to freely pass through. TFUSI is used to rule out neurological complications of premature birth including subarachnoid hemorrhage (SAH), intraventricular (IVH), subependimal (SEPH), subdural (SDH) or intracerebral (ICH) hemorrhages, as well as hypoxic brain injuries. TFUSI is widely used in the clinic owing to its low cost, safety, accessibility, and noninvasive nature. Nevertheless, the accuracy of TFUSI is limited. To address several limitations of current clinical imaging modalities, we develop a novel transfontanelle photoacoustic imaging (TFPAI) probe, which, for the first time, should allow for non-invasive structural and functional imaging of the infant brain. In this study, we test the feasibility of TFPAI for detection of experimentally-induced intra ventricular and Intraparenchymal hemorrhage phantoms in a sheep model with a surgically-induced cranial window which will serve as a model of neonatal fontanelle. This study is towards using the probe we develop for bedside monitoring of neonates with various disease conditions and complications affecting brain perfusion and oxygenation, including apnea, asphyxia, as well as for detection of various types of intracranial hemorrhages (SAH, IVH, SEPH, SDH, ICH).

SU-E-T-56: Brain Metastasis Treatment Plans for Contrast-Enhanced Synchrotron Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Obeid, L; Adam, J; Tessier, A

2014-06-01

Purpose: Iodine-enhanced radiotherapy is an innovative treatment combining the selective accumulation of an iodinated contrast agent in brain tumors with irradiations using monochromatic medium energy x-rays. The aim of this study is to compare dynamic stereotactic arc-therapy and iodineenhanced SSRT. Methods: Five patients bearing brain metastasis received a standard helical 3D-scan without iodine. A second scan was acquired 13 min after an 80 g iodine infusion. Two SSRT treatment plans (with/without iodine) were performed for each patient using a dedicated Monte Carlo (MC) treatment planning system (TPS) based on the ISOgray TPS. Ten coplanar beams (6×6 cm2, shaped with collimator)more » were simulated. MC statistical error objective was less than 5% in the 50% isodose. The dynamic arc-therapy plan was achieved on the Iplan Brainlab TPS. The treatment plan validation criteria were fixed such that 100% of the prescribed dose is delivered at the beam isocentre and the 70% isodose contains the whole target volume. The comparison elements were the 70% isodose volume, the average and maximum doses delivered to organs at risk (OAR): brainstem, optical nerves, chiasma, eyes, skull bone and healthy brain parenchyma. Results: The stereotactic dynamic arc-therapy remains the best technique in terms of dose conformation. Iodine-enhanced SSRT presents similar performances to dynamic arc-therapy with increased brainstem and brain parenchyma sparing. One disadvantage of SSRT is the high dose to the skull bone. Iodine accumulation in metastasis may increase the dose by 20–30%, allowing a normal tissue sparing effect at constant prescribed dose. Treatment without any iodine enhancement (medium-energy stereotactic radiotherapy) is not relevant with degraded HDVs (brain, parenchyma and skull bone) comparing to stereotactic dynamic arc-therapy. Conclusion: Iodine-enhanced SSRT exhibits a good potential for brain metastasis treatment regarding the dose distribution and OAR criteria.« less

k-space sampling optimization for ultrashort TE imaging of cortical bone: Applications in radiation therapy planning and MR-based PET attenuation correction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Lingzhi, E-mail: hlingzhi@gmail.com, E-mail: raymond.muzic@case.edu; Traughber, Melanie; Su, Kuan-Hao

Purpose: The ultrashort echo-time (UTE) sequence is a promising MR pulse sequence for imaging cortical bone which is otherwise difficult to image using conventional MR sequences and also poses strong attenuation for photons in radiation therapy and PET imaging. The authors report here a systematic characterization of cortical bone signal decay and a scanning time optimization strategy for the UTE sequence through k-space undersampling, which can result in up to a 75% reduction in acquisition time. Using the undersampled UTE imaging sequence, the authors also attempted to quantitatively investigate the MR properties of cortical bone in healthy volunteers, thus demonstratingmore » the feasibility of using such a technique for generating bone-enhanced images which can be used for radiation therapy planning and attenuation correction with PET/MR. Methods: An angularly undersampled, radially encoded UTE sequence was used for scanning the brains of healthy volunteers. Quantitative MR characterization of tissue properties, including water fraction and R2{sup ∗} = 1/T2{sup ∗}, was performed by analyzing the UTE images acquired at multiple echo times. The impact of different sampling rates was evaluated through systematic comparison of the MR image quality, bone-enhanced image quality, image noise, water fraction, and R2{sup ∗} of cortical bone. Results: A reduced angular sampling rate of the UTE trajectory achieves acquisition durations in proportion to the sampling rate and in as short as 25% of the time required for full sampling using a standard Cartesian acquisition, while preserving unique MR contrast within the skull at the cost of a minimal increase in noise level. The R2{sup ∗} of human skull was measured as 0.2–0.3 ms{sup −1} depending on the specific region, which is more than ten times greater than the R2{sup ∗} of soft tissue. The water fraction in human skull was measured to be 60%–80%, which is significantly less than the >90% water fraction in brain. High-quality, bone-enhanced images can be generated using a reduced sampled UTE sequence with no visible compromise in image quality and they preserved bone-to-air contrast with as low as a 25% sampling rate. Conclusions: This UTE strategy with angular undersampling preserves the image quality and contrast of cortical bone, while reducing the total scanning time by as much as 75%. The quantitative results of R2{sup ∗} and the water fraction of skull based on Dixon analysis of UTE images acquired at multiple echo times provide guidance for the clinical adoption and further parameter optimization of the UTE sequence when used for radiation therapy and MR-based PET attenuation correction.« less

SU-F-303-12: Implementation of MR-Only Simulation for Brain Cancer: A Virtual Clinical Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glide-Hurst, C; Zheng, W; Kim, J

2015-06-15

Purpose: To perform a retrospective virtual clinical trial using an MR-only workflow for a variety of brain cancer cases by incorporating novel imaging sequences, tissue segmentation using phase images, and an innovative synthetic CT (synCT) solution. Methods: Ten patients (16 lesions) were evaluated using a 1.0T MR-SIM including UTE-DIXON imaging (TE = 0.144/3.4/6.9ms). Bone-enhanced images were generated from DIXON-water/fat and inverted UTE. Automated air segmentation was performed using unwrapped UTE phase maps. Segmentation accuracy was assessed by calculating intersection and Dice similarity coefficients (DSC) using CT-SIM as ground truth. SynCTs were generated using voxel-based weighted summation incorporating T2, FLAIR, UTE1,more » and bone-enhanced images. Mean absolute error (MAE) characterized HU differences between synCT and CT-SIM. Dose was recalculated on synCTs; differences were quantified using planar gamma analysis (2%/2 mm dose difference/distance to agreement) at isocenter. Digitally reconstructed radiographs (DRRs) were compared. Results: On average, air maps intersected 80.8 ±5.5% (range: 71.8–88.8%) between MR-SIM and CT-SIM yielding DSCs of 0.78 ± 0.04 (range: 0.70–0.83). Whole-brain MAE between synCT and CT-SIM was 160.7±8.8 HU, with the largest uncertainty arising from bone (MAE = 423.3±33.2 HU). Gamma analysis revealed pass rates of 99.4 ± 0.04% between synCT and CT-SIM for the cohort. Dose volume histogram analysis revealed that synCT tended to yield slightly higher doses. Organs at risk such as the chiasm and optic nerves were most sensitive due to their proximities to air/bone interfaces. DRRs generated via synCT and CT-SIM were within clinical tolerances. Conclusion: Our approach for MR-only simulation for brain cancer treatment planning yielded clinically acceptable results relative to the CT-based benchmark. While slight dose differences were observed, reoptimization of treatment plans and improved image registration can address this limitation. Future work will incorporate automated registration between setup images (cone-beam CT and kilovoltage images) for synCT and CT-SIM. Submitting institution holds research agreements with Philips HealthCare, Best, Netherlands and Varian Medical Systems, Palo Alto, CA. Research partially sponsored via an Internal Mentored Research Grant.« less

Human exposure to metals: levels in autopsy tissues of individuals living near a hazardous waste incinerator.

PubMed

Mari, Montse; Nadal, Martí; Schuhmacher, Marta; Barbería, Eneko; García, Francisco; Domingo, José L

2014-06-01

The concentrations of a number of metals were determined in the brain, bone, kidney, liver, and lung of 20 autopsied subjects who had lived, at least 10 years, in the neighborhood of a hazardous waste incinerator (HWI) in Tarragona (Catalonia, Spain). Results were compared with those obtained in 1998 (baseline survey) and previous surveys (2003 and 2007). Arsenic, Be, Ni, Tl, and V showed concentrations below the corresponding detection limits in all tissues. Cadmium showed the highest levels in the kidney, with a mean value of 21.15 μg/g. However, Cd was found below the detection limit in the brain and bone. Chromium showed similar concentrations in the kidney, brain, and lung (range of mean values, 0.57-0.66 μg/g) and higher in the bone (1.38 μg/g). In turn, Hg was below the detection limit in all tissues with the exception of the kidney, where the mean concentration was 0.15 μg/g (range, <0.05-0.58 μg/g). On the other hand, Mn could be detected in all tissues showing the highest levels in the liver and kidney (1.45 and 1.09 μg/g, respectively). Moreover, Pb showed the highest concentrations in bone (mean, 1.39 μg/g; range, <0.025-4.88 μg/g). Finally, Sn could be detected only in some tissue samples, reaching the highest values in the bone (0.17 μg/g). The current metal levels in human tissues from individuals living near the HWI of Tarragona are comparable and of a similar magnitude to previously reported results corresponding to general populations, as well as those of our previous surveys.

Accuracy of UTE-MRI-based patient setup for brain cancer radiation therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Yingli; Cao, Minsong; Kaprealian, Tania

2016-01-15

Purpose: Radiation therapy simulations solely based on MRI have advantages compared to CT-based approaches. One feature readily available from computed tomography (CT) that would need to be reproduced with MR is the ability to compute digitally reconstructed radiographs (DRRs) for comparison against on-board radiographs commonly used for patient positioning. In this study, the authors generate MR-based bone images using a single ultrashort echo time (UTE) pulse sequence and quantify their 3D and 2D image registration accuracy to CT and radiographic images for treatments in the cranium. Methods: Seven brain cancer patients were scanned at 1.5 T using a radial UTEmore » sequence. The sequence acquired two images at two different echo times. The two images were processed using an in-house software to generate the UTE bone images. The resultant bone images were rigidly registered to simulation CT data and the registration error was determined using manually annotated landmarks as references. DRRs were created based on UTE-MRI and registered to simulated on-board images (OBIs) and actual clinical 2D oblique images from ExacTrac™. Results: UTE-MRI resulted in well visualized cranial, facial, and vertebral bones that quantitatively matched the bones in the CT images with geometric measurement errors of less than 1 mm. The registration error between DRRs generated from 3D UTE-MRI and the simulated 2D OBIs or the clinical oblique x-ray images was also less than 1 mm for all patients. Conclusions: UTE-MRI-based DRRs appear to be promising for daily patient setup of brain cancer radiotherapy with kV on-board imaging.« less

Leptin: a potential mediator for protective effects of fat mass on bone tissue.

PubMed

Thomas, Thierry

2003-02-01

Body weight is among the most powerful predictors of bone status, and adipose tissue plays a substantial role in weight-related protective effects on bone. An understanding of the mechanisms underlying the relation between adipose tissue and bone may open up new perspectives for treatment. Leptin, which is known to regulate appetite and energy expenditures, may also contribute to mediate the effects of fat mass on bone. Although reported data are somewhat conflicting, there is some evidence that leptin may decrease bone formation via a central nervous effect and may stimulate both bone formation and bone resorption via direct peripheral effects on stromal precursor cells. The net result of these central and peripheral effects may depend on serum leptin levels and blood-brain barrier permeability, of which the first increase and the second decrease as obesity develops. Further work is needed to improve our understanding of these effects.

Image-guided total marrow and total lymphatic irradiation using helical tomotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schultheiss, Timothy E.; Wong, Jeffrey; Liu, An

2007-03-15

Purpose: To develop a treatment technique to spare normal tissue and allow dose escalation in total body irradiation (TBI). We have developed intensity-modulated radiotherapy techniques for the total marrow irradiation (TMI), total lymphatic irradiation, or total bone marrow plus lymphatic irradiation using helical tomotherapy. Methods and Materials: For TBI, we typically use 12 Gy in 10 fractions delivered at an extended source-to-surface distance (SSD). Using helical tomotherapy, it is possible to deliver equally effective doses to the bone marrow and lymphatics while sparing normal organs to a significant degree. In the TMI patients, whole body skeletal bone, including the ribsmore » and sternum, comprise the treatment target. In the total lymphatic irradiation, the target is expanded to include the spleen and major lymph node areas. Sanctuary sites for disease (brain and testes) are included when clinically indicated. Spared organs include the lungs, esophagus, parotid glands, eyes, oral cavity, liver, kidneys, stomach, small and large intestine, bladder, and ovaries. Results: With TBI, all normal organs received the TBI dose; with TMI, total lymphatic irradiation, and total bone marrow plus lymphatic irradiation, the visceral organs are spared. For the first 6 patients treated with TMI, the median dose to organs at risk averaged 51% lower than would be achieved with TBI. By putting greater weight on the avoidance of specific organs, greater sparing was possible. Conclusion: Sparing of normal tissues and dose escalation is possible using helical tomotherapy. Late effects such as radiation pneumonitis, veno-occlusive disease, cataracts, neurocognitive effects, and the development of second tumors should be diminished in severity and frequency according to the dose reduction realized for the organs at risk.« less

Common endocrine control of body weight, reproduction, and bone mass

NASA Technical Reports Server (NTRS)

Takeda, Shu; Elefteriou, Florent; Karsenty, Gerard

2003-01-01

Bone mass is maintained constant between puberty and menopause by the balance between osteoblast and osteoclast activity. The existence of a hormonal control of osteoblast activity has been speculated for years by analogy to osteoclast biology. Through the search for such humoral signal(s) regulating bone formation, leptin has been identified as a strong inhibitor of bone formation. Furthermore, intracerebroventricular infusion of leptin has shown that the effect of this adipocyte-derived hormone on bone is mediated via a brain relay. Subsequent studies have led to the identification of hypothalamic groups of neurons involved in leptin's antiosteogenic function. In addition, those neurons or neuronal pathways are distinct from neurons responsible for the regulation of energy metabolism. Finally, the peripheral mediator of leptin's antiosteogenic function has been identified as the sympathetic nervous system. Sympathomimetics administered to mice decreased bone formation and bone mass. Conversely, beta-blockers increased bone formation and bone mass and blunted the bone loss induced by ovariectomy.

Towards optical brain imaging: getting light through a bone

NASA Astrophysics Data System (ADS)

Thompson, J. V.; Hokr, B. H.; Nodurft, D. T.; Yakovlev, V. V.

2018-06-01

Optical imaging and detection in biological samples is severely limited by scattering effects. In particular, optical techniques for measuring conditions beneath the skull and within the bone marrow hold significant promise when it comes to speed, sensitivity and specificity. However, the strong optical scattering due to bone hinders the realization of these methods. In this article, we propose a technique to enhance the transmittance of light through bone. This is achieved by injecting light below the top surface of the bone and utilizing multiple scattering to increase transmittance. This technique suggests that enhancements of 2-6 times may be realized by injection of light 1 mm below the surface of the bone. By enhancing the transmittance of light through bone, we will greatly improve our ability to utilize optical methods to better understand and diagnose conditions within biological media.

T cells establish and maintain CNS viral infection in HIV-infected humanized mice.

PubMed

Honeycutt, Jenna B; Liao, Baolin; Nixon, Christopher C; Cleary, Rachel A; Thayer, William O; Birath, Shayla L; Swanson, Michael D; Sheridan, Patricia; Zakharova, Oksana; Prince, Francesca; Kuruc, JoAnn; Gay, Cynthia L; Evans, Chris; Eron, Joseph J; Wahl, Angela; Garcia, J Victor

2018-06-04

The human brain is an important site of HIV replication and persistence during antiretroviral therapy (ART). Direct evaluation of HIV infection in the brains of otherwise healthy individuals is not feasible; therefore, we performed a large-scale study of bone marrow/liver/thymus (BLT) humanized mice as an in vivo model to study HIV infection in the brain. Human immune cells, including CD4+ T cells and macrophages, were present throughout the BLT mouse brain. HIV DNA, HIV RNA, and/or p24+ cells were observed in the brains of HIV-infected animals, regardless of the HIV isolate used. HIV infection resulted in decreased numbers of CD4+ T cells, increased numbers of CD8+ T cells, and a decreased CD4+/CD8+ T cell ratio in the brain. Using humanized T cell-only mice (ToM), we demonstrated that T cells establish and maintain HIV infection of the brain in the complete absence of human myeloid cells. HIV infection of ToM resulted in CD4+ T cell depletion and a reduced CD4+/CD8+ T cell ratio. ART significantly reduced HIV levels in the BLT mouse brain, and the immune cell populations present were indistinguishable from those of uninfected controls, which demonstrated the effectiveness of ART in controlling HIV replication in the CNS and returning cellular homeostasis to a pre-HIV state.

Magnetic Resonance-Based Automatic Air Segmentation for Generation of Synthetic Computed Tomography Scans in the Head Region.

PubMed

Zheng, Weili; Kim, Joshua P; Kadbi, Mo; Movsas, Benjamin; Chetty, Indrin J; Glide-Hurst, Carri K

2015-11-01

To incorporate a novel imaging sequence for robust air and tissue segmentation using ultrashort echo time (UTE) phase images and to implement an innovative synthetic CT (synCT) solution as a first step toward MR-only radiation therapy treatment planning for brain cancer. Ten brain cancer patients were scanned with a UTE/Dixon sequence and other clinical sequences on a 1.0 T open magnet with simulation capabilities. Bone-enhanced images were generated from a weighted combination of water/fat maps derived from Dixon images and inverted UTE images. Automated air segmentation was performed using unwrapped UTE phase maps. Segmentation accuracy was assessed by calculating segmentation errors (true-positive rate, false-positive rate, and Dice similarity indices using CT simulation (CT-SIM) as ground truth. The synCTs were generated using a voxel-based, weighted summation method incorporating T2, fluid attenuated inversion recovery (FLAIR), UTE1, and bone-enhanced images. Mean absolute error (MAE) characterized Hounsfield unit (HU) differences between synCT and CT-SIM. A dosimetry study was conducted, and differences were quantified using γ-analysis and dose-volume histogram analysis. On average, true-positive rate and false-positive rate for the CT and MR-derived air masks were 80.8% ± 5.5% and 25.7% ± 6.9%, respectively. Dice similarity indices values were 0.78 ± 0.04 (range, 0.70-0.83). Full field of view MAE between synCT and CT-SIM was 147.5 ± 8.3 HU (range, 138.3-166.2 HU), with the largest errors occurring at bone-air interfaces (MAE 422.5 ± 33.4 HU for bone and 294.53 ± 90.56 HU for air). Gamma analysis revealed pass rates of 99.4% ± 0.04%, with acceptable treatment plan quality for the cohort. A hybrid MRI phase/magnitude UTE image processing technique was introduced that significantly improved bone and air contrast in MRI. Segmented air masks and bone-enhanced images were integrated into our synCT pipeline for brain, and results agreed well with clinical CTs, thereby supporting MR-only radiation therapy treatment planning in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

In-home virtual reality videogame telerehabilitation in adolescents with hemiplegic cerebral palsy.

PubMed

Golomb, Meredith R; McDonald, Brenna C; Warden, Stuart J; Yonkman, Janell; Saykin, Andrew J; Shirley, Bridget; Huber, Meghan; Rabin, Bryan; Abdelbaky, Moustafa; Nwosu, Michelle E; Barkat-Masih, Monica; Burdea, Grigore C

2010-01-01

Golomb MR, McDonald BC, Warden SJ, Yonkman J, Saykin AJ, Shirley B, Huber M, Rabin B, AbdelBaky M, Nwosu ME, Barkat-Masih M, Burdea GC. In-home virtual reality videogame telerehabilitation in adolescents with hemiplegic cerebral palsy. To investigate whether in-home remotely monitored virtual reality videogame-based telerehabilitation in adolescents with hemiplegic cerebral palsy can improve hand function and forearm bone health, and demonstrate alterations in motor circuitry activation. A 3-month proof-of-concept pilot study. Virtual reality videogame-based rehabilitation systems were installed in the homes of 3 participants and networked via secure Internet connections to the collaborating engineering school and children's hospital. Adolescents (N=3) with severe hemiplegic cerebral palsy. Participants were asked to exercise the plegic hand 30 minutes a day, 5 days a week using a sensor glove fitted to the plegic hand and attached to a remotely monitored videogame console installed in their home. Games were custom developed, focused on finger movement, and included a screen avatar of the hand. Standardized occupational therapy assessments, remote assessment of finger range of motion (ROM) based on sensor glove readings, assessment of plegic forearm bone health with dual-energy x-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT), and functional magnetic resonance imaging (fMRI) of hand grip task. All 3 adolescents showed improved function of the plegic hand on occupational therapy testing, including increased ability to lift objects, and improved finger ROM based on remote measurements. The 2 adolescents who were most compliant showed improvements in radial bone mineral content and area in the plegic arm. For all 3 adolescents, fMRI during grip task contrasting the plegic and nonplegic hand showed expanded spatial extent of activation at posttreatment relative to baseline in brain motor circuitry (eg, primary motor cortex and cerebellum). Use of remotely monitored virtual reality videogame telerehabilitation appears to produce improved hand function and forearm bone health (as measured by DXA and pQCT) in adolescents with chronic disability who practice regularly. Improved hand function appears to be reflected in functional brain changes. Copyright (c) 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Three-layer reconstruction for large defects of the anterior skull base.

PubMed

Sinha, Uttam K; Johnson, Terence E; Crockett, Dennis; Vadapalli, Satish; Gruen, Peter

2002-03-01

To evaluate and discuss a three-layer rigid reconstruction technique for large anterior skull base defects. Prospective, nonrandomized, non-blinded. Tertiary teaching medical center. Twenty consecutive patients underwent craniofacial resection for a variety of pathology. All patients had large anterior cranial base defects involving the cribriform plate, fovea ethmoidalis, and medial portion of the roof of the orbit at least on one side. A few patients had more extensive defects involving both roof of the orbits, planum sphenoidale, and bones of the upper third of the face. The defects were reconstructed with a three-layer technique. A watertight seal was obtained with a pericranial flap separating the neurocranium from the viscerocranium. Rigid support was provided by bone grafts fixed to a titanium mesh, anchored laterally to the orbital roofs. All patients had a computed tomography scan of the skull on the first or second postoperative day. Patients were observed for immediate and long-term postoperative complications after such reconstruction. Postoperative computed tomography scans showed small pneumocephalus in all patients. It resolved spontaneously and did not produce neurologic deficits in any patient. There was no cerebrospinal fluid leak, hematoma, or infection. On long-term follow-up, exposures of bone graft or mesh, brain herniation, or transmission of brain pulsation to the eyes were not observed in any patient. Three-layer reconstruction using bone grafts, titanium mesh, and pericranial flap provides an alternative technique for repair of large anterior cranial base defects. It is safe and effective, and provides rigid protection to the brain.

An exercise-based randomized controlled trial on brain, cognition, physical health and mental health in overweight/obese children (ActiveBrains project): Rationale, design and methods.

PubMed

Cadenas-Sánchez, Cristina; Mora-González, José; Migueles, Jairo H; Martín-Matillas, Miguel; Gómez-Vida, José; Escolano-Margarit, María Victoria; Maldonado, José; Enriquez, Gala María; Pastor-Villaescusa, Belén; de Teresa, Carlos; Navarrete, Socorro; Lozano, Rosa María; de Dios Beas-Jiménez, Juan; Estévez-López, Fernando; Mena-Molina, Alejandra; Heras, María José; Chillón, Palma; Campoy, Cristina; Muñoz-Hernández, Victoria; Martínez-Ávila, Wendy Daniela; Merchan, María Elisa; Perales, José C; Gil, Ángel; Verdejo-García, Antonio; Aguilera, Concepción M; Ruiz, Jonatan R; Labayen, Idoia; Catena, Andrés; Ortega, Francisco B

2016-03-01

The new and recent advances in neuroelectric and neuroimaging technologies provide a new era for further exploring and understanding how brain and cognition function can be stimulated by environmental factors, such as exercise, and particularly to study whether physical exercise influences brain development in early ages. The present study, namely the ActiveBrains project, aims to examine the effects of a physical exercise programme on brain and cognition, as well as on selected physical and mental health outcomes in overweight/obese children. A total of 100 participants aged 8 to 11 years are randomized into an exercise group (N=50) or a control group (N=50). The intervention lasts 20-weeks, with 3-5 sessions per week of 90 min each, and is mainly focused on high-intensity aerobic exercise yet also includes muscle-strengthening exercises. The extent to what the intervention effect remains 8-months after the exercise programme finishes is also studied in a subsample. Brain structure and function and cognitive performance are assessed using structural and functional magnetic resonance imaging and electroencephalographic recordings. Secondary outcomes include physical health outcomes (e.g. physical fitness, body fatness, bone mass and lipid-metabolic factors) and mental health outcomes (e.g. chronic stress indicators and overall behavioural and personality measurements such as anxiety or depression). This project will substantially contribute to the existing knowledge and will have an impact on societies, since early stimulation of brain development might have long lasting consequences on cognitive performance, academic achievement and in the prevention of behavioural problems and the promotion of psychological adjustment and mental health. Clinical trials. Gov identifier: NCT02295072. Copyright © 2016 Elsevier Inc. All rights reserved.

Mechanisms of mononuclear phagocyte recruitment in Alzheimer's disease.

PubMed

Hickman, Suzanne E; El Khoury, Joseph

2010-04-01

Alzheimer's disease (AD) is associated with a significant neuroinflammatory component. Mononuclear phagocytes including monocytes and microglia are the principal cells involved, and they accumulate at perivascular sites of beta-amyloid (Abeta) deposition and in senile plaques. Recent evidence suggests that mononuclear phagocyte accumulation in the AD brain is dependent on chemokines. CCL2, a major monocyte chemokine, is upregulated in the AD brain. Interaction of CCL2 with its receptor CCR2 regulates mononuclear phagocyte accumulation in a mouse model of AD. CCR2 deficiency leads to lower mononuclear phagocyte accumulation and is associated with higher brain Abeta levels, specifically around blood vessels, suggesting that monocytes accumulate at sites of Abeta deposition in an initial attempt to clear these deposits and stop or delay their neurotoxic effects. Indeed, enhancing mononuclear phagocyte accumulation delays progression of AD. Here we review the mechanisms of mononuclear phagocyte accumulation in AD and discuss the potential roles of additional chemokines and their receptors in this process. We also propose a multi-step model for recruitment of mononuclear phagocytes into the brain. The first step involves egress of monocyte/microglial precursors from the bone marrow into the blood. The second step is crossing the blood-brain barrier to the perivascular areas and into the brain parenchyma. The final step includes movement of monocytes/microglia from areas of the brain that lack any amyloid deposition to senile plaques. Understanding the mechanism of recruitment of mononuclear phagocytes to the AD brain is necessary to further understand the role of these cells in the pathogenesis of AD and to identify any potential therapeutic use of these cells for the treatment of this disease.

Unilateral Opening of Rat Blood-Brain Barrier Assisted by Diagnostic Ultrasound Targeted Microbubbles Destruction.

PubMed

Xu, Yali; Cui, Hai; Zhu, Qiong; Hua, Xing; Xia, Hongmei; Tan, Kaibin; Gao, Yunhua; Zhao, Jing; Liu, Zheng

2016-01-01

Objective. Blood-brain barrier (BBB) is a key obstacle that prevents the medication from blood to the brain. Microbubble-enhanced cavitation by focused ultrasound can open the BBB and proves to be valuable in the brain drug delivery. The study aimed to explore the feasibility, efficacy, and safety of unilateral opening of BBB using diagnostic ultrasound targeted microbubbles destruction in rats. Methods. A transtemporal bone irradiation of diagnostic ultrasound and intravenous injection of lipid-coated microbubbles were performed at unilateral hemisphere. Pathological changes were monitored. Evans Blue extravasation grades, extraction from brain tissue, and fluorescence optical density were quantified. Lanthanum nitrate was traced by transmission electron microscopy. Results. After diagnostic ultrasound mediated microbubbles destruction, Evans Blue extravasation and fluorescence integrated optical density were significantly higher in the irradiated hemisphere than the contralateral side (all p < 0.01). Erythrocytes extravasations were demonstrated in the ultrasound-exposed hemisphere (4 ± 1, grade 2) while being invisible in the control side. Lanthanum nitrate tracers leaked through interendothelial cleft and spread to the nerve fiber existed in the irradiation side. Conclusions. Transtemporal bone irradiation under DUS mediated microbubble destruction provides us with a more accessible, safer, and higher selective BBB opening approach in rats, which is advantageous in brain targeted drugs delivery.

Monitoring the injured brain: registered, patient specific atlas models to improve accuracy of recovered brain saturation values

NASA Astrophysics Data System (ADS)

Clancy, Michael; Belli, Antonio; Davies, David; Lucas, Samuel J. E.; Su, Zhangjie; Dehghani, Hamid

2015-07-01

The subject of superficial contamination and signal origins remains a widely debated topic in the field of Near Infrared Spectroscopy (NIRS), yet the concept of using the technology to monitor an injured brain, in a clinical setting, poses additional challenges concerning the quantitative accuracy of recovered parameters. Using high density diffuse optical tomography probes, quantitatively accurate parameters from different layers (skin, bone and brain) can be recovered from subject specific reconstruction models. This study assesses the use of registered atlas models for situations where subject specific models are not available. Data simulated from subject specific models were reconstructed using the 8 registered atlas models implementing a regional (layered) parameter recovery in NIRFAST. A 3-region recovery based on the atlas model yielded recovered brain saturation values which were accurate to within 4.6% (percentage error) of the simulated values, validating the technique. The recovered saturations in the superficial regions were not quantitatively accurate. These findings highlight differences in superficial (skin and bone) layer thickness between the subject and atlas models. This layer thickness mismatch was propagated through the reconstruction process decreasing the parameter accuracy.

Chronic toxicology of cannabis.

PubMed

Reece, Albert Stuart

2009-07-01

Cannabis is the most widely used illicit drug worldwide. As societies reconsider the legal status of cannabis, policy makers and clinicians require sound knowledge of the acute and chronic effects of cannabis. This review focuses on the latter. A systematic review of Medline, PubMed, PsychInfo, and Google Scholar using the search terms "cannabis," "marijuana," "marihuana," "toxicity," "complications," and "mechanisms" identified 5,198 papers. This list was screened by hand, and papers describing mechanisms and those published in more recent years were chosen preferentially for inclusion in this review. There is evidence of psychiatric, respiratory, cardiovascular, and bone toxicity associated with chronic cannabis use. Cannabis has now been implicated in the etiology of many major long-term psychiatric conditions including depression, anxiety, psychosis, bipolar disorder, and an amotivational state. Respiratory conditions linked with cannabis include reduced lung density, lung cysts, and chronic bronchitis. Cannabis has been linked in a dose-dependent manner with elevated rates of myocardial infarction and cardiac arrythmias. It is known to affect bone metabolism and also has teratogenic effects on the developing brain following perinatal exposure. Cannabis has been linked to cancers at eight sites, including children after in utero maternal exposure, and multiple molecular pathways to oncogenesis exist. Chronic cannabis use is associated with psychiatric, respiratory, cardiovascular, and bone effects. It also has oncogenic, teratogenic, and mutagenic effects all of which depend upon dose and duration of use.

Phenotypic Integration of Neurocranium and Brain

PubMed Central

RICHTSMEIER, JOAN T.; ALDRIDGE, KRISTINA; DeLEON, VALERIE B.; PANCHAL, JAYESH; KANE, ALEX A.; MARSH, JEFFREY L.; YAN, PENG; COLE, THEODORE M.

2009-01-01

Evolutionary history of Mammalia provides strong evidence that the morphology of skull and brain change jointly in evolution. Formation and development of brain and skull co-occur and are dependent upon a series of morphogenetic and patterning processes driven by genes and their regulatory programs. Our current concept of skull and brain as separate tissues results in distinct analyses of these tissues by most researchers. In this study, we use 3D computed tomography and magnetic resonance images of pediatric individuals diagnosed with premature closure of cranial sutures (craniosynostosis) to investigate phenotypic relationships between the brain and skull. It has been demonstrated previously that the skull and brain acquire characteristic dysmorphologies in isolated craniosynostosis, but relatively little is known of the developmental interactions that produce these anomalies. Our comparative analysis of phenotypic integration of brain and skull in premature closure of the sagittal and the right coronal sutures demonstrates that brain and skull are strongly integrated and that the significant differences in patterns of association do not occur local to the prematurely closed suture. We posit that the current focus on the suture as the basis for this condition may identify a proximate, but not the ultimate cause for these conditions. Given that premature suture closure reduces the number of cranial bones, and that a persistent loss of skull bones is demonstrated over the approximately 150 million years of synapsid evolution, craniosynostosis may serve as an informative model for evolution of the mammalian skull. PMID:16526048

Phenotypic integration of neurocranium and brain.

PubMed

Richtsmeier, Joan T; Aldridge, Kristina; DeLeon, Valerie B; Panchal, Jayesh; Kane, Alex A; Marsh, Jeffrey L; Yan, Peng; Cole, Theodore M

2006-07-15

Evolutionary history of Mammalia provides strong evidence that the morphology of skull and brain change jointly in evolution. Formation and development of brain and skull co-occur and are dependent upon a series of morphogenetic and patterning processes driven by genes and their regulatory programs. Our current concept of skull and brain as separate tissues results in distinct analyses of these tissues by most researchers. In this study, we use 3D computed tomography and magnetic resonance images of pediatric individuals diagnosed with premature closure of cranial sutures (craniosynostosis) to investigate phenotypic relationships between the brain and skull. It has been demonstrated previously that the skull and brain acquire characteristic dysmorphologies in isolated craniosynostosis, but relatively little is known of the developmental interactions that produce these anomalies. Our comparative analysis of phenotypic integration of brain and skull in premature closure of the sagittal and the right coronal sutures demonstrates that brain and skull are strongly integrated and that the significant differences in patterns of association do not occur local to the prematurely closed suture. We posit that the current focus on the suture as the basis for this condition may identify a proximate, but not the ultimate cause for these conditions. Given that premature suture closure reduces the number of cranial bones, and that a persistent loss of skull bones is demonstrated over the approximately 150 million years of synapsid evolution, craniosynostosis may serve as an informative model for evolution of the mammalian skull. Copyright 2006 Wiley-Liss, Inc.

A modified transcondylar screw to accommodate anatomical skull base variations.

PubMed

Ghaly, R F; Lissounov, A

2017-01-01

Occipitocervical instability may be attributed to congenital, bony/ligamentous abnormalities, trauma, neoplasm, degenerative bone disease, and failed atlantoaxial fixation. Indications for occipitocervical fixation include the prevention of disabling pain, cranial nerve dysfunction, paralysis, or even sudden death. The screw trajectory for the modified transcondylar screw (mTCS) is optimally planned utilizing a three-dimensional skull reconstructed image. The modified mTCS technique is helpful where there is a loss of bone, such as after prior suboccipital craniotomy and/or an inadequate occipital condyle. The new proposed technique is similar to the classical transcondylar screw placement but follows a deeper course along the bony lip of foramen magnum toward clivus from a dorsolateral approach. The modified mTCS technique allows for direct visualization and, therefore, helps to avoid damage to the hypoglossal nerve and lateral aspect of brain stem.

Preservation of cranial nerves during removal of the brain for an enhanced student experience in neuroanatomy classes.

PubMed

Long, Jennifer; Roberts, David J H; Pickering, James D

2014-01-01

Neuroanatomy teaching at the University of Leeds includes the examination of isolated brains by students working in small groups. This requires the prosected brains to exhibit all 12 pairs of cranial nerves. Traditional methods of removing the brain from the skull involve elevating the frontal lobes and cutting each cranial nerve as the brain is reflected posteriorly. This can leave a substantial length of each nerve attached to the skull base rather than to the removed brain. We have found a posterior approach more successful. In this study, five adult heads were disarticulated at the level of the thyroid cartilage and placed, prone, in a head stand. A wedge of bone from the occipital region was removed before the cerebellum and brainstem were elevated to visualize the cranial nerves associated with the medulla oblongata, cerebellopontine angle and mesencephalic-pontine junction prior to cutting them as close to the skull as possible. Five brains were successfully removed from the skull, each having a full complement of cranial nerves of good length attached to them. This approach significantly increases the length and number of cranial nerves remaining attached to the brain, which supports student education. For integration into head and neck dissection courses, careful consideration will be required to ensure the necks are suitably dissected and to decide whether the cranial nerves are best left attached to the skull base or brain. Copyright © 2013 Wiley Periodicals, Inc.

First-trimester sonographic findings associated with a Dandy-Walker malformation and inferior vermian hypoplasia.

PubMed

Bornstein, Eran; Goncalves Rodríguez, José Luis; Álvarez Pavón, Erika Carolina; Quiroga, Héctor; Or, Drorit; Divon, Michael Y

2013-10-01

We report 2 cases in which first-trimester measurements of the intracranial translucency and the brain stem-to-occipital bone diameter were markedly enlarged. This finding was thought to represent an abnormal fourth ventricle-cisterna magna complex. Subsequently, the diagnoses of a Dandy-Walker malformation with partial vermian agenesis in 1 case and inferior vermian hypoplasia in the other were established and confirmed by either postmortem autopsy or postnatal magnetic resonance imaging. These cases suggest that evaluation of the fourth ventricle-cisterna magna complex, by measuring the intracranial translucency or brain stem-to-occipital bone diameter may identify some cases with structural malformations of the cerebellum as early as the first trimester.

Delivery of Nano-Tethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse

DTIC Science & Technology

2015-12-01

Hounsfield units (HU) of the brain were translated into corresponding optical properties (absorption coefficient, scattering coefficient, and anisotropy...factor) using lookup tables (Fig 2). The lookup tables were prepared from earlier studies which derived the Hounsfield units and optical properties of... Hounsfield Units /HU) are segmented and translated into optical properties of the brain tissue (white/gray matter, CSF, skull bone, etc.). Monte

Computed tomographic findings of cerebral fat embolism following multiple bone fractures.

PubMed

Law, Huong Ling; Wong, Siong Lung; Tan, Suzet

2013-02-01

Fat embolism to the lungs and brain is an uncommon complication following fractures. Few reports with descriptions of computed tomographic (CT) findings of emboli to the brain or cerebral fat embolism are available. We report a case of cerebral fat embolism following multiple skeletal fractures and present its CT findings here.

Quantitative analysis of MRI-guided attenuation correction techniques in time-of-flight brain PET/MRI.

PubMed

Mehranian, Abolfazl; Arabi, Hossein; Zaidi, Habib

2016-04-15

In quantitative PET/MR imaging, attenuation correction (AC) of PET data is markedly challenged by the need of deriving accurate attenuation maps from MR images. A number of strategies have been developed for MRI-guided attenuation correction with different degrees of success. In this work, we compare the quantitative performance of three generic AC methods, including standard 3-class MR segmentation-based, advanced atlas-registration-based and emission-based approaches in the context of brain time-of-flight (TOF) PET/MRI. Fourteen patients referred for diagnostic MRI and (18)F-FDG PET/CT brain scans were included in this comparative study. For each study, PET images were reconstructed using four different attenuation maps derived from CT-based AC (CTAC) serving as reference, standard 3-class MR-segmentation, atlas-registration and emission-based AC methods. To generate 3-class attenuation maps, T1-weighted MRI images were segmented into background air, fat and soft-tissue classes followed by assignment of constant linear attenuation coefficients of 0, 0.0864 and 0.0975 cm(-1) to each class, respectively. A robust atlas-registration based AC method was developed for pseudo-CT generation using local weighted fusion of atlases based on their morphological similarity to target MR images. Our recently proposed MRI-guided maximum likelihood reconstruction of activity and attenuation (MLAA) algorithm was employed to estimate the attenuation map from TOF emission data. The performance of the different AC algorithms in terms of prediction of bones and quantification of PET tracer uptake was objectively evaluated with respect to reference CTAC maps and CTAC-PET images. Qualitative evaluation showed that the MLAA-AC method could sparsely estimate bones and accurately differentiate them from air cavities. It was found that the atlas-AC method can accurately predict bones with variable errors in defining air cavities. Quantitative assessment of bone extraction accuracy based on Dice similarity coefficient (DSC) showed that MLAA-AC and atlas-AC resulted in DSC mean values of 0.79 and 0.92, respectively, in all patients. The MLAA-AC and atlas-AC methods predicted mean linear attenuation coefficients of 0.107 and 0.134 cm(-1), respectively, for the skull compared to reference CTAC mean value of 0.138cm(-1). The evaluation of the relative change in tracer uptake within 32 distinct regions of the brain with respect to CTAC PET images showed that the 3-class MRAC, MLAA-AC and atlas-AC methods resulted in quantification errors of -16.2 ± 3.6%, -13.3 ± 3.3% and 1.0 ± 3.4%, respectively. Linear regression and Bland-Altman concordance plots showed that both 3-class MRAC and MLAA-AC methods result in a significant systematic bias in PET tracer uptake, while the atlas-AC method results in a negligible bias. The standard 3-class MRAC method significantly underestimated cerebral PET tracer uptake. While current state-of-the-art MLAA-AC methods look promising, they were unable to noticeably reduce quantification errors in the context of brain imaging. Conversely, the proposed atlas-AC method provided the most accurate attenuation maps, and thus the lowest quantification bias. Copyright © 2016 Elsevier Inc. All rights reserved.

Homozygous TREM2 mutation in a family with atypical frontotemporal dementia.

PubMed

Le Ber, Isabelle; De Septenville, Anne; Guerreiro, Rita; Bras, José; Camuzat, Agnès; Caroppo, Paola; Lattante, Serena; Couarch, Philippe; Kabashi, Edor; Bouya-Ahmed, Kawtar; Dubois, Bruno; Brice, Alexis

2014-10-01

TREM2 mutations were first identified in Nasu-Hakola disease, a rare autosomal recessive disease characterized by recurrent fractures because of bone cysts and presenile dementia. Recently, homozygous and compound heterozygous TREM2 mutations were identified in rare families with frontotemporal lobar degeneration (FTLD) but without bone involvement. We identified a p.Thr66Met heterozygous mutation in a new consanguineous Italian family. Two sibs had early onset autosomal recessive FTLD without severe bone disorders. Atypical signs were present in this family: early parietal and hippocampus involvement, parkinsonism, epilepsy, and corpus callosum thickness on brain magnetic resonance imaging. This study further demonstrates the implication of TREM2 mutations in FTLD phenotypes. It illustrates the variability of bone phenotype and underlines the frequency of atypical signs in TREM2 carriers. This and previous studies evidence that TREM2 mutation screening should be limited to autosomal recessive FTLD with atypical phenotypes characterized by: (1) a very young age at onset (20-50 years); (2) early parietal and hippocampal deficits; (3) the presence of seizures and parkinsonism; (4) suggestive extensive white matter lesions and corpus callosum thickness on brain magnetic resonance imaging. Copyright © 2014 Elsevier Inc. All rights reserved.

Homozygous TREM2 mutation in a family with atypical frontotemporal dementia

PubMed Central

Bras, José; Camuzat, Agnès; Caroppo, Paola; Lattante, Serena; Couarch, Philippe; Kabashi, Edor; Bouya-Ahmed, Kawtar; Dubois, Bruno; Brice, Alexis

2014-01-01

TREM2 mutations were first identified in Nasu-Hakola disease, a rare autosomal recessive disease characterized by recurrent fractures because of bone cysts and presenile dementia. Recently, homozygous and compound heterozygous TREM2 mutations were identified in rare families with frontotemporal lobar degeneration (FTLD) but without bone involvement. We identified a p.Thr66Met heterozygous mutation in a new consanguineous Italian family. Two sibs had early onset autosomal recessive FTLD without severe bone disorders. Atypical signs were present in this family: early parietal and hippocampus involvement, parkinsonism, epilepsy, and corpus callosum thickness on brain magnetic resonance imaging. This study further demonstrates the implication of TREM2 mutations in FTLD phenotypes. It illustrates the variability of bone phenotype and underlines the frequency of atypical signs in TREM2 carriers. This and previous studies evidence that TREM2 mutation screening should be limited to autosomal recessive FTLD with atypical phenotypes characterized by: (1) a very young age at onset (20–50 years); (2) early parietal and hippocampal deficits; (3) the presence of seizures and parkinsonism; (4) suggestive extensive white matter lesions and corpus callosum thickness on brain magnetic resonance imaging. PMID:24910390

Bone marrow stromal cells promote neuroplasticity of cerebral ischemic rats via a phosphorylated CRMP2-mediated mechanism.

PubMed

He, Xiang; Jiang, Ling; Dan, Qi-Qin; Lv, Qiang; Hu, Yue; Liu, Jia; Wang, Shu-Fen; Wang, Ting-Hua

2017-03-01

Collapsin response mediator protein 2 (CRMP2), an important protein involved in axonal growth and the maintenance of neuronal membrane integrity, has proved to be altered in nervous system diseases. This study was aimed to investigate the role of CRMP2 in bone marrow stromal cells (BMSCs) treating rats with cerebral ischemia. BMSCs were isolated from shaft of the femurs, tibiae, and humeri and were intra-carotid administrated immediately after middle cerebral artery occlusion (MCAO). Modified Neurological Severity Scores (mNSS) was conducted at 3, 7, 14dpo and the electrophysiologic evaluation was evaluated at 14dpo. Then all rats were sacrificed and brain tissues were harvested for RT-PCR, Western blot and Immunohistochemistry analysis. We found BMSCs treatment significantly improved the neurobehavioral performance impaired by ischemic brain injury, accompanied with the notably increasing levels of Synaptophysin (SYP) and Growth associated protein 43 (GAP43). We also found the protein level of phosphorylated CRMP2 (p-CRMP2) and phosphorylation-mediated protein including Glycogen synthase kinase 3 Beta (GSK3β), Cyclin-dependent kinase 5 (CDK5) were dramatically downregulated in ischemic rats following BMSCs transplant. Furthermore, the GSK3β-mediated factors including neurotrophic and signaling factors were all significantly upregulated in BMSCs-treated group. On the basis of these findings, we suggest that the neuroplasticity effect of BMSCs on cerebral ischemia may be associated with the phosphorylated modulation of CRMP2. Copyright © 2016 Elsevier B.V. All rights reserved.

Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications

PubMed Central

Torossian, Frédéric; Guerton, Bernadette; Anginot, Adrienne; Alexander, Kylie A.; Desterke, Christophe; Soave, Sabrina; Tseng, Hsu-Wen; Arouche, Nassim; Boutin, Laetitia; Kulina, Irina; Salga, Marjorie; Jose, Beulah; Pettit, Allison R.; Clay, Denis; Vlachos, Erica; Genet, Guillaume; Debaud, Charlotte; Denormandie, Philippe; Genet, François; Sims, Natalie A.; Banzet, Sébastien; Levesque, Jean-Pierre; Lataillade, Jean-Jacques; Le Bousse-Kerdilès, Marie-Caroline

2017-01-01

Neurogenic heterotopic ossification (NHO) is the formation of ectopic bone generally in muscles surrounding joints following spinal cord or brain injury. We investigated the mechanisms of NHO formation in 64 patients and a mouse model of spinal cord injury–induced NHO. We show that marrow from human NHOs contains hematopoietic stem cell (HSC) niches, in which mesenchymal stromal cells (MSCs) and endothelial cells provide an environment supporting HSC maintenance, proliferation, and differentiation. The transcriptomic signature of MSCs from NHOs shows a neuronal imprinting associated with a molecular network required for HSC support. We demonstrate that oncostatin M (OSM) produced by activated macrophages promotes osteoblastic differentiation and mineralization of human muscle-derived stromal cells surrounding NHOs. The key role of OSM was confirmed using an experimental model of NHO in mice defective for the OSM receptor (OSMR). Our results provide strong evidence that macrophages contribute to NHO formation through the osteogenic action of OSM on muscle cells within an inflammatory context and suggest that OSM/OSMR could be a suitable therapeutic target. Altogether, the evidence of HSCs in ectopic bones growing at the expense of soft tissue in spinal cord/brain-injured patients indicates that inflammation and muscle contribute to HSC regulation by the brain-bone-blood triad. PMID:29093266

Long-term effects of treatment on endocrine function in children with brain tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duffner, P.K.; Cohen, M.E.; Anderson, S.W.

1983-11-01

Fourteen children with brain tumors received endocrine evaluations at least one year following completion of cranial irradiation. Treatment consisted of operation (13 patients), craniospinal irradiation (6), whole brain irradiation (5), posterior fossa irradiation (3), and chemotherapy (10). Endocrine evaluation included bone age roentgenography and measurement of growth hormone (using sequential arginine and insulin stimulation), thyroxine, thyroid-stimulating hormone, plasma cortisol, testosterone, prolactin, and urinary follicle-stimulating hormone and luteinizing hormone. Ten of 12 children (83%) had abnormal responses to both tests of growth hormone stimulation. All growth hormone-deficient patients treated prior to puberty and tested at least 2 years following completion ofmore » cranial irradiation had decelerated linear growth. Results of thyroid function tests were abnormal in 4 patients: 2 patients had evidence of primary hypothyroidism, and 2 showed secondary or tertiary hypothyroidism. Two patients had inadequate cortisol responses to insulin hypoglycemia. Urinary follicle-stimulating hormone and luteinizing hormone, serum prolactin, and serum testosterone levels were appropriate for age in all patients.« less

Genetically fluorescent melanoma bone and organ metastasis models.

PubMed

Yang, M; Jiang, P; An, Z; Baranov, E; Li, L; Hasegawa, S; Al-Tuwaijri, M; Chishima, T; Shimada, H; Moossa, A R; Hoffman, R M

1999-11-01

We report here the establishment and metastatic properties of bright, highly stable, green fluorescent protein (GFP) expression transductants of the B16 mouse malignant melanoma cell line and the LOX human melanoma line. The highly fluorescent malignant melanoma cell lines allowed the visualization of skeletal and multiorgan metastases after i.v. injection of B16 cells in C57BL/6 mice and intradermal injection of LOX cells in nude mice. The melanoma cell lines were transduced with the pLEIN expression retroviral vector containing the GFP and neomycin resistance genes. Stable B16F0 and LOX clones expressing high levels of GFP were selected stepwise in vitro in levels of G418 of up to 800 microg/ml. Extensive bone and bone marrow metastases of B16F0 were visualized by GFP expression when the animals were sacrificed 3 weeks after cell implantation. Metastases for both cell lines were visualized in many organs, including the brain, lung, pleural membrane, liver, kidney, adrenal gland, lymph nodes, skeleton, muscle, and skin by GFP fluorescence. This is the first observation of experimental skeletal metastases of melanoma, which was made possible by GFP expression. These models should facilitate future studies of the mechanism and therapy of bone and multiorgan metastasis of melanoma.

Aromatase imaging with [N-methyl-C-11]vorozole PET in healthy men and women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biegon, Anat; Fowler, Joanna S.; Alexoff, David L.

Aromatase, the last and obligatory enzyme catalyzing estrogen biosynthesis from androgenic precursors, can be labeled in vivo with ¹¹C-vorozole. Aromatase inhibitors are widely used in breast cancer and other endocrine conditions. The present study aims to provide baseline information defining aromatase distribution in healthy men and women, against which its perturbation in pathological situations can be studied. Methods: ¹¹C-vorozole (111-296 MBq/subject) was injected I.V in 13 men and 20 women (age range 23 to 67). PET data were acquired over a 90 minute period. Each subject had 4 scans, 2/day separated by 2-6 weeks, including brain and torso or pelvismore » scans. Young women were scanned at 2 discrete phases of the menstrual cycle (midcycle and late luteal). Men and postmenopausal women were also scanned following pretreatment with a clinical dose of the aromatase inhibitor letrozole (“blocking” studies). Time activity curves were obtained and standard uptake values (SUV) calculated for major organs including brain, heart, lungs, liver, kidneys, spleen, muscle, bone and male and female reproductive organs (penis, testes, uterus, ovaries). Organ and whole body radiation exposures were calculated using Olinda software. Results: Liver uptake was higher than all other organs, but was not blocked by pretreatment with letrozole. Mean SUVs in men were higher than in women, and brain uptake was blocked by letrozole. Male brain SUVs were also higher than all other organs (ranging from 0.48±0.05 in lungs to 1.5±0.13 in kidneys). Mean ovarian SUVs (3.08±0.7) were comparable to brain levels and higher than all other organs. Furthermore, ovarian SUVs In young women around the time of ovulation (midcycle) were significantly higher than those measured in the late luteal phase, while aging and cigarette smoking reduced ¹¹C-vorozole uptake. Conclusions: PET with ¹¹C-vorozole is useful for assessing physiological changes in estrogen synthesis capacity in the human body. Baseline levels in breasts, lungs and bones are low, supporting further investigation of this tracer as a new tool for detection of aromatase-overexpressing primary tumors or metastases in these organs and optimization of treatment in cancer and other disorders in which aromatase inhibitors are useful.« less

Aromatase imaging with [N-methyl-C-11]vorozole PET in healthy men and women

DOE PAGES

Biegon, Anat; Fowler, Joanna S.; Alexoff, David L.; ...

2015-02-19

Aromatase, the last and obligatory enzyme catalyzing estrogen biosynthesis from androgenic precursors, can be labeled in vivo with ¹¹C-vorozole. Aromatase inhibitors are widely used in breast cancer and other endocrine conditions. The present study aims to provide baseline information defining aromatase distribution in healthy men and women, against which its perturbation in pathological situations can be studied. Methods: ¹¹C-vorozole (111-296 MBq/subject) was injected I.V in 13 men and 20 women (age range 23 to 67). PET data were acquired over a 90 minute period. Each subject had 4 scans, 2/day separated by 2-6 weeks, including brain and torso or pelvismore » scans. Young women were scanned at 2 discrete phases of the menstrual cycle (midcycle and late luteal). Men and postmenopausal women were also scanned following pretreatment with a clinical dose of the aromatase inhibitor letrozole (“blocking” studies). Time activity curves were obtained and standard uptake values (SUV) calculated for major organs including brain, heart, lungs, liver, kidneys, spleen, muscle, bone and male and female reproductive organs (penis, testes, uterus, ovaries). Organ and whole body radiation exposures were calculated using Olinda software. Results: Liver uptake was higher than all other organs, but was not blocked by pretreatment with letrozole. Mean SUVs in men were higher than in women, and brain uptake was blocked by letrozole. Male brain SUVs were also higher than all other organs (ranging from 0.48±0.05 in lungs to 1.5±0.13 in kidneys). Mean ovarian SUVs (3.08±0.7) were comparable to brain levels and higher than all other organs. Furthermore, ovarian SUVs In young women around the time of ovulation (midcycle) were significantly higher than those measured in the late luteal phase, while aging and cigarette smoking reduced ¹¹C-vorozole uptake. Conclusions: PET with ¹¹C-vorozole is useful for assessing physiological changes in estrogen synthesis capacity in the human body. Baseline levels in breasts, lungs and bones are low, supporting further investigation of this tracer as a new tool for detection of aromatase-overexpressing primary tumors or metastases in these organs and optimization of treatment in cancer and other disorders in which aromatase inhibitors are useful.« less

Evaluation of an attenuation correction method for PET/MR imaging of the head based on substitute CT images.

PubMed

Larsson, Anne; Johansson, Adam; Axelsson, Jan; Nyholm, Tufve; Asklund, Thomas; Riklund, Katrine; Karlsson, Mikael

2013-02-01

The aim of this study was to evaluate MR-based attenuation correction of PET emission data of the head, based on a previously described technique that calculates substitute CT (sCT) images from a set of MR images. Images from eight patients, examined with (18)F-FLT PET/CT and MRI, were included. sCT images were calculated and co-registered to the corresponding CT images, and transferred to the PET/CT scanner for reconstruction. The new reconstructions were then compared with the originals. The effect of replacing bone with soft tissue in the sCT-images was also evaluated. The average relative difference between the sCT-corrected PET images and the CT-corrected PET images was 1.6% for the head and 1.9% for the brain. The average standard deviations of the relative differences within the head were relatively high, at 13.2%, primarily because of large differences in the nasal septa region. For the brain, the average standard deviation was lower, 4.1%. The global average difference in the head when replacing bone with soft tissue was 11%. The method presented here has a high rate of accuracy, but high-precision quantitative imaging of the nasal septa region is not possible at the moment.

Three-dimensional printing (3DP) of neonatal head phantom for ultrasound: thermocouple embedding and simulation of bone.

PubMed

Gatto, Matteo; Memoli, Gianluca; Shaw, Adam; Sadhoo, Neelaksh; Gelat, Pierre; Harris, Russell A

2012-09-01

A neonatal head phantom, comprising of an ellipsoidal geometry and including a circular aperture for simulating the fontanel was designed and fabricated, in order to allow an objective assessment of thermal rise in tissues during trans-cranial ultrasonic scanning of pre-term neonates. The precise position of a series of thermocouples was determined on the basis of finite-element analysis, which identified crucial target points for the thermal monitoring within the phantom geometry. Three-Dimensional Printing (3DP) was employed for the manufacture of the skull phantom, which was subsequently filled with dedicated brain-mimic material. A novel 3DP material combination was found to be able to mimic the acoustic properties of neonatal skull bone. Similarly, variations of a standard recipe for tissue mimic were examined, until one was found to mimic the brain of an infant. A specific strategy was successfully pursued to embed a thermocouple within the 3DP skull phantom during the manufacturing process. An in-process machine vision system was used to assess the correct position of the deposited thermocouple inside the fabricated skull phantom. An external silicone-made skin-like covering completed the phantom and was manufactured through a Direct Rapid Tooling (DRT) technique. Copyright © 2011 IPEM. Published by Elsevier Ltd. All rights reserved.

Novel Radiomitigator for Radiation-Induced Bone Loss

NASA Technical Reports Server (NTRS)

Schreurs, A-S; Shirazi-fard, Y.; Terada, M.; Alwood, J. S.; Steczina, S.; Medina, C.; Tahimic, C. G. T.; Globus, R. K.

2016-01-01

Radiation-induced bone loss can occur with radiotherapy patients, accidental radiation exposure and during long-term spaceflight. Bone loss due to radiation is due to an early increase in oxidative stress, inflammation and bone resorption, resulting in an imbalance in bone remodeling. Furthermore, exposure to high-Linear Energy Transfer (LET) radiation will impair the bone forming progenitors and reduce bone formation. Radiation can be classified as high-LET or low-LET based on the amount of energy released. Dried Plum (DP) diet prevents bone loss in mice exposed to total body irradiation with both low-LET and high-LET radiation. DP prevents the early radiation-induced bone resorption, but furthermore, we show that DP protects the bone forming osteoblast progenitors from high-LET radiation. These results provide insight that DP re-balances the bone remodeling by preventing resorption and protecting the bone formation capacity. This data is important considering that most of the current osteoporosis treatments only block the bone resorption but do not protect bone formation. In addition, DP seems to act on both the oxidative stress and inflammation pathways. Finally, we have preliminary data showing the potential of DP to be radio-protective at a systemic effect and could possible protect other tissues at risk of total body-irradiation such as skin, brain and heart.

Effect of cell therapy on recovery of cognitive functions in rats during the delayed period after brain injury.

PubMed

Roshal, L M; Tzyb, A F; Pavlova, L N; Soushkevitch, G N; Semenova, J B; Javoronkov, L P; Kolganova, O I; Konoplyannikov, A G; Shevchuk, A S; Yujakov, V V; Karaseva, O V; Ivanova, T F; Chernyshova, T A; Konoplyannikova, O A; Bandurko, L N; Marey, M V; Sukhikh, G T

2009-07-01

We studied the effect of systemic transplantation of human stem cells from various tissues on cognitive functions of the brain in rats during the delayed period after experimental brain injury. Stem cells were shown to increase the efficacy of medical treatment with metabolic and symptomatic drugs for recovery of cognitive functions. They accelerated the formation of the conditioned defense response. Fetal neural stem cells had a stronger effect on some parameters of cognitive function 2 months after brain injury. The efficacy of bone marrow mesenchymal stem cells from adult humans or fetuses was higher 3 months after brain injury.

Bone marrow-derived macrophages from aged rats are more responsive to inflammatory stimuli.

PubMed

Barrett, James P; Costello, Derek A; O'Sullivan, Joan; Cowley, Thelma R; Lynch, Marina A

2015-04-09

Lipopolysaccharide (LPS) and interferon-γ (IFNγ) increase expression of tumour necrosis factor-α (TNFα) that characterizes the M1 activation state of macrophages. Whereas it is accepted that the immune system undergoes changes with age, there is inconsistency in the literature with respect to the impact of age on the response of macrophages to inflammatory stimuli. Here, we investigate the effect of age on the responsiveness of bone marrow-derived macrophages (BMDMs) to LPS and IFNγ. The context for addressing this question is that macrophages, which infiltrate the brain of aged animals, will encounter the neuroinflammatory environment that has been described with age. Brain tissue, prepared from young and aged rats, was assessed for expression of inflammatory markers by PCR and for evidence of infiltration of macrophages by flow cytometry. BMDMs were prepared from the long bones of young and aged rats, maintained in culture for 8 days and incubated in the presence or absence of LPS (100 ng/ml) or IFNγ (50 ng/ml). Cells were harvested and assessed for mRNA expression of markers of M1 activation including TNFα and NOS2, or for expression of IFNγR1 and TLR4 by western immunoblotting. To assess whether BMDMs induced glial activation, mixed glial cultures were incubated in the presence of conditioned media obtained from unstimulated BMDMs of young and aged rats and evaluated for expression of inflammatory markers. Markers associated with M1 activation were expressed to a greater extent in BMDMs from aged rats in response to LPS and IFNγ, compared with cells from young rats. The increased responsiveness was associated with increases in IFNγ receptor (IFNγR) and Toll-like receptor 4 (TLR4). The data show that conditioned media from BMDMs of aged rats increased the expression of pro-inflammatory mediators in glial cells. Significantly, there was an age-related increase in macrophage infiltration into the brain, and this was combined with increased expression of IFNγ and the Toll-like receptor 4 agonist, high-mobility group protein B1 (HMGB1). Exposure of infiltrating macrophages to the inflammatory microenvironment that develops in the brain with age is likely to contribute to a damaging cascade that negatively impacts neuronal function.

Novel Neuromuscular Electrical Stimulation System for Treatment of Dysphagia after Brain Injury

PubMed Central

TOYAMA, Keiichi; MATSUMOTO, Shuji; KURASAWA, Miho; SETOGUCHI, Haruka; NOMA, Tomokazu; TAKENAKA, Keita; SOEDA, Akina; SHIMODOZONO, Megumi; KAWAHIRA, Kazumi

2014-01-01

The purpose of this study was to compare the effects of a novel neuromuscular electrical stimulation (NMES) to the effects of conventional treatment in patients with dysphagia after brain injury. In total, 26 patients were non-randomly divided into an experimental group (n = 12) and a control group (n = 14). The experimental group received NMES intervention followed by conventional treatment, including thermal-tactile stimulation with intensive repetition of a dry-swallow task. The control group received conventional treatment without NMES. NMES at a fixed pulse duration of 50 μs and a frequency of 50 Hz was delivered over the skin areas above the motor point of the target muscles, i.e., the bilateral geniohyoid, mylohyoid/anterior belly of the digastric, and thyrohyoid muscles, using a high-voltage pulsed-current device. The two groups received 40-min treatments once a day, 5 days per week, for 8 weeks. Outcome, assessed before and 8 weeks after treatment, was evaluated with regard to the videofluoroscopic dysphagia scale (VDS), the anterior and superior displacement of the hyoid bone and larynx, and the functional oral intake scale. Both groups exhibited improvement, but the experimental group exhibited more significant improvement in the displacement of the hyoid bone and larynx, VDS-total score, and VDS-pharyngeal score than the control group did. The results suggest that NMES combined with conventional treatment is superior to conventional treatment alone in patients with dysphagia following treatment for brain injury. Further investigations are necessary to examine the effects of NMES in patients with more varied types of diseases. PMID:24670314

Orexin Regulates Bone Remodeling via a Dominant Positive Central Action and a Subordinate Negative Peripheral Action

PubMed Central

Wei, Wei; Motoike, Toshiyuki; Krzeszinski, Jing Y.; Jin, Zixue; Xie, Xian-Jin; Dechow, Paul C.; Yanagisawa, Masashi; Wan, Yihong

2014-01-01

SUMMARY Orexin neuropeptides promote arousal, appetite, reward, and energy expenditure. However, whether orexin affects bone mass accrual is unknown. Here we show that orexin functions centrally through orexin receptor 2 (OX2R) in the brain to enhance bone formation. OX2R-null mice exhibit low-bone-mass owing to elevated circulating leptin; whereas central administration of an OX2R-selective agonist augments bone mass. Conversely, orexin also functions peripherally through orexin receptor 1 (OX1R) in the bone to suppress bone formation. OX1R-null mice exhibit high-bone-mass owing to a mesenchymal stem cell differentiation shift from adipocyte to osteoblast that results from higher osseous ghrelin expression. The central action is dominant over the peripheral action because bone mass is reduced in orexin-null and OX1R2R-double-null mice but enhanced in orexin over-expressing transgenic mice. These findings reveal orexin as a critical rheostat of skeletal homeostasis that exerts a yin-yang dual regulation, and highlight orexin as a therapeutic target for osteoporosis. PMID:24794976

Linear undisplaced fracture of temporoparietal bone acting as spontaneous early decompressive craniotomy in a neonate

PubMed Central

Vankipuram, Siddharth; Balasubramanium, Srikant; Tyagi, Devendra K.; Savant, H. V.

2015-01-01

Decompressive craniotomy (DC) is used to treat intracranial hypertension associated with traumatic brain injury. Early DC is associated with better outcomes. We present a neonate with a history of fall with computed tomography scan showing a large frontoparietal contusion and associated parietal and temporal bone fracture. This acted as a spontaneous DC causing bony segment to separate due to which the edematous brain could be accommodated. Despite the presence of a large contusion, the child was neurologically intact and medically managed. The neonate presented with a posttraumatic leptomeningeal cyst 2 months later, which had to be repaired surgically. We discuss how a linear undisplaced fracture acts as spontaneous DC and the role of early DC in improving outcomes. PMID:26557171

[Focused ultrasound therapy: current status and potential applications in neurosurgery].

PubMed

Dervishi, E; Aubry, J-F; Delattre, J-Y; Boch, A-L

2013-12-01

High Intensity Focused Ultrasound (HIFU) therapy is an innovative approach for tissue ablation, based on high intensity focused ultrasound beams. At the focus, HIFU induces a temperature elevation and the tissue can be thermally destroyed. In fact, this approach has been tested in a number of clinical studies for the treatment of several tumors, primarily the prostate, uterine, breast, bone, liver, kidney and pancreas. For transcranial brain therapy, the skull bone is a major limitation, however, new adaptive techniques of phase correction for focusing ultrasound through the skull have recently been implemented by research systems, paving the way for HIFU therapy to become an interesting alternative to brain surgery and radiotherapy. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Vitamin D in older population: new roles for this 'classic actor'?

PubMed

Lauretani, Fulvio; Maggio, Marcello; Valenti, Giorgio; Dall'Aglio, Elisabetta; Ceda, Gian Paolo

2010-12-01

Vitamin D is a group of lipophilic hormones with pleiotropic actions. It has been traditionally related to bone metabolism, although several studies in the last decade have suggested its role in muscle strength and falls, cardiovascular and neurological diseases, insulin-resistance and diabetes, malignancies, autoimmune diseases and infections. Vitamin D appears to be a hormone with several actions and is fundamental for many biological systems including bone, skeletal muscle, brain and heart. The estimated worldwide prevalence of vitamin D deficiency of 50% in elderly subjects underlines the importance of vitamin D deficiency for public health. In this review, we will describe changes in vitamin D levels with age in both sexes, cut off values to define Vitamin D status, the impact of vitamin D deficiency in age-related disease and finally different therapeutic options available to treat Vitamin D deficiency in older populations.

Numerical Simulation of Focused Shock Shear Waves in Soft Solids and a Two-Dimensional Nonlinear Homogeneous Model of the Brain

PubMed Central

Giammarinaro, B.; Coulouvrat, F.; Pinton, G.

2016-01-01

Shear waves that propagate in soft solids, such as the brain, are strongly nonlinear and can develop into shock waves in less than one wavelength. We hypothesize that these shear shock waves could be responsible for certain types of traumatic brain injuries (TBI) and that the spherical geometry of the skull bone could focus shear waves deep in the brain, generating diffuse axonal injuries. Theoretical models and numerical methods that describe nonlinear polarized shear waves in soft solids such as the brain are presented. They include the cubic nonlinearities that are characteristic of soft solids and the specific types of nonclassical attenuation and dispersion observed in soft tissues and the brain. The numerical methods are validated with analytical solutions, where possible, and with self-similar scaling laws where no known solutions exist. Initial conditions based on a human head X-ray microtomography (CT) were used to simulate focused shear shock waves in the brain. Three regimes are investigated with shock wave formation distances of 2.54 m, 0.018 m, and 0.0064 m. We demonstrate that under realistic loading scenarios, with nonlinear properties consistent with measurements in the brain, and when the shock wave propagation distance and focal distance coincide, nonlinear propagation can easily overcome attenuation to generate shear shocks deep inside the brain. Due to these effects, the accelerations in the focal are larger by a factor of 15 compared to acceleration at the skull surface. These results suggest that shock wave focusing could be responsible for diffuse axonal injuries. PMID:26833489

Effect of growth hormone deficiency on brain MRI findings among children with growth restrictions.

PubMed

Naderi, Fariba; Eslami, Samira Rajabi; Mirak, Sohrab Afshari; Khak, Mohammad; Amiri, Jalaladin; Beyrami, Bahram; Shekarchi, Babak; Poureisa, Masoud

2015-01-01

Growth hormone deficiency (GHD) is a major problem among children with short stature. In this study, the role of brain magnetic resonance imaging (MRI) in defining the underlying defects among short children with GHD is evaluated. In a cross-sectional study, data of 158 children were evaluated. Growth hormone (GH) levels were measured using stimulating tests and brain MRI with gadolinium contrast was applied, as well. Some 25.3% of patients had GHD with a mean age of 8.01±3.40 years. MRI results showed 35 as normal, four with pituitary hypoplasia, and one with microadenoma. The MRI results were significantly associated with GH levels and presence of other endocrine disorders. There was a significant association between prenatal disorders and patients' bone age delay. In patients with severe GHD and patients with multiple pituitary hormone deficiencies, MRI is more likely to be abnormal, and bone age is much delayed in patients with history of prenatal disorders.

Penetrating brain injury caused by nail guns: two case reports and a review of the literature.

PubMed

Luo, Wei; Liu, Hai; Hao, Shuyu; Zhang, Ying; Li, Jingsheng; Liu, Baiyun

2012-01-01

To the best of the authors' knowledge, there are few case reports of penetrating brain injuries (PBI) caused by nail guns and these have usually involved incomplete penetration of the skull. Complete penetration of a nail into the intracranial cavity is extremely rare. Here, two such cases are presented. In the first, the nail entered through the right temporal bone, lodged in the right temporal lobe and was removed via craniotomy with intra-operative ultrasound guidance. In the second, the nail destroyed the left parietal bone, damaged the left internal capsule and lodged in the left temporal lobe near the left petrous apex and the brain stem. According to the latest literature retrieval, this is the first reported case of nail-gun injury to the internal capsule. The position of the nail precluded removal without further neurologic damage. Treatment strategies designed to optimize outcome, with or without surgery, and possible complications are discussed in this report.

Genetics Home Reference: SADDAN

MedlinePlus

... CLOSE navigation Home Page Search Home Health ... delay and acanthosis nigricans) is a rare disorder of bone growth characterized by skeletal, brain, and skin abnormalities. All people with this ...

Oxygen, a Key Factor Regulating Cell Behavior during Neurogenesis and Cerebral Diseases

PubMed Central

Zhang, Kuan; Zhu, Lingling; Fan, Ming

2011-01-01

Oxygen is vital to maintain the normal functions of almost all the organs, especially for brain which is one of the heaviest oxygen consumers in the body. The important roles of oxygen on the brain are not only reflected in the development, but also showed in the pathological processes of many cerebral diseases. In the current review, we summarized the oxygen levels in brain tissues tested by real-time measurements during the embryonic and adult neurogenesis, the cerebral diseases, or in the hyperbaric/hypobaric oxygen environment. Oxygen concentration is low in fetal brain (0.076–7.6 mmHg) and in adult brain (11.4–53.2 mmHg), decreased during stroke, and increased in hyperbaric oxygen environment. In addition, we reviewed the effects of oxygen tensions on the behaviors of neural stem cells (NSCs) in vitro cultures at different oxygen concentration (15.2–152 mmHg) and in vivo niche during different pathological states and in hyperbaric/hypobaric oxygen environment. Moderate hypoxia (22.8–76 mmHg) can promote the proliferation of NSCs and enhance the differentiation of NSCs into the TH-positive neurons. Next, we briefly presented the oxygen-sensitive molecular mechanisms regulating NSCs proliferation and differentiation recently found including the Notch, Bone morphogenetic protein and Wnt pathways. Finally, the future perspectives about the roles of oxygen on brain and NSCs were given. PMID:21503147

Oxygen, a Key Factor Regulating Cell Behavior during Neurogenesis and Cerebral Diseases.

PubMed

Zhang, Kuan; Zhu, Lingling; Fan, Ming

2011-01-01

Oxygen is vital to maintain the normal functions of almost all the organs, especially for brain which is one of the heaviest oxygen consumers in the body. The important roles of oxygen on the brain are not only reflected in the development, but also showed in the pathological processes of many cerebral diseases. In the current review, we summarized the oxygen levels in brain tissues tested by real-time measurements during the embryonic and adult neurogenesis, the cerebral diseases, or in the hyperbaric/hypobaric oxygen environment. Oxygen concentration is low in fetal brain (0.076-7.6 mmHg) and in adult brain (11.4-53.2 mmHg), decreased during stroke, and increased in hyperbaric oxygen environment. In addition, we reviewed the effects of oxygen tensions on the behaviors of neural stem cells (NSCs) in vitro cultures at different oxygen concentration (15.2-152 mmHg) and in vivo niche during different pathological states and in hyperbaric/hypobaric oxygen environment. Moderate hypoxia (22.8-76 mmHg) can promote the proliferation of NSCs and enhance the differentiation of NSCs into the TH-positive neurons. Next, we briefly presented the oxygen-sensitive molecular mechanisms regulating NSCs proliferation and differentiation recently found including the Notch, Bone morphogenetic protein and Wnt pathways. Finally, the future perspectives about the roles of oxygen on brain and NSCs were given.

Bone marrow-derived mesenchymal stem cells ameliorate sodium nitrite-induced hypoxic brain injury in a rat model

PubMed Central

Ali, Elham H.A.; Ahmed-Farid, Omar A.; Osman, Amany A. E.

2017-01-01

Sodium nitrite (NaNO2) is an inorganic salt used broadly in chemical industry. NaNO2 is highly reactive with hemoglobin causing hypoxia. Mesenchymal stem cells (MSCs) are capable of differentiating into a variety of tissue specific cells and MSC therapy is a potential method for improving brain functions. This work aims to investigate the possible therapeutic role of bone marrow-derived MSCs against NaNO2 induced hypoxic brain injury. Rats were divided into control group (treated for 3 or 6 weeks), hypoxic (HP) group (subcutaneous injection of 35 mg/kg NaNO2 for 3 weeks to induce hypoxic brain injury), HP recovery groups N-2wR and N-3wR (treated with the same dose of NaNO2 for 2 and 3 weeks respectively, followed by 4-week or 3-week self-recovery respectively), and MSCs treated groups N-2wSC and N-3wSC (treated with the same dose of NaNO2 for 2 and 3 weeks respectively, followed by one injection of 2 × 106 MSCs via the tail vein in combination with 4 week self-recovery or intravenous injection of NaNO2 for 1 week in combination with 3 week self-recovery). The levels of neurotransmitters (norepinephrine, dopamine, serotonin), energy substances (adenosine monophosphate, adenosine diphosphate, adenosine triphosphate), and oxidative stress markers (malondialdehyde, nitric oxide, 8-hydroxy-2′-deoxyguanosine, glutathione reduced form, and oxidized glutathione) in the frontal cortex and midbrain were measured using high performance liquid chromatography. At the same time, hematoxylin-eosin staining was performed to observe the pathological change of the injured brain tissue. Compared with HP group, pathological change of brain tissue was milder, the levels of malondialdehyde, nitric oxide, oxidized glutathione, 8-hydroxy-2′-deoxyguanosine, norepinephrine, serotonin, glutathione reduced form, and adenosine triphosphate in the frontal cortex and midbrain were significantly decreased, and glutathione reduced form/oxidized glutathione and adenosine monophosphate/adenosine triphosphate ratio were significantly increased in the MSCs treated groups. These findings suggest that bone marrow-derived MSCs exhibit neuroprotective effects against NaNO2-induced hypoxic brain injury through exerting anti-oxidative effects and providing energy to the brain. PMID:29323037

Magnetic Resonance–Based Automatic Air Segmentation for Generation of Synthetic Computed Tomography Scans in the Head Region

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Weili; Kim, Joshua P.; Kadbi, Mo

2015-11-01

Purpose: To incorporate a novel imaging sequence for robust air and tissue segmentation using ultrashort echo time (UTE) phase images and to implement an innovative synthetic CT (synCT) solution as a first step toward MR-only radiation therapy treatment planning for brain cancer. Methods and Materials: Ten brain cancer patients were scanned with a UTE/Dixon sequence and other clinical sequences on a 1.0 T open magnet with simulation capabilities. Bone-enhanced images were generated from a weighted combination of water/fat maps derived from Dixon images and inverted UTE images. Automated air segmentation was performed using unwrapped UTE phase maps. Segmentation accuracy was assessedmore » by calculating segmentation errors (true-positive rate, false-positive rate, and Dice similarity indices using CT simulation (CT-SIM) as ground truth. The synCTs were generated using a voxel-based, weighted summation method incorporating T2, fluid attenuated inversion recovery (FLAIR), UTE1, and bone-enhanced images. Mean absolute error (MAE) characterized Hounsfield unit (HU) differences between synCT and CT-SIM. A dosimetry study was conducted, and differences were quantified using γ-analysis and dose-volume histogram analysis. Results: On average, true-positive rate and false-positive rate for the CT and MR-derived air masks were 80.8% ± 5.5% and 25.7% ± 6.9%, respectively. Dice similarity indices values were 0.78 ± 0.04 (range, 0.70-0.83). Full field of view MAE between synCT and CT-SIM was 147.5 ± 8.3 HU (range, 138.3-166.2 HU), with the largest errors occurring at bone–air interfaces (MAE 422.5 ± 33.4 HU for bone and 294.53 ± 90.56 HU for air). Gamma analysis revealed pass rates of 99.4% ± 0.04%, with acceptable treatment plan quality for the cohort. Conclusions: A hybrid MRI phase/magnitude UTE image processing technique was introduced that significantly improved bone and air contrast in MRI. Segmented air masks and bone-enhanced images were integrated into our synCT pipeline for brain, and results agreed well with clinical CTs, thereby supporting MR-only radiation therapy treatment planning in the brain.« less

Endocrine Regulation of Bone and Energy Metabolism in Hibernating Mammals

PubMed Central

Doherty, Alison H.; Florant, Gregory L.; Donahue, Seth W.

2014-01-01

Precise coordination among organs is required to maintain homeostasis throughout hibernation. This is particularly true in balancing bone remodeling processes (bone formation and resorption) in hibernators experiencing nutritional deprivation and extreme physical inactivity, two factors normally leading to pronounced bone loss in non-hibernating mammals. In recent years, important relationships between bone, fat, reproductive, and brain tissues have come to light. These systems share interconnected regulatory mechanisms of energy metabolism that potentially protect the skeleton during hibernation. This review focuses on the endocrine and neuroendocrine regulation of bone/fat/energy metabolism in hibernators. Hibernators appear to have unique mechanisms that protect musculoskeletal tissues while catabolizing their abundant stores of fat. Furthermore, the bone remodeling processes that normally cause disuse-induced bone loss in non-hibernators are compared to bone remodeling processes in hibernators, and possible adaptations of the bone signaling pathways that protect the skeleton during hibernation are discussed. Understanding the biological mechanisms that allow hibernators to survive the prolonged disuse and fasting associated with extreme environmental challenges will provide critical information regarding the limit of convergence in mammalian systems and of skeletal plasticity, and may contribute valuable insight into the etiology and treatment of human diseases. PMID:24556365

Emerging treatments for traumatic brain injury

PubMed Central

Xiong, Ye; Mahmood, Asim; Chopp, Michael

2009-01-01

Background This review summarizes promising approaches for the treatment of traumatic brain injury (TBI), which are either in preclinical or clinical trials. Objective The pathophysiology underlying neurological deficits after TBI is described. An overview of select therapies for TBI with neuroprotective and neurorestorative effects is presented. Methods A literature review of pre-clinical TBI studies and clinical TBI trials related to neuroprotective and neurorestorative therapeutic approaches is provided. Results/conclusion Nearly all phase II/III clinical trials in neuroprotection have failed to show any consistent improvement in outcome for TBI patients. The next decade will witness an increasing number of clinical trials which seek to translate preclinical research discoveries to the clinic. Promising drug- or cell-based therapeutic approaches include erythropoietin and its carbamylated form, statins, bone marrow stromal cells, stem cells singularly or in combination or with biomaterials to reduce brain injury via neuroprotection and promote brain remodeling via angiogenesis, neurogenesis, and synaptogenesis with a final goal to improve functional outcome of TBI patients. In addition, enriched environment and voluntary physical exercise show promise in promoting functional outcome after TBI, and should be evaluated alone or in combination with other treatments as therapeutic approaches for TBI. PMID:19249984

Improved superficial brain hemorrhage visualization in susceptibility weighted images by constrained minimum intensity projection

NASA Astrophysics Data System (ADS)

Castro, Marcelo A.; Pham, Dzung L.; Butman, John

2016-03-01

Minimum intensity projection is a technique commonly used to display magnetic resonance susceptibility weighted images, allowing the observer to better visualize hemorrhages and vasculature. The technique displays the minimum intensity in a given projection within a thick slab, allowing different connectivity patterns to be easily revealed. Unfortunately, the low signal intensity of the skull within the thick slab can mask superficial tissues near the skull base and other regions. Because superficial microhemorrhages are a common feature of traumatic brain injury, this effect limits the ability to proper diagnose and follow up patients. In order to overcome this limitation, we developed a method to allow minimum intensity projection to properly display superficial tissues adjacent to the skull. Our approach is based on two brain masks, the largest of which includes extracerebral voxels. The analysis of the rind within both masks containing the actual brain boundary allows reclassification of those voxels initially missed in the smaller mask. Morphological operations are applied to guarantee accuracy and topological correctness, and the mean intensity within the mask is assigned to all outer voxels. This prevents bone from dominating superficial regions in the projection, enabling superior visualization of cortical hemorrhages and vessels.

Acute Toxicity Study of Zerumbone-Loaded Nanostructured Lipid Carrier on BALB/c Mice Model

PubMed Central

Rahman, Heshu Sulaiman; Rasedee, Abdullah; Othman, Hemn Hassan; Chartrand, Max Stanley; Namvar, Farideh; Abdul Samad, Nozlena; Andas, Reena Joys; Ng, Kuan Beng; How, Chee Wun

2014-01-01

Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration. PMID:25276798

Bone Tissue Donation: Tendency and Hurdles.

PubMed

El Hage, S; Dos Santos, M J; de Moraes, E L; de Barros E Silva, L B

2018-03-01

The aim of this study was to identify the percentage of bone tissue donation in a brain death situation and the tendency of donation rate of this tissue in an organ procurement organization in the county of Sao Paulo from 2001 to 2016. It is a retrospective and quantitative study, based on the Organ and Tissue Donation Term of donors who died of brain death between 2001 and 2016. A logistic regression model was applied, and the odds of donation were identified throughout the years, regarding the odds ratio different from zero. Finally, it was measured the accuracy of the odds ratio through the confidence interval. The analysis has shown a significant change on the trend of bone donation (P < .001). In this case, the odds ratio was >1, indicating that the donation rate has increased. However, the percentage of growth is still considered low. The study evidences a growth trend regarding the donation of bone tissue, but the percentage is still too low to adequately meet the demand of patients who need this modality of therapeutic intervention. It is believed that educational campaigns of donation are not emphasizing the donation of tissues for transplantation, which may be directly impacting their consent rates. Copyright © 2018 Elsevier Inc. All rights reserved.

[A case of cerebral fat embolism after artificial bone replacement operation for femoral head fracture].

PubMed

Kontani, Satoru; Nakamura, Akinobu; Tokumi, Hiroshi; Hirose, Genjirou

2014-01-01

A 83 years old woman was slipped and injured with right femoral neck fracture. After three days from the fracture, she underwent an artificial head bone replacement operation. Immediately after surgery, she complained of chest discomfort, nausea and dyspnea. A few hours later, she became comatose. Brain CT showed no abnormality and clinical diagnosis of heart failure was made without pulmonary embolism on enhanced chest CT. Magnetic resonance imaging (MRI) of the brain next day showed multiple small patchy hyperintense lesion in bilateral hemispheres on diffusion-weighted images (DWI), producing a "star field pattern''. Based on Criteria of Gurd, this patient had one major criterion and four minor criteria. And according to the Criteria of Schonfeld, this patient had 5 points, consistent with clinical diagnosis of fat embolism. Because of these criteria, she was diagnosed as cerebral fat embolism syndrome. We started supported care and edaravon. Two weeks after surgery, her condition recovered and remaind to stuporous state even six month after surgery. We experienced a typical case of cerebral fat embolism, after bone surgery with diagnostic findings on MRI-DWI. Diagnosis of cerebral fat embolism syndrome requires a history of long bone fracture and/or replacing surgery with typical finding on MRI images, such as "star field pattern''.

Acute toxicity study of zerumbone-loaded nanostructured lipid carrier on BALB/c mice model.

PubMed

Rahman, Heshu Sulaiman; Rasedee, Abdullah; Othman, Hemn Hassan; Chartrand, Max Stanley; Namvar, Farideh; Yeap, Swee Keong; Abdul Samad, Nozlena; Andas, Reena Joys; Muhammad Nadzri, Nabilah; Anasamy, Theebaa; Ng, Kuan Beng; How, Chee Wun

2014-01-01

Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration.

Sterile Inflammation of Brain, due to Activation of Innate Immunity, as a Culprit in Psychiatric Disorders

PubMed Central

Ratajczak, Mariusz Z.; Pedziwiatr, Daniel; Cymer, Monika; Kucia, Magda; Kucharska-Mazur, Jolanta; Samochowiec, Jerzy

2018-01-01

Evidence has accumulated that the occurrence of psychiatric disorders is related to chronic inflammation. In support of this linkage, changes in the levels of circulating pro-inflammatory cytokines and chemokines in the peripheral blood (PB) of psychiatric patients as well as correlations between chronic inflammatory processes and psychiatric disorders have been described. Furthermore, an inflammatory process known as “sterile inflammation” when initiated directly in brain tissue may trigger the onset of psychoses. In this review, we will present the hypothesis that prolonged or chronic activation of the complement cascade (ComC) directly triggers inflammation in the brain and affects the proper function of this organ. Based on the current literature and our own work on mechanisms activating the ComC we hypothesize that inflammation in the brain is initiated by the mannan-binding lectin pathway of ComC activation. This activation is triggered by an increase in brain tissue of danger-associated molecular pattern (DAMP) mediators, including extracellular ATP and high-mobility group box 1 (HMGB1) protein, which are recognized by circulating pattern-recognition receptors, including mannan-binding lectin (MBL), that activate the ComC. On the other hand, this process is controlled by the anti-inflammatory action of heme oxygenase 1 (HO-1). In this review, we will try to connect changes in the release of DAMPs in the brain with inflammatory processes triggered by the innate immunity involving activation of the ComC as well as the inflammation-limiting effects of the anti-inflammatory HO-1 pathway. We will also discuss parallel observations that during ComC activation subsets of stem cells are mobilized into PB from bone marrow that are potentially involved in repair mechanisms. PMID:29541038

Sterile Inflammation of Brain, due to Activation of Innate Immunity, as a Culprit in Psychiatric Disorders.

PubMed

Ratajczak, Mariusz Z; Pedziwiatr, Daniel; Cymer, Monika; Kucia, Magda; Kucharska-Mazur, Jolanta; Samochowiec, Jerzy

2018-01-01

Evidence has accumulated that the occurrence of psychiatric disorders is related to chronic inflammation. In support of this linkage, changes in the levels of circulating pro-inflammatory cytokines and chemokines in the peripheral blood (PB) of psychiatric patients as well as correlations between chronic inflammatory processes and psychiatric disorders have been described. Furthermore, an inflammatory process known as "sterile inflammation" when initiated directly in brain tissue may trigger the onset of psychoses. In this review, we will present the hypothesis that prolonged or chronic activation of the complement cascade (ComC) directly triggers inflammation in the brain and affects the proper function of this organ. Based on the current literature and our own work on mechanisms activating the ComC we hypothesize that inflammation in the brain is initiated by the mannan-binding lectin pathway of ComC activation. This activation is triggered by an increase in brain tissue of danger-associated molecular pattern (DAMP) mediators, including extracellular ATP and high-mobility group box 1 (HMGB1) protein, which are recognized by circulating pattern-recognition receptors, including mannan-binding lectin (MBL), that activate the ComC. On the other hand, this process is controlled by the anti-inflammatory action of heme oxygenase 1 (HO-1). In this review, we will try to connect changes in the release of DAMPs in the brain with inflammatory processes triggered by the innate immunity involving activation of the ComC as well as the inflammation-limiting effects of the anti-inflammatory HO-1 pathway. We will also discuss parallel observations that during ComC activation subsets of stem cells are mobilized into PB from bone marrow that are potentially involved in repair mechanisms.

PXR (NR1I2): splice variants in human tissues, including brain, and identification of neurosteroids and nicotine as PXR activators.

PubMed

Lamba, Vishal; Yasuda, Kazuto; Lamba, Jatinder K; Assem, Mahfoud; Davila, Julio; Strom, Stephen; Schuetz, Erin G

2004-09-15

To gain insight on the expression of pregnane X receptor (PXR), we analyzed PXR.1 and PXR alternatively spliced transcripts in a panel of 36 human tissues. PXR.1 was expressed in many more tissues than previously determined, including human bone marrow and select regions of the human brain. In each of these tissues, we observed alternative splicing of various exons of PXR that generated multiple distinct PXR isoforms. The most abundant PXR alternative mRNA transcripts lacked 111 nucleotides, deleting 37 amino acids from the PXR LBD (PXR.2), or lacked 123 nt, deleting 41 amino acids from the PXR LBD (PXR.3). CYP3A4, a gene transcriptionally regulated by PXR, showed incomplete overlap with PXR in its tissue distribution. Quantitation of PXR mRNAs in human liver demonstrated that PXR.2 and PXR.3 represented 6.7% and 0.32% of total PXR mRNA transcripts. Brain expression of PXR prompted analysis of whether some brain acting chemicals were PXR ligands. The neurosteroids allopregnanolone and pregnanolone activated PXR and induced transcription of a CYP3A4-luciferase reporter. Nicotine, the psychoactive and addictive chemical in cigarettes, and a known inducer of brain CYP2B6, was an efficacious activator of PXR and inducer of CYP3A4 transcription. Because nicotine activation of PXR will enhance metabolism of nicotine to the non-psychoactive cotinine, these results provide one molecular mechanism for the development of tolerance to nicotine. Moreover, the identification of PXR in many human tissues, such as brain, and activation by tissue specific ligands (such as neurosteroids) suggests additional biological roles for this receptor in these tissues.

Biomechanical changes in the head associated with penetrating injuries of the maxilla and mandible: an experimental investigation.

PubMed

Tan, Yinghui; Zhou, Shuxia; Jiang, Hetian

2002-05-01

In this experiment, we studied the craniocerebral injury that occurs due to the transmission of forces when maxillofacial gunshot wounds are sustained by the facial bones and cranium. Forty fresh pigs' heads were wounded by one of the following methods: steel spheres weighing 1.03 g at an impact velocity of 1,400 m/s, steel spheres weighing 1.03 g at an impact velocity of 800 m/s, M193 military bullets, or M56 military bullets. Pressure waves in the brain, acceleration of the head, and stress changes in the facial bones and cranium at the moment of the impact were recorded by pressure and acceleration transducers and strain gauges and were statistically compared. Some obvious differences between the mechanical values obtained from high-and low-velocity missile wounds were found. A negative relationship between the peak value of the pressure wave in the brain and the distance from the point of impact to the transducer was obtained. The acceleration of the head in the direction of the ballistic path was the strongest in absolute value. There were differences in the stress values between the mandible and the temporal bone. Acceleration of the head, pressure wave changes in the brain, and injury from bony stress conduction all play important roles in associated craniocerebral damage after maxillofacial firearm wounds. Copyright 2002 American Association of Oral and Maxillofacial Surgeons

In vivo imaging models of bone and brain metastases and pleural carcinomatosis with a novel human EML4-ALK lung cancer cell line

PubMed Central

Nanjo, Shigeki; Nakagawa, Takayuki; Takeuchi, Shinji; Kita, Kenji; Fukuda, Koji; Nakada, Mitsutoshi; Uehara, Hisanori; Nishihara, Hiroshi; Hara, Eiji; Uramoto, Hidetaka; Tanaka, Fumihiro; Yano, Seiji

2015-01-01

EML4-ALK lung cancer accounts for approximately 3–7% of non-small-cell lung cancer cases. To investigate the molecular mechanism underlying tumor progression and targeted drug sensitivity/resistance in EML4-ALK lung cancer, clinically relevant animal models are indispensable. In this study, we found that the lung adenocarcinoma cell line A925L expresses an EML4-ALK gene fusion (variant 5a, E2:A20) and is sensitive to the ALK inhibitors crizotinib and alectinib. We further established highly tumorigenic A925LPE3 cells, which also have the EML4-ALK gene fusion (variant 5a) and are sensitive to ALK inhibitors. By using A925LPE3 cells with luciferase gene transfection, we established in vivo imaging models for pleural carcinomatosis, bone metastasis, and brain metastasis, all of which are significant clinical concerns of advanced EML4-ALK lung cancer. Interestingly, crizotinib caused tumors to shrink in the pleural carcinomatosis model, but not in bone and brain metastasis models, whereas alectinib showed remarkable efficacy in all three models, indicative of the clinical efficacy of these ALK inhibitors. Our in vivo imaging models of multiple organ sites may provide useful resources to analyze further the pathogenesis of EML4-ALK lung cancer and its response and resistance to ALK inhibitors in various organ microenvironments. PMID:25581823

Carmustine

MedlinePlus

... injection is used to treat certain types of brain tumors. Carmustine injection is also used along with prednisone to treat multiple myeloma (a type of cancer of the bone marrow). It is also used ...

Hoyeraal-Hreidarsson syndrome: magnetic resonance imaging findings.

PubMed

Kuwashima, Shigeko

2009-10-01

Hoyeraal-Hreidarsson syndrome (HH) has been defined as a severe variant of dyskeratosis congenita (DKC). We report here a case of a 6-year-old girl with HH who presented with bone marrow hypoplasia, skin pigmentation, nail dystrophy, growth retardation, and bilateral retinal hemorrhage. Brain MRI revealed cerebellar hypoplasia, hypoplasia of the corpus callosum, a small pituitary gland, a small brain stem, and focal long T2 lesions in the thalamus and brain stem. A brain computed tomography scan revealed intracranial calcification as well. To the best of our knowledge, a small pituitary gland and focal long T2 lesions in the thalamus and brain stem have never been reported as a feature of HH.

Stress-induced recruitment of bone marrow-derived monocytes to the brain promotes anxiety-like behavior.

PubMed

Wohleb, Eric S; Powell, Nicole D; Godbout, Jonathan P; Sheridan, John F

2013-08-21

Social stress is associated with altered immunity and higher incidence of anxiety-related disorders. Repeated social defeat (RSD) is a murine stressor that primes peripheral myeloid cells, activates microglia, and induces anxiety-like behavior. Here we show that RSD-induced anxiety-like behavior corresponded with an exposure-dependent increase in circulating monocytes (CD11b(+)/SSC(lo)/Ly6C(hi)) and brain macrophages (CD11b(+)/SSC(lo)/CD45(hi)). Moreover, RSD-induced anxiety-like behavior corresponded with brain region-dependent cytokine and chemokine responses involved with myeloid cell recruitment. Next, LysM-GFP(+) and GFP(+) bone marrow (BM)-chimeric mice were used to determine the neuroanatomical distribution of peripheral myeloid cells recruited to the brain during RSD. LysM-GFP(+) mice showed that RSD increased recruitment of GFP(+) macrophages to the brain and increased their presence within the perivascular space (PVS). In addition, RSD promoted recruitment of GFP(+) macrophages into the PVS and parenchyma of the prefrontal cortex, amygdala, and hippocampus of GFP(+) BM-chimeric mice. Furthermore, mice deficient in chemokine receptors associated with monocyte trafficking [chemokine receptor-2 knockout (CCR2(KO)) or fractalkine receptor knockout (CX3CR1(KO))] failed to recruit macrophages to the brain and did not develop anxiety-like behavior following RSD. Last, RSD-induced macrophage trafficking was prevented in BM-chimeric mice generated with CCR2(KO) or CX3CR1(KO) donor cells. These findings indicate that monocyte recruitment to the brain in response to social stress represents a novel cellular mechanism that contributes to the development of anxiety.

Stress-Induced Recruitment of Bone Marrow-Derived Monocytes to the Brain Promotes Anxiety-Like Behavior

PubMed Central

Wohleb, Eric S.; Powell, Nicole D.

2013-01-01

Social stress is associated with altered immunity and higher incidence of anxiety-related disorders. Repeated social defeat (RSD) is a murine stressor that primes peripheral myeloid cells, activates microglia, and induces anxiety-like behavior. Here we show that RSD-induced anxiety-like behavior corresponded with an exposure-dependent increase in circulating monocytes (CD11b+/SSClo/Ly6Chi) and brain macrophages (CD11b+/SSClo/CD45hi). Moreover, RSD-induced anxiety-like behavior corresponded with brain region-dependent cytokine and chemokine responses involved with myeloid cell recruitment. Next, LysM-GFP+ and GFP+ bone marrow (BM)-chimeric mice were used to determine the neuroanatomical distribution of peripheral myeloid cells recruited to the brain during RSD. LysM-GFP+ mice showed that RSD increased recruitment of GFP+ macrophages to the brain and increased their presence within the perivascular space (PVS). In addition, RSD promoted recruitment of GFP+ macrophages into the PVS and parenchyma of the prefrontal cortex, amygdala, and hippocampus of GFP+ BM-chimeric mice. Furthermore, mice deficient in chemokine receptors associated with monocyte trafficking [chemokine receptor-2 knockout (CCR2KO) or fractalkine receptor knockout (CX3CR1KO)] failed to recruit macrophages to the brain and did not develop anxiety-like behavior following RSD. Last, RSD-induced macrophage trafficking was prevented in BM-chimeric mice generated with CCR2KO or CX3CR1KO donor cells. These findings indicate that monocyte recruitment to the brain in response to social stress represents a novel cellular mechanism that contributes to the development of anxiety. PMID:23966702

Time-Dependent Changes in T1 during Fracture Healing in Juvenile Rats: A Quantitative MR Approach

PubMed Central

Baron, Katharina; Neumayer, Bernhard; Amerstorfer, Eva; Scheurer, Eva; Diwoky, Clemens; Stollberger, Rudolf; Sprenger, Hanna; Weinberg, Annelie M.

2016-01-01

Quantitative magnetic resonance imaging (qMRI) offers several advantages in imaging and determination of soft tissue alterations when compared to qualitative imaging techniques. Although applications in brain and muscle tissues are well studied, its suitability to quantify relaxation times of intact and injured bone tissue, especially in children, is widely unknown. The objective observation of a fracture including its age determination can become of legal interest in cases of child abuse or maltreatment. Therefore, the aim of this study is the determination of time dependent changes in intact and corresponding injured bones in immature rats via qMRI, to provide the basis for an objective and radiation-free approach for fracture dating. Thirty-five MR scans of 7 Sprague-Dawley rats (male, 4 weeks old, 100 ± 5 g) were acquired on a 3T MRI scanner (TimTrio, Siemens AG, Erlangen, Germany) after the surgical infliction of an epiphyseal fracture in the tibia. The images were taken at days 1, 3, 7, 14, 28, 42 and 82 post-surgery. A proton density-weighted and a T1-weighted 3D FLASH sequence were acquired to calculate the longitudinal relaxation time T1 of the fractured region and the surrounding tissues. The calculation of T1 in intact and injured bone resulted in a quantitative observation of bone development in intact juvenile tibiae as well as the bone healing process in the injured tibiae. In both areas, T1 decreased over time. To evaluate the differences in T1 behaviour between the intact and injured bone, the relative T1 values (bone-fracture) were calculated, showing clear detectable alterations of T1 after fracture occurrence. These results indicate that qMRI has a high potential not only for clinically relevant applications to detect growth defects or developmental alterations in juvenile bones, but also for forensically relevant applications such as the dating of fractures in cases of child abuse or maltreatment. PMID:27832068

Use of a Minimally Invasive Retractor System for Retrieval of Intracranial Fragments in Wartime Trauma.

PubMed

Rymarczuk, George N; Davidson, Laurence; Severson, Meryl A; Armonda, Rocco A

2015-10-01

Wartime penetrating brain injury can result in deep-seated parenchymal and intraventicular shrapnel, bullets, and bone. Large fragments pose a risk of secondary injury from migration, infection, and metal toxicity. It has been recommended that aggressive removal of fragments be avoided. The goal of this study is to report our technique of minimally invasive removal of select deep-seated fragments using a tubular retractor system. A retrospective review of our database of service members presenting with penetrating traumatic brain injuries incurred during Operations Iraqi Freedom and Enduring Freedom and treated at the Walter Reed Army Medical Center and the National Naval Medical Center was performed. Six individuals were identified in which the Vycor ViewSite retractor system (Vycor Medical, Boca Raton, Florida, USA) was used to remove a ventricular or deep intraparenchymal fragment. All patients were male and ranged in age from 21 to 29 years. Fragment location included the foramen of Monro; the atrium of the right lateral ventricle; parasagittally within the right occipital lobe; the occipital horn of the right lateral ventricle; the deep white matter of the dominant temporal lobe; and within the posterior right temporal lobe deep to the junction of the transverse and sigmoid dural venous sinuses. Fragments included in-driven bone, shrapnel from improvised explosive devices, and bullets. In all cases the fragment was successfully removed. No patient had worsening of their neurologic condition following surgery. Deep parenchymal and intraventricular fragments can be safely removed using a tubular retractor system. Published by Elsevier Inc.

Generation of synthetic CT using multi-scale and dual-contrast patches for brain MRI-only external beam radiotherapy.

PubMed

Aouadi, Souha; Vasic, Ana; Paloor, Satheesh; Torfeh, Tarraf; McGarry, Maeve; Petric, Primoz; Riyas, Mohamed; Hammoud, Rabih; Al-Hammadi, Noora

2017-10-01

To create a synthetic CT (sCT) from conventional brain MRI using a patch-based method for MRI-only radiotherapy planning and verification. Conventional T1 and T2-weighted MRI and CT datasets from 13 patients who underwent brain radiotherapy were included in a retrospective study whereas 6 patients were tested prospectively. A new contribution to the Non-local Means Patch-Based Method (NMPBM) framework was done with the use of novel multi-scale and dual-contrast patches. Furthermore, the training dataset was improved by pre-selecting the closest database patients to the target patient for computation time/accuracy balance. sCT and derived DRRs were assessed visually and quantitatively. VMAT planning was performed on CT and sCT for hypothetical PTVs in homogeneous and heterogeneous regions. Dosimetric analysis was done by comparing Dose Volume Histogram (DVH) parameters of PTVs and organs at risk (OARs). Positional accuracy of MRI-only image-guided radiation therapy based on CBCT or kV images was evaluated. The retrospective (respectively prospective) evaluation of the proposed Multi-scale and Dual-contrast Patch-Based Method (MDPBM) gave a mean absolute error MAE=99.69±11.07HU (98.95±8.35HU), and a Dice in bones DI bone =83±0.03 (0.82±0.03). Good agreement with conventional planning techniques was obtained; the highest percentage of DVH metric deviations was 0.43% (0.53%) for PTVs and 0.59% (0.75%) for OARs. The accuracy of sCT/CBCT or DRR sCT /kV images registration parameters was <2mm and <2°. Improvements with MDPBM, compared to NMPBM, were significant. We presented a novel method for sCT generation from T1 and T2-weighted MRI potentially suitable for MRI-only external beam radiotherapy in brain sites. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Beyond the functional matrix hypothesis: a network null model of human skull growth for the formation of bone articulations

PubMed Central

Esteve-Altava, Borja; Rasskin-Gutman, Diego

2014-01-01

Craniofacial sutures and synchondroses form the boundaries among bones in the human skull, providing functional, developmental and evolutionary information. Bone articulations in the skull arise due to interactions between genetic regulatory mechanisms and epigenetic factors such as functional matrices (soft tissues and cranial cavities), which mediate bone growth. These matrices are largely acknowledged for their influence on shaping the bones of the skull; however, it is not fully understood to what extent functional matrices mediate the formation of bone articulations. Aiming to identify whether or not functional matrices are key developmental factors guiding the formation of bone articulations, we have built a network null model of the skull that simulates unconstrained bone growth. This null model predicts bone articulations that arise due to a process of bone growth that is uniform in rate, direction and timing. By comparing predicted articulations with the actual bone articulations of the human skull, we have identified which boundaries specifically need the presence of functional matrices for their formation. We show that functional matrices are necessary to connect facial bones, whereas an unconstrained bone growth is sufficient to connect non-facial bones. This finding challenges the role of the brain in the formation of boundaries between bones in the braincase without neglecting its effect on skull shape. Ultimately, our null model suggests where to look for modified developmental mechanisms promoting changes in bone growth patterns that could affect the development and evolution of the head skeleton. PMID:24975579

The effect of distant metastases sites on survival in de novo stage-IV breast cancer: A SEER database analysis.

PubMed

Wu, San-Gang; Li, Hui; Tang, Li-Ying; Sun, Jia-Yuan; Zhang, Wen-Wen; Li, Feng-Yan; Chen, Yong-Xiong; He, Zhen-Yu

2017-06-01

To investigate the effect of distant metastases sites on survival in patients with de novo stage-IV breast cancer. From 2010 to 2013, patients with a diagnosis of de novo stage-IV breast cancer were identified using the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on breast cancer-specific survival and overall survival. A total of 7575 patients were identified. The most common metastatic sites were bone, followed by lung, liver, and brain. Patients with hormone receptor+/human epidermal growth factor receptor 2- and hormone receptor+/human epidermal growth factor receptor 2+ status were more prone to bone metastases. Lung and brain metastases were common in hormone receptor-/human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2- subtypes, and patients with hormone receptor+/ human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2+ subtypes were more prone to liver metastases. Patients with liver and brain metastases had unfavorable prognosis for breast cancer-specific survival and overall survival, whereas bone and lung metastases had no effect on patient survival in multivariate analyses. The hormone receptor-/human epidermal growth factor receptor 2- subtype conferred a significantly poorer outcome in terms of breast cancer-specific survival and overall survival. hormone receptor+/human epidermal growth factor receptor 2+ disease was associated with the best prognosis in terms of breast cancer-specific survival and overall survival. Patients with liver and brain metastases were more likely to experience poor prognosis for breast cancer-specific survival and overall survival by various breast cancer subtypes. Distant metastases sites have differential impact on clinical outcomes in stage-IV breast cancer. Follow-up screening for brain and liver metastases might be effective in improving breast cancer-specific survival and overall survival.

The Effect of Brain-Derived Neurotrophic Factor on Periodontal Furcation Defects

PubMed Central

Jimbo, Ryo; Tovar, Nick; Janal, Malvin N.; Mousa, Ramy; Marin, Charles; Yoo, Daniel; Teixeira, Hellen S.; Anchieta, Rodolfo B.; Bonfante, Estevam A.; Konishi, Akihiro; Takeda, Katsuhiro; Kurihara, Hidemi; Coelho, Paulo G.

2014-01-01

This study aimed to observe the regenerative effect of brain-derived neurotrophic factor (BDNF) in a non-human primate furcation defect model. Class II furcation defects were created in the first and second molars of 8 non-human primates to simulate a clinical situation. The defect was filled with either, Group A: BDNF (500 µg/ml) in high-molecular weight-hyaluronic acid (HMW-HA), Group B: BDNF (50 µg/ml) in HMW-HA, Group C: HMW-HA acid only, Group D: empty defect, or Group E: BDNF (500 µg/ml) in saline. The healing status for all groups was observed at different time-points with micro computed tomography. The animals were euthanized after 11 weeks, and the tooth-bone specimens were subjected to histologic processing. The results showed that all groups seemed to successfully regenerate the alveolar buccal bone, however, only Group A regenerated the entire periodontal tissue, i.e., alveolar bone, cementum and periodontal ligament. It is suggested that the use of BDNF in combination with a scaffold such as the hyaluronic acid in periodontal furcation defects may be an effective treatment option. PMID:24454754

WAIF1 Is a Cell-Surface CTHRC1 Binding Protein Coupling Bone Resorption and Formation.

PubMed

Matsuoka, Kazuhiko; Kohara, Yukihiro; Naoe, Yoshinori; Watanabe, Atsushi; Ito, Masako; Ikeda, Kyoji; Takeshita, Sunao

2018-04-06

The osteoclast-derived collagen triple helix repeat containing 1 (CTHRC1) protein stimulates osteoblast differentiation, but the underlying mechanism remains unclear. Here, we identified Wnt-activated inhibitory factor 1 (WAIF1)/5T4 as a cell-surface protein binding CTHRC1. The WAIF1-encoding Trophoblast glycoprotein (Tpbg) gene, which is abundantly expressed in the brain and bone but not in other tissues, showed the same expression pattern as Cthrc1. Tpbg downregulation in marrow stromal cells reduced CTHRC1 binding and CTHRC1-stimulated alkaline phosphatase activity through PKCδ activation of MEK/ERK, suggesting a novel WAIF1/PKCδ/ERK pathway triggered by CTHRC1. Unexpectedly, osteoblast lineage-specific deletion of Tpbg downregulated Rankl expression in mouse bones and reduced both bone formation and resorption; importantly, it impaired bone mass recovery following RANKL-induced resorption, reproducing the phenotype of osteoclast-specific Cthrc1 deficiency. Thus, the binding of osteoclast-derived CTHRC1 to WAIF1 in stromal cells activates PKCδ-ERK osteoblastogenic signaling and serves as a key molecular link between bone resorption and formation during bone remodeling. © 2018 American Society for Bone and Mineral Research. © 2018 American Society for Bone and Mineral Research.

MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia.

PubMed

Rowe, P S; de Zoysa, P A; Dong, R; Wang, H R; White, K E; Econs, M J; Oudet, C L

2000-07-01

Oncogenic hypophosphatemic osteomalacia (OHO) is characterized by a renal phosphate leak, hypophosphatemia, low-serum calcitriol (1,25-vitamin-D3), and abnormalities in skeletal mineralization. Resection of OHO tumors results in remission of the symptoms, and there is evidence that a circulating phosphaturic factor plays a role in the bone disease. This paper describes the characterization and cloning of a gene that is a candidate for the tumor-secreted phosphaturic factor. This new gene has been named MEPE (matrix extracellular phosphoglycoprotein) and has major similarities to a group of bone-tooth mineral matrix phospho-glycoproteins (osteopontin (OPN; HGMW-approved symbol SPP1), dentin sialo phosphoprotein (DSPP), dentin matrix protein 1 (DMP1), bone sialoprotein II (IBSP), and bone morphogenetic proteins (BMP). All the proteins including MEPE contain RGD sequence motifs that are proposed to be essential for integrin-receptor interactions. Of further interest is the finding that MEPE, OPN, DSPP, DMP1, IBSP, and BMP3 all map to a defined region in chromosome 4q. Refined mapping localizes MEPE to 4q21.1 between ESTs D4S2785 (WI-6336) and D4S2844 (WI-3770). MEPE is 525 residues in length with a short N-terminal signal peptide. High-level expression of MEPE mRNA occurred in all four OHO tumors screened. Three of 11 non-OHO tumors screened contained trace levels of MEPE expression (detected only after RT-PCR and Southern 32P analysis). Normal tissue expression was found in bone marrow and brain with very-low-level expression found in lung, kidney, and human placenta. Evidence is also presented for the tumor secretion of clusterin (HGMW-approved symbol CLU) and its possible role as a cytotoxic factor in one of the OHO patients described.

Variability of the temporal bone surface's topography: implications for otologic surgery

NASA Astrophysics Data System (ADS)

Lecoeur, Jérémy; Noble, Jack H.; Balachandran, Ramya; Labadie, Robert F.; Dawant, Benoit M.

2012-02-01

Otologic surgery is performed for a variety of reasons including treatment of recurrent ear infections, alleviation of dizziness, and restoration of hearing loss. A typical ear surgery consists of a tympanomastoidectomy in which both the middle ear is explored via a tympanic membrane flap and the bone behind the ear is removed via mastoidectomy to treat disease and/or provide additional access. The mastoid dissection is performed using a high-speed drill to excavate bone based on a pre-operative CT scan. Intraoperatively, the surface of the mastoid component of the temporal bone provides visual feedback allowing the surgeon to guide their dissection. Dissection begins in "safe areas" which, based on surface topography, are believed to be correlated with greatest distance from surface to vital anatomy thus decreasing the chance of injury to the brain, large blood vessels (e.g. the internal jugular vein and internal carotid artery), the inner ear, and the facial nerve. "Safe areas" have been identified based on surgical experience with no identifiable studies showing correlation of the surface with subsurface anatomy. The purpose of our study was to investigate whether such a correlation exists. Through a three-step registration process, we defined a correspondence between each of twenty five clinically-applicable temporal bone CT scans of patients and an atlas and explored displacement and angular differences of surface topography and depth of critical structures from the surface of the skull. The results of this study reflect current knowledge of osteogenesis and anatomy. Based on two features (distance and angular difference), two regions (suprahelical and posterior) of the temporal bone show the least variability between surface and subsurface anatomy.

Targeted Knockdown of Bone Morphogenetic Protein Signaling within Neural Progenitors Protects the Brain and Improves Motor Function following Postnatal Hypoxia-Ischemia

PubMed Central

Dettman, Robert W.; Birch, Derin; Fernando, Augusta; Kessler, John A.; Dizon, Maria L.V.

2018-01-01

Hypoxic-ischemic injury (HI) to the neonatal human brain results in myelin loss that, in some children, can manifest as cerebral palsy. Previously, we had found that neuronal overexpression of the bone morphogenic protein (BMP) inhibitor noggin during development increased oligodendroglia and improved motor function in an experimental model of HI utilizing unilateral common carotid artery ligation followed by hypoxia. As BMPs are known to negatively regulate oligodendroglial fate specification of neural stem cells and alter differentiation of committed oligodendroglia, BMP signaling is likely an important mechanism leading to myelin loss. Here, we showed that BMP signaling is upregulated within oligodendroglia of the neonatal brain. We tested the hypothesis that inhibition of BMP signaling specifically within neural progenitor cells (NPCs) is sufficient to protect oligodendroglia. We conditionally deleted the BMP receptor 2 subtype (BMPR2) in NG2-expressing cells after HI. We found that BMPR2 deletion globally protects the brain as assessed by MRI and protects motor function as assessed by digital gait analysis, and that conditional deletion of BMPR2 maintains oligodendrocyte marker expression by immunofluorescence and Western blot and prevents loss of oligodendroglia. Finally, BMPR2 deletion after HI results in an increase in noncompacted myelin. Thus, our data indicate that inhibition of BMP signaling specifically in NPCs may be a tractable strategy to protect the newborn brain from HI. PMID:29324456

RAS mutations affect pattern of metastatic spread and increase propensity for brain metastasis in colorectal cancer.

PubMed

Yaeger, Rona; Cowell, Elizabeth; Chou, Joanne F; Gewirtz, Alexandra N; Borsu, Laetitia; Vakiani, Efsevia; Solit, David B; Rosen, Neal; Capanu, Marinela; Ladanyi, Marc; Kemeny, Nancy

2015-04-15

RAS and PIK3CA mutations in metastatic colorectal cancer (mCRC) have been associated with worse survival. We sought to evaluate the impact of RAS and PIK3CA mutations on cumulative incidence of metastasis to potentially curable sites of liver and lung and other sites such as bone and brain. We performed a computerized search of the electronic medical record of our institution for mCRC cases genotyped for RAS or PIK3CA mutations from 2008 to 2012. Cases were reviewed for patient characteristics, survival, and site-specific metastasis. Among the 918 patients identified, 477 cases were RAS wild type, and 441 cases had a RAS mutation (394 at KRAS exon 2, 29 at KRAS exon 3 or 4, and 18 in NRAS). RAS mutation was significantly associated with shorter median overall survival (OS) and on multivariate analysis independently predicted worse OS (HR, 1.6; P < .01). RAS mutant mCRC exhibited a significantly higher cumulative incidence of lung, bone, and brain metastasis and on multivariate analysis was an independent predictor of involvement of these sites (HR, 1.5, 1.6, and 3.7, respectively). PIK3CA mutations occurred in 10% of the 786 cases genotyped, did not predict for worse survival, and did not exhibit a site-specific pattern of metastatic spread. The metastatic potential of CRC varies with the presence of RAS mutation. RAS mutation is associated with worse OS and increased incidence of lung, bone, and brain metastasis. An understanding of this site-specific pattern of spread may help to inform physicians' assessment of symptoms in patients with mCRC. © 2014 American Cancer Society.

Bioinspired Collagen Scaffolds in Cranial Bone Regeneration: From Bedside to Bench

PubMed Central

Volpicelli, Elizabeth J.

2018-01-01

Calvarial defects are common reconstructive dilemmas secondary to a variety of etiologies including traumatic brain injury, cerebrovascular disease, oncologic resection, and congenital anomalies. Reconstruction of the calvarium is generally undertaken for the purposes of cerebral protection, contour restoration for psychosocial well-being, and normalization of neurological dysfunction frequently found in patients with massive cranial defects. Current methods for reconstruction using autologous grafts, allogeneic grafts, or allo-plastic materials have significant drawbacks that are unique to each material. The combination of wide medical relevance and the need for a better clinical solution render defects of the cranial skeleton an ideal target for development of regenerative strategies focused on calvarial bone. With the improved understanding of the instructive properties of tissue-specific extracellular matrices and the advent of precise nanoscale modulation in materials science, strategies in regenerative medicine have shifted in paradigm. Previously considered to be simple carriers of stem cells and growth factors, increasing evidence exists for differential materials directing lineage specific differentiation of progenitor cells and tissue regeneration. In this work, we review the clinical challenges for calvarial reconstruction, the anatomy and physiology of bone, and extracellular matrix-inspired, collagen-based materials that have been tested for in vivo cranial defect healing. PMID:28585295

A lead isotope distribution study in swine tissue using ICP-MS

USGS Publications Warehouse

May, T.W.; Wiedmeyer, Ray H.; Brown, L.D.; Casteel, S.W.

1999-01-01

In the United States lead is an ubiquitous environmental pollutant that is a serious human health hazard, especially for women of childbearing age, developing fetuses, and young children. Information concerning the uptake and distribution of lead to maternal and fetal tissues during pregnancy is poorly documented. A study was designed using domestic swine and lead isotope enrichment methodology to focus on maternal absorption and distribution of lead into bone and soft tissues, including the fetal compartment, under varying conditions of oral lead exposure and during altered physiological states (pregnant vs unbred). Total lead levels and Pb207/Pb206 ratios in bone (femur and vertebra), blood, and soft tissues (liver, kidney, brain) were determined by ICP-MS. Lead in fetal tissues derived from maternal bone could be differentiated from that derived from exogenous dosing. Unbred swine absorbed much less lead than pregnant females receiving the same dose. The accuracy and precision of ICP-MS at the instrumental level and for the entire method (sample collection, digestion, and analysis) were evaluated for both Pb207/Pb206 ratios and total lead. Several changes were suggested in method design to improve both instrumental and total method precision.

Maggots in the Brain: Sequelae of Ignored Scalp Wound.

PubMed

Aggarwal, Ashish; Maskara, Prasant

2018-01-01

A 26-year-old male had suffered a burn injury to his scalp in childhood and ignored it. He presented with a complaint of something crawling on his head. Inspection of his scalp revealed multiple maggots on the brain surface with erosion of overlying bone and scalp. He was successfully managed by surgical debridement and regular dressing. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Curculigoside on Memory Impairment and Bone Loss via Anti-Oxidative Character in APP/PS1 Mutated Transgenic Mice.

PubMed

Zhao, Lu; Liu, Sha; Wang, Yin; Zhang, Qiaoyan; Zhao, Wenjuan; Wang, Zejian; Yin, Ming

2015-01-01

Alzheimer's disease (AD) and osteoporosis are two closely related multifactorial progressively degenerative diseases that predominantly affect aged people. These two diseases share many common risk factors, including old age, being female, smoking, excessive drinking, low estrogen, and vitamin D3 levels. Additionally, oxidative damage and the dysfunction of the antioxidant system play important roles in the pathogenesis of osteoporosis and AD. Aβ not only leads to impaired memory but also plays a crucial role in the demineralization process of bone tissues of older people and women with menopause. Curculigoside can promote calcium deposition and increase the levels of ALP and Runx2 in osteoblasts under oxidative stress via anti-oxidative character. Therefore, we investigated the effects of CUR on the spatial learning and memory by the Morris water maze and brain immunohistochemistry, and bone microstructure and material properties of femurs by micro-computed tomography and mechanical testing in APP/PS1 mutated transgenic mice. Oral administration of CUR can significantly enhance learning performance and ameliorate bone loss in APP/PS1 mutated transgenic mice, and the mechanism may be related to its antioxidant effect. Based on these results, CUR has real potential as a new natural resource for developing medicines or dietary supplements for the prevention and treatment of the two closely linked multifactorial progressive degenerative disorders, AD and osteoporosis.

Preclinical Evaluation of 18F-JNJ64349311, a Novel PET Tracer for Tau Imaging.

PubMed

Declercq, Lieven; Rombouts, Frederik; Koole, Michel; Fierens, Katleen; Mariën, Jonas; Langlois, Xavier; Andrés, José Ignacio; Schmidt, Mark; Macdonald, Gregor; Moechars, Diederik; Vanduffel, Wim; Tousseyn, Thomas; Vandenberghe, Rik; Van Laere, Koen; Verbruggen, Alfons; Bormans, Guy

2017-06-01

In this study, we have synthesized and evaluated 18 F-JNJ64349311, a tracer with high affinity for aggregated tau (inhibition constant value, 8 nM) and high (≥500×) in vitro selectivity for tau over β-amyloid, in comparison with the benchmark compound 18 F-AV1451 ( 18 F-T807) in mice, rats, and a rhesus monkey. Methods: In vitro binding characteristics were determined for Alzheimer's disease, progressive supranuclear palsy, and corticobasal degeneration patient brain tissue slices using autoradiography studies. Ex vivo biodistribution studies were performed in mice. Radiometabolites were quantified in the brain and plasma of mice and in the plasma of a rhesus monkey using high-performance liquid chromatography. Dynamic small-animal PET studies were performed in rats and a rhesus monkey to evaluate tracer pharmacokinetics in the brain. Results: Mouse biodistribution studies showed moderate initial brain uptake and rapid brain washout. Radiometabolite analyses after injection of 18 F-JNJ64349311 in mice showed the presence of a polar radiometabolite in plasma, but not in the brain. Semiquantitative autoradiography studies on postmortem tissue sections of human Alzheimer's disease brains showed highly displaceable binding to tau-rich regions. No specific binding was, however, found on human progressive supranuclear palsy and corticobasal degeneration brain slices. Small-animal PET scans of Wistar rats revealed moderate initial brain uptake (SUV, ∼1.5 at 1 min after injection) and rapid brain washout. Gradual bone uptake was, however, also observed. Blocking and displacement did not affect brain time-activity curves, suggesting no off-target specific binding of the tracer in the healthy rat brain. A small-animal PET scan of a rhesus monkey revealed moderate initial brain uptake (SUV, 1.9 at 1 min after injection) with a rapid washout. In the monkey, no bone uptake was detected during the 120-min scan. Conclusion: This biologic evaluation suggests that 18 F-JNJ64349311 is a promising tau PET tracer candidate, with a favorable pharmacokinetic profile, as compared with 18 F-AV1451. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Brain Sex Matters: estrogen in cognition and Alzheimer’s disease

PubMed Central

Li, Rena; Cui, Jie; Shen, Yong

2014-01-01

Estrogens are the primary female sex hormones and play important roles in both reproductive and non-reproductive systems. Estrogens can be synthesized in non-reproductive tissues such as liver, heart, muscle, bone and the brain. During the past decade, increasing evidence suggests that brain estrogen can not only be synthesized by neurons, but also by astrocytes. Brain estrogen also works locally at the site of synthesis in paracrine and/or intracrine fashion to maintain important tissue-specific functions. Here, we will focus on the biology of brain estrogen and its impact on cognitive function and Alzheimer’s disease. This comprehensive review provides new insights into brain estrogens by presenting a better understanding of the tissue-specific estrogen effects and their roles in healthy ageing and cognitive function. PMID:24418360

Nevirapine Loaded Core Shell Gold Nanoparticles by Double Emulsion Solvent Evaporation: In vitro and In vivo Evaluation.

PubMed

Dalvi, Bhagyashree R; Siddiqui, Ejaz A; Syed, Asad S; Velhal, Shilpa M; Ahmad, Absar; Bandivdekar, Atmaram B; Devarajan, Padma V

2016-01-01

HIV/AIDS is a macrophage resident infection localized in the reticuloendothelial system and remote locations of brain and bone marrow. We present core shell nanoparticles of gold(AuNPs) and nevirapine(NVP) for targeted delivery to the multiple HIV reservoirs. The aim of the study was to design core shell NVP loaded AuNPs with high drug loading and to evaluate biodistribution of the nanoparticles in possible HIV reservoirs in vivo. A specific objective was to assess the possible synergy of AuNPs with NVP on anti-HIV activity in vitro. Core shell nanoparticles were prepared by double emulsion solvent evaporation method and characterized. Glyceryl monostearate-nevirapine-gold nanoparticles(GMS-NVP-AuNPs) revealed high entrapment efficiency (>70%), high loading (~40%), particle size <250 nm and zeta potential -35.9± 1.41mv and exhibited sustained release with good stability. Surface plasmon resonance indicated shell formation while SEM coupled EDAX confirmed the presence of Au. TEM confirmed formation of spherical core shell nanoparticles. GMS-NVP-AuNPs revealed low hemolysis (<10 %) and serum stability upto 6 h. GMS-NVP-AuNPs exhibited rapid, high and sustained accumulation in the possible HIV reservoir organs, including the major organs of liver, spleen, lymph nodes, thymus and also remote locations of brain, ovary and bone marrow. High cell viability and enhanced uptake in PBMC's and TZM-bl cells were observed. While uptake in PBMC's proposed monocytes/macrophages enabled brain delivery. GMS-NVP-AuNPs demonstrated synergistic anti-HIV activity. The superior anti-HIV activity in vitro coupled with extensive localization of the nanoparticles in multiple HIV reservoirs suggests great promise of the core shell GMS-NVP-AuNPs for improved therapy of HIV.

A novel approach to pharmaco-EEG for investigating analgesics: assessment of spectral indices in single-sweep evoked brain potentials.

PubMed

Gram, Mikkel; Graversen, Carina; Nielsen, Anders K; Arendt-Nielsen, Thomas; Mørch, Carsten D; Andresen, Trine; Drewes, Asbjørn M

2013-12-01

To compare results from analysis of averaged and single-sweep evoked brain potentials (EPs) by visual inspection and spectral analysis in order to identify an objective measure for the analgesic effect of buprenorphine and fentanyl. Twenty-two healthy males were included in a randomized study to assess the changes in EPs after 110 sweeps of painful electrical stimulation to the median nerve following treatment with buprenorphine, fentanyl or placebo patches. Bone pressure, cutaneous heat and electrical pain ratings were assessed. EPs and pain assessments were obtained before drug administration, 24, 48, 72 and 144 h after beginning of treatment. Features from EPs were extracted by three different approaches: (i) visual inspection of amplitude and latency of the main peaks in the average EPs, (ii) spectral distribution of the average EPs and (iii) spectral distribution of the EPs from single-sweeps. Visual inspection revealed no difference between active treatments and placebo (all P > 0.05). Spectral distribution of the averaged potentials showed a decrease in the beta (12-32 Hz) band for fentanyl (P = 0.036), which however did not correlate with pain ratings. Spectral distribution in the single-sweep EPs revealed significant increases in the theta, alpha and beta bands for buprenorphine (all P < 0.05) as well as theta band increase for fentanyl (P = 0.05). For buprenorphine, beta band activity correlated with bone pressure and cutaneous heat pain (both P = 0.04, r = 0.90). In conclusion single-sweep spectral band analysis increases the information on the response of the brain to opioids and may be used to identify the response to analgesics. © 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.

Detecting occlusion inside a ventricular catheter using photoacoustic imaging through skull

NASA Astrophysics Data System (ADS)

Tavakoli, Behnoosh; Guo, Xiaoyu; Taylor, Russell H.; Kang, Jin U.; Boctor, Emad M.

2014-03-01

Ventricular catheters are used to treat hydrocephalus by diverting the excess of the cerebrospinal fluid (CSF) to the reabsorption site so as to regulate the intracranial pressure. The failure rate of these shunts is extremely high due to the ingrown tissue that blocks the CSF flow. We have studied a method to image the occlusion inside the shunt through the skull. In this approach the pulsed laser light coupled to the optical fiber illuminate the occluding tissue inside the catheter and an external ultrasound transducer is applied to detect the generated photoacoustic signal. The feasibility of this method is investigated using a phantom made of ovis aries brain tissue and adult human skull. We were able to image the target inside the shunt located 20mm deep inside the brain through about 4mm thick skull bone. This study could lead to the development of a simple, safe and non-invasive device for percutaneous restoration of patency to occluded shunts. This will eliminate the need of the surgical replacement of the occluded catheters which expose the patients to risks including hemorrhage and brain injury.

Amphotericin B Liposomal Injection

MedlinePlus

... spinal cord and brain) and visceral leishmaniasis (a parasitic disease that usually affects spleen, liver, and bone ... supplements, and herbal products you are taking or plan to take. Be sure to mention any of ...

Transitional change in rat fetal cell proliferation in response to ghrelin and des-acyl ghrelin during the last stage of pregnancy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inoue, Yoshiyuki; Nakahara, Keiko; Kangawa, Kenji

Expression of mRNA for the ghrelin receptor, GHS-R1a, was detected in various peripheral and central tissues of fetal rats, including skin, bone, heart, liver, gut, brain and spinal cord, on embryonic day (ED)15 and ED17. However, its expression in skin, bone, heart and liver, but not in gut, brain and spinal cord, became relatively weak on ED19 and disappeared after birth (ND2). Ghrelin and des-acyl ghrelin facilitated the proliferation of cultured fetal (ED17, 19), but not neonatal (ND2), skin cells. On the other hand, with regard to cells from the spinal cord and hypothalamus, the proliferative effect of ghrelin continuedmore » after birth, whereas the effect of des-acyl ghrelin on neurogenesis in these tissues was lost at the ED19 fetal and ND2 neonatal stages. Immunohistochemistry revealed that the cells in the hypothalamus induced to proliferate by ghrelin at the ND2 stage were positive for nestin and glial fibrillary acidic protein. These results suggest that in the period immediately prior to, and after birth, rat fetal cells showing proliferation in response to ghrelin and des-acyl ghrelin are at a transitional stage characterized by alteration of the expression of GHS-R1a and an undefined des-acyl ghrelin receptor, their responsiveness varying among different tissues.« less

Effect of skull flexural properties on brain response during dynamic head loading - biomed 2013.

PubMed

Harrigan, T P; Roberts, J C; Ward, E E; Carneal, C M; Merkle, A C

2013-01-01

The skull-brain complex is typically modeled as an integrated structure, similar to a fluid-filled shell. Under dynamic loads, the interaction of the skull and the underlying brain, cerebrospinal fluid, and other tissue produces the pressure and strain histories that are the basis for many theories meant to describe the genesis of traumatic brain injury. In addition, local bone strains are of interest for predicting skull fracture in blunt trauma. However, the role of skull flexure in the intracranial pressure response to blunt trauma is complex. Since the relative time scales for pressure and flexural wave transmission across the skull are not easily separated, it is difficult to separate out the relative roles of the mechanical components in this system. This study uses a finite element model of the head, which is validated for pressure transmission to the brain, to assess the influence of skull table flexural stiffness on pressure in the brain and on strain within the skull. In a Human Head Finite Element Model, the skull component was modified by attaching shell elements to the inner and outer surfaces of the existing solid elements that modeled the skull. The shell elements were given the properties of bone, and the existing solid elements were decreased so that the overall stiffness along the surface of the skull was unchanged, but the skull table bending stiffness increased by a factor of 2.4. Blunt impact loads were applied to the frontal bone centrally, using LS-Dyna. The intracranial pressure predictions and the strain predictions in the skull were compared for models with and without surface shell elements, showing that the pressures in the mid-anterior and mid-posterior of the brain were very similar, but the strains in the skull under the loads and adjacent to the loads were decreased 15% with stiffer flexural properties. Pressure equilibration to nearly hydrostatic distributions occurred, indicating that the important frequency components for typical impact loading are lower than frequencies based on pressure wave propagation across the skull. This indicates that skull flexure has a local effect on intracranial pressures but that the integrated effect of a dome-like structure under load is a significant part of load transfer in the skull in blunt trauma.

[A case of fat embolism syndrome associated with pathological femoral fracture caused by metastatic adenocarcinoma of the lung].

PubMed

Sato, Takashi; Soejima, Kenzo; Nakayama, Sohei; Satomi, Ryosuke; Sayama, Koichi; Asano, Koichiro

2010-10-01

A 76-year-old woman with multiple bone metastases from lung adenocarcinoma was admitted due to a pathological femoral fracture. On the night after admission, her consciousness deteriorated rapidly and she developed progressive respiratory failure. Computed tomography of the chest revealed diffuse ground glass opacities in both lungs, and magnetic resonance imaging of the brain showed multiple acute infarctions. Her condition improved after several days of supportive treatment with oxygen, corticosteroids and diuretics. Fat embolism syndrome should be considered as a differential diagnosis if consciousness disturbance and respiratory failure occur in patients with metastatic bone carcinoma and pathological long bone fractures.

Group B Strep Infection

MedlinePlus

... tract, lungs, bones and joints, heart valve (called endocarditis), or the fluid around the brain and spinal ... Family Health, Infants and Toddlers, WomenTags: arthritis, caregiving, endocarditis, group B, infection, maternal-fetal, maternity, postpartum, sepsis, ...

Exposure to urban air pollution and bone health in clinically healthy six-year-old children.

PubMed

Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Francolira, Maricela; Torres-Jardón, Ricardo; Peña-Cruz, Bernardo; Palacios-López, Carolina; Zhu, Hongtu; Kong, Linglong; Mendoza-Mendoza, Nicolás; Montesinoscorrea, Hortencia; Romero, Lina; Valencia-Salazar, Gildardo; Kavanaugh, Michael; Frenk, Silvestre

2013-01-01

Air pollution induces systemic inflammation, as well as respiratory, myocardial and brain inflammation in children. Peak bone mass is influenced by environmental factors. We tested the hypothesis that six-year-olds with lifetime exposures to urban air pollution will have alterations in inflammatory markers and bone mineral density (BMD) as opposed to low-polluted city residents when matched for BMI, breast feeding history, skin phototype, age, sex and socioeconomic status. This pilot study included 20 children from Mexico City (MC) (6.17 years ± 0.63 years) and 15 controls (6.27 years ± 0.76 years). We performed full paediatric examinations, a history of outdoor exposures, seven-day dietary recalls, serum inflammatory markers and dual-energy X-ray absorptiometry (DXA). Children in MC had significantly higher concentrations of IL-6 (p=0.001), marked reductions in total blood neutrophils (p= 0.0002) and an increase in monocytes (p=0.005). MC children also had an insufficient Vitamin D intake and spent less time outdoors than controls (p<0.001) in an environment characterized by decreased UV light, with ozone and fine particulates concentrations above standard values. There were no significant differences between the cohorts in DXA Z scores. The impact of systemic inflammation, vitamin D insufficiency, air pollution, urban violence and poverty may have long-term bone detrimental outcomes in exposed paediatric populations as they grow older, increasing the risk of low bone mass and osteoporosis. The selection of reference populations for DXA must take into account air pollution exposures.

Indications for cellular migration from the central nervous system to its draining lymph nodes in CD11c-GFP+ bone-marrow chimeras following EAE.

PubMed

Schiefenhövel, Fridtjof; Immig, Kerstin; Prodinger, Carolin; Bechmann, Ingo

2017-07-01

The concept as to how the brain maintains its immune privilege has initially been based on observations that it is lacking classical lymph vessels and later, the absence of dendritic cells (DC). This view has been challenged by several groups demonstrating drainage/migration of injected tracers and cells into cervical lymph nodes (CLNs) and the presence of brain antigens in CLNs in the course of various brain pathologies. Using CD11c-diphtheria toxin receptor (DTR)-green fluorescent protein (GFP) transgenic (tg) mice, we have shown the existence of CD11c + cells, a main DC marker, within the brain parenchyma. Since injecting tracers or cells may cause barrier artefacts, we have now transplanted wild type (wt)-bone marrow (BM) to lethally irradiated CD11c-DTR-GFP tg mice to restrict the CD11c-DTR-GFP + population to the brain and induced experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). We observed ramified GFP + cells in the olfactory bulb, the cribriform plate, the nasal mucosa and superficial CLNs. We measured a significant increase of host gfp genomic DNA (gDNA) levels in lymph nodes (LNs) previously described as draining stations for the central nervous system (CNS). Using flow cytometry analysis, we observed an increase of the percentage of CD11c-GFP + cells in brain parenchyma in the course of EAE which is most likely due to an up-regulation of CD11c of resident microglial cells since levels of gfp gDNA did not increase. Our data supports the hypothesis that brain-resident antigen presenting cells (APC) are capable of migrating to CNS-draining LNs to present myelin-associated epitopes.

Adult hippocampus derived soluble factors induce a neuronal-like phenotype in mesenchymal stem cells.

PubMed

Rivera, Francisco J; Sierralta, Walter D; Minguell, Jose J; Aigner, Ludwig

2006-10-02

Bone marrow-derived mesenchymal stem cells (MSCs) are not restricted in their differentiation fate to cells of the mesenchymal lineage. They acquire a neural phenotype in vitro and in vivo after transplantation in the central nervous system. Here we investigated whether soluble factors derived from different brain regions are sufficient to induce a neuronal phenotype in MSCs. We incubated bone marrow-derived MSCs in conditioned medium (CM) derived from adult hippocampus (HCM), cortex (CoCM) or cerebellum (CeCM) and analyzed the cellular morphology and the expression of neuronal and glial markers. In contrast to muscle derived conditioned medium, which served as control, conditioned medium derived from the different brain regions induced a neuronal morphology and the expression of the neuronal markers GAP-43 and neurofilaments in MSCs. Hippocampus derived conditioned medium had the strongest activity. It was independent of NGF or BDNF; and it was restricted to the neuronal differentiation fate, since no induction of the astroglial marker GFAP was observed. The work indicates that soluble factors present in the brain are sufficient to induce a neuronal phenotype in MSCs.

Advances in diagnosis and treatment of metastatic cervical cancer

PubMed Central

2016-01-01

Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases. PMID:27171673

Advances in diagnosis and treatment of metastatic cervical cancer.

PubMed

Li, Haoran; Wu, Xiaohua; Cheng, Xi

2016-07-01

Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases.

[Disorders of endocrine function after brain tumor therapy in childhood].

PubMed

Marx, M; Langer, T; Beck, J D; Dörr, H G

1999-07-01

Advances in the therapy of malignant brain tumors in children have led to a significant improvement in survival rates over the last few decades. As a result, the recognition and treatment of late effects have become more important. In addition to secondary tumors and deficiencies in cognitive and intellectual skills, the resulting endocrine disturbances play an important role. Own data and literature review. Deviations from the normal growth hormone secretion are usually recognized first and are most common, and have already been observed after conventional whole brain irradiation with 18 Gy. With some delay, other hypothalamo-pituitary deficiencies may occur, including panhypopituitarism. Puberty may come too early or too late or may not appear at all. Girls in particular, frequently experience an early and rapid pubertal development after brain tumor therapy, which may lead to further reduction in height due to an accelerated bone maturation. Functional disturbances of the thyroid and adrenal glands due to hypothalamic or pituitary deficiency are less common, and usually seen only after a radiation dose of over 40 Gy. Survivors of childhood brain tumors must be considered as long-term survivors, in whom the first therapy-induced long-term side effects appear almost immediately after the end of therapy. Maximum quality of life for the individual patient can only be achieved by long-term care and close cooperation of specialists in the different medical disciplines involved.

Beyond the functional matrix hypothesis: a network null model of human skull growth for the formation of bone articulations.

PubMed

Esteve-Altava, Borja; Rasskin-Gutman, Diego

2014-09-01

Craniofacial sutures and synchondroses form the boundaries among bones in the human skull, providing functional, developmental and evolutionary information. Bone articulations in the skull arise due to interactions between genetic regulatory mechanisms and epigenetic factors such as functional matrices (soft tissues and cranial cavities), which mediate bone growth. These matrices are largely acknowledged for their influence on shaping the bones of the skull; however, it is not fully understood to what extent functional matrices mediate the formation of bone articulations. Aiming to identify whether or not functional matrices are key developmental factors guiding the formation of bone articulations, we have built a network null model of the skull that simulates unconstrained bone growth. This null model predicts bone articulations that arise due to a process of bone growth that is uniform in rate, direction and timing. By comparing predicted articulations with the actual bone articulations of the human skull, we have identified which boundaries specifically need the presence of functional matrices for their formation. We show that functional matrices are necessary to connect facial bones, whereas an unconstrained bone growth is sufficient to connect non-facial bones. This finding challenges the role of the brain in the formation of boundaries between bones in the braincase without neglecting its effect on skull shape. Ultimately, our null model suggests where to look for modified developmental mechanisms promoting changes in bone growth patterns that could affect the development and evolution of the head skeleton. © 2014 Anatomical Society.

Spreading Depolarizations Have Prolonged Direct Current Shifts and Are Associated with Poor Outcome in Brain Trauma

DTIC Science & Technology

2011-01-01

prognosis. Keywords: cortical spreading depression; electroencephalography; craniotomy ; signal processing; acute brain injury Introduction Cortical...Mannheim, Germany). Inclusion criteria were the clinical decision for craniotomy for lesion evacuation and/or decompression and age ~ 18 years...externalized through a burr hole in the skull (if the bone flap was replaced) and tu nne lied beneath the scalp to exit 2-3 em from the craniotomy

Dry mouth during cancer treatment

MedlinePlus

... transplant Mastectomy Oral cancer Throat or larynx cancer Patient Instructions Abdominal radiation - discharge After chemotherapy - discharge Bleeding during cancer treatment Bone marrow transplant - discharge Brain radiation - discharge Breast radiation - discharge Chemotherapy - what to ask your doctor ...

Protocadherin-7 induces bone metastasis of breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Ai-Min; Tian, Ai-Xian; Zhang, Rui-Xue

2013-07-05

Highlights: •PCDH7 is overexpression in high bone metastatic MDA-MB-231 cells. •PCDH7 is up-regulation in bone metastatic breast cancer tissues. •Suppression of PCDH7 inhibits cell proliferation, migration, and invasion in vitro. •PCDH7 induces breast cancer bone metastasis in vivo. -- Abstract: Breast cancer had a propensity to metastasize to bone, resulting in serious skeletal complications associated with poor outcome. Previous study showed that Protocadherin-7 (PCDH7) play an important role in brain metastatic breast cancer, however, the role of PCDH7 in bone metastatic breast cancer has never been explored. In the present study, we found that PCDH7 expression was up-regulation in bonemore » metastatic breast cancer tissues by real-time PCR and immunohistochemistry assays. Furthermore, suppression of PCDH7 inhibits breast cancer cell proliferation, migration, and invasion in vitro by MTT, scratch, and transwell assays. Most importantly, overexpression of PCDH7 promotes breast cancer cell proliferation and invasion in vitro, and formation of bone metastasis in vivo. These data provide an important insight into the role of PCDH7 in bone metastasis of breast cancer.« less

Does wet hair in cold weather cause sinus headache and posterior eye pain? A possible mechanism through selective brain cooling system.

PubMed

Kaya, Abdullah; Calışkan, Halil

2012-12-01

As a general observation, wet hair in cold weather seems to be a predisposing factor for sinus headache and posterior eye pain. We offer a mechanism through selective brain cooling system for this observation. Selective brain cooling (SBC) is a mechanism to protect brain from hyperthermia. Components of SBC are head skin and upper respiratory tract (nose and paranasal sinuses). Cool venous blood from head skin and mucous membranes of nose and paranasal sinuses drains to intracranial dural sinuses and provide brain cooling. Brain will be cooled very much when head skin exposes to hypothermia such a condition like wet hair in cold weather. We suggest that, in order to reduce brain cooling activity, some alterations are being occurred within paranasal sinuses. For this purpose, sinus ostiums may close and mucus may accumulate to reduce air within sinuses. Also there may be some vasomotor changes to prevent heat loss. We hypothesize that this possible alterations may occur within paranasal sinuses as a control mechanism for brain temperature control during exposure of head skin to hypothermia. Paranasal sinuses may also cool brain directly by a very thin layer of bone separates the posterior ethmoid air sinus from the subarachnoid space and only thin plates of bone separate the sphenoidal sinuses from internal carotid artery and cavernous sinuses. Because of their critical role in the SBC, posterior ethmoid air sinus and sphenoidal sinuses may be affected from this alterations more than other paranasal sinuses. This situation may cause posterior eye pain. This mechanism can explain why a person who expose to hypothermia with wet hair or a person who don't use a beret or a hat during cold weather gets sinus headache and posterior eye pain. These symptoms could lead to an incorrect diagnosis of sinusitis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Muscle metastasis from non-small cell lung cancer: two cases and literature review.

PubMed

Tezcan, Y; Koc, M

2014-08-01

Non-small cell lung cancers (NSCLC) is the most commonly observed group among lung cancers. Adenocancers are histopathologically more common. Males are more affected than females, an effect which is directly related to smoking. They generally cause distant haematogenous and lymphatic metastasis. Distant haematogenous metastases are often seen in contralateral lung, brain, bone, adrenals, and liver. Muscle metastases from NSCLC are quite rare and male cases are more frequently affected compared to female cases. NSCLC cases with muscle metastasis are at the same time accompanied by distant organ metastases such as bone, brain, and liver. All treatment approaches are considered to be palliative in these cases, which are symptomatologically quite severe. In the present study, we presented the rarely observed cases of two male patients with muscle metastasis from NSCLC together with the related literature.

Characterizing and Targeting Bone Marrow-Derived Inflammatory Cells in Driving the Malignancy and Progression of Childhood Astrocytic Brain Tumors

DTIC Science & Technology

2016-11-01

importance of myeloid derived ID2/VEGFR2 signaling in low-grade to high-grade glioma transformation . 15. SUBJECT TERMS Glioma, Pediatric, bone-marrow...derived-cells, endothelial, mesenchymal, myeloid, hematopoietic, differentiation, malignant, transformation , VEGFR2, ID2. 16. SECURITY CLASSIFICATION OF...subsequent recruitment, in order to suppress the malignant transformation of gliomas. In this project, we have initiated the study of BMDCs with RCAS and

In vivo imaging models of bone and brain metastases and pleural carcinomatosis with a novel human EML4-ALK lung cancer cell line.

PubMed

Nanjo, Shigeki; Nakagawa, Takayuki; Takeuchi, Shinji; Kita, Kenji; Fukuda, Koji; Nakada, Mitsutoshi; Uehara, Hisanori; Nishihara, Hiroshi; Hara, Eiji; Uramoto, Hidetaka; Tanaka, Fumihiro; Yano, Seiji

2015-03-01

EML4-ALK lung cancer accounts for approximately 3-7% of non-small-cell lung cancer cases. To investigate the molecular mechanism underlying tumor progression and targeted drug sensitivity/resistance in EML4-ALK lung cancer, clinically relevant animal models are indispensable. In this study, we found that the lung adenocarcinoma cell line A925L expresses an EML4-ALK gene fusion (variant 5a, E2:A20) and is sensitive to the ALK inhibitors crizotinib and alectinib. We further established highly tumorigenic A925LPE3 cells, which also have the EML4-ALK gene fusion (variant 5a) and are sensitive to ALK inhibitors. By using A925LPE3 cells with luciferase gene transfection, we established in vivo imaging models for pleural carcinomatosis, bone metastasis, and brain metastasis, all of which are significant clinical concerns of advanced EML4-ALK lung cancer. Interestingly, crizotinib caused tumors to shrink in the pleural carcinomatosis model, but not in bone and brain metastasis models, whereas alectinib showed remarkable efficacy in all three models, indicative of the clinical efficacy of these ALK inhibitors. Our in vivo imaging models of multiple organ sites may provide useful resources to analyze further the pathogenesis of EML4-ALK lung cancer and its response and resistance to ALK inhibitors in various organ microenvironments. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Human Muse Cells Reconstruct Neuronal Circuitry in Subacute Lacunar Stroke Model.

PubMed

Uchida, Hiroki; Niizuma, Kuniyasu; Kushida, Yoshihiro; Wakao, Shohei; Tominaga, Teiji; Borlongan, Cesario V; Dezawa, Mari

2017-02-01

Multilineage-differentiating stress-enduring (muse) cells are endogenous nontumorigenic stem cells with pluripotency harvestable as pluripotent marker SSEA-3 + cells from the bone marrow from cultured bone marrow-mesenchymal stem cells. After transplantation into neurological disease models, muse cells exert repair effects, but the exact mechanism remains inconclusive. We conducted mechanism-based experiments by transplanting serum/xeno-free cultured-human bone marrow-muse cells into the perilesion brain at 2 weeks after lacunar infarction in immunodeficient mice. Approximately 28% of initially transplanted muse cells remained in the host brain at 8 weeks, spontaneously differentiated into cells expressing NeuN (≈62%), MAP2 (≈30%), and GST-pi (≈12%). Dextran tracing revealed connections between host neurons and muse cells at the lesioned motor cortex and the anterior horn. Muse cells extended neurites through the ipsilateral pyramidal tract, crossed to contralateral side, and reached to the pyramidal tract in the dorsal funiculus of spinal cord. Muse-transplanted stroke mice displayed significant recovery in cylinder tests, which was reverted by the human-selective diphtheria toxin. At 10 months post-transplantation, human-specific Alu sequence was detected only in the brain but not in other organs, with no evidence of tumor formation. Transplantation at the delayed subacute phase showed muse cells differentiated into neural cells, facilitated neural reconstruction, improved functions, and displayed solid safety outcomes over prolonged graft maturation period, indicating their therapeutic potential for lacunar stroke. © 2016 The Authors.

A testbed for optimizing electrodes embedded in the skull or in artificial skull replacement pieces used after injury

PubMed Central

Jiang, JingLe; Marathe, Amar R.; Keene, Jennifer C.; Taylor, Dawn M.

2016-01-01

Background Custom-fitted skull replacement pieces are often used after a head injury or surgery to replace damaged bone. Chronic brain recordings are beneficial after injury/surgery for monitoring brain health and seizure development. Embedding electrodes directly in these artificial skull replacement pieces would be a novel, low-risk way to perform chronic brain monitoring in these patients. Similarly, embedding electrodes directly in healthy skull would be a viable minimally-invasive option for many other neuroscience and neurotechnology applications requiring chronic brain recordings. New Method We demonstrate a preclinical testbed that can be used for refining electrode designs embedded in artificial skull replacement pieces or for embedding directly into the skull itself. Options are explored to increase the surface area of the contacts without increasing recording contact diameter to maximize recording resolution. Results Embedding electrodes in real or artificial skull allows one to lower electrode impedance without increasing the recording contact diameter by making use of conductive channels that extend into the skull. The higher density of small contacts embedded in the artificial skull in this testbed enables one to optimize electrode spacing for use in real bone. Comparison with Existing Methods For brain monitoring applications, skull-embedded electrodes fill a gap between electroencephalograms recorded on the scalp surface and the more invasive epidural or subdural electrode sheets. Conclusions Embedding electrodes into the skull or in skull replacement pieces may provide a safe, convenient, minimally-invasive alternative for chronic brain monitoring. The manufacturing methods described here will facilitate further testing of skull-embedded electrodes in animal models. PMID:27979758

A testbed for optimizing electrodes embedded in the skull or in artificial skull replacement pieces used after injury.

PubMed

Jiang, JingLe; Marathe, Amar R; Keene, Jennifer C; Taylor, Dawn M

2017-02-01

Custom-fitted skull replacement pieces are often used after a head injury or surgery to replace damaged bone. Chronic brain recordings are beneficial after injury/surgery for monitoring brain health and seizure development. Embedding electrodes directly in these artificial skull replacement pieces would be a novel, low-risk way to perform chronic brain monitoring in these patients. Similarly, embedding electrodes directly in healthy skull would be a viable minimally-invasive option for many other neuroscience and neurotechnology applications requiring chronic brain recordings. We demonstrate a preclinical testbed that can be used for refining electrode designs embedded in artificial skull replacement pieces or for embedding directly into the skull itself. Options are explored to increase the surface area of the contacts without increasing recording contact diameter to maximize recording resolution. Embedding electrodes in real or artificial skull allows one to lower electrode impedance without increasing the recording contact diameter by making use of conductive channels that extend into the skull. The higher density of small contacts embedded in the artificial skull in this testbed enables one to optimize electrode spacing for use in real bone. For brain monitoring applications, skull-embedded electrodes fill a gap between electroencephalograms recorded on the scalp surface and the more invasive epidural or subdural electrode sheets. Embedding electrodes into the skull or in skull replacement pieces may provide a safe, convenient, minimally-invasive alternative for chronic brain monitoring. The manufacturing methods described here will facilitate further testing of skull-embedded electrodes in animal models. Published by Elsevier B.V.

Erythropoietin as a novel brain and kidney protective agent.

PubMed

Moore, E M; Bellomo, R; Nichol, A D

2011-05-01

Erythropoietin is a 30.4 kDa glycoprotein produced by the kidney, which is mostly known for its physiological function in regulating red blood cell production in the bone marrow Accumulating evidence, however suggests that erythropoietin has additional organ protective effects, which may specifically be useful in protecting the brain and kidneys from injury. Experimental evidence suggests that these protective mechanisms are multi-factorial in nature and may include inhibition of apoptotic cell death, stimulation of cellular regeneration, inhibition of deleterious pathways and promotion of recovery. In this article we review the physiology of erythropoietin, assess previous work that supports the role of erythropoietin as a general tissue protective agent and explain the mechanisms by which it may achieve this tissue protective effect. We then focus on specific laboratory and clinical data that suggest that erythropoietin has a strong brain protective and kidney protective effect. In addition, we comment on the implications of these studies for clinicians at the bedside and for researchers designing controlled trials to further elucidate the true clinical utility of erythropoietin as a neuroprotective and nephroprotective agent. Finally, we describe EPO-TBI, a double-blinded multi-centre randomised controlled trial involving the authors that is being conducted to investigate the organ protective effects of erythropoietin on the brain, and also assesses its effect on the kidneys.

The measurement of intracranial pressure and brain displacement due to short-duration dynamic overpressure loading

NASA Astrophysics Data System (ADS)

Iwaskiw, A. S.; Ott, K. A.; Armiger, R. S.; Wickwire, A. C.; Alphonse, V. D.; Voo, L. M.; Carneal, C. M.; Merkle, A. C.

2018-01-01

The experimental measurement of biomechanical responses that correlate with blast-induced traumatic brain injury (bTBI) has proven challenging. These data are critical for both the development and validation of computational and physical head models, which are used to quantify the biomechanical response to blast as well as to assess fidelity of injury mitigation strategies, such as personal protective equipment. Therefore, foundational postmortem human surrogate (PMHS) experimental data capturing the biomechanical response are necessary for human model development. Prior studies have measured short-duration pressure transmission to the brain (Kinetic phase), but have failed to reproduce and measure the longer-duration inertial loading that can occur (Kinematic phase). Four fully instrumented PMHS were subjected to short-duration dynamic overpressure in front-facing and rear-facing orientations, where intracranial pressure (ICP), global head kinematics, and brain motion (as measured by high-speed X-ray) with respect to the skull were recorded. Peak ICP results generally increased with increased dose, and a mirrored pressure response was seen when comparing the polarity of frontal bone versus occipital bone ICP sensors. The head kinematics were delayed when compared to the pressure response and showed higher peak angles for front-facing tests as compared to rear-facing. Brain displacements were approximately 2-6 mm, and magnitudes did not change appreciably between front- and rear-facing tests. These data will be used to inform and validate models used to assess bTBI.

Syrinx of the Spinal Cord and Brain Stem

MedlinePlus

... View The Professional Version For doctors and medical students Consumer Version Merck Manual Consumer Version × MERCK MANUAL - ... View The Professional Version For doctors and medical students Home Medical Topics Blood Disorders Bone, Joint, and ...

Cochlear hearing loss in patients with Laron syndrome.

PubMed

Attias, Joseph; Zarchi, Omer; Nageris, Ben I; Laron, Zvi

2012-02-01

The aim of this prospective clinical study was to test auditory function in patients with Laron syndrome, either untreated or treated with insulin-like growth factor I (IGF-I). The study group consisted of 11 patients with Laron syndrome: 5 untreated adults, 5 children and young adults treated with replacement IGF-I starting at bone age <2 years, and 1 adolescent who started replacement therapy at bone age 4.6 years. The auditory evaluation included pure tone and speech audiometry, tympanometry and acoustic reflexes, otoacoustic emissions, loudness dynamics, auditory brain stem responses and a hyperacusis questionnaire. All untreated patients and the patient who started treatment late had various degrees of sensorineural hearing loss and auditory hypersensitivity; acoustic middle ear reflexes were absent in most of them. All treated children had normal hearing and no auditory hypersensitivity; most had recordable middle ear acoustic reflexes. In conclusion, auditory defects seem to be associated with Laron syndrome and may be prevented by starting treatment with IGF-I at an early developmental age.

Bone marrow-CNS connections: Implications in the pathogenesis of diabetic retinopathy

PubMed Central

Douglas, Yellowlees; Bhatwadekar, Ashay D.; Shaw, Lynn C.; Carnegie, Debra; Caballero, Sergio; Li, Quihong; Calzi, Sergio Li; Raizada, Mohan K.; Stitt, Alan W.; Grant, Maria B.

2013-01-01

Diabetic retinopathy is the fourth most common cause of blindness in adults. Current therapies, including anti-VEGF therapy, have partial efficacy in arresting the progression of proliferative diabetic retinopathy and diabetic macular edema. This review provides an overview of a novel, innovative approach to viewing diabetic retinopathy as the result of an inflammatory cycle that affects the bone marrow (BM) and the central and sympathetic nervous systems. Diabetes associated inflammation may be the result of BM neuropathy which skews haematopoiesis towards generation of increased inflammatory cells but also reduced production of endothelial progenitor cells responsible for maintaining healthy endothelial function and renewal. The resulting systemic inflammation further impacts the hypothalamus, promoting insulin resistance and diabetes, and initiates an inflammatory cascade that adversely impacts both macrovascular and microvascular complications, including diabetic retinopathy (DR). This review examines the idea of using anti-inflammatory agents that cross not only the blood-retinal barrier to enter the retina but also have the capability to target the central nervous system and cross the blood-brain barrier to reduce neuroinflammation. This neuroinflammation in key sympathetic centers serves to not only perpetuate BM pathology but promote insulin resistance which is characteristic of type 2 diabetic patients (T2D) but is also seen in T1D. A case series of morbidly obese T2D patients with retinopathy and neuropathy treated with minocycline, a well-tolerated antibiotic that crosses both the blood-retina and blood-brain barrier is presented. Our results indicates that minocycine shows promise for improving visual acuity, reducing pain from peripheral neuropathy, promoting weight loss and improving blood pressure control and we postulate that these observed beneficial effects are due to a reduction of chronic inflammation. PMID:22609081

TU-AB-204-03: Advances in CBCT for Orhtopaedics and Bone Health Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zbijewski, W.

This symposium highlights advanced cone-beam CT (CBCT) technologies in four areas of emerging application in diagnostic imaging and image-guided interventions. Each area includes research that extends the spatial, temporal, and/or contrast resolution characteristics of CBCT beyond conventional limits through advances in scanner technology, acquisition protocols, and 3D image reconstruction techniques. Dr. G. Chen (University of Wisconsin) will present on the topic: Advances in C-arm CBCT for Brain Perfusion Imaging. Stroke is a leading cause of death and disability, and a fraction of people having an acute ischemic stroke are suitable candidates for endovascular therapy. Critical factors that affect both themore » likelihood of successful revascularization and good clinical outcome are: 1) the time between stroke onset and revascularization; and 2) the ability to distinguish patients who have a small volume of irreversibly injured brain (ischemic core) and a large volume of ischemic but salvageable brain (penumbra) from patients with a large ischemic core and little or no penumbra. Therefore, “time is brain” in the care of the stroke patients. C-arm CBCT systems widely available in angiography suites have the potential to generate non-contrast-enhanced CBCT images to exclude the presence of hemorrhage, time-resolved CBCT angiography to evaluate the site of occlusion and collaterals, and CBCT perfusion parametric images to assess the extent of the ischemic core and penumbra, thereby fulfilling the imaging requirements of a “one-stop-shop” in the angiography suite to reduce the time between onset and revascularization therapy. The challenges and opportunities to advance CBCT technology to fully enable the one-stop-shop C-arm CBCT platform for brain imaging will be discussed. Dr. R. Fahrig (Stanford University) will present on the topic: Advances in C-arm CBCT for Cardiac Interventions. With the goal of providing functional information during cardiac interventions, significant effort has been expended to improve the quantitative accuracy of C-arm CBCT reconstructions. The challenge is to improve image quality while providing very short turnaround between data acquisition and volume data visualization. Corrections for x-ray scatter, view aliasing and patient motion that require no more than 2 iterations keep processing time short while reducing artifact. Fast, multi-sweep acquisitions can be used to permit assessment of left ventricular function, and visualization of radiofrequency lesions created to treat arrhythmias. Workflows for each imaging goal have been developed and validated against gold standard clinical CT or histology. The challenges, opportunities, and limitations of the new functional C-arm CBCT imaging techniques will be discussed. Dr. W. Zbijewski (Johns Hopkins University) will present on the topic: Advances in CBCT for Orthopaedics and Bone Health Imaging. Cone-beam CT is particularly well suited for imaging of musculoskeletal extremities. Owing to the high spatial resolution of flat-panel detectors, CBCT can surpass conventional CT in imaging tasks involving bone visualization, quantitative analysis of subchondral trabecular structure, and visualization and monitoring of subtle fractures that are common in orthopedic radiology. A dedicated CBCT platform has been developed that offers flexibility in system design and provides not only a compact configuration with improved logistics for extremities imaging but also enables novel diagnostic capabilities such as imaging of weight-bearing lower extremities in a natural stance. The design, development and clinical performance of dedicated extremities CBCT systems will be presented. Advanced capabilities for quantitative volumetric assessment of joint space morphology, dual-energy image-based quantification of bone composition, and in-vivo analysis of bone microarchitecture will be discussed, along with emerging applications in the diagnosis of arthritis and osteoporosis and assessment of novel therapies. Finally, Dr. J. Boone (UC Davis) will present on the topic: Advances in CBCT for Breast Imaging. Breast CT has been studied as an imaging tool for diagnostic breast evaluation and for potential breast cancer screening. The breast CT application lends itself to CBCT because of the small dimensions of the breast, the tapered shape of the breast towards higher cone angle, and the fact that there are no bones in the breast. The performance of various generations of breast CT scanners developed in recent years will be discussed, focusing on advances in spatial resolution and image noise characteristics. The results will also demonstrate the results of clinical trials using both computer and human observers. Learning Objectives: Understand the challenges, key technological advances, and emerging opportunities of CBCT in: Brain perfusion imaging, including assessment of ischemic stroke Cardiac imaging for functional assessment in cardiac interventions Orthopedics imaging for evaluation of musculoskeletal trauma, arthritis, and osteoporosis Breast imaging for screening and diagnosis of breast cancer. Work presented in this symposium includes research support by: Siemens Healthcare (Dr. Chen); NIH and Siemens Healthcare (Dr. Fahrig); NIH and Carestream Health (Dr. Zbijewski); and NIH (Dr. Boone)« less

[Traumatic intracerebral pneumocephalus communicating with two different paranasal sinuses: a case report].

PubMed

Wakamoto, H; Miyazaki, H; Hayashi, T; Shimamoto, Y; Ishiyama, N

1998-02-01

We report a case of a 17-year-old male who had hit the front of his head in a traffic accident. CT scan revealed contusional hemorrhage and pneumocephalus of the left frontal lobe 10 hours after the accident. A month later he complained of rhinorrhea and CT scan revealed intracerebral pneumocephalus. One day he complained of headache and began to vomit after he sneezed. CT scan revealed that the pneumocephalus had become worse and air had spread throughout the subarachnoid space. Bone CT scan revealed the air communicated from the frontal sinus to the intracerebral air cavity. 3D-CT scan revealed bone defect in the roof of the ethmoid sinus. The intraoperative findings revealed that the intracerebral air cavity communicated with the frontal sinus and ethmoid sinus. Though the brain which dropped into the paranasal sinus, adhered to the dura mater around the bone defect, a part of the brain had come off from the dura mater around the frontal sinus. We suspected that the intracerebral air cavity communicated with the frontal sinus initially. When the air cavity communicated with the ethmoid sinus secondarily, intracranial pressure abated and air came into the subarachnoid space from the frontal sinus.

Hyperostotic Esthesioneuroblastoma: Rare Variant and Fibrous Dysplasia Mimicker

PubMed Central

Knott, Phillip Daniel

2014-01-01

A 65-year-old male presented with a 3-year history of orbital symptoms. An imaging-based diagnosis of fibrous dysplasia involving the skull base was made at another institution. CT showed a diffuse sinonasal mass and ground-glass appearance of the bones of the anterior skull base with bony defects and mucocele formation. MRI demonstrated an accompanying intracranial and orbital rind of soft tissue mass along the hyperostotic bones. FDG-PET showed corresponding intense hypermetabolism. Small cysts were observed at the tumor-brain interface. Biopsy revealed esthesioneuroblastoma with bone infiltration that is compatible with the hyperostotic variant of esthesioneuroblastoma. There are a few cases of hyperostotic esthesioneuroblastoma reported in the literature. PMID:24497807

Noninvasive Blood-Brain Barrier Opening in Live Mice

NASA Astrophysics Data System (ADS)

Choi, James J.; Pernot, Mathieu; Small, Scott; Konofagou, Elisa E.

2006-05-01

Most therapeutic agents cannot be delivered to the brain because of brain's natural defense: the Blood-Brain Barrier (BBB). It has recently been shown that Focused Ultrasound (FUS) can produce reversible and localized BBB opening in the brain when applied in the presence of ultrasound contrast agents post-craniotomy in rabbits [1]. However, a major limitation of ultrasound in the brain is the strong phase aberration and attenuation of the skull bone, and, as a result, no study of trans-cranial ultrasound-targeted drug treatment in the brain in vivo has been reported as of yet. In this study, the feasibility of BBB opening in the hippocampus of wildtype mice using FUS through the intact skull and skin was investigated. In order to investigate the effect of the skull, simulations of ultrasound wave propagation (1.5 MHz) through the skull using μCT data, and needle hydrophone measurements through an ex-vivo skull were made. The pressure field showed minimal attenuation (18% of the pressure amplitude) and a well-focused pattern through the left and right halves of the parietal bone. In experiments in vivo, the brains of four mice were sonicated through intact skull and skin. Ultrasound sonications (burst length: 20 ms; duty cycle: 20%; acoustic pressure range: 2.0 to 2.7 MPa) was applied 5 times for 30 s per shot with a 30 s delay between shots. Prior to sonication, ultrasound contrast agents (Optison; 10 μL) were injected intravenously. Contrast material enhanced high resolution MR Imaging (9.4 Tesla) was able to distinguish opening of large vessels in the region of the hippocampus. These results demonstrate the feasibility of locally opening the BBB in the mouse hippocampus using focused ultrasound through intact skull and skin. Future investigations will deal with optimization and reproducibility of the technique as well as application on Alzheimer's-model mice.

Posterior brain in fetuses with open spina bifida at 11 to 13 weeks.

PubMed

Lachmann, Robert; Chaoui, Rabih; Moratalla, Jose; Picciarelli, Gemma; Nicolaides, Kypros H

2011-01-01

To measure the changes in the posterior fossa in first-trimester fetuses with open spina bifida (OSB). The brain stem diameter and brain stem to occipital bone (BSOB) diameter were measured in stored images of the mid-sagittal view of the fetal face at 11(+0) to 13(+6) weeks from 30 fetuses with OSB and 1000 normal controls. In the control group, the brain stem and BSOB diameter increased significantly with crown-rump length (CRL) and the brain stem to BSOB ratio decreased. In the spina bifida group, the brain stem diameter was above the 95th percentile of the control group in 29 (96.7%) cases, the BSOB diameter was below the 5th percentile in 26 (86.7%) and the brain stem to BSOB ratio was above the 95th percentile in all cases. At 11 to 13 weeks the majority of fetuses with OSB have measurable abnormalities in the posterior brain.

Role of a Burr Hole and Calvarial Bone Marrow-Derived Stem Cells in the Ischemic Rat Brain: A Possible Mechanism for the Efficacy of Multiple Burr Hole Surgery in Moyamoya Disease.

PubMed

Nam, Taek-Kyun; Park, Seung-Won; Park, Yong-Sook; Kwon, Jeong-Taik; Min, Byung-Kook; Hwang, Sung-Nam

2015-09-01

This study investigates the role of a burr hole and calvarial bone marrow-derived stem cells (BMSCs) in a transient ischemic brain injury model in the rat and postulates a possible mechanism for the efficacy of multiple cranial burr hole (MCBH) surgery in moyamoya disease (MMD). Twenty Sprague-Dawley rats (250 g, male) were divided into four groups : normal control group (n=5), burr hole group (n=5), ischemia group (n=5), and ischemia+burr hole group (n=5). Focal ischemia was induced by the transient middle cerebral artery occlusion (MCAO). At one week after the ischemic injury, a 2 mm-sized cranial burr hole with small cortical incision was made on the ipsilateral (left) parietal area. Bromodeoxyuridine (BrdU, 50 mg/kg) was injected intraperitoneally, 2 times a day for 6 days after the burr hole trephination. At one week after the burr hole trephination, brains were harvested. Immunohistochemical stainings for BrdU, CD34, VEGF, and Doublecortin and Nestin were done. In the ischemia+burr hole group, BrdU (+), CD34 (+), and Doublecortin (+) cells were found in the cortical incision site below the burr hole. A number of cells with Nestin (+) or VEGF (+) were found in the cerebral parenchyma around the cortical incision site. In the other groups, BrdU (+), CD34 (+), Doublecortin (+), and Nestin (+) cells were not detected in the corresponding area. These findings suggest that BrdU (+) and CD34 (+) cells are bone marrow-derived stem cells, which may be derived from the calvarial bone marrow through the burr hole. The existence of CD34 (+) and VEGF (+) cells indicates increased angiogenesis, while the existence of Doublecortin (+), Nestin (+) cells indicates increased neurogenesis. Based on these findings, the BMSCs through burr holes seem to play an important role for the therapeutic effect of the MCBH surgery in MMD.

Fosfomycin i.v. for Treatment of Severely Infected Patients

ClinicalTrials.gov

2018-05-08

Bacterial Infections; Bone Diseases, Infectious; Osteomyelitis; Central Nervous System Bacterial Infections; Meningitis, Bacterial; Encephalitis; Brain Abscess; Urinary Tract Infections; Respiratory Tract Infections; Pneumonia, Bacterial; Skin Diseases, Bacterial; Soft Tissue Infections; Intraabdominal Infections; Sepsis; Bacteremia; Endocarditis, Bacterial

Genetics Home Reference: ataxia-pancytopenia syndrome

MedlinePlus

... brain that coordinates movement (the cerebellum ) and blood-forming cells in the bone marrow . The age when ... J, Gorcenco S, Rundberg Nilsson A, Ripperger T, Kokkonen H, Bryder D, Fioretos T, Henter JI, Möttönen M, ...

Aids to radiological differential diagnosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapman, S.; Nakielny, R.

This book is composed of lists of differential diagnoses divided into categories: bone, spine, joints, respiratory, cardio-vascular, abdomen, gastrointestinal, urinary tract, soft tissues, face and neck, and skull and brain. It does not contain any reproductions of radiographs.

Dimensional, Geometrical, and Physical Constraints in Skull Growth.

PubMed

Weickenmeier, Johannes; Fischer, Cedric; Carter, Dennis; Kuhl, Ellen; Goriely, Alain

2017-06-16

After birth, the skull grows and remodels in close synchrony with the brain to allow for an increase in intracranial volume. Increase in skull area is provided primarily by bone accretion at the sutures. Additional remodeling, to allow for a change in curvatures, occurs by resorption on the inner surface of the bone plates and accretion on their outer surfaces. When a suture fuses too early, normal skull growth is disrupted, leading to a deformed final skull shape. The leading theory assumes that the main stimulus for skull growth is provided by mechanical stresses. Based on these ideas, we first discuss the dimensional, geometrical, and kinematic synchrony between brain, skull, and suture growth. Second, we present two mechanical models for skull growth that account for growth at the sutures and explain the various observed dysmorphologies. These models demonstrate the particular role of physical and geometrical constraints taking place in skull growth.

Dimensional, Geometrical, and Physical Constraints in Skull Growth

NASA Astrophysics Data System (ADS)

Weickenmeier, Johannes; Fischer, Cedric; Carter, Dennis; Kuhl, Ellen; Goriely, Alain

2017-06-01

After birth, the skull grows and remodels in close synchrony with the brain to allow for an increase in intracranial volume. Increase in skull area is provided primarily by bone accretion at the sutures. Additional remodeling, to allow for a change in curvatures, occurs by resorption on the inner surface of the bone plates and accretion on their outer surfaces. When a suture fuses too early, normal skull growth is disrupted, leading to a deformed final skull shape. The leading theory assumes that the main stimulus for skull growth is provided by mechanical stresses. Based on these ideas, we first discuss the dimensional, geometrical, and kinematic synchrony between brain, skull, and suture growth. Second, we present two mechanical models for skull growth that account for growth at the sutures and explain the various observed dysmorphologies. These models demonstrate the particular role of physical and geometrical constraints taking place in skull growth.

TU-AB-204-01: Advances in C-Arm CBCT for Brain Perfusion Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, G.

This symposium highlights advanced cone-beam CT (CBCT) technologies in four areas of emerging application in diagnostic imaging and image-guided interventions. Each area includes research that extends the spatial, temporal, and/or contrast resolution characteristics of CBCT beyond conventional limits through advances in scanner technology, acquisition protocols, and 3D image reconstruction techniques. Dr. G. Chen (University of Wisconsin) will present on the topic: Advances in C-arm CBCT for Brain Perfusion Imaging. Stroke is a leading cause of death and disability, and a fraction of people having an acute ischemic stroke are suitable candidates for endovascular therapy. Critical factors that affect both themore » likelihood of successful revascularization and good clinical outcome are: 1) the time between stroke onset and revascularization; and 2) the ability to distinguish patients who have a small volume of irreversibly injured brain (ischemic core) and a large volume of ischemic but salvageable brain (penumbra) from patients with a large ischemic core and little or no penumbra. Therefore, “time is brain” in the care of the stroke patients. C-arm CBCT systems widely available in angiography suites have the potential to generate non-contrast-enhanced CBCT images to exclude the presence of hemorrhage, time-resolved CBCT angiography to evaluate the site of occlusion and collaterals, and CBCT perfusion parametric images to assess the extent of the ischemic core and penumbra, thereby fulfilling the imaging requirements of a “one-stop-shop” in the angiography suite to reduce the time between onset and revascularization therapy. The challenges and opportunities to advance CBCT technology to fully enable the one-stop-shop C-arm CBCT platform for brain imaging will be discussed. Dr. R. Fahrig (Stanford University) will present on the topic: Advances in C-arm CBCT for Cardiac Interventions. With the goal of providing functional information during cardiac interventions, significant effort has been expended to improve the quantitative accuracy of C-arm CBCT reconstructions. The challenge is to improve image quality while providing very short turnaround between data acquisition and volume data visualization. Corrections for x-ray scatter, view aliasing and patient motion that require no more than 2 iterations keep processing time short while reducing artifact. Fast, multi-sweep acquisitions can be used to permit assessment of left ventricular function, and visualization of radiofrequency lesions created to treat arrhythmias. Workflows for each imaging goal have been developed and validated against gold standard clinical CT or histology. The challenges, opportunities, and limitations of the new functional C-arm CBCT imaging techniques will be discussed. Dr. W. Zbijewski (Johns Hopkins University) will present on the topic: Advances in CBCT for Orthopaedics and Bone Health Imaging. Cone-beam CT is particularly well suited for imaging of musculoskeletal extremities. Owing to the high spatial resolution of flat-panel detectors, CBCT can surpass conventional CT in imaging tasks involving bone visualization, quantitative analysis of subchondral trabecular structure, and visualization and monitoring of subtle fractures that are common in orthopedic radiology. A dedicated CBCT platform has been developed that offers flexibility in system design and provides not only a compact configuration with improved logistics for extremities imaging but also enables novel diagnostic capabilities such as imaging of weight-bearing lower extremities in a natural stance. The design, development and clinical performance of dedicated extremities CBCT systems will be presented. Advanced capabilities for quantitative volumetric assessment of joint space morphology, dual-energy image-based quantification of bone composition, and in-vivo analysis of bone microarchitecture will be discussed, along with emerging applications in the diagnosis of arthritis and osteoporosis and assessment of novel therapies. Finally, Dr. J. Boone (UC Davis) will present on the topic: Advances in CBCT for Breast Imaging. Breast CT has been studied as an imaging tool for diagnostic breast evaluation and for potential breast cancer screening. The breast CT application lends itself to CBCT because of the small dimensions of the breast, the tapered shape of the breast towards higher cone angle, and the fact that there are no bones in the breast. The performance of various generations of breast CT scanners developed in recent years will be discussed, focusing on advances in spatial resolution and image noise characteristics. The results will also demonstrate the results of clinical trials using both computer and human observers. Learning Objectives: Understand the challenges, key technological advances, and emerging opportunities of CBCT in: Brain perfusion imaging, including assessment of ischemic stroke Cardiac imaging for functional assessment in cardiac interventions Orthopedics imaging for evaluation of musculoskeletal trauma, arthritis, and osteoporosis Breast imaging for screening and diagnosis of breast cancer. Work presented in this symposium includes research support by: Siemens Healthcare (Dr. Chen); NIH and Siemens Healthcare (Dr. Fahrig); NIH and Carestream Health (Dr. Zbijewski); and NIH (Dr. Boone)« less

CT-based attenuation correction and resolution compensation for I-123 IMP brain SPECT normal database: a multicenter phantom study.

PubMed

Inui, Yoshitaka; Ichihara, Takashi; Uno, Masaki; Ishiguro, Masanobu; Ito, Kengo; Kato, Katsuhiko; Sakuma, Hajime; Okazawa, Hidehiko; Toyama, Hiroshi

2018-06-01

Statistical image analysis of brain SPECT images has improved diagnostic accuracy for brain disorders. However, the results of statistical analysis vary depending on the institution even when they use a common normal database (NDB), due to different intrinsic spatial resolutions or correction methods. The present study aimed to evaluate the correction of spatial resolution differences between equipment and examine the differences in skull bone attenuation to construct a common NDB for use in multicenter settings. The proposed acquisition and processing protocols were those routinely used at each participating center with additional triple energy window (TEW) scatter correction (SC) and computed tomography (CT) based attenuation correction (CTAC). A multicenter phantom study was conducted on six imaging systems in five centers, with either single photon emission computed tomography (SPECT) or SPECT/CT, and two brain phantoms. The gray/white matter I-123 activity ratio in the brain phantoms was 4, and they were enclosed in either an artificial adult male skull, 1300 Hounsfield units (HU), a female skull, 850 HU, or an acrylic cover. The cut-off frequency of the Butterworth filters was adjusted so that the spatial resolution was unified to a 17.9 mm full width at half maximum (FWHM), that of the lowest resolution system. The gray-to-white matter count ratios were measured from SPECT images and compared with the actual activity ratio. In addition, mean, standard deviation and coefficient of variation images were calculated after normalization and anatomical standardization to evaluate the variability of the NDB. The gray-to-white matter count ratio error without SC and attenuation correction (AC) was significantly larger for higher bone densities (p < 0.05). The count ratio error with TEW and CTAC was approximately 5% regardless of bone density. After adjustment of the spatial resolution in the SPECT images, the variability of the NDB decreased and was comparable to that of the NDB without correction. The proposed protocol showed potential for constructing an appropriate common NDB from SPECT images with SC, AC and spatial resolution compensation.

Role of CXCR4-mediated bone marrow colonization in CNS infiltration by T cell acute lymphoblastic leukemia.

PubMed

Jost, Tanja Rezzonico; Borga, Chiara; Radaelli, Enrico; Romagnani, Andrea; Perruzza, Lisa; Omodho, Lorna; Cazzaniga, Giovanni; Biondi, Andrea; Indraccolo, Stefano; Thelen, Marcus; Te Kronnie, Geertruy; Grassi, Fabio

2016-06-01

Infiltration of the central nervous system is a severe trait of T cell acute lymphoblastic leukemia. Inhibition of CXC chemokine receptor 4 significantly ameliorates T cell acute lymphoblastic leukemia in murine models of the disease; however, signaling by CXC chemokine receptor 4 is important in limiting the divagation of peripheral blood mononuclear cells out of the perivascular space into the central nervous system parenchyma. Therefore, Inhibition of CXC chemokine receptor 4 potentially may untangle T cell acute lymphoblastic leukemia cells from retention outside the brain. Here, we show that leukemic lymphoblasts massively infiltrate cranial bone marrow, with diffusion to the meninges without invasion of the brain parenchyma, in mice that underwent xenotransplantation with human T cell acute lymphoblastic leukemia cells or that developed leukemia from transformed hematopoietic progenitors. We tested the hypothesis that T cell acute lymphoblastic leukemia neuropathology results from meningeal infiltration through CXC chemokine receptor 4-mediated bone marrow colonization. Inhibition of leukemia engraftment in the bone marrow by pharmacologic CXC chemokine receptor 4 antagonism significantly ameliorated neuropathologic aspects of the disease. Genetic deletion of CXCR4 in murine hematopoietic progenitors abrogated leukemogenesis induced by constitutively active Notch1, whereas lack of CCR6 and CCR7, which have been shown to be involved in T cell and leukemia extravasation into the central nervous system, respectively, did not influence T cell acute lymphoblastic leukemia development. We hypothesize that lymphoblastic meningeal infiltration as a result of bone marrow colonization is responsible for the degenerative alterations of the neuroparenchyma as well as the alteration of cerebrospinal fluid drainage in T cell acute lymphoblastic leukemia xenografts. Therefore, CXC chemokine receptor 4 may constitute a pharmacologic target for T cell acute lymphoblastic leukemia neuropathology. © Society for Leukocyte Biology.

Prognostic impact of metastatic pattern in stage IV breast cancer at initial diagnosis.

PubMed

Leone, Bernardo Amadeo; Vallejo, Carlos Teodoro; Romero, Alberto Omar; Machiavelli, Mario Raúl; Pérez, Juan Eduardo; Leone, Julieta; Leone, José Pablo

2017-02-01

To analyze the prognostic influence of metastatic pattern (MP) compared with other biologic and clinical factors in stage IV breast cancer at initial diagnosis (BCID) and evaluate factors associated with specific sites of metastases (SSM). We evaluated women with stage IV BCID with known metastatic sites, reported to the Surveillance, Epidemiology and End Results program from 2010 to 2013. MP was categorized as bone-only, visceral, bone and visceral (BV), and other. Univariate and multivariate analyses determined the effects of each variable on overall survival (OS). Logistic regression examined factors associated with SSM. We included 9143 patients. Bone represented 37.5% of patients, visceral 21.9%, BV 28.8%, and other 11.9%. Median OS by MP was as follows: bone 38 months, visceral 21 months, BV 19 months, and other 33 months (P < 0.0001). Univariate analysis showed that higher number of metastatic sites had worse prognosis. In multivariate analysis, older age (hazard ratio 1.9), black race (hazard ratio 1.17), grade 3/4 tumors (hazard ratio 1.6), triple-negative (hazard ratio 2.24), BV MP (hazard ratio 2.07), and unmarried patients (hazard ratio 1.25) had significantly shorter OS. As compared with HR+/HER2- tumors, triple-negative and HR-/HER2+ had higher odds of brain, liver, lung, and other metastases. HR+/HER2+ had higher odds of liver metastases. All three subtypes had lower odds of bone metastases. There were substantial differences in OS according to MP. Tumor subtypes have a clear influence among other factors on SSM. We identified several prognostic factors that could guide therapy selection in treatment naïve patients.

Intravenous transplantation of allogeneic bone marrow mesenchymal stem cells and its directional migration to the necrotic femoral head.

PubMed

Li, Zhang-hua; Liao, Wen; Cui, Xi-long; Zhao, Qiang; Liu, Ming; Chen, You-hao; Liu, Tian-shu; Liu, Nong-le; Wang, Fang; Yi, Yang; Shao, Ning-sheng

2011-01-09

In this study, we investigated the feasibility and safety of intravenous transplantation of allogeneic bone marrow mesenchymal stem cells (MSCs) for femoral head repair, and observed the migration and distribution of MSCs in hosts. MSCs were labeled with green fluorescent protein (GFP) in vitro and injected into nude mice via vena caudalis, and the distribution of MSCs was dynamically monitored at 0, 6, 24, 48, 72 and 96 h after transplantation. Two weeks after the establishment of a rabbit model of femoral head necrosis, GFP labeled MSCs were injected into these rabbits via ear vein, immunological rejection and graft versus host disease were observed and necrotic and normal femoral heads, bone marrows, lungs, and livers were harvested at 2, 4 and 6 w after transplantation. The sections of these tissues were observed under fluorescent microscope. More than 70 % MSCs were successfully labeled with GFP at 72 h after labeling. MSCs were uniformly distributed in multiple organs and tissues including brain, lungs, heart, kidneys, intestine and bilateral hip joints of nude mice. In rabbits, at 6 w after intravenous transplantation, GFP labeled MSCs were noted in the lungs, liver, bone marrow and normal and necrotic femoral heads of rabbits, and the number of MSCs in bone marrow was higher than that in the, femoral head, liver and lungs. Furthermore, the number of MSCs peaked at 6 w after transplantation. Moreover, no immunological rejection and graft versus host disease were found after transplantation in rabbits. Our results revealed intravenously implanted MSCs could migrate into the femoral head of hosts, and especially migrate directionally and survive in the necrotic femoral heads. Thus, it is feasible and safe to treat femoral head necrosis by intravenous transplantation of allogeneic MSCs.

Human brains found in a fire-affected 4000-years old Bronze Age tumulus layer rich in soil alkalines and boron in Kutahya, Western Anatolia.

PubMed

Altinoz, M A; Ince, B; Sav, A; Dincer, A; Cengiz, S; Mercan, S; Yazici, Z; Bilgen, M N

2014-02-01

Undecomposed human bodies and organs always attracted interest in terms of understanding biological tissue stability and immortality. Amongst these, cases of natural mummification found in glaciers, bog sediments and deserts caused even more attention. In 2010, an archeological excavation of a Bronze Age layer in a tumulus near the Western Anatolia city Kütahya revealed fire affected regions with burnt human skeletons and charred wooden objects. Inside of the cracked skulls, undecomposed brains were discernible. To analyze the burial taphonomy of the rare phenomenon of brain preservation, we analyzed brains, bone, teeth and surrounding soils elements using Inductively Coupled Plasma-Mass Spectrometer (ICP-MS). Adipocere formation or saponification of postmortem tissue fat requires high levels of alkalinity and especially potassium. Indeed, ICP-MS analysis of the brain, teeth and bone and also of the surrounding soil revealed high levels of potassium, magnesium, aluminum and boron, which are compatible with the famous role of Kütahya in tile production with its soil containing high level of alkalines and tile-glazing boron. Fatty acid chromatography revealed simultaneous saturation of fats and protection of fragile unsaturated fatty acids consistent with soil-presence of both pro-oxidant and anti-oxidant trace metals. Computerized tomography revealed protection of diencephalic, metencephalic and occipital tissue in one of the best-preserved specimens. Boron was previously found as an intentional preservative of Tutankhamen and Deir el Bahari mummies. Here, in natural soil with its insect-repellant, anti-bacterial and fire-resistance qualities it may be a factor to preserve heat-affected brains as almost bioporcellain specimens. Copyright © 2013 Elsevier GmbH. All rights reserved.

Transcranial functional ultrasound imaging of the brain using microbubble-enhanced ultrasensitive Doppler

PubMed Central

Errico, Claudia; Osmanski, Bruno-Félix; Pezet, Sophie; Couture, Olivier; Lenkei, Zsolt; Tanter, Mickael

2016-01-01

Functional ultrasound (fUS) is a novel neuroimaging technique, based on high-sensitivity ultrafast Doppler imaging of cerebral blood volume, capable of measuring brain activation and connectivity in rodents with high spatiotemporal resolution (100 μm, 1 ms). However, the skull attenuates acoustic waves, so fUS in rats currently requires craniotomy or a thinned-skull window. Here we propose a non-invasive approach by enhancing the fUS signal with a contrast agent, inert gas microbubbles. Plane-wave illumination of the brain at high frame rate (500 Hz compounded sequence with three tilted plane waves, PRF = 1500Hz with a 128 element 15 MHz linear transducer), yields highly-resolved neurovascular maps. We compared fUS imaging performance through the intact skull bone (transcranial fUS) versus a thinned-skull window in the same animal. First, we show that the vascular network of the adult rat brain can be imaged transcranially only after a bolus intravenous injection of microbubbles, which leads to a 9 dB gain in the contrast-to-tissue ratio. Next, we demonstrate that functional increase in the blood volume of the primary sensory cortex after targeted electrical-evoked stimulations of the sciatic nerve is observable transcranially in presence of contrast agents, with high reproducibility (Pearson's coefficient ρ = 0.7 ± 0.1, p = 0.85). Our work demonstrates that the combination of ultrafast Doppler imaging and injection of contrast agent allows non-invasive functional brain imaging through the intact skull bone in rats. These results should ease non-invasive longitudinal studies in rodents and open a promising perspective for the adoption of highly resolved fUS approaches for the adult human brain. PMID:26416649

Low bone mineral density and fragility fractures in permanent vegetative state patients.

PubMed

Oppl, Bastian; Michitsch, Gabriele; Misof, Barbara; Kudlacek, Stefan; Donis, Johann; Klaushofer, Klaus; Zwerina, Jochen; Zwettler, Elisabeth

2014-01-01

Disuse of the musculoskeletal system causes bone loss. Whether patients in vegetative state, a dramatic example of immobilization after severe brain injury, suffer from bone loss and fractures is currently unknown. Serum markers of bone turnover, bone mineral density (BMD) measurements, and clinical data were cross-sectionally analyzed in 30 consecutive vegetative state patients of a dedicated apallic care unit between 2003 and 2007 and compared with age- and sex-matched healthy individuals. Vegetative state patients showed low calcium levels and vitamin D deficiency compared with healthy controls. Serum bone turnover markers revealed high turnover as evidenced by markedly elevated carboxy-terminal telopeptide of type I collagen (β-crosslaps) and increased levels of alkaline phosphatase. BMD measured by dual-energy X-ray absorptiometry (DXA) scanning showed strongly decreased T- and Z-scores for hip and spine. Over a period of 5 years, 8 fragility fractures occurred at peripheral sites in 6 of 30 patients (n = 3 femur, n = 2 tibia, n = 2 fibula, n = 1 humerus). In conclusion, high bone turnover and low BMD is highly prevalent in vegetative state patients, translating into a clinically relevant problem as shown by fragility fractures in 20% of patients over a time period of 5 years. . © 2014 American Society for Bone and Mineral Research.

Endothelial Activation and Blood-Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells.

PubMed

Gust, Juliane; Hay, Kevin A; Hanafi, Laïla-Aïcha; Li, Daniel; Myerson, David; Gonzalez-Cuyar, Luis F; Yeung, Cecilia; Liles, W Conrad; Wurfel, Mark; Lopez, Jose A; Chen, Junmei; Chung, Dominic; Harju-Baker, Susanna; Özpolat, Tahsin; Fink, Kathleen R; Riddell, Stanley R; Maloney, David G; Turtle, Cameron J

2017-12-01

Lymphodepletion chemotherapy followed by infusion of CD19-targeted chimeric antigen receptor-modified T (CAR-T) cells can be complicated by neurologic adverse events (AE) in patients with refractory B-cell malignancies. In 133 adults treated with CD19 CAR-T cells, we found that acute lymphoblastic leukemia, high CD19 + cells in bone marrow, high CAR-T cell dose, cytokine release syndrome, and preexisting neurologic comorbidities were associated with increased risk of neurologic AEs. Patients with severe neurotoxicity demonstrated evidence of endothelial activation, including disseminated intravascular coagulation, capillary leak, and increased blood-brain barrier (BBB) permeability. The permeable BBB failed to protect the cerebrospinal fluid from high concentrations of systemic cytokines, including IFNγ, which induced brain vascular pericyte stress and their secretion of endothelium-activating cytokines. Endothelial activation and multifocal vascular disruption were found in the brain of a patient with fatal neurotoxicity. Biomarkers of endothelial activation were higher before treatment in patients who subsequently developed grade ≥4 neurotoxicity. Significance: We provide a detailed clinical, radiologic, and pathologic characterization of neurotoxicity after CD19 CAR-T cells, and identify risk factors for neurotoxicity. We show endothelial dysfunction and increased BBB permeability in neurotoxicity and find that patients with evidence of endothelial activation before lymphodepletion may be at increased risk of neurotoxicity. Cancer Discov; 7(12); 1404-19. ©2017 AACR. See related commentary by Mackall and Miklos, p. 1371 This article is highlighted in the In This Issue feature, p. 1355 . ©2017 American Association for Cancer Research.

Imaging characteristics of hemophagocytic lymphohistiocytosis.

PubMed

Fitzgerald, Nancy E; MacClain, Kenneth L

2003-06-01

Hemophagocytic lymphohistiocytosis (HLH) is a nonmalignant disorder of immune regulation, with overproduction of cytokines and diminished immune surveillance. Symptoms are nonspecific and may affect multiple organs, including the central nervous system. Neuroimaging findings have been described in case reports and small series; body imaging findings have not been described extensively. OBJECTIVE. To summarize findings of the most frequently performed imaging studies of the brain, chest and abdomen in patients with HLH. Retrospective review of chest radiographs and CT, abdominal ultrasound and CT, brain CT and MRI, skeletal surveys, and autopsy data. Twenty-five patients were diagnosed and treated for HLH at our institution over an 11-year period; 15 patients (60%) died. Common chest radiograph findings included alveolar-interstitial opacities with pleural effusions, often with rapid evolution and resolution. Hepatosplenomegaly, gallbladder wall thickening, hyperechoic kidneys and ascites were common abdominal findings, which resolved after therapy in some cases. Brain-imaging studies revealed nonspecific periventricular white-matter abnormalities, brain-volume loss and enlargement of extra-axial fluid spaces. Three infant cases, one with intracranial hemorrhage, one with multiple pathologic rib fractures and one with diaphyseal periosteal reaction involving multiple long bones on skeletal survey, raised suspicion of child abuse at presentation. Abuse was not substantiated in any case. Clinicians and radiologists should be aware of the radiographic manifestations of HLH, which are nonspecific and overlap with infectious, inflammatory and neoplastic disorders. Findings in the chest (similar to acute respiratory distress syndrome) and abdomen may progress rapidly and then regress with institution of appropriate anti-HLH therapy. CNS findings may be progressive. In some infants, initial imaging findings may mimic nonaccidental trauma.

Bone up: craniomandibular development and hard-tissue biomineralization in neonate mice.

PubMed

Thompson, Khari D; Weiss-Bilka, Holly E; McGough, Elizabeth B; Ravosa, Matthew J

2017-10-01

The presence of regional variation in the osteogenic abilities of cranial bones underscores the fact that the mechanobiology of the mammalian skull is more complex than previously recognized. However, the relationship between patterns of cranial bone formation and biomineralization remains incompletely understood. In four strains of mice, micro-computed tomography was used to measure tissue mineral density during perinatal development in three skull regions (calvarium, basicranium, mandible) noted for variation in loading environment, embryological origin, and ossification mode. Biomineralization levels increased during perinatal ontogeny in the mandible and calvarium, but did not increase in the basicranium. Tissue mineral density levels also varied intracranially, with density in the mandible being highest, in the basicranium intermediate, and in the calvarium lowest. Perinatal increases in, and elevated levels of, mandibular biomineralization appear related to the impending postweaning need to resist elevated masticatory stresses. Similarly, perinatal increases in calvarial biomineralization may be linked to ongoing brain expansion, which is known to stimulate sutural bone formation in this region. The lack of perinatal increase in basicranial biomineralization could be a result of earlier developmental maturity in the cranial base relative to other skull regions due to its role in supporting the brain's mass throughout ontogeny. These results suggest that biomineralization levels and age-related trajectories throughout the skull are influenced by the functional environment and ontogenetic processes affecting each region, e.g., onset of masticatory loads in the mandible, whereas variation in embryology and ossification mode may only have secondary effects on patterns of biomineralization. Knowledge of perinatal variation in tissue mineral density, and of normal cranial bone formation early in development, may benefit clinical therapies aiming to correct developmental defects and traumatic injuries in the skull, and more generally characterize loading environments and skeletal adaptations in mammals by highlighting the need for multi-level analyses for evaluating functional performance of cranial bone. Copyright © 2017 Elsevier GmbH. All rights reserved.

Excess cancer mortality among children and adolescents in residential districts polluted by petrochemical manufacturing plants in Taiwan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bi Jen Pan; Yu Jue Hong; Gwo Chin Chang

1994-12-31

We have collected data on the cancer deaths of children and adolescents 0-19 yr old living in a residential area near 3 large petroleum and petrochemical complexes in and near Kaohsiung city (petrochemical industrial districts, PIDs) in the period of 1971-1990 and compared these with the cancer deaths of children and adolescents 0-19 yr old among the entire population of Taiwan (national reference) and among the residents of 26 administrative districts, comprising all of Kaohsiung city and Kaohsiung county (local reference), except for 8 sparsely populated, rural districts. Having scrutinized all cancer death certificates, we have identified various statistically significantmore » excess deaths, as compared with the national and local reference, due to cancers at all sites. Cancer of the bone, brain, and bladder in boys and girls 0-9 yr and 10-19 yr of age in the 1981-1990 decade that followed the establishment of petrochemical production in the PIDs was studied. However, excess cancer deaths seemed to have clustered in the 10-19 yr age group, who had been potentially exposed to the petrochemical pollutants for the longest period of time from the youngest age. Almost all bone, brain, and bladder cancer deaths registered were within 3 km of the 3 complexes. Bone and brain cancers in particular occurred in girls in the PIDs more frequently than in boys, even though these are believed to occur more in males than females elsewhere. 32 refs., 1 fig., 6 tabs.« less

Zoledronic acid inhibits macrophage/microglia-assisted breast cancer cell invasion

PubMed Central

Rietkötter, Eva; Menck, Kerstin; Bleckmann, Annalen; Farhat, Katja; Schaffrinski, Meike; Schulz, Matthias; Hanisch, Uwe-Karsten; Binder, Claudia; Pukrop, Tobias

2013-01-01

The bisphosphonate zoledronic acid (ZA) significantly reduces complications of bone metastasis by inhibiting resident macrophages, the osteoclasts. Recent clinical trials indicate additional anti-metastatic effects of ZA outside the bone. However, which step of metastasis is influenced and whether this is due to direct toxicity on cancer cells or inhibition of the tumor promoting microenvironment, is unknown. In particular, tumor-associated and resident macrophages support each step of organ metastasis and could be a crucial target of ZA. Thus, we comparatively investigate the ZA effects on: i) different types of macrophages, ii) on breast cancer cells but also iii) on macrophage-induced invasion. We demonstrate that ZA concentrations reflecting the plasma level affected viability of human macrophages, murine bone marrow-derived macrophages as well as their resident brain equivalents, the microglia, while it did not influence the tested cancer cells. However, the effects on the macrophages subsequently reduced the macrophage/microglia-induced invasiveness of the cancer cells. In line with this, manipulation of microglia by ZA in organotypic brain slice cocultures reduced the tissue invasion by carcinoma cells. The characterization of human macrophages after ZA treatment revealed a phenotype/response shift, in particular after external stimulation. In conclusion, we show that therapeutic concentrations of ZA affect all types of macrophages but not the cancer cells. Thus, anti-metastatic effects of ZA are predominantly caused by modulating the microenvironment. Most importantly, our findings demonstrate that ZA reduced microglia-assisted invasion of cancer cells to the brain tissue, indicating a potential therapeutic role in the prevention of cerebral metastasis. PMID:24036536

Patterns of breast cancer relapse in accordance to biological subtype.

PubMed

Ignatov, Atanas; Eggemann, Holm; Burger, Elke; Ignatov, Tanja

2018-04-19

To evaluate the pattern of recurrence of breast cancer according to its biological subtype in a large cohort of patients treated with therapy representative of current practice. Patients treated between 2000 and 2016 with known biological subtype were eligible. Data were prospectively collected. Primary endpoint was the subtype-dependent pattern and time of recurrence. Loco-regional and distant site and time of recurrence were assessed. Median follow-up time was 80.8 months. For 12,053 (82.5%) of 14,595 patients with primary non-metastatic invasive breast cancer a subtype classification was possible. The luminal A subtype had the highest 10-year survival followed by luminal B and luminal/HER2. The worst survival demonstrated HER2 enriched and TNBC. HER2 and TNBC had the highest rate of recurrence in the first 5 years, whereas the rate of recurrence for luminal A and luminal B tumors was initially low, but remained continuously even after 10 years of follow-up. Luminal A tumors demonstrated the lowest rate of distant metastases predominantly in bone. So did luminal B tumors. HER2 enriched subtype was characterized with increased rate of loco-regional recurrence and distant metastases in bone, liver and brain. Luminal/HER2 had pattern of relapse similar to HER2 enriched tumors, with exception of loco-regional relapse and brain metastases. TNBC had higher rate of lung, bone and brain metastases as well as loco-regional relapse. Breast cancer subtypes are associated with different time and pattern of recurrence and it should be considered during treatment decision.

Brain stem/brain stem occipital bone ratio and the four-line view in nuchal translucency images of fetuses with open spina bifida.

PubMed

Iuculano, Ambra; Zoppi, Maria Angelica; Piras, Alessandra; Arras, Maurizio; Monni, Giovanni

2014-09-10

Abstract Objective: Brain stem depth/brain stem occipital bone distance (BS/BSOB ratio) and the four-line view, in images obtained for nuchal translucency (NT) screening in fetuses with open spina bifida (OSB). Methods: Single center, retrospective study based on the assessment of NT screening images of fetuses with OSB. A ratio between the BS depth and the BSOB distance was calculated (BS/BSOB ratio) and the four-line view observed, and the sensitivity for a BS/BSOB ratio superior/equal to 1, and for the lack of detection of the four-line view were calculated. Results: There were 17 cases of prenatal diagnosis OSB. In six cases, the suspicion on OSB was raised during NT screening, in six cases, the diagnosis was made before 20 weeks and in five cases during anomaly scan. The BS/BSOB ratio was superior/equal to 1 in all 17 cases, and three lines, were visualized in 15/17 images of the OSB cases, being the sensitivity 100% (95% CI, 81 to 100%) and 88% (95% CI, 65 to 96%). Conclusion: Assessment of BS/BSOB ratio and four-line view in NT images is feasible detecting affected by OSB with high sensitivity. The presence of associated anomalies or of an enlarged NT enhances the early detection.

Frontal sinuses and head-butting in goats: a finite element analysis.

PubMed

Farke, Andrew A

2008-10-01

Frontal sinuses in goats and other mammals have been hypothesized to function as shock absorbers, protecting the brain from blows during intraspecific combat. Furthermore, sinuses are thought to form through removal of ;structurally unnecessary' bone. These hypotheses were tested using finite element modeling. Three-dimensional models of domesticated goat (Capra hircus) skulls were constructed, with variable frontal bone and frontal sinus morphology, and loaded to simulate various head-butting behaviors. In general, models with sinuses experienced higher strain energy values (a proxy for shock absorption) than did models with unvaulted frontal bones, and the latter often had higher magnitudes than models with solid vaulted frontal bones. Furthermore, vaulted frontal bones did not reduce magnitudes of principal strain on the surface of the endocranial cavity relative to models with unvaulted frontal bones under most loading conditions. Thus, these results were only partially consistent with sinuses, or the bone that walls the sinuses, acting as shock absorbers. It is hypothesized that the keratinous horn sheaths and cranial sutures are probably more important for absorbing blows to the head. Models with sinuses did exhibit a more ;efficient' distribution of stresses, as visualized by histograms in which models with solid frontal bones had numerous unloaded elements. This is consistent with the hypothesis that sinuses result at least in part from the removal of mechanically unnecessary bone.

High neuropeptide Y release associates with Ewing sarcoma bone dissemination - in vivo model of site-specific metastases

PubMed Central

Hong, Sung-Hyeok; Tilan, Jason U.; Galli, Susana; Izycka-Swieszewska, Ewa; Polk, Taylor; Horton, Meredith; Mahajan, Akanksha; Christian, David; Jenkins, Shari; Acree, Rachel; Connors, Katherine; Ledo, Phuong; Lu, Congyi; Lee, Yi-Chien; Rodriguez, Olga; Toretsky, Jeffrey A.; Albanese, Chris; Kitlinska, Joanna

2015-01-01

Ewing sarcoma (ES) develops in bones or soft tissues of children and adolescents. The presence of bone metastases is one of the most adverse prognostic factors, yet the mechanisms governing their formation remain unclear. As a transcriptional target of EWS-FLI1, the fusion protein driving ES transformation, neuropeptide Y (NPY) is highly expressed and released from ES tumors. Hypoxia up-regulates NPY and activates its pro-metastatic functions. To test the impact of NPY on ES metastatic pattern, ES cell lines, SK-ES1 and TC71, with high and low peptide release, respectively, were used in an orthotopic xenograft model. ES cells were injected into gastrocnemius muscles of SCID/beige mice, the primary tumors excised, and mice monitored for the presence of metastases. SK-ES1 xenografts resulted in thoracic extra-osseous metastases (67%) and dissemination to bone (50%) and brain (25%), while TC71 tumors metastasized to the lungs (70%). Bone dissemination in SK-ES1 xenografts associated with increased NPY expression in bone metastases and its accumulation in bone invasion areas. The genetic silencing of NPY in SK-ES1 cells reduced bone degradation. Our study supports the role for NPY in ES bone invasion and provides new models for identifying pathways driving ES metastases to specific niches and testing anti-metastatic therapeutics. PMID:25714031

Deer Bone Extract Prevents Against Scopolamine-Induced Memory Impairment in Mice

PubMed Central

Du, Chun Nan; Min, A Young; Kim, Hyun Jeong; Shin, Suk Kyung; Yu, Ha Ni; Sohn, Eun Jeong; Ahn, Chang-Won; Jung, Sung Ug; Park, Soo-Hyun

2015-01-01

Abstract Deer bone has been used as a health-enhancing food as well as an antiaging agent in traditional Oriental medicine. Recently, the water extract of deer bone (DBE) showed a neuroprotective action against glutamate or Aβ1–42-induced cell death of mouse hippocampal cells by exerting antioxidant activity through the suppression of MAP kinases. The present study is to examine whether DBE improves memory impairment induced by scopolamine. DBE (50, 100 or 200 mg/kg) was administered orally to mice for 14 days, and then scopolamine (2 mg/kg, i.p.) was administered together with DBE for another 7 days. Memory performance was evaluated in the Morris water maze (MWM) test and passive avoidance test. Also, brain acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activity, biomarkers of oxidative stress and the loss of neuronal cells in the hippocampus, was evaluated by histological examinations. Administration of DBE significantly restored memory impairments induced by scopolamine in the MWM test (escape latency and number of crossing platform area), and in the passive avoidance test. Treatment with DBE inhibited the AChE activity and increased the ChAT activity in the brain of memory-impaired mice induced by scopolamine. Additionally, the administration of DBE significantly prevented the increase of lipid peroxidation and the decrease of glutathione level in the brain of mice treated with scopolamine. Also, the DBE treatment restored the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase to control the level. Furthermore, scopolamine-induced oxidative damage of neurons in hippocampal CA1 and CA3 regions were prevented by DBE treatment. It is suggested that DBE may be useful for memory improvement through the regulation of cholinergic marker enzyme activities and the suppression of oxidative damage of neurons in the brain of mice treated with scopolamine. PMID:25546299

Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baba, Justin S; Endres, Christopher; Foss, Catherine

2013-01-01

We have developed a SPECT imaging system, AwakeSPECT, to enable molecular brain imaging of untrained mice that are conscious, unanesthetized, and unrestrained. We accomplished this with head tracking and motion correction techniques. Methods: The capability of the system for motion-corrected imaging was demonstrated with a 99mTc-pertechnetate phantom, 99mTcmethylene diphosphonate bone imaging, and measurement of the binding potential of the dopamine transporter radioligand 123I-ioflupane in mouse brain in the awake and anesthetized (isoflurane) states. Stress induced by imaging in the awake state was assessed through measurement of plasma corticosterone levels. Results: AwakeSPECT provided high-resolution bone images reminiscent of those obtained frommore » CT. The binding potential of 123I-ioflupane in the awake state was on the order of 50% of that obtained with the animal under anesthesia, consistent with previous studies in nonhuman primates. Levels of stress induced were on the order of those seen in other behavioral tasks and imaging studies of awake animals. Conclusion: These results demonstrate the feasibility of SPECT molecular brain imaging of mice in the conscious, unrestrained state and demonstrate the effects of isoflurane anesthesia on radiotracer uptake.« less

Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baba, Justin S.; Endres, Christopher J.; Foss, Catherine A.

2013-06-01

We have developed a SPECT imaging system, AwakeSPECT, to enable molecular brain imaging of untrained mice that are conscious, unanesthetized, and unrestrained. We accomplished this with head tracking and motion correction techniques. Methods: The capability of the system for motion-corrected imaging was demonstrated with a ^99mTc-pertechnetate phantom, ^99mTc-methylene diphosphonate bone imaging, and measurement of the binding potential of the dopamine transporter radioligand ^123I-ioflupane in mouse brain in the awake and anesthetized (isoflurane) states. Stress induced by imaging in the awake state was assessed through measurement of plasma corticosterone levels. Results: AwakeSPECT provided high-resolution bone images reminiscent of those obtained frommore » CT. The binding potential of ^123I-ioflupane in the awake state was on the order of 50% of that obtained with the animal under anesthesia, consistent with previous studies in nonhuman primates. Levels of stress induced were on the order of those seen in other behavioral tasks and imaging studies of awake animals. Conclusion: These results demonstrate the feasibility of SPECT molecular brain imaging of mice in the conscious, unrestrained state and demonstrate the effects of isoflurane anesthesia on radiotracer uptake.« less

Recurrent Fat Embolic Strokes in a Patient With Duchenne Muscular Dystrophy With Long Bone Fractures and a Patent Foramen Ovale.

PubMed

Bugnitz, Christopher J; Cripe, Linda H; Lo, Warren D; Flanigan, Kevin M

2016-10-01

Individuals with Duchenne muscular dystrophy have an increased risk of long bone fractures. Such fractures are sometimes associated with brain dysfunction due to fat embolism syndrome, although this syndrome has seldom been documented in muscular dystrophy patients. We describe a child with Duchenne muscular dystrophy who developed fat embolism syndrome with neurological dysfunction following multiple long bone fractures. He experienced recurrent cerebral infarctions that probably resulted from embolization through a patent foramen ovale. The patent foramen ovale was closed by an occluder device in the cardiac catheterization laboratory, and he did not experience further infarctions. Fat embolism with ischemic cerebral infarction can occur in individuals with Duchenne muscular dystrophy following long bone fractures. In this setting it is important to identify and close atrial level shunts in order to prevent additional infarctions. Copyright © 2016 Elsevier Inc. All rights reserved.

The human brain and face: mechanisms of cranial, neurological and facial development revealed through malformations of holoprosencephaly, cyclopia and aberrations in chromosome 18

PubMed Central

Gondré-Lewis, Marjorie C; Gboluaje, Temitayo; Reid, Shaina N; Lin, Stephen; Wang, Paul; Green, William; Diogo, Rui; Fidélia-Lambert, Marie N; Herman, Mary M

2015-01-01

The study of inborn genetic errors can lend insight into mechanisms of normal human development and congenital malformations. Here, we present the first detailed comparison of cranial and neuro pathology in two exceedingly rare human individuals with cyclopia and alobar holoprosencephaly (HPE) in the presence and absence of aberrant chromosome 18 (aCh18). The aCh18 fetus contained one normal Ch18 and one with a pseudo-isodicentric duplication of chromosome 18q and partial deletion of 18p from 18p11.31 where the HPE gene, TGIF, resides, to the p terminus. In addition to synophthalmia, the aCh18 cyclopic malformations included a failure of induction of most of the telencephalon – closely approximating anencephaly, unchecked development of brain stem structures, near absence of the sphenoid bone and a malformed neurocranium and viscerocranium that constitute the median face. Although there was complete erasure of the olfactory and superior nasal structures, rudiments of nasal structures derived from the maxillary bone were evident, but with absent pharyngeal structures. The second non-aCh18 cyclopic fetus was initially classified as a true Cyclops, as it appeared to have a proboscis and one median eye with a single iris, but further analysis revealed two eye globes as expected for synophthalmic cyclopia. Furthermore, the proboscis was associated with the medial ethmoid ridge, consistent with an incomplete induction of these nasal structures, even as the nasal septum and paranasal sinuses were apparently developed. An important conclusion of this study is that it is the brain that predicts the overall configuration of the face, due to its influence on the development of surrounding skeletal structures. The present data using a combination of macroscopic, computed tomography (CT) and magnetic resonance imaging (MRI) techniques provide an unparalleled analysis on the extent of the effects of median defects, and insight into normal development and patterning of the brain, face and their skeletal support. PMID:26278930

The human brain and face: mechanisms of cranial, neurological and facial development revealed through malformations of holoprosencephaly, cyclopia and aberrations in chromosome 18.

PubMed

Gondré-Lewis, Marjorie C; Gboluaje, Temitayo; Reid, Shaina N; Lin, Stephen; Wang, Paul; Green, William; Diogo, Rui; Fidélia-Lambert, Marie N; Herman, Mary M

2015-09-01

The study of inborn genetic errors can lend insight into mechanisms of normal human development and congenital malformations. Here, we present the first detailed comparison of cranial and neuro pathology in two exceedingly rare human individuals with cyclopia and alobar holoprosencephaly (HPE) in the presence and absence of aberrant chromosome 18 (aCh18). The aCh18 fetus contained one normal Ch18 and one with a pseudo-isodicentric duplication of chromosome 18q and partial deletion of 18p from 18p11.31 where the HPE gene, TGIF, resides, to the p terminus. In addition to synophthalmia, the aCh18 cyclopic malformations included a failure of induction of most of the telencephalon - closely approximating anencephaly, unchecked development of brain stem structures, near absence of the sphenoid bone and a malformed neurocranium and viscerocranium that constitute the median face. Although there was complete erasure of the olfactory and superior nasal structures, rudiments of nasal structures derived from the maxillary bone were evident, but with absent pharyngeal structures. The second non-aCh18 cyclopic fetus was initially classified as a true Cyclops, as it appeared to have a proboscis and one median eye with a single iris, but further analysis revealed two eye globes as expected for synophthalmic cyclopia. Furthermore, the proboscis was associated with the medial ethmoid ridge, consistent with an incomplete induction of these nasal structures, even as the nasal septum and paranasal sinuses were apparently developed. An important conclusion of this study is that it is the brain that predicts the overall configuration of the face, due to its influence on the development of surrounding skeletal structures. The present data using a combination of macroscopic, computed tomography (CT) and magnetic resonance imaging (MRI) techniques provide an unparalleled analysis on the extent of the effects of median defects, and insight into normal development and patterning of the brain, face and their skeletal support. © 2015 Anatomical Society.

Involvement of PI3K and ROCK signaling pathways in migration of bone marrow-derived mesenchymal stem cells through human brain microvascular endothelial cell monolayers.

PubMed

Lin, Mei-Na; Shang, De-Shu; Sun, Wei; Li, Bo; Xu, Xin; Fang, Wen-Gang; Zhao, Wei-Dong; Cao, Liu; Chen, Yu-Hua

2013-06-04

Bone marrow-derived mesenchymal stem cells (MSC) represent an important and easily available source of stem cells for potential therapeutic use in neurological diseases. The entry of circulating cells into the central nervous system by intravenous administration requires, firstly, the passage of the cells across the blood-brain barrier (BBB). However, little is known of the details of MSC transmigration across the BBB. In the present study, we employed an in vitro BBB model constructed using a human brain microvascular endothelial cell monolayer to study the mechanism underlying MSC transendothelial migration. Transmigration assays, transendothelial electrical resistance (TEER) and horseradish peroxidase (HRP) flux assays showed that MSC could transmigrate through human brain microvascular endothelial cell monolayers by a paracellular pathway. Cell fractionation and immunofluorescence assays confirmed the disruption of tight junctions. Inhibition assays showed that a Rho-kinase (ROCK) inhibitor (Y27632) effectively promoted MSC transendothelial migration; conversely, a PI3K inhibitor (LY294002) blocked MSC transendothelial migration. Interestingly, adenovirus-mediated interference with ROCK in MSC significantly increased MSC transendothelial migration, and overexpression of a PI3K dominant negative mutant in MSC cells could block transendothelial migration. Our findings provide clear evidence that the PI3K and ROCK pathways are involved in MSC migration through human brain microvascular endothelial cell monolayers. The information yielded by this study may be helpful in constructing gene-modified mesenchymal stem cells that are able to penetrate the BBB effectively for cell therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

Soft-tissue and phase-contrast imaging at the Swiss Light Source

NASA Astrophysics Data System (ADS)

Schneider, Philipp; Mohan, Nishant; Stampanoni, Marco; Muller, Ralph

2004-05-01

Recent results show that bone vasculature is a major contributor to local tissue porosity, and therefore can be directly linked to the mechanical properties of bone tissue. With the advent of third generation synchrotron radiation (SR) sources, micro-computed tomography (μCT) with resolutions in the order of 1 μm and better has become feasible. This technique has been employed frequently to analyze trabecular architecture and local bone tissue properties, i.e. the hard or mineralized bone tissue. Nevertheless, less is known about the soft tissues in bone, mainly due to inadequate imaging capabilities. Here, we discuss three different methods and applications to visualize soft tissues. The first approach is referred to as negative imaging. In this case the material around the soft tissue provides the absorption contrast necessary for X-ray based tomography. Bone vasculature from two different mouse strains was investigated and compared qualitatively. Differences were observed in terms of local vessel number and vessel orientation. The second technique represents corrosion casting, which is principally adapted for imaging of vascular systems. The technique of corrosion casting has already been applied successfully at the Swiss Light Source. Using the technology we were able to show that pathological features reminiscent of Alzheimer"s disease could be distinguished in the brain vasculature of APP transgenic mice. The third technique discussed here is phase contrast imaging exploiting the high degree of coherence of third generation synchrotron light sources, which provide the necessary physical conditions for phase contrast. The in-line approach followed here for phase contrast retrieval is a modification of the Gerchberg-Saxton-Fienup type. Several measurements and theoretical thoughts concerning phase contrast imaging are presented, including mathematical phase retrieval. Although up-to-now only phase images have been computed, the approach is now ready to retrieve the phase for a large number of angular positions of the specimen allowing application of holotomography, which is the three-dimensional reconstruction of phase images.

Brain infarction due to vertebral artery dissection caused by a bone protrusion from the condylar fossa in a juvenile case.

PubMed

Fujii, Mutsumi; Ohgushi, Miki; Chin, Takaaki

2018-02-06

A 16-year-old boy presented with multiple posterior circulation ischemic strokes resulting from vertebral artery (VA) dissection. Three-dimensional computed tomography showed aberrant sub-occipital bone protuberance, proximal to the VA dissection. Since the patient was a habitual neck cracker, VA dissection was thought to result from the impact shock of the rotational head movement. This could be due to either the osseous prominence or the compression between the prominence and the C1. Although it is a rare etiology of Bow Hunter's syndrome, VA dissection due to sub-occipital bone spur because of neck cracking should be considered in the diagnosis of Bow Hunter's syndrome in juvenile patients.

Bone metastasis from ovarian cancer. Clinical analysis of 26 cases.

PubMed

Zhang, Min; Sun, Jimei

2013-12-01

To study the clinical characteristics of bone metastasis from ovarian cancer, and facilitate physicians to develop treatment strategies. This retrospective study was carried out in the Provincial Hospital Affiliated to Shandong University, Shandong, China. Twenty-six cases of bone metastasis from ovarian cancer treated between January 2002 and May 2008 were reviewed, and the clinical data were collected. In the current study, the incidence of bone metastasis is 0.82%. Twelve cases of bone metastasis occurred in the cervical vertebra, 10 in the lumbar vertebra, 8 in the pelvis, 7 in the thoracic vertebra, 5 in the limbs, one in the ribs, and 2 in the sternum. Lung metastasis occurred concomitantly in 9 cases, liver metastasis in 5 cases, brain metastasis in 4 cases, splenic metastasis in 3 cases, adrenal metastasis in 2 cases, and lymphatic metastasis in 12 cases. Twenty-three cases (88.5%) of bone metastasis were detected in stage III-IV, and 3 (11.5%) in stage II (p=0.000). The survival time in cases treated using comprehensive therapy was longer than those using radiotherapy or chemotherapy alone (p=0.047). Bone metastasis from ovarian cancer is rare, however, the increasing pathological stage of ovarian cancer may add to the risk of bone metastasis, especially in the cases with lung or lymphatic metastasis. The pelvis and vertebral bone are the most common location of bone metastasis, and comprehensive treatment may improve the survival time of patients.

Disseminated sinus histiocytosis with massive lymphadenopathy: its pathologic aspects.

PubMed

Buchino, J J; Byrd, R P; Kmetz, D R

1982-01-01

Sinus histiocytosis with massive lymphadenopathy (SHML) is generally regarded as a benign, self-limited, pseudolymphomatous process requiring little or no therapy. We studied a 13-year-old black boy with a ten-year clinical course of SHML that had varying, intermittent sites of extranodal involvement, including bone, submandibular gland, trachea, eye, and spinal cord. At the time of death, which was attributed to SHML, additional extranodal sites of involvement included thymus, kidney, heart, liver, and base of brain. Microscopic examination of the SHML lesions at the time of autopsy revealed varying stages of development, from proliferation to involution. This case illustrates that SHML may involve multiple organ systems, can kill, and that histologic evaluation of disease activity at one site cannot be used as an indicator of activity at another.

Genetics Home Reference: inclusion body myopathy with early-onset Paget disease and frontotemporal dementia

MedlinePlus

... condition damages parts of the brain that control reasoning, personality, social skills, speech, and language. Personality changes, ... Clearinghouse: Paget's Disease of Bone: An Endocrine Society Clinical Practice Guideline Genetic Testing (1 link) Genetic Testing ...

Trans-nasal-trans-sphenoidal brain injury by a fencing foil: an unusual case report and brief literature review.

PubMed

Özay, Rafet; Balkan, Mehmet S; Tönge, Çağhan; Şekerci, Zeki

2017-11-01

In this report, the authors present an unusual case of a 10-year-old child who suffered a severe headache and rhinorrhea that occurred as a result of fencing foil sports injury via trans-nasal-trans-sphenoidal (TNTS) pathway. Following trauma, the child had shown neurological symptoms such a pupil dilatation, change in consciousness and mild hemiparesia. Imaging demonstrated destruction of bone structures including posterior wall of sphenoid sinus and antero-superior part of sella turcica, and also a contusion at right thalamic region. For treatment of rhinorrhea lumbar drainage system (LDS) had planted in order to relieve cerebrospinal fluid (CSF) leakage. After the treatment, the patient had fully recovered without any need of further surgical intervention. CSF leakage had prevented and neurological symptoms were completely treated. This case represents the first report of brain injury via TNTS pathway in a sports practice. Diagnosis, clinic follow-up and treatment options of this rare accidental sports injury are discussed.

Diprosopia in a cat.

PubMed

Camón, J; Ruberte, J; Ordóñez, G

1990-05-01

A diprosopic cat is described. In the head, two snouts, three eyes and two pinnae were present. The mandible was single and immobile because labial skin of both upper lips and single lower lip was partly fused. Superimposition of upper and lower dental arches was impossible and the mouths remained permanently open. Two incomplete oral cavities were present and the two tongues were joined at their base. The brain was duplicated in part. In the cranium only occipital and temporal bones were normal, the basisphenoid was bifurcated and the remaining bones were duplicated. Embryological mechanisms are discussed.

B-Receptor Signaling in Cardiomyopathy

ClinicalTrials.gov

2015-11-16

Carcinomas; Amyloidosis; Anal Cancer; Anemia; Cholangiocarcinoma of the Extrahepatic Bile Duct; Transitional Cell Carcinoma of Bladder; Bone Marrow Transplant Failure; Bone Cancer; Cancer of Brain and Nervous System; Breast Cancer; Carcinoma of the Large Intestine; Endocrine Cancer; Esophageal Cancer; Eye Cancer; Gall Bladder Cancer; Gastric (Stomach) Cancer; Gastrooesophageal Cancer; Gastrointestinal Stromal Tumor (GIST); Gynecologic Cancers; Head and Neck Cancers; Hepatobiliary Neoplasm; Kidney (Renal Cell) Cancer; Leukemia; Lung Cancer; Hodgkin Disease; Lymphoma, Non-Hodgkin; Mesothelioma; Multiple Myeloma; Myelodysplastic Syndromes (MDS); Neuroendocrine Tumors; Myeloproliferative Disorders; Pancreatic Cancer; Prostate Cancer; Skin Cancer; Soft Tissue Sarcoma; Testicular Cancer; Thymus Cancer; Thyroid Cancer

MO-F-CAMPUS-J-05: Toward MRI-Only Radiotherapy: Novel Tissue Segmentation and Pseudo-CT Generation Techniques Based On T1 MRI Sequences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aouadi, S; McGarry, M; Hammoud, R

Purpose: To develop and validate a 4 class tissue segmentation approach (air cavities, background, bone and soft-tissue) on T1 -weighted brain MRI and to create a pseudo-CT for MRI-only radiation therapy verification. Methods: Contrast-enhanced T1-weighted fast-spin-echo sequences (TR = 756ms, TE= 7.152ms), acquired on a 1.5T GE MRI-Simulator, are used.MRIs are firstly pre-processed to correct for non uniformity using the non parametric, non uniformity intensity normalization algorithm. Subsequently, a logarithmic inverse scaling log(1/image) is applied, prior to segmentation, to better differentiate bone and air from soft-tissues. Finally, the following method is enrolled to classify intensities into air cavities, background, bonemore » and soft-tissue:Thresholded region growing with seed points in image corners is applied to get a mask of Air+Bone+Background. The background is, afterward, separated by the scan-line filling algorithm. The air mask is extracted by morphological opening followed by a post-processing based on knowledge about air regions geometry. The remaining rough bone pre-segmentation is refined by applying 3D geodesic active contours; bone segmentation evolves by the sum of internal forces from contour geometry and external force derived from image gradient magnitude.Pseudo-CT is obtained by assigning −1000HU to air and background voxels, performing linear mapping of soft-tissue MR intensities in [-400HU, 200HU] and inverse linear mapping of bone MR intensities in [200HU, 1000HU]. Results: Three brain patients having registered MRI and CT are used for validation. CT intensities classification into 4 classes is performed by thresholding. Dice and misclassification errors are quantified. Correct classifications for soft-tissue, bone, and air are respectively 89.67%, 77.8%, and 64.5%. Dice indices are acceptable for bone (0.74) and soft-tissue (0.91) but low for air regions (0.48). Pseudo-CT produces DRRs with acceptable clinical visual agreement to CT-based DRR. Conclusion: The proposed approach makes it possible to use T1-weighted MRI to generate accurate pseudo-CT from 4-class segmentation.« less

Towards Implementing an MR-based PET Attenuation Correction Method for Neurological Studies on the MR-PET Brain Prototype

PubMed Central

Catana, Ciprian; van der Kouwe, Andre; Benner, Thomas; Michel, Christian J.; Hamm, Michael; Fenchel, Matthias; Fischl, Bruce; Rosen, Bruce; Schmand, Matthias; Sorensen, A. Gregory

2013-01-01

A number of factors have to be considered for implementing an accurate attenuation correction (AC) in a combined MR-PET scanner. In this work, some of these challenges were investigated and an AC method based entirely on the MR data obtained with a single dedicated sequence was developed and used for neurological studies performed with the MR-PET human brain scanner prototype. Methods The focus was on the bone/air segmentation problem, the bone linear attenuation coefficient selection and the RF coil positioning. The impact of these factors on the PET data quantification was studied in simulations and experimental measurements performed on the combined MR-PET scanner. A novel dual-echo ultra-short echo time (DUTE) MR sequence was proposed for head imaging. Simultaneous MR-PET data were acquired and the PET images reconstructed using the proposed MR-DUTE-based AC method were compared with the PET images reconstructed using a CT-based AC. Results Our data suggest that incorrectly accounting for the bone tissue attenuation can lead to large underestimations (>20%) of the radiotracer concentration in the cortex. Assigning a linear attenuation coefficient of 0.143 or 0.151 cm−1 to bone tissue appears to give the best trade-off between bias and variability in the resulting images. Not identifying the internal air cavities introduces large overestimations (>20%) in adjacent structures. Based on these results, the segmented CT AC method was established as the “silver standard” for the segmented MR-based AC method. Particular to an integrated MR-PET scanner, ignoring the RF coil attenuation can cause large underestimations (i.e. up to 50%) in the reconstructed images. Furthermore, the coil location in the PET field of view has to be accurately known. Good quality bone/air segmentation can be performed using the DUTE data. The PET images obtained using the MR-DUTE- and CT-based AC methods compare favorably in most of the brain structures. Conclusion An MR-DUTE-based AC method was implemented considering all these factors and our preliminary results suggest that this method could potentially be as accurate as the segmented CT method and it could be used for quantitative neurological MR-PET studies. PMID:20810759

Toward implementing an MRI-based PET attenuation-correction method for neurologic studies on the MR-PET brain prototype.

PubMed

Catana, Ciprian; van der Kouwe, Andre; Benner, Thomas; Michel, Christian J; Hamm, Michael; Fenchel, Matthias; Fischl, Bruce; Rosen, Bruce; Schmand, Matthias; Sorensen, A Gregory

2010-09-01

Several factors have to be considered for implementing an accurate attenuation-correction (AC) method in a combined MR-PET scanner. In this work, some of these challenges were investigated, and an AC method based entirely on the MRI data obtained with a single dedicated sequence was developed and used for neurologic studies performed with the MR-PET human brain scanner prototype. The focus was on the problem of bone-air segmentation, selection of the linear attenuation coefficient for bone, and positioning of the radiofrequency coil. The impact of these factors on PET data quantification was studied in simulations and experimental measurements performed on the combined MR-PET scanner. A novel dual-echo ultrashort echo time (DUTE) MRI sequence was proposed for head imaging. Simultaneous MR-PET data were acquired, and the PET images reconstructed using the proposed DUTE MRI-based AC method were compared with the PET images that had been reconstructed using a CT-based AC method. Our data suggest that incorrectly accounting for the bone tissue attenuation can lead to large underestimations (>20%) of the radiotracer concentration in the cortex. Assigning a linear attenuation coefficient of 0.143 or 0.151 cm(-1) to bone tissue appears to give the best trade-off between bias and variability in the resulting images. Not identifying the internal air cavities introduces large overestimations (>20%) in adjacent structures. On the basis of these results, the segmented CT AC method was established as the silver standard for the segmented MRI-based AC method. For an integrated MR-PET scanner, in particular, ignoring the radiofrequency coil attenuation can cause large underestimations (i.e.,

Ameliorative effect of black grape juice on systemic alterations and mandibular osteoradionecrosis induced by whole brain irradiation in rats.

PubMed

Freitas, Robson B; González, Paquita; Martins, Nara Maria B; Andrade, Edson R; Cesteros Morante, María Jesús; Conles Picos, Iban; Costilla García, Serafín; Bauermann, Liliane F; Barrio, Juan Pablo

2017-02-01

Whole brain irradiation (WBI) causes a variety of secondary side-effects including anorexia and bone necrosis. We evaluated the radiomodifying effect of black grape juice (BGJ) on WBI alterations in rats measuring food and water intake, body weight, hemogram, and morphological and histological mandibular parameters. Forty male rats (200-250 g) were exposed to eight sessions of cranial X-ray irradiation. The total dose absorbed was 32 Gy delivered over 2 weeks. Four groups were defined: (i) NG: non-irradiated, glucose and fructose solution-supplemented (GFS); (ii) NJ: non-irradiated, BGJ-supplemented; (iii) RG: irradiated, GFS-supplemented; and (iv) RJ: irradiated, BGJ-supplemented. Rats received daily BGJ or GFS dosing by gavage starting 4 days before, continuing during, and ending 4 days after WBI. RJ rats ingested more food and water and showed less body weight loss than RG rats during the irradiation period. Forty days after WBI, irradiated animals started losing weight again compared with controls as a consequence of masticatory hypofunction by mandibular osteoradionecrosis (ORN). Osteoclastic activity and inflammation were apparent in RG rat mandibles. BGJ was able to attenuate the severity of ORN as well as to improve white and red blood cell counts. Fractionated whole brain irradiation induces mandibular changes that interfere with normal feeding. BGJ can be used to mitigate systemic side-effects of brain irradiation and ORN.

Signaling mechanisms regulating adult neural stem cells and neurogenesis

PubMed Central

Faigle, Roland; Song, Hongjun

2012-01-01

Background Adult neurogenesis occurs throughout life in discrete regions of the mammalian brain and is tightly regulated via both extrinsic environmental influences and intrinsic genetic factors. In recent years, several crucial signaling pathways have been identified in regulating self-renewal, proliferation, and differentiation of neural stem cells, as well as migration and functional integration of developing neurons in the adult brain. Scope of review Here we review our current understanding of signaling mechanisms, including Wnt, notch, sonic hedgehog, growth and neurotrophic factors, bone morphogenetic proteins, neurotransmitters, transcription factors, and epigenetic modulators, and crosstalk between these signaling pathways in the regulation of adult neurogenesis. We also highlight emerging principles in the vastly growing field of adult neural stem cell biology and neural plasticity. Major conclusions Recent methodological advances have enabled the field to identify signaling mechanisms that fine-tune and coordinate neurogenesis in the adult brain, leading to a better characterization of both cell-intrinsic and environmental cues defining the neurogenic niche. Significant questions related to niche cell identity and underlying regulatory mechanisms remain to be fully addressed and will be the focus of future studies. General significance A full understanding of the role and function of individual signaling pathways in regulating neural stem cells and generation and integration of newborn neurons in the adult brain may lead to targeted new therapies for neurological diseases in humans. PMID:22982587

Creating a normative database of age-specific 3D geometrical data, bone density, and bone thickness of the developing skull: a pilot study.

PubMed

Delye, Hans; Clijmans, Tim; Mommaerts, Maurice Yves; Sloten, Jos Vnder; Goffin, Jan

2015-12-01

Finite element models (FEMs) of the head are used to study the biomechanics of traumatic brain injury and depend heavily on the use of accurate material properties and head geometry. Any FEM aimed at investigating traumatic head injury in children should therefore use age-specific dimensions of the head, as well as age-specific material properties of the different tissues. In this study, the authors built a database of age-corrected skull geometry, skull thickness, and bone density of the developing skull to aid in the development of an age-specific FEM of a child's head. Such a database, containing age-corrected normative skull geometry data, can also be used for preoperative surgical planning and postoperative long-term follow-up of craniosynostosis surgery results. Computed tomography data were processed for 187 patients (age range 0-20 years old). A 3D surface model was calculated from segmented skull surfaces. Skull models, reference points, and sutures were processed into a MATLAB-supported database. This process included automatic calculation of 2D measurements as well as 3D measurements: length of the coronal suture, length of the lambdoid suture, and the 3D anterior-posterior length, defined as the sum of the metopic and sagittal suture. Skull thickness and skull bone density calculations were included. Cephalic length, cephalic width, intercoronal distance, lateral orbital distance, intertemporal distance, and 3D measurements were obtained, confirming the well-established general growth pattern of the skull. Skull thickness increases rapidly in the first year of life, slowing down during the second year of life, while skull density increases with a fast but steady pace during the first 3 years of life. Both skull thickness and density continue to increase up to adulthood. This is the first report of normative data on 2D and 3D measurements, skull bone thickness, and skull bone density for children aged 0-20 years. This database can help build an age-specific FEM of a child's head. It can also help to tailor preoperative virtual planning in craniosynostosis surgery toward patient-specific normative target values and to perform objective long-term follow-up in craniosynostosis surgery.

Deficiency of circadian clock protein BMAL1 in mice results in a low bone mass phenotype.

PubMed

Samsa, William E; Vasanji, Amit; Midura, Ronald J; Kondratov, Roman V

2016-03-01

The circadian clock is an endogenous time keeping system that controls the physiology and behavior of many organisms. The transcription factor Brain and Muscle ARNT-like Protein 1 (BMAL1) is a component of the circadian clock and necessary for clock function. Bmal1(-/-) mice display accelerated aging and many accompanying age associated pathologies. Here, we report that mice deficient for BMAL1 have a low bone mass phenotype that is absent at birth and progressively worsens over their lifespan. Accelerated aging of these mice is associated with the formation of bony bridges occurring across the metaphysis to the epiphysis, resulting in shorter long bones. Using micro-computed tomography we show that Bmal1(-/-) mice have reductions in cortical and trabecular bone volume and other micro-structural parameters and a lower bone mineral density. Histology shows a deficiency of BMAL1 results in a reduced number of active osteoblasts and osteocytes in vivo. Isolation of bone marrow derived mesenchymal stem cells from Bmal1(-/-) mice demonstrate a reduced ability to differentiate into osteoblasts in vitro, which likely explains the observed reductions in osteoblasts and osteocytes, and may contribute to the observed osteopenia. Our data support the role of the circadian clock in the regulation of bone homeostasis and shows that BMAL1 deficiency results in a low bone mass phenotype. Copyright © 2016 Elsevier Inc. All rights reserved.

Deficiency of Circadian Clock Protein BMAL1 in Mice Results in a Low Bone Mass Phenotype

PubMed Central

Samsa, William E.; Vasanji, Amit; Midura, Ronald J.; Kondratov, Roman V.

2016-01-01

The circadian clock is an endogenous time keeping system that controls the physiology and behavior of many organisms. The transcription factor Brain and Muscle ARNT-like Protein 1 (BMAL1) is a component of the circadian clock and necessary for clock function. Bmal1−/− mice display accelerated aging and many accompanying age associated pathologies. Here, we report that mice deficient for BMAL1 have a low bone mass phenotype that is absent at birth and progressively worsens over their lifespan. Accelerated aging of these mice is associated with the formation of bony bridges occurring across the metaphysis to the epiphysis, resulting in shorter long bones. Using micro-computed tomography we show that Bmal1−/− mice have reductions in cortical and trabecular bone volume and other micro-structural parameters and a lower bone mineral density. Histology shows a deficiency of BMAL1 results in a reduced number of active osteoblasts and osteocytes in vivo. Isolation of bone marrow derived mesenchymal stem cells from Bmal1−/− mice demonstrate a reduced ability to differentiate into osteoblasts in vitro, which likely explains the observed reductions in osteoblasts and osteocytes, and may contribute to the observed osteopenia. Our data support the role of the circadian clock in the regulation of bone homeostasis and shows that BMAL1 deficiency results in a low bone mass phenotype. PMID:26789548

Bioinorganic Activity of Technetium Radiopharmaceuticals.

ERIC Educational Resources Information Center

Pinkerton, Thomas C.; And Others

1985-01-01

Technetium radiopharmaceuticals are diagnostic imaging agents used in the field of nuclear medicine to visualize tissues, anatomical structures, and metabolic disorders. Bioavailability of technetium complexes, thyroid imaging, brain imaging, kidney imaging, imaging liver function, bone imaging, and heart imaging are the major areas discussed. (JN)

Tips for Teens: The Truth about Heroin

MedlinePlus

... produces drug cravings, restlessness,muscle and bone pain,insomnia,diarrhea, vomiting,and other symptoms that usually last about aweek, but may last for many months. Yes.Heroin enters the neurons or cells of the brain and changes the speed of the chemicals in ...

Minimal debridement or simple wound closure as the only surgical treatment in war victims with low-velocity penetrating head injuries. Indications and management protocol based upon more than 8 years follow-up of 99 cases from Iran-Iraq conflict.

PubMed

Amirjamshidi, Abbass; Abbassioun, Kazem; Rahmat, Hamid

2003-08-01

During military conflicts, surviving victims traditionally underwent large enough craniectomy or craniotomy to achieve extensive debridement of the in-driven bone, shell fragments, and debris. Meanwhile, the completely as well as the partially devitalized adjacent brain tissue would also be debrided. This might have led to additional neurologic deficit or lesser degree of recovery of functions. We studied the efficacy and safety of much more limited or even absence of surgical intervention in a selected group of wartime head-wounded patients. Among 1,150 war victims with penetrating head wounds referred to two major centers affiliated with Tehran University of Medical Sciences during the 8-year period spanning the Iran-Iraq conflict, there were 191 head-wounded patients who underwent either no surgical intervention or a very limited debridement. We have attempted to follow up as closely as possible for more than 8 years. Ninety-nine of them fulfilled the criteria to be included in this series. Close follow-up for development of cerebral infections, functional recovery, or development of new neurologic deficits and epilepsy were performed. At least 3 contrast-enhanced CT scans were taken for each patient. All patients were victims of the battle-field areas with low- to moderate-velocity missile or shell fragment injury. The Glasgow Coma Scale (GCS) scores of the patients were between 8-14 when visited by the first attending neurosurgery staff. The factors considered to be effective in the outcome analysis were the entry point, the number of the in-driven bone fragments, the retained shell fragments, the brain compartments affected, and the paranasal sinus or skull base involvement with or without cerebrospinal fluid (CSF) fistula. There were 13 unilobar, 44 bilobar, 4 trilobar, 38 transventricular, and 3 skull base lesions. The number of retained metal fragments varied between 1 to 6. The number of retained bone fragments varied between 1 to 5 in 73 victims and more than five chips in other cases. The outcome was good (back to work) in 90 patients and poor (severely disabled) in 4. Five patients died because of severity of brain damage and meningitis. The effect of the different enumerated variables upon the outcome was measured using chi(2) and Fisher exact test, which was nonsignificant for all of the variables except for the orbitofacial entry point of injury (p = 0.00006). This study seems to indicate that not only is reoperation for retained bone or shell fragments unnecessary, but surgeons having modern neuroradiological instruments available to detect the proper explanation for changes in GCS of the patients may decide not to proceed with any surgical intervention in a good number of patients. As a result of the "no surgical treatment protocol," one can preserve cerebral tissue without exposing the patient to undue risk of seizures, infection, or death by leaving behind some or all the in-driven bone and shell fragments.

Far-field brainstem responses evoked by vestibular and auditory stimuli exhibit increases in interpeak latency as brain temperature is decreased

NASA Technical Reports Server (NTRS)

Hoffman, L. F.; Horowitz, J. M.

1984-01-01

The effect of decreasing of brain temperature on the brainstem auditory evoked response (BAER) in rats was investigated. Voltage pulses, applied to a piezoelectric crystal attached to the skull, were used to evoke stimuli in the auditory system by means of bone-conducted vibrations. The responses were recorded at 37 C and 34 C brain temperatures. The peaks of the BAER recorded at 34 C were delayed in comparison with the peaks from the 37 C wave, and the later peaks were more delayed than the earlier peaks. These results indicate that an increase in the interpeak latency occurs as the brain temperature is decreased. Preliminary experiments, in which responses to brief angular acceleration were used to measure the brainstem vestibular evoked response (BVER), have also indicated increases in the interpeak latency in response to the lowering of brain temperature.

26Al incorporation into the tissues of suckling rats through maternal milk

NASA Astrophysics Data System (ADS)

Yumoto, S.; Nagai, H.; Kobayashi, K.; Tada, W.; Horikawa, T.; Matsuzaki, H.

2004-08-01

Aluminium (Al) is highly neurotoxic and inhibits prenatal and postnatal development of the brain in humans and experimental animals. However, Al incorporation into the brain of sucklings through maternal milk has not yet been well clarified because Al lacks a suitable isotope for radioactive tracer experiments. Using 26Al as a tracer, we measured 26Al incorporation into the brain of suckling rats by accelerator mass spectrometry. Lactating rats were subcutaneously injected with 26AlCl3 from day 1 to day 20 postpartum. Suckling rats were weaned from day 21 postpartum. From day 5 to day 20 postpartum, the 26Al levels measured in the brain, liver, kidneys and bone of suckling rats increased significantly. After weaning, the amounts of 26Al in the liver and kidneys decreased remarkably. However, the 26Al amount in the brain had diminished only slightly up to 140 days after weaning.

Mechanical Evaluation of the Skeletal Structure and Tissue of the Woodpecker and Its Shock Absorbing System

NASA Astrophysics Data System (ADS)

Oda, Juhachi; Sakamoto, Jiro; Sakano, Kenichi

A woodpecker strikes its beak toward a tree repeatedly. But, the damage of brain or the brain concussion doesn’t occur by this action. Human cannot strike strongly the head without the damage of a brain. Therefore, it is predicted that the brain of a woodpecker is protected from the shock by some methods and that the woodpecker has the original mechanism to absorb a shock. In this study, the endoskeltal structure, especially head part structure of woodpecker is dissected and the impact-proof system is analyzed by FEM and model experiment. From the results, it is obvious that the woodpecker has the original impact-proof system as the unique states of hyoid bone, skull, tissue and brain. Moreover it is considered that woodpecker has the advanced impact-proof system relating with not only the head part but also with the whole body.

A comparison between anisotropic analytical and multigrid superposition dose calculation algorithms in radiotherapy treatment planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Vincent W.C., E-mail: htvinwu@polyu.edu.hk; Tse, Teddy K.H.; Ho, Cola L.M.

2013-07-01

Monte Carlo (MC) simulation is currently the most accurate dose calculation algorithm in radiotherapy planning but requires relatively long processing time. Faster model-based algorithms such as the anisotropic analytical algorithm (AAA) by the Eclipse treatment planning system and multigrid superposition (MGS) by the XiO treatment planning system are 2 commonly used algorithms. This study compared AAA and MGS against MC, as the gold standard, on brain, nasopharynx, lung, and prostate cancer patients. Computed tomography of 6 patients of each cancer type was used. The same hypothetical treatment plan using the same machine and treatment prescription was computed for each casemore » by each planning system using their respective dose calculation algorithm. The doses at reference points including (1) soft tissues only, (2) bones only, (3) air cavities only, (4) soft tissue-bone boundary (Soft/Bone), (5) soft tissue-air boundary (Soft/Air), and (6) bone-air boundary (Bone/Air), were measured and compared using the mean absolute percentage error (MAPE), which was a function of the percentage dose deviations from MC. Besides, the computation time of each treatment plan was recorded and compared. The MAPEs of MGS were significantly lower than AAA in all types of cancers (p<0.001). With regards to body density combinations, the MAPE of AAA ranged from 1.8% (soft tissue) to 4.9% (Bone/Air), whereas that of MGS from 1.6% (air cavities) to 2.9% (Soft/Bone). The MAPEs of MGS (2.6%±2.1) were significantly lower than that of AAA (3.7%±2.5) in all tissue density combinations (p<0.001). The mean computation time of AAA for all treatment plans was significantly lower than that of the MGS (p<0.001). Both AAA and MGS algorithms demonstrated dose deviations of less than 4.0% in most clinical cases and their performance was better in homogeneous tissues than at tissue boundaries. In general, MGS demonstrated relatively smaller dose deviations than AAA but required longer computation time.« less

Historical trends in the use of radiation therapy for pediatric cancers: 1973-2008.

PubMed

Jairam, Vikram; Roberts, Kenneth B; Yu, James B

2013-03-01

This study was undertaken to assess historical trends in the use of radiation therapy (RT) for pediatric cancers over the past 4 decades. The National Cancer Institute's Surveillance, Epidemiology, and End Results database of the 9 original tumor registries (SEER-9) was queried to identify patients aged 0 to 19 years with acute lymphoblastic leukemia, acute myeloid leukemia, bone and joint cancer, cancer of the brain and nervous system, Hodgkin lymphoma, neuroblastoma, non-Hodgkin lymphoma, soft tissue cancer, Wilms tumor, or retinoblastoma from 1973 to 2008. Patients were grouped into 4-year time epochs. The number and percentage of patients who received RT as part of their initial treatment were calculated per epoch by each diagnosis group from 1973 to 2008. RT use for acute lymphoblastic leukemia, non-Hodgkin lymphoma, and retinoblastoma declined sharply from 57%, 57%, and 30% in 1973 to 1976 to 11%, 15%, and 2%, respectively, in 2005 to 2008. Similarly, smaller declines in RT use were also seen in brain cancer (70%-39%), bone cancer (41%-21%), Wilms tumor (75%-53%), and neuroblastoma (60%-25%). RT use curves for Wilms tumor and neuroblastoma were nonlinear with nadirs in 1993 to 1996 at 39% and 19%, respectively. There were minimal changes in RT use for Hodgkin lymphoma, soft tissue cancer, or acute myeloid leukemia, roughly stable at 72%, 40%, and 11%, respectively. Almost all patients treated with RT were given external beam RT exclusively. However, from 1985 to 2008, treatments involving brachytherapy, radioisotopes, or combination therapy increased in frequency, comprising 1.8%, 4.6%, and 11.9% of RT treatments in brain cancer, soft tissue cancer, and retinoblastoma, respectively. The use of RT is declining over time in 7 of 10 pediatric cancer categories. A limitation of this study is a potential under-ascertainment of RT use in the SEER-9 database including the delayed use of RT. Copyright © 2013 Elsevier Inc. All rights reserved.

Historical Trends in the Use of Radiation Therapy for Pediatric Cancers: 1973-2008

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jairam, Vikram; Roberts, Kenneth B.; Yale Cancer Center, New Haven, Connecticut

Purpose: This study was undertaken to assess historical trends in the use of radiation therapy (RT) for pediatric cancers over the past 4 decades. Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results database of the 9 original tumor registries (SEER-9) was queried to identify patients aged 0 to 19 years with acute lymphoblastic leukemia, acute myeloid leukemia, bone and joint cancer, cancer of the brain and nervous system, Hodgkin lymphoma, neuroblastoma, non-Hodgkin lymphoma, soft tissue cancer, Wilms tumor, or retinoblastoma from 1973 to 2008. Patients were grouped into 4-year time epochs. The number and percentage of patients whomore » received RT as part of their initial treatment were calculated per epoch by each diagnosis group from 1973 to 2008. Results: RT use for acute lymphoblastic leukemia, non-Hodgkin lymphoma, and retinoblastoma declined sharply from 57%, 57%, and 30% in 1973 to 1976 to 11%, 15%, and 2%, respectively, in 2005 to 2008. Similarly, smaller declines in RT use were also seen in brain cancer (70%-39%), bone cancer (41%-21%), Wilms tumor (75%-53%), and neuroblastoma (60%-25%). RT use curves for Wilms tumor and neuroblastoma were nonlinear with nadirs in 1993 to 1996 at 39% and 19%, respectively. There were minimal changes in RT use for Hodgkin lymphoma, soft tissue cancer, or acute myeloid leukemia, roughly stable at 72%, 40%, and 11%, respectively. Almost all patients treated with RT were given external beam RT exclusively. However, from 1985 to 2008, treatments involving brachytherapy, radioisotopes, or combination therapy increased in frequency, comprising 1.8%, 4.6%, and 11.9% of RT treatments in brain cancer, soft tissue cancer, and retinoblastoma, respectively. Conclusions: The use of RT is declining over time in 7 of 10 pediatric cancer categories. A limitation of this study is a potential under-ascertainment of RT use in the SEER-9 database including the delayed use of RT.« less

Co-registration of multi-modality imaging allows for comprehensive analysis of tumor-induced bone disease

PubMed Central

Seeley, Erin H.; Wilson, Kevin J.; Yankeelov, Thomas E.; Johnson, Rachelle W.; Gore, John C.; Caprioli, Richard M.; Matrisian, Lynn M.; Sterling, Julie A.

2014-01-01

Bone metastases are a clinically significant problem that arises in approximately 70% of metastatic breast cancer patients. Once established in bone, tumor cells induce changes in the bone microenvironment that lead to bone destruction, pain, and significant morbidity. While much is known about the later stages of bone disease, less is known about the earlier stages or the changes in protein expression in the tumor micro-environment. Due to promising results of combining magnetic resonance imaging (MRI) and Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry (MALDI IMS) ion images in the brain, we developed methods for applying these modalities to models of tumor-induced bone disease in order to better understand the changes in protein expression that occur within the tumor-bone microenvironment. Specifically, we integrated three dimensional-volume reconstructions of spatially resolved MALDI IMS with high-resolution anatomical and diffusion weighted MRI data and histology in an intratibial model of breast tumor-induced bone disease. This approach enables us to analyze proteomic profiles from MALDI IMS data with corresponding in vivo imaging and ex vivo histology data. To the best of our knowledge, this is the first time these three modalities have been rigorously registered in the bone. The MALDI mass-to-charge ratio peaks indicate differential expression of calcyclin, ubiquitin, and other proteins within the tumor cells, while peaks corresponding to hemoglobin A and calgranulin A provided molecular information that aided in the identification of areas rich in red and white blood cells, respectively. This multimodality approach will allow us to comprehensively understand the bone-tumor microenvironment and thus may allow us to better develop and test approaches for inhibiting bone metastases. PMID:24487126

Boron and silicon: Effects on growth, plasma lipids, urinary cyclic AMP and bone and brain mineral composition of male rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seaborn, C.D.; Nielsen, F.H.

1994-06-01

Because boron resembles silicon in its chemical properties, an experiment was performed to determine if excessive dietary boron would affect the response to silicon deprivation and, conversely, if silicon would influence the effects of an excessive intake of boron. Male weanling Sprague-Dawley rats were assigned to groups of 6 or 12 in a two-by-two factorially arranged experiment. Supplemented to a ground corn/casein diet containing 1.2 [mu]g silicon and 3 [mu]g boron per gram were silicon as sodium metasilicate at 0 or 50 [mu]g/g and boron as orthoboric acid at 0 or 500 [mu]g/g diet. At nine weeks, animals fed highmore » dietary boron had significantly decreased final body weights, liver-weight-to-body-weight ratios, urinary cAMP concentrations, plasma triglyceride, cholesterol, glycine, valine, leucine, and lysine concentrations and skull copper, sodium, and manganese concentrations. High dietary boron also significantly increased brain-weight-to-body-weight ratios, magnesium concentrations of femur, brain, and plasma, zinc concentration of femur, and iron concentration of skull. The bone mineral findings suggest that excess dietary boron exerts subtle effects on bone composition. Dietary silicon affected blood urea nitrogen, hematocrit, hemoglobin, and the concentrations of plasma threonine and aspartic acid in animals fed excess boron. Depression of the testes-weight-to-body-weight ratio of animals fed 500 [mu]g boron per gram diet was most marked in animals not fed silicon. Although excessive dietary boron did not markedly enhanced the response of rats to silicon deprivation, dietary silicon affected their response to high dietary boron. Thus, dietary silicon apparently can influence boron toxicity.« less

Site of metastasis and breast cancer mortality: a Danish nationwide registry-based cohort study.

PubMed

Ording, Anne Gulbech; Heide-Jørgensen, Uffe; Christiansen, Christian Fynbo; Nørgaard, Mette; Acquavella, John; Sørensen, Henrik Toft

2017-01-01

Survival among patients with metastatic breast cancer may vary according to the site of metastasis and receptor status. We used Danish nationwide medical registries to establish a cohort of patients with metastatic breast cancer (870 with de novo metastatic disease and 3518 with recurrent disease with distant metastasis) diagnosed during 1997-2011. We examined 1-year and >1 to 5-year mortality associated with first site of metastasis and receptor expression status of the primary tumor. Cox proportional regression was used to compute confounder-adjusted mortality rate ratios (MRRs) associated with site of metastasis, stratified by receptor status. Overall 1-year and >1 to 5-year mortality risks were 36 and 69 %, respectively. Risk of death within 1 year was highest for brain-only (62 %) and liver-only (43 %) involvement and nearly the same for patients with lung-only (32 %), bone-only (32 %) involvement, and other/combination of sites (34 %). Using bone-only metastasis as reference, women with brain-only metastasis had more than two-fold increased risk of dying. The adjusted MRR for women with liver-only metastasis also was increased, though less pronounced. Patients with lung-only [adjusted MRR 0.9 (95 % confidence interval (CI) 0.8, 1.1)] or other metastases [adjusted MRR 1.0 (95 % CI 0.9, 1.2)] had similar mortality as patients with bone-only metastasis. Positive hormonal receptor status was a favorable prognostic factor. Metastatic breast cancer has a serious prognosis. Patients with brain-only metastasis had the highest mortality. Positive hormonal receptor status on the primary tumor was a favorable prognostic factor for all metastatic sites.

Neuronal hypothalamic regulation of body metabolism and bone density is galanin dependent.

PubMed

Idelevich, Anna; Sato, Kazusa; Nagano, Kenichi; Rowe, Glenn; Gori, Francesca; Baron, Roland

2018-06-01

In the brain, the ventral hypothalamus (VHT) regulates energy and bone metabolism. Whether this regulation uses the same or different neuronal circuits is unknown. Alteration of AP1 signaling in the VHT increases energy expenditure, glucose utilization, and bone density, yet the specific neurons responsible for each or all of these phenotypes are not identified. Using neuron-specific, genetically targeted AP1 alterations as a tool in adult mice, we found that agouti-related peptide-expressing (AgRP-expressing) or proopiomelanocortin-expressing (POMC-expressing) neurons, predominantly present in the arcuate nucleus (ARC) within the VHT, stimulate whole-body energy expenditure, glucose utilization, and bone formation and density, although their effects on bone resorption differed. In contrast, AP1 alterations in steroidogenic factor 1-expressing (SF1-expressing) neurons, present in the ventromedial hypothalamus (VMH), increase energy but decrease bone density, suggesting that these effects are independent. Altered AP1 signaling also increased the level of the neuromediator galanin in the hypothalamus. Global galanin deletion (VHT galanin silencing using shRNA) or pharmacological galanin receptor blockade counteracted the observed effects on energy and bone. Thus, AP1 antagonism reveals that AgRP- and POMC-expressing neurons can stimulate body metabolism and increase bone density, with galanin acting as a central downstream effector. The results obtained with SF1-expressing neurons, however, indicate that bone homeostasis is not always dictated by the global energy status, and vice versa.

Calvarial bone cavernous hemangioma with intradural invasion: An unusual aggressive course-Case report and literature review.

PubMed

Nasi, Davide; Somma, Lucia di; Iacoangeli, Maurizio; Liverotti, Valentina; Zizzi, Antonio; Dobran, Mauro; Gladi, Maurizio; Scerrati, Massimo

2016-01-01

Cavernous hemangioma of the skull is a rare pathological diagnosis, accounting for 0.2% of bone tumors and 7% of skull tumors. Usually calvarial bone cavernous hemangioma are associated with a benign clinical course and, despite their enlargement and subsequent erosion of the surrounding bone, the inner table of the skull remains intact and the lesion is completely extracranial. The authors present the unique case of a huge left frontal bone cavernous malformation with intradural extension and brain compression determining a right hemiparesis. Calvarial cavernous hemangiomas are benign tumors. They arise from vessels in the diploic space and tend to involve the outer table of the skull with relative sparing of the inner table. More extensive involvement of the inner table and extradural space is very unusual and few cases are reported in literature. To the best of our knowledge, intradural invasion of calvarial hemangioma has not been previously reported. Our case highlights the possibility of an aggressive course of this rare benign pathology. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Calvarial bone cavernous hemangioma with intradural invasion: An unusual aggressive course—Case report and literature review

PubMed Central

Nasi, Davide; Somma, Lucia di; Iacoangeli, Maurizio; Liverotti, Valentina; Zizzi, Antonio; Dobran, Mauro; Gladi, Maurizio; Scerrati, Massimo

2016-01-01

Introduction Cavernous hemangioma of the skull is a rare pathological diagnosis, accounting for 0.2% of bone tumors and 7% of skull tumors. Usually calvarial bone cavernous hemangioma are associated with a benign clinical course and, despite their enlargement and subsequent erosion of the surrounding bone, the inner table of the skull remains intact and the lesion is completely extracranial. Presentation of a case The authors present the unique case of a huge left frontal bone cavernous malformation with intradural extension and brain compression determining a right hemiparesis. Discussion Calvarial cavernous hemangiomas are benign tumors. They arise from vessels in the diploic space and tend to involve the outer table of the skull with relative sparing of the inner table. More extensive involvement of the inner table and extradural space is very unusual and few cases are reported in literature. To the best of our knowledge, intradural invasion of calvarial hemangioma has not been previously reported. Conclusion Our case highlights the possibility of an aggressive course of this rare benign pathology. PMID:27061482

An unusual case of cerebral penetrating injury by a driven bone fragment secondary to blunt head trauma.

PubMed

Lee, Jae Il; Ko, Jun Kyeung; Cha, Seung Heon; Han, In Ho

2011-12-01

Temple trauma that appears initially localized to the skin might possess intracranial complications. Early diagnosis and management of such complications are important, to avoid neurologic sequelae. Non-penetrating head injuries with intracranial hemorrhage caused by a driven bone fragment are extremely rare. A 53-year-old male was referred to our hospital because of intracerebral hemorrhage. He was a mechanic and one day before admission to a local clinic, tip of metallic rod hit his right temple while cutting the rod. Initial brain computed tomography (CT) and magnetic resonance imaging demonstrated scanty subdural hematoma at right temporal lobe and left falx and intracerebral hematoma at both frontal lobes. Facial CT with 3-D reconstruction images showed a small bony defect at the right sphenoid bone's greater wing and a small bone fragment at the left frontal lobe, crossing the falx. We present the unusual case of a temple trauma patient in whom a sphenoid bone fragment migrated from its origin upward, to the contralateral frontal lobe, producing hematoma along its trajectory.

Intracranial pressure changes during mouse development.

PubMed

Moazen, Mehran; Alazmani, Ali; Rafferty, Katherine; Liu, Zi-Jun; Gustafson, Jennifer; Cunningham, Michael L; Fagan, Michael J; Herring, Susan W

2016-01-04

During early stages of postnatal development, pressure from the growing brain as well as cerebrospinal fluid, i.e. intracranial pressure (ICP), load the calvarial bones. It is likely that such loading contributes to the peripheral bone formation at the sutural edges of calvarial bones, especially shortly after birth when the brain is growing rapidly. The aim of this study was to quantify ICP during mouse development. A custom pressure monitoring system was developed and calibrated. It was then used to measure ICP in a total of seventy three wild type mice at postnatal (P) day 3, 10, 20, 31 and 70. Retrospectively, the sample in each age group with the closest ICP to the average value was scanned using micro-computed tomography to estimate cranial growth. ICP increased from 1.33±0.87mmHg at P3 to 1.92±0.78mmHg at P10 and 3.60±1.08mmHg at P20. In older animals, ICP plateaued at about 4mmHg. There were statistically significant differences between the ICP at the P3 vs. P20, and P10 vs. P20. In the samples that were scanned, intracranial volume and skull length followed a similar pattern of increase up to P20 and then plateaued at older ages. These data are consistent with the possibility of ICP being a contributing factor to bone formation at the sutures during early stages of development. The data can be further used for development and validation of computational models of skull growth. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sex-dependent changes in brain CB1R expression and functionality and immune CB2R expression as a consequence of maternal deprivation and adolescent cocaine exposure.

PubMed

Llorente-Berzal, Alvaro; Assis, María A; Rubino, Tiziana; Zamberletti, Erica; Marco, Eva M; Parolaro, Daniela; Ambrosio, Emilio; Viveros, María-Paz

2013-08-01

Early life stress has been associated with several psychiatric disorders, including drug addiction. Actually, maternal deprivation (MD) alters the endocannabinoid system, which participates in motivation and reward for drugs, including cocaine. At youth, the rate of cocaine abuse is alarmingly increasing. Herein, we have investigated the consequences of MD and/or adolescent cocaine exposure in brain CB1Rs and CB2Rs in immune tissues. Control and maternally deprived (24h on postnatal day, pnd, 9) male and female Wistar rats were administered cocaine (8mg/kg/day) or saline during adolescence (pnd 28-42). At adulthood, [(3)H]-CP-55,940 autoradiographic binding was employed for the analysis of CB1R density and CP-55,940-stimulated [(35)S]-GTPgammaS binding for CB1R functionality; CB2R expression was analyzed by Western blotting. Sex differences in CB1R expression and functionality were found, and MD induced important and enduring sex-dependent changes. In addition, the plastic changes induced by adolescent cocaine administration in brain CB1Rs were differentially influenced by early life events. MD increased spleen CB2R expression while adolescent cocaine administration attenuated this effect; cocaine exposure also diminished CB2R expression in bone marrow. Present findings provide evidence for changes in brain CB1R expression and functionality and immune CB2R expression as a consequence of early life stress and adolescent cocaine exposure, and indicate functional interactions between both treatments, which in many regions differ between males and females. Copyright © 2013 Elsevier Ltd. All rights reserved.

Functional roles of the sweet taste receptor in oral and extraoral tissues

PubMed Central

Laffitte, Anni; Neiers, Fabrice; Briand, Loïc

2014-01-01

Purpose of review This review summarizes and discusses the current knowledge about the physiological roles of the sweet taste receptor in oral and extraoral tissues. Recent findings The expression of a functional sweet taste receptor has been reported in numerous extragustatory tissues, including the gut, pancreas, bladder, brain and, more recently, bone and adipose tissues. In the gut, this receptor has been suggested to be involved in luminal glucose sensing, the release of some satiety hormones, the expression of glucose transporters, and the maintenance of glucose homeostasis. More recently, the sweet taste receptor was proposed to regulate adipogenesis and bone biology. Summary The perception of sweet taste is mediated by the T1R2/T1R3 receptor, which is expressed in the oral cavity, wherein it provides input on the caloric and macronutrient contents of ingested food. This receptor recognizes all the chemically diverse compounds perceived as sweet by human beings, including natural sugars and sweeteners. Importantly, the expression of a functional sweet taste receptor has been reported in numerous extragustatory tissues, wherein it has been proposed to regulate metabolic processes. This newly recognized role of the sweet taste receptor makes this receptor a potential novel therapeutic target for the treatment of obesity and related metabolic dysfunctions, such as diabetes and hyperlipidemia. PMID:24763065

The metastasis suppressor RARRES3 as an endogenous inhibitor of the immunoproteasome expression in breast cancer cells

NASA Astrophysics Data System (ADS)

Anderson, Alison M.; Kalimutho, Murugan; Harten, Sarah; Nanayakkara, Devathri M.; Khanna, Kum Kum; Ragan, Mark A.

2017-01-01

In breast cancer metastasis, the dynamic continuum involving pro- and anti-inflammatory regulators can become compromised. Over 600 genes have been implicated in metastasis to bone, lung or brain but how these genes might contribute to perturbation of immune function is poorly understood. To gain insight, we adopted a gene co-expression network approach that draws on the functional parallels between naturally occurring bone marrow-derived mesenchymal stem cells (BM-MSCs) and cancer stem cells (CSCs). Our network analyses indicate a key role for metastasis suppressor RARRES3, including potential to regulate the immunoproteasome (IP), a specialized proteasome induced under inflammatory conditions. Knockdown of RARRES3 in near-normal mammary epithelial and breast cancer cell lines increases overall transcript and protein levels of the IP subunits, but not of their constitutively expressed counterparts. RARRES3 mRNA expression is controlled by interferon regulatory factor IRF1, an inducer of the IP, and is sensitive to depletion of the retinoid-related receptor RORA that regulates various physiological processes including immunity through modulation of gene expression. Collectively, these findings identify a novel regulatory role for RARRES3 as an endogenous inhibitor of IP expression, and contribute to our evolving understanding of potential pathways underlying breast cancer driven immune modulation.

Space research on organs and tissues

NASA Technical Reports Server (NTRS)

Tischler, Marc E.; Morey-Holton, Emily

1993-01-01

Studies in space on various physiological systems have and will continue to provide valuable information on how they adapt to reduced gravitational conditions, and how living in a 1 g (gravity) environment has guided their development. Muscle and bone are the most notable tissues that respond to unweighting caused by lack of gravity. The function of specific muscles and bones relates directly to mechanical loading, so that removal of 'normal forces' in space, or in bedridden patients, causes dramatic loss of tissue mass. The cardiovascular system is also markedly affected by reduced gravity. Adaptation includes decreased blood flow to the lower extremities, thus decreasing the heart output requirement. Return to 1 g is associated with a period of reconditioning due to the deconditioning that occurs in space. Changes in the cardiovascular system are also related to responses of the kidney and certain endocrine (hormone-producing) organs. Changes in respiratory function may also occur, suggesting an effect on the lungs, though this adaptation is poorly understood. The neurovestibular system, including the brain and organs of the inner ear, must adapt to the disorientation caused by lack of gravity. Preliminary findings have been reported for liver. Additionally, endocrine organs responsible for release of hormones such as insulin, growth hormone, glucocorticoids, and thyroid hormone may respond to spaceflight.

18F-NaF PET Demonstrating Unusual Focal Tracer Activity in the Brain.

PubMed

Thenkondar, Anuradha; Jafari, Lida; Sooriash, Robbie; Hajsadeghi, Fereshteh; Berenji, Gholam R; Li, Yuxin

2017-02-01

A 60-year-old man with enlarged prostate, hypertension, and diabetes was referred for F-NaF PET/CT to evaluate possible metastatic lesions. The patient appeared asymptomatic on the day of the study, without any signs indicating stroke. Patient also had no known history of malignancy or cerebrovascular disease. He had mild elevation of the prostate-specific antigen level, and biopsy of his prostate was not performed. Patient had long-standing history of chronic back pain and abdominal pain. The PET bone scan demonstrated a large area of very intense tracer uptake in the brain. A subsequent brain MRI revealed prior stroke in the same area.

Gadolinium toxicity and treatment.

PubMed

Ramalho, Joana; Ramalho, Miguel; Jay, Michael; Burke, Lauren M; Semelka, Richard C

2016-12-01

Gadolinium based contrast agents (GBCAs) play an important role in the diagnostic evaluation of many patients. The safety of these agents has been once again questioned after gadolinium deposits were observed and measured in brain and bone of patients with normal renal function. This retention of gadolinium in the human body has been termed "gadolinium storage condition". The long-term and cumulative effects of retained gadolinium in the brain and elsewhere are not as yet understood. Recently, patients who report that they suffer from chronic symptoms secondary to gadolinium exposure and retention created gadolinium-toxicity on-line support groups. Their self-reported symptoms have recently been published. Bone and joint complaints, and skin changes were two of the most common complaints. This condition has been termed "gadolinium deposition disease". In this review we will address gadolinium toxicity disorders, from acute adverse reactions to GBCAs to gadolinium deposition disease, with special emphasis on the latter, as it is the most recently described and least known. Copyright © 2016 Elsevier Inc. All rights reserved.

A voxel-based investigation for MRI-only radiotherapy of the brain using ultra short echo times

NASA Astrophysics Data System (ADS)

Edmund, Jens M.; Kjer, Hans M.; Van Leemput, Koen; Hansen, Rasmus H.; Andersen, Jon AL; Andreasen, Daniel

2014-12-01

Radiotherapy (RT) based on magnetic resonance imaging (MRI) as the only modality, so-called MRI-only RT, would remove the systematic registration error between MR and computed tomography (CT), and provide co-registered MRI for assessment of treatment response and adaptive RT. Electron densities, however, need to be assigned to the MRI images for dose calculation and patient setup based on digitally reconstructed radiographs (DRRs). Here, we investigate the geometric and dosimetric performance for a number of popular voxel-based methods to generate a so-called pseudo CT (pCT). Five patients receiving cranial irradiation, each containing a co-registered MRI and CT scan, were included. An ultra short echo time MRI sequence for bone visualization was used. Six methods were investigated for three popular types of voxel-based approaches; (1) threshold-based segmentation, (2) Bayesian segmentation and (3) statistical regression. Each approach contained two methods. Approach 1 used bulk density assignment of MRI voxels into air, soft tissue and bone based on logical masks and the transverse relaxation time T2 of the bone. Approach 2 used similar bulk density assignments with Bayesian statistics including or excluding additional spatial information. Approach 3 used a statistical regression correlating MRI voxels with their corresponding CT voxels. A similar photon and proton treatment plan was generated for a target positioned between the nasal cavity and the brainstem for all patients. The CT agreement with the pCT of each method was quantified and compared with the other methods geometrically and dosimetrically using both a number of reported metrics and introducing some novel metrics. The best geometrical agreement with CT was obtained with the statistical regression methods which performed significantly better than the threshold and Bayesian segmentation methods (excluding spatial information). All methods agreed significantly better with CT than a reference water MRI comparison. The mean dosimetric deviation for photons and protons compared to the CT was about 2% and highest in the gradient dose region of the brainstem. Both the threshold based method and the statistical regression methods showed the highest dosimetrical agreement. Generation of pCTs using statistical regression seems to be the most promising candidate for MRI-only RT of the brain. Further, the total amount of different tissues needs to be taken into account for dosimetric considerations regardless of their correct geometrical position.

Brain-mediated dysregulation of the bone marrow activity in angiotensin II-induced hypertension.

PubMed

Jun, Joo Yun; Zubcevic, Jasenka; Qi, Yanfei; Afzal, Aqeela; Carvajal, Jessica Marulanda; Thinschmidt, Jeffrey S; Grant, Maria B; Mocco, J; Raizada, Mohan K

2012-11-01

Oxidative stress in the brain is implicated in increased sympathetic drive, inflammatory status, and vascular dysfunctions, associated with development and establishment of hypertension. However, little is known about the mechanism of this impaired brain-vascular communication. Here, we tested the hypothesis that increased oxidative stress in the brain cardioregulatory areas, such as the paraventricular nucleus of the hypothalamus, is driven by mitochondrial reactive oxygen species and leads to increased inflammatory cells (ICs) and decreased/dysfunctional endothelial progenitor cells (EPCs), thereby compromising vasculature repair and accelerating hypertension. Chronic angiotensin II infusion resulted in elevated blood pressure and sympathetic vasomotor drive, decreased spontaneous baroreflex gain, and increased microglia activation in the paraventricular nucleus. This was associated with 46% decrease in bone marrow (BM)-derived EPCs and 250% increase in BM ICs, resulting in 5-fold decrease of EPC/IC ratio in the BM. Treatment with mitochondrial-targeted antioxidant, a scavenger of mitochondrial O(2)(-·), intracerebroventricularly but not subcutaneously attenuated angiotensin II-induced hypertension, decreased activation of microglia in the paraventricular nucleus, and normalized EPCs/ICs. This functional communication between the brain and BM was confirmed by retrograde neuronal labeling from the BM with green fluorescent protein-tagged pseudorabies virus. Administration of green fluorescent protein-tagged pseudorabies virus into the BM resulted in predominant labeling of paraventricular nucleus neurons within 3 days, with some fluorescence in the nucleus tractus solitarius, the rostral ventrolateral medulla, and subfornical organ. Taken together, these data demonstrate that inhibition of mitochondrial reactive oxygen species attenuates angiotensin II-induced hypertension and corrects the imbalance in EPCs/ICs in the BM. They suggest that an imbalance in vascular reparative and ICs may perpetuate vascular pathophysiology in this model of hypertension.

The neurologic findings in Taybi-Linder syndrome (MOPD I/III): case report and review of the literature.

PubMed

Pierce, Melinda J; Morse, Richard P

2012-03-01

Taybi-Linder syndrome, also known as microcephalic osteodysplastic primordial dwarfism types I and III, is a rare disorder with presumed autosomal recessive inheritance. It is characterized by intrauterine growth retardation, distinctive bone dysplasia, and central nervous system malformations. We present two siblings with Taybi-Linder syndrome, with an emphasis on the neurological profile in this disease, which includes brain malformations, intractable epilepsy, sensory deficits, profound cognitive deficits, and neuroendocrine dysfunction. We also present distinctive correlative neuroimaging (MRI) and electroencephalographic (EEG) findings. Increased knowledge of the neurological profile of Taybi-Linder syndrome may be helpful for clinicians and genetic counselors managing these patients. Copyright © 2012 Wiley Periodicals, Inc.

Computed tomographic detection of sinusitis responsible for intracranial and extracranial infections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carter, B.L.; Bankoff, M.S.; Fisk, J.D.

1983-06-01

Computed tomography (CT) is now used extensively for the evaluation of orbital, facial, and intracranial infections. Nine patients are presented to illustrate the importance of detecting underlying and unsuspected sinusitis. Prompt treatment of the sinusitis is essential to minimize the morbidity and mortality associated with complications such as brain abscess, meningitis, orbital cellulitis, and osteomyelitis. A review of the literature documents the persistence of these complications despite the widespread use of antibiotic therapy. Recognition of the underlying sinusitis is now possible with CT if the region of the sinuses is included and bone-window settings are used during the examination ofmore » patients with orbital and intracranial infection.« less

Bilateral parotid gland enlargement and palpable nephromegaly in infant acute lymphoblastic leukemia: case report and review of the literature.

PubMed

Saha, Aniket; Dandekar, Smita; Milla, Sarah; Roman, Elizabeth; Bhatla, Teena

2014-04-01

Acute lymphoblastic leukemia (ALL) in infants below 1 year of age accounts for 2.5% to 5% of childhood ALL. Most children with ALL present with fever, bruising, mucosal bleeding, bone pain, pallor, hepatosplenomegaly, and lymphadenopathy. Common sites of extramedullary involvement at diagnosis include liver, spleen, lymph nodes, brain, and testes. Nephromegaly has also been reported. We present a novel case of bilateral parotid enlargement along with bilateral palpable nephromegaly in a patient with newly diagnosed infant ALL. This unique presentation highlights the importance of considering ALL in the differential diagnosis of parotid enlargement especially when associated with abnormal blood counts.

Psychosocial reactions in the spouses of patients suffering polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy.

PubMed

Hakola, H P

1990-01-01

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLO-SL) is a rare hereditary disease affecting both brain and bones. Skeletal symptoms begin in early adulthood and neuropsychiatric symptoms at approximately age 30. Progressive dementia associated with an accentuated frontal lobe syndrome handicaps the patients. The author describes inadequate psychosocial reactions of the spouses of 21 Finnish PLO-SL patients. The reactions included rejection and divorce in 8 cases and rejection without divorce in 1 case. Jealousy, violence, and alcoholism were common in male spouses. The author suggests that some of the spouses' negative psychosocial reactions may be lessened if the family is informed early about the nature of the disorder.

Serratia marcescens osteomyelitis in Cushing's disease

PubMed Central

Martins, Hugo F G; Raposo, Alexandra; Baptista, Isabel; Almeida, Julio

2015-01-01

We report a case of a 46-year-old man with fever, hypotension and arthralgias of the ankles and knees after brain surgery for a pituitary tumour causing Cushing's disease. Blood and urine cultures isolated Serratia marcescens; antibiotic susceptibility testing showed sensitivity to piperacillin-tazobactan and ciprofloxacin. Articular MRI showed inflammation and necrosis of both knees and ankles, and left hip and right elbow (compatible with osteomyelitis). Culture of an ankle abscess on the ankle joint was positive for Serratia marcescens. Bone scintigraphy confirmed osteomyelitic lesions. Medical treatment included antibiotics and strong opioid therapy for 14 weeks. The patient was discharged clinically improved maintaining ciprofloxacin for 24 additional weeks based on clinical and analytic recovery. PMID:26621903

Bone tumor

MedlinePlus

Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

Design and Construction of a Multi-Organ Microfluidic Chip Mimicking the in vivo Microenvironment of Lung Cancer Metastasis.

PubMed

Xu, Zhiyun; Li, Encheng; Guo, Zhe; Yu, Ruofei; Hao, Hualong; Xu, Yitong; Sun, Zhao; Li, Xiancheng; Lyu, Jianxin; Wang, Qi

2016-10-05

Metastasis is a complex pathophysiological process. As the main cause of cancer mortality in humans it represents a serious challenge to both basic researchers and clinicians. Here we report the design and construction of a multi-organ microfluidic chip that closely mimics the in vivo microenvironment of lung cancer metastasis. This multi-organs-on-a-chip includes an upstream "lung" and three downstream "distant organs", with three polydimethylsiloxane (PDMS) layers and two thin PDMS microporous membranes bonded to form three parallel microchannels. Bronchial epithelial, lung cancer, microvascular endothelial, mononuclear, and fibroblast cells were grown separated by the biomembrane in upstream "lung", while astrocytes, osteocytes, and hepatocytes were grown in distant chambers, to mimic lung cancer cell metastasis to the brain, bone, and liver. After culture in this system, lung cancer cells formed a "tumor mass", showed epithelial-mesenchymal transition (with altered expression of E-cadherin, N-cadherin, Snail1, and Snail2) and invasive capacity. A549 cells co-cultured with astrocytes overexpressed CXCR4 protein, indicating damage of astrocytes after cancer cell metastasis to the brain. Osteocytes overexpressed RANKL protein indicates damage of osteocytes after cancer cell metastasis to the bone, and hepatocytes overexpressed AFP protein indicates damage to hepatocytes after cancer cell metastasis to the liver. Finally, in vivo imaging of cancer growth and metastasis in a nude mice model validated the performance of metastasis in the organs-on-chip system. This system provides a useful tool to mimic the in vivo microenvironment of cancer metastasis and to investigate cell-cell interactions during metastasis.

Generation of Organ-conditioned Media and Applications for Studying Organ-specific Influences on Breast Cancer Metastatic Behavior.

PubMed

Piaseczny, Matthew M; Pio, Graciella M; Chu, Jenny E; Xia, Ying; Nguyen, Kim; Goodale, David; Allan, Alison

2016-06-13

Breast cancer preferentially metastasizes to the lymph node, bone, lung, brain and liver in breast cancer patients. Previous research efforts have focused on identifying factors inherent to breast cancer cells that are responsible for this observed metastatic pattern (termed organ tropism), however much less is known about factors present within specific organs that contribute to this process. This is in part because of a lack of in vitro model systems that accurately recapitulate the organ microenvironment. To address this, an ex vivo model system has been established that allows for the study of soluble factors present within different organ microenvironments. This model consists of generating conditioned media from organs (lymph node, bone, lung, and brain) isolated from normal athymic nude mice. The model system has been validated by demonstrating that different breast cancer cell lines display cell-line specific and organ-specific malignant behavior in response to organ-conditioned media that corresponds to their in vivo metastatic potential. This model system can be used to identify and evaluate specific organ-derived soluble factors that may play a role in the metastatic behavior of breast and other types of cancer cells, including influences on growth, migration, stem-like behavior, and gene expression, as well as the identification of potential new therapeutic targets for cancer. This is the first ex vivo model system that can be used to study organ-specific metastatic behavior in detail and evaluate the role of specific organ-derived soluble factors in driving the process of cancer metastasis.

Skull flexure as a contributing factor in the mechanism of injury in the rat when exposed to a shock wave.

PubMed

Bolander, Richard; Mathie, Blake; Bir, Cynthia; Ritzel, David; VandeVord, Pamela

2011-10-01

The manner in which energy from an explosion is transmitted into the brain is currently a highly debated topic within the blast injury community. This study was conducted to investigate the injury biomechanics causing blast-related neurotrauma in the rat. Biomechanical responses of the rat head under shock wave loading were measured using strain gauges on the skull surface and a fiber optic pressure sensor placed within the cortex. MicroCT imaging techniques were applied to quantify skull bone thickness. The strain gauge results indicated that the response of the rat skull is dependent on the intensity of the incident shock wave; greater intensity shock waves cause greater deflections of the skull. The intracranial pressure (ICP) sensors indicated that the peak pressure developed within the brain was greater than the peak side-on external pressure and correlated with surface strain. The bone plates between the lambda, bregma, and midline sutures are probable regions for the greatest flexure to occur. The data provides evidence that skull flexure is a likely candidate for the development of ICP gradients within the rat brain. This dependency of transmitted stress on particular skull dynamics for a given species should be considered by those investigating blast-related neurotrauma using animal models.

Effect of age on the expression of Pex (Phex) in the mouse.

PubMed

Meyer, R A; Young, C G; Meyer, M H; Garges, P L; Price, D K

2000-04-01

Pex is a newly discovered gene (also called Phex) whose mutation is the cause of X-linked hypophosphatemia. Other members of this gene family encode endopeptidases that activate or inactivate endocrine and paracrine factors. Though embryonic bone expresses mRNA for the Pex gene at relatively high levels, we have found Pex expression to be widespread in adult organs and to be poorly expressed in adult bone. This led to the hypothesis that Pex mRNA expression changes with age. To test this, genetically normal mice of the B6C3H hybrid strain were studied at 0 (newborn), 2, 3, 10, and 72 weeks of age. Organs known to express Pex were collected, and RNA was extracted from them. Following reverse transcription, cDNA was amplified by the polymerase chain reaction with primers for Pex and G3PDH, a housekeeping gene. The amplimers were separated by electrophoresis, blotted onto nylon membranes, and hybridized with radioactively labeled internal oligonucleotide probes. The radioactivity was quantified, and the data were analyzed as the Pex/G3PDH ratio. The brain samples had high levels of Pex mRNA expression that rose slightly with age. Calvaria, kidney, and lung samples had the highest Pex mRNA expression at birth. In these organs Pex mRNA expression fell with age to undetectable or barely detectable levels. Thymus, heart, and skeletal muscle samples had low Pex mRNA expression at birth that did not change with age. Some organs showed a decline in G3PDH levels with age, but Pex expression decreased more, leading to a reduced Pex/G3PDH ratio. The widespread expression of mRNA for Pex suggests a role beyond that of phosphate homeostasis. The high level of expression in newborn animals suggests a role in growth and development. This seems to occur in addition to its role for the endocrine regulation of phosphate homeostasis by as yet unknown humoral agents that must occur throughout life. In summary, Pex mRNA expression is high in brain and bone at birth. Expression remains high in brain with age but falls with age in bone, kidney, and lung.

Brain injury due to air gun shot: report of three adult cases.

PubMed

Dalgıç, Ali; Okay, Onder; Ergüngör, Fikret Mehmet; Uçkun, Ozhan; Nacar, Osman Arıkan; Yıldırım, Ali Erdem

2010-09-01

Air guns (AGs) are arms that use air or another compressed gas to propel a projectile. Generally, brain injury may occur in children due to their incomplete skull development; however, the less-resistant and thin region of the skull in adults may also be penetrated by an AG shot. In this paper, we present three adult cases treated in our clinic for brain injury caused by an AG. The first case had brain and skull damage related to the high pressure of the compressed gas, and the others additionally had foreign bodies in their brain. All of the patients were operated. Two were discharged without neurological deficit; the third case had a permanent slight hemiparesis. Average follow-up was 11 months and no abscess formation was observed in this period. AGs are known as low-velocity arms; however, they have the potential to cause brain injury, and brain penetration may occur especially in the relatively less resistant and thin sites of the skull such as the orbit and temporal and occipital bones. As cerebrospinal fluid leakage is one of the expected conditions, urgent surgery is usually required.

Bone Cancer—Patient Version

Cancer.gov

Bone cancer is rare and includes several types. Some bone cancers, including osteosarcoma and Ewing sarcoma, are seen most often in children and young adults. Start here to find information on bone cancer treatment, research, and statistics.

Fat Embolism Syndrome: A Case Report and Review Literature.

PubMed

Uransilp, Nattaphol; Muengtaweepongsa, Sombat; Chanalithichai, Nuttawut; Tammachote, Nattapol

2018-01-01

Fat embolism syndrome (FES) is a life-threatening complication in patients with orthopedic trauma, especially long bone fractures. The diagnosis of fat embolism is made by clinical features alone with no specific laboratory findings. FES has no specific treatment and requires supportive care, although it can be prevented by early fixation of bone fractures. Here, we report a case of FES in a patient with right femoral neck fracture, which was diagnosed initially by Gurd's criteria and subsequently confirmed by typical appearances on magnetic resonance imaging (MRI) of the brain. The patient received supportive management and a short course of intravenous methylprednisolone.

Optoacoustic technique for noninvasive monitoring of blood oxygenation: a feasibility study

NASA Astrophysics Data System (ADS)

Esenaliev, Rinat O.; Larina, Irina V.; Larin, Kirill V.; Deyo, Donald J.; Motamedi, Massoud; Prough, Donald S.

2002-08-01

Replacement of invasive monitoring of cerebral venous oxygenation with noninvasive techniques offers great promise in the management of life-threatening neurologic illnesses including traumatic brain injury. We developed and built an optoacoustic system to noninvasively monitor cerebral venous oxygenation; the system includes a nanosecond Nd:YAG laser and a specially designed optoacoustic probe. We tested the system in vitro in sheep blood with experimentally varied oxygenation. Our results demonstrated that (1) the amplitude and temporal profile of the optoacoustic waves increase with blood oxygenation in the range from 24% to 92%, (2) optoacoustic signals can be detected despite optical and acoustic attenuation by thick bone, and (3) the system is capable of real-time and continuous measurements. These results suggest that the optoacoustic technique is technically feasible for continuous, noninvasive monitoring of cerebral venous oxygenation.

FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin

PubMed Central

Kode, Aruna; Mosialou, Ioanna; Silva, Barbara C.; Rached, Marie-Therese; Zhou, Bin; Wang, Ji; Townes, Tim M.; Hen, Rene; DePinho, Ronald A.; Guo, X. Edward; Kousteni, Stavroula

2012-01-01

Serotonin is a critical regulator of bone mass, fulfilling different functions depending on its site of synthesis. Brain-derived serotonin promotes osteoblast proliferation, whereas duodenal-derived serotonin suppresses it. To understand the molecular mechanisms of duodenal-derived serotonin action on osteoblasts, we explored its transcriptional mediation in mice. We found that the transcription factor FOXO1 is a crucial determinant of the effects of duodenum-derived serotonin on bone formation We identified two key FOXO1 complexes in osteoblasts, one with the transcription factor cAMP-responsive element–binding protein 1 (CREB) and another with activating transcription factor 4 (ATF4). Under normal levels of circulating serotonin, the proliferative activity of FOXO1 was promoted by a balance between its interaction with CREB and ATF4. However, high circulating serotonin levels prevented the association of FOXO1 with CREB, resulting in suppressed osteoblast proliferation. These observations identify FOXO1 as the molecular node of an intricate transcriptional machinery that confers the signal of duodenal-derived serotonin to inhibit bone formation. PMID:22945629

Some Kinds of Cancer Kids Get

MedlinePlus

... normal grow too fast and spread out of control. A group or mass of growing cells is called a ... person, these white blood cells multiply out of control. They fill up the bone ... Cancer A brain tumor is a group or clump of fast-growing cells that can ...

Genes that mediate breast cancer metastasis to the brain.

PubMed

Bos, Paula D; Zhang, Xiang H-F; Nadal, Cristina; Shu, Weiping; Gomis, Roger R; Nguyen, Don X; Minn, Andy J; van de Vijver, Marc J; Gerald, William L; Foekens, John A; Massagué, Joan

2009-06-18

The molecular basis for breast cancer metastasis to the brain is largely unknown. Brain relapse typically occurs years after the removal of a breast tumour, suggesting that disseminated cancer cells must acquire specialized functions to take over this organ. Here we show that breast cancer metastasis to the brain involves mediators of extravasation through non-fenestrated capillaries, complemented by specific enhancers of blood-brain barrier crossing and brain colonization. We isolated cells that preferentially infiltrate the brain from patients with advanced disease. Gene expression analysis of these cells and of clinical samples, coupled with functional analysis, identified the cyclooxygenase COX2 (also known as PTGS2), the epidermal growth factor receptor (EGFR) ligand HBEGF, and the alpha2,6-sialyltransferase ST6GALNAC5 as mediators of cancer cell passage through the blood-brain barrier. EGFR ligands and COX2 were previously linked to breast cancer infiltration of the lungs, but not the bones or liver, suggesting a sharing of these mediators in cerebral and pulmonary metastases. In contrast, ST6GALNAC5 specifically mediates brain metastasis. Normally restricted to the brain, the expression of ST6GALNAC5 in breast cancer cells enhances their adhesion to brain endothelial cells and their passage through the blood-brain barrier. This co-option of a brain sialyltransferase highlights the role of cell-surface glycosylation in organ-specific metastatic interactions.

TU-AB-204-02: Advances in C-Arm CBCT for Cardiac Interventions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fahrig, R.

This symposium highlights advanced cone-beam CT (CBCT) technologies in four areas of emerging application in diagnostic imaging and image-guided interventions. Each area includes research that extends the spatial, temporal, and/or contrast resolution characteristics of CBCT beyond conventional limits through advances in scanner technology, acquisition protocols, and 3D image reconstruction techniques. Dr. G. Chen (University of Wisconsin) will present on the topic: Advances in C-arm CBCT for Brain Perfusion Imaging. Stroke is a leading cause of death and disability, and a fraction of people having an acute ischemic stroke are suitable candidates for endovascular therapy. Critical factors that affect both themore » likelihood of successful revascularization and good clinical outcome are: 1) the time between stroke onset and revascularization; and 2) the ability to distinguish patients who have a small volume of irreversibly injured brain (ischemic core) and a large volume of ischemic but salvageable brain (penumbra) from patients with a large ischemic core and little or no penumbra. Therefore, “time is brain” in the care of the stroke patients. C-arm CBCT systems widely available in angiography suites have the potential to generate non-contrast-enhanced CBCT images to exclude the presence of hemorrhage, time-resolved CBCT angiography to evaluate the site of occlusion and collaterals, and CBCT perfusion parametric images to assess the extent of the ischemic core and penumbra, thereby fulfilling the imaging requirements of a “one-stop-shop” in the angiography suite to reduce the time between onset and revascularization therapy. The challenges and opportunities to advance CBCT technology to fully enable the one-stop-shop C-arm CBCT platform for brain imaging will be discussed. Dr. R. Fahrig (Stanford University) will present on the topic: Advances in C-arm CBCT for Cardiac Interventions. With the goal of providing functional information during cardiac interventions, significant effort has been expended to improve the quantitative accuracy of C-arm CBCT reconstructions. The challenge is to improve image quality while providing very short turnaround between data acquisition and volume data visualization. Corrections for x-ray scatter, view aliasing and patient motion that require no more than 2 iterations keep processing time short while reducing artifact. Fast, multi-sweep acquisitions can be used to permit assessment of left ventricular function, and visualization of radiofrequency lesions created to treat arrhythmias. Workflows for each imaging goal have been developed and validated against gold standard clinical CT or histology. The challenges, opportunities, and limitations of the new functional C-arm CBCT imaging techniques will be discussed. Dr. W. Zbijewski (Johns Hopkins University) will present on the topic: Advances in CBCT for Orthopaedics and Bone Health Imaging. Cone-beam CT is particularly well suited for imaging of musculoskeletal extremities. Owing to the high spatial resolution of flat-panel detectors, CBCT can surpass conventional CT in imaging tasks involving bone visualization, quantitative analysis of subchondral trabecular structure, and visualization and monitoring of subtle fractures that are common in orthopedic radiology. A dedicated CBCT platform has been developed that offers flexibility in system design and provides not only a compact configuration with improved logistics for extremities imaging but also enables novel diagnostic capabilities such as imaging of weight-bearing lower extremities in a natural stance. The design, development and clinical performance of dedicated extremities CBCT systems will be presented. Advanced capabilities for quantitative volumetric assessment of joint space morphology, dual-energy image-based quantification of bone composition, and in-vivo analysis of bone microarchitecture will be discussed, along with emerging applications in the diagnosis of arthritis and osteoporosis and assessment of novel therapies. Finally, Dr. J. Boone (UC Davis) will present on the topic: Advances in CBCT for Breast Imaging. Breast CT has been studied as an imaging tool for diagnostic breast evaluation and for potential breast cancer screening. The breast CT application lends itself to CBCT because of the small dimensions of the breast, the tapered shape of the breast towards higher cone angle, and the fact that there are no bones in the breast. The performance of various generations of breast CT scanners developed in recent years will be discussed, focusing on advances in spatial resolution and image noise characteristics. The results will also demonstrate the results of clinical trials using both computer and human observers. Learning Objectives: Understand the challenges, key technological advances, and emerging opportunities of CBCT in: Brain perfusion imaging, including assessment of ischemic stroke Cardiac imaging for functional assessment in cardiac interventions Orthopedics imaging for evaluation of musculoskeletal trauma, arthritis, and osteoporosis Breast imaging for screening and diagnosis of breast cancer. Work presented in this symposium includes research support by: Siemens Healthcare (Dr. Chen); NIH and Siemens Healthcare (Dr. Fahrig); NIH and Carestream Health (Dr. Zbijewski); and NIH (Dr. Boone)« less

TU-AB-204-00: Advances in Cone-Beam CT and Emerging Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

This symposium highlights advanced cone-beam CT (CBCT) technologies in four areas of emerging application in diagnostic imaging and image-guided interventions. Each area includes research that extends the spatial, temporal, and/or contrast resolution characteristics of CBCT beyond conventional limits through advances in scanner technology, acquisition protocols, and 3D image reconstruction techniques. Dr. G. Chen (University of Wisconsin) will present on the topic: Advances in C-arm CBCT for Brain Perfusion Imaging. Stroke is a leading cause of death and disability, and a fraction of people having an acute ischemic stroke are suitable candidates for endovascular therapy. Critical factors that affect both themore » likelihood of successful revascularization and good clinical outcome are: 1) the time between stroke onset and revascularization; and 2) the ability to distinguish patients who have a small volume of irreversibly injured brain (ischemic core) and a large volume of ischemic but salvageable brain (penumbra) from patients with a large ischemic core and little or no penumbra. Therefore, “time is brain” in the care of the stroke patients. C-arm CBCT systems widely available in angiography suites have the potential to generate non-contrast-enhanced CBCT images to exclude the presence of hemorrhage, time-resolved CBCT angiography to evaluate the site of occlusion and collaterals, and CBCT perfusion parametric images to assess the extent of the ischemic core and penumbra, thereby fulfilling the imaging requirements of a “one-stop-shop” in the angiography suite to reduce the time between onset and revascularization therapy. The challenges and opportunities to advance CBCT technology to fully enable the one-stop-shop C-arm CBCT platform for brain imaging will be discussed. Dr. R. Fahrig (Stanford University) will present on the topic: Advances in C-arm CBCT for Cardiac Interventions. With the goal of providing functional information during cardiac interventions, significant effort has been expended to improve the quantitative accuracy of C-arm CBCT reconstructions. The challenge is to improve image quality while providing very short turnaround between data acquisition and volume data visualization. Corrections for x-ray scatter, view aliasing and patient motion that require no more than 2 iterations keep processing time short while reducing artifact. Fast, multi-sweep acquisitions can be used to permit assessment of left ventricular function, and visualization of radiofrequency lesions created to treat arrhythmias. Workflows for each imaging goal have been developed and validated against gold standard clinical CT or histology. The challenges, opportunities, and limitations of the new functional C-arm CBCT imaging techniques will be discussed. Dr. W. Zbijewski (Johns Hopkins University) will present on the topic: Advances in CBCT for Orthopaedics and Bone Health Imaging. Cone-beam CT is particularly well suited for imaging of musculoskeletal extremities. Owing to the high spatial resolution of flat-panel detectors, CBCT can surpass conventional CT in imaging tasks involving bone visualization, quantitative analysis of subchondral trabecular structure, and visualization and monitoring of subtle fractures that are common in orthopedic radiology. A dedicated CBCT platform has been developed that offers flexibility in system design and provides not only a compact configuration with improved logistics for extremities imaging but also enables novel diagnostic capabilities such as imaging of weight-bearing lower extremities in a natural stance. The design, development and clinical performance of dedicated extremities CBCT systems will be presented. Advanced capabilities for quantitative volumetric assessment of joint space morphology, dual-energy image-based quantification of bone composition, and in-vivo analysis of bone microarchitecture will be discussed, along with emerging applications in the diagnosis of arthritis and osteoporosis and assessment of novel therapies. Finally, Dr. J. Boone (UC Davis) will present on the topic: Advances in CBCT for Breast Imaging. Breast CT has been studied as an imaging tool for diagnostic breast evaluation and for potential breast cancer screening. The breast CT application lends itself to CBCT because of the small dimensions of the breast, the tapered shape of the breast towards higher cone angle, and the fact that there are no bones in the breast. The performance of various generations of breast CT scanners developed in recent years will be discussed, focusing on advances in spatial resolution and image noise characteristics. The results will also demonstrate the results of clinical trials using both computer and human observers. Learning Objectives: Understand the challenges, key technological advances, and emerging opportunities of CBCT in: Brain perfusion imaging, including assessment of ischemic stroke Cardiac imaging for functional assessment in cardiac interventions Orthopedics imaging for evaluation of musculoskeletal trauma, arthritis, and osteoporosis Breast imaging for screening and diagnosis of breast cancer. Work presented in this symposium includes research support by: Siemens Healthcare (Dr. Chen); NIH and Siemens Healthcare (Dr. Fahrig); NIH and Carestream Health (Dr. Zbijewski); and NIH (Dr. Boone)« less

TU-AB-204-04: Advances in CBCT for Breast Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boone, J.

This symposium highlights advanced cone-beam CT (CBCT) technologies in four areas of emerging application in diagnostic imaging and image-guided interventions. Each area includes research that extends the spatial, temporal, and/or contrast resolution characteristics of CBCT beyond conventional limits through advances in scanner technology, acquisition protocols, and 3D image reconstruction techniques. Dr. G. Chen (University of Wisconsin) will present on the topic: Advances in C-arm CBCT for Brain Perfusion Imaging. Stroke is a leading cause of death and disability, and a fraction of people having an acute ischemic stroke are suitable candidates for endovascular therapy. Critical factors that affect both themore » likelihood of successful revascularization and good clinical outcome are: 1) the time between stroke onset and revascularization; and 2) the ability to distinguish patients who have a small volume of irreversibly injured brain (ischemic core) and a large volume of ischemic but salvageable brain (penumbra) from patients with a large ischemic core and little or no penumbra. Therefore, “time is brain” in the care of the stroke patients. C-arm CBCT systems widely available in angiography suites have the potential to generate non-contrast-enhanced CBCT images to exclude the presence of hemorrhage, time-resolved CBCT angiography to evaluate the site of occlusion and collaterals, and CBCT perfusion parametric images to assess the extent of the ischemic core and penumbra, thereby fulfilling the imaging requirements of a “one-stop-shop” in the angiography suite to reduce the time between onset and revascularization therapy. The challenges and opportunities to advance CBCT technology to fully enable the one-stop-shop C-arm CBCT platform for brain imaging will be discussed. Dr. R. Fahrig (Stanford University) will present on the topic: Advances in C-arm CBCT for Cardiac Interventions. With the goal of providing functional information during cardiac interventions, significant effort has been expended to improve the quantitative accuracy of C-arm CBCT reconstructions. The challenge is to improve image quality while providing very short turnaround between data acquisition and volume data visualization. Corrections for x-ray scatter, view aliasing and patient motion that require no more than 2 iterations keep processing time short while reducing artifact. Fast, multi-sweep acquisitions can be used to permit assessment of left ventricular function, and visualization of radiofrequency lesions created to treat arrhythmias. Workflows for each imaging goal have been developed and validated against gold standard clinical CT or histology. The challenges, opportunities, and limitations of the new functional C-arm CBCT imaging techniques will be discussed. Dr. W. Zbijewski (Johns Hopkins University) will present on the topic: Advances in CBCT for Orthopaedics and Bone Health Imaging. Cone-beam CT is particularly well suited for imaging of musculoskeletal extremities. Owing to the high spatial resolution of flat-panel detectors, CBCT can surpass conventional CT in imaging tasks involving bone visualization, quantitative analysis of subchondral trabecular structure, and visualization and monitoring of subtle fractures that are common in orthopedic radiology. A dedicated CBCT platform has been developed that offers flexibility in system design and provides not only a compact configuration with improved logistics for extremities imaging but also enables novel diagnostic capabilities such as imaging of weight-bearing lower extremities in a natural stance. The design, development and clinical performance of dedicated extremities CBCT systems will be presented. Advanced capabilities for quantitative volumetric assessment of joint space morphology, dual-energy image-based quantification of bone composition, and in-vivo analysis of bone microarchitecture will be discussed, along with emerging applications in the diagnosis of arthritis and osteoporosis and assessment of novel therapies. Finally, Dr. J. Boone (UC Davis) will present on the topic: Advances in CBCT for Breast Imaging. Breast CT has been studied as an imaging tool for diagnostic breast evaluation and for potential breast cancer screening. The breast CT application lends itself to CBCT because of the small dimensions of the breast, the tapered shape of the breast towards higher cone angle, and the fact that there are no bones in the breast. The performance of various generations of breast CT scanners developed in recent years will be discussed, focusing on advances in spatial resolution and image noise characteristics. The results will also demonstrate the results of clinical trials using both computer and human observers. Learning Objectives: Understand the challenges, key technological advances, and emerging opportunities of CBCT in: Brain perfusion imaging, including assessment of ischemic stroke Cardiac imaging for functional assessment in cardiac interventions Orthopedics imaging for evaluation of musculoskeletal trauma, arthritis, and osteoporosis Breast imaging for screening and diagnosis of breast cancer. Work presented in this symposium includes research support by: Siemens Healthcare (Dr. Chen); NIH and Siemens Healthcare (Dr. Fahrig); NIH and Carestream Health (Dr. Zbijewski); and NIH (Dr. Boone)« less

A bony connection signals laryngeal echolocation in bats.

PubMed

Veselka, Nina; McErlain, David D; Holdsworth, David W; Eger, Judith L; Chhem, Rethy K; Mason, Matthew J; Brain, Kirsty L; Faure, Paul A; Fenton, M Brock

2010-02-18

Echolocation is an active form of orientation in which animals emit sounds and then listen to reflected echoes of those sounds to form images of their surroundings in their brains. Although echolocation is usually associated with bats, it is not characteristic of all bats. Most echolocating bats produce signals in the larynx, but within one family of mainly non-echolocating species (Pteropodidae), a few species use echolocation sounds produced by tongue clicks. Here we demonstrate, using data obtained from micro-computed tomography scans of 26 species (n = 35 fluid-preserved bats), that proximal articulation of the stylohyal bone (part of the mammalian hyoid apparatus) with the tympanic bone always distinguishes laryngeally echolocating bats from all other bats (that is, non-echolocating pteropodids and those that echolocate with tongue clicks). In laryngeally echolocating bats, the proximal end of the stylohyal bone directly articulates with the tympanic bone and is often fused with it. Previous research on the morphology of the stylohyal bone in the oldest known fossil bat (Onychonycteris finneyi) suggested that it did not echolocate, but our findings suggest that O. finneyi may have used laryngeal echolocation because its stylohyal bones may have articulated with its tympanic bones. The present findings reopen basic questions about the timing and the origin of flight and echolocation in the early evolution of bats. Our data also provide an independent anatomical character by which to distinguish laryngeally echolocating bats from other bats.

A collaboration investigating endocannabinoid signalling in brain and bone.

PubMed

Zimmer, Andreas

2016-05-01

Investigations into the cellular and molecular mechanisms underlying the psychoactive effects of cannabis preparations have led to the discovery of the endocannabinoid system. Interest in the central nervous system effects was initially the main focus of the research, but it soon became evident that the endocannabinoid system affects virtually every organ. The research field has therefore experienced a tremendous growth over the last decade and is now truly interdisciplinary. This short review provides a personal account of an interdisciplinary collaboration between Itai Bab from the Hebrew University of Jerusalem and the author. It describes the discovery of the endocannabinoid system in bone and the analysis of its functions. I am summarising the role of CB1 signalling as a modulator of sympathetic inhibition of bone formation. Thus, activation of CB1 receptors on sympathetic nerve terminals in bone, presumably from endocannabinoids released from apposing osteoblasts, reduces the inhibition of bone formation of sympathetic norepinephrine. CB2 receptors on osteoblasts and osteoclasts also modulate the proliferation and functions of these cells. Thus, activation of CB2 stimulates bone formation and represses bone resorption, whereas the genetic disruption of CB2 results in an osteoporosis-like phenotype. This signalling mechanism is clinically relevant, as shown by the association of polymorphisms in the CB2 receptor gene, CNR2, with bone density and osteoporosis. Finally, the review provides a summary of the recently discovered role of endocannabinoid signalling in one elongation. This review will also discuss the benefits of interdisciplinary and international collaborations.

Locally Produced BDNF Promotes Sclerotic Change in Alveolar Bone after Nerve Injury

PubMed Central

Ida-Yonemochi, Hiroko; Yamada, Yurie; Yoshikawa, Hiroyuki

2017-01-01

Brain-derived neurotrophic factor (BDNF), which is released due to nerve injury, is known to promote the natural healing of injured nerves. It is often observed that damage of mandibular canal induces local sclerotic changes in alveolar bone. We reported that peripheral nerve injury promotes the local production of BDNF; therefore, it was possible to hypothesize that peripheral nerve injury affects sclerotic changes in the alveolar bone. This study aimed to evaluate the effect of BDNF on osteogenesis using in vitro osteoblast-lineage cell culture and an in vivo rat osteotomy model. MC3T3-E1 cells were cultured with BDNF and were examined for cell proliferative activity, chemotaxis and mRNA expression levels of osteoblast differentiation markers. For in vivo study, inferior alveolar nerve (IAN) injury experiments and mandibular cortical osteotomy were performed using a rat model. In the osteotomy model, exogenous BDNF was applied to bone surfaces after corticotomy of the mandible, and we morphologically analyzed the new bone formation. As a result, mRNA expression of osteoblast differentiation marker, osteocalcin, was significantly increased by BDNF, although cell proliferation and migration were not affected. In the in vivo study, osteopontin-positive new bone formation was significantly accelerated in the BDNF-grafted groups, and active bone remodeling, involving trkB-positive osteoblasts and osteocytes, continued after 28 days. In conclusion, BDNF stimulated the differentiation of MC3T3-E1 cells and it promoted new bone formation and maturation. These results suggested that local BDNF produced by peripheral nerve injury contributes to accelerating sclerotic changes in the alveolar bone. PMID:28072837

Brain surface temperature under a craniotomy

PubMed Central

Kalmbach, Abigail S.

2012-01-01

Many neuroscientists access surface brain structures via a small cranial window, opened in the bone above the brain region of interest. Unfortunately this methodology has the potential to perturb the structure and function of the underlying brain tissue. One potential perturbation is heat loss from the brain surface, which may result in local dysregulation of brain temperature. Here, we demonstrate that heat loss is a significant problem in a cranial window preparation in common use for electrical recording and imaging studies in mice. In the absence of corrective measures, the exposed surface of the neocortex was at ∼28°C, ∼10°C below core body temperature, and a standing temperature gradient existed, with tissue below the core temperature even several millimeters into the brain. Cooling affected cellular and network function in neocortex and resulted principally from increased heat loss due to convection and radiation through the skull and cranial window. We demonstrate that constant perfusion of solution, warmed to 37°C, over the brain surface readily corrects the brain temperature, resulting in a stable temperature of 36–38°C at all depths. Our results indicate that temperature dysregulation may be common in cranial window preparations that are in widespread use in neuroscience, underlining the need to take measures to maintain the brain temperature in many physiology experiments. PMID:22972953

Responds of Bone Cells to Microgravity: Ground-Based Research

NASA Astrophysics Data System (ADS)

Zhang, Jian; Li, Jingbao; Xu, Huiyun; Yang, Pengfei; Xie, Li; Qian, Airong; Zhao, Yong; Shang, Peng

2015-11-01

Severe loss of bone occurs due to long-duration spaceflight. Mechanical loading stimulates bone formation, while bone degradation happens under mechanical unloading. Bone remodeling is a dynamic process in which bone formation and bone resorption are tightly coupled. Increased bone resorption and decreased bone formation caused by reduced mechanical loading, generally result in disrupted bone remodeling. Bone remodeling is orchestrated by multiple bone cells including osteoblast, osteocyte, osteoclast and mesenchymal stem cell. It is yet not clear that how these bone cells sense altered gravity, translate physical stimulus into biochemical signals, and then regulate themselves structurally and functionally. In this paper, studies elucidating the bioeffects of microgravity on bone cells (osteoblast, osteocyte, osteoclast, mesenchymal stem cell) using various platforms including spaceflight and ground-based simulated microgravity were summarized. Promising gravity-sensitive signaling pathways and protein molecules were proposed.

Deep Learning MR Imaging-based Attenuation Correction for PET/MR Imaging.

PubMed

Liu, Fang; Jang, Hyungseok; Kijowski, Richard; Bradshaw, Tyler; McMillan, Alan B

2018-02-01

Purpose To develop and evaluate the feasibility of deep learning approaches for magnetic resonance (MR) imaging-based attenuation correction (AC) (termed deep MRAC) in brain positron emission tomography (PET)/MR imaging. Materials and Methods A PET/MR imaging AC pipeline was built by using a deep learning approach to generate pseudo computed tomographic (CT) scans from MR images. A deep convolutional auto-encoder network was trained to identify air, bone, and soft tissue in volumetric head MR images coregistered to CT data for training. A set of 30 retrospective three-dimensional T1-weighted head images was used to train the model, which was then evaluated in 10 patients by comparing the generated pseudo CT scan to an acquired CT scan. A prospective study was carried out for utilizing simultaneous PET/MR imaging for five subjects by using the proposed approach. Analysis of covariance and paired-sample t tests were used for statistical analysis to compare PET reconstruction error with deep MRAC and two existing MR imaging-based AC approaches with CT-based AC. Results Deep MRAC provides an accurate pseudo CT scan with a mean Dice coefficient of 0.971 ± 0.005 for air, 0.936 ± 0.011 for soft tissue, and 0.803 ± 0.021 for bone. Furthermore, deep MRAC provides good PET results, with average errors of less than 1% in most brain regions. Significantly lower PET reconstruction errors were realized with deep MRAC (-0.7% ± 1.1) compared with Dixon-based soft-tissue and air segmentation (-5.8% ± 3.1) and anatomic CT-based template registration (-4.8% ± 2.2). Conclusion The authors developed an automated approach that allows generation of discrete-valued pseudo CT scans (soft tissue, bone, and air) from a single high-spatial-resolution diagnostic-quality three-dimensional MR image and evaluated it in brain PET/MR imaging. This deep learning approach for MR imaging-based AC provided reduced PET reconstruction error relative to a CT-based standard within the brain compared with current MR imaging-based AC approaches. © RSNA, 2017 Online supplemental material is available for this article.

76 FR 1592 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-11

...: Advanced Meat Recovery Systems. OMB Control Number: 0583-0130. Summary of Collection: The Food Safety and... Recovery (AMR) systems ensure that bones used for AMR systems do not contain brain, trigeminal ganglia, or... dorsal root ganglia (DRG); to document their testing protocols, to assess manner that does not cause...

Regulation of Metastatic Breast Cancer Dormancy

DTIC Science & Technology

2015-09-01

individual cell motility to disseminate and eventually extravasate into common metastatic niches such as the brain, bone and liver. Once attaining the...Engineer tagged MCF7 cells with shRNA against E-cadherin and engineer tagged MDA-MB-361 and MDA- MB-231 cells to express or prevent expression of E

A case of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome presenting with hypertrophic pachymeningitis.

PubMed

Shiraishi, Wataru; Hayashi, Shintaro; Iwanaga, Yasutaka; Murai, Hiroyuki; Yamamoto, Akifumi; Kira, Jun-ichi

2015-02-15

A 43-year-old woman with a 3-year history of headache, fever, and swelling of the forehead, presented to our hospital. A general examination revealed palmar and plantar pustules. Blood analyses showed an elevated white blood cell count, C-reactive protein level, and erythrocyte sedimentation rate. Brain MRI revealed a partially thickened cranial bone with gadolinium enhancement, and also abnormally enhanced dura mater. Bone scintigraphy showed involvement of the cranial bone and bilateral sternoclavicular joints. Palmar skin biopsy indicated palmoplantar pustulosis. From these results, SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome with associated hypertrophic pachymeningitis was diagnosed. After corticosteroid therapy and tonsillectomy, the clinical symptoms and radiological abnormalities were improved. Clinicians should be aware of SAPHO as a potential unusual cause of hypertrophic pachymeningitis. Copyright © 2014 Elsevier B.V. All rights reserved.

TU-B-210-01: MRg HIFU - Bone and Soft Tissue Tumor Ablation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghanouni, P.

MR guided focused ultrasound (MRgFUS), or alternatively high-intensity focused ultrasound (MRgHIFU), is approved for thermal ablative treatment of uterine fibroids and pain palliation in bone metastases. Ablation of malignant tumors is under active investigation in sites such as breast, prostate, brain, liver, kidney, pancreas, and soft tissue. Hyperthermia therapy with MRgFUS is also feasible, and may be used in conjunction with radiotherapy and for local targeted drug delivery. MRI allows in situ target definition and provides continuous temperature monitoring and subsequent thermal dose mapping during HIFU. Although MRgHIFU can be very precise, treatment of mobile organs is challenging and advancedmore » techniques are required because of artifacts in MR temperature mapping, the need for intercostal firing, and need for gated HIFU or tracking of the lesion in real time. The first invited talk, “MR guided Focused Ultrasound Treatment of Tumors in Bone and Soft Tissue”, will summarize the treatment protocol and review results from treatment of bone tumors. In addition, efforts to extend this technology to treat both benign and malignant soft tissue tumors of the extremities will be presented. The second invited talk, “MRI guided High Intensity Focused Ultrasound – Advanced Approaches for Ablation and Hyperthermia”, will provide an overview of techniques that are in or near clinical trials for thermal ablation and hyperthermia, with an emphasis of applications in abdominal organs and breast, including methods for MRTI and tracking targets in moving organs. Learning Objectives: Learn background on devices and techniques for MR guided HIFU for cancer therapy Understand issues and current status of clinical MRg HIFU Understand strategies for compensating for organ movement during MRgHIFU Understand strategies for strategies for delivering hyperthermia with MRgHIFU CM - research collaboration with Philips.« less

Sclerosteosis involving the temporal bone: histopathologic aspects.

PubMed

Nager, G T; Hamersma, H

1986-01-01

Sclerosteosis is a rare, potentially lethal, autosomal recessive, progressive craniotubular sclerosing bone dysplasia with characteristic facial and skeletal features. The temporal bone changes include a marked increase in overall size, extensive sclerosis, narrowing of the external auditory canal, and severe constriction of the internal auditory meatus, fallopian canal, eustachian tube, and middle ear cleft. Attenuation of the bony canals of the 9th, 10th, and 11th cranial nerves, reduction in size of the internal carotid artery, and severe obliteration of the sigmoid sinus and jugular bulb also occur. Loss of hearing, generally bilateral, is a frequent symptom. It often manifests in early childhood and initially is expressed as sound conduction impairment. Later, a sensorineural hearing loss and loss of vestibular nerve function often develop. Impairment of facial nerve function is another feature occasionally present at birth. In the beginning, a unilateral intermittent facial weakness may occur which eventually progresses to a bilateral permanent facial paresis. The histologic examination of the temporal bones from a patient with sclerosteosis explains the mechanisms involved in the progressive impairment of sound conduction and loss of cochlear, vestibular, and facial nerve function. There is a decrease of the arterial blood supply to the brain and an obstruction of the venous drainage from it. The histopathology reveals the obstacles to decompression of the middle ear cleft, ossicular chain, internal auditory and facial canals, and the risks, and in many instances the contraindications, to such procedures. On the other hand, decompression of the sigmoid sinus and jugular bulb should be considered as an additional life-saving procedure in conjunction with the prophylactic craniotomy recommended in all adult patients.

Dual energy computed tomography for the head.

PubMed

Naruto, Norihito; Itoh, Toshihide; Noguchi, Kyo

2018-02-01

Dual energy CT (DECT) is a promising technology that provides better diagnostic accuracy in several brain diseases. DECT can generate various types of CT images from a single acquisition data set at high kV and low kV based on material decomposition algorithms. The two-material decomposition algorithm can separate bone/calcification from iodine accurately. The three-material decomposition algorithm can generate a virtual non-contrast image, which helps to identify conditions such as brain hemorrhage. A virtual monochromatic image has the potential to eliminate metal artifacts by reducing beam-hardening effects. DECT also enables exploration of advanced imaging to make diagnosis easier. One such novel application of DECT is the X-Map, which helps to visualize ischemic stroke in the brain without using iodine contrast medium.

Development of the software tool for generation and visualization of the finite element head model with bone conduction sounds

NASA Astrophysics Data System (ADS)

Nikolić, Dalibor; Milošević, Žarko; Saveljić, Igor; Filipović, Nenad

2015-12-01

Vibration of the skull causes a hearing sensation. We call it Bone Conduction (BC) sound. There are several investigations about transmission properties of bone conducted sound. The aim of this study was to develop a software tool for easy generation of the finite element (FE) model of the human head with different materials based on human head anatomy and to calculate sound conduction through the head. Developed software tool generates a model in a few steps. The first step is to do segmentation of CT medical images (DICOM) and to generate a surface mesh files (STL). Each STL file presents a different layer of human head with different material properties (brain, CSF, different layers of the skull bone, skin, etc.). The next steps are to make tetrahedral mesh from obtained STL files, to define FE model boundary conditions and to solve FE equations. This tool uses PAK solver, which is the open source software implemented in SIFEM FP7 project, for calculations of the head vibration. Purpose of this tool is to show impact of the bone conduction sound of the head on the hearing system and to estimate matching of obtained results with experimental measurements.

Generation of brain pseudo-CTs using an undersampled, single-acquisition UTE-mDixon pulse sequence and unsupervised clustering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su, Kuan-Hao; Hu, Lingzhi; Traughber, Melanie

Purpose: MR-based pseudo-CT has an important role in MR-based radiation therapy planning and PET attenuation correction. The purpose of this study is to establish a clinically feasible approach, including image acquisition, correction, and CT formation, for pseudo-CT generation of the brain using a single-acquisition, undersampled ultrashort echo time (UTE)-mDixon pulse sequence. Methods: Nine patients were recruited for this study. For each patient, a 190-s, undersampled, single acquisition UTE-mDixon sequence of the brain was acquired (TE = 0.1, 1.5, and 2.8 ms). A novel method of retrospective trajectory correction of the free induction decay (FID) signal was performed based on point-spreadmore » functions of three external MR markers. Two-point Dixon images were reconstructed using the first and second echo data (TE = 1.5 and 2.8 ms). R2{sup ∗} images (1/T2{sup ∗}) were then estimated and were used to provide bone information. Three image features, i.e., Dixon-fat, Dixon-water, and R2{sup ∗}, were used for unsupervised clustering. Five tissue clusters, i.e., air, brain, fat, fluid, and bone, were estimated using the fuzzy c-means (FCM) algorithm. A two-step, automatic tissue-assignment approach was proposed and designed according to the prior information of the given feature space. Pseudo-CTs were generated by a voxelwise linear combination of the membership functions of the FCM. A low-dose CT was acquired for each patient and was used as the gold standard for comparison. Results: The contrast and sharpness of the FID images were improved after trajectory correction was applied. The mean of the estimated trajectory delay was 0.774 μs (max: 1.350 μs; min: 0.180 μs). The FCM-estimated centroids of different tissue types showed a distinguishable pattern for different tissues, and significant differences were found between the centroid locations of different tissue types. Pseudo-CT can provide additional skull detail and has low bias and absolute error of estimated CT numbers of voxels (−22 ± 29 HU and 130 ± 16 HU) when compared to low-dose CT. Conclusions: The MR features generated by the proposed acquisition, correction, and processing methods may provide representative clustering information and could thus be used for clinical pseudo-CT generation.« less

Evaluation of ultrasound techniques for brain injury detection

NASA Astrophysics Data System (ADS)

Mobley, Joel; Kasili, Paul M.; Norton, Stephen J.; Vo-Dinh, Tuan

1998-05-01

In this work, we examine the physics underlying wave propagation in the head to evaluate various ultrasonic transducers for use in a brian injury detection device. The results of measurements of the attenuation coefficient and phase velocity for ultrasonic propagation in samples of brain tissue and skull bone from sheep are presented. The material properties are then used to investigate the propagation of ultrasonic pressure fields in the head. The ultrasound fields for three different transducers are calculated for propagation in a simulated brain/skull model. The model is constructed using speed-of-sound and mass density values of the two tissue types. The impact of the attenuation on the ultrasound fields is then examined. Finally, the relevant points drawn from these discussions are summarized. We hope to minimize the confounding effects of the skull by using sub-MHz ultrasound while maintaining the necessary temporal and spatial resolution to successfully detect injury in the brain.

Synergistic induction of astrocytic differentiation by factors secreted from meninges in the mouse developing brain.

PubMed

Kawamura, Yoichiro; Katada, Sayako; Noguchi, Hirofumi; Yamamoto, Hiroyuki; Sanosaka, Tsukasa; Iihara, Koji; Nakashima, Kinichi

2017-11-01

Astrocytes, which support diverse neuronal functions, are generated from multipotent neural stem/precursor cells (NS/PCs) during brain development. Although many astrocyte-inducing factors have been identified and studied in vitro, the regions and/or cells that produce these factors in the developing brain remain elusive. Here, we show that meninges-produced factors induce astrocytic differentiation of NS/PCs. Consistent with the timing when astrocytic differentiation of NS/PCs increases, expression of astrocyte-inducing factors is upregulated. Meningeal secretion-mimicking combinatorial treatment of NS/PCs with bone morphogenetic protein 4, retinoic acid and leukemia inhibitory factor synergistically activate the promoter of a typical astrocytic marker, glial fibrillary acidic protein. Taken together, our data suggest that meninges play an important role in astrocytic differentiation of NS/PCs in the developing brain. © 2017 Federation of European Biochemical Societies.

Immune heterogeneity in neuroinflammation: dendritic cells in the brain.

PubMed

Colton, Carol A

2013-03-01

Dendritic cells (DC) are critical to an integrated immune response and serve as the key link between the innate and adaptive arms of the immune system. Under steady state conditions, brain DC's act as sentinels, continually sampling their local environment. They share this function with macrophages derived from the same basic hemopoietic (bone marrow-derived) precursor and with parenchymal microglia that arise from a unique non-hemopoietic origin. While multiple cells may serve as antigen presenting cells (APCs), dendritic cells present both foreign and self-proteins to naïve T cells that, in turn, carry out effector functions that serve to protect or destroy. The resulting activation of the adaptive response is a critical step to resolution of injury or infection and is key to survival. In this review we will explore the critical roles that DCs play in the brain's response to neuroinflammatory disease with emphasis on how the brain's microenvironment impacts these actions.

Ultrasonic modulation of neural circuit activity.

PubMed

Tyler, William J; Lani, Shane W; Hwang, Grace M

2018-06-01

Ultrasound (US) is recognized for its use in medical imaging as a diagnostic tool. As an acoustic energy source, US has become increasingly appreciated over the past decade for its ability to non-invasively modulate cellular activity including neuronal activity. Data obtained from a host of experimental models has shown that low-intensity US can reversibly modulate the physiological activity of neurons in peripheral nerves, spinal cord, and intact brain circuits. Experimental evidence indicates that acoustic pressures exerted by US act, in part, on mechanosensitive ion channels to modulate activity. While the precise mechanisms of action enabling US to both stimulate and suppress neuronal activity remain to be clarified, there are several advantages conferred by the physics of US that make it an appealing option for neuromodulation. For example, it can be focused with millimeter spatial resolutions through skull bone to deep-brain regions. By increasing our engineering capability to leverage such physical advantages while growing our understanding of how US affects neuronal function, the development of a new generation of non-invasive neurotechnology can be developed using ultrasonic methods. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Brain abscess as the initial presentation of a macroprolactinoma: Case report.

PubMed

Rubio-Almanza, Matilde; Cámara-Gómez, Rosa; de San Román-Mena, Laila Pérez; Simal-Julián, Juan Antonio; Ramos-Prol, Agustín; Botella-Asunción, Carlos; Merino-Torres, Juan Francisco

2015-01-01

Macroprolactinomas may behave invasively and infiltrate the skull base, causing a subsequent thinning that can also lead to a bone defect and a direct route of entry for pathogens. We describe the case of a 34-year-old male admitted to hospital with fever (38°C), headache, stiffness in the neck, diplopia and neurological impairment. Brain magnetic resonance imaging showed two bilateral abscesses in the fronto-parietal areas with intracranial venous sinus thrombosis and a pituitary adenoma that extended from the suprasellar region, eroding the sellar floor into the sphenoid sinus. Laboratory hormone measurements showed increased levels of prolactin and low levels of FSH, LH and testosterone. The patient received antibiotic treatment and surgery was performed. The patient developed central deafness as a neurological deficit. It is advisable to include pituitary adenoma in the differential diagnosis of meningitis even though its onset as intracranial abscess and rectus sinus thrombosis is extremely rare. Copyright © 2014 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

A Wireless 32-Channel Implantable Bidirectional Brain Machine Interface

PubMed Central

Su, Yi; Routhu, Sudhamayee; Moon, Kee S.; Lee, Sung Q.; Youm, WooSub; Ozturk, Yusuf

2016-01-01

All neural information systems (NIS) rely on sensing neural activity to supply commands and control signals for computers, machines and a variety of prosthetic devices. Invasive systems achieve a high signal-to-noise ratio (SNR) by eliminating the volume conduction problems caused by tissue and bone. An implantable brain machine interface (BMI) using intracortical electrodes provides excellent detection of a broad range of frequency oscillatory activities through the placement of a sensor in direct contact with cortex. This paper introduces a compact-sized implantable wireless 32-channel bidirectional brain machine interface (BBMI) to be used with freely-moving primates. The system is designed to monitor brain sensorimotor rhythms and present current stimuli with a configurable duration, frequency and amplitude in real time to the brain based on the brain activity report. The battery is charged via a novel ultrasonic wireless power delivery module developed for efficient delivery of power into a deeply-implanted system. The system was successfully tested through bench tests and in vivo tests on a behaving primate to record the local field potential (LFP) oscillation and stimulate the target area at the same time. PMID:27669264

A Method for the Measurement of Acoustic Impedance and Speed of Sound in a Small Region of Bone using a Fused Quartz Rod as a Transmission Line

NASA Astrophysics Data System (ADS)

Hatakeyama, Rokuro; Yoshizawa, Masazumi; Moriya, Tadashi

2000-11-01

Precise correction for γ-ray attenuation in skull bone has been a significant problem in obtaining quantitative single photon emission computed tomography (SPECT) images. The correction for γ-ray attenuation is approximately proportional to the density and thickness of the bone under investigation. If the acoustic impedance and the speed of sound in bone are measurable using ultrasonic techniques, then the density and thickness of the bone sample can be calculated. Whole bone usually consists of three layers, and each layer has a different ultrasonic character. Thus, the speed of sound must be measured in a small section of each layer in order to determine the overall density of whole bone. It is important to measure the attenuation constant in order to determine the appropriate level for the ultrasonic input signal. We have developed a method for measuring the acoustic impedance, speed of sound, and attenuation constant in a small region of a bone sample using a fused quartz rod as a transmission line. In the present study, we obtained the following results: impedance of compact bone; 5.30(±0.40)× 106 kg/(m2s), speed of sound; 3780± 250 m/s, and attenuation constant; 2.70± 0.50 Np/m. These results were used to obtain the densities of compact bone, spongy bone and bone marrow in a bovine bone sample and as well as the density of pig skull bone, which were found to be 1.40± 0.30 g/cm3, 1.19± 0.50 g/cm3, 0.90± 0.30 g/cm3 and 1.26± 0.30 g/cm3, respectively. Using a thin solid transmission line, the proposed method makes it possible to determine the density of a small region of a bone sample. It is expected that the proposed method, which is based on ultrasonic measurement, will be useful for application in brain SPECT.

Prospective sonographic detection of spina bifida at 11-14 weeks and systematic literature review.

PubMed

Orlandi, Emanuela; Rossi, Cinzia; Perino, Antonio; Cucinella, Gaspare; Orlandi, Francesco

2016-01-01

To conduct a literature review to assess the effectiveness of first trimester ultrasonographic markers of spina bifida (SB) integrating data with our prospective experience. The analysis of the SB cases that we prospectively detected in the first trimester, between January 2012 and February 2014, and a systematic review of all the papers evaluating the effectiveness of SB ultrasonographic markers at 11-14 weeks, namely brain stem diameter (BS), fourth ventricle/intracranial translucency (IT), cisterna magna (CM), brain stem/occipital bone distance (BSOB), the ratio between BS and BSOB. Some studies assess only the effectiveness of IT, others include more parameters, and few include them all. We prospectively detected four SB cases, three open (OSB) and one closed (CSB), in a low risk population undergoing first trimester screening. In the three OSB, CM (in 2/3 cases) and BSOB (3/3) distance were below the 5th percentile, BS and BS/BSOB ratio (3/3) were above the 95th percentile. In the CSB, all the measurements were within normal limits. The literature and our data agree that most fetuses with OSB demonstrate in the first trimester positive sonographic markers in the posterior fossa, but additional prospective studies are needed to establish the best protocol for OSB screening.

A New Ghost Cell/Level Set Method for Moving Boundary Problems: Application to Tumor Growth

PubMed Central

Macklin, Paul

2011-01-01

In this paper, we present a ghost cell/level set method for the evolution of interfaces whose normal velocity depend upon the solutions of linear and nonlinear quasi-steady reaction-diffusion equations with curvature-dependent boundary conditions. Our technique includes a ghost cell method that accurately discretizes normal derivative jump boundary conditions without smearing jumps in the tangential derivative; a new iterative method for solving linear and nonlinear quasi-steady reaction-diffusion equations; an adaptive discretization to compute the curvature and normal vectors; and a new discrete approximation to the Heaviside function. We present numerical examples that demonstrate better than 1.5-order convergence for problems where traditional ghost cell methods either fail to converge or attain at best sub-linear accuracy. We apply our techniques to a model of tumor growth in complex, heterogeneous tissues that consists of a nonlinear nutrient equation and a pressure equation with geometry-dependent jump boundary conditions. We simulate the growth of glioblastoma (an aggressive brain tumor) into a large, 1 cm square of brain tissue that includes heterogeneous nutrient delivery and varied biomechanical characteristics (white matter, gray matter, cerebrospinal fluid, and bone), and we observe growth morphologies that are highly dependent upon the variations of the tissue characteristics—an effect observed in real tumor growth. PMID:21331304

Performance Enhancement of the RatCAP Awake Rate Brain PET System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaska, P.; Vaska, P.; Woody, C.

The first full prototype of the RatCAP PET system, designed to image the brain of a rat while conscious, has been completed. Initial results demonstrated excellent spatial resolution, 1.8 mm FWHM with filtered backprojection and <1.5 mm FWHM with a Monte Carlo based MLEM method. However, noise equivalent countrate studies indicated the need for better timing to mitigate the effect of randoms. Thus, the front-end ASIC has been redesigned to minimize time walk, an accurate coincidence time alignment method has been implemented, and a variance reduction technique for the randoms is being developed. To maximize the quantitative capabilities required formore » neuroscience, corrections are being implemented and validated for positron range and photon noncollinearity, scatter (including outside the field of view), attenuation, randoms, and detector efficiency (deadtime is negligible). In addition, a more robust and compact PCI-based optical data acquisition system has been built to replace the original VME-based system while retaining the linux-based data processing and image reconstruction codes. Finally, a number of new animal imaging experiments have been carried out to demonstrate the performance of the RatCAP in real imaging situations, including an F-18 fluoride bone scan, a C-11 raclopride scan, and a dynamic C-11 methamphetamine scan.« less

Peripheral and Central Effects of Repeated Social Defeat Stress: Monocyte Trafficking, Microglial Activation, and Anxiety

PubMed Central

Reader, Brenda F.; Jarrett, Brant L.; McKim, Daniel B.; Wohleb, Eric S.; Godbout, Jonathan P.; Sheridan, John F.

2015-01-01

The development and exacerbation of depression and anxiety are associated with exposure to repeated psychosocial stress. Stress is known to affect the bidirectional communication between the nervous and immune systems leading to elevated levels of stress mediators including glucocorticoids (GCs) and catecholamines and increased trafficking of proinflammatory immune cells. Animal models, like the repeated social defeat (RSD) paradigm, were developed to explore this connection between stress and affective disorders. RSD induces activation of the sympathetic nervous system (SNS) and hypothalamic-pituitary (HPA) axis activation, increases bone marrow production and egress of primed, GC-insensitive monocytes, and stimulates the trafficking of these cells to tissues including the spleen, lung, and brain. Recently, the observation that these monocytes have the ability to traffic to the brain perivascular spaces and parenchyma have provided mechanisms by which these peripheral cells may contribute to the prolonged anxiety-like behavior associated with RSD. The data that have been amassed from the RSD paradigm and others recapitulate many of the behavioral and immunological phenotypes associated with human anxiety disorders and may serve to elucidate potential avenues of treatment for these disorders. Here, we will discuss novel and key data that will present an overview of the neuroendocrine, immunological and behavioral responses to social stressors. PMID:25596319

Genetically induced abnormal cranial development in human trisomy 18 with holoprosencephaly: comparisons with the normal tempo of osteogenic-neural development.

PubMed

Reid, Shaina N; Ziermann, Janine M; Gondré-Lewis, Marjorie C

2015-07-01

Craniofacial malformations are common congenital defects caused by failed midline inductive signals. These midline defects are associated with exposure of the fetus to exogenous teratogens and with inborn genetic errors such as those found in Down, Patau, Edwards' and Smith-Lemli-Opitz syndromes. Yet, there are no studies that analyze contributions of synchronous neurocranial and neural development in these disorders. Here we present the first in-depth analysis of malformations of the basicranium of a holoprosencephalic (HPE) trisomy 18 (T18; Edwards' syndrome) fetus with synophthalmic cyclopia and alobar HPE. With a combination of traditional gross dissection and state-of-the-art computed tomography, we demonstrate the deleterious effects of T18 caused by a translocation at 18p11.31. Bony features included a single developmentally unseparated frontal bone, and complete dual absence of the anterior cranial fossa and ethmoid bone. From a superior view with the calvarium plates removed, there was direct visual access to the orbital foramen and hard palate. Both the eyes and the pituitary gland, normally protected by bony structures, were exposed in the cranial cavity and in direct contact with the brain. The middle cranial fossa was shifted anteriorly, and foramina were either missing or displaced to an abnormal location due to the absence or misplacement of its respective cranial nerve (CN). When CN development was conserved in its induction and placement, the respective foramen developed in its normal location albeit with abnormal gross anatomical features, as seen in the facial nerve (CNVII) and the internal acoustic meatus. More anteriorly localized CNs and their foramina were absent or heavily disrupted compared with posterior ones. The severe malformations exhibited in the cranial fossae, orbital region, pituitary gland and sella turcica highlight the crucial involvement of transcription factors such as TGIF, which is located on chromosome 18 and contributes to neural patterning, in the proper development of neural and cranial structures. Our study of a T18 specimen emphasizes the intricate interplay between bone and brain development in midline craniofacial abnormalities in general. © 2015 Anatomical Society.

Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

PubMed Central

Florencio-Silva, Rinaldo; Sasso-Cerri, Estela; Simões, Manuel Jesus; Cerri, Paulo Sérgio

2015-01-01

Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling. PMID:26247020

Cancer-associated bone disease.

PubMed

Rizzoli, R; Body, J-J; Brandi, M-L; Cannata-Andia, J; Chappard, D; El Maghraoui, A; Glüer, C C; Kendler, D; Napoli, N; Papaioannou, A; Pierroz, D D; Rahme, M; Van Poznak, C H; de Villiers, T J; El Hajj Fuleihan, G

2013-12-01

Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and working groups to assist physicians in clinical decision making, providing them with evidence-based care pathways to prevent skeletal-related events and bone loss. The goal of this paper is to put forth an IOF position paper addressing bone diseases and cancer and summarizing the position papers of other organizations.

Resveratrol as an anti-cancer agent: A review.

PubMed

Rauf, Abdur; Imran, Muhammad; Butt, Masood Sadiq; Nadeem, Muhammad; Peters, Dennis G; Mubarak, Mohammad S

2018-06-13

Owing to their antimicrobial, antioxidant, and anti-inflammatory activity, grapes (Vitis vinifera L.) are the archetypal paradigms of fruits used not only for nutritional purposes, but also for exclusive therapeutics. Grapes are a prominent and promising source of phytochemicals, especially resveratrol, a phytoalexin antioxidant found in red grapes which has both chemopreventive and therapeutic effects against various ailments. Resveratrol's role in reducing different human cancers, including breast, cervical, uterine, blood, kidney, liver, eye, bladder, thyroid, esophageal, prostate, brain, lung, skin, gastric, colon, head and neck, bone, ovarian, and cervical, has been reviewed. This review covers the literature that deals with the anti-cancer mechanism of resveratrol with special reference to antioxidant potential. Furthermore, this article summarizes the literature pertaining to resveratrol as an anti-cancer agent.

Cerebral Fat Embolism: Recognition, Complications, and Prognosis.

PubMed

Godoy, Daniel Agustín; Di Napoli, Mario; Rabinstein, Alejandro A

2017-09-20

Fat embolism syndrome (FES) is a rare syndrome caused by embolization of fat particles into multiple organs including the brain. It typically manifests with petechial rash, deteriorating mental status, and progressive respiratory insufficiency, usually occurring within 24-48 h of trauma with long-bone fractures or an orthopedic surgery. The diagnosis of FES is based on clinical and imaging findings, but requires exclusion of alternative diagnoses. Although there is no specific treatment for FES, prompt recognition is important because it can avoid unnecessary interventions and clarify prognosis. Patients with severe FES can become critically ill, but even comatose patients with respiratory failure may recover favorably. Prophylactic measures, such as early stabilization of fractures and certain intraoperative techniques, may help decrease the incidence and severity of FES.

Anal metastasis as the sentinel and isolated presentation of invasive ductal breast carcinoma.

PubMed

Rengifo, C; Titi, S; Walls, J

2016-05-01

Breast cancer currently affects 1 in 8 women in the UK during their lifetime. Common sites for breast cancer metastasis include the axillary lymph nodes, bones, lung, liver, brain, soft tissue and adrenal glands. There is well documented evidence detailing breast metastasis to the gastrointestinal tract but anal metastasis is exceptionally rare. We present the case of a 78-year-old woman with an anal metastasis as the sentinel and isolated presentation of an invasive ductal breast carcinoma. As advances in the treatment of breast cancer improve, and with an ageing and expanding population, there will be an increasing number of cancer survivors, and more of these unusual presentations may be encountered in the future.

Disseminated Skeletal Muscle and Cardiac Metastasis from Squamous Cell Carcinoma of the Lung Detected with FDG and FLT PET/CT.

PubMed

Jain, Tarun Kumar; Rayamajhi, Sampanna Jung; Basher, Rajender Kumar; Gupta, Dheeraj; Maturu, Venkata Nagarjuna; Mittal, Bhagwant Rai

2016-09-01

Lung cancer is one of the leading cancers all over the world. Positron emission tomography (PET) using 18F fluorodeoxyglucose (18F FDG) is useful for staging of the disease and decide the appropriate management. 3'-deoxy-3'-18 F-fluorothymidine (18F FLT) is a tracer being extensively evaluated currently and is said to represent tumor proliferation. Common sites of metastases from lung cancer include adrenal glands, bone, and brain. Muscle metastasis and cardiac metastasis are uncommon findings. We report a case of squamous cell carcinoma of the lung with metastases to multiple skeletal muscles and myocardium detected with both FDG and FLT PET/computed tomography (CT).

Disseminated Skeletal Muscle and Cardiac Metastasis from Squamous Cell Carcinoma of the Lung Detected with FDG and FLT PET/CT

PubMed Central

Jain, Tarun Kumar; Rayamajhi, Sampanna Jung; Basher, Rajender Kumar; Gupta, Dheeraj; Maturu, Venkata Nagarjuna; Mittal, Bhagwant Rai

2016-01-01

Lung cancer is one of the leading cancers all over the world. Positron emission tomography (PET) using 18F fluorodeoxyglucose (18F FDG) is useful for staging of the disease and decide the appropriate management. 3’-deoxy-3’-18 F-fluorothymidine (18F FLT) is a tracer being extensively evaluated currently and is said to represent tumor proliferation. Common sites of metastases from lung cancer include adrenal glands, bone, and brain. Muscle metastasis and cardiac metastasis are uncommon findings. We report a case of squamous cell carcinoma of the lung with metastases to multiple skeletal muscles and myocardium detected with both FDG and FLT PET/computed tomography (CT). PMID:27651747

Multilayered tissues model for wave propagation loss assessment in cochlear implants

NASA Astrophysics Data System (ADS)

Paun, Maria-Alexandra; Dehollain, Catherine

2017-05-01

In this paper, a study of the power loss attenuation of the plane wave travelling through the tissue layers, from the outside to the inside of the skull within a cochlear implant, is performed. Different implantation depths of the internal antenna from 10 to 30 mm are considered. To this purpose, the gain and attenuation in dB are studied. A multilayer tissue model is developed, consisting of mainly skin, mastoid bone and brain. An s-parameter analysis is also carried out, using loop antennas and simulated head tissue. Ansoft Ansys® HFSS software is used for electro-magnetic simulations of the antennas, placed in different types of human tissues. Smith charts for antenna placed in both skin and multi-tissue model are included.

Normal development and growth of the human neurocranium and cranial base.

PubMed

Friede, H

1981-01-01

The literature on normal development and growth of certain areas of the human head is reviewed, starting with the early induction of the desmal neurocranium. the development of the brain capsule with its dural reinforcement bands and their connection with the basicranium is discussed, as is the primordial chondrocranium, including its bone replacement. Growth of the calvaria and the three cranial fossae is also analysed. Special interest is focused on the anterior fossa, as knowledge of the growth in this area is very important for an understanding of pathogenesis and possibilities of treating premature craniosynostosis. Finally it is stressed that close observation of the effects of treatment on this pathology may increase our knowledge of normal growth.

Fat Embolism Syndrome: A Case Report and Review Literature

PubMed Central

Uransilp, Nattaphol

2018-01-01

Fat embolism syndrome (FES) is a life-threatening complication in patients with orthopedic trauma, especially long bone fractures. The diagnosis of fat embolism is made by clinical features alone with no specific laboratory findings. FES has no specific treatment and requires supportive care, although it can be prevented by early fixation of bone fractures. Here, we report a case of FES in a patient with right femoral neck fracture, which was diagnosed initially by Gurd's criteria and subsequently confirmed by typical appearances on magnetic resonance imaging (MRI) of the brain. The patient received supportive management and a short course of intravenous methylprednisolone. PMID:29853905

Morbidity of Cushing's Syndrome and Impact of Treatment.

PubMed

Webb, Susan M; Valassi, Elena

2018-06-01

Cortisol excess in Cushing's syndrome is associated with metabolic, cardiovascular, and cognitive alterations, only partially reversible after resolution of hypercortisolism. Elevated cardiovascular risk may persist after eucortisolism has been achieved. Fractures and low bone mineral density are also described in Cushing's syndrome in remission. Hypercortisolism may induce irreversible structural and functional changes in the brain, leading to neuropsychiatric disorders in the active phase of the disease, which persist. Sustained deterioration of the cardiovascular system, bone remodeling, and cognitive function along with neuropsychological impairment are associated with high morbidity and poor quality of life before and after remission. Copyright © 2018 Elsevier Inc. All rights reserved.

Macronutrient Intake and Distribution in the Etiology, Prevention and Treatment of Osteosarcopenic Obesity.

PubMed

Kelly, Owen J; Gilman, Jennifer C; Kim, Youjin; Ilich, Jasminka Z

2017-01-01

Osteosarcopenic obesity, the combined deterioration of bone, muscle and fat tissues, could become the ultimate trajectory of aging. Aging stem cells are deregulated by low-grade chronic inflammation and possibly by diet. The metabolic shift of stem cells towards adipogenesis results in osteo obesity, sarco obesity and obesity. Macronutrients have numerous physiological functions but are regarded mainly for their energy contribution. Currently, no nutritional causes or treatment/prevention guidelines exist for osteosarcopenic obesity. The aim of this review is to assemble the evidence to elucidate if the macronutrient composition of the Western diet has an effect on the development of osteosarcopenic obesity. In view of the role of brain in locomotion a section examining the macronutrients as possible modulators of brain functioning was included. An extensive literature search of PubMed and Medline was conducted for human data using combinations and synonyms of osteoporosis, sarcopenia and obesity, and energy, carbohydrate, protein and lipid, and brain. US National Health and Nutrition Examination Survey (NHANES) food intake data from 2002-2012 were obtained and transposed to Microsoft Excel for analysis. NHANES data showed that energy imbalances in aging, excess high glycemic carbohydrate, lower protein intakes and low long chain polyunsaturated fat intakes may contribute to osteosarcopenic obesity. 135 articles were included in the review. Early humans probably consumed a diet closer to what the human body was designed for; however, we do not know the ideal energy and macronutrient proportions for optimal health or for preventing/treating aging and osteosarcopenic obesity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Morinda citrifolia L. Leaf Extract Protects against Cerebral Ischemia and Osteoporosis in an In Vivo Experimental Model of Menopause

PubMed Central

Thipkaew, Cholathip; Thukham-mee, Wipawee; Wannanon, Panakaporn

2018-01-01

We aimed to determine the protective effects against cerebral ischemia and osteoporosis of Morinda citrifolia extract in experimental menopause. The neuroprotective effect was assessed by giving M. citrifolia leaf extract at doses of 2, 10, and 50 mg/kg BW to the bilateral ovariectomized (OVX) rats for 7 days. Then, they were occluded in the right middle cerebral artery (MCAO) for 90 minutes. The neurological score, brain infarction volume, oxidative stress status, and ERK1/2 and eNOS activities were assessed 24 hours later. M. citrifolia improved neurological score, brain infarction, and brain oxidative stress status in the cortex of OVX rats plus the MCAO. No changes in ERK 1/2 signal pathway and NOS expression were observed in this area. Our data suggested that the neuroprotective effect of the extract might occur partly via the improvement of oxidative stress status in the cortex. The antiosteoporotic effect in OVX rats was also assessed after an 84-day intervention of M. citrifolia. The serum levels of calcium, osteocalcin, and alkaline phosphatase and osteoblast density in the tibia were increased, but the density of osteoclast was decreased in OVX rats which received the extract. Therefore, the current data suggested that the extract possessed antiosteoporotic effect by increasing bone formation but decreasing bone resorption. PMID:29765488

Morinda citrifolia L. Leaf Extract Protects against Cerebral Ischemia and Osteoporosis in an In Vivo Experimental Model of Menopause.

PubMed

Wattanathorn, Jintanaporn; Thipkaew, Cholathip; Thukham-Mee, Wipawee; Muchimapura, Supaporn; Wannanon, Panakaporn; Tong-Un, Terdthai

2018-01-01

We aimed to determine the protective effects against cerebral ischemia and osteoporosis of Morinda citrifolia extract in experimental menopause. The neuroprotective effect was assessed by giving M. citrifolia leaf extract at doses of 2, 10, and 50 mg/kg BW to the bilateral ovariectomized (OVX) rats for 7 days. Then, they were occluded in the right middle cerebral artery (MCAO) for 90 minutes. The neurological score, brain infarction volume, oxidative stress status, and ERK1/2 and eNOS activities were assessed 24 hours later. M. citrifolia improved neurological score, brain infarction, and brain oxidative stress status in the cortex of OVX rats plus the MCAO. No changes in ERK 1/2 signal pathway and NOS expression were observed in this area. Our data suggested that the neuroprotective effect of the extract might occur partly via the improvement of oxidative stress status in the cortex. The antiosteoporotic effect in OVX rats was also assessed after an 84-day intervention of M. citrifolia . The serum levels of calcium, osteocalcin, and alkaline phosphatase and osteoblast density in the tibia were increased, but the density of osteoclast was decreased in OVX rats which received the extract. Therefore, the current data suggested that the extract possessed antiosteoporotic effect by increasing bone formation but decreasing bone resorption.

Fat embolism syndrome: Clinical and imaging considerations: Case report and review of literature

PubMed Central

Shaikh, Nissar; Parchani, Ashok; Bhat, Venkatraman; Kattren, Marie Anne

2008-01-01

Fat embolism syndrome (FES) is a serious clinical disorder occurring after trauma, orthopedic procedures and rarely in non-traumatic patients. Fat emboli develop in nearly all patients with bone fractures, but they are usually asymptomatic. Small number of patients develop signs and symptoms of various organ system dysfunction due to either mechanical obstruction of capillaries by fat emboli or due to hydrolysis of fat to fatty acids. A triad of lung, brain and skin involvement develop after an asymptomatic period of 24 to 72 hours. This symptom complex is called FES. The incidence reported is up to 30%, but many mild cases may recover unnoticed. Diagnosis of fat embolism is clinical with nonspecific, insensitive diagnostic test results. Treatment of fat embolism syndrome remains supportive and in most cases can be prevented by early fixation of large bone factures. Here we report two cases of traumatic fat embolism, which were diagnosed initially by Gurd's criteria and subsequently confirmed by typical appearance on magnetic resonance imaging (MRI) of the brain in these patients. These patients were successfully treated with supportive management. In conclusion, diagnosis of FES needs high index of suspicion, exclusion of other conditions and use of clinical criteria in combination with imaging. Magnetic resonance imaging of the brain is of great importance in diagnosis and management of these patients. PMID:19826589

Occipital anaplastic oligodendroglioma with multiple organ metastases after a short clinical course: a case report and literature review

PubMed Central

2014-01-01

Background It is generally believed that malignant gliomas never metastasize outside the central nervous system (CNS). However, the notion that oligodendrogliomas (OGDs) cells cannot spread outside CNS is being challenged. Methods We described in detail the clinical story of one patient with anaplastic OGD, which metastasized to lymph nodes, bone marrowand bones Genetic analyses included detection of 1p and 19q chromosomal arms, methylation status of MGMT promoter, and PTEN exon mutations. A search of worldwide literature was conducted for reports of metastatic OGDs using NCBI-PubMed, with the keywords “extracranial”, “extraneural”, “oligodendroglioma”, “oligodendrogliomas”, “metastatic”, “metastasis”, and “metastases”, in different combinations. Results An open biopsy of the infiltrated bones in our patient revealed that malignant cells had replaced the patient’s marrow. Moreover, the diagnosis of multiple-organ metastases of anaplastic OGD was confirmed based on immunohistochemical staining. Genetic analyses showed that the tumors originated from previously resected brain lesions. None of the lesions had 1p and 19q deletions, but hypermethylation of MGMT promoter, and the G → A transversion at codon 234 of PTEN exon 2 were detected. Literatures review yielded 60 reports of metastatic OGDs from 1951 to the present, which with our patient makes 61 cases. Concerning these 61 patients, there were 110 infiltrated sites correlated closely with primary OGDs. The most frequent metastatic sites were bone and bone marrow (n = 47; 42.7%), lymph nodes (n = 22; 20.0%), liver (n = 7; 6.4%), scalp (n = 6; 5.5%), lung (n = 6; 5.5%), pleura (n = 4; 3.6%), chest wall (n = 3; 2.7%), iliopsoas muscle (n = 2; 1.8%), soft tissue (n = 2; 1.8%), and parotid gland (n = 2; 1.8%). Conclusions Extracranial metastases in anaplastic OGD are very rare but they do occur; bone and bone marrow may be the most common sites. Detection of certain molecular markers such as deletion of 1p and 19q chromosomal arms, hypermethylation of MGMT promoter, and characteristic PTEN exon mutations may help differentiate subtypes which are more prone to extracranial metastases. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8749838611478560. PMID:24447608

A case of extensive hyperostosis frontalis interna in an 87-year-old female human cadaver.

PubMed

Talarico, Ernest F; Prather, Andrew D; Hardt, Kevin D

2008-04-01

Hyperostosis frontalis interna (HFI) is a condition that involves thickening of the inner surface of the frontal bone with sparing of the midline. Little is known about the etiology and clinical presentation of HFI. We report unusual findings in a woman with extensive Type D hyperostosis of the frontal bone and a large hyperostotic nodule in the parietal bone with impingement on the precentral gyrus, distinguishing this from the common form of HFI. The scalp was dissected from the cranial vault, and the calvaria and brain were removed and digitally imaged. Bone specimens were embedded in methyl methacrylate plastic, sectioned, and stained using the Von Kossa Method with MacNeal's tetrachrome. Medical records were reviewed, and additional history was obtained through interviews with the donor's family. The calvaria had extensive, bilateral thickening of the frontal bone with irregular topography and clearly demarcated borders. The dura was adherent to all hyperostotic regions. A 3.5-cm nodule was visible on the inner table of the left parietal bone. The dura and cerebrum showed compression in this region, but it was unclear if this resulted in clinical ramifications. Microscopic analysis revealed a larger proportion of cancellous bone was present in regions of macroscopic hyperostosis. Quantitative analysis of sections through areas of gross hyperostosis demonstrated a lower proportion of lamellar bone than in the control. The patient exhibited symptoms that have been correlated to HFI in previous studies. We suggest that the HFI disease process was responsible for the manifestation of these symptoms in this patient. (c) 2008 Wiley-Liss, Inc.

Emergency management of fat embolism syndrome

PubMed Central

Shaikh, Nissar

2009-01-01

Fat emboli occur in all patients with long-bone fractures, but only few patients develop systemic dysfunction, particularly the triad of skin, brain, and lung dysfunction known as the fat embolism syndrome (FES). Here we review the FES literature under different subheadings. The incidence of FES varies from 1–29%. The etiology may be traumatic or, rarely, nontraumatic. Various factors increase the incidence of FES. Mechanical and biochemical theories have been proposed for the pathophysiology of FES. The clinical manifestations include respiratory and cerebral dysfunction and a petechial rash. Diagnosis of FES is difficult. The other causes for the above-mentioned organ dysfunction have to be excluded. The clinical criteria along with imaging studies help in diagnosis. FES can be detected early by continuous pulse oximetry in high-risk patients. Treatment of FES is essentially supportive. Medications, including steroids, heparin, alcohol, and dextran, have been found to be ineffective. PMID:19561953

Vitamin D and the skin: Focus on a complex relationship: A review

PubMed Central

Mostafa, Wedad Z.; Hegazy, Rehab A.

2014-01-01

The “sunshine” vitamin is a hot topic that attracted ample attention over the past decades, specially that a considerable proportion of the worldwide population are deficient in this essential nutrient. Vitamin D was primarily acknowledged for its importance in bone formation, however; increasing evidence point to its interference with the proper function of nearly every tissue in our bodies including brain, heart, muscles, immune system and skin. Thereby its deficiency has been incriminated in a long panel of diseases including cancers, autoimmune diseases, cardiovascular and neurological disorders. Its involvement in the pathogenesis of different dermatological diseases is no exception and has been the subject of much research over the recent years. In the current review, we will throw light on this highly disputed vitamin that is creating a significant concern from a dermatological perspective. Furthermore, the consequences of its deficiency on the skin will be in focus. PMID:26644915

Long-term effects of a ketogenic diet on body composition and bone mineralization in GLUT-1 deficiency syndrome: a case series.

PubMed

Bertoli, Simona; Trentani, Claudia; Ferraris, Cinzia; De Giorgis, Valentina; Veggiotti, Pierangelo; Tagliabue, Anna

2014-06-01

The only known treatment of glucose transporter 1 deficiency syndrome (GLUT-1 DS) is a ketogenic diet (KD), which provides the brain with an alternative fuel. Studies in children with intractable epilepsy have shown that a prolonged KD can induce a progressive loss of bone mineral content associated with poor bone health status, probably as a consequence of a chronic acidic environment. The aim of this study is to determine the long-term effects of a KD on body composition and bone mineral status of patients with GLUT-1 DS, is currently unknown. In this case series, we report the changes in body composition and bone mineral status observed in three adult patients with GLUT-1 DS who have been treated with a KD for more than 5 y. A long-term KD did not produce appreciable changes in weight and body composition of adults with GLUT-1 DS. Moreover, we found no evidence of potential adverse effects of a KD on bone health. In summary, this case series contributes to a small but growing body of literature that investigated the potential long-term effects of a KD on bone health. Our data suggest that maintaining a KD for more than 5 y does not pose any major negative effects on body composition, bone mineral content, and bone mineral density in adults with GLUT-1 DS, a finding that is at variance with previous reports focusing on children with intractable epilepsy. Further studies with larger sizes are needed to confirm and expand our findings. Copyright © 2014 Elsevier Inc. All rights reserved.

Repair of bony lateral skull base defects equal to or larger than 10 mm by extracorporeally sewed unit-sandwich graft.

PubMed

Indorewala, Shabbir; Nemade, Gaurav; Indorewala, Abuzar; Mahajan, Gauri

2018-06-23

To see effectiveness of the senior author's repair technique for repair of large (equal to or larger than 10 mm) bony lateral skull base defects. Retrospective. Secondary/tertiary care center. We performed retrospective review of 9 surgeries done in our institution between January 2010 and December 2013 for repair of large lateral bony skull base defects. We defined skull base defects extra-cranially and repaired them intra-cranially. We made an extracorporeal sandwich of autologous fascia-bone-fascia (fascia lata and nasal septal bone) and sewed it together to make it into a unit-sandwich graft. This extracorporeally sewed unit-sandwich graft was then inserted to close the large skull base defects either via (1) a cranial slit-window, or (2) the skull base defect itself. Since skull base is bony, bony repair is preferred. Bone plates that are easily available for skull base repair are calvarial and nasal septal bone. Occasionally, harvest of split calvarial bone carries risk of major complications. We preferred nasal septal bone. Harvesting of septal bone even in children using a posterior incision should not disturb the cartilage growth centers. All nine patients were operated by this technique. We had four patients with cerebrospinal fluid leak, and five patients with brain herniation. All these patients had complete reversal of herniation of cranial contents and cessation of cerebrospinal fluid leak. On imaging, in 6 cases the bone graft remained in original intended position after 12 months of surgery. The bone graft was not identifiable in 3 cases. The senior author's technique using autologous multi-layered graft is simple to master, repeatable and very effective.

Microarchitecture of irradiated bone: comparison with healthy bone

NASA Astrophysics Data System (ADS)

Bléry, Pauline; Amouriq, Yves; Guédon, Jeanpierre; Pilet, Paul; Normand, Nicolas; Durand, Nicolas; Espitalier, Florent; Arlicot, Aurore; Malard, Olivier; Weiss, Pierre

2012-03-01

The squamous cell carcinomas of the upper aero-digestive tract represent about ten percent of cancers. External radiation therapy leads to esthetic and functional consequences, and to a decrease of the bone mechanical abilities. For these patients, the oral prosthetic rehabilitation, including possibilities of dental implant placement, is difficult. The effects of radiotherapy on bone microarchitecture parameters are not well known. Thus, the purpose of this study is to assess the effects of external radiation on bone micro architecture in an experimental model of 25 rats using micro CT. 15 rats were irradiated on the hind limbs by a single dose of 20 Grays, and 10 rats were non irradiated. Images of irradiated and healthy bone were compared. Bone microarchitecture parameters (including trabecular thickness, trabecular number, trabecular separation, connectivity density and tissue and bone volume) between irradiated and non-irradiated bones were calculated and compared using a Mann and Whitney test. After 7 and 12 weeks, images of irradiated and healthy bone are different. Differences on the irradiated and the healthy bone populations exhibit a statistical significance. Trabecular number, connectivity density and closed porosity are less important on irradiated bone. Trabecular thickness and separation increase for irradiated bone. These parameters indicate a decrease of irradiated bone properties. Finally, the external irradiation induces changes on the bone micro architecture. This knowledge is of prime importance for better oral prosthetic rehabilitation, including implant placement.

Engineering 3D Models of Tumors and Bone to Understand Tumor-Induced Bone Disease and Improve Treatments.

PubMed

Kwakwa, Kristin A; Vanderburgh, Joseph P; Guelcher, Scott A; Sterling, Julie A

2017-08-01

Bone is a structurally unique microenvironment that presents many challenges for the development of 3D models for studying bone physiology and diseases, including cancer. As researchers continue to investigate the interactions within the bone microenvironment, the development of 3D models of bone has become critical. 3D models have been developed that replicate some properties of bone, but have not fully reproduced the complex structural and cellular composition of the bone microenvironment. This review will discuss 3D models including polyurethane, silk, and collagen scaffolds that have been developed to study tumor-induced bone disease. In addition, we discuss 3D printing techniques used to better replicate the structure of bone. 3D models that better replicate the bone microenvironment will help researchers better understand the dynamic interactions between tumors and the bone microenvironment, ultimately leading to better models for testing therapeutics and predicting patient outcomes.

A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia.

PubMed

Fanganiello, R D; Kimonis, V E; Côrte, C C; Nitrini, R; Passos-Bueno, M R

2011-04-01

Inclusion body myopathy associated with Paget disease and frontotemporal dementia (IBMPFD) is a progressive and usually misdiagnosed autosomal dominant disorder. It is clinically characterized by a triad of features: proximal and distal myopathy, early onset Paget disease of bone (PDB), and frontotemporal dementia (FTD). It is caused by missense mutations in the valosin-containing protein (VCP) gene. We describe here the clinical and molecular findings of the first Brazilian family identified with IBMPFD. Progressive myopathy affecting the limb girdles was detected by clinical examination followed by muscle biopsy and creatine kinase measurement. PDB was suggested after anatomopathological bone examination and FTD was diagnosed by clinical, neuropsychological and language evaluations. Brain magnetic resonance revealed severe atrophy of the anterior temporal lobes, including the hippocampi. A R93C mutation in VCP was detected by direct sequencing screening in subject W (age 62) and in his mother. Four more individuals diagnosed with "dementia" were reported in this family. We also present a comprehensive genotype-phenotype correlation analysis of mutations in VCP in 182 patients from 29 families described in the literature and show that while IBM is a conspicuously penetrant symptom, PDB has a lower penetrance when associated with mutations in the AAAD1 domain and FTD has a lower penetrance when associated with mutations in the Junction (L1-D1) domain. Furthermore, the R93C mutation is likely to be associated with the penetrance of all the clinical symptoms of the triad.

Intravascular lymphomatosis presenting as acute hemispheric dysfunction.

PubMed

Hwang, Woo Sub; Jung, Chul Won; Ko, Young Hye; Seo, Sang Won; Na, Duk L

2012-11-01

Intravascular lymphomatosis (IVL) is known to affect both hemispheres of the brain and manifests clinically as seizures or dementia. To our knowledge, there have been no cases in which acute hemispheric dysfunction is manifested in IVL. We present a 54-year-old man who showed steroid responsive acute hemispheric dysfunction. A technetium 99m-ethyl cysteinate dimer single-photon emission computed tomographic scan of the brain revealed hypoperfusion in the right hemisphere. The bone marrow biopsy specimen confirmed malignant lymphoid cells in vessels, which suggested IVL. Our case signifies the diversity of clinical manifestations in IVL. Copyright © 2012. Published by Elsevier Inc.

Potential utility of natural products as regulators of breast cancer-assoicated aromatase promoters

USDA-ARS?s Scientific Manuscript database

Aromatase, the key enzyme in estrogen biosynthesis, converts androstenedione to estrone and testosterone to estradiol. The enzyme is expressed in various tissues such as ovary, placenta, bone, brain, skin, and adipose tissue. Aromatase enzyme is encoded by a single gene CYP 19A1 and its expression i...

Feasibility of MRI-only treatment planning for proton therapy in brain and prostate cancers: Dose calculation accuracy in substitute CT images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koivula, Lauri

Purpose: Magnetic resonance imaging (MRI) is increasingly used for radiotherapy target delineation, image guidance, and treatment response monitoring. Recent studies have shown that an entire external x-ray radiotherapy treatment planning (RTP) workflow for brain tumor or prostate cancer patients based only on MRI reference images is feasible. This study aims to show that a MRI-only based RTP workflow is also feasible for proton beam therapy plans generated in MRI-based substitute computed tomography (sCT) images of the head and the pelvis. Methods: The sCTs were constructed for ten prostate cancer and ten brain tumor patients primarily by transforming the intensity valuesmore » of in-phase MR images to Hounsfield units (HUs) with a dual model HU conversion technique to enable heterogeneous tissue representation. HU conversion models for the pelvis were adopted from previous studies, further extended in this study also for head MRI by generating anatomical site-specific conversion models (a new training data set of ten other brain patients). This study also evaluated two other types of simplified sCT: dual bulk density (for bone and water) and homogeneous (water only). For every clinical case, intensity modulated proton therapy (IMPT) plans robustly optimized in standard planning CTs were calculated in sCT for evaluation, and vice versa. Overall dose agreement was evaluated using dose–volume histogram parameters and 3D gamma criteria. Results: In heterogeneous sCTs, the mean absolute errors in HUs were 34 (soft tissues: 13, bones: 92) and 42 (soft tissues: 9, bones: 97) in the head and in the pelvis, respectively. The maximum absolute dose differences relative to CT in the brain tumor clinical target volume (CTV) were 1.4% for heterogeneous sCT, 1.8% for dual bulk sCT, and 8.9% for homogenous sCT. The corresponding maximum differences in the prostate CTV were 0.6%, 1.2%, and 3.6%, respectively. The percentages of dose points in the head and pelvis passing 1% and 1 mm gamma index criteria were over 91%, 85%, and 38% with heterogeneous, dual bulk, and homogeneous sCTs, respectively. There were no significant changes to gamma index pass rates for IMPT plans first optimized in CT and then calculated in heterogeneous sCT versus IMPT plans first optimized in heterogeneous sCT and then calculated on standard CT. Conclusions: This study demonstrates that proton therapy dose calculations on heterogeneous sCTs are in good agreement with plans generated with standard planning CT. An MRI-only based RTP workflow is feasible in IMPT for brain tumors and prostate cancers.« less

Use of Video Goggles to Distract Patients During PET/CT Studies of School-Aged Children.

PubMed

Gelfand, Michael J; Harris, Jennifer M; Rich, Amanda C; Kist, Chelsea S

2016-12-01

This study was designed to evaluate the effectiveness of video goggles in distracting children undergoing PET/CT and to determine whether the goggles create CT and PET artifacts. Video goggles with small amounts of internal radioopaque material were used. During whole-body PET/CT imaging, 30 nonsedated patients aged 4-13 y watched videos of their choice using the goggles. Fifteen of the PET/CT studies were performed on a scanner installed in 2006, and the other 15 were performed on a scanner installed in 2013. The fused scans were reviewed for evidence of head movement, and the individual PET and CT scans of the head were reviewed for the presence and severity of streak artifact. The CT exposure settings were recorded for each scan at the anatomic level at which the goggles were worn. Only one of the 30 scans had evidence of significant head motion. Two of the 30 had minor coregistration problems due to motion, and 27 of the 30 had very good to excellent coregistration. For the 2006 scanner, 2 of the 14 evaluable localization CT scans of the head demonstrated no streak artifact in brain tissue, 6 of the 14 had mild streak artifact in brain tissue, and 6 of the 14 had moderate streak artifact in brain tissue. Mild streak artifact in bone was noted in 2 of the 14 studies. For the 2013 scanner, 7 of 15 studies had mild streak artifact in brain tissue and 8 of 15 had no streak artifact in brain tissue, whereas none of the 15 had streak artifact in bone. There were no artifacts attributable to the goggles on the 18 F-FDG PET brain images of any of the 29 evaluable studies. The average CT exposure parameters at the level of the orbits were 36% lower on the 2013 scanner than on the 2006 scanner. Video goggles may be used successfully to distract children undergoing PET with localization CT. The goggles cause no significant degradation of the PET brain images or the CT skull images. The degree of artifact on brain tissue images varies from none to moderate and depends on the CT equipment used. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Transient receptor potential melastatin subfamily member 2 cation channel regulates detrimental immune cell invasion in ischemic stroke.

PubMed

Gelderblom, Mathias; Melzer, Nico; Schattling, Benjamin; Göb, Eva; Hicking, Gordon; Arunachalam, Priyadharshini; Bittner, Stefan; Ufer, Friederike; Herrmann, Alexander M; Bernreuther, Christian; Glatzel, Markus; Gerloff, Christian; Kleinschnitz, Christoph; Meuth, Sven G; Friese, Manuel A; Magnus, Tim

2014-11-01

Brain injury during stroke results in oxidative stress and the release of factors that include extracellular Ca(2+), hydrogen peroxide, adenosine diphosphate ribose, and nicotinic acid adenine dinucleotide phosphate. These alterations of the extracellular milieu change the activity of transient receptor potential melastatin subfamily member 2 (TRPM2), a nonselective cation channel expressed in the central nervous system and the immune system. Our goal was to evaluate the contribution of TRPM2 to the tissue damage after stroke. In accordance with current quality guidelines, we independently characterized Trpm2 in a murine ischemic stroke model in 2 different laboratories. Gene deficiency of Trpm2 resulted in significantly improved neurological outcome and decreased infarct size. Besides an already known moderate neuroprotective effect of Trpm2 deficiency in vitro, ischemic brain invasion by neutrophils and macrophages was particularly reduced in Trpm2-deficient mice. Bone marrow chimeric mice revealed that Trpm2 deficiency in the peripheral immune system is responsible for the protective phenotype. Furthermore, experiments with mixed bone marrow chimeras demonstrated that Trpm2 is essential for the migration of neutrophils and, to a lesser extent, also of macrophages into ischemic hemispheres. Notably, the pharmacological TRPM2 inhibitor, N-(p-amylcinnamoyl)anthranilic acid, was equally protective in the stroke model. Although a neuroprotective effect of TRPM2 in vitro is well known, we can show for the first time that the detrimental role of TRPM2 in stroke primarily depends on its role in activating peripheral immune cells. Targeting TRPM2 systemically represents a promising therapeutic approach for ischemic stroke. © 2014 American Heart Association, Inc.

Premature primary tooth eruption in cognitive/motor-delayed ADNP-mutated children

PubMed Central

Gozes, I; Van Dijck, A; Hacohen-Kleiman, G; Grigg, I; Karmon, G; Giladi, E; Eger, M; Gabet, Y; Pasmanik-Chor, M; Cappuyns, E; Elpeleg, O; Kooy, R F; Bedrosian-Sermone, S

2017-01-01

A major flaw in autism spectrum disorder (ASD) management is late diagnosis. Activity-dependent neuroprotective protein (ADNP) is a most frequent de novo mutated ASD-related gene. Functionally, ADNP protects nerve cells against electrical blockade. In mice, complete Adnp deficiency results in dysregulation of over 400 genes and failure to form a brain. Adnp haploinsufficiency results in cognitive and social deficiencies coupled to sex- and age-dependent deficits in the key microtubule and ion channel pathways. Here, collaborating with parents/caregivers globally, we discovered premature tooth eruption as a potential early diagnostic biomarker for ADNP mutation. The parents of 44/54 ADNP-mutated children reported an almost full erupted dentition by 1 year of age, including molars and only 10 of the children had teeth within the normal developmental time range. Looking at Adnp-deficient mice, by computed tomography, showed significantly smaller dental sacs and tooth buds at 5 days of age in the deficient mice compared to littermate controls. There was only trending at 2 days, implicating age-dependent dysregulation of teething in Adnp-deficient mice. Allen Atlas analysis showed Adnp expression in the jaw area. RNA sequencing (RNAseq) and gene array analysis of human ADNP-mutated lymphoblastoids, whole-mouse embryos and mouse brains identified dysregulation of bone/nervous system-controlling genes resulting from ADNP mutation/deficiency (for example, BMP1 and BMP4). AKAP6, discovered here as a major gene regulated by ADNP, also links cognition and bone maintenance. To the best of our knowledge, this is the first time that early primary (deciduous) teething is related to the ADNP syndrome, providing for early/simple diagnosis and paving the path to early intervention/specialized treatment plan. PMID:28221363

Knowledge about transplantation and attitudes toward organ donation: a survey among medical students in northeast Brazil.

PubMed

Dutra, M M D; Bonfim, T A S; Pereira, I S; Figueiredo, I C; Dutra, A M D; Lopes, A A

2004-05-01

During the registration for the second semester of 2002, 779 of the 1001 students from the Medical School, Federal University of Bahia, Brazil, answered an anonymous multiple-choice questionnaire including demographic variables, knowledge about transplantation issues, and willingness to donate organs. Mean age was 21.9 +/- 2.9 years (range: 17 to 51 years); 59.5% were men. Regarding the knowledge of which organs and tissues could be transplanted, 99.1% answered kidneys, 96.1% heart, 88.2% liver, 41.1% lung, 24.0% pancreas, 9% bowel, 98.3% corneas, 89.5% bone marrow, 38.1% heart valves, 47.7% skin, and 18.5% bone and tendons. Regarding the criteria of death, 82.4% answered that it is the lack of all brain activity, 8.2% cardiac arrest, 5.2% irreversible coma, and 4.2% did not know. As to the Brazilian transplantation law, 47.3% did not know, 51% had heard about it, and 1.7% answered that they knew the law in detail. As to the willingness to donate organs, 538 (69.2%) were donors. Of 239 nondonors, 51.1% answered the reason for not donating was the lack of confidence in the heath system, 14.3% had no knowledge of the matter, 17.7% were concerned about organ removal before brain death, and 1.7% for religious reasons. The percentage of those willing to donate organs was greater among spiritualists than among Catholics and Protestants. The results of this study support a greater emphasis on providing information regarding transplantation in medical schools to improve the knowledge of future heath care professionals about transplantation and organ donation issues.

Ewing's sarcoma of the cranial vault: a case report.

PubMed

Feki, Jihene; Guermazi, Zeineb; Kammoun, Brahim; Khanfir, Afef; Toumi, Nabil; Boudawara, Tahiya; Boudawara, Zaher; Daoud, Jamel; Frikha, Mounir

2017-12-01

Ewing's sarcoma is a malignant tumor that mainly affects young patients. It represents 10% of primary malignant tumors of the bone and 3% of malignant tumors of the child. Cranial localization is extremely rare representing less than 1% of all the localizations. We report a case of a 10-year-old girl who presented with an intracranial hypertension syndrome with left parietal mass of progressive installation. The X-ray skull showed a lytic lesion with irregular margins involving the left parietal bone. Brain magnetic resonance imaging revealed extensive parietal bone destruction involving both the inner and outer tables. The girl was operated in emergency. Histological examination concluded to Ewing's Sarcoma. The resection was incomplete (R1). The girl received induction's chemotherapy. The cerebral scanner evaluation showed no abnormalities. Then, she received consolidation's chemotherapy with concomitant local radiation therapy. Currently, the girl is in complete remission with a seven-month decline.

[Clinical predictors correlated to outcome of war missile penetrating brain injury].

PubMed

Splavski, Bruno; Vranković, Duro; Saftić, Robert; Muzević, Dario; Kosuta, Maja; Gmajnić, Rudika

2006-09-01

The purpose of this retrospective study was to review and discuss the outcome of surgical management and other clinical predictors influencing the prognosis of war missile penetrating brain injuries. To determine clinical predictors that influence the prognosis of war missile penetrating brain injury, 126 surgically treated patients who had sustained such an injury during the two-year period of war in Croatia (1991-1993) were retrospectively analyzed. Investigated clinical features were: Glasgow Coma Scale (GCS) score on admission; extent of brain injury; time between injury and hospital admission; presence of intracranially retained foreign bodies or bone fragments; development of postinjury and posttraumatic complications; and Glasgow Outcome Score (GOS) at six-month follow up. The data were statistically analyzed. Sixty-seven patients survived penetrating missile brain injury, in most of them with GCS score above 8 on admission. The mean time interval to hospital admission in this group of patients was less than two hours. Twelve of 67 patients developed different complications. All patients recovered well according to GOS (GOS 5 and 4) at six-month follow up. Fifty-nine patients died. The wounded who were in moribund state on the hospital admission (n = 11), and those who died during surgery (n = 8) were excluded from the analysis. The remaining 40 patients who did not survive were analyzed. The majority of them had GCS score 3-8 on admission. They mostly sustained bilateral hemispheric lesion, and/or ventricular lesion, and developed brain edema. The mean time interval between injury and hospital admission was over two hours in this group of patients. Postoperative complication developed in 9 of 40 patients. The patients with GCS score exceeding 8 had by far more favorable outcome in comparison to those with GCS score less than 8. Considering the extent of injury, patients suffering unihemispheric brain wounds had a more favorable outcome than those with lesions of both hemispheres, and particularly those with transventricular lesions. The time between injury and hospital admission proved to be another important prognostic factor. The majority of patients admitted up to one hour of injury survived, while two thirds of those admitted between one and three hours of injury succumbed. The presence of intracranially retained foreign bodies and bone fragments, and postinjury and postoperative complications implied worse outcome in comparison with their absence. The state of consciousness on admission was the most sensitive criterion as far as the prognosis is concerned. The outcome also depended on the extent of brain damage since the wounds associated with a high mortality rate were predominantly bihemispheric. Concerning survival, the time between injury and hospital admission also appeared to be important, as well as intracranially retained foreign bodies and bone fragments, and development of complications. There was no relationship between the presence of retained fragments and development of infection, suggesting that it is not necessary to reoperate for retained fragments. We assume that early surgery is essential for treatment outcome, although it is not necessary to reoperate for retained fragments.

Bone's mechanostat: a 2003 update.

PubMed

Frost, Harold M

2003-12-01

The still-evolving mechanostat hypothesis for bones inserts tissue-level realities into the former knowledge gap between bone's organ-level and cell-level realities. It concerns load-bearing bones in postnatal free-living bony vertebrates, physiologic bone loading, and how bones adapt their strength to the mechanical loads on them. Voluntary mechanical usage determines most of the postnatal strength of healthy bones in ways that minimize nontraumatic fractures and create a bone-strength safety factor. The mechanostat hypothesis predicts 32 things that occur, including the gross anatomical bone abnormalities in osteogenesis imperfecta; it distinguishes postnatal situations from baseline conditions at birth; it distinguishes bones that carry typical voluntary loads from bones that have other chief functions; and it distinguishes traumatic from nontraumatic fractures. It provides functional definitions of mechanical bone competence, bone quality, osteopenias, and osteoporoses. It includes permissive hormonal and other effects on bones, a marrow mediator mechanism, some limitations of clinical densitometry, a cause of bone "mass" plateaus during treatment, an "adaptational lag" in some children, and some vibration effects on bones. The mechanostat hypothesis may have analogs in nonosseous skeletal organs as well. Copyright 2003 Wiley-Liss, Inc.

Fat embolism syndrome

PubMed Central

Richards, Robin R.

1997-01-01

Fat embolism syndrome, an important contributor to the development of acute respiratory distress syndrome, has been associated with both traumatic and nontraumatic disorders. Fat embolization after long bone trauma is probably common as a subclinical event. Fat emboli can deform and pass through the lungs, resulting in systemic embolization, most commonly to the brain and kidneys. The diagnosis of fat embolism syndrome is based on the patient’s history, supported by clinical signs of pulmonary, cerebral and cutaneous dysfunction and confirmed by the demonstration of arterial hypoxemia in the absence of other disorders. Treatment of fat embolism syndrome consists of general supportive measures, including splinting, maintenance of fluid and electrolyte balance and the administration of oxygen. Endotracheal intubation and mechanical ventilatory assistance can be indicated. The role of corticosteroids remains controversial. Early stabilization of long bone fractures has been shown to decrease the incidence of pulmonary complications. Clinical and experimental studies suggest that the exact method of fracture fixation plays a minor role in the development of pulmonary dysfunction. As more is learned about the specifics of the various triggers for the development of fat embolism syndrome, it is hoped that the prospect of more specific therapy for the prevention and treatment of this disorder will become a reality. PMID:9336522

Circulating osteogentic precursor cells in non-hereditary heterotopic ossification.

PubMed

Egan, Kevin P; Duque, Gustavo; Keenan, Mary Ann; Pignolo, Robert J

2018-04-01

Non-hereditary heterotopic ossification (NHHO) may occur after musculoskeletal trauma, central nervous system (CNS) injury, or surgery. We previously described circulating osteogenic precursor (COP) cells as a bone marrow-derived type 1 collagen + CD45 + subpopulation of mononuclear adherent cells that are able of producing extraskeletal ossification in a murine in vivo implantation assay. In the current study, we performed a tissue analysis of COP cells in NHHO secondary to defined conditions, including traumatic brain injury, spinal cord injury, cerebrovascular accident, trauma without neurologic injury, and joint arthroplasty. All bone specimens revealed the presence of COP cells at 2-14 cells per high power field. COP cells were localized to early fibroproliferative and neovascular lesions of NHHO with evidence for their circulatory status supported by their presence near blood vessels in examined lesions. This study provides the first systematic evaluation of COP cells as a contributory histopathological finding associated with multiple forms of NHHO. These data support that circulating, hematopoietic-derived cells with osteogenic potential can seed inflammatory sites, such as those subject to soft tissue injury, and due to their migratory nature, may likely be involved in seeding sites distant to CNS injury. Copyright © 2018 Elsevier Inc. All rights reserved.

A theory of marks and mind: the effect of notational systems on hominid brain evolution and child development with an emphasis on exchanges between mothers and children.

PubMed

Sheridan, Susan Rich

2005-01-01

A model of human language requires a theory of meaningful marks. Humans are the only species who use marks to think. A theory of marks identifies children's scribbles as significant behavior, while hypothesizing the importance of rotational systems to hominid brain evolution. By recognizing the importance of children's scribbles and drawings in developmental terms as well as in evolutionary terms, a marks-based rather than a predominantly speech-based theory of the human brain, language, and consciousness emerges. Combined research in anthropology, primatology, art history, neurology, child development (including research with deaf and blind children), gender studies and literacy suggests the importance of notational systems to human language, revealing the importance of mother/child interactions around marks and sounds to the development of an expressive, communicative, symbolic human brain. An understanding of human language is enriched by identifying marks carved on bone 1.9 million years ago as observational lunar calendar-keeping, pushing proto-literacy back dramatically. Neurologically, children recapitulate the meaningful marks of early hominins when they scribble and draw, reminding us that literacy belongs to humankind's earliest history. Even more than speech, such meaningful marks played - and continue to play - decisive roles in human brain evolution. The hominid brain required a model for integrative, transformative neural transfer. The research strongly suggests that humankind's multiple literacies (art, literature, scientific writing, mathematics and music) depended upon dyadic exchanges between hominid mothers and children, and that this exchange and sharing of visuo-spatial information drove the elaboration of human speech in terms of syntax, grammar and vocabulary. The human brain was spatial before it was linguistic. The child scribbles and draws before it speaks or writes. Children babble and scribble within the first two years of life. Hands and mouths are proximal on the sensory-motor cortex. Gestures accompany speech. Illiterate brains mis-pronounce nonsense sounds. Literate brains do not. Written language (work of the hands) enhances spoken language (work of the mouth). Until brain scans map the neurological links between human gesture, speech and marks in the context of mother/caregiver/child interactions, and research with literate and illiterate brains document even more precisely the long-term differences between these brains, the evolutionary pressure of marks on especially flexible maternal and infant brain tissue that occurred 1.9 million years, radically changing primate brain capabilities, requires an integrated theory of marks and mind.

Neural cells derived from adult bone marrow and umbilical cord blood.

PubMed

Sanchez-Ramos, Juan R

2002-09-15

Under experimental conditions, tissue-specific stem cells have been shown to give rise to cell lineages not normally found in the organ or tissue of residence. Neural stem cells from fetal brain have been shown to give rise to blood cell lines and conversely, bone marrow stromal cells have been reported to generate skeletal and cardiac muscle, oval hepatocytes, as well as glia and neuron-like cells. This article reviews studies in which cells from postnatal bone marrow or umbilical cord blood were induced to proliferate and differentiate into glia and neurons, cellular lineages that are not their normal destiny. The review encompasses in vitro and in vivo studies with focus on experimental variables, such as the source and characterization of cells, cell-tracking methods, and markers of neural differentiation. The existence of stem/progenitor cells with previously unappreciated proliferation and differentiation potential in postnatal bone marrow and in umbilical cord blood opens up the possibility of using stem cells found in these tissues to treat degenerative, post-traumatic and hereditary diseases of the central nervous system. Copyright 2002 Wiley-Liss, Inc.

Assessing the effect of dietary calcium intake and 25 OHD status on bone turnover in women in Pakistan.

PubMed

Khan, Aysha Habib; Naureen, Ghazala; Iqbal, Romaina; Dar, Farhan Javed

2013-01-01

Bone health assessed in three towns of Karachi, Pakistan in females showed poor calcium intake, vitamin D deficiency, secondary hyperparathyroidism, and high bone turnover. Correlates of high bone turnover included females residing in Saddar Town, underweight females less than 30 years of age from low socio-economic status, and secondary hyperparathyroidism. To assess bone health and association of dietary calcium and 25 hydroxy vitamin D with bone turnover in the community-dwelling females of Karachi. Bone health was assessed in three randomly selected towns of Karachi, Pakistan. One premenopausal female fulfilling the inclusion criteria from each household was included in the study. Dietary calcium was assessed through a food frequency questionnaire and biochemical markers including calcium, phosphates, albumin, magnesium, creatinine, and SGPT, intact parathyroid hormone, 25 hydroxy vitamin D, and N-telopeptide of type I collagen were measured to assess the bone health. Three hundred and five females were included from three towns. Overall, 90.5% of females had vitamin D deficiency with 42.6 and 23.3% having secondary hyperparathyroidism and high bone turn over respectively. Prevalence of vitamin D deficiency, secondary hyperparathyroidism, and high bone turnover was significantly different among towns. Mean vitamin D levels were significantly low and iPTH levels significantly high in females with high bone turnover. Calcium intake was not significantly different among females with normal, high, and low bone turnover. Correlates of high bone turnover included females residing in Saddar Town, underweight females less than 30 years of age belonging to low socio-economic status, and secondary hyperparathyroidism. Compromised bone health is seen in community-dwelling females of Karachi. There is a need to perform large-scale community-based studies in all age groups to understand the interplay of markers in our population to understand the impact of these variables translating into the risk of osteoporosis.

Facts a New Patient Needs to Know about Paget's Disease of Bone

MedlinePlus

... Patient Needs to Know About Paget’s Disease of Bone What Is Paget’s Disease of Bone? Paget’s disease of bone causes bones to grow ... Paget’s disease. These include: NIH Osteoporosis and Related Bone Diseases ~ National Resource Center Website: http://www.bones. ...

The prognosis analysis of different metastasis pattern in patients with different breast cancer subtypes: a SEER based study.

PubMed

Wang, Haiyong; Zhang, Chenyue; Zhang, Jingze; Kong, Li; Zhu, Hui; Yu, Jinming

2017-04-18

Studies on prognosis of different metastasis patterns in patients with different breast cancer subtypes (BCS) are limited. Therefore, we identified 7862 breast cancer patients with distant metastasis from 2010 to 2013 using Surveillance, Epidemiology, wand End Results (SEER) population-based data. The results showed that bone was the most common metastatic site and brain was the least common metastatic site, and the patients with HR+/HER2- occupied the highest metastasis proportion, the lowest metastasis proportion were found in HR-/HER2+ patients. Univariate and multivariate logistic regression analysis were used to analyze the association, and it was found that there were significant differences of distant metastasis patterns in patients with different BCS(different P value). Importantly, univariate and multivariate Cox regression analysis were used to analyze the prognosis. It was proven that only bone metastasis was not a prognostic factor in the HR+/HER2-, HR+/HER2+ and HR-/HER2+ subgroup (all, P > 0.05), and patients with brain metastasis had the worst cancer specific survival (CSS) in all the subgroups of BCS (all, P<0.01). Interestingly, for patients with two metastatic sites, those with bone and lung metastasis had best CSS in the HR+/HER2- (P<0.001) and HR+/HER2+ subgroups (P=0.009) However, for patients with three and four metastatic sites, there was no statistical difference in their CSS (all, P>0.05).

The prognosis analysis of different metastasis pattern in patients with different breast cancer subtypes: a SEER based study

PubMed Central

Wang, Haiyong; Zhang, Chenyue; Zhang, Jingze; Kong, Li; Zhu, Hui; Yu, Jinming

2017-01-01

Studies on prognosis of different metastasis patterns in patients with different breast cancer subtypes (BCS) are limited. Therefore, we identified 7862 breast cancer patients with distant metastasis from 2010 to 2013 using Surveillance, Epidemiology, wand End Results (SEER) population-based data. The results showed that bone was the most common metastatic site and brain was the least common metastatic site, and the patients with HR+/HER2− occupied the highest metastasis proportion, the lowest metastasis proportion were found in HR-/HER2+ patients. Univariate and multivariate logistic regression analysis were used to analyze the association, and it was found that there were significant differences of distant metastasis patterns in patients with different BCS(different P value). Importantly, univariate and multivariate Cox regression analysis were used to analyze the prognosis. It was proven that only bone metastasis was not a prognostic factor in the HR+/HER2-, HR+/HER2+ and HR-/HER2+ subgroup (all, P > 0.05), and patients with brain metastasis had the worst cancer specific survival (CSS) in all the subgroups of BCS (all, P<0.01). Interestingly, for patients with two metastatic sites, those with bone and lung metastasis had best CSS in the HR+/HER2- (P<0.001) and HR+/HER2+ subgroups (P=0.009) However, for patients with three and four metastatic sites, there was no statistical difference in their CSS (all, P>0.05). PMID:28038448

Variability of the cranial and dental phenotype in Williams syndrome.

PubMed

Axelsson, Stefan

2005-01-01

Williams syndrome (WS) is a rare congenital disorder involving the cardiovascular system, connective tissue, and the central nervous system, resulting in mild to moderate mental retardation, a specific cognitive profile, unique personality characteristics, distinctive facial features, and cardiovascular disease. The majority of individuals with a clinical diagnosis of WS have a contiguous gene deletion at chromosome 7 (7q11.23). Physical features include characteristic facial features with full prominent cheeks, wide mouth, long philtrum, small nose with depressed nasal bridge, heavy orbital ridges, medial eyebrow flare, dental abnormalities, hoarse voice, growth retardation, and cardiovascular abnormalities (most commonly supravalvular aortic stenosis and/or peripheral pulmonary artery stenosis). The cognitive profile is distinctive, consisting of strengths in auditory memory, language, and face-processing, but extreme weakness in visuospatial, numerical and problem-solving abilities. Neurological studies have identified a significantly decreased brain volume in adult individuals with WS with relatively normal development of the limbic, frontal and cerebellar structures. The aims were to analyse the neurocranium, the craniofacial region, and the dentition in a well defined Norwegian group of individuals with WS. In order to accomplish this, normative cephalometric standards for the neurocranium, including the cranial base and the sella turcica, were established for Norwegian males and females from 6 to 21 years of age, using lateral radiographic cephalograms from the Oslo University Craniofacial Growth Archive. The study material comprised radiographic lateral cephalograms, orthopantomograms and dental casts from 62 individuals with WS ranging from 4 to 44 years. The lateral cephalograms, orthopantomograms and dental casts were analysed using standard methods reported in the literature. Neurocranium: The results from the cephalometric analyses showed that the size and shape of the neurocranium in WS differed from normal controls. A flattening of the superior aspect of the parietal bone was found and the posterior prominence of the occipital bone was larger. These findings were in concordance with published neuroanatomical/neuropathological studies on WS and fit well with the reported anatomical aberrations in the WS brain, e.g. a smaller brain volume where some parts are of relatively normal size while others are decreased. The anterior and posterior cranial base was shorter in WS, but with a normal cranial base angle. The thickness of the calvarian bones, especially the frontal and occipital bones, was greater in WS than in normal controls. Sella turcica: The size of the sella turcica was somewhat smaller in WS compared with normal controls, though not significant. Aberrant types of shape of the sella turcica in WS are demonstrated. The correlation between prenatal malformation in the pituitary gland/sella turcica and the postnatal morphology of the sella turcica is discussed. The craniofacial skeleton: Two areas, in addition to the cranial base, have been identified to contribute to the characteristic facial appearance in WS; the anterior inclination of the maxilla, and the shape of the mandible. The severely deficient bony chin in combination with the high mandibular plane angle can explain earlier clinical descriptions of a retrusive mandible in WS. Frequent mouth breathing during childhood and the smaller cranial base may be associated with the characteristic craniofacial pattern. Dentition: In individuals with WS over 10 years of age 40.5 per cent had agenesis of one or more permanent teeth and 11.9 percent had agenesis of 6 teeth or more. The missing permanent teeth in the maxilla most commonly included 2nd premolars, 1st premolars, and lateral incisors. In the mandible most commonly 2nd premolars, 1st premolars, and central incisors were absent. The tooth crowns of permanent teeth were smaller, both in the mesio-distal and labio-lingual dimension. The permanent tooth crowns have several characteristic deviations from normal shape; especially incisors in both jaws were tapered or screwdriver-shaped. An evaluation of taurodontism on permanent molars was performed. However, most of the molars rated as being taurodontic had short total tooth lengths and could thus be rated taurodontic without meeting the classical definition. These studies have shown aberrations in the neurocranium including the sella turcica in WS not previously reported. In the craniofacial skeleton specific traits have been identified to contribute to the characteristic facial appearance in WS. Dental aberrations in the permanent dentition including agenesis, smaller size, and aberrant shape of teeth, are common in WS.

Diet-induced obesity, gut microbiota and bone, including alveolar bone loss.

PubMed

Eaimworawuthikul, Sathima; Thiennimitr, Parameth; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2017-06-01

Obesity is a major risk factor for several pathologies, including jaw bone resorption. The underlying mechanisms involved in pathological conditions resulting from obesity include chronic systemic inflammation and the development of insulin resistance. Although numerous studies have indicated the importance of the role of gut microbiota in the pathogenesis of inflammation and insulin resistance in obesity, only a few studies have established a relationship between obesity, gut microbiota and status of the jaw bone. This review aims to summarize current findings relating to these issues, focusing on the role of obesity and gut microbiota on jaw bone health, including possible mechanisms which can explain this link. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cancer-associated bone disease

PubMed Central

Body, J.-J.; Brandi, M.-L.; Cannata-Andia, J.; Chappard, D.; El Maghraoui, A.; Glüer, C.C.; Kendler, D.; Napoli, N.; Papaioannou, A.; Pierroz, D.D.; Rahme, M.; Van Poznak, C.H.; de Villiers, T.J.; El Hajj Fuleihan, G.

2016-01-01

Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and working groups to assist physicians in clinical decision making, providing them with evidence-based care pathways to prevent skeletal-related events and bone loss. The goal of this paper is to put forth an IOF position paper addressing bone diseases and cancer and summarizing the position papers of other organizations. PMID:24146095

Cytology of Bone.

PubMed

Barger, Anne M

2017-01-01

Cytology of bone is a useful diagnostic tool. Aspiration of lytic or proliferative lesions can assist with the diagnosis of inflammatory or neoplastic processes. Bacterial, fungal, and protozoal organisms can result in significant osteomyelitis, and these organisms can be identified on cytology. Neoplasms of bone including primary bone tumors such as osteosarcoma, chondrosarcoma, fibrosarcoma, synovial cell sarcoma, and histiocytic sarcoma and tumors of bone marrow including plasma cell neoplasia and lymphoma and metastatic neoplasia can result in significant bone lysis or proliferation and can be diagnosed effectively with cytology. Copyright © 2016 Elsevier Inc. All rights reserved.

Thermal effects of diagnostic ultrasound in an anthropomorphic skull model.

PubMed

Vyskocil, E; Pfaffenberger, S; Kollmann, C; Gleiss, A; Nawratil, G; Kastl, S; Unger, E; Aumayr, K; Schuhfried, O; Huber, K; Wojta, J; Gottsauner-Wolf, M

2012-12-01

Exposure to diagnostic ultrasound (US) can significantly heat biological tissue although conventional routine examinations are regarded as safe. The risk of unwanted thermal effects increases with a high absorption coefficient and extended insonation time. Certain applications of transcranial diagnostic US (TC-US) require prolonged exposure. An anthropomorphic skull model (ASM) was developed to evaluate thermal effects induced by TC-US of different modalities. The objective was to determine whether prolonged continuous TC-US application results in potentially harmful temperature increases. The ASM consists of a human skull with tissue mimicking material and exhibits acoustic and anatomical characteristics of the human skull and brain. Experiments are performed with a diagnostic US device testing four different US modalities: Duplex PW (pulsed wave) Doppler, PW Doppler, color flow Doppler and B-mode. Temperature changes are recorded during 180 minutes of insonation. All measurements revealed significant temperature increases during insonation independent of the US modality. The maximum temperature elevation of + 5.25° C (p < 0.001) was observed on the surface of the skull exposed to duplex PW Doppler. At the bone-brain border a maximum temperature increae of + 2.01 °C (p < 0.001) was noted. Temperature increases within the brain were < 1.23 °C (p = 0.001). The highest values were registered using the duplex PW Doppler modality. TC-US induces significant local heating effects in an ASM. An application duration that extends routine clinical periods causes potentially harmful heating especially in tissue close to bone. TC-US elevates the temperature in the brain mimicking tissue but is not capable of producing harmful temperature increases during routine examinations. However, the risk of thermal injury in brain tissue increases significantly after an exposure time of > 2 hours. © Georg Thieme Verlag KG Stuttgart · New York.

Holoprosencephaly: signalling interactions between the brain and the face, the environment and the genes, and the phenotypic variability in animal models and humans

PubMed Central

Graf, Daniel; Marcucio, Ralph

2014-01-01

Holoprosencephaly (HPE) is the most common developmental defect of the forebrain characterized by inadequate or absent midline division of the forebrain into cerebral hemispheres, with concomitant midline facial defects in the majority of cases. Understanding the pathogenesis of HPE requires knowledge of the relationship between the developing brain and the facial structures during embryogenesis. A number of signalling pathways control and coordinate the development of the brain and face, including Sonic hedgehog (SHH), Bone Morphogenetic Protein (BMP), Fibroblast Growth Factor (FGF), and Nodal signalling. Mutations in these pathways have been identified in animal models of HPE and human patients. Due to incomplete penetrance and variable expressivity of HPE, patients carrying defined mutations may not manifest the disease at all, or have a spectrum of defects. It is currently unknown what drives manifestation of HPE in genetically at risk individuals, but it has been speculated that other gene mutations and environmental factors may combine as cumulative insults. HPE can be diagnosed in utero by a high-resolution prenatal ultrasound or a fetal magnetic resonance imaging, sometimes in combination with molecular testing from chorionic villi or amniotic fluid sampling. Currently, there are no effective preventive methods for HPE. Better understanding of the mechanisms of gene-environment interactions in HPE would provide avenues for such interventions. PMID:25339593

Bone Cancer—Health Professional Version

Cancer.gov

There are several types of bone cancer. Osteosarcoma usually starts in osteoblasts, a type of bone cell that becomes new bone tissue. Ewing sarcoma arises from a primordial bone marrow–derived mesenchymal stem cell. Find evidence-based information on bone cancer including treatment, research, genetics, and statistics.

Microgravity

NASA Image and Video Library

2004-04-15

Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. Cell culturing, such as this bone cell culture, is an important part of biomedical research. The BioDyn payload includes a tissue engineering investigation. The commercial affiliate, Millenium Biologix, Inc., has been conducting bone implant experiments to better understand how synthetic bone can be used to treat bone-related illnesses and bone damaged in accidents. On STS-95, the BioDyn payload will include a bone cell culture aimed to help develop this commercial synthetic bone product. Millenium Biologix, Inc., is exploring the potential for making human bone implantable materials by seeding its proprietary artificial scaffold material with human bone cells. The product of this tissue engineering experiment using the Bioprocessing Modules (BPMs) on STS-95 is space-grown bone implants, which could have potential for dental implants, long bone grafts, and coating for orthopedic implants such as hip replacements.

Microgravity

NASA Image and Video Library

2004-04-15

Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. Cell culturing, such as this bone cell culture, is an important part of biomedical research. The BioDyn payload includes a tissue engineering investigation. The commercial affiliate, Millenium Biologix, Inc. has been conducting bone implant experiments to better understand how synthetic bone can be used to treat bone-related illnesses and bone damaged in accidents. On STS-95, the BioDyn payload will include a bone cell culture aimed to help develop this commercial synthetic bone product. Millenium Biologix, Inc. is exploring the potential for making human bone implantable materials by seeding its proprietary artificial scaffold material with human bone cells. The product of this tissue engineering experiment using the Bioprocessing Modules (BPMs) on STS-95 is space-grown bone implants, which could have potential for dental implants, long bone grafts, and coating for orthopedic implants such as hip replacements.

Engineering 3D Models of Tumors and Bone to Understand Tumor-Induced Bone Disease and Improve Treatments

PubMed Central

Kwakwa, Kristin A.; Vanderburgh, Joseph P.; Guelcher, Scott A.

2018-01-01

Purpose of Review Bone is a structurally unique microenvironment that presents many challenges for the development of 3D models for studying bone physiology and diseases, including cancer. As researchers continue to investigate the interactions within the bone microenvironment, the development of 3D models of bone has become critical. Recent Findings 3D models have been developed that replicate some properties of bone, but have not fully reproduced the complex structural and cellular composition of the bone microenvironment. This review will discuss 3D models including polyurethane, silk, and collagen scaffolds that have been developed to study tumor-induced bone disease. In addition, we discuss 3D printing techniques used to better replicate the structure of bone. Summary 3D models that better replicate the bone microenvironment will help researchers better understand the dynamic interactions between tumors and the bone microenvironment, ultimately leading to better models for testing therapeutics and predicting patient outcomes. PMID:28646444

78 FR 53781 - Notice of Inventory Completion: Indiana Department of Natural Resources, Division of Historic...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-30

... associated funerary objects include 20 bifaces; 11 bone pins; 4 bone beads; 3 Matanzas points; 3 chert drills; 2 bone awls; 1 knife; 1 unidentified point; and 3,517 artifacts found nearby including shell, animal bone, nutshell, hematite, charcoal, and chert flakes. Determinations Made by the Indiana Department of...

Isolation and characterization of a metastatic hybrid cell line generated by ER negative and ER positive breast cancer cells in mouse bone marrow.

PubMed

Mukhopadhyay, Keya De; Bandyopadhyay, Abhik; Chang, Ting-Tung A; Elkahloun, Abdel G; Cornell, John E; Yang, Junhua; Goins, Beth A; Yeh, I-Tien; Sun, Lu-Zhe

2011-01-01

The origin and the contribution of breast tumor heterogeneity to its progression are not clear. We investigated the effect of a growing orthotopic tumor formed by an aggressive estrogen receptor (ER)-negative breast cancer cell line on the metastatic potential of a less aggressive ER-positive breast cancer cell line for the elucidation of how the presence of heterogeneous cancer cells might affect each other's metastatic behavior. ER positive ZR-75-1/GFP/puro cells, resistant to puromycin and non-tumorigenic/non-metastatic without exogenous estrogen supplementation, were injected intracardiacally into mice bearing growing orthotopic tumors, formed by ER negative MDA-MB-231/GFP/Neo cells resistant to G418. A variant cell line B6, containing both estrogen-dependent and -independent cells, were isolated from GFP expressing cells in the bone marrow and re-inoculated in nude mice to generate an estrogen-independent cell line B6TC. The presence of ER negative orthotopic tumors resulted in bone metastasis of ZR-75-1 without estrogen supplementation. The newly established B6TC cell line was tumorigenic without estrogen supplementation and resistant to both puromycin and G418 suggesting its origin from the fusion of MDA-MB-231/GFP/Neo and ZR-75-1/GFP/puro in the mouse bone marrow. Compared to parental cells, B6TC cells were more metastatic to lung and bone after intracardiac inoculation. More significantly, B6TC mice also developed brain metastasis, which was not observed in the MDA-MB-231/GFP/Neo cell-inoculated mice. Low expression of ERα and CD24, and high expression of EMT-related markers such as Vimentin, CXCR4, and Integrin-β1 along with high CD44 and ALDH expression indicated stem cell-like characteristics of B6TC. Gene microarray analysis demonstrated a significantly different gene expression profile of B6TC in comparison to those of parental cell lines. Spontaneous generation of the novel hybrid cell line B6TC, in a metastatic site with stem cell-like properties and propensity to metastasize to brain, suggest that cell fusion can contribute to tumor heterogeneity.

Treatment of Adult Severe Traumatic Brain Injury Using Autologous Bone Marrow Mononuclear Cells

DTIC Science & Technology

2013-06-01

P:F value was aberrant based on wean protocol/vent settings. The chest X-ray for this day and the next did show pathology specifically pleural ... effusion and atelectasis, but no diffuse opacities consistent with ARDS/ALI. 3 Subject 10, Day 3 – On this day the subject was started on Dobhoff tube

The Activation of Embedded Words in Spoken Word Identification Is Robust but Constrained: Evidence from the Picture-Word Interference Paradigm

ERIC Educational Resources Information Center

Bowers, Jeffrey S.; Davis, Colin J.; Mattys, Sven L.; Damian, Markus F.; Hanley, Derek

2009-01-01

Three picture-word interference (PWI) experiments assessed the extent to which embedded subset words are activated during the identification of spoken superset words (e.g., "bone" in "trombone"). Participants named aloud pictures (e.g., "brain") while spoken distractors were presented. In the critical condition,…

Identification and Biological Evaluation of Coactivator Binding Inhibitors for the Estrogen Receptor

ERIC Educational Resources Information Center

Gunther, Jillian Rebecca

2009-01-01

The physiologic effects of estrogen action through the estrogen receptor (ER) are widespread, as this hormone exerts actions in both reproductive (e.g., uterus) and non-reproductive (e.g., bone, brain) tissues in both men and women. As such, the regulation of the activity of this ligand-activated transcription factor is highly relevant to the…

Characterizing and Targeting Bone Marrow-Derived Inflammatory Cells in Driving the Malignancy and Progression of Childhood Astrocytic Brain Tumors

DTIC Science & Technology

2014-09-01

CD16) by flow cytometery in peripheral of low-grade astrocytoma patients (LGA) vs glioblastoma patients ( GBM ). Figure 2. IHC of CD11b...patients (LGA), glioblastoma patients ( GBM ), and healthy volunteers. Figure 4. Statistic dots-plot on frequency of CD11b+/VEGFR2(KDR)+ cells

Not All Analogies Are Created Equal: Associative and Categorical Analogy Processing following Brain Damage

ERIC Educational Resources Information Center

Schmidt, Gwenda L.; Cardillo, Eileen R.; Kranjec, Alexander; Lehet, Matthew; Widick, Page; Chatterjee, Anjan

2012-01-01

Current research on analogy processing assumes that different conceptual relations are treated similarly. However, just as words and concepts are related in distinct ways, different kinds of analogies may employ distinct types of relationships. An important distinction in how words are related is the difference between associative (dog-bone) and…

Managment of frontal sinus fracture: obliteration sinus with cancellous bone graft.

PubMed

Muminagic, Sahib; Masic, Tarik; Babajic, Emina; Asotic, Mithat

2011-01-01

Frontal sinus fractures make up about 2-15% of all facial fractures.This is relatively low frequency of occurrence, but it has a large potential of complication and may involve not only the frontal sinuse but more importantly the brain and the eyes. The management depends of the complexity. If anterior wall is fractured with grossly involved nasofrontal duct (NFD) in the injury it is paramount to occlude NFD. Very often, sinus obliteration is done at the same time. In our expirience autogenous cancellous bone graft is considered to be the best grafting material. It has the less short - or long-term complications and the donor site morbidity is insignificant.

Molecular genetics of craniosynostosis

NASA Astrophysics Data System (ADS)

Caterine; Auerkari, Elza Ibrahim

2018-03-01

Tight regulation process and complex interplay occur along the osteogenic interfaces of the cranial sutures in normal growth and development of the skull. Cranial sutures serve as sites of bone growth while maintaining a state of patency to accommodate the developing brain. Cranial sutures are fibro-cellular structures that separate the rigid plates of the skull bones. Premature fusion of one or more cranial sutures leads to a condition known as craniosynostosis. Craniosynostosis is one of the most common craniofacial anomalies with a prevalence of 1 in 2,500 newborns. Several genes have been identified in the pathogenesis of craniosynostosis. Molecular signaling events and the intracellular signal transduction pathways implicated in the suture pathobiology will provide a useful approach for therapeutic targeting.

Breast cancer lung metastasis: Molecular biology and therapeutic implications.

PubMed

Jin, Liting; Han, Bingchen; Siegel, Emily; Cui, Yukun; Giuliano, Armando; Cui, Xiaojiang

2018-03-26

Distant metastasis accounts for the vast majority of deaths in patients with cancer. Breast cancer exhibits a distinct metastatic pattern commonly involving bone, liver, lung, and brain. Breast cancer can be divided into different subtypes based on gene expression profiles, and different breast cancer subtypes show preference to distinct organ sites of metastasis. Luminal breast tumors tend to metastasize to bone while basal-like breast cancer (BLBC) displays a lung tropism of metastasis. However, the mechanisms underlying this organ-specific pattern of metastasis still remain to be elucidated. In this review, we will summarize the recent advances regarding the molecular signaling pathways as well as the therapeutic strategies for treating breast cancer lung metastasis.

Skull base, orbits, temporal bone, and cranial nerves: anatomy on MR imaging.

PubMed

Morani, Ajaykumar C; Ramani, Nisha S; Wesolowski, Jeffrey R

2011-08-01

Accurate delineation, diagnosis, and treatment planning of skull base lesions require knowledge of the complex anatomy of the skull base. Because the skull base cannot be directly evaluated, imaging is critical for the diagnosis and management of skull base diseases. Although computed tomography (CT) is excellent for outlining the bony detail, magnetic resonance (MR) imaging provides better soft tissue detail and is helpful for evaluating the adjacent meninges, brain parenchyma, and bone marrow of the skull base. Thus, CT and MR imaging are often used together for evaluating skull base lesions. This article focuses on the radiologic anatomy of the skull base pertinent to MR imaging evaluation. Copyright © 2011 Elsevier Inc. All rights reserved.

Otogenic pneumocephalus as a complication of multiple myeloma.

PubMed

Maguire, Melissa J; Nath, Uma; Bignardi, Guiseppe E

2012-09-01

We report a case of otogenic pneumocephalus in an 80-year-old woman with multiple myeloma. The pneumocephalus was associated with Haemophilus influenzae otitis media and reactive meningitis in the absence of an intracranial brain abscess. Myeloma causes thinning of bone trabeculae and destructive lytic bone lesions. This can predispose to a risk of pathologic fractures and, in patients with skull vault involvement, to the rare complication of pneumocephalus. Therefore, pneumocephalus should be considered in the differential diagnosis of acute headache in patients with multiple myeloma, especially those with skull vault involvement. Prompt computed tomography and liaison between the otolaryngology and neurology teams may assist in making an early diagnosis and preventing life-threatening intracranial complications.

Running and Osteoarthritis: Does Recreational or Competitive Running Increase the Risk?

PubMed

2017-06-01

Exercise, like running, is good for overall health and, specifically, our hearts, lungs, muscles, bones, and brains. However, some people are concerned about the impact of running on longterm joint health. Does running lead to higher rates of arthritis in knees and hips? While many researchers find that running protects bone health, others are concerned that this exercise poses a high risk for age-related changes to hips and knees. A study published in the June 2017 issue of JOSPT suggests that the difference in these outcomes depends on the frequency and intensity of running. J Orthop Sports Phys Ther 2017;47(6):391. doi:10.2519/jospt.2017.0505.

Penetrating brain injury with a metal bar and a knife: Report of two interesting cases.

PubMed

Tabibkhooei, Alireza; Taheri, Morteza; Rohani, Sadra; Chanideh, Iran; Rahatlou, Hessam

2018-04-01

Introduction Penetrating brain injury (PBI) is uncommon among the civilian population. Here, we report two interesting cases of PBI. Case presentation The first patient was a 20-year-old male who sustained a penetrating head injury with a metal bar during an accident at work. The patient underwent early surgical intervention, and related meningitis was treated with antibiotics. The patient was discharged 45 days later with no deficit. The second patient was a 34-year-old male who was the victim of a violence attack and was admitted to hospital. He was struck by a knife to his right temporal bone. A brain computed tomography scan and magnetic resonance imaging (MRI) demonstrated the tract of the knife within the brain parenchyma. The patient underwent conservative treatment. After several weeks, the patient was discharged in good health. Conclusion Although severe PBI has a poorer prognosis than a blunt brain injury, in treating of these patients, aggressive and timely surgical intervention, proper wide-spectrum antibiotic administration, stringent and diligent care in the intensive-care unit and careful management of the associated complications are mandated.

Hematopoietic Stem Cells in Neural-crest Derived Bone Marrow.

PubMed

Jiang, Nan; Chen, Mo; Yang, Guodong; Xiang, Lusai; He, Ling; Hei, Thomas K; Chotkowski, Gregory; Tarnow, Dennis P; Finkel, Myron; Ding, Lei; Zhou, Yanheng; Mao, Jeremy J

2016-12-21

Hematopoietic stem cells (HSCs) in the endosteum of mesoderm-derived appendicular bones have been extensively studied. Neural crest-derived bones differ from appendicular bones in developmental origin, mode of bone formation and pathological bone resorption. Whether neural crest-derived bones harbor HSCs is elusive. Here, we discovered HSC-like cells in postnatal murine mandible, and benchmarked them with donor-matched, mesoderm-derived femur/tibia HSCs, including clonogenic assay and long-term culture. Mandibular CD34 negative, LSK cells proliferated similarly to appendicular HSCs, and differentiated into all hematopoietic lineages. Mandibular HSCs showed a consistent deficiency in lymphoid differentiation, including significantly fewer CD229 + fractions, PreProB, ProB, PreB and B220 + slgM cells. Remarkably, mandibular HSCs reconstituted irradiated hematopoietic bone marrow in vivo, just as appendicular HSCs. Genomic profiling of osteoblasts from mandibular and femur/tibia bone marrow revealed deficiencies in several HSC niche regulators among mandibular osteoblasts including Cxcl12. Neural crest derived bone harbors HSCs that function similarly to appendicular HSCs but are deficient in the lymphoid lineage. Thus, lymphoid deficiency of mandibular HSCs may be accounted by putative niche regulating genes. HSCs in craniofacial bones have functional implications in homeostasis, osteoclastogenesis, immune functions, tumor metastasis and infections such as osteonecrosis of the jaw.

Apatinib + CPT-11 + S-1 for treatment of refractory brain metastases in patient with triple-negative breast cancer: Case report and literature review.

PubMed

Hu, Ting; Liu, Cuiwei; Li, Qiuhui; Xiong, Jie; Ma, Yuxi; Wu, Gang; Zhao, Yanxia

2018-04-01

Brain metastasis (BM) is a rising challenge in forward-looking oncology, as its treatment choices are very limited, especially, after the failure of local treatment schemes. We report on a 39-year-old Chinese woman who was diagnosed with stage IV triple-negative breast cancer(TNBC) with multiple brain, lung, and bone metastases. She had previously, undergone whole-brain radiation therapy. Paclitaxel, platinum, UTD1, capecitabine, gemcitabine, vinorelbine, and single-agent apatinib were then administered as first- to fifth-line therapies. She exhibited progression each time after a short period of disease stabilization. Triple-negative breast cancer. The patient chose treatment with apatinib+CPT-11+S-1 as the sixth-line therapy. A remarkable response of the brain, and lung metastases, and alleviation of the brain edema were achieved, and these effects persisted for 7 months. We describe the significant anti-tumor effect of apatinib + CPT-11 + S-1 against BMs from breast cancer. This report is the first to suggest potential approaches to BM treatment using this scheme and describes the effects of an apatinib-containing regimen on BMs.

Apatinib + CPT-11 + S-1 for treatment of refractory brain metastases in patient with triple-negative breast cancer

PubMed Central

Hu, Ting; Liu, Cuiwei; Li, Qiuhui; Xiong, Jie; Ma, Yuxi; Wu, Gang; Zhao, Yanxia

2018-01-01

Abstract Rationale: Brain metastasis (BM) is a rising challenge in forward-looking oncology, as its treatment choices are very limited, especially, after the failure of local treatment schemes. Patient concerns: We report on a 39-year-old Chinese woman who was diagnosed with stage IV triple-negative breast cancer(TNBC) with multiple brain, lung, and bone metastases. She had previously, undergone whole-brain radiation therapy. Paclitaxel, platinum, UTD1, capecitabine, gemcitabine, vinorelbine, and single-agent apatinib were then administered as first- to fifth-line therapies. She exhibited progression each time after a short period of disease stabilization. Diagnoses: Triple-negative breast cancer. Interventions: The patient chose treatment with apatinib+CPT-11+S-1 as the sixth-line therapy. Outcomes: A remarkable response of the brain, and lung metastases, and alleviation of the brain edema were achieved, and these effects persisted for 7 months. Lessons: We describe the significant anti-tumor effect of apatinib + CPT-11 + S-1 against BMs from breast cancer. This report is the first to suggest potential approaches to BM treatment using this scheme and describes the effects of an apatinib-containing regimen on BMs. PMID:29642175

Dendritic Cell Transmigration through Brain Microvessel Endothelium Is Regulated by MIP-1α Chemokine and Matrix Metalloproteinases1

PubMed Central

Zozulya, Alla L.; Reinke, Emily; Baiu, Dana C.; Karman, Jozsef; Sandor, Matyas; Fabry, Zsuzsanna

2007-01-01

Dendritic cells (DCs) accumulate in the CNS during inflammatory diseases, but the exact mechanism regulating their traffic into the CNS remains to be defined. We now report that MIP-1α increases the transmigration of bone marrow-derived, GFP-labeled DCs across brain microvessel endothelial cell monolayers. Furthermore, occludin, an important element of endothelial tight junctions, is reorganized when DCs migrate across brain capillary endothelial cell monolayers without causing significant changes in the barrier integrity as measured by transendothelial electrical resistance. We show that DCs produce matrix metalloproteinases (MMP) -2 and -9 and GM6001, an MMP inhibitor, decreases both baseline and MIP-1α -induced DC transmigration. These observations suggest that DC transmigration across brain endothelial cell monolayers is partly MMP dependent. The migrated DCs express higher levels of CD40, CD80, and CD86 costimulatory molecules and induce T cell proliferation, indicating that the transmigration of DCs across brain endothelial cell monolayers contributes to the maintenance of DC Ag-presenting function. The MMP dependence of DC migration across brain endothelial cell monolayers raises the possibility that MMP blockers may decrease the initiation of T cell recruitment and neuroinflammation in the CNS. PMID:17182592

Transcranial amelioration of inflammation and cell death after brain injury

NASA Astrophysics Data System (ADS)

Roth, Theodore L.; Nayak, Debasis; Atanasijevic, Tatjana; Koretsky, Alan P.; Latour, Lawrence L.; McGavern, Dorian B.

2014-01-01

Traumatic brain injury (TBI) is increasingly appreciated to be highly prevalent and deleterious to neurological function. At present, no effective treatment options are available, and little is known about the complex cellular response to TBI during its acute phase. To gain insights into TBI pathogenesis, we developed a novel murine closed-skull brain injury model that mirrors some pathological features associated with mild TBI in humans and used long-term intravital microscopy to study the dynamics of the injury response from its inception. Here we demonstrate that acute brain injury induces vascular damage, meningeal cell death, and the generation of reactive oxygen species (ROS) that ultimately breach the glial limitans and promote spread of the injury into the parenchyma. In response, the brain elicits a neuroprotective, purinergic-receptor-dependent inflammatory response characterized by meningeal neutrophil swarming and microglial reconstitution of the damaged glial limitans. We also show that the skull bone is permeable to small-molecular-weight compounds, and use this delivery route to modulate inflammation and therapeutically ameliorate brain injury through transcranial administration of the ROS scavenger, glutathione. Our results shed light on the acute cellular response to TBI and provide a means to locally deliver therapeutic compounds to the site of injury.

Molecular Abnormalities Underlying Bone Fragility in Chronic Kidney Disease

PubMed Central

Iwasaki, Yoshiko; Kazama, Junichiro James

2017-01-01

Prevention of bone fractures is one goal of therapy for patients with chronic kidney disease-mineral and bone disorder (CKD-MBD), as indicated by the Kidney Disease: Improving Global Outcomes guidelines. CKD patients, including those on hemodialysis, are at higher risk for fractures and fracture-related death compared to people with normal kidney function. However, few clinicians focus on this issue as it is very difficult to estimate bone fragility. Additionally, uremia-related bone fragility has a more complicated pathological process compared to osteoporosis. There are many uremia-associated factors that contribute to bone fragility, including severe secondary hyperparathyroidism, skeletal resistance to parathyroid hormone, and bone mineralization disorders. Uremia also aggravates bone volume loss, disarranges microarchitecture, and increases the deterioration of material properties of bone through abnormal bone cells or excess oxidative stress. In this review, we outline the prevalence of fractures, the interaction of CKD-MBD with osteoporosis in CKD patients, and discuss possible factors that exacerbate the mechanical properties of bone. PMID:28421193

Langerhans Cell Histiocytosis in an Adult with Involvement of the Calvarium, Cerebral Cortex and Brainstem: Discussion of Pathophysiology and Rationale for the Use of Intravenous Immune Globulin

PubMed Central

Dardis, Christopher; Aung, Thandar; Shapiro, William; Fortune, John; Coons, Stephen

2015-01-01

We report a case of Langerhans cell histiocytosis in a 64-year-old male who presented with symptoms and signs of brain involvement, including seizures and hypopituitarism. The diagnosis was confirmed with a biopsy of a lytic skull lesion. The disease affecting the bone showed no sign of progression following a short course of cladribine. Signs of temporal lobe involvement led to an additional biopsy, which showed signs of nonspecific neurodegeneration and which triggered status epilepticus. Lesions noted in the brainstem were typical for the paraneoplastic inflammation reported in this condition. These lesions improved after treatment with cladribine. They remained stable while on treatment with intravenous immune globulin. PMID:25873887

Optic pathway glioma as part of a constitutional mismatch-repair deficiency syndrome in a patient meeting the criteria for neurofibromatosis type 1.

PubMed

Yeung, Jacky T; Pollack, Ian F; Shah, Sapana; Jaffe, Ronald; Nikiforova, Marina; Jakacki, Regina I

2013-01-01

Patients with constitutional mismatch repair-deficiency (CMMR-D) caused by the biallelic deletions of mismatch repair (MMR) genes have a high likelihood of developing malignancies of the bone marrow, bowel, and brain. Affected individuals often have phenotypic features of neurofibromatosis type 1 (NF-1), including café-au-lait spots. Optic pathway gliomas (OPGs), a common manifestation of NF-1, have not been reported. We report the case of a 3-year-old male with an extensive OPG who met the diagnostic criteria for NF-1. He was subsequently found to have multiple colonic polyps and bi-allelic loss of PMS2. Testing for NF-1 was negative. Copyright © 2012 Wiley Periodicals, Inc.

Disseminated gestational choriocarcinoma presenting with hepatic and uveal metastases, hook effect, and choriocarcinoma syndrome.

PubMed

Aswani, Yashant; Thakkar, Hemangini; Hira, Priya

2016-01-01

Choriocarcinoma is a human chorionic gonadotrophin (HCG)-secreting tumor that comprises vascular channels. It has a tendency for widespread metastasis, common sites for which include the lung, vagina, brain, liver, bone, intestine, and kidney. We describe a 30-year-old female who presented with hepatitis-like features and bilateral diminution of vision, and subsequently developed hemothorax and hemoperitoneum-all rare and seemingly unrelated manifestations which were finally attributable to metastases from gestational choriocarcinoma. To further complicate the clinical scenario, the serum HCG of the patient was mildly raised (due to a phenomenon called hook effect). Subsequently, the patient developed disseminated intravascular coagulation and succumbed to her illness. In this report, we discuss the imaging findings of choriocarcinoma, its potential sites of metastases, and the hook effect.

Magnetic resonance imaging of the central nervous system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1988-02-26

This report reviews the current applications of magnetic resonance imaging of the central nervous system. Since its introduction into the clinical environment in the early 1980's, this technology has had a major impact on the practice of neurology. It has proved to be superior to computed tomography for imaging many diseases of the brain and spine. In some instances it has clearly replaced computed tomography. It is likely that it will replace myelography for the assessment of cervicomedullary junction and spinal regions. The magnetic field strengths currently used appear to be entirely safe for clinical application in neurology except inmore » patients with cardiac pacemakers or vascular metallic clips. Some shortcomings of magnetic resonance imaging include its expense, the time required for scanning, and poor visualization of cortical bone.« less

Skull base trauma: diagnosis and management.

PubMed

Samii, Madjid; Tatagiba, Marcos

2002-03-01

The singular anatomical relationship of the base of the skull is responsible for the particular problems that may arise after injury. Extensive dural laceration and severe neurovascular damage may accompany skull base injuries. Trauma to the anterior skull base is frequently related to the paranasal sinuses, and trauma to the middle and the posterior skull base usually affects the petrous bone. Injury to the anterior fossa including the paranasal sinuses may produce CSF leakage, damage the olfactory nerves, optic nerves, and orbita contents. Fractures may affect the carotid canal, injure the internal carotid artery and result in carotid-cavernous fistula. Trauma to the petrous bone may cause facial palsy and deafness, and CSF leakage with otorrhoea or paradoxal rhinoliquorrhoea. Trauma to the posterior fossa may lacerate the major venous sinuses, and affect the cranio-cervical stability. Each one of these injuries will need a particular strategy. Decision making for management as a whole must consider all aspects, including the fact that these injuries frequently involve polytraumatized patients. Decisions regarding the timing of surgery and the sequence of the surgical procedures must be made with great care. Modern surgical techniques and recent technologies including functional preservation of the olfactory nerves in frontobasal trauma, visual evoked potentials, assisted optic nerve decompression, facial nerve reconstruction, interventional technique for intravascular repair of vascular injuries, and recent developments in cochlea implants and brain stem implants, all contributed significantly to improve outcome and enhance the quality of life of patients. This article reviews basic principles of management of skull base trauma stressing the role of these advanced techniques.

Alkmaion's discovery that brain creates mind: a revolution in human knowledge comparable to that of Copernicus and of Darwin.

PubMed

Doty, Robert W

2007-07-13

Without special examination the brain offers no clue that it is the organ of the mind. From the dawn of time man thus either ignored the problem as to the source of thought, or attributed it to a variety of anatomical structures, usually the heart. The brain held no place in such intuitions, and in most languages it is analogized to bone marrow. Furthermore, nothing in early medical systems claimed any intellectual capacity for the brain; and the Egyptians, so fastidious in care for their afterlife, heedlessly discarded the brain in funerary practice. It was thus a unique event in world history when Alkmaion of Kroton (Alcmaeon, ca. 500 bc), based on anatomical evidence, proposed that the brain was essential for perception. Although no writings of Alkmaion survived, it was probably via a fortuitous linkage that his idea of the mental primacy of the brain was transmitted to, and preserved within, the teachings of the Hippocratic school. Nothing, of course, was secure as to mechanism, two millennia unfolding until the search for mind passed from the ventricles to the cerebral cortex. Nonetheless, Alkmaion was the beginning, and the ensuing understanding that he initiated is still transforming humanity's perception of the natural world, and their place within it.

Altered bone material properties in HLA-B27 rats include reduced mineral to matrix ratio and altered collagen cross-links.

PubMed

Gamsjaeger, Sonja; Srivastava, Apurva K; Wergedal, Jon E; Zwerina, Jochen; Klaushofer, Klaus; Paschalis, Eleftherios P; Tatakis, Dimitris N

2014-11-01

Spondyloarthropathy and inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, are often associated with severe osteopenia/osteoporosis in both children and adults. HLA-B27 transgenic rats present a phenotype that includes severe colitis and severely accelerated alveolar bone loss. The purpose of this study was to evaluate long bone density status, systemic bone metabolic markers, and intrinsic bone material properties in HLA-B27 transgenic (TG) rats, and compare them with those of age- and sex-matched wild-type (WT) animals. The results indicate that in the HLA-B27 rat, an animal susceptible to both alveolar bone loss (ABL) and long bone osteopenia, there is a statistically significant negative correlation between ABL and long bone bone mineral density (BMD), as well as mineral/matrix ratio at active bone-forming trabecular surfaces. The TG animals had a lower mineral/matrix ratio and higher relative proteoglycan and advanced glycation end product (ϵ-N-Carboxymethyl-L-lysine) content and pyridinoline/divalent collagen cross-link ratio compared with WT. These results may provide better understanding of the interrelationship between osteoporosis and oral bone loss, the underlying causes of the inferior bone strength in the HLA-B27 transgenic animals, and could prove to be a useful model in the elucidation of the pathophysiology of spondyloarthropathy and IBD-associated osteopenia/osteoporosis and in the evaluation of pharmacological intervention(s) against such conditions. © 2014 American Society for Bone and Mineral Research.

Novel modeling of cancer cell signaling pathways enables systematic drug repositioning for distinct breast cancer metastases.

PubMed

Zhao, Hong; Jin, Guangxu; Cui, Kemi; Ren, Ding; Liu, Timothy; Chen, Peikai; Wong, Solomon; Li, Fuhai; Fan, Yubo; Rodriguez, Angel; Chang, Jenny; Wong, Stephen T C

2013-10-15

A new type of signaling network element, called cancer signaling bridges (CSB), has been shown to have the potential for systematic and fast-tracked drug repositioning. On the basis of CSBs, we developed a computational model to derive specific downstream signaling pathways that reveal previously unknown target-disease connections and new mechanisms for specific cancer subtypes. The model enables us to reposition drugs based on available patient gene expression data. We applied this model to repurpose known or shelved drugs for brain, lung, and bone metastases of breast cancer with the hypothesis that cancer subtypes have their own specific signaling mechanisms. To test the hypothesis, we addressed specific CSBs for each metastasis that satisfy (i) CSB proteins are activated by the maximal number of enriched signaling pathways specific to a given metastasis, and (ii) CSB proteins are involved in the most differential expressed coding genes specific to each breast cancer metastasis. The identified signaling networks for the three types of breast cancer metastases contain 31, 15, and 18 proteins and are used to reposition 15, 9, and 2 drug candidates for the brain, lung, and bone metastases. We conducted both in vitro and in vivo preclinical experiments as well as analysis on patient tumor specimens to evaluate the targets and repositioned drugs. Of special note, we found that the Food and Drug Administration-approved drugs, sunitinib and dasatinib, prohibit brain metastases derived from breast cancer, addressing one particularly challenging aspect of this disease. ©2013 AACR.

Cell Culturing of Cytoskeleton

NASA Technical Reports Server (NTRS)

2004-01-01

Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. Cell culturing, such as this bone cell culture, is an important part of biomedical research. The BioDyn payload includes a tissue engineering investigation. The commercial affiliate, Millenium Biologix, Inc., has been conducting bone implant experiments to better understand how synthetic bone can be used to treat bone-related illnesses and bone damaged in accidents. On STS-95, the BioDyn payload will include a bone cell culture aimed to help develop this commercial synthetic bone product. Millenium Biologix, Inc., is exploring the potential for making human bone implantable materials by seeding its proprietary artificial scaffold material with human bone cells. The product of this tissue engineering experiment using the Bioprocessing Modules (BPMs) on STS-95 is space-grown bone implants, which could have potential for dental implants, long bone grafts, and coating for orthopedic implants such as hip replacements.

Cell Culturing of Cytoskeleton

NASA Technical Reports Server (NTRS)

2004-01-01

Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. Cell culturing, such as this bone cell culture, is an important part of biomedical research. The BioDyn payload includes a tissue engineering investigation. The commercial affiliate, Millenium Biologix, Inc. has been conducting bone implant experiments to better understand how synthetic bone can be used to treat bone-related illnesses and bone damaged in accidents. On STS-95, the BioDyn payload will include a bone cell culture aimed to help develop this commercial synthetic bone product. Millenium Biologix, Inc. is exploring the potential for making human bone implantable materials by seeding its proprietary artificial scaffold material with human bone cells. The product of this tissue engineering experiment using the Bioprocessing Modules (BPMs) on STS-95 is space-grown bone implants, which could have potential for dental implants, long bone grafts, and coating for orthopedic implants such as hip replacements.

Computational exploration of wave propagation and heating from transcranial focused ultrasound for neuromodulation

NASA Astrophysics Data System (ADS)

Mueller, Jerel K.; Ai, Leo; Bansal, Priya; Legon, Wynn

2016-10-01

Objective. While ultrasound is largely established for use in diagnostic imaging, its application for neuromodulation is relatively new and crudely understood. The objective of the present study was to investigate the effects of tissue properties and geometry on the wave propagation and heating in the context of transcranial neuromodulation. Approach. A computational model of transcranial-focused ultrasound was constructed and validated against empirical data. The models were then incrementally extended to investigate a number of issues related to the use of ultrasound for neuromodulation, including the effect on wave propagation of variations in geometry of skull and gyral anatomy as well as the effect of multiple tissue and media layers, including scalp, skull, CSF, and gray/white matter. In addition, a sensitivity analysis was run to characterize the influence of acoustic properties of intracranial tissues. Finally, the heating associated with ultrasonic stimulation waveforms designed for neuromodulation was modeled. Main results. The wave propagation of a transcranially focused ultrasound beam is significantly influenced by the cranial domain. The half maximum acoustic beam intensity profiles are insensitive overall to small changes in material properties, though the inclusion of sulci in models results in greater peak intensity values compared to a model without sulci (1%-30% greater). Finally, heating using currently employed stimulation parameters in humans is highest in bone (0.16 °C) and is negligible in brain (4.27 × 10-3 °C) for a 0.5 s exposure. Significance. Ultrasound for noninvasive neuromodulation holds great promise and appeal for its non-invasiveness, high spatial resolution and deep focal lengths. Here we show gross brain anatomy and biological material properties to have limited effect on ultrasound wave propagation and to result in safe heating levels in the skull and brain.

Computational exploration of wave propagation and heating from transcranial focused ultrasound for neuromodulation.

PubMed

Mueller, Jerel K; Ai, Leo; Bansal, Priya; Legon, Wynn

2016-10-01

While ultrasound is largely established for use in diagnostic imaging, its application for neuromodulation is relatively new and crudely understood. The objective of the present study was to investigate the effects of tissue properties and geometry on the wave propagation and heating in the context of transcranial neuromodulation. A computational model of transcranial-focused ultrasound was constructed and validated against empirical data. The models were then incrementally extended to investigate a number of issues related to the use of ultrasound for neuromodulation, including the effect on wave propagation of variations in geometry of skull and gyral anatomy as well as the effect of multiple tissue and media layers, including scalp, skull, CSF, and gray/white matter. In addition, a sensitivity analysis was run to characterize the influence of acoustic properties of intracranial tissues. Finally, the heating associated with ultrasonic stimulation waveforms designed for neuromodulation was modeled. The wave propagation of a transcranially focused ultrasound beam is significantly influenced by the cranial domain. The half maximum acoustic beam intensity profiles are insensitive overall to small changes in material properties, though the inclusion of sulci in models results in greater peak intensity values compared to a model without sulci (1%-30% greater). Finally, heating using currently employed stimulation parameters in humans is highest in bone (0.16 °C) and is negligible in brain (4.27 × 10(-3) °C) for a 0.5 s exposure. Ultrasound for noninvasive neuromodulation holds great promise and appeal for its non-invasiveness, high spatial resolution and deep focal lengths. Here we show gross brain anatomy and biological material properties to have limited effect on ultrasound wave propagation and to result in safe heating levels in the skull and brain.

Intranasal delivery of hypoxia-preconditioned bone marrow-derived mesenchymal stem cells enhanced regenerative effects after intracerebral hemorrhagic stroke in mice.

PubMed

Sun, Jinmei; Wei, Zheng Zachory; Gu, Xiaohuan; Zhang, James Ya; Zhang, Yongbo; Li, Jimei; Wei, Ling

2015-10-01

Intracerebral hemorrhagic stroke (ICH) causes high mortality and morbidity with very limited treatment options. Cell-based therapy has emerged as a novel approach to replace damaged brain tissues and promote regenerative processes. In this study we tested the hypothesis that intranasally delivered hypoxia-preconditioned BMSCs could reach the brain, promote tissue repair and improve functional recovery after ICH. Hemorrhagic stroke was induced in adult C57/B6 mice by injection of collagenase IV into the striatum. Animals were randomly divided into three groups: sham group, intranasal BMSC treatment group, and vehicle treatment group. BMSCs were pre-treated with hypoxic preconditioning (HP) and pre-labeled with Hoechst before transplantation. Behavior tests, including the mNSS score, rotarod test, adhesive removal test, and locomotor function evaluation were performed at varying days, up to 21days, after ICH to evaluate the therapeutic effects of BMSC transplantation. Western blots and immunohistochemistry were performed to analyze the neurotrophic effects. Intranasally delivered HP-BMSCs were identified in peri-injury regions. NeuN+/BrdU+ co-labeled cells were markedly increased around the hematoma region, and growth factors, including BDNF, GDNF, and VEGF were significantly upregulated in the ICH brain after BMSC treatment. The BMSC treatment group showed significant improvement in behavioral performance compared with the vehicle group. Our data also showed that intranasally delivered HP-BMSCs migrated to peri-injury regions and provided growth factors to increase neurogenesis after ICH. We conclude that intranasal administration of BMSC is an effective treatment for ICH, and that it enhanced neuroregenerative effects and promoted neurological functional recovery after ICH. Overall, the investigation supports the potential therapeutic strategy for BMSC transplantation therapy against hemorrhagic stroke. Copyright © 2015 Elsevier Inc. All rights reserved.

Serial nonenhancing magnetic resonance imaging scans of high grade glioblastoma multiforme.

PubMed Central

Moore-Stovall, J.; Venkatesh, R.

1993-01-01

Magnetic resonance imaging (MRI) from clinical experience has proven to be superior to all other diagnostic imaging modalities, including computed tomography (CT) in the detection of intracranial neoplasms. Although glioblastoma multiforme presents a challenge for all diagnostic imaging modalities including MRI, MRI is paramount to CT in detecting subtle abnormal water accumulation in brain tissue caused by tumor even before there is disruption of the blood brain barrier. Currently, clinical research and investigational trials on nonionic gadolinium contrast agents have proven that nonionic gadolinium HP-DO3A (ProHance) contrast agents have lower osmolality and greater stability, which make them superior compounds to gadolinium diethylenetriamine-pentacetic acid (Gd-DTPA). Therefore, the nonionic gadolinium contrasts have been safely administered more rapidly, in higher or multiple doses for contrast enhanced MRI without adverse side effects or changes in serum iron or total bilirubin, and the intensity of the area of enhancement and number of lesions detected were superior to that of Gd-DTPA (Magnevist) at the standard dose (0.1 mmol/Kg). Perhaps if the nonionic gadolinium contrast agent, ProHance, had been approved by the Food and Drug Administration (FDA) when this MRI was performed in 1990 it would have aided in providing contrast enhancement and visualization of the tumor lesion to assist in patient diagnosis and management. Magnetic resonance imaging also provides unique multiplanar capabilities that allow for optimal visualization of the temporal and occipital lobes of the brain without bone interference.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9A Figure 9B Figure 10 Figure 11 Figure 12 Figure 13 PMID:8382751

Musculoskeletal changes in mice from 20-50 cGy of simulated galactic cosmic rays.

PubMed

Bandstra, Eric R; Thompson, Raymond W; Nelson, Gregory A; Willey, Jeffrey S; Judex, Stefan; Cairns, Mark A; Benton, Eric R; Vazquez, Marcelo E; Carson, James A; Bateman, Ted A

2009-07-01

On a mission to Mars, astronauts will be exposed to a complex mix of radiation from galactic cosmic rays. We have demonstrated a loss of bone mass from exposure to types of radiation relevant to space flight at doses of 1 and 2 Gy. The effects of space radiation on skeletal muscle, however, have not been investigated. To evaluate the effect of simulated galactic cosmic radiation on muscle fiber area and bone volume, we examined mice from a study in which brains were exposed to collimated iron-ion radiation. The collimator transmitted a complex mix of charged secondary particles to bone and muscle tissue that represented a low-fidelity simulation of the space radiation environment. Measured radiation doses of uncollimated secondary particles were 0.47 Gy at the proximal humerus, 0.24-0.31 Gy at the midbelly of the triceps brachii, and 0.18 Gy at the proximal tibia. Compared to nonirradiated controls, the proximal humerus of irradiated mice had a lower trabecular bone volume fraction, lower trabecular thickness, greater cortical porosity, and lower polar moment of inertia. The tibia showed no differences in any bone parameter. The triceps brachii of irradiated mice had fewer small-diameter fibers and more fibers containing central nuclei. These results demonstrate a negative effect on the skeletal muscle and bone systems of simulated galactic cosmic rays at a dose and LET range relevant to a Mars exploration mission. The presence of evidence of muscle remodeling highlights the need for further study.

Peripheral and central effects of repeated social defeat stress: monocyte trafficking, microglial activation, and anxiety.

PubMed

Reader, B F; Jarrett, B L; McKim, D B; Wohleb, E S; Godbout, J P; Sheridan, J F

2015-03-19

The development and exacerbation of depression and anxiety are associated with exposure to repeated psychosocial stress. Stress is known to affect the bidirectional communication between the nervous and immune systems leading to elevated levels of stress mediators including glucocorticoids (GCs) and catecholamines and increased trafficking of proinflammatory immune cells. Animal models, like the repeated social defeat (RSD) paradigm, were developed to explore this connection between stress and affective disorders. RSD induces activation of the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis activation, increases bone marrow production and egress of primed, GC-insensitive monocytes, and stimulates the trafficking of these cells to tissues including the spleen, lung, and brain. Recently, the observation that these monocytes have the ability to traffic to the brain perivascular spaces and parenchyma have provided mechanisms by which these peripheral cells may contribute to the prolonged anxiety-like behavior associated with RSD. The data that have been amassed from the RSD paradigm and others recapitulate many of the behavioral and immunological phenotypes associated with human anxiety disorders and may serve to elucidate potential avenues of treatment for these disorders. Here, we will discuss novel and key data that will present an overview of the neuroendocrine, immunological and behavioral responses to social stressors. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

[10]-gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancer in vivo.

PubMed

Martin, Ana Carolina B M; Fuzer, Angelina M; Becceneri, Amanda B; da Silva, James Almada; Tomasin, Rebeka; Denoyer, Delphine; Kim, Soo-Hyun; McIntyre, Katherine A; Pearson, Helen B; Yeo, Belinda; Nagpal, Aadya; Ling, Xiawei; Selistre-de-Araújo, Heloisa S; Vieira, Paulo Cézar; Cominetti, Marcia R; Pouliot, Normand

2017-09-22

There is increasing interest in the use of non-toxic natural products for the treatment of various pathologies, including cancer. In particular, biologically active constituents of the ginger oleoresin ( Zingiber officinale Roscoe) have been shown to mediate anti-tumour activity and to contribute to the anti-inflammatory, antioxidant, antimicrobial, and antiemetic properties of ginger. Here we report on the inhibitory properties of [10]-gingerol against metastatic triple negative breast cancer (TNBC) in vitro and in vivo . We show that [10]-gingerol concentration-dependently induces apoptotic death in mouse and human TNBC cell lines in vitro . In addition, [10]-gingerol is well tolerated in vivo , induces a marked increase in caspase-3 activation and inhibits orthotopic tumour growth in a syngeneic mouse model of spontaneous breast cancer metastasis. Importantly, using both spontaneous and experimental metastasis assays, we show for the first time that [10]-gingerol significantly inhibits metastasis to multiple organs including lung, bone and brain. Remarkably, inhibition of brain metastasis was observed even when treatment was initiated after surgical removal of the primary tumour. Taken together, these results indicate that [10]-gingerol may be a safe and useful complementary therapy for the treatment of metastatic breast cancer and warrant further investigation of its efficacy, either alone or in combination with standard systemic therapies, in pre-clinical models of metastatic breast cancer and in patients.

[10]-gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancer in vivo

PubMed Central

Becceneri, Amanda B.; da Silva, James Almada; Tomasin, Rebeka; Denoyer, Delphine; Kim, Soo-Hyun; McIntyre, Katherine A.; Pearson, Helen B.; Yeo, Belinda; Nagpal, Aadya; Ling, Xiawei; Selistre-de-Araújo, Heloisa S.; Vieira, Paulo Cézar

2017-01-01

There is increasing interest in the use of non-toxic natural products for the treatment of various pathologies, including cancer. In particular, biologically active constituents of the ginger oleoresin (Zingiber officinale Roscoe) have been shown to mediate anti-tumour activity and to contribute to the anti-inflammatory, antioxidant, antimicrobial, and antiemetic properties of ginger. Here we report on the inhibitory properties of [10]-gingerol against metastatic triple negative breast cancer (TNBC) in vitro and in vivo. We show that [10]-gingerol concentration-dependently induces apoptotic death in mouse and human TNBC cell lines in vitro. In addition, [10]-gingerol is well tolerated in vivo, induces a marked increase in caspase-3 activation and inhibits orthotopic tumour growth in a syngeneic mouse model of spontaneous breast cancer metastasis. Importantly, using both spontaneous and experimental metastasis assays, we show for the first time that [10]-gingerol significantly inhibits metastasis to multiple organs including lung, bone and brain. Remarkably, inhibition of brain metastasis was observed even when treatment was initiated after surgical removal of the primary tumour. Taken together, these results indicate that [10]-gingerol may be a safe and useful complementary therapy for the treatment of metastatic breast cancer and warrant further investigation of its efficacy, either alone or in combination with standard systemic therapies, in pre-clinical models of metastatic breast cancer and in patients. PMID:29069785

Mechanism and developmental changes in iron transport across the blood-brain barrier.

PubMed

Morgan, Evan H; Moos, Torben

2002-01-01

Transferrin and iron uptake by the brain were measured using [(59)Fe-(125)I]transferrin injected intravenously in rats aged from 15 days to 22 weeks. The values for both decreased with age. In rats aged 18 and 70 days the uptake was measured at short time intervals after the injection. When expressed as the volume of distribution (Vd), which represents the volume of plasma from which the transferrin and iron were derived, the results for iron were greater than those of transferrin as early as 7 min after injection and the difference increased rapidly with time, especially in the younger animals. A very similar time course was found for uptake by bone marrow (femurs) where iron uptake involves receptor-mediated endocytosis of Fe-transferrin, release of iron in the cell and recycling of apo-transferrin to the blood. It is concluded that, during transport of transferrin-bound plasma iron into the brain, a similar process occurs in brain capillary endothelial cells (BCECs) and that transcytosis of transferrin into the brain interstitium is only a minor pathway. Also, the high rate of iron transport into the brain in young animals, when iron requirements are high due to rapid growth of the brain, is a consequence of the level of expression and rate of recycling of transferrin receptors on BCECs. As the animal and brain mature both decrease. Copyright 2002 S. Karger AG, Basel

Platelet-rich plasma for long bone healing

PubMed Central

Lenza, Mário; Ferraz, Silvia de Barros; Viola, Dan Carai Maia; dos Santos, Oscar Fernando Pavão; Cendoroglo, Miguel; Ferretti, Mario

2013-01-01

ABSTRACT Objective: To evaluate effectiveness of the use of platelet-rich plasma as coadjuvant for union of long bones. Methods: The search strategy included the Cochrane Library (via Central) and MEDLINE (via PubMed). There were no limits as to language or publication media. The latest search strategy was conducted in December 2011. It included randomized clinical trials that evaluated the use of platelet-rich plasma as coadjuvant medication to accelerate union of long bones (acute fractures, pseudoarthrosis and bone defects). The outcomes of interest for this review include bone regeneration, adverse events, costs, pain, and quality of life. The authors selected eligible studies, evaluated the methodological quality, and extracted the data. It was not possible to perform quantitative analysis of the grouped studies (meta-analyses). Results: Two randomized prospective clinical trials were included, with a total of 148 participants. One of them compared recombinant human morphogenic bone protein-7 versus platelet-rich plasma for the treatment of pseudoarthrosis; the other evaluated the effects of three coadjuvant treatments for union of valgising tibial osteotomies (platelet-rich plasma, platelet-rich plasma plus bone marrow stromal cells, and no coadjuvant treatment). Both had low statistical power and moderate to high risk of bias. Conclusion: There was no conclusive evidence that sustained the use of platelet-rich plasma as a coadjuvant to aid bone regeneration of fractures, pseudoarthrosis, or bone defects. PMID:23579757

Osteonic organization of limb bones in mammals, including humans, and birds: a preliminary study.

PubMed

Castrogiovanni, Paola; Imbesi, Rosa; Fisichella, Marco; Mazzone, Venera

2011-01-01

As it is well known, bone tissue is characterized by a calcified extracellular matrix which makes this tissue suitable to support the body and protect the inner organs. Lamellar bone tissue is organized in lamellae, 3-7 microm in thickness, and arranged concentrically around vascular channels: the basic structure in this type of organization is called Haversian system or osteon and the diameter of osteons depends on the number of lamellae. Shape and regional density of osteons are related to the bone segment and the specific functional requirements to meet. Aim of this study is to correlate the compact bone tissue microstructure in various classes of mammals, including humans, and birds in order to find an adequate identification key. The results of our study show that in bone tissue samples from various classes of mammals, including humans, and birds the osteonic structure shows peculiar features, often depending on the rate of bone remodelling, different in different animal species. We conclude that a careful microscopic analysis of bone tissue and the characterization of distinctive osteonic features could give a major contribution to forensic medicine to obtain a more reliable recognition of bone findings.

Biomaterials and bone mechanotransduction

NASA Technical Reports Server (NTRS)

Sikavitsas, V. I.; Temenoff, J. S.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

2001-01-01

Bone is an extremely complex tissue that provides many essential functions in the body. Bone tissue engineering holds great promise in providing strategies that will result in complete regeneration of bone and restoration of its function. Currently, such strategies include the transplantation of highly porous scaffolds seeded with cells. Prior to transplantation the seeded cells are cultured in vitro in order for the cells to proliferate, differentiate and generate extracellular matrix. Factors that can affect cellular function include the cell-biomaterial interaction, as well as the biochemical and the mechanical environment. To optimize culture conditions, good understanding of these parameters is necessary. The new developments in bone biology, bone cell mechanotransduction, and cell-surface interactions are reviewed here to demonstrate that bone mechanotransduction is strongly influenced by the biomaterial properties.

Bone Disease after Kidney Transplantation

PubMed Central

Bouquegneau, Antoine; Salam, Syrazah; Delanaye, Pierre; Eastell, Richard

2016-01-01

Bone and mineral disorders occur frequently in kidney transplant recipients and are associated with a high risk of fracture, morbidity, and mortality. There is a broad spectrum of often overlapping bone diseases seen after transplantation, including osteoporosis as well as persisting high– or low–turnover bone disease. The pathophysiology underlying bone disorders after transplantation results from a complex interplay of factors, including preexisting renal osteodystrophy and bone loss related to a variety of causes, such as immunosuppression and alterations in the parathyroid hormone-vitamin D-fibroblast growth factor 23 axis as well as changes in mineral metabolism. Management is complex, because noninvasive tools, such as imaging and bone biomarkers, do not have sufficient sensitivity and specificity to detect these abnormalities in bone structure and function, whereas bone biopsy is not a widely available diagnostic tool. In this review, we focus on recent data that highlight improvements in our understanding of the prevalence, pathophysiology, and diagnostic and therapeutic strategies of mineral and bone disorders in kidney transplant recipients. PMID:26912549

Scaffold Design for Bone Regeneration

PubMed Central

Polo-Corrales, Liliana; Latorre-Esteves, Magda; Ramirez-Vick, Jaime E.

2014-01-01

The use of bone grafts is the standard to treat skeletal fractures, or to replace and regenerate lost bone, as demonstrated by the large number of bone graft procedures performed worldwide. The most common of these is the autograft, however, its use can lead to complications such as pain, infection, scarring, blood loss, and donor-site morbidity. The alternative is allografts, but they lack the osteoactive capacity of autografts and carry the risk of carrying infectious agents or immune rejection. Other approaches, such as the bone graft substitutes, have focused on improving the efficacy of bone grafts or other scaffolds by incorporating bone progenitor cells and growth factors to stimulate cells. An ideal bone graft or scaffold should be made of biomaterials that imitate the structure and properties of natural bone ECM, include osteoprogenitor cells and provide all the necessary environmental cues found in natural bone. However, creating living tissue constructs that are structurally, functionally and mechanically comparable to the natural bone has been a challenge so far. This focus of this review is on the evolution of these scaffolds as bone graft substitutes in the process of recreating the bone tissue microenvironment, including biochemical and biophysical cues. PMID:24730250

AIDS: Secretions and Implications for Nursing Care-Givers.

DTIC Science & Technology

1992-05-06

addition, infected cells may be found in many different organs, often at the same time: the brain, lymph nodes , thymus gland, bone marrow, lungs, skin...symptomatic disease with diffuse non-malignant lymph node hypertrophy. Aside from these symptoms of lymphadenopathy, patients are typically healthy...a person physically and mentally crippled. AIDS dementia complex (ADC) or subacute HIV encephalopathy, primary lymphomas, toxoplasmosis , cryptococcal

Energy Sparing Orexigenic Inflammation of Obesity.

PubMed

Lee, Aileen; Dixit, Vishwa Deep

2017-07-05

The neuro-immune interactions that integrate host metabolism in health and disease are unclear. A new study by Valdearcos et al. (2017) describes how sensing of high-fat diet by microglia, brain's resident innate immune cells, recruits additional bone-marrow-derived myeloid cells into the hypothalamus to produce inflammation and cause weight gain. Copyright © 2017 Elsevier Inc. All rights reserved.

Subthalamic nucleus deep brain stimulation improves deglutition in Parkinson's disease.

PubMed

Ciucci, Michelle R; Barkmeier-Kraemer, Julie M; Sherman, Scott J

2008-04-15

Relatively little is known about the role of the basal ganglia in human deglutition. Deep brain stimulation (DBS) affords us a model for examining deglutition in humans with known impairment of the basal ganglia. The purpose of this study was to examine the effects of subthalamic nuclei (STN) DBS on the oral and pharyngeal stages of deglutition in individuals with Parkinson's Disease (PD). It was hypothesized that DBS would be associated with improved deglutition. Within participant, comparisons were made between DBS in the ON and OFF conditions using the dependent variables: pharyngeal transit time, maximal hyoid bone excursion, oral total composite score, and pharyngeal total composite score. Significant improvement occurred for the pharyngeal composite score and pharyngeal transit time in the DBS ON condition compared with DBS OFF. Stimulation of the STN may excite thalamocortical or brainstem targets to sufficiently overcome the bradykinesia/hypokinesia associated with PD and return some pharyngeal stage motor patterns to performance levels approximating those of "normal" deglutition. However, the degree of hyoid bone excursion and oral stage measures did not improve, suggesting that these motor acts may be under the control of different sensorimotor pathways within the basal ganglia. 2007 Movement Disorder Society

Bone as a source of organism vitality and regeneration.

PubMed

Mackiewicz, Zygmunt; Niklińska, Wiesława Ewa; Kowalewska, Jolanta; Chyczewski, Lech

2011-01-01

The most important features that determine the vital role of bone include: a) a continuous supply of calcium, which is indispensible for every cell of the entire organism at all times, and b) the delivery of circulating blood cells and some adult stem cells to keep the body vigorous, ready for self-reparation, and continuously rebuilding throughout life. These functions of bones are no less important than protecting the body cavities, serving as mechanical levers connected to the muscles, and determining the shape and dimensions of the entire organism. The aim of this review was to address some basic cellular and molecular knowledge to better understand the complex interactions of bone structural components. The apprehension of osteoblast differentiation and its local regulation has substantially increased in recent years. It has been suggested that osteocytes, cells within the bone matrix, act as regulatory mechanosensors. Therefore immobility as well as limited activity has a dramatic effect on bone structure and influences a broad spectrum of bone physiology-related functions as well as the functions of many other organs. Lifelong bone rebuilding is modulated through several pathways, including the Wnt pathway that regulates bone formation and resorption. In the adult skeleton, bone is continuously renewed in response to a variety of stimuli, such as the specific process of remodeling dependent on RANK/ /RANKL/OPG interactions. Better understanding of bone biology provides opportunities for the development of more effective prevention and treatment modalities for a variety of bone diseases, including new approaches to adult stem cell-based therapies.

Autoimmune Encephalitis Following Bone Marrow Transplantation.

PubMed

Rathore, Geetanjali S; Leung, Kathryn S; Muscal, Eyal

2015-09-01

Neurological complications, especially encephalopathy and seizures, are commonly seen in bone marrow transplant patients. Infections, chemotoxicity, graft versus host disease, or secondary central nervous system malignancies are the most common underlying etiologies. There is increased awareness that autoimmune encephalitis may cause neurological dysfunction in immunocompetent children. The potential role of such a mechanism in children undergoing bone marrow transplantation is unknown. We report a boy who developed autoimmune encephalitis with voltage-gated potassium channel-associated and thyroid autoantibodies subsequent to transplantation. A 7-year-old boy presented with a change in behavior, poor attention, cognitive deficits, and abnormal movements 15 months after undergoing transplantation for idiopathic aplastic anemia. He had clinical and subclinical seizures and brain magnetic resonance imaging hyperintensities bilaterally in the uncal regions. His evaluation revealed high titers of voltage-gated potassium channel, leucine-rich glioma-inactivated 1 protein, and thyroglobulin antibodies suggestive of autoimmune limbic encephalitis. He showed significant improvement in behavior and neuropsychological testing and has remained seizure-free on levetiracetam after immunotherapy with corticosteroids and intravenous immunoglobulin. Systemic autoimmune manifestations in bone marrow transplant patients have been well-documented, but autoimmune encephalitis after transplantation has yet to be described in children. Copyright © 2015 Elsevier Inc. All rights reserved.

[Surgical treatment of pulmonary metastases from colon and rectal cancer].

PubMed

Togashi, Ken-ichi; Aoki, K; Hirahara, H; Sugawara, M; Oguma, F

2004-09-01

We retrospectively studied the surgical treatment for pulmonary metastases from colon and rectal cancer. A total of 24 patients (9 males and 15 females; mean age 61 years) underwent 29 thoracotomies for metastatic colon carcinoma, while 22 patients (16 males and 6 females; mean age 63 years) underwent 29 thoracotomies for metastatic rectal cancer. The median interval between the primary procedure and lung resection for metastases was 26 months in the patients with colon carcinoma and 32 months in the patients with rectal cancer. In the patients with colon carcinoma, 16 underwent wedge resection or segmentectomy (including 4 video-assisted procedures) and 13 (54%) underwent lobectomy or pneumonectomy. In the patients with rectal cancer, 15 underwent wedge or segmentectomy (including 1 video-assisted procedure), 13 (59%) underwent lobectomy or pneumonectomy, and 1 underwent exploratory thoracotomy. All procedures except exploratory thoracotomy were curative operations. There was no mortality. Overall 5-year survival was 56% (n=46). Five-year survival was 65% for patients with colon metastases (n=24) and 45% for patients with rectal metastases (n=22), and there was no significant difference. Recurrent sites were 4 lungs (36%), 4 livers (36%), 1 bone, 1 uterus, and 1 peritoneum in patients with colon carcimoma, and 10 lungs (43%), 5 brains (22%), 3 livers (13%), 1 bone, and 1 vagina in patients with rectal cancer. Pulmonary resection for metastases from colon carcinoma may have better prognosis than that from rectal cancer. However, further investigation may be required to obtain convincing conclusions.

Systemic influences contribute to prolonged microvascular rarefaction after brain irradiation: a role for endothelial progenitor cells

PubMed Central

Ashpole, Nicole M.; Warrington, Junie P.; Mitschelen, Matthew C.; Yan, Han; Sosnowska, Danuta; Gautam, Tripti; Farley, Julie A.; Csiszar, Anna; Ungvari, Zoltan

2014-01-01

Whole brain radiation therapy (WBRT) induces profound cerebral microvascular rarefaction throughout the hippocampus. Despite the vascular loss and localized cerebral hypoxia, angiogenesis fails to occur, which subsequently induces long-term deficits in learning and memory. The mechanisms underlying the absence of vessel recovery after WBRT are unknown. We tested the hypotheses that vascular recovery fails to occur under control conditions as a result of loss of angiogenic drive in the circulation, chronic tissue inflammation, and/or impaired endothelial cell production/recruitment. We also tested whether systemic hypoxia, which is known to promote vascular recovery, reverses these chronic changes in inflammation and endothelial cell production/recruitment. Ten-week-old C57BL/6 mice were subjected to a clinical series of fractionated WBRT: 4.5-Gy fractions 2 times/wk for 4 wk. Plasma from radiated mice increased in vitro endothelial cell proliferation and adhesion compared with plasma from control mice, indicating that WBRT did not suppress the proangiogenic drive. Analysis of cytokine levels within the hippocampus revealed that IL-10 and IL-12(p40) were significantly increased 1 mo after WBRT; however, systemic hypoxia did not reduce these inflammatory markers. Enumeration of endothelial progenitor cells (EPCs) in the bone marrow and circulation indicated that WBRT reduced EPC production, which was restored with systemic hypoxia. Furthermore, using a bone marrow transplantation model, we determined that bone marrow-derived endothelial-like cells home to the hippocampus after systemic hypoxia. Thus, the loss of production and homing of EPCs have an important role in the prolonged vascular rarefaction after WBRT. PMID:25038144

The roles of vascular endothelial growth factor in bone repair and regeneration

PubMed Central

Hu, Kai; Olsen, Bjorn R.

2016-01-01

Vascular endothelial growth factor-A (VEGF) is one of the most important growth factors for regulation of vascular development and angiogenesis. Since bone is a highly vascularized organ and angiogenesis plays an important role in osteogenesis, VEGF also influences skeletal development and postnatal bone repair. Compromised bone repair and regeneration in many patients can be attributed to impaired blood supply; thus, modulation of VEGF levels in bones represents a potential strategy for treating compromised bone repair and improving bone regeneration. This review (i) summarizes the roles of VEGF at different stages of bone repair, including the phases of inflammation, endochondral ossification, intramembranous ossification during callus formation and bone remodeling; (ii) discusses different mechanisms underlying the effects of VEGF on osteoblast function, including paracrine, autocrine and intracrine signaling during bone repair; (iii) summarizes the role of VEGF in the bone regenerative procedure, distraction osteogenesis; and (iv) reviews evidence for the effects of VEGF in the context of repair and regeneration techniques involving the use of scaffolds, skeletal stem cells and growth factors. PMID:27353702

Understanding the low uptake of bone-anchored hearing aids: a review.

PubMed

Powell, R; Wearden, A; Pardesi, S M; Green, K

2017-03-01

Bone-anchored hearing aids improve hearing for patients for whom conventional behind-the-ear aids are problematic. However, uptake of bone-anchored hearing aids is low and it is important to understand why this is the case. A narrative review was conducted. Studies examining why people accept or decline bone-anchored hearing aids and satisfaction levels of people with bone-anchored hearing aids were reviewed. Reasons for declining bone-anchored hearing aids included limited perceived benefits, concerns about surgery, aesthetic concerns and treatment cost. No studies providing in-depth analysis of the reasons for declining or accepting bone-anchored hearing aids were identified. Studies of patient satisfaction showed that most participants reported benefits with bone-anchored hearing aids. However, most studies used cross-sectional and/or retrospective designs and only included people with bone-anchored hearing aids. Important avenues for further research are in-depth qualitative research designed to fully understand the decision-making process for bone-anchored hearing aids and rigorous quantitative research comparing satisfaction of people who receive bone-anchored hearing aids with those who receive alternative (or no) treatments.

77 FR 19694 - Notice of Intent To Repatriate Cultural Items: U.S. Department of Defense, Army Corps of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-02

... objects include 1 lot of fragmented mammal bones; 1 charcoal sample; 1 piece of mussel shell; 1 piece of... objects include 2 pieces of burned mammal bone; 1 burned rodent jaw; 28 pieces of debitage; 8 pipe bowl... other unknown burial numbers. The 658 unassociated funerary artifacts include 1 hollowed bone fragment...

Mechanical Signaling for Bone Modeling and Remodeling

PubMed Central

Robling, Alexander G.; Turner, Charles H.

2012-01-01

Proper development of the skeleton in utero and during growth requires mechanical stimulation. Loading results in adaptive changes in bone that strengthen bone structure. Bone’s adaptive response is regulated by the ability of resident bone cells to perceive and translate mechanical energy into a cascade of structural and biochemical changes within the cells — a process known as mechanotransduction. Mechanotransduction pathways are among the most anabolic in bone, and consequently, there is great interest in elucidating how mechanical loading produces its observed effects, including increased bone formation, reduced bone loss, changes in bone cell differentiation and lifespan, among others. A molecular understanding of these processes is developing, and with it comes a profound new insight into the biology of bone. In this article, we review the nature of the physical stimulus to which bone cells mount an adaptive response, including the identity of the sensor cells, their attributes and physical environment, and putative mechanoreceptors they express. Particular attention is allotted to the focal adhesion and Wnt signaling, in light of their emerging role in bone mechanotransduction. The cellular mechanisms for increased bone loss during disuse, and reduced bone loss during loading are considered. Finally, we summarize the published data on bone cell accommodation, whereby bone cells stop responding to mechanical signaling events. Collectively, these data highlight the complex yet finely orchestrated process of mechanically regulated bone homeostasis. PMID:19817708

Solitary juvenile xanthogranuloma of the temporal muscle and bone penetrating the dura mater in a 2-month-old boy.

PubMed

Cornips, Erwin M J; Cox, Kimberly E M; Creytens, David H K V; Granzen, Bernd; Weber, Jacobiene W; Ter Laak-Poort, Mariel P

2009-12-01

Juvenile xanthogranuloma (JXG) is a rare histiocytic disorder primarily observed during the first 2 years of life. Most patients present with a solitary cutaneous lesion; however, others present with extracutaneous manifestations or even with systemic involvement. The authors describe a 2-month-old boy in whom was diagnosed a unifocal extracutaneous JXG involving the temporal bone. Unlike 3 other cases of solitary JXGs of the temporal bone in the literature, the present case involved destruction of the dura mater and leptomeningeal enhancement surrounding the entire temporal lobe. The lesion did not regress after an initial biopsy procedure and had to be removed more radically because of progressive mass effect on the brain. The child recently underwent a reconstructive skull procedure and is doing well almost 2 years postoperatively without evidence of disease. This case demonstrates that even in instances of extensive disease a favorable outcome is possible without chemotherapy.

In vitro stabilization of a low-tin bone-imaging agent (99mTc-Sn-HEDP) by ascorbic acid.

PubMed

Tofe, A J; Francis, M D

1976-09-01

The presence of oxidants in the 99mTc-pertechnetate and of oxygen in diagnostic kits containing low concentrations of Sn(II) has a detrimental effect upon in vitro and in vivo stability. Maintaining a nitrogen atmosphere or increasing the Sn(II) concentration inhibits the formation of 99mTcO4-. However, the latter remedy is likely to cause uptake in the reticuloendothelial system and has been associated with false positive or negative brain scans. We used ascorbic acid (an antioxidant) to ensure the in vitro stability with the low-Sn(II) bone agent disodium etidronate. In vitro stability studies by instant thin-layer chromatography, using high-acitivity generators and "instant pertechnetate," yielded less than 2% free pertechnetate at 24 hr after preparation. Distribution studies in guinea pigs show neither altered distribution of the bone agent nor abnormal distribution of ascorbic acid, suggesting its sole function as a noncomplexing stabilizer.

Durable clinical remission of a skull metastasis under intralesional Viscum album extract therapy: Case report.

PubMed

Werthmann, Paul Georg; Huber, Roman; Kienle, Gunver Sophia

2018-06-09

Skull metastases are rare, they can eventually cause pain, and can invade the brain. Viscum album extracts (VAEs) are used as an adjuvant treatment in cancer. A 68-year-old patient with rectal cancer presented with lung metastases, and metastases to multiple bone sites, the chest wall, and the liver were later identified. Histological examination of one of the bone lesions revealed an additional thyroid carcinoma. An osteolytic parietal bone lesion progressed to a painful metastasis of the skull despite radiotherapy and chemotherapy. The VAEs were applied weekly into the metastasis, followed by pain relief and softening of the lesion. The lesion partially regressed (>50%) after 8 months of continued VAE treatment and remained stable for 2 years. This case shows a durable clinical remission of a skull metastasis under VAE. Further investigations of intratumoral VAE treatment seem worthwhile-especially in symptomatic skull metastases not responding to radiotherapy or systemic therapies. © 2018 The Authors Head & Neck Published by Wiley Periodicals, Inc.

Optimising implant anchorage (augmentation) during fixation of osteoporotic fractures: is there a role for bone-graft substitutes?

PubMed

Larsson, Sune; Procter, Philip

2011-09-01

When stabilising a fracture the contact between the screw and the surrounding bone is crucial for mechanical strength. Through development of screws with new thread designs, as well as optimisation of other properties, improved screw purchase has been gained. Other alternatives to improve screw fixation in osteoporotic bone, as well as normal bone if needed, includes the use of various coatings on the screw that will induce a bonding between the implant surface and the bone implant, as well as application of drugs such as bisphosphonates locally in the screw hole to induce improved screw anchorage through their anticatabolic effect on the bone tissue. As failure of internal fixation of fractures in osteoporotic bone typically occurs through breakage of the bone that surrounds the implant, rather than the implant itself, an alternative strategy in osteoporotic bone can include augmentation of the bone around the screw. This is useful when screws alone are being used for fixation, as it will increase pull-out resistance, but also when conventional plates and screws are used. In angularly stable plate-screw systems, screw back-out is not a problem if the locking mechanism between the screws and the plate works. However, augmentation that will strengthen the bone around the screws can also be useful in conjunction with angle-stable plate-screw systems, as the augmentation will provide valuable support when subjected to loading that might cause cut-out. For many years conventional bone cement, polymethylmethacrylate (PMMA), has been used for augmentation, but due to side effects--including great difficulties if removal becomes necessary--the use of PMMA has never gained wide acceptance. With the introduction of bone substitutes, such as calcium phosphate cement, it has been shown that augmentation around screws can be achieved without the drawbacks seen with PMMA. When dealing with fixation of fractures in osteoporotic bone where screw stability might be inadequate, it therefore seems an attractive option to include bone substitutes for augmentation around screws as part of the armamentarium. Clinical studies now are needed to determine the indications in which bone augmentation with bone-graft substitutes (BGSs) would merit clinical usage. Copyright © 2011. Published by Elsevier Ltd.

Cranioplasty: Indications, procedures, and outcome - An institutional experience.

PubMed

Andrabi, Syed M; Sarmast, Arif H; Kirmani, Altaf R; Bhat, Abdul R

2017-01-01

Cranioplasty, the repair of a skull vault defect by insertion of an object (bone or nonbiological materials such as metal or plastic plates), is a well-known procedure in modern neurosurgery. Brain protection and cosmetic aspects are the major indications of cranioplasty. A retroprospective study was conducted for evaluating the indications, materials used, complications, and outcome of cranioplasty. This study was prospective from August 2013 to September 2015 and retrospective from August 2010 to July 2013. In the retrospective study, patients files were retrieved from the mentioned date (August 2010 to July 2013) from the medical records and the findings were recorded. Abstracted data included age at the time of cranioplasty (years), sex (male or female), medical comorbidities (hypertension, diabetes), indications for craniectomy [Road traffic accident (RTA), fall from height (FFH), hit by stone or cricket ball, physical assault, stroke, infection, shell injury, bullet injury, and intraoperative swelling], laterality of cranioplasty (bilateral, unilateral, or bifrontal), time between craniectomy and cranioplasty (weeks), type of graft (autologous or artificial), type of prosthesis if used (methylmethacrylate, titanium), storage of bone flap if used (subcutaneous or deep freezer), operative time (minutes), and complications fallowing cranioplasty. Of the 236 patients included in the study, maximum were in the age group of 21-30 years i.e., 30.93% ( n = 73). Mean age of the patients was 33.44 years. A total of 196 (83.05%) were autologous and 40 (16.95%) were artificial. Out of the 40 patients who underwent artificial cranioplasty, 36 (15.25%) had methylmethacrylate graft and 4 (1.7%) had titanium mesh implant. Bone was not preserved in 16.95% ( n = 40), preserved in subcutaneous tissue in abdominal wall in 2.54% ( n = 6), and preserved in deep freezer in 80.51% ( n = 190) of the patients. Cranioplasty as a procedure is not without complications; however, if performed properly and at proper time with an aseptic technique, good results are achieved.

Bilateral tympanokeratomas (cholesteatomas) with bilateral otitis media, unilateral otitis interna and acoustic neuritis in a dog.

PubMed

Østevik, Liv; Rudlang, Kathrine; Holt Jahr, Tuva; Valheim, Mette; Njaa, Bradley Lyndon

2018-05-22

An aural cholesteatoma, more appropriately named tympanokeratoma, is an epidermoid cyst of the middle ear described in several species, including dogs, humans and Mongolian gerbils. The cyst lining consists of stratified, keratinizing squamous epithelium with central accumulation of a keratin debris. This case report describes vestibular ganglioneuritis and perineuritis in a dog with chronic otitis, bilateral tympanokeratomas and presumed extension of otic infection to the central nervous system. An 11-year-old intact male Dalmatian dog with chronic bilateral otitis externa and sudden development of symptoms of vestibular disease was examined. Due to the dog's old age the owner opted for euthanasia without any further examination or treatment and the dog was submitted for necropsy. Transection of the ears revealed grey soft material in the external ear canals and pearly white, dry material consistent with keratin in the tympanic bullae bilaterally. The brain and meninges were grossly unremarkable. Microscopical findings included bilateral otitis externa and media, unilateral otitis interna, ganglioneuritis and perineuritis of the spiral ganglion of the vestibulocochlear nerve and multifocal to coalescing, purulent meningitis. A keratinizing squamous epithelial layer continuous with the external acoustic meatus lined the middle ear compartments, consistent with bilateral tympanokeratomas. Focal bony erosion of the petrous portion of the temporal bone and squamous epithelium and Gram-positive bacterial cocci were evident in the left cochlea. The findings suggest that meningitis developed secondary to erosion of the temporal bone and ganglioneuritis and/or perineuritis of the vestibulocochlear nerve. Middle ear tympanokeratoma is an important and potentially life-threatening otic condition in the dog. Once a tympanokeratoma has developed expansion of the cyst can lead to erosion of bone and extension of otic infection to the inner ear, vestibulocochlear ganglion and nerve potentially leading to bacterial infection of the central nervous system.

Dengue death with evidence of hemophagocytic syndrome and dengue virus infection in the bone marrow.

PubMed

Ab-Rahman, Hasliana Azrah; Wong, Pooi-Fong; Rahim, Hafiz; Abd-Jamil, Juraina; Tan, Kim-Kee; Sulaiman, Syuhaida; Lum, Chai-See; Syed-Omar, Syarifah-Faridah; AbuBakar, Sazaly

2015-01-01

HPS is a potentially life-threatening histiocytic disorder that has been described in various viral infections including dengue. Its involvement in severe and fatal dengue is probably more common but is presently under recognized. A 38-year-old female was admitted after 5 days of fever. She was deeply jaundiced, leukopenic and thrombocytopenic. Marked elevation of transaminases, hyperbilirubinemia and hypoalbuminemia were observed. She had deranged INR values and prolonged aPTT accompanied with hypofibrinogenemia. She also had splenomegaly. She was positive for dengue IgM. Five days later she became polyuric and CT brain image showed gross generalized cerebral edema. Her conditions deteriorated by day 9, became confused with GCS of 9/15. Her BMAT showed minimal histiocytes. Her serum ferritin level peaked at 13,670.00 µg/mL and her sCD163 and sCD25 values were markedly elevated at 4750.00 ng/mL and 4191.00 pg/mL, respectively. She succumbed to the disease on day 10 and examination of her tissues showed the presence of dengue virus genome in the bone marrow. It is described here, a case of fatal dengue with clinical features of HPS. Though BMAT results did not show the presence of macrophage hemophagocytosis, other laboratory features were consistent with HPS especially marked elevation of ferritin, sCD163 and sCD25. Detection of dengue virus in the patient's bone marrow, fifteen days after the onset of fever was also consistent with the suggestion that the HPS is associated with dengue virus infection. The findings highlight HPS as a possible complication leading to severe dengue and revealed persistent dengue virus infection of the bone marrow. Detection of HPS markers; ferritin, sCD163 and sCD25, therefore, should be considered for early recognition of HPS-associated dengue.

A novel ciliopathic skull defect arising from excess neural crest.

PubMed

Tabler, Jacqueline M; Rice, Christopher P; Liu, Karen J; Wallingford, John B

2016-09-01

The skull is essential for protecting the brain from damage, and birth defects involving disorganization of skull bones are common. However, the developmental trajectories and molecular etiologies by which many craniofacial phenotypes arise remain poorly understood. Here, we report a novel skull defect in ciliopathic Fuz mutant mice in which only a single bone pair encases the forebrain, instead of the usual paired frontal and parietal bones. Through genetic lineage analysis, we show that this defect stems from a massive expansion of the neural crest-derived frontal bone. This expansion occurs at the expense of the mesodermally-derived parietal bones, which are either severely reduced or absent. A similar, though less severe, phenotype was observed in Gli3 mutant mice, consistent with a role for Gli3 in cilia-mediated signaling. Excess crest has also been shown to drive defective palate morphogenesis in ciliopathic mice, and that defect is ameliorated by reduction of Fgf8 gene dosage. Strikingly, skull defects in Fuz mutant mice are also rescued by loss of one allele of fgf8, suggesting a potential route to therapy. In sum, this work is significant for revealing a novel skull defect with a previously un-described developmental etiology and for suggesting a common developmental origin for skull and palate defects in ciliopathies. Copyright © 2016 Elsevier Inc. All rights reserved.

Cerebral fat embolism syndrome after long bone fracture due to gunshot injury.

PubMed

Duran, Latif; Kayhan, Servet; Kati, Celal; Akdemir, Hizir Ufuk; Balci, Kemal; Yavuz, Yucel

2014-03-01

Cerebral fat embolism syndrome is a lethal complication of long-bone fractures and clinically manifasted with respiratory distress, altered mental status, and petechial rash. We presented a 20-year-old male admitted with gun-shot wounds to his left leg. Twenty-four hours after the event, he had generalized tonic clonic seizures, decorticate posture and a Glascow Coma Scale of seven with localization of painful stimuli. Subsequent magnetic resonance imaging of the brain showed a star-field pattern defining multiple lesions of restricted diffusion. On a 4-week follow-up, he had returned to normal neurological function. Despite the severity of the neurological condition upon initial presentation, the case cerebral fat embolism illustrates that, cerebral dysfunction associated with cerebral fat embolism illustrates reversible.

Aggregatibacter actinomycetemcomitans osteomyelitis in a 12 year old boy: case report emphasizing the importance of tissue culture, and review of literature.

PubMed

Sharma, Ketaki; Mudgil, Poonam; Whitehall, John S; Gosbell, Iain

2017-03-14

Aggregatibacter actinomycetemcomitans most commonly causes periodontitis but has been reported to infect heart valves, soft tissue, brain and lungs, and distal bones. Osteomyelitis distal to the jaw is rarely described. We report an unusual and rare case of chronic osteomyelitis caused by A. actinomycetemcomitans in the toe of a paediatric patient, and review the available literature. The infection was managed with intravenous antibiotics followed by oral antibiotics. This is an unusual presentation of A. actinomycetemcomitans causing chronic osteomyelitis presumed due to nidation in a minimally damaged bone, associated with bacteraemia of an oral commensal. It occurred in the toe, without obvious dental predisposition; associated with minimal clinical disturbance and with muted immune response.

Bone Lengthening in the Pediatric Upper Extremity.

PubMed

Farr, Sebastian; Mindler, Gabriel; Ganger, Rudolf; Girsch, Werner

2016-09-07

➤Bone lengthening has been used successfully for several congenital and acquired conditions in the pediatric clavicle, humerus, radius, ulna, and phalanges.➤Common indications for bone lengthening include achondroplasia, radial longitudinal deficiency, multiple hereditary exostosis, brachymetacarpia, symbrachydactyly, and posttraumatic and postinfectious growth arrest.➤Most authors prefer distraction rates of <1 mm/day for each bone in the upper extremity except the humerus, which can safely be lengthened by 1 mm/day.➤Most authors define success by the amount of radiographic bone lengthening, joint motion after lengthening, and subjective patient satisfaction rather than validated patient-related outcome measures.➤Bone lengthening of the upper extremity is associated with a high complication rate, with complications including pin-track infections, fixation device failure, nerve lesions, nonunion, fracture of regenerate bone, and joint dislocations. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

Lessons from rare diseases of cartilage and bone.

PubMed

Gallagher, James A; Ranganath, Lakshminarayan R; Boyde, Alan

2015-06-01

Studying severe phenotypes of rare syndromes can elucidate disease mechanisms of more common disorders and identify potential therapeutic targets. Lessons from rare bone diseases contributed to the development of the most successful class of bone active agents, the bisphosphonates. More recent research on rare bone diseases has helped elucidate key pathways and identify new targets in bone resorption and bone formation including cathepsin K and sclerostin, for which drugs are now in clinical trials. By contrast, there has been much less focus on rare cartilage diseases and osteoarthritis (OA) remains a common disease with no effective therapy. Investigation of rare cartilage syndromes is identifying new potential targets in OA including GDF5 and lubricin. Research on the arthropathy of the ultra-rare disease alkaptonuria has identified several new features of the OA phenotype, including high density mineralized protrusions (HDMPs) which constitute a newly identified mechanism of joint destruction. Copyright © 2015 Elsevier Ltd. All rights reserved.

78 FR 76507 - Revised Medical Criteria for Evaluating Cancer (Malignant Neoplastic Diseases)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-17

... blast (immature) cells in the peripheral blood or bone marrow is 10 percent or greater. We propose this... evaluate cancer treatment by bone marrow or stem cell transplantation, including transplantation using stem... evaluate cancers treated with bone marrow or stem cell transplantation, including transplantation using...

I.V. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat.

PubMed

Nomura, T; Honmou, O; Harada, K; Houkin, K; Hamada, H; Kocsis, J D

2005-01-01

I.V. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat cerebral ischemia models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared the efficacy of systemic delivery of human mesenchymal stem cells and human mesenchymal stem cells transfected with a fiber-mutant F/RGD adenovirus vector with a brain-derived neurotrophic factor gene (brain-derived neurotrophic factor-human mesenchymal stem cells). A permanent middle cerebral artery occlusion was induced by intraluminal vascular occlusion with a microfilament. Human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells were i.v. injected into the rats 6 h after middle cerebral artery occlusion. Lesion size was assessed at 6 h, 1, 3 and 7 days using MR imaging, and histological methods. Functional outcome was assessed using the treadmill stress test. Both human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells reduced lesion volume and elicited functional improvement compared with the control sham group, but the effect was greater in the brain-derived neurotrophic factor-human mesenchymal stem cell group. ELISA analysis of the infarcted hemisphere revealed an increase in brain-derived neurotrophic factor in the human mesenchymal stem cell groups, but a greater increase in the brain-derived neurotrophic factor-human mesenchymal stem cell group. These data support the hypothesis that brain-derived neurotrophic factor contributes to neuroprotection in cerebral ischemia and cellular delivery of brain-derived neurotrophic factor can be achieved by i.v. delivery of human mesenchymal stem cells.

A Clinical Study of Autologous Bone Marrow Mononuclear Cells for Cerebral Palsy Patients: A New Frontier

PubMed Central

Sharma, Alok; Sane, Hemangi; Gokulchandran, Nandini; Kulkarni, Pooja; Sundaram, Jyothi; Paranjape, Amruta; Shetty, Akshata; Bhagwanani, Khushboo; Biju, Hema; Badhe, Prerna

2015-01-01

Cerebral palsy is a nonprogressive heterogeneous group of neurological disorders with a growing rate of prevalence. Recently, cellular therapy is emerging as a potential novel treatment strategy for cerebral palsy. The various mechanisms by which cellular therapy works include neuroprotection, immunomodulation, neurorestoration, and neurogenesis. We conducted an open label, nonrandomized study on 40 cases of cerebral palsy with an aim of evaluating the benefit of cellular therapy in combination with rehabilitation. These cases were administered autologous bone marrow mononuclear cells intrathecally. The follow-up was carried out at 1 week, 3 months, and 6 months after the intervention. Adverse events of the treatment were also monitored in this duration. Overall, at six months, 95% of patients showed improvements. The study population was further divided into diplegic, quadriplegic, and miscellaneous group of cerebral palsy. On statistical analysis, a significant association was established between the symptomatic improvements and cell therapy in diplegic and quadriplegic cerebral palsy. PET-CT scan done in 6 patients showed metabolic improvements in areas of the brain correlating to clinical improvements. The results of this study demonstrate that cellular therapy may accelerate the development, reduce disability, and improve the quality of life of patients with cerebral palsy. PMID:25788947

Androgen receptor (AR) pathophysiological roles in androgen-related diseases in skin, bone/muscle, metabolic syndrome and neuron/immune systems: lessons learned from mice lacking AR in specific cells

PubMed Central

Chang, Chawnshang; Yeh, Shuyuan; Lee, Soo Ok; Chang, Ta-min

2013-01-01

The androgen receptor (AR) is expressed ubiquitously and plays a variety of roles in a vast number of physiological and pathophysiological processes. Recent studies of AR knockout (ARKO) mouse models, particularly the cell type- or tissue-specific ARKO models, have uncovered many AR cell type- or tissue-specific pathophysiological roles in mice, which otherwise would not be delineated from conventional castration and androgen insensitivity syndrome studies. Thus, the AR in various specific cell types plays pivotal roles in production and maturation of immune cells, bone mineralization, and muscle growth. In metabolism, the ARs in brain, particularly in the hypothalamus, and the liver appear to participate in regulation of insulin sensitivity and glucose homeostasis. The AR also plays key roles in cutaneous wound healing and cardiovascular diseases, including atherosclerosis and abdominal aortic aneurysm. This article will discuss the results obtained from the total, cell type-, or tissue-specific ARKO models. The understanding of AR cell type- or tissue-specific physiological and pathophysiological roles using these in vivo mouse models will provide useful information in uncovering AR roles in humans and eventually help us to develop better therapies via targeting the AR or its downstream signaling molecules to combat androgen/AR-related diseases. PMID:24653668

Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration

PubMed Central

Gu, Wenyi; Wu, Chengtie; Chen, Jiezhong; Xiao, Yin

2013-01-01

Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically. PMID:23836972

Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration.

PubMed

Gu, Wenyi; Wu, Chengtie; Chen, Jiezhong; Xiao, Yin

2013-01-01

Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically.

Biophotons, microtubules and CNS, is our brain a "holographic computer"?

PubMed

Grass, F; Klima, H; Kasper, S

2004-01-01

Several experiments show that there is a cell to cell communication by light in different cell types. This article describes theoretical mechanisms and subcellular structures that could be involved in this phenomenon. Special consideration is given to the nervous system, since it would have excellent conditions for such mechanisms. Neurons are large colourless cells with wide arborisations, have an active metabolism generating photons, contain little pigment, and have a prominent cytoskeleton consisting of hollow microtubules. As brain and spinal cord are protected from environmental light by bone and connective tissue, the signal to noise ratio should be high for photons as signal. Fluorescent and absorbing substances should interfere with such a communication system. Of all biogenic amines nature has chosen the ones with the strongest fluorescence as neurotransmitters for mood reactions: serotonin, dopamine and norepinephrine. If these mechanisms are of relevance our brain would have to be looked upon as a "holographic computer".

Bone remodeling and regulating biomarkers in women at the time of breast cancer diagnosis.

PubMed

Yao, Song; Zhang, Yali; Tang, Li; Roh, Janise M; Laurent, Cecile A; Hong, Chi-Chen; Hahn, Theresa; Lo, Joan C; Ambrosone, Christine B; Kushi, Lawrence H; Kwan, Marilyn L

2017-02-01

The majority of breast cancer patients receive endocrine therapy, including aromatase inhibitors known to cause increased bone resorption. Bone-related biomarkers at the time of breast cancer diagnosis may predict future risk of osteoporosis and fracture after endocrine therapy. In a large population of 2,401 female breast cancer patients who later underwent endocrine therapy, we measured two bone remodeling biomarkers, TRAP5b and BAP, and two bone regulating biomarkers, RANKL and OPG, in serum samples collected at the time of breast cancer diagnosis. We analyzed these biomarkers and their ratios with patients' demographic, lifestyle, clinical tumor characteristics, as well as bone health history. The presence of bone metastases, prior bisphosphonate (BP) treatment, and blood collection after chemotherapy had a significant impact on biomarker levels. After excluding these cases and controlling for blood collection time, several factors, including age, race/ethnicity, body mass index, physical activity, alcohol consumption, smoking, and hormonal replacement therapy, were significantly associated with bone biomarkers, while vitamin D or calcium supplements and tumor characteristics were not. When prior BP users were included in, recent history of osteoporosis and fracture was also associated. Our findings support further investigation of these biomarkers with bone health outcomes after endocrine therapy initiation in women with breast cancer.

Imaging Characteristics of Children with Auditory Neuropathy Spectrum Disorder

PubMed Central

Roche, Joseph P.; Huang, Benjamin Y.; Castillo, Mauricio; Bassim, Marc K.; Adunka, Oliver F.; Buchman, Craig A.

2013-01-01

Objective To identify and define the imaging characteristics of children with auditory neuropathy spectrum disorder (ANSD). Design Retrospective medical records review and analysis of both temporal bone computed tomography (CT) and magnetic resonance images (MRI) in from children with the diagnosis of ANSD. Setting Tertiary referral center. Patients 118 children with the electrophysiological characteristics of ANSD with available imaging studies for review. Interventions Two neuroradiologists and a neurotologist reviewed each study and consensus descriptions were established. Main outcome measures The type and number of imaging findings were tabulated. Results Sixty-eight (64%) MRIs revealed at least one imaging abnormality while selective use of CT identified 23 (55%) with anomalies. The most prevalent MRI findings included cochlear nerve deficiency (n=51; 28% of 183 nerves), brain abnormalities (n=42; 40% of 106 brains) and prominent temporal horns (n=33, 16% of 212 temporal lobes). The most prevalent CT finding from selective use of CT was cochlear dysplasia (n=13; 31%). Conclusions MRI will identify many abnormalities in children with ANSD that are not readily discernable on CT. Specifically, both developmental and acquired abnormalities of the brain, posterior cranial fossa, and cochlear nerves are not uncommonly seen in this patient population. Inner ear anomalies are well delineated using either imaging modality. Since many of the central nervous system findings identified in this study using MRI can alter the treatment and prognosis for these children, we believe that MRI should be the initial imaging study of choice for children with ANSD. PMID:20593543

Diagnostic Imaging of Pregnant Women – The Role of Magnetic Resonance Imaging

PubMed Central

Bekiesińska-Figatowska, Monika; Romaniuk-Doroszewska, Anna; Szkudlińska-Pawlak, Sylwia; Duczkowska, Agnieszka; Mądzik, Jarosław; Szopa-Krupińska, Martyna; Maciejewski, Tomasz M.

2017-01-01

Summary Background Presentation of magnetic resonance imaging (MRI) findings in pregnant women in the Department of Diagnostic Imaging, Institute of Mother and Child, Warsaw, Poland. Material/Methods Forty-three symptomatic pregnant women underwent MRI between 9 and 33 weeks of gestation (mean of 23 weeks). Moreover, we included 2 pregnant women who underwent fetal MRI and had incidental abnormalities. Results In 9 cases, we excluded the suspected brain abnormalities. In 4 cases, we found unremarkable changes in the brain without clinical significance. One patient was diagnosed with multiple sclerosis, one with cortical dysplasia, one with pineal hemorrhage and one with a brain tumor. On abdominal MRI, 2 patients had normal findings, one patient had colon cancer with a hepatic metastasis, one patient had a hepatic angioma, one patient had an extraadrenal pheochromocytoma, one patient had an abscess in the iliopsoas muscle, 9 patients had myomas, two patients had ovarian simple cysts, two endometrial cysts, three dermoid cysts, one patient had sacrococcygeal teratoma, one patient had a cystadenofibroma (partial borderline tumor), one patient had an androgenic ovarian tumor and two patients had hyperreactio luteinalis. One patient was diagnosed with transient osteoporosis of the hip and one with a stress fracture of the sacral bone. Conclusions Magnetic resonance imaging is the best imaging modality for pregnant women. Although ultrasonography is the method of choice, doubtful cases as well as structures that cannot be examined with ultrasonography can be non-invasively evaluated with MRI. PMID:28507642

Localized scleroderma en coup de sabre in the Neurology Clinic.

PubMed

Pinho, João; Rocha, João; Sousa, Filipa; Macedo, Cristiana; Soares-Fernandes, João; Cerqueira, João; Maré, Ricardo; Lourenço, Esmeralda; Pereira, João

2016-07-01

Localized scleroderma en coup de sabre (LScs) is a form of localized scleroderma thought to be an autoimmune disorder. Central nervous system involvement is not rare and neurological manifestations include seizures, focal neurological deficits, headache and neuropsychiatric changes. Patients attending the Neurology Clinic with the final diagnosis of LScs with neurological manifestations were identified and clinical and imagiological records reviewed. Five patients (0.024%) had LScs with neurological involvement, presenting with transient focal neurologic deficits, seizures, headache or migraine with aura. Neuroimaging studies confirmed localized skin depression and showed bone thinning, white matter lesions, brain calcifications, sulcal effacement and meningeal enhancement. Three patients experienced clinical improvement after immunosuppressive therapy, and in two of these patients neuroimaging findings also improved. Recognizing typical dermatologic changes is keystone for the diagnosis of LScs with neurological involvement. It is a diagnosis of exclusion and extensive etiological diagnostic evaluation should be performed. Treatment options, including conservative follow-up or immunosuppressive therapy, should be carefully considered. Copyright © 2016 Elsevier B.V. All rights reserved.

3D bioactive composite scaffolds for bone tissue engineering.

PubMed

Turnbull, Gareth; Clarke, Jon; Picard, Frédéric; Riches, Philip; Jia, Luanluan; Han, Fengxuan; Li, Bin; Shu, Wenmiao

2018-09-01

Bone is the second most commonly transplanted tissue worldwide, with over four million operations using bone grafts or bone substitute materials annually to treat bone defects. However, significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma, cancer, infection and arthritis. Developing bioactive three-dimensional (3D) scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering (BTE). A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts. However, individual groups of materials including polymers, ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone. Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds. This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers, hydrogels, metals, ceramics and bio-glasses in BTE. Scaffold fabrication methodology, mechanical performance, biocompatibility, bioactivity, and potential clinical translations will be discussed.

Hydrogels That Allow and Facilitate Bone Repair, Remodeling, and Regeneration

PubMed Central

Short, Aaron R.; Koralla, Deepthi; Deshmukh, Ameya; Wissel, Benjamin; Stocker, Benjamin; Calhoun, Mark; Dean, David; Winter, Jessica O.

2015-01-01

Bone defects can originate from a variety of causes, including trauma, cancer, congenital deformity, and surgical reconstruction. Success of the current “gold standard” treatment (i.e., autologous bone grafts) is greatly influenced by insufficient or inappropriate bone stock. There is thus a critical need for the development of new, engineered materials for bone repair. This review describes the use of natural and synthetic hydrogels as scaffolds for bone tissue engineering. We discuss many of the advantages that hydrogels offer as bone repair materials, including their potential for osteoconductivity, biodegradability, controlled growth factor release, and cell encapsulation. We also discuss the use of hydrogels in composite devices with metals, ceramics, or polymers. These composites are useful because of the low mechanical moduli of hydrogels. Finally, the potential for thermosetting and photo-cross-linked hydrogels as three-dimensionally (3D) printed, patient-specific devices is highlighted. Three-dimensional printing enables controlled spatial distribution of scaffold materials, cells, and growth factors. Hydrogels, especially natural hydrogels present in bone matrix, have great potential to augment existing bone tissue engineering devices for the treatment of critical size bone defects. PMID:26693013